US20110118600A1 - External Autonomic Modulation - Google Patents

External Autonomic Modulation Download PDF

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Publication number
US20110118600A1
US20110118600A1 US12/725,450 US72545010A US2011118600A1 US 20110118600 A1 US20110118600 A1 US 20110118600A1 US 72545010 A US72545010 A US 72545010A US 2011118600 A1 US2011118600 A1 US 2011118600A1
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US
United States
Prior art keywords
energy
renal
ultrasound
artery
region
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US12/725,450
Inventor
Michael Gertner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Otsuka Medical Devices Co Ltd
Original Assignee
Kona Medical Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kona Medical Inc filed Critical Kona Medical Inc
Priority to US12/725,450 priority Critical patent/US20110118600A1/en
Assigned to Kona Medical, Inc. reassignment Kona Medical, Inc. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GERTNER, MICHAEL
Priority to JP2012533385A priority patent/JP5794580B2/en
Priority to EP10810835.8A priority patent/EP2344039B1/en
Priority to KR1020157004249A priority patent/KR101567285B1/en
Priority to CN201080002316.4A priority patent/CN102164542B/en
Priority to US12/902,135 priority patent/US20110092880A1/en
Priority to CN201080052675.0A priority patent/CN102740925B/en
Priority to EP15196135.6A priority patent/EP3005944A1/en
Priority to KR1020127012159A priority patent/KR101545775B1/en
Priority to BR112012008538A priority patent/BR112012008538A2/en
Priority to RU2012119540/14A priority patent/RU2523129C2/en
Priority to MYPI2012001623A priority patent/MY160595A/en
Priority to CA2777228A priority patent/CA2777228A1/en
Priority to PCT/US2010/052197 priority patent/WO2011046880A2/en
Priority to EP10823909.6A priority patent/EP2488250B1/en
Priority to CN201510013394.9A priority patent/CN104800973A/en
Priority to AU2010307029A priority patent/AU2010307029B2/en
Priority to CN201510013395.3A priority patent/CN104771138A/en
Priority to US12/902,133 priority patent/US9174065B2/en
Priority to PCT/US2010/052193 priority patent/WO2011046879A1/en
Priority to CN201510014506.2A priority patent/CN104856731A/en
Priority to US12/966,962 priority patent/US8556834B2/en
Priority to US12/966,954 priority patent/US20110172528A1/en
Priority to US12/966,943 priority patent/US20110172527A1/en
Priority to US13/019,273 priority patent/US8374674B2/en
Priority to US13/048,830 priority patent/US8517962B2/en
Priority to US13/048,842 priority patent/US8469904B2/en
Priority to US13/048,837 priority patent/US8986231B2/en
Priority to US13/048,844 priority patent/US8986211B2/en
Priority to US13/091,116 priority patent/US9119951B2/en
Priority to US13/111,837 priority patent/US9005143B2/en
Publication of US20110118600A1 publication Critical patent/US20110118600A1/en
Priority to US13/228,366 priority patent/US20110319765A1/en
Priority to US13/246,775 priority patent/US20120016226A1/en
Priority to US13/246,763 priority patent/US20120022409A1/en
Priority to HK11110882.7A priority patent/HK1156491A1/en
Priority to US13/417,194 priority patent/US9358401B2/en
Priority to IL219083A priority patent/IL219083A/en
Priority to US13/487,135 priority patent/US9579518B2/en
Priority to US13/487,121 priority patent/US20120238918A1/en
Priority to US13/487,118 priority patent/US20120245494A1/en
Priority to US13/523,835 priority patent/US8992447B2/en
Priority to US13/535,070 priority patent/US8512262B2/en
Priority to US13/717,401 priority patent/US20130190716A1/en
Priority to US13/751,133 priority patent/US9352171B2/en
Priority to US13/896,247 priority patent/US9199097B2/en
Priority to US13/896,252 priority patent/US20130253381A1/en
Priority to US13/904,853 priority patent/US20140058188A1/en
Priority to US13/960,743 priority patent/US20140039479A1/en
Priority to US13/966,212 priority patent/US20130331739A1/en
Priority to US14/015,331 priority patent/US20140074076A1/en
Priority to US14/099,834 priority patent/US9125642B2/en
Priority to US14/207,516 priority patent/US20140194785A1/en
Priority to US14/207,526 priority patent/US20140336497A1/en
Priority to US14/207,511 priority patent/US20140194784A1/en
Priority to US14/207,642 priority patent/US20140194786A1/en
Priority to US14/562,477 priority patent/US20150202466A1/en
Priority to JP2015082029A priority patent/JP5943441B2/en
Priority to IL238653A priority patent/IL238653A0/en
Priority to US14/939,670 priority patent/US20160059044A1/en
Priority to US15/662,179 priority patent/US10772681B2/en
Priority to US16/412,379 priority patent/US11154356B2/en
Assigned to OTSUKA MEDICAL DEVICES CO., LTD. reassignment OTSUKA MEDICAL DEVICES CO., LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: Kona Medical, Inc.
Priority to US17/486,826 priority patent/US20220202483A1/en
Abandoned legal-status Critical Current

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Definitions

  • Energy delivery from a distance involves transmission of energy waves to affect a target some distance a way. It allows for more efficient delivery of energy to targets and greater cost efficiency and technologic flexibility on the generating side. For example, cellular phones receive targets from towers close to the user and the towers communicate with one another over a long range; this way, the cell phones can be low powered and communicate over a relatively small range yet the network can quickly communicate across the world. Similarly, electricity distribution from large generation stations to the users is more efficient than the users themselves looking for solutions.
  • Laparoscopic surgery In terms of treating a patient, delivering energy over a distance affords great advantages as far as targeting accuracy, technologic flexibility, and importantly, limited invasiveness into the patient.
  • laparoscopic surgery has replaced much of the previous open surgical procedures and lead to creation of new procedures and devices as well as a more efficient procedural flow for disease treatment.
  • Laparoscopic tools deliver the surgeon's energy to the tissues of the patient from a distance and results in improved imaging of the region being treated as well as the ability for many surgeons to visualize the region at the same time. Perhaps most important is the fact that patients have much less pain, fewer complications, and the overall costs of the procedures are lower.
  • an imaging system is provided, as is a therapeutic delivery system.
  • regions of the eye other than the retina are targeted with ablative or sub-ablative energy from outside the eye.
  • the ciliary muscles are targeted and in some embodiments, the zonules surrounding the lens are targeted.
  • presbyopia is treated and in certain embodiments, elevated intraocular pressure is treated.
  • the macula is targeted with non-ablative focused energy.
  • Non-ablative focused or unfocused energy can be utilized to assist in the transcleral or intravitreal release of bioactive agents into the eye.
  • non-focal, non-ablative energy is applied to the sclera to assist in the transcleral migration of bioactive materials to the choroidal space below the retina.
  • ducts such as the fallopian tubes or the vas deferens are targeted for permanent or semi-permanent sterilization using ablative energy.
  • vascular structures such as the saphenous vein, femoral vein, and iliac veins are directly targeted to treat venous diseases such as occlusions or faulty venous valves.
  • intra-vascular clots, devices, or other vascular abnormalities such as aneurysms or arterial-venous malformations, are targeted.
  • sympathetic nerves surrounding arteries are targeted for ablation or sub-ablative interruption.
  • the renal nerves which surround the pedicles of the kidneys are targeted.
  • circles or elliptical rings are created around the renal arteries and in some embodiments, the circles or rings are created closer to the bifurcation of the renal arteries as they reach the kidneys.
  • nerves running down the aorta are targeted as they branch off to the renal arteries.
  • the nerves are targeted at the dorsal or ventral roots as they leave the spinal canal.
  • ultrasonic or ionizing energy is passed through the blood vessel to affect a change in the walls or the surroundings of the vessel.
  • whole or partial sympathetic ganglia positioned close to blood vessels are targeted.
  • ganglia along the sympathetic chain along the spine are targeted as entire structures to target and alter physiologic processes.
  • the dorsal roots of the spinal cord are targeted with energy to partially or fully ablate the renal afferent nerves traveling through them.
  • nerves to joints are targeted with ablative or non-ablative energy such as for example, the spine, the knee, or the hip.
  • vessels are detected and placed in a coordinate frame to be treated with the focused energy system but regions (for example, nerves) just outside the vessels are treated.
  • regions for example, nerves
  • the carotid artery, superior mesenteric artery, aorta, vena cava, renal veins, iliac arteries, ophthalmic artery, and ciliary arteries are all arteries which are potential targets for interruption of surrounding nerves, particularly autonomic nerves.
  • the vessels are the targets localized by the external imaging and energy delivery systems.
  • a device and method to interrupt nerve fibers, at least partially, from a position external to a patient is described.
  • the embodiment involves the application of energy from a region external to the patient to the region of the nerve fibers.
  • energy is delivered from multiple directions and meet at the region of the nerve so as to deliver the effect.
  • an external energy source delivers energy from two difference positions to focus energy on a region of interest (for example, the sympathetic nerve regions of the renal arteries).
  • image detectors are embedded in the devices delivering the energy so that the imaging of the region of interest is also determined from two different angles to determine the location of the target in three dimensions.
  • range finders e.g. acoustic or sonar
  • Time of flight type analysis is the technical term to determined th distance and orietation of the blood vessel (e.g. Oraya).
  • a renal artery is detected using doppler ultrasound technology.
  • doppler ultrasound technology By detecting the position of the renal arteries from more than one angle via doppler triangulation, a three dimensional map can be created and the renal artery can be mapped into a coordinate reference frame. A pattern of energy can be applied to the renal artery based on the knowledge of the coordinate reference frame.
  • an algorithm is utilized to localize the delivery of focused ultrasound to heat the adventitia of the artery which contains the sympathetic nerves to the kidney and thereby decreasing the sympathetic stimulus to the kidney to potentially control hypertension, renal disease, and heart disease.
  • ultrasound is passed through the posterior of a patient, avoiding the ribs and passing the ultrasound to the region of the renal arteries.
  • vessels are detected via doppler ultrasound and placed in a coordinate frame to be treated with the focused energy system.
  • the carotid artery, superior mesenteric artery, aorta, vena cava, renal veins, iliac arteries, ophthalmic artery, and ciliary arteries are all arteries which are potential targets of sympathetic nerve interruption.
  • the techniques described can be applied to any other blood vessel adventitia or nerve plexus surrounding any blood vessel in the body.
  • the location of the stomach is utilized because of its position overlying the celiac plexus and its position partially overlying the abdominal aorta.
  • a nasogastric tube is placed inside the stomach and can be utilized to stimulate or inhibit the celiac axis through the stomach wall using focused or non-focused energy sources.
  • the celiac axis or associated nerves can also be directly ablated using energy based transducers through the stomach or through the aorta or from an external position.
  • ionizing radiation is used and generated from equipment such as a megavoltage linear accelerator, proton beam accelerator, or orthovoltage X-ray generator.
  • CT scan imaging or other imaging systems such as ultrasound
  • MRI can be used to target the region around the renal arteries where the sympathetic nerves sit.
  • the ionizing radiation sources may also be coupled to CT or MRI scanners which can further aid in the identification of the region of the sympathetic nerve plexus.
  • the ultrasound transducers are placed externally and the renal arteries are located in more than one axis using a doppler signal detected from the renal artery blood flow.
  • an arrangement of the ultrasound transducers is such that each transducer has the ability to be moved relative to one another and with respect to the target (e.g. renal blood vessels, aorta, femoral arteries, veins etc.). Such movement allows for adjustment of focal distance and position in the X-Y plan which may change with position.
  • target e.g. renal blood vessels, aorta, femoral arteries, veins etc.
  • a kidney and a renal artery, or just a kidney is targeted with the ultrasound transducers.
  • ultrasound transducers are used to detect Doppler blood flow and simulate the position of the heating spot at the focal region of the transducers. Focused ultrasound energy is then applied to the region surrounding the blood flow, utilizing the Doppler signal as the position to target.
  • a three dimensional view of the renal arteries and renal pedicle is obtained using the ultrasonic images so that the heated region is simulated in three dimensions so as to avoid the critical structures around the renal pedicle such as the renal vein, adrenal artery, and the adrenal gland itself.
  • the ultrasound transducer scans the region to be treated to create a three dimensional image coordinate reference for the artery and arterial region.
  • heating of the renal vein is in fact permissible.
  • a three-dimensional image of a renal artery enables precise placement of the heat generating spot because there are nerves proximal to the generated spot.
  • coupling of the renal artery doppler signal using two separate detectors allows the three dimensional coordinates of the renal artery to be determined in real space.
  • the 3D location of the heating via the therapeutic ultrasound transducers can be determined, in theory, quite quickly. Heating damage to organs surrounding the renal arteries can also be determined, modeled, and minimized.
  • a puncture in the skin may be needed so as to take advantage of additional refinements in technology or to treat patients (e.g. obese patients) who are not amenable to completely external therapy.
  • the puncture in the skin may enable a catheter to be passed into an artery or vein and to the renal artery or vein.
  • a catheter is placed percutaneously, directly to the nerve region surrounding the vessels; that is, not transvascularly but through the skin into the retroperitoneum and to the region of the renal nerves.
  • catheters may be placed through the subcutaneous tissues and into the space around the renal artery or vein.
  • the sympathetic nerves can be ablated or the nerve conduction pathways can otherwise be interrupted to result in a decrease in neurotransmitter release from the sympathetic terminals at the level of the kidney.
  • cardiac afferent nerves have been known to dampen the carotid body response when activated which results in a loss of the parasympathetic response to elevated blood pressure.
  • the cardiac afferent nerves can be ablated so that the baroreceptor response remains sensitive to increased blood pressure and can stimulate the parasympathetic system to decrease adrenergic drive in the face of elevated blood pressure.
  • the sympathetic or parasympathetic nerves leading to the eye are ablated, stimulated, partially ablated, or partially stimulated so as to control intraocular hypertension or other physiologic processes.
  • These sympathetic nerves are well known as being causative for increases in intraocular pressure. Indeed, a best selling pharmaceutical, tenoptic, acts against the adrenergic response in the eye and so ablating the sympathetic nerves would offer a more permanent fix to the elevated intraocular blood pressure.
  • the ultrasound transducers used for ablation also contain at least one imaging transducer.
  • the imaging transducer can be utilized for quick imaging and registration with the MRI or the transducer can be utilized for detection of fiducials within the treatment region.
  • fiducials can be placed in the field or may be naturally present such as for example, a Doppler flow signal in a renal artery.
  • an intravascular catheter is placed with a recognizeable beacon to indicate the position of the catheter, artery, and hence the nerves surrounding the artery.
  • radiation e.g. ionizing radiation
  • ionizing radiation is applied to the region outside the artery to prevent re-growth of the sympathetic nerves after ablation.
  • ablative energy is applied to a region of a fallopian tube to close the tube and prevent ovulation and transfer of ovum to a uterus.
  • a method of inhibiting the function of a nerve traveling with an artery comprises; providing an external imaging modality to determine the location of the artery through the skin of a patient; placing the artery in a three dimensional coordinate reference based on the imaging; placing a therapeutic energy generation source in a three dimensional coordinate reference frame; coupling the three dimensional coordinate frame of the energy source and the artery; modeling the delivery of energy to the adventitial region of the artery or a region adjacent to the artery where a nerve travels; delivering therapeutic energy from the therapeutic energy source, from at least two different angles, through the skin of a patient, to intersect at an artery or the region adjacent to the artery to at least partially inhibit the function of a nerve.
  • the imaging source is one of: ultrasound, MRI, and CT.
  • the therapeutic energy is ultrasound.
  • the energy delivered to the region of the nerves is at the level of 10-100 watts/cm2 or 100-400 watts/cm2, 400-800 watts/cm2, 800-2 kW/cm2, 2-50 kW/cm2, 51-200 kW cm/2. In some instances the level is up to and exceeding 1 MW/cm2.
  • a duty cycle of 100% is utilized by the system and in some embodiments, the duty cycle is 50-99% or lower, for example, 1-49%.
  • intensity is important and the dose is delivered over a period less than 2 seconds or less than 30 seconds or less than a minute.
  • the energy delivered is not heat but vibratory energy with minimal heating.
  • the artery is a renal artery.
  • the fiducial is placed internal to the patient.
  • the fiducial is temporarily placed in a position internal to the patient.
  • the fiducial is a catheter placed in the artery of the patient.
  • the catheter is detectable using an acoustic signal and said imaging modality is ultrasound.
  • the method involves therapeutic energy from the energy source which is delivered in a distribution along the length of the artery.
  • the therapeutic energy is ionizing radiation.
  • a system to inhibit the function of a nerve traveling with a renal artery comprises a detector to determine the location of the renal artery and renal nerve through the skin of a patient; an ultrasound component to deliver therapeutic energy through the skin from at least two directions to the nerve surrounding the renal artery; a modeling algorithm comprising an input and an output said input to the modeling algorithm comprising a three dimensional coordinate space containing a therapeutic energy source and the position of the renal artery; and, the output from the modeling algorithm comprises: the direction and energy level of the ultrasound component; a locateable fiducial, adapted to be temporarily placed in the artery of a patient and communicate with the detector to determine the location of the renal artery in a three dimensional reference, the information regarding the location transmittable as the input to the model.
  • the fiducial is a passive reflector of ultrasound placed inside the artery.
  • the fiducial has an air interface inside a balloon.
  • the fiducial is an intravascular balloon with air inside which can be detected from outside the patient.
  • the system fiducial generates radiofrequency energy which is detectable outside the patient by a detector.
  • the system fiducial is activated to transmit energy based on a signal from an ultrasound generator.
  • the system output from the model instructs the ultrasound component to deliver a lesion on the artery in which the major axis of the lesion is longitudinal along the length of the artery.
  • the system output from the model instructs the ultrasound component to deliver multiple lesions around an artery simultaneously.
  • the energy is delivered across the kidney with the energy crossing the kidney not affecting the kidney in any way.
  • the system output from the model instructs the ultrasound component to deliver a circumferential lesion around the artery in which the HIFU overlap reaches across the artery and/or vein.
  • the ultrasound overlap has a maximal diameter of about 1 cm and covering the renal artery, the renal vein, and the renal nerves. Such energy can be applied within 30 s, 1 1 minute, or within 3-5 minutes.
  • a lesion is placed around the renal artery just proximal to the bifurcation of the artery at the hilum of the kidney.
  • a lesion is placed around the artery by targeting approximately the center of the artery.
  • outflow restrictions are created in the kidney or in the renal vein (for example) to indicate a high pressure state to the kidney which will lead to the kidney autoregulating system blood pressure lower.
  • a clinical feedback loop is utilized in which application of energy to control hypertension is followed by an assay for the effect
  • the assay might include one of: ultrasound of the kidneys, assessment of microneurometry in the periphery, biopsy of the kidney, evaluation of the concentration of norepinephrine in the blood.
  • a skin patch acts as a detector of sympathetic activity, the sympathetic activity being altered by heat applied to one or more regions of the autonomic nervous system.
  • FIGS. 1 a - b depict the focusing of energy sources on nerves of the autonomic nervous system.
  • FIG. 1 c depicts an imaging system.
  • FIG. 2 depicts targeting and/or therapeutic ultrasound delivered through the stomach to the autonomic nervous system posterior to the stomach.
  • FIG. 3 a depicts focusing of energy waves on the renal nerves
  • FIG. 3 b depicts a coordinate reference frame
  • FIG. 4 depicts the application of energy to the autonomic nervous system surrounding the carotid arteries
  • FIGS. 5 a - b depict the application of focused energy to the autonomic nervous system of the eye.
  • FIG. 6 depict the application of lesions to the kidney deep inside the calyces.
  • FIG. 7 a depicts a patient in an imaging system receiving treating with focused energy waves.
  • FIG. 7 b depicts visualization of a kidney being treated.
  • FIG. 7 depicts a close up view of the renal nerve region of the kidney being treated.
  • FIG. 7 d depicts a method to treat the autonomic nervous system using MRI and energy transducers.
  • FIG. 8 a depicts a percutaneous approach to treating the autonomic nervous system surrounding the kidneys.
  • FIG. 8 b depicts an intravascular approach to treating the autonomic nervous system.
  • FIGS. 9 a - c depicts the application of energy from inside the aorta to regions outside the aorta.
  • FIG. 10 depicts steps to treat a disease using HIFU.
  • FIG. 11 a depicts treatment of brain lesions using cross sectional imaging.
  • FIG. 11 b depicts an image on a viewer showing therapy of the region of the brain being treated.
  • FIG. 11 c depicts another view of a brain lesion.
  • FIG. 12 depicts treatment of the renal nerve region using a laparoscopic approach.
  • FIG. 13 depicts a methodology for destroying a region of tissue using imaging markers.
  • FIG. 14 depicts the partial treatment of a nerve bundle using converging imaging waves.
  • FIG. 15 depicts the application of focused energy to the vertebral column.
  • FIG. 16 depicts the types of lesions which are created around the renal arteries to affect a response.
  • FIG. 17 a depicts the application of multiple transducers to treat regions of the autonomic nervous system.
  • FIGS. 17 b - c depict methods and devices to treat a specific region surrounding an artery.
  • FIG. 17 d depicts a method for localizing HIFU transducers relative to Doppler ultrasound signals.
  • FIG. 17 e depicts an arrangement of transducers relative to a target
  • FIG. 17 f depicts ablation zones in a multi-focal region in cross-section.
  • FIG. 18 depicts the application of energy internally within the kidney.
  • FIG. 19 depicts the direction of energy wave propagation to treat regions of the autonomic nervous system around the kidney region.
  • FIG. 20 depicts the application of ultrasound waves through the wall of the aorta
  • FIG. 21 a depicts application of focused energy to the ciliary muscles and processes of the eye.
  • FIG. 21 b depicts the application of focused non-ablative energy to the back of the eye to enhance drug or gene delivery or another therapy such as ionizing radiation.
  • FIG. 22 depicts the application of focused energy to nerves surrounding the knee joint.
  • FIG. 23 - b depicts the application of energy to the fallopian tube to sterilize a patient.
  • FIG. 24 depicts an algorithm to assess the effect of the neural modulation procedure on the autonomic nervous system. After a procedure is performed on the renal nerves, assessment of the autonomic response is performed by, for example, simulating the autonomic nervous system in one or more places.
  • Hypertension is a disease of extreme national and international importance. There are 80 million patients in the US alone who have hypertension and over 200 million in developed countries worldwide. In the United States, there are 60 million patients who have uncontrolled hypertension meaning that they are either non-compliant or cannot take the medication because of the side effect profile. Up to 10 million people might have completely resistant hypertension in which they do not reach target levels no matter what the medication regimen. The morbidities associated with uncontrolled hypertension are profound, including stroke, heart attack, kidney failure, peripheral arterial disease, etc. A convenient and straightforward minimally invasive procedure to treat hypertension would be a very welcome advance in the treatment of this disease.
  • CHF Congestive Heart Failure
  • kidney failure can lead to a downward spiral and further worsening kidney function.
  • the kidney in the forward flow heart failure described above, (systolic heart failure) the kidney becomes ischemic.
  • backward heart failure diastolic heart failure
  • the kidneys become congested vis-à-vis renal vein hypertension. Therefore, the kidney can contribute to its own worsening failure.
  • kidneys can be summarized under three broad categories: filtering blood and excreting waste products generated by the body's metabolism; regulating salt, water, electrolyte and acid-base balance; and secreting hormones to maintain vital organ blood flow.
  • a patient Without properly functioning kidneys, a patient will suffer water retention, reduced urine flow and an accumulation of waste toxins in the blood and body. These conditions result from reduced renal function or renal failure (kidney failure) and are believed to increase the workload of the heart.
  • kidney failure will cause the heart to further deteriorate as fluids are retained and blood toxins accumulate due to the poorly functioning kidneys. The resulting hypertension also has dramatic influence on the progression of cerebrovascular disease and stroke.
  • the autonomic nervous system is a network of nerves which affect almost every organ and physiologic system to a variable degree.
  • the system is composed of sympathetic and parasympathetic nerves.
  • the sympathetic nerves to the kidney traverse the sympathetic chain along the spine and synapse within the ganglia of the chain or within the celiac ganglia, then proceeding to innervate the kidney via post-ganglionic fibers inside the “renal nerves.”
  • the renal nerves which travel along the renal hila (artery and to some extent the vein), are the post-ganglionic sympathetic nerves and the afferent nerves from the kidney.
  • the afferent nerves from the kidney travel within the dorsal root (if they are pain fibers)and into the anterior root if they are sensory fibers, then into the spinal cord and ultimately to specialized regions of the brain.
  • the afferent nerves deliver information from the kidneys back to the sympathetic nervous system via the brain; their ablation or inhibition is at least partially responsible for the improvement seen in blood pressure after renal nerve ablation, or dennervation, or partial disruption. It has also been suggested and partially proven experimentally that the baroreceptor response at the level of the carotid sinus is mediated by the renal artery afferent nerves such that loss of the renal artery afferent nerve response blunts the response of the carotid baroreceptors to changes in arterial blood pressure.
  • the wall of the renal artery is invariably damaged by the RF probe and patients whose vessels have a great deal of atherosclerosis cannot be treated safely.
  • the energy may not consistently lead to ablation or interruption.
  • the use of internal catheters may not allow for treatment inside the kidney or inside the aorta if more selective or less selective blockade of the renal sympathetic nerves is desired.
  • Ultrasound is a cyclically generated sound pressure wave with a frequency greater than the upper limit of human hearing . . . 20 kilohertz (kHz).
  • ultrasound is widely utilized because of its ability to penetrate tissues. Reflection of the sound waves reveals a signature of the underlying tissues and as such, ultrasound can be used extensively for diagnostics and potentially therapeutics as well in the medical field.
  • ultrasound has the ability to both penetrate tissues and can be focused to create ablation zones. Because of its simultaneous ability to image, ultrasound can be utilized for precise targeting of lesions inside the body.
  • Ultrasound intensity is measured by the power per cm 2 . Generally, high intensity refers to intensities over 1 kW/cm 2 . Low intensity ultrasound encompasses the rage up to 1 kW/cm 2 from about 1 or 10 Watts per cm2.
  • Ultrasound can be utilized for its forward propagating waves and resulting reflected waves or where energy deposition in the tissue and either heating or slight disruption of the tissues is desired.
  • lower frequency ultrasonic beams e.g. ⁇ 1 MHz
  • ⁇ 1 MHz can be focused at a depth within tissue, creating a heating zone or a defined region of cavitation in which micro-bubbles are created, cell membranes are opened to admit bioactive molecules, or damage is otherwise created in the tissue.
  • These features of ultrasound generally utilize frequencies in the 0.25 Megahertz (MHz) to 10 MHz range depending on the depth required for effect. Focusing is or may be required so that the surface of the tissue is not excessively injured or heated by single beams.
  • many single beams can be propagated through the tissue at different angles to decrease the energy deposition along any single path yet allow the beams to converge at a focal spot deep within the tissue.
  • reflected beams from multiple angles may be utilized in order to create a three dimensional representation of the region to be treated in a coordinate space.
  • Time of flight measurements with ultrasound can be used to range find, or find distances between objects in tissues. Such measurements can be utilized to place objects such as vessels into three dimensional coordinate reference frames so that energy can be utilized to target the tissues.
  • SONAR is the acronym for sound navigation and ranging and is a method of acoustic localization. Sound waves are transmitted through a medium and the time for the sound to reflect back to the transmitter is indicative of the position of the object of interest. Doppler signals are generated by a moving object. The change in the forward and reflected wave results in a velocity for the object.
  • Lithotripsy was introduced in the early part of the 1980's. Lithotripsy utilizes shockwaves to treat stones in the kidney.
  • the Dournier lithotripsy system was the first system produced for this purpose. The lithotripsy system sends ultrasonic waves through the patient's body to the kidney to selectively heat and vibrate the kidney stones; that is, selectively over the adjacent tissue.
  • Histotripsy is a term given to a technique in which tissue is essentially vaporized using cavitation rather than heating (transcutaneous non-thermal mechanical tissue fractionation). These mini explosions do not require high temperature and can occur in less than a second.
  • the generated pressure wave is in the range of megapascals (MPa) and even up to or exceeding 100 MPa. To treat small regions of tissue very quickly, this technique can be very effective.
  • the border of the viable and non-viable tissue is typically very sharp and the mechanism of action has been shown to be cellular disruption.
  • Cross-sectional imaging is utilized to visualize the internal anatomy of patients via radiation (CT) or magnetic fields (MRI). Ultrasound can also be utilized to obtain cross-sections of specific regions but only at high frequencies; therefore, ultrasound is typically limited to imaging superficial body regions. CT and MRI are often more amenable to cross sectional imaging because the radiation penetrates well into tissues. In addition, the scale of the body regions is maintained such that the anatomy within the coordinate references remains intact relative to one another; that is, distances between structures can be measured.
  • CT scans and MRIs and even ultrasound devices can be utilized to create three dimensional representations and reconstructed cross-sectional images of patients; anatomy can be placed in a coordinate reference frame using a three dimensional representation. Once in the reference frame, energy devices (transducers) can be placed in positions and energy emitting devices directed such that specific regions of the body are targeted. Once knowledge of the transducer position is known relative to the position of the target in the patient body, energy can be delivered to the target.
  • ultrasound is focused on the region of the renal arteries or veins from outside the patient; the ultrasound is delivered from multiple angles to the target, allowing the current invention to overcome many of the deficiencies in previous methods and devices put forward to ablate renal sympathetic nerves which surround the renal arteries.
  • one embodiment of this invention allows for precise visualization of the ablation zone so that the operator can be confident that the correct region is ablated and that the incorrect region is not ablated. Because some embodiments do not require a puncture in the skin, they are considerably less invasive, which is more palatable and safer from the patient standpoint. Moreover, unusual anatomies and atherosclerotic vessels can be treated using external energy triangulated on the renal arteries to affect the sympathetic and afferent nerves to and from the kidney respectively.
  • the human renal anatomy includes the kidneys 100 which are supplied with oxygenated blood by the renal arteries 200 and are connected to the heart via the abdominal aorta 300 .
  • Deoxygenated blood flows from the kidneys to the heart via the renal veins (not shown) and thence the inferior vena cava (not shown).
  • the renal anatomy includes the cortex, the medulla, and the hilum.
  • Blood is delivered to the cortex where it filters through the glomeruli and is then delivered to the medulla where it is further filtered through a series of reabsorption and filtration steps in the loops of henle and individual nephrons; the ultrafiltrate then percolates to the ureteral collecting system and is delivered to the ureters and bladder for ultimate excretion.
  • the hila is the region where the major vessels (renal artery and renal vein) and nerves 150 (efferent sympathetic, afferent sensory, and parasympathetic nerves) travel to and from the kidneys.
  • the renal nerves 150 contain post-ganglionic efferent nerves which supply sympathetic innervation to the kidneys.
  • Energy transducers 500 deliver energy transcutaneously to the region of the sympathetic ganglia 520 or the post-ganglionic renal nerves 150 or the nerves leading to the adrenal gland 400 .
  • the energy is generated from outside the patient, from multiple directions, and through the skin to the region of the renal nerves 150 which surround the renal artery 640 .
  • the energy can be focused or non-focused but in one preferred embodiment, the energy is focused with high intensity focused ultrasound (HIFU). Focusing with low intensity focused ultrasound (LIFU) may also occur. Focusing occurs by delivering energy from at least two different angles through the skin to meet at a focal point where the highest energy intensity and density occurs.
  • HIFU high intensity focused ultrasound
  • LIFU low intensity focused ultrasound
  • a therapy is delivered and the therapy can be sub-threshold nerve interruption (partial ablation), ablation (complete interruption) of the nerves, controlled interruption of the nerve conduction apparatus, partial ablation, or targeted drug delivery.
  • the region can be heated to a temperature of less than 60 degrees for non-ablative therapy or can be heated greater than 60 degrees for heat based destruction (abalation).
  • temperatures in the 40 degree range can be used and if generated for a time period greater than several minutes, will result in ablation. Heating aside, a vibratory effect for a much shorter period of time at temperatures below 60 degrees Celsius can result in partial or complete paralysis of destruction of the nerves.
  • an imaging modality is included as well in the system.
  • the imaging modality can be ultrasound based, MRI based, CT (Xray) based.
  • CT Xray
  • the imaging modality can be utilized to target the region of ablation and determined the distances to the target.
  • the delivered energy can be ionizing or non-ionizing energy.
  • non-ionizing energy can include electromagnetic energy (e.g. a magnetic field, light, an electric field), radiofrequency energy, and light based energy.
  • ionizing energy include x-ray, proton beam, gamma rays, electron beams, and alpha rays.
  • the energy modalities are combined. For example, heat ablation of the nerves is performed and then ionizing radiation is delivered to the region to prevent re-growth of the nerves.
  • ionizing radiation is applied first as an ablation modality and then heat applied afterward in the case of re-growth of the tissue as re-radiation may not be possible (complement energy utilization). Ionizing radiation may prevent or inhibit the re-growth of the nervous tissue around the vessel if there is indeed re-growth of the nervous tissue. Therefore, another method of treating the nerves is to first heat the nerves and then apply ionizing radiation to prevent re-growth.
  • external neuromodulation is performed in which low energy ultrasound is applied to the nerve region to modulate the nerves.
  • low intensity e.g. non-thermal
  • HIFU thermal modulation
  • the actual power flux to the region to be ablated is dependent on the environment including surrounding blood flow and other structures.
  • the energy does not have to be so strictly focused to the target because it's a non-ablative energy; that is, the vibration or mechanical pressure may be the effector energy and the target may have a different threshold for effect depending on the tissue.
  • transducers 500 in FIG. 1 a provide the ability to apply a range of different energy and power levels as well as modeling capability to target different regions and predict the response.
  • a renal artery is detected 640 with the assistance of imaging techniques 600 such as Doppler ultrasound, B-mode ultrasound, MRI, or a CT scan.
  • imaging techniques 600 such as Doppler ultrasound, B-mode ultrasound, MRI, or a CT scan.
  • measurements in multiple directions on a series of slices can be performed so as to create a three-dimensional representation of the area of interest.
  • Doppler triangulation for example
  • another triangulation technique By detecting the position of the renal arteries from more than one angle via Doppler triangulation (for example) or another triangulation technique, a three dimensional positional map can be created and the renal artery can be mapped into a coordinate reference frame.
  • locating the direction and lengths of the blood vessels in three dimensional coordinate reference is the predominant component of the procedure to target the sympathetic nerves.
  • a pattern of energy can be applied to the vicinity of the renal artery from a device well outside the vicinity (and outside of the patient altogether) based on knowledge of the coordinate reference frame.
  • an algorithm is utilized to localize the delivery of focused ultrasound to heat or apply mechanical energy to the adventitia and surrounding regions of the artery which contain sympathetic nerves to the kidney and afferent nerves from the kidney, thereby decreasing the sympathetic stimulus to the kidney and its afferent signaling back to the autonomic nervous system; affecting these targets will modulate the propensity toward hypertension which would otherwise occur.
  • the ultrasonic energy delivery can be modeled mathematically by predicting the wave dissipation using the distances and measurements taken with the imaging modalities of the tissues and path lengths.
  • the Doppler signal from the artery is identified from at least two different directions and the direction of the artery is reconstructed in three dimensional space.
  • a line is created and with knowledge of the thickness of the vessel, a tube, or cylinder, can be created to represent the blood vessel as a virtual model.
  • the tube is represented in three dimensional space over time and its coordinates are known relative to the therapeutic transducers outside of the skin of the patient.
  • Therapeutic energy can be applied from more than one direction as well and can focus on the cylinder (blood anterior vessel wall, central axis, or posterior wall.
  • Focused energy e.g. ultrasound
  • Focused energy can be applied to the center of the vessel (within the flow), on the posterior wall of the vessel, in between (e.g. when there is a back to back artery and vein next to one another) the artery vessel and a venous vessel, etc.
  • Imaging 600 of the sympathetic nerves or the sympathetic region is also utilized so as to assess the direction and orientation of the transducers relative to the target 620 .
  • Continuous feedback of the position of the transducers 500 relative to the target 620 is provided by the imaging system in which the coordinate space of the imaging system.
  • the imaging may be a cross-sectional imaging technology such as CT or MRI or it may be an ultrasound imaging technology which yields faster real time imaging.
  • the imaging may be a combination of technologies such as the fusion of MRI/CT and ultrasound.
  • the imaging system can detect the position of the target in real time at frequencies ranging from 1 hz to thousands and tens of thousands of images per second.
  • cross-sectional imaging e.g. MRI/CT
  • ultrasound is linked to the three dimensional reference frame and utilized to track the patient's body in real time under the ultrasound linked to the cross-sectional imaging.
  • the lack of resolution provided by the ultrasound is made up for by the cross-sectional imaging since only a few consistent anatomic landmarks are required for an ultrasound image to be linked to the MRI image.
  • the progressively new ultrasound images are linked to the MRI images and therefore MRI “movement” can be seen at a frequency not otherwise available to an MRI series.
  • ultrasound is the energy used to inhibit nerve conduction in the sympathetic nerves.
  • focused ultrasound (HIFU) from outside the body through the skin is the energy used to inhibit sympathetic stimulation of the kidney by delivering waves from a position external to the body of a patient and focusing the waves on the sympathetic nerves on the inside of the patient and which surround the renal artery of the patient.
  • transducers 900 can emit ultrasound energy to the region of the renal sympathetic nerves at the renal pedicle.
  • an image of the renal artery 620 using an ultrasound, MRI, or CT scan can be utilized to determine the position of the kidney 610 and the renal artery 620 target.
  • Doppler ultrasound can be used to determine the location and direction of a Doppler signal from an artery and therefore enable the arteries 200 and hence the sympathetic nerves 220 ( FIG. 3 a ) around the artery to be much more visible so as to process the images and then utilize focused external energy to pinpoint the location and therapy of the sympathetic nerves.
  • ultrasound is likely the most appropriate imaging modality.
  • FIG. 1 a also depicts the delivery of focused energy to the sympathetic nerve trunks which run along the vertebral column; the renal artery efferent nerves travel in these trunks and synapse to ganglia within the trunks.
  • ablation of the dorsal roots at the level of the ganglia or dorsal root nerves at T9-T11 would produce the same or similar effect to ablation at the level of the renal arteries.
  • FIG. 1 b illustrates the application of ionizing energy to the region of the sympathetic nerves on the renal arteries 620 or renal veins.
  • energy levels of greater than 20 Gy are required for linear accelerators or low energy x-ray machines to ablate nervous tissue using ionizing energy; however, lower energy is required to stun, inhibit nervous tissue, or prevent re-growth of nervous tissue; in some embodiment, energy levels as low as 2-5 Gy or 5-10 Gy or 10-15 Gy are delivered in a single or fractionated doses.
  • Combinations of ionizing energy and other forms of energy can be utilized in this embodiment as well so as to prevent re-growth of the nervous tissue.
  • a combination of heat and/or vibration and/or cavitation and/or ionizing radiation might be utilized to prevent re-growth of nervous tissue after the partial or full ablation of the nervous tissue surrounding the renal artery.
  • FIG. 2 illustrates the renal anatomy and surrounding anatomy with greater detail in that organs such as the stomach are shown in its anatomic position overlying the abdominal aorta and renal arteries.
  • energy is delivered through the stomach to reach an area behind the stomach.
  • the stomach is utilized as a conduit to access the celiac ganglion, a region which would otherwise be difficult to reach.
  • the aorta 705 is shown underneath the stomach and the celiac ganglion 710 is depicted surrounding the superior mesenteric artery and aorta.
  • a transorally placed tube 720 is placed through the esophagus and into the stomach.
  • the tube overlies the celiac ganglion when placed in the stomach and can therefore be used to deliver sympatholytic devices or pharmaceuticals which inhibit or stimulate the autonomic celiac ganglia behind the stomach; these therapies would be delivered via transabdominal ultrasound or fluoroscopic guidance (for imaging) through the stomach. Similar therapies can be delivered to the inferior mesenteric ganglion, renal nerves, or sympathetic nerves traveling along the aorta through the stomach or other portion of the gastrointestinal tract.
  • the energy delivery transducers 730 , 731 are depicted external to the patient and can be utilized to augment the therapy being delivered through the stomach to the celiac ganglion.
  • Temporary neurostimulators can also be placed through the tube, such as, for example, in an ICU setting where temporary blockage of the autonomic ganglia may be required. Temporary neurostimulators can be used to over pace the celiac ganglion nerve fibers and inhibit their function as a nerve synapse. Inhibition of the celiac ganglion may achieve a similar function as ablation or modulation of the sympathetic nerves around the renal arteries. That is, the decrease in the sympathetic activity to the kidneys (now obtained with a more proximal inhibition) leads to the lowering of blood pressure in the patient by decreasing the degree of sympathetic outflow from the sympathetic nerve terminals.
  • the blood pressure lowering effect is more profound given that the celiac ganglia are pre-ganglionic and have more nerve fibers to a greater number of regions than each renal nerve. The effect is also likely more permanent than the effect on the post-ganglionic nerve fibers.
  • FIG. 3 a illustrates the renal anatomy more specifically in that the renal nerves 220 extending longitudinally along the renal artery 200 , are located generally within, or just outside the adventitia, of the outer portion of the artery.
  • Arteries are typically composed of three layers: the first is the intimal, the second is the media, and the third is the adventitia.
  • the outer layer, the adventitia is a fibrous tissue which contains blood vessels and nerves.
  • the renal nerves are generally postganglionic sympathetic nerves although there are some ganglia which exist distal to the takeoff from the aorta such that some of the nerve fibers along the renal artery are in fact pre-ganglionic. By the time the fibers reach the kidney, the majority of the fibers are post-ganglionic.
  • Energy generators 900 deliver energy to the renal nerves accompanying the renal artery, depositing energy from multiple directions to target inhibition of the renal nerve complex.
  • the energy generators can deliver ultrasound energy, ionizing radiation, light (photon) therapy, or microwave energy to the region.
  • the energy can be non-focused in the case where a pharmaceutical agent is targeted to the region to be ablated or modulated. Preferably, however, the energy is focused, being applied from multiple angles from outside the body of the patient to reach the region of interest (e.g. sympathetic nerves surrounding blood vessels).
  • the energy transducers 900 are placed in an X-Y-Z coordinate reference frame 950 , as are the organs such as the kidneys.
  • cross-sectional imaging using MRI, CT scan, and/or ultrasound is utilized to couple the internal anatomy to the energy transducers.
  • the transducers 900 in this embodiment are focused on the region of the renal nerves at the level of the renal blood vessels, the arteries and veins.
  • High intensity ultrasound applied to the region with only a few degrees of temperature rise may have the same effect and this energy range may be in the 0.5 kW/cm2 to the 500 kW/cm2 range.
  • cooling may be applied to the skin if the temperature rise is deemed too large to be acceptable.
  • the ultrasound transducers can be pulsed or can be alternated with another set of transducers to effectively spread the heat across the surface of the skin.
  • the region around the renal arteries is imaged using CT scan, MRI, thermography, infrared imaging, optical coherence tomography (OCT), photoacoustic imaging, pet imaging, SPECT imaging, or ultrasound, and the images are placed into a three dimensional coordinate reference frame.
  • Energy transducers which can deliver ultrasound, light, radiation, ionizing radiation, or microwave energy are placed in the same three-dimensional reference frame as the renal arteries at which time an algorithm can determine how to direct the transducers to deliver energy to the region of the nerves.
  • the algorithm consists of a targeting feature (planning feature) which allows for prediction of the position and energy deposition of the energy leaving the transducer.
  • the original imaging utilized to locate the renal sympathetic region can be used to track the motion of the region during treatment.
  • the imaging technology used at time zero is taken as the baseline scan and subsequent scans at time t 1 are compared to the baseline scan.
  • the frequency of updates can range from a single scan every few seconds to many scans per second.
  • ultrasound as the imaging technology
  • the location might be updated at a frame rate greater than 50 Hz and up to several hundred Hz or thousand Hz.
  • the imaging refresh rate might be closer to 30 Hz.
  • internally placed fiducials transmit positional information at a high frequency and this information is utilized to fuse the target with an initial external imaging apparatus.
  • Internal fiducials might be one more imageable elements including doppler signal, regions of blood vessels, ribs, kidneys, blood vessels other than the target (e.g. vena cava). These fiducials can be used to track the region being treated and/or to triangulate to the region to be treated.
  • a test dose of energy can be applied to the renal sympathetic region and then a test performed to determine if an effect was created. For example, a small amount of heat can be delivered to the region of the sympathetic nerves and then a test of sympathetic activity such as microneurometry (detection of sympathetic nerve activity around muscles and nerves which correlate with the beating heart) can be performed.
  • a test of sympathetic activity such as microneurometry (detection of sympathetic nerve activity around muscles and nerves which correlate with the beating heart) can be performed.
  • microneurometry detection of sympathetic nerve activity around muscles and nerves which correlate with the beating heart
  • Past research and current clinical data have shown that the sympathetic nerves to the peripheral muscles are affected by interruption of the renal afferent nerves.
  • the temperature rise with the small degree of heat can be determined through the use of MRI thermometry and the temperature rise can be determined or limited to an amount which is reversible.
  • ultrasonic imaging can be utilized to determine the approximate temperature rise of the tissue region.
  • the speed of ultrasonic waves is dependent on temperature and therefore the relative speed of the ultrasound transmission from a region being heated will depend on the temperature, therefore providing measureable variables to monitor.
  • microbubbles are utilized to determine the rise in temperature. Microbubbles expand and then degrade when exposed to increasing temperature so that they can then predict the temperature of the region being heated.
  • a technique called ultrasound elastography an also be utilized.
  • the elastic properties of tissue are dependent on temperature and therefore the elastography may be utilized to track features of temperature change.
  • the microbubbles can also be utilized to augment the therapeutic effect of the region being targeted. For example, the microbubbles can be utilized to release a pharmaceutical when the ultrasound reaches them.
  • a test may be performed on the baroreceptor complex at the region of the carotid artery bifurcation.
  • pressure can be applied to the carotid artery complex; typically, with an intact baroreceptor complex, the systemic blood pressure would decrease after application of pressure to the carotid artery.
  • the baroreceptors will not be sensitive to changes in blood pressure and therefore the efficacy of the application of the energy to the renal nerves can be determined.
  • FIG. 4 illustrates a system in which external energy 1020 is applied to a portion of the autonomic nervous system, the carotid body complex 1000 , through the internal jugular vein 1005 , and to the carotid body 1000 and/or vagus nerve 1020 region.
  • Ablative energy or electrical stimulation energy can be utilized to affect the transmission of signals to and from these nerves.
  • the transmission in this complex can be augmented, interrupted, inhibited with over-stimulation, or a combination of these effects via energy (e.g. ultrasound, electrical stimulation, etc.)
  • a catheter 1010 is advanced into the internal jugular vein 1005 and when in position, stimulation or ablative energy 1020 is directed toward the autonomic nerves, the vagus nerve, and the carotid sinus from the catheter positioned in the venous system.
  • a similar type of catheter can be inserted into the region of the renal arteries or renal veins to stimulate or inhibit the renal nerves from the inside of the vessel.
  • a catheter delivering unfocused ultrasound energy in the range of 50 mW/cm 2 to 50 W/cm 2 can be placed into the renal artery and the energy transmitted radially around the artery to the nerves.
  • This therapy can be delivered on an acute basis such as for example in an ICU or critical care setting.
  • the therapy would be acute and intermittent, with the source outside the patient and the catheter within the patient as shown in FIG. 4 .
  • the therapy can be utilized during times of stress for the patient such that the sympathetic system is slowed down. After the intensive care admission is nearing a close, the catheter and unit can be removed from the patient.
  • FIGS. 5 a - b illustrates the eye in close up detail with sympathetic nerves surrounding the posterior of the eye.
  • glaucoma is a problem of world-wide importance.
  • the most commonly prescribed medication to treat glaucoma is timoptic, which is a non-selective ⁇ 1 and ⁇ 2 (adrenergic) antagonist. Compliance with this pharmaceutical is a major problem and limits its effectiveness in preventing the complications of glaucoma, the major complication being progression of visual dysfunction.
  • Ultrasound, or other energy transducers 7000 can be applied to focus energy from an external region (e.g. a distance from the eye in an external location) anterior to the eye or to a region posteriorly behind the eye 2500 on the sympathetic 2010 or parasympathetic ganglia, all of which will affect lowering of intra-ocular pressure.
  • the energy transducers 700 apply ablative or near ablative energy to the adventitia of the blood vessel.
  • the energy is not ablative but vibratory at frequencies and penetration depths sufficient to inhibit the function of the nerves which are responsible for intra-ocular pressure.
  • FIG. 5 b depicts the anatomy behind the eye.
  • a catheter 2000 is tunneled through the vasculature to the region of the sympathetic nerves surrounding the arteries of the eye 2010 and utilized to ablate, stun, or otherwise modulate the efferent and/or afferent nerves through the wall of the vasculature.
  • FIG. 6 illustrates an overall schematic of the renal artery, renal vein, the collecting system, and the more distal vessels and collecting system within the renal parenchyma.
  • the individual nerves of the autonomic nervous system typically follow the body vasculature and they are shown in close proximity 3000 to the renal artery as the artery enters the kidney 3100 proper. Any one or multiple of these structures can influence the function of the kidney.
  • Ablative or non-ablative energy can be applied to the renal vein, the renal artery, the aorta or the vena cava, the renal hilum, the renal parenchyma, the renal medulla, the renal cortex, etc.
  • selective lesions, constrictions or implants 3200 are placed in the calyces of the kidney to control or impede blood flow to specific regions of the kidney.
  • Such lesions or implants can be placed on the arterial 3010 or venous sides 3220 of the kidney.
  • the lesions/implants are created so as to selectively block certain portions of the sympathetic nerves within the kidney.
  • the lesions also may be positioned so as to ablate regions of the kidney which produce hormones, such as renin, which can be detrimental to a patient in excess.
  • the implants or constrictions can be placed in the aorta 3210 or the renal vein 3220 .
  • the implants can be active implants, generating stimulating energy chronically or multiple ablative or inhibitory doses discretely over time.
  • the implants might cause an increase in the pressure within the kidney which will prevent the downward spiral of systolic heart failure described above. That is, once the pressure in the kidney is restored or artificially elevated by increased venous pressure, the relative renal hypotension signaling to retain electrolytes and water will not be present any longer and the kidney will “feel” full and the renal sympathetic stimulation will be turned off.
  • a stent which creates a stenosis is implanted using a catheter delivery system 3000 .
  • a stricture is created using heat delivered either externally or internally.
  • an implant is placed between girota's fascia and the cortex of the kidney.
  • FIG. 7 a depicts at least partial ablation of the renal sympathetic nerves 4400 to the kidney using an imaging system such as an MRI machine or CT scanner 4000 .
  • the MRI/CT scan can be linked to a focused ultrasound (HIFU) machine to perform the ablations of the sympathetic nerves 4400 around the region of the renal artery 4500 .
  • the MRI/CT scan performs the imaging 4010 and transmits data (e.g. three dimensional representations of the regions of interest) to the ultrasound controller which then directs the ultrasound to target the region of interest with low intensity ultrasound (50-1000 mW/cm2) heat (>1000 mW/cm2), cavitation, or a combination of these modalities and/or including introduction of enhancing agents locally or systemically (sonodynamic therapy).
  • a doppler ultrasound or other 3D/4D ultrasound is performed and the data pushed to the MRI system to assist with localization of the pathology; alternatively, the ultrasound data are utilized to directly control the direction of the energy being used to target the physiologic processes and CT/MRI is not obtained.
  • this imaging and ablation system from a position external to a patient, many regions of the kidney can be treated such as the internal calyces, the cortex, the medulla, the hilum and the region near to the aorta.
  • thermal spectroscopy using MRI or ultrasound thermometry/elastography
  • thermal imaging is a well-known feature of MRI scanners
  • the data for thermal spectroscopy exists within the MRI scan and can be extrapolated from the recorded data in real time by comparing regions of interest before and after or during treatment.
  • Temperature data overlaid on the MRI scan enables the operator of the machine to visualize the increase in temperature and therefore the location of the heating to insure that the correct region has indeed been ablated and that excessive energy is not applied to the region.
  • Having temperature data also enables control of the ablation field as far as applying the correct temperature for ablation to the nerves.
  • Elastography is a technique in which the shear waves of the ultrasound beam and reflectance are detected.
  • the tissue characteristics change as the tissue is heated and the tissue properties change.
  • An approximate temperature can be assigned to the tissue based on elastography and the progress of the heating can be monitored.
  • MRI scanners 4000 generally consist of a magnet and an RF coil.
  • the magnet might be an electromagnet or a permanent magnet.
  • the coil is typically a copper coil which generates a radiofrequency field.
  • permanent magnets have been utilized to create scanners which are able to be used in almost any setting, for example a private office setting.
  • Office based MRI scanners enable imaging to be performed quickly in the convenience of a physicians offices as well as requiring less magnetic force (less than 0.5 Tesla) and as a consequence, less shielding.
  • the lower tesla magnets also provides for special advantages as far as diversity of imaging and resolution of certain features.
  • the permanent magnet MRI scanners are open scanners and do not encapsulate the patient during the scan.
  • a permanent magnet MRI is utilized to obtain an MRI image of the region of interest 4010 .
  • High intensity focused 4100 ultrasound is used to target the region of interest 4600 identified using the MRI.
  • Image 4010 is monitored by a health care professional to ensure that the region of interest is being treated and can stop the therapy if the region is not being treated.
  • an imaging algorithm can be initiated in which the region of interest is identified and then subsequent images are compared to the initial demarcated region of interest.
  • the region around the renal arteries can be easily imaged as can any other region such as the eye, brain, prostate, breast, liver, colon, spleen, aorta, hip, knee, spine, venous tree, and pancreas.
  • the imaging from the MRI can be utilized to precisely focus the ultrasound beam to the region of interest around the renal arteries or elsewhere in the body.
  • the actual nerves to be modified or modulated can be directly visualized and targeted with the energy delivered through the body from the ultrasound transducers.
  • One disadvantage of MRI can be the frame acquisition (difficulty in tracking the target) rate as well as the cost of introducing an MRI machine into the treatment paradigm.
  • FIG. 7 b depicts a method of treating a region with high intensity focused ultrasound (HIFU).
  • Imaging with an MRI 4520 or Doppler ultrasound 4510 (or preferably both) is performed.
  • MRI can be used to directly or indirectly (e.g. using functional MRI or spectroscopy) to visualize the sympathetic nerves.
  • T1 weighted or T2 weighted images can be obtained using the MRI scanner.
  • the MRI scanner can also obtain temperature data regarding the effectiveness of the ablation zone as well as the degree to which the zone is being heated and which parts of the zones are being heated. Other spectroscopic parameters can be added as well such as blood flow and even nerve activity.
  • Ultrasound can be used to add blood flow to the images using Doppler imaging.
  • the spectroscopic data can be augmented by imaging moieties such as particles, imaging agents, or particles coupled to imaging agents which are injected into the patient intravenously, or locally, and proximal to the region of the renal arteries; these imaging moieties may be visualized on MRI, ultrasound, or CT scan.
  • Imaging moieties such as particles, imaging agents, or particles coupled to imaging agents which are injected into the patient intravenously, or locally, and proximal to the region of the renal arteries; these imaging moieties may be visualized on MRI, ultrasound, or CT scan.
  • Ultrasound can also be utilized to determine information regarding heating.
  • the reflectance of the ultrasonic waves changes as the temperature of the tissue changes. By comparing the initial images with the subsequent images after heating, the temperature changes can be determined.
  • the kidneys are detected by a cross-sectional imaging modality such as MRI, ultrasound, or CT scan.
  • a cross-sectional imaging modality such as MRI, ultrasound, or CT scan.
  • the imaging data is placed into a three dimensional coordinate system which is linked to one or more ultrasound (e.g. HIFU) transducers which focus ultrasound onto the region of the renal arteries in the coordinate frame.
  • the linking, or coupling, of the imaging to the therapeutic transducers is accomplished by determining the 3 dimensional position of the target by creating an anatomic model.
  • the transducers are placed in a relative three dimensional coordinate frame as well.
  • the transducers can be placed in the imaging field during the MRI or CT scan such that the cross-sectional pictures include the transducers.
  • ultrasound is utilized and the ultrasound image can be directly correlated to the origin of the imaging transducer.
  • the therapeutic transducer in some embodiments is the same as the imaging transducer and therefore the therapeutic transducer is by definition coupled in a coordinate reference once the imaging transducer coordinates are known. If the therapeutic transducer and the imaging transducer are different devices, then they can be coupled by knowledge of the relative position of the two devices.
  • the region of interest (ROI) is highlighted in a software algorithm . . . for example, the renal arteries, the calyces, the medullary region, the cortex, the renal hila, the celiac ganglia, the aorta, or any of the veins of the venous system as well.
  • the adrenal gland, the vessels traveling to the adrenal gland, or the autonomic nerves traveling to the adrenal gland are targeted with focused ultrasound and then either the medulla or the cortex of the adrenal gland or the nerves and arteries leading to the gland are partially or fully ablated with ultrasonic energy.
  • the targeting region or focus of the ultrasound is the point of maximal intensity.
  • targeting focus is placed in the center of the artery such that the walls on either side receive equivalent amounts of energy or power and can be heated more evenly than if one wall of the blood vessel is targeted.
  • the center of the focus might be placed at the boundary of the vein and the artery.
  • the tissue is heated 4560 and a technique such as MRI thermography 4570 or ultrasound thermography is utilized to determine the tissue temperature.
  • MRI thermography 4570 or ultrasound thermography is utilized to determine the tissue temperature.
  • the anatomic data from the MRI scan or the Doppler ultrasound is then referenced to ensure the proper degree of positioning and the degree of energy transduction is again further assessed by the modeling algorithm 4545 to set the parameters for the energy transducers 4550 . If there is movement of the target, the transducers may have to be turned off and the patient repositioned.
  • Ablation can also be augmented using agents such as magnetic nanoparticles or liposomal nanoparticles which are responsive to a radiofrequency field generated by a magnet. These particles can be selectively heated by the magnetic field. The particles can also be enhanced such that they will target specific organs and tissues using targeting moieties such as antibodies, peptides, etc. In addition to the delivery of heat, the particles can be activated to deliver drugs, bioactive agents, or imaging agents at the region at which action is desired (e.g. the renal artery). The particles can be introduced via an intravenous route, a subcutaneous route, or a percutaneous route.
  • Doppler ultrasound 4510 may be provided as well.
  • the renal arteries are (if renal arteries or regions surrounding the arteries are the target) placed in a 3D coordinate reference frame 4530 using a software algorithm with or without the help of fiducial markers.
  • Data is supplied to ultrasound transducers 4540 from a heat modeling algorithm 4545 and the transducers are energized with the appropriate phase and power to heat the region of the renal artery to between 40 degrees C. and 90 degrees C. within a time span of several minutes.
  • the position within the 3D coordinate reference is also integrated into the treatment algorithm so that the ultrasound transducers can be moved into the appropriate position.
  • the ultrasound transducers may have frequencies below 1 megahertz (MHz), from 1-20 MHz, or above 30 Mhz.
  • ultrasonic waves can be utilized directly to either heat an area or to activate pharmaceuticals in the region of interest.
  • particles can release pharmaceutical when they are heated by the magnetic field.
  • Liposomes can release a payload when they are activated with focused ultrasound.
  • Ultrasound waves have a natural focusing ability if a transducer is placed in the vicinity of the target and the target contains an activateable moiety such as a bioactive drug or material (e.g. a nanoparticle sensitive to acoustic waves). Examples of sonodynamically activated moieties include some porphyrin derivatives.
  • the region can be partially heated with the focused ultrasound to stun or partially ablate the nerves.
  • a physiologic test such as the testing of blood pressure or measuring norepinephrine levels in the blood can be performed to ensure that the correct region was indeed targeted for ablation.
  • additional treatments may be performed.
  • a fiducial is utilized to demarcate the region of interest.
  • a fiducial can be intrinsic (e.g. part of the anatomy) or the fiducial can be extrinsic (e.g. placed in position).
  • the fiducial can be an implanted fiducial, a fiducial or device placed in the blood vessels, or a device placed percutaneously through a catheterization or other procedure.
  • the fiducial can also be a bone, such as a rib, or another internal organ, for example, the liver.
  • the fiducial is a beacon or balloon or balloon with a beacon which is detectable via ultrasound.
  • the blood flow in the renal arteries is the fiducial and its relative direction is determined via Doppler analysis.
  • the renal arteries and specifically, the region around the renal arteries are placed into a three dimensional coordinate frame utilizing the internal fiducials.
  • a variant of global positioning system technology can be utilized to track the fiducials within the artery or around the arteries.
  • the three dimensional coordinate frame is transmitted to the therapeutic ultrasound transducers and then the transducers and anatomy are coupled to the same coordinate frame.
  • the HIFU is delivered from the transducers, calculating the position of the transducers based on the position of the target in the reference frame.
  • a virtual fiducial is created via an imaging system.
  • an imaging system For example, in the case of a blood vessel such as the renal artery, an image of the blood vessel using B-mode ultrasound can be obtained which correlates to the blood vessel being viewed in direct cross section ( 1700 ; FIG. 17C ).
  • the center of the vessel can be aligned with the center of an ultrasound array (e.g. HIFU array 1600 ) and the transducers can be focused and applied to the vessel, applying heat to regions around the vessels 1680 .
  • an ultrasound array e.g. HIFU array 1600
  • the directionality of the transducers allows for a lesion which runs lengthwise along the vessel 1620 , 1630 , 1640 .
  • a longitudinal lesion can be produced along the artery to insure maximal inhibition of nerve function.
  • the center of the therapeutic ultrasound transducer is off center relative to the center of the vessel so that the energy is applied across the vessel wall at an angle.
  • an artery such as a renal artery is viewed in cross-section or close to a cross-section under ultrasound guidance.
  • the blood vessel is substantially parallel to the axis of the spherical transducer so as to facilitate lesion production.
  • the setup of the ultrasound transducers 1600 has previously been calibrated to create multiple focal lesions 1620 , 1630 , 1640 along the artery if the artery is in cross-section 1680 .
  • the fiducial is an intravascular fiducial such as a balloon or a hermetically sealed transmitting device.
  • the balloon is detectable via radiotransmitter within the balloon which is detectable by the external therapeutic transducers.
  • the balloon can have three transducers, each capable of relaying their position so that the balloon can be placed in a three dimensional coordinate reference.
  • the energy transducing devices can deliver energy (e.g. focused ultrasound) to the blood vessel (e.g. the renal arteries) or the region surrounding the blood vessels (e.g. the renal nerves).
  • the balloon and transmitters also enable the ability to definitively track the vasculature in the case of movement (e.g. the renal arteries).
  • the balloon measures temperature or is a conduit for coolant applied during the heating of the artery or nerves.
  • Delivery of therapeutic ultrasound energy to the tissue inside the body is accomplished via the ultrasound transducers which are directed to deliver the energy to the target in the coordinate frame.
  • the position of the region of ablation is compared to its baseline position, both in a three dimensional coordinate reference frame.
  • the ongoing positional monitoring and information is fed into an algorithm which determines the new targeting direction of the energy waves toward the target.
  • the energy delivery is stopped and the patient repositioned. If the position is not too far from the original position, then the energy transducers can be repositioned either mechanically (e.g. through physical movement) or electrically via phased array (e.g.
  • transducers are placed on the patient in different positions and each is turned on or off to result in the necessary energy delivery. With a multitude of transducers placed on the patient, a greater territory can be covered with the therapeutic ultrasound.
  • the therapeutic positions can also serve as imaging positions for intrinsic and/or extrinsic fiducials.
  • ultrasound can be utilized to deliver cavitating energy which may enable drug delivery at certain frequencies. Cavitating energy can also lead to ablation of tissue at the area of the focus.
  • a systemic dose of a drug can be delivered to the region of interest and the region targeted with the cavitating or other forms of ultrasonic energy.
  • Other types of therapeutic delivery modalities include ultrasound sensitive bubbles or radiation sensitive nanoparticles, all of which enhance the effect of the energy at the target of interest.
  • Ultrasound may also be utilized to create tumor vaccines in vivo.
  • sub-ablative doses of energy is applied to a tumor to induce a stress response or to heat shock response to increase the anti-tumor or immune response to the tumor.
  • the energy can be applied from an external position to and internal position or from an internal position to an external position.
  • FIG. 8 a depicts a percutaneous procedure 5000 and device 5010 in which the region around the renal artery 5030 is directly approached through the skin from an external position.
  • a combination of imaging and ablation may be performed to ablate the region around the renal artery to treat hypertension, end stage renal disease, and heart failure.
  • Probe 5010 is positioned through the skin and in proximity to the kidney 5030 .
  • the probe may include sensors which detect heat or temperature or may enable augmentation of the therapeutic energy delivery.
  • Ablative, ionizing energy, heat, or light may be applied to the region to inhibit the sympathetic nerves around the renal artery using the probe 510 .
  • Ultrasound, radiofrequency, microwave, direct heating elements, and balloons with heat or energy sources may be applied to the region of the sympathetic nerves.
  • the percutaneous procedure is performed under MRI, CT, or ultrasound guidance to obtain localization or information about the degree of heat being applied.
  • ultrasound is applied but at a sub-ablative dose. That is, the energy level is enough to damage or inhibit the nerves but the temperature is such that the nerves are not ablated but paralyzed or partially inhibited by the energy.
  • a particularly preferred embodiment would be to perform the procedure under guidance from an MRI scanner because the region being heated can be determined anatomically in real time as well via temperature maps. As described above the images after heating can be compared to those at baseline and the signals are compared at the different temperatures.
  • selective regions of the kidney are ablated through the percutaneous access route; for example, regions which secrete hormones which are detrimental to a patient or to the kidneys or other organs.
  • Using energy applied external to the patient through the skin and from different angles affords the ability to target any region in or on the kidney or along the renal nerves or at the region of the adrenal gland, aorta, or sympathetic chain. This greater breadth in the number of regions to be targeted is enabled by the combination of external imaging and external delivery of the energy from a multitude of angles through the skin of the patient to the target.
  • the renal nerves can be targeted at their takeoff from the aorta onto the renal artery, at their synapses at the celiac ganglia, or at their bifurcation point along the renal artery.
  • probe 5010 can be utilized to detect temperature or motion of the region while the ultrasound transducers are applying the energy to the region.
  • a motion sensor, position beacon, or accelerometer can be used to provide feedback for the HIFU transducers.
  • an optional temperature or imaging modality may be placed on the probe 5010 .
  • the probe 5010 can also be used to locate the position within the laparoscopic field for the ablations to be performed.
  • intravascular devices 5050 , 5055 are depicted which apply energy to the region around the renal arteries 5065 .
  • the intravascular devices can be utilized to apply radiofrequency, ionizing radiation, and/or ultrasound (either focused or unfocused) energy to the renal artery and surrounding regions.
  • MRI or ultrasound or direct thermometry can be further utilized to detect the region where the heat is being applied while the intravascular catheter is in place.
  • devices 5050 , 5055 apply ultrasound energy which inhibits nerve function not by heating, but by mechanisms such as periodic pressure changes, radiation pressure, streaming or flow in viscous media, and pressures associated with cavitation, defined as the formation of holes in liquid media. Heat can selectively be added to these energies but not to create a temperature which ablates the nerves, only facilitates the mechanism of vibration and pressure.
  • the ultrasound is not focused but radiates outward from the source to essentially create a cylinder of ultrasonic waves that intersect with the wall of the blood vessel.
  • An interfacial material between the ultrasound transducer and the wall of the artery may be provided such that the ultrasound is efficiently transduced through the arterial wall to the region of the nerves around the artery.
  • the ultrasound directly enters the blood and propagates through the ultrasound wall to affect the nerves.
  • cooling is provided around the ultrasound catheter which protects the inside of the vessel yet allows the ultrasound to penetrate through the wall to the regions outside the artery.
  • a stabilization method for the ultrasound probe is also included in such a procedure.
  • the stabilization method might include a stabilizing component added to the probe and may include a range finding element component of the ultrasound. Imaging can be performed externally or internally in this embodiment in which a catheter is placed inside the renal ateries.
  • the devices 5050 , 5055 can be utilized to direct externally applied energy (e.g. ultrasound) to the correct place around the artery as the HIFU transducers deliver the energy to the region.
  • the intravascular probe 5050 can be utilized as a homing beacon for the imaging technology utilized for the externally delivered HIFU.
  • the physiologic process of arterial expansion is targeted.
  • an ultrasound transducer 6005 is placed near the wall of an aneurysm 6030 .
  • Ultrasonic energy is applied to the wall 6030 of the aneurysm to thicken the wall and prevent further expansion of the aneurysm.
  • clot within the aneurysm is targeted as well so that the clot is broken up or dissolved with the ultrasonic energy.
  • a material is placed in the aneurysm sac and the focused or non-focused ultrasound utilized to harden or otherwise induce the material in the sac to stick to the aorta or clot in the aneurysm and thus close the aneurysm permanently.
  • an ultrasound catheter is placed in an aorta at the region of an aneurysm wall or close to a material in an aneurysmal wall.
  • the material can be a man-made material placed by an operator or it can be material such as thrombus which is in the aneurysm naturally. Ultrasound is applied to the wall, or the material, resulting in hardening of the wall or of the material, strengthening the aneurysm wall and preventing expansion.
  • FIG. 9 b depicts a clot prevention device 6012 within a blood vessel such as the aorta or vena cava 6000 .
  • the ultrasound catheter 6005 is applied to the clot prevention device (filter) 6012 so as to remove the clot from the device or to free the device 6012 from the wall of the blood vessel in order to remove it from the blood vessel 6000 .
  • FIG. 9 c depicts a device and method in which the celiac plexus 6020 close to the aorta 6000 is ablated or partially heated using heat or vibrational energy from an ultrasonic energy source 6005 which can apply focused or unfocused sound waves 6007 at frequencies ranging from 20 kilohertz to 5 Mhz and at powers ranging from 1 mW to over 100 kW in a focused or unfocused manner.
  • Full, or partial ablation of the celiac plexus 6020 can result in a decrease in blood pressure via a similar mechanism as applying ultrasonic energy to the renal nerves; the ablation catheter is a focused ultrasound catheter but can also be a direct (unfocused) ultrasonic, a microwave transducer, or a resistive heating element.
  • FIG. 10 depicts a method 6100 to treat a patient with high intensity or low intensity focused ultrasound (HIFU or LIFU) 6230 .
  • a CT and/or MRI scan and/or thermography and/or ultrasound (1D, 2D, 3D) is performed 6110 .
  • a fiducial or other marking on or in the patient 6120 is optionally used to mark and track 6140 the patient.
  • the fiducial can be an implanted fiducial, a temporary fiducial, or a fiducial intrinsic to the patient (e.g. bone, blood vessel, arterial wall) which can be imaged using the CT/MRI/Ultrasound devices 6110 .
  • the fiducial can further be a temporary fiducial such as a catheter temporarily placed in an artery or vein of a patient or a percutaneously placed catheter.
  • a planning step 6130 for the HIFU treatment is performed in which baseline readings such as position of the organ and temperature are determined; a HIFU treatment is then planned using a model (e.g. finite element model) to predict heat transfer, or pressure to heat transfer, from the ultrasound transducers 6130 .
  • the planning step incorporates the information on the location of the tissue or target from the imaging devices 6110 and allows placement of the anatomy into a three dimensional coordinate reference such that modeling 6130 can be performed.
  • the planning step 6130 includes determination of the positioning of the ultrasound transducers as far as position of the focus in the patient.
  • X, Y, Z, and up to three angular coordinates are used to determine the position of the ultrasonic focus in the patient based on the cross sectional imaging 6110 .
  • the HIFU transducers might have their own position sensors built in so that the position relative to the target can be assessed. Alternatively, the HIFU transducers can be rigidly fixed to the table on which the patient rests so that the coordinates relative to the table and the patient are easily obtainable.
  • the flow of heat is also modeled in the planning step 6130 so that the temperature at a specific position with the ultrasound can be planned and predicted.
  • the pressure wave from the transducer is modeled as it penetrates through the tissue to the target.
  • the tissue can be treated as water with a minimal loss due to interfaces.
  • the relative power and phase of the ultrasonic wave at the target can be determined by the positional coupling between the probe and target.
  • a convective heat transfer term is added to model heat transfer due to blood flow, particularly in the region of an artery.
  • a conductive heat transfer term is also modeled in the equation for heat flow and temperature.
  • Another variable which is considered in the planning step is the size of the lesion and the error in its position.
  • the temperature of the regions may need to be increased to a temperature of 60-90 degrees Celsius to permanently ablate nerves in the region. Temperatures of 40-60 degrees may temporarily inhibit or block the nerves in these regions and these temperatures can be used to determine that a patient will respond to a specific treatment without permanently ablating the nerve region. Subsequently, additional therapy can be applied at a later time so as to complete the job or perhaps, re-inhibit the nerve regions.
  • Each element of temperature and position contains an error variable which propagates through the equation of the treatment.
  • the errors are modeled to obtain a virtual representation of the temperature mapped to position. This map is correlated to the position of the ultrasound transducers in the treatment of the region of interest.
  • the patient may move, in which case the fiducials 6120 track the movement and the position of the treatment zone is re-analyzed 6150 and the treatment is restarted or the transducers are moved either mechanically or electrically to a new focus position.
  • a cross-sectional technique of imaging is used in combination with a modality such as ultrasound to create a fusion type of image.
  • the cross-sectional imaging is utilized to create a three dimensional data set of the anatomy.
  • the ultrasound providing two dimensional images, is linked to the three dimensional imaging provided by the cross-sectional machine through fiducial matches between the ultrasound and the MRI.
  • the corresponding data is determined (coupled to) the cross-sectional (e.g. MRI image) and a viewing station can show the movement in the three dimensional dataset.
  • the ultrasound provides real time images and the coupling to the MRI or other cross-sectional image depicts the ultrasound determined position in the three dimensional space.
  • FIG. 11 depicts the treatment of another disease in the body of a patient, this time in the head of a patient.
  • Subdural and epidural hematomas occur as a result of bleeding of blood vessels in the dural or epidural spaces of the brain, spinal column, and scalp.
  • FIG. 11 depicts a CT or MRI scanner 7300 and a patient 7400 therein.
  • An image is obtained of the brain 7000 using a CT or MRI scan. The image is utilized to couple the treatment zone 7100 to the ultrasound array utilized to heat the region.
  • a subdural hematoma either acute or chronic, is treated.
  • an epidural hematoma is treated.
  • the region of leaking capillaries and blood vessels are heated to stop the bleeding, or in the case of a chronic subdural hematoma, the oozing of the inflammatory capillaries.
  • a patient 7400 with a subdural or epidural hematoma is chosen for treatment and a CT scan or MRI 7300 is obtained of the treatment region.
  • Treatment planning ensues and the chronic region of the epidural 7200 or sub-dural 7010 hematoma is targeted for treatment with the focused ultrasound 7100 transducer technology.
  • the target of interest is placed in a coordinate reference frame as are the ultrasound transducers.
  • Therapy 7100 ensues once the two are couple together.
  • the focused ultrasound heats the region of the hematoma to dissolve the clot and/or stop the leakage from the capillaries which lead to the accumulation of fluid around the brain 7420 .
  • the technology can be used in place of or in addition to a burr hole, which is a hole placed through the scalp to evacuate the fluid.
  • FIG. 12 depicts a laparoscopic based approach 8000 to the renal artery region in which the sympathetic nerves 8210 can be ligated, interrupted, or otherwise modulated.
  • laparoscopy the abdomen of a patient is insufflated and laparoscopic instruments introduced into the insufflated abdomen. The retroperitoneum is accessible through a flank approach or through a transabdominal approach.
  • a laparoscopic instrument 8200 with a distal tip 8220 can apply heat or another form of energy or deliver a drug to the region of the sympathetic nerves 8210 .
  • the laparoscopic implement can also be utilized to ablate or alter the region of the celiac plexus 8300 and surrounding ganglia.
  • the laparoscope can have an ultrasound transducer attached, a temperature probe attached, a microwave transducer attached, or a radiofrequency transducer attached.
  • the laparoscope can be utilized to directly ablate or stun the nerves(e.g. with a lower frequency/energy) surrounding vessels or can be used to ablate or stun nerve ganglia which travel with the blood vessels. Similar types of modeling and imaging can be utilized with the percutaneous approach as with the external approach to the renal nerves.
  • FIG. 13 depicts an algorithm for the treatment of a region of interest.
  • MRI and/or CT with or without a imaging agent 8410 can be utilized to demarcate the region of interest (for example, the ablation zone) and then ablation 8420 can be performed around the zone identified by the agent using any of the modalities above.
  • This algorithm is applicable to any of the therapeutic modalities described above including external HIFU, laparoscopic instruments, intravascular catheters, percutaneous catheters, as well as any of the treatment regions including the renal nerves, the eye, the kidneys, the aorta, or any of the other nerves surrounding peripheral arteries or veins.
  • Imaging 8430 with CT, MRI, ultrasound, or PET can be utilized in real time.
  • imaging with an imaging (for example, a molecular imaging agent or a contrast agent such as gadolinium) agent 8410 can be performed again.
  • the extent of ablation can also be monitored by monitoring the temperature or the appearance of the ablated zone under an imaging modality.
  • ultrasonic diagnostic techniques such as elastography are utilized to determine the progress toward heating or ablation of a region.
  • FIG. 14 depicts ablation in which specific nerve fibers of a nerve are targeted using different temperature gradients or temperatures 8500 .
  • temperature is determined by MRI thermometry or with another technique such as ultrasound, then the temperature can be kept at a temperature in which only certain nerve fibers are targeted for destruction or inhibition.
  • part or all of the nerve can be turned off temporarily to then test the downstream effect of the nerve being turned off.
  • the sympathetic nerves around the renal artery can be turned off with a small amount of heat or other energy (e.g. vibrational energy) and then the effect can be determined.
  • norepinephrine levels in the systemic blood or renal vein can be assayed; alternatively, the stimulation effect of the nerves can be tested after temporary cessation of activity (e.g. skin reactivy, blood pressure lability, cardiac activity, pulmonary activity. Varying frequencies of vibration can be utilized to inhibit specific nerve fibers versus others.
  • the efferent nerve fibers are inhibited and in other embodiments, the afferent nerve fibers are inhibited. In some embodiments, both types of nerve fibers are inhibited, temporarily or permanently.
  • FIG. 15 depicts treatment 8600 of a vertebral body or intervertebral disk 8610 in which nerves within 8640 or around the vertebral column 8630 are targeted with ultrasound 8625 waves.
  • nerves around the facet joints are targeted.
  • nerves leading to the disks or vertebral endplates are targeted.
  • FIG. 16 depicts a set of lesion types, sizes, and anatomies 8710 a - h which lead to de-innervation of the different portions of the sympathetic nerve tree.
  • the lesions can be annular, cigar shaped, linear, doughnut and/or spherical; the lesions can be placed around the renal arteries 8705 , inside the kidney 8710 , and/or around the aorta 8700 .
  • the renal arterial tree 8700 comprises renal arteries 8705 and kidneys 8715 .
  • Lesions 8710 a - h are different types of lesions which are created around the aorta 8700 and vascular tree. Lesions can be placed in a spiral shape along the length of the artery.
  • FIG. 17 a depicts a multi-transducer HIFU device 1100 which applies a finite lesion 1150 along an artery 1140 (e.g. a renal artery) leading to a kidney 1130 .
  • the lesion can be spherical in shape, cigar shaped 1050 , annular shaped 1050 , or point shaped; however, in a preferred embodiment, the lesion runs along the length of the artery and has a cigar shaped.
  • This lesion is generated by a spherical type of ultrasound array in a preferred embodiment.
  • FIG. 17 c depicts the pathway of the spherical or cylindrical type of ultrasound array 1600 .
  • Ultrasound transducers 1610 are aligned along the edge of a cylinder aimed so that they intersect at one or more focal spots 1620 , 1630 , 1640 .
  • the transducers 1610 are positioned along the cylinder 1650 such that some are closer to one focus or the other so that a range of distances to the artery is created.
  • the patient and artery are positioned such that their centers 1700 co-localize with the center of the ultrasound array 1600 . Once the centers are co-localized, the HIFU energy can be activated to create lesions along the length of the artery wall 1640 , 1620 , 1630 at different depths and positions around the artery.
  • 17 b is a lengthwise lesion, longer than in thickness or height, which will run along the length of an artery when the artery is placed along the center axis of the cylinder.
  • the nerve ablations are positioned along a clock face 1680 around the vessel.
  • a treatment workstation 1300 gives multiple views of the treatment zone with both physical appearance and anatomy 1050 .
  • Physical modeling is performed in order to predict lesion depth and the time to produce the lesion; this information is fed back to the ultrasound transducers 1100 .
  • the position of the lesion is also constantly monitored in a three dimensional coordinate frame and the transducer focus at lesions center 1150 continually updated.
  • motion tracking prevents the lesion or patient from moving too far out of the treatment zone during the ablation. If the patient does move outside the treatment zone during the therapy, then the therapy can be stopped. Motion tracking can be performed using the ultrasound transducers, tracking frames and position or with transducers from multiple angles, creating a three dimensional image with the transducers. Alternatively, a video imaging system can be used to track patient movements, as can a series of accelerometers positioned on the patient which indicate movement.
  • FIG. 18 depicts a micro-catheter 8810 which can be placed into renal calyces 8820 ; this catheter allows the operator to specifically ablate or stimulate 8830 regions of the kidney 8800 .
  • the catheter can be used to further allow for targeting of the region around the renal arteries and kidneys by providing additional imaging capability or by assisting in movement tracking or reflection of the ultrasound waves to create or position the lesion.
  • the catheter or device at or near the end of the catheter may transmit signals outside the patient to direct an energy delivery device which delivers energy through the skin. Signaling outside the patient may comprise energies such as radiofrequency transmission outside the patient or radiofrequency from outside to the inside to target the region surrounding the catheter.
  • a micro catheter is delivered to the renal arteries and into the branches of the renal arteries in the kidney.
  • a signal is generated from the catheter into the kidney and out of the patient to an energy delivery system.
  • the position of the catheter in a three dimensional coordinate reference is determined and the energy source is activated to deliver energy to the region indicated by the microcatheter.
  • the microcatheter may be utilized to place a flow restrictor inside the kidney (e.g. inside a renal vein) to “trick” the kidney into thinking its internal pressure is higher than it might be.
  • the kidney generates signals to the central nervous system to lower sympathetic output to target organs.
  • the microcatheter can generate ultrasound, radiofrequency, microwave, or X-ray energy.
  • the microcatheter can be utilized to ablate regions in the renal vein or intraparenchymal venous portion as well.
  • ablation is not required but vibratory energy emanating from the probe is utilized to affect, on a permanent or temporary basis, the mechanoreceptors or chemoreceptors in the location of the hilum of the kidney.
  • FIG. 19 depicts the application of acoustic waves to the region of the renal artery 8910 and kidney 8920 using physically separated transducers 8930 , 8931 .
  • FIG. 19 depicts delivery of ultrasound transverse to the renal arteries and not longitudinal to the artery. The direction of energy delivery is the posterior of the patient because the renal artery is the first vessel seen when traveling from the skin toward the anterior direction facilitating delivery of the therapy.
  • the transducers 8930 , 8931 are placed under, or inferior to the rib of the patient or between the ribs of a patient; next, the transducers apply an ultrasound wave propagating forward toward the anterior abdominal wall and image the region of the renal arteries and renal veins, separating them from one another. In some embodiments, such delivery might be advantageous, if for example, a longitudinal view of the artery is unobtainable or a faster treatment paradigm is desirable.
  • the transducers 8930 , 8931 communicate with one another and are connected to a computer model of the region of interest being imaged (ROI), the ROI based on an MRI scan performed just prior to the start of the procedure and throughout the procedure. Importantly, the transducers are placed posterior in the cross section of the patient, an area with more direct access to the kidney region. The angle between the imaging transducers is
  • an MRI is not performed but ultrasound is utilized to obtain all or part of the view in FIG. 19 .
  • 8930 might contain an imaging transducer as well as a therapeutic energy source (e.g. ionizing energy, HIFU, low energy focused ultrasound, etc.).
  • a therapeutic energy source e.g. ionizing energy, HIFU, low energy focused ultrasound, etc.
  • FIG. 20 depicts an alternative method 9000 and device to ablate the renal nerves 9015 or the nerves leading to the renal nerves at the aorta-renal artery ostium 9010 .
  • the intravascular device 9020 is placed into the aorta 9050 and advanced to the region of the renal arteries 9025 .
  • Energy is applied from the transducer 9020 and focused 9040 (in the case of HIFU, LIFU, ionizing radiation) to the region of the takeoff of the renal arteries 9025 from the aorta 9050 .
  • This intravascular procedure can be guided using MRI and/or MRI thermometry or it can be guided using fluoroscopy, ultrasound, or MRI.
  • non-focused ultrasound can be applied to the region around the renal ostium or higher in the aorta.
  • Non-focused ultrasound in some embodiments may require cooling of the tissues surrounding the probe using one or more coolants but in some embodiments, the blood of the aorta will take the place of the coolant; HIFU, or focused ultrasound, may not need the cooling because the waves are by definition focused from different angles to the region around the aorta.
  • the vena cava and renal veins can also be used as a conduit for the focused ultrasound transducer to deliver energy to the region as well.
  • the vena cava is accessed and vibratory energy is passed through the walls of the vena cava and renal vein to the renal arteries, around which the nerves to the kidney travel.
  • the veins, having thinner walls, allow energy to pass through more readily.
  • FIG. 21 depicts an eyeball 9100 . Also depicted are the zonules 9130 and ultrasound transducer 9120 .
  • the transducer 9120 applies focused ultrasound energy to the region surrounding the zonules, or the zonules themselves, in order to tighten them such that a presbyopic patient can accommodate and visualize object up close. Similarly, heat or vibration to the ciliary muscles, which then slows down the outflow of aqueous humor at the region of interest so that the pressure within the eye cannot build up to a high level.
  • the ultrasound transducer 9120 can also be utilized to deliver drug therapy to the region of the lens, ciliary body, zonules, intravitreal cavity, anterior cavity, posterior cavity, etc.
  • the ultrasonic transducers 9170 are focused on the particular region of the eye so that tissues along the path of the ultrasound are not damaged by the ultrasound and the focus region and region of effect is the position where the waves meet in the eye.
  • the transducers are directed through the pars plana region of the eye to target the macula 9180 at the posterior pole 9175 of the eye. This configuration might allow for heat, vibratory stimulation, drug delivery, gene delivery, augmentation of laser or ionizing radiation therapy, etc.
  • focused ultrasound is not required and generic vibratory waves are transmitted through the eye at frequencies from 20 kHz to 10 MHz.
  • Such energy may be utilized to break up clots in, for example, retinal venous or arterial occlusions which are creating ischemia in the retina.
  • This energy can be utilized in combination with drugs utilized specifically for breaking up clots in the veins of the retina.
  • FIG. 22 depicts a peripheral joint 9200 being treated with heat and/or vibrational energy.
  • Ultrasound transducer 9210 emits waves toward the knee joint to block nerves 9260 just underneath the bone periostium.
  • a knee joint is depicted, it should be understood that many joints can be treated including small joints in the hand, intervertebral joints, the hip, the ankle, the wrist, and the shoulder.
  • Unfocused or focused ultrasonic energy can be applied to the joint region to inhibit nerve function reversibly or irreversibly. Such inhibition of nerve function can be utilized to treat arthritis, post-operative pain, tendonitis, tumor pain, etc.
  • FIG. 23 a - b depicts closure of a fallopian tube 9300 of a uterus 9320 using externally applied ultrasound 9310 so as to prevent pregnancy.
  • MRI or preferably ultrasound can be utilized for the imaging modality. Thermometry can be utilized as well so as to see the true ablation zone in real time.
  • the fallopian tube 9300 can be visualized using ultrasound, MRI, CT scan or a laparoscope.
  • external energy 9310 for example, ultrasound, can be utilized to close the fallopian tube to prevent pregnancy.
  • ultrasound is applied to the uterus or fallopian tubes to aid in pregnancy by improving the receptivity of the sperm and/or egg for one another.
  • This augmentation of conception can be applied to the sperm and egg outside of the womb as well, for example, in a test tube.
  • a method is depicted in which the fallopian tubes are visualized 9340 using MRI, CT, or ultrasound.
  • HIFU 9350 is applied under visualization with MRI or ultrasound.
  • the collagen in the wall is heated until the walls of the fallopian tube close off.
  • the patient is sterilized 9360 .
  • it may be required to determine how effective the heating is progressing. If additional heat is required, then additional HIFU may be added to the fallopian tubes until there is closure of the tube and the patient is sterilized 9360 .

Abstract

In some embodiments, nerves surrounding arteries or leading to organs are targeted with energy sources to correct or modulate physiologic processes. In some embodiments, different types of energy sources are utilized singly or combined with one another. In some embodiments, bioactive agents or devices activated by the energy sources are delivered to the region of interest and the energy is enhanced by such agents.

Description

    PRIORITY DATA
  • This applications claims priority to the following applications:
  • 61/303307 filed Feb. 10, 2010 Provisional Patent
  • 12/685655 filed Jan. 11, 2010 Non-Provisional Patent
  • 60/256983 filed Oct. 31, 2009 Provisional Patent
  • 60/250857 filed Oct. 12, 2009 Provisional Patent
  • 61/261741 filed Nov. 16, 2009 Provisional Patent
  • 61/291359 filed Dec. 30, 2009 Provisional Patent
  • BACKGROUND
  • Energy delivery from a distance involves transmission of energy waves to affect a target some distance a way. It allows for more efficient delivery of energy to targets and greater cost efficiency and technologic flexibility on the generating side. For example, cellular phones receive targets from towers close to the user and the towers communicate with one another over a long range; this way, the cell phones can be low powered and communicate over a relatively small range yet the network can quickly communicate across the world. Similarly, electricity distribution from large generation stations to the users is more efficient than the users themselves looking for solutions.
  • In terms of treating a patient, delivering energy over a distance affords great advantages as far as targeting accuracy, technologic flexibility, and importantly, limited invasiveness into the patient. In a simple form, laparoscopic surgery has replaced much of the previous open surgical procedures and lead to creation of new procedures and devices as well as a more efficient procedural flow for disease treatment. Laparoscopic tools deliver the surgeon's energy to the tissues of the patient from a distance and results in improved imaging of the region being treated as well as the ability for many surgeons to visualize the region at the same time. Perhaps most important is the fact that patients have much less pain, fewer complications, and the overall costs of the procedures are lower.
  • Continued advances in computing, miniaturization and economization of energy delivery technologies, and improved imaging will lead to still greater opportunities to apply energy from a distance into the patient and treat disease.
  • SUMMARY OF INVENTION
  • What is described herein are procedures and devices which advance the art of medical procedures involving transmitted energy to treat disease. That is, the procedures and devices described below follow along the lines of: 1) transmitting energy to produce an effect in a patient from a distance; 2) allowing for improved imaging or targeting at the site of treatment; 3) creating efficiencies through utilization of larger and more powerful devices from a position of distance from the patient as opposed to attempting to be directly in contact with the target.
  • In some embodiments, an imaging system is provided, as is a therapeutic delivery system.
  • In some embodiments, regions of the eye other than the retina are targeted with ablative or sub-ablative energy from outside the eye.
  • In some embodiments, the ciliary muscles are targeted and in some embodiments, the zonules surrounding the lens are targeted. In certain embodiments related to the eye, presbyopia is treated and in certain embodiments, elevated intraocular pressure is treated.
  • In some embodiments, the macula is targeted with non-ablative focused energy. Non-ablative focused or unfocused energy can be utilized to assist in the transcleral or intravitreal release of bioactive agents into the eye.
  • In some embodiments, non-focal, non-ablative energy is applied to the sclera to assist in the transcleral migration of bioactive materials to the choroidal space below the retina.
  • In some embodiments, ducts such as the fallopian tubes or the vas deferens are targeted for permanent or semi-permanent sterilization using ablative energy.
  • In some embodiments, vascular structures such as the saphenous vein, femoral vein, and iliac veins are directly targeted to treat venous diseases such as occlusions or faulty venous valves.
  • In some embodiments, intra-vascular clots, devices, or other vascular abnormalities such as aneurysms or arterial-venous malformations, are targeted.
  • In some embodiments, sympathetic nerves surrounding arteries are targeted for ablation or sub-ablative interruption. In some embodiments, the renal nerves which surround the pedicles of the kidneys are targeted. In some embodiments, circles or elliptical rings are created around the renal arteries and in some embodiments, the circles or rings are created closer to the bifurcation of the renal arteries as they reach the kidneys. In other embodiments, nerves running down the aorta are targeted as they branch off to the renal arteries. In some embodiments, the nerves are targeted at the dorsal or ventral roots as they leave the spinal canal.
  • In some embodiments, ultrasonic or ionizing energy is passed through the blood vessel to affect a change in the walls or the surroundings of the vessel.
  • In some embodiments, whole or partial sympathetic ganglia positioned close to blood vessels are targeted. In some embodiments, ganglia along the sympathetic chain along the spine are targeted as entire structures to target and alter physiologic processes. In other embodiments, the dorsal roots of the spinal cord are targeted with energy to partially or fully ablate the renal afferent nerves traveling through them.
  • In some embodiments, nerves to joints are targeted with ablative or non-ablative energy such as for example, the spine, the knee, or the hip.
  • In some embodiments, vessels are detected and placed in a coordinate frame to be treated with the focused energy system but regions (for example, nerves) just outside the vessels are treated. For example, the carotid artery, superior mesenteric artery, aorta, vena cava, renal veins, iliac arteries, ophthalmic artery, and ciliary arteries are all arteries which are potential targets for interruption of surrounding nerves, particularly autonomic nerves. The vessels, however, are the targets localized by the external imaging and energy delivery systems.
  • In some embodiments, a device and method to interrupt nerve fibers, at least partially, from a position external to a patient is described. The embodiment involves the application of energy from a region external to the patient to the region of the nerve fibers. In some embodiments, energy is delivered from multiple directions and meet at the region of the nerve so as to deliver the effect.
  • In some embodiments, an external energy source delivers energy from two difference positions to focus energy on a region of interest (for example, the sympathetic nerve regions of the renal arteries).
  • In another embodiment, image detectors are embedded in the devices delivering the energy so that the imaging of the region of interest is also determined from two different angles to determine the location of the target in three dimensions.
  • In another embodiment, range finders (e.g. acoustic or sonar) are used to detect distances or positions of structures. Time of flight type analysis is the technical term to determined th distance and orietation of the blood vessel (e.g. Oraya).
  • In some embodiments, a renal artery is detected using doppler ultrasound technology. By detecting the position of the renal arteries from more than one angle via doppler triangulation, a three dimensional map can be created and the renal artery can be mapped into a coordinate reference frame. A pattern of energy can be applied to the renal artery based on the knowledge of the coordinate reference frame. Once the renal artery is placed in the coordinate frame, an algorithm is utilized to localize the delivery of focused ultrasound to heat the adventitia of the artery which contains the sympathetic nerves to the kidney and thereby decreasing the sympathetic stimulus to the kidney to potentially control hypertension, renal disease, and heart disease.
  • In one embodiment, ultrasound is passed through the posterior of a patient, avoiding the ribs and passing the ultrasound to the region of the renal arteries.
  • In other embodiments, vessels are detected via doppler ultrasound and placed in a coordinate frame to be treated with the focused energy system. For example, the carotid artery, superior mesenteric artery, aorta, vena cava, renal veins, iliac arteries, ophthalmic artery, and ciliary arteries are all arteries which are potential targets of sympathetic nerve interruption. In some embodiments, the techniques described can be applied to any other blood vessel adventitia or nerve plexus surrounding any blood vessel in the body.
  • In some embodiments, the location of the stomach is utilized because of its position overlying the celiac plexus and its position partially overlying the abdominal aorta. In this embodiment, a nasogastric tube is placed inside the stomach and can be utilized to stimulate or inhibit the celiac axis through the stomach wall using focused or non-focused energy sources.
  • In some embodiments, the celiac axis or associated nerves can also be directly ablated using energy based transducers through the stomach or through the aorta or from an external position.
  • In another embodiment, ionizing radiation is used and generated from equipment such as a megavoltage linear accelerator, proton beam accelerator, or orthovoltage X-ray generator.
  • In some embodiments, CT scan imaging or other imaging systems (for example, ultrasound), such as MRI can be used to target the region around the renal arteries where the sympathetic nerves sit.
  • In some embodiments, the ionizing radiation sources may also be coupled to CT or MRI scanners which can further aid in the identification of the region of the sympathetic nerve plexus.
  • In some embodiments, the ultrasound transducers are placed externally and the renal arteries are located in more than one axis using a doppler signal detected from the renal artery blood flow.
  • In some embodiments, an arrangement of the ultrasound transducers is such that each transducer has the ability to be moved relative to one another and with respect to the target (e.g. renal blood vessels, aorta, femoral arteries, veins etc.). Such movement allows for adjustment of focal distance and position in the X-Y plan which may change with position.
  • In some embodiments, a kidney and a renal artery, or just a kidney, is targeted with the ultrasound transducers.
  • In some embodiments, ultrasound transducers are used to detect Doppler blood flow and simulate the position of the heating spot at the focal region of the transducers. Focused ultrasound energy is then applied to the region surrounding the blood flow, utilizing the Doppler signal as the position to target.
  • In some embodiments, a three dimensional view of the renal arteries and renal pedicle is obtained using the ultrasonic images so that the heated region is simulated in three dimensions so as to avoid the critical structures around the renal pedicle such as the renal vein, adrenal artery, and the adrenal gland itself. In some embodiments, the ultrasound transducer scans the region to be treated to create a three dimensional image coordinate reference for the artery and arterial region. In some embodiments, heating of the renal vein is in fact permissible.
  • In some embodiments, a three-dimensional image of a renal artery enables precise placement of the heat generating spot because there are nerves proximal to the generated spot. In some embodiments, coupling of the renal artery doppler signal using two separate detectors allows the three dimensional coordinates of the renal artery to be determined in real space. In some embodiments, once the renal artery position is determined in real space, the 3D location of the heating via the therapeutic ultrasound transducers can be determined, in theory, quite quickly. Heating damage to organs surrounding the renal arteries can also be determined, modeled, and minimized.
  • In some embodiments, a puncture in the skin may be needed so as to take advantage of additional refinements in technology or to treat patients (e.g. obese patients) who are not amenable to completely external therapy. In this embodiment, the puncture in the skin may enable a catheter to be passed into an artery or vein and to the renal artery or vein. In some embodiments, a catheter is placed percutaneously, directly to the nerve region surrounding the vessels; that is, not transvascularly but through the skin into the retroperitoneum and to the region of the renal nerves.
  • In other embodiments, catheters may be placed through the subcutaneous tissues and into the space around the renal artery or vein. In either of these embodiments, the sympathetic nerves can be ablated or the nerve conduction pathways can otherwise be interrupted to result in a decrease in neurotransmitter release from the sympathetic terminals at the level of the kidney.
  • In addition to, or in place of, the renal sympathetic nerves, in some embodiments, it may be desirable to ablate or partially inhibit nerves which relate to the carotid or aortic baroreceptors. For example, cardiac afferent nerves have been known to dampen the carotid body response when activated which results in a loss of the parasympathetic response to elevated blood pressure. In such a scenario, the cardiac afferent nerves can be ablated so that the baroreceptor response remains sensitive to increased blood pressure and can stimulate the parasympathetic system to decrease adrenergic drive in the face of elevated blood pressure.
  • In some embodiments, the sympathetic or parasympathetic nerves leading to the eye are ablated, stimulated, partially ablated, or partially stimulated so as to control intraocular hypertension or other physiologic processes. These sympathetic nerves are well known as being causative for increases in intraocular pressure. Indeed, a best selling pharmaceutical, tenoptic, acts against the adrenergic response in the eye and so ablating the sympathetic nerves would offer a more permanent fix to the elevated intraocular blood pressure.
  • In one embodiment, the ultrasound transducers used for ablation also contain at least one imaging transducer. The imaging transducer can be utilized for quick imaging and registration with the MRI or the transducer can be utilized for detection of fiducials within the treatment region. Such fiducials can be placed in the field or may be naturally present such as for example, a Doppler flow signal in a renal artery. In one embodiment, an intravascular catheter is placed with a recognizeable beacon to indicate the position of the catheter, artery, and hence the nerves surrounding the artery.
  • In another embodiment, radiation (e.g. ionizing radiation) is applied to the region outside the artery to prevent re-growth of the sympathetic nerves after ablation.
  • In another embodiment, ablative energy is applied to a region of a fallopian tube to close the tube and prevent ovulation and transfer of ovum to a uterus.
  • In one embodiment, a method of inhibiting the function of a nerve traveling with an artery comprises; providing an external imaging modality to determine the location of the artery through the skin of a patient; placing the artery in a three dimensional coordinate reference based on the imaging; placing a therapeutic energy generation source in a three dimensional coordinate reference frame; coupling the three dimensional coordinate frame of the energy source and the artery; modeling the delivery of energy to the adventitial region of the artery or a region adjacent to the artery where a nerve travels; delivering therapeutic energy from the therapeutic energy source, from at least two different angles, through the skin of a patient, to intersect at an artery or the region adjacent to the artery to at least partially inhibit the function of a nerve.
  • In some embodiments, the imaging source is one of: ultrasound, MRI, and CT.
  • In some embodiments, the therapeutic energy is ultrasound. In some embodiments, the energy delivered to the region of the nerves is at the level of 10-100 watts/cm2 or 100-400 watts/cm2, 400-800 watts/cm2, 800-2 kW/cm2, 2-50 kW/cm2, 51-200 kW cm/2. In some instances the level is up to and exceeding 1 MW/cm2. In some embodiments, a duty cycle of 100% is utilized by the system and in some embodiments, the duty cycle is 50-99% or lower, for example, 1-49%.
  • In some embodiments, intensity is important and the dose is delivered over a period less than 2 seconds or less than 30 seconds or less than a minute. In some embodiments, the energy delivered is not heat but vibratory energy with minimal heating.
  • In some embodiments, the artery is a renal artery.
  • In some embodiments the involve placing the artery in a three dimensional reference frame involving locating the artery using a doppler ultrasound signal.
  • In some embodiments, the fiducial is placed internal to the patient.
  • In some embodiments, the fiducial is temporarily placed in a position internal to the patient.
  • In some embodiments the fiducial is a catheter placed in the artery of the patient.
  • In some embodiments the catheter is detectable using an acoustic signal and said imaging modality is ultrasound.
  • In some embodiments, the method involves therapeutic energy from the energy source which is delivered in a distribution along the length of the artery.
  • In some embodiments the therapeutic energy is ionizing radiation.
  • In some embodiments, a system to inhibit the function of a nerve traveling with a renal artery comprises a detector to determine the location of the renal artery and renal nerve through the skin of a patient; an ultrasound component to deliver therapeutic energy through the skin from at least two directions to the nerve surrounding the renal artery; a modeling algorithm comprising an input and an output said input to the modeling algorithm comprising a three dimensional coordinate space containing a therapeutic energy source and the position of the renal artery; and, the output from the modeling algorithm comprises: the direction and energy level of the ultrasound component; a locateable fiducial, adapted to be temporarily placed in the artery of a patient and communicate with the detector to determine the location of the renal artery in a three dimensional reference, the information regarding the location transmittable as the input to the model.
  • In some embodiments, the fiducial is a passive reflector of ultrasound placed inside the artery.
  • In some embodiments, the fiducial has an air interface inside a balloon. In some embodiments, the fiducial is an intravascular balloon with air inside which can be detected from outside the patient.
  • In some embodiments, the system fiducial generates radiofrequency energy which is detectable outside the patient by a detector.
  • In some embodiments, the system fiducial is activated to transmit energy based on a signal from an ultrasound generator.
  • In some embodiments, the system output from the model instructs the ultrasound component to deliver a lesion on the artery in which the major axis of the lesion is longitudinal along the length of the artery.
  • In some embodiments, the system output from the model instructs the ultrasound component to deliver multiple lesions around an artery simultaneously. In some embodiments, the energy is delivered across the kidney with the energy crossing the kidney not affecting the kidney in any way.
  • In some embodiments, the system output from the model instructs the ultrasound component to deliver a circumferential lesion around the artery in which the HIFU overlap reaches across the artery and/or vein. In some embodiments, the ultrasound overlap has a maximal diameter of about 1 cm and covering the renal artery, the renal vein, and the renal nerves. Such energy can be applied within 30 s, 11 minute, or within 3-5 minutes.
  • In some embodiments, a lesion is placed around the renal artery just proximal to the bifurcation of the artery at the hilum of the kidney.
  • In some embodiments, a lesion is placed around the artery by targeting approximately the center of the artery.
  • In some embodiments, outflow restrictions are created in the kidney or in the renal vein (for example) to indicate a high pressure state to the kidney which will lead to the kidney autoregulating system blood pressure lower.
  • In some embodiments, a clinical feedback loop is utilized in which application of energy to control hypertension is followed by an assay for the effect, the assay might include one of: ultrasound of the kidneys, assessment of microneurometry in the periphery, biopsy of the kidney, evaluation of the concentration of norepinephrine in the blood.
  • In one embodiment, a skin patch acts as a detector of sympathetic activity, the sympathetic activity being altered by heat applied to one or more regions of the autonomic nervous system.
  • DESCRIPTION OF FIGURES
  • FIGS. 1 a-b depict the focusing of energy sources on nerves of the autonomic nervous system.
  • FIG. 1 c depicts an imaging system.
  • FIG. 2 depicts targeting and/or therapeutic ultrasound delivered through the stomach to the autonomic nervous system posterior to the stomach.
  • FIG. 3 a depicts focusing of energy waves on the renal nerves
  • FIG. 3 b depicts a coordinate reference frame
  • FIG. 4 depicts the application of energy to the autonomic nervous system surrounding the carotid arteries
  • FIGS. 5 a-b depict the application of focused energy to the autonomic nervous system of the eye.
  • FIG. 6 depict the application of lesions to the kidney deep inside the calyces.
  • FIG. 7 a depicts a patient in an imaging system receiving treating with focused energy waves.
  • FIG. 7 b depicts visualization of a kidney being treated.
  • FIG. 7 depicts a close up view of the renal nerve region of the kidney being treated.
  • FIG. 7 d depicts a method to treat the autonomic nervous system using MRI and energy transducers.
  • FIG. 8 a depicts a percutaneous approach to treating the autonomic nervous system surrounding the kidneys.
  • FIG. 8 b depicts an intravascular approach to treating the autonomic nervous system.
  • FIGS. 9 a-c depicts the application of energy from inside the aorta to regions outside the aorta.
  • FIG. 10 depicts steps to treat a disease using HIFU.
  • FIG. 11 a depicts treatment of brain lesions using cross sectional imaging.
  • FIG. 11 b depicts an image on a viewer showing therapy of the region of the brain being treated.
  • FIG. 11 c depicts another view of a brain lesion.
  • FIG. 12 depicts treatment of the renal nerve region using a laparoscopic approach.
  • FIG. 13 depicts a methodology for destroying a region of tissue using imaging markers.
  • FIG. 14 depicts the partial treatment of a nerve bundle using converging imaging waves.
  • FIG. 15 depicts the application of focused energy to the vertebral column.
  • FIG. 16 depicts the types of lesions which are created around the renal arteries to affect a response.
  • FIG. 17 a depicts the application of multiple transducers to treat regions of the autonomic nervous system.
  • FIGS. 17 b-c depict methods and devices to treat a specific region surrounding an artery.
  • FIG. 17 d depicts a method for localizing HIFU transducers relative to Doppler ultrasound signals.
  • FIG. 17 e depicts an arrangement of transducers relative to a target
  • FIG. 17 f depicts ablation zones in a multi-focal region in cross-section.
  • FIG. 18 depicts the application of energy internally within the kidney.
  • FIG. 19 depicts the direction of energy wave propagation to treat regions of the autonomic nervous system around the kidney region.
  • FIG. 20 depicts the application of ultrasound waves through the wall of the aorta
  • FIG. 21 a depicts application of focused energy to the ciliary muscles and processes of the eye.
  • FIG. 21 b depicts the application of focused non-ablative energy to the back of the eye to enhance drug or gene delivery or another therapy such as ionizing radiation.
  • FIG. 22 depicts the application of focused energy to nerves surrounding the knee joint.
  • FIG. 23-b depicts the application of energy to the fallopian tube to sterilize a patient.
  • FIG. 24 depicts an algorithm to assess the effect of the neural modulation procedure on the autonomic nervous system. After a procedure is performed on the renal nerves, assessment of the autonomic response is performed by, for example, simulating the autonomic nervous system in one or more places.
  • DETAILED DESCRIPTION OF THE INVENTION
  • Hypertension is a disease of extreme national and international importance. There are 80 million patients in the US alone who have hypertension and over 200 million in developed countries worldwide. In the United States, there are 60 million patients who have uncontrolled hypertension meaning that they are either non-compliant or cannot take the medication because of the side effect profile. Up to 10 million people might have completely resistant hypertension in which they do not reach target levels no matter what the medication regimen. The morbidities associated with uncontrolled hypertension are profound, including stroke, heart attack, kidney failure, peripheral arterial disease, etc. A convenient and straightforward minimally invasive procedure to treat hypertension would be a very welcome advance in the treatment of this disease.
  • Congestive Heart Failure (“CHF”) is a condition which occurs when the heart becomes damaged and blood flow is reduced to the organs of the body. If blood flow decreases sufficiently, kidney function becomes altered, which results in fluid retention, abnormal hormone secretions and increased constriction of blood vessels. These results increase the workload of the heart and further decrease the capacity of the heart to pump blood through the kidneys and circulatory system.
  • It is believed that progressively decreasing perfusion of the kidneys is a principal non-cardiac cause perpetuating the downward spiral of CHF. For example, as the heart struggles to pump blood, the cardiac output is maintained or decreased and the kidneys conserve fluid and electrolytes to maintain the stroke volume of the heart. The resulting increase in pressure further overloads the cardiac muscle such that the cardiac muscle has to work harder to pump against a higher pressure. The already damaged cardiac muscle is then further stressed and damaged by the increased pressure. Moreover, the fluid overload and associated clinical symptoms resulting from these physiologic changes result in additional hospital admissions, poor quality of life, and additional costs to the health care system. In addition to exacerbating heart failure, kidney failure can lead to a downward spiral and further worsening kidney function. For example, in the forward flow heart failure described above, (systolic heart failure) the kidney becomes ischemic. In backward heart failure (diastolic heart failure), the kidneys become congested vis-à-vis renal vein hypertension. Therefore, the kidney can contribute to its own worsening failure.
  • The functions of the kidneys can be summarized under three broad categories: filtering blood and excreting waste products generated by the body's metabolism; regulating salt, water, electrolyte and acid-base balance; and secreting hormones to maintain vital organ blood flow. Without properly functioning kidneys, a patient will suffer water retention, reduced urine flow and an accumulation of waste toxins in the blood and body. These conditions result from reduced renal function or renal failure (kidney failure) and are believed to increase the workload of the heart. In a CHF patient, renal failure will cause the heart to further deteriorate as fluids are retained and blood toxins accumulate due to the poorly functioning kidneys. The resulting hypertension also has dramatic influence on the progression of cerebrovascular disease and stroke.
  • The autonomic nervous system is a network of nerves which affect almost every organ and physiologic system to a variable degree. Generally, the system is composed of sympathetic and parasympathetic nerves. For example, the sympathetic nerves to the kidney traverse the sympathetic chain along the spine and synapse within the ganglia of the chain or within the celiac ganglia, then proceeding to innervate the kidney via post-ganglionic fibers inside the “renal nerves.” Within the renal nerves, which travel along the renal hila (artery and to some extent the vein), are the post-ganglionic sympathetic nerves and the afferent nerves from the kidney. The afferent nerves from the kidney travel within the dorsal root (if they are pain fibers)and into the anterior root if they are sensory fibers, then into the spinal cord and ultimately to specialized regions of the brain. The afferent nerves deliver information from the kidneys back to the sympathetic nervous system via the brain; their ablation or inhibition is at least partially responsible for the improvement seen in blood pressure after renal nerve ablation, or dennervation, or partial disruption. It has also been suggested and partially proven experimentally that the baroreceptor response at the level of the carotid sinus is mediated by the renal artery afferent nerves such that loss of the renal artery afferent nerve response blunts the response of the carotid baroreceptors to changes in arterial blood pressure.
  • It has been established in animal models that the heart failure condition results in abnormally high sympathetic activation of the kidneys. An increase in renal sympathetic nerve activity leads to decreased removal of water and sodium from the body, as well as increased renin secretion which stimulates aldosterone secretion from the adrenal gland. Increased renin secretion can lead to vasoconstriction of blood vessels supplying the kidneys, which leads to a decrease in renal blood flow. Reduction in sympathetic renal nerve activity, e.g., via de-innervation, may reverse these processes. Similarly, in obese patients, the sympathetic drive is very high and is felt to be one of the causes of hypertension in obese patients.
  • Recent clinical work has shown that de-innervation of the renal sympathetic chain and other nerves which enter the kidney through the hilum can lead to profound systemic effects in patients with hypertension, heart failure, and other organ system diseases. Such treatment can lead to long term reduction in the need for blood pressure medications and improvements in blood pressure (O'Brien Lancet 2009 373; 9681 incorporated by reference). The devices used in this trial were highly localized radiofrequency (RF) ablation to ablate the renal artery adventitia with the presumption that the nerves surrounding the renal artery are being inhibited in the heating zone as well. The procedure is performed in essentially a blind fashion in that the exact location of the nerve plexus is not known prior to, during, or after the procedure. In addition, the wall of the renal artery is invariably damaged by the RF probe and patients whose vessels have a great deal of atherosclerosis cannot be treated safely. In addition, depending on the distance of the nerves from the vessel wall, the energy may not consistently lead to ablation or interruption. Finally, the use of internal catheters may not allow for treatment inside the kidney or inside the aorta if more selective or less selective blockade of the renal sympathetic nerves is desired.
  • Ultrasound is a cyclically generated sound pressure wave with a frequency greater than the upper limit of human hearing . . . 20 kilohertz (kHz). In medicine, ultrasound is widely utilized because of its ability to penetrate tissues. Reflection of the sound waves reveals a signature of the underlying tissues and as such, ultrasound can be used extensively for diagnostics and potentially therapeutics as well in the medical field. As a therapy, ultrasound has the ability to both penetrate tissues and can be focused to create ablation zones. Because of its simultaneous ability to image, ultrasound can be utilized for precise targeting of lesions inside the body. Ultrasound intensity is measured by the power per cm2. Generally, high intensity refers to intensities over 1 kW/cm2. Low intensity ultrasound encompasses the rage up to 1 kW/cm2 from about 1 or 10 Watts per cm2.
  • Ultrasound can be utilized for its forward propagating waves and resulting reflected waves or where energy deposition in the tissue and either heating or slight disruption of the tissues is desired. For example, rather than relying on reflections for imaging, lower frequency ultrasonic beams (e.g. <1 MHz) can be focused at a depth within tissue, creating a heating zone or a defined region of cavitation in which micro-bubbles are created, cell membranes are opened to admit bioactive molecules, or damage is otherwise created in the tissue. These features of ultrasound generally utilize frequencies in the 0.25 Megahertz (MHz) to 10 MHz range depending on the depth required for effect. Focusing is or may be required so that the surface of the tissue is not excessively injured or heated by single beams. In other words, many single beams can be propagated through the tissue at different angles to decrease the energy deposition along any single path yet allow the beams to converge at a focal spot deep within the tissue. In addition, reflected beams from multiple angles may be utilized in order to create a three dimensional representation of the region to be treated in a coordinate space.
  • Time of flight measurements with ultrasound can be used to range find, or find distances between objects in tissues. Such measurements can be utilized to place objects such as vessels into three dimensional coordinate reference frames so that energy can be utilized to target the tissues. SONAR is the acronym for sound navigation and ranging and is a method of acoustic localization. Sound waves are transmitted through a medium and the time for the sound to reflect back to the transmitter is indicative of the position of the object of interest. Doppler signals are generated by a moving object. The change in the forward and reflected wave results in a velocity for the object.
  • Lithotripsy was introduced in the early part of the 1980's. Lithotripsy utilizes shockwaves to treat stones in the kidney. The Dournier lithotripsy system was the first system produced for this purpose. The lithotripsy system sends ultrasonic waves through the patient's body to the kidney to selectively heat and vibrate the kidney stones; that is, selectively over the adjacent tissue.
  • Histotripsy is a term given to a technique in which tissue is essentially vaporized using cavitation rather than heating (transcutaneous non-thermal mechanical tissue fractionation). These mini explosions do not require high temperature and can occur in less than a second. The generated pressure wave is in the range of megapascals (MPa) and even up to or exceeding 100 MPa. To treat small regions of tissue very quickly, this technique can be very effective. The border of the viable and non-viable tissue is typically very sharp and the mechanism of action has been shown to be cellular disruption.
  • Cross-sectional imaging is utilized to visualize the internal anatomy of patients via radiation (CT) or magnetic fields (MRI). Ultrasound can also be utilized to obtain cross-sections of specific regions but only at high frequencies; therefore, ultrasound is typically limited to imaging superficial body regions. CT and MRI are often more amenable to cross sectional imaging because the radiation penetrates well into tissues. In addition, the scale of the body regions is maintained such that the anatomy within the coordinate references remains intact relative to one another; that is, distances between structures can be measured.
  • With ultrasound, scaling can be more difficult because of unequal penetration as the waves propagate deeper through the tissue. CT scans and MRIs and even ultrasound devices can be utilized to create three dimensional representations and reconstructed cross-sectional images of patients; anatomy can be placed in a coordinate reference frame using a three dimensional representation. Once in the reference frame, energy devices (transducers) can be placed in positions and energy emitting devices directed such that specific regions of the body are targeted. Once knowledge of the transducer position is known relative to the position of the target in the patient body, energy can be delivered to the target.
  • In one embodiment, ultrasound is focused on the region of the renal arteries or veins from outside the patient; the ultrasound is delivered from multiple angles to the target, allowing the current invention to overcome many of the deficiencies in previous methods and devices put forward to ablate renal sympathetic nerves which surround the renal arteries.
  • Specifically, one embodiment of this invention allows for precise visualization of the ablation zone so that the operator can be confident that the correct region is ablated and that the incorrect region is not ablated. Because some embodiments do not require a puncture in the skin, they are considerably less invasive, which is more palatable and safer from the patient standpoint. Moreover, unusual anatomies and atherosclerotic vessels can be treated using external energy triangulated on the renal arteries to affect the sympathetic and afferent nerves to and from the kidney respectively.
  • With reference to FIG. 1A, the human renal anatomy includes the kidneys 100 which are supplied with oxygenated blood by the renal arteries 200 and are connected to the heart via the abdominal aorta 300. Deoxygenated blood flows from the kidneys to the heart via the renal veins (not shown) and thence the inferior vena cava (not shown). The renal anatomy includes the cortex, the medulla, and the hilum. Blood is delivered to the cortex where it filters through the glomeruli and is then delivered to the medulla where it is further filtered through a series of reabsorption and filtration steps in the loops of henle and individual nephrons; the ultrafiltrate then percolates to the ureteral collecting system and is delivered to the ureters and bladder for ultimate excretion.
  • The hila is the region where the major vessels (renal artery and renal vein) and nerves 150 (efferent sympathetic, afferent sensory, and parasympathetic nerves) travel to and from the kidneys. The renal nerves 150 contain post-ganglionic efferent nerves which supply sympathetic innervation to the kidneys.
  • Energy transducers 500 (FIG. 1 a) deliver energy transcutaneously to the region of the sympathetic ganglia 520 or the post-ganglionic renal nerves 150 or the nerves leading to the adrenal gland 400. The energy is generated from outside the patient, from multiple directions, and through the skin to the region of the renal nerves 150 which surround the renal artery 640. The energy can be focused or non-focused but in one preferred embodiment, the energy is focused with high intensity focused ultrasound (HIFU). Focusing with low intensity focused ultrasound (LIFU) may also occur. Focusing occurs by delivering energy from at least two different angles through the skin to meet at a focal point where the highest energy intensity and density occurs. At this spot, a therapy is delivered and the therapy can be sub-threshold nerve interruption (partial ablation), ablation (complete interruption) of the nerves, controlled interruption of the nerve conduction apparatus, partial ablation, or targeted drug delivery. The region can be heated to a temperature of less than 60 degrees for non-ablative therapy or can be heated greater than 60 degrees for heat based destruction (abalation). To ablate the nerves, even temperatures in the 40 degree range can be used and if generated for a time period greater than several minutes, will result in ablation. Heating aside, a vibratory effect for a much shorter period of time at temperatures below 60 degrees Celsius can result in partial or complete paralysis of destruction of the nerves. If the temperature is increased beyond 50-60 degrees, the time required for heating is decreased considerably to affect the nerve via the sole mechanism of heating. In some embodiments, an imaging modality is included as well in the system. The imaging modality can be ultrasound based, MRI based, CT (Xray) based. The imaging modality can be utilized to target the region of ablation and determined the distances to the target.
  • The delivered energy can be ionizing or non-ionizing energy. Forms of non-ionizing energy can include electromagnetic energy (e.g. a magnetic field, light, an electric field), radiofrequency energy, and light based energy. Forms of ionizing energy include x-ray, proton beam, gamma rays, electron beams, and alpha rays. In some embodiments, the energy modalities are combined. For example, heat ablation of the nerves is performed and then ionizing radiation is delivered to the region to prevent re-growth of the nerves.
  • Alternatively, ionizing radiation is applied first as an ablation modality and then heat applied afterward in the case of re-growth of the tissue as re-radiation may not be possible (complement energy utilization). Ionizing radiation may prevent or inhibit the re-growth of the nervous tissue around the vessel if there is indeed re-growth of the nervous tissue. Therefore, another method of treating the nerves is to first heat the nerves and then apply ionizing radiation to prevent re-growth.
  • In some embodiments, external neuromodulation is performed in which low energy ultrasound is applied to the nerve region to modulate the nerves. For example, it has been shown in the past that low intensity (e.g. non-thermal) ultrasound can affect nerves at powers which range from 30-500 mW/Cm2 whereas HIFU (thermal modulation), by definition generates heat at a focus, requires power levels exceeding 1000 W/Cm2. The actual power flux to the region to be ablated is dependent on the environment including surrounding blood flow and other structures. With low intensity ultrasound, the energy does not have to be so strictly focused to the target because it's a non-ablative energy; that is, the vibration or mechanical pressure may be the effector energy and the target may have a different threshold for effect depending on the tissue. However, even low energy ultrasound may require focusing if excessive heat to the skin is a worry or if there are other susceptible structures in the path and only a pinpoint region of therapy is desired. Nonetheless, transducers 500 in FIG. 1 a provide the ability to apply a range of different energy and power levels as well as modeling capability to target different regions and predict the response.
  • In FIG. 1 a, and in one embodiment, a renal artery is detected 640 with the assistance of imaging techniques 600 such as Doppler ultrasound, B-mode ultrasound, MRI, or a CT scan. With an image of the region to be treated, measurements in multiple directions on a series of slices can be performed so as to create a three-dimensional representation of the area of interest. By detecting the position of the renal arteries from more than one angle via Doppler triangulation (for example) or another triangulation technique, a three dimensional positional map can be created and the renal artery can be mapped into a coordinate reference frame. In this respect, given that the renal nerves surround the renal blood vessels in the hilum, locating the direction and lengths of the blood vessels in three dimensional coordinate reference is the predominant component of the procedure to target the sympathetic nerves. Within the three dimensional reference frame, a pattern of energy can be applied to the vicinity of the renal artery from a device well outside the vicinity (and outside of the patient altogether) based on knowledge of the coordinate reference frame.
  • For example, once the renal artery is placed in the coordinate reference frame with the origin of the energy delivery device, an algorithm is utilized to localize the delivery of focused ultrasound to heat or apply mechanical energy to the adventitia and surrounding regions of the artery which contain sympathetic nerves to the kidney and afferent nerves from the kidney, thereby decreasing the sympathetic stimulus to the kidney and its afferent signaling back to the autonomic nervous system; affecting these targets will modulate the propensity toward hypertension which would otherwise occur. The ultrasonic energy delivery can be modeled mathematically by predicting the wave dissipation using the distances and measurements taken with the imaging modalities of the tissues and path lengths.
  • In one embodiment of an algorithm, the Doppler signal from the artery is identified from at least two different directions and the direction of the artery is reconstructed in three dimensional space. With two points in space, a line is created and with knowledge of the thickness of the vessel, a tube, or cylinder, can be created to represent the blood vessel as a virtual model. The tube is represented in three dimensional space over time and its coordinates are known relative to the therapeutic transducers outside of the skin of the patient. Therapeutic energy can be applied from more than one direction as well and can focus on the cylinder (blood anterior vessel wall, central axis, or posterior wall.
  • Focused energy (e.g. ultrasound) can be applied to the center of the vessel (within the flow), on the posterior wall of the vessel, in between (e.g. when there is a back to back artery and vein next to one another) the artery vessel and a venous vessel, etc.
  • Imaging 600 of the sympathetic nerves or the sympathetic region (the target) is also utilized so as to assess the direction and orientation of the transducers relative to the target 620. Continuous feedback of the position of the transducers 500 relative to the target 620 is provided by the imaging system in which the coordinate space of the imaging system. The imaging may be a cross-sectional imaging technology such as CT or MRI or it may be an ultrasound imaging technology which yields faster real time imaging. In some embodiments, the imaging may be a combination of technologies such as the fusion of MRI/CT and ultrasound. The imaging system can detect the position of the target in real time at frequencies ranging from 1 hz to thousands and tens of thousands of images per second.
  • In the example of fusion, cross-sectional imaging (e.g. MRI/CT) is utilized to place the body of the patient in a three dimensional coordinate frame and then ultrasound is linked to the three dimensional reference frame and utilized to track the patient's body in real time under the ultrasound linked to the cross-sectional imaging. The lack of resolution provided by the ultrasound is made up for by the cross-sectional imaging since only a few consistent anatomic landmarks are required for an ultrasound image to be linked to the MRI image. As the body moves under the ultrasound, the progressively new ultrasound images are linked to the MRI images and therefore MRI “movement” can be seen at a frequency not otherwise available to an MRI series.
  • In one embodiment, ultrasound is the energy used to inhibit nerve conduction in the sympathetic nerves. In one embodiment, focused ultrasound (HIFU) from outside the body through the skin is the energy used to inhibit sympathetic stimulation of the kidney by delivering waves from a position external to the body of a patient and focusing the waves on the sympathetic nerves on the inside of the patient and which surround the renal artery of the patient.
  • As is depicted in FIG. 3, transducers 900 can emit ultrasound energy to the region of the renal sympathetic nerves at the renal pedicle. As shown in FIG. 1 a, an image of the renal artery 620 using an ultrasound, MRI, or CT scan can be utilized to determine the position of the kidney 610 and the renal artery 620 target. Doppler ultrasound can be used to determine the location and direction of a Doppler signal from an artery and therefore enable the arteries 200 and hence the sympathetic nerves 220 (FIG. 3 a) around the artery to be much more visible so as to process the images and then utilize focused external energy to pinpoint the location and therapy of the sympathetic nerves. In this embodiment, ultrasound is likely the most appropriate imaging modality.
  • FIG. 1 a also depicts the delivery of focused energy to the sympathetic nerve trunks which run along the vertebral column; the renal artery efferent nerves travel in these trunks and synapse to ganglia within the trunks. In another embodiment, ablation of the dorsal roots at the level of the ganglia or dorsal root nerves at T9-T11 (through which the afferent renal nerves travel) would produce the same or similar effect to ablation at the level of the renal arteries.
  • FIG. 1 b illustrates the application of ionizing energy to the region of the sympathetic nerves on the renal arteries 620 or renal veins. In general, energy levels of greater than 20 Gy (Gray) are required for linear accelerators or low energy x-ray machines to ablate nervous tissue using ionizing energy; however, lower energy is required to stun, inhibit nervous tissue, or prevent re-growth of nervous tissue; in some embodiment, energy levels as low as 2-5 Gy or 5-10 Gy or 10-15 Gy are delivered in a single or fractionated doses.
  • Combinations of ionizing energy and other forms of energy can be utilized in this embodiment as well so as to prevent re-growth of the nervous tissue. For example, a combination of heat and/or vibration and/or cavitation and/or ionizing radiation might be utilized to prevent re-growth of nervous tissue after the partial or full ablation of the nervous tissue surrounding the renal artery.
  • FIG. 2 illustrates the renal anatomy and surrounding anatomy with greater detail in that organs such as the stomach are shown in its anatomic position overlying the abdominal aorta and renal arteries. In this embodiment, energy is delivered through the stomach to reach an area behind the stomach. In this embodiment, the stomach is utilized as a conduit to access the celiac ganglion, a region which would otherwise be difficult to reach. The aorta 705 is shown underneath the stomach and the celiac ganglion 710 is depicted surrounding the superior mesenteric artery and aorta. A transorally placed tube 720 is placed through the esophagus and into the stomach. The tube overlies the celiac ganglion when placed in the stomach and can therefore be used to deliver sympatholytic devices or pharmaceuticals which inhibit or stimulate the autonomic celiac ganglia behind the stomach; these therapies would be delivered via transabdominal ultrasound or fluoroscopic guidance (for imaging) through the stomach. Similar therapies can be delivered to the inferior mesenteric ganglion, renal nerves, or sympathetic nerves traveling along the aorta through the stomach or other portion of the gastrointestinal tract. The energy delivery transducers 730,731 are depicted external to the patient and can be utilized to augment the therapy being delivered through the stomach to the celiac ganglion.
  • Temporary neurostimulators can also be placed through the tube, such as, for example, in an ICU setting where temporary blockage of the autonomic ganglia may be required. Temporary neurostimulators can be used to over pace the celiac ganglion nerve fibers and inhibit their function as a nerve synapse. Inhibition of the celiac ganglion may achieve a similar function as ablation or modulation of the sympathetic nerves around the renal arteries. That is, the decrease in the sympathetic activity to the kidneys (now obtained with a more proximal inhibition) leads to the lowering of blood pressure in the patient by decreasing the degree of sympathetic outflow from the sympathetic nerve terminals. In the celiac ganglia, the blood pressure lowering effect is more profound given that the celiac ganglia are pre-ganglionic and have more nerve fibers to a greater number of regions than each renal nerve. The effect is also likely more permanent than the effect on the post-ganglionic nerve fibers.
  • FIG. 3 a illustrates the renal anatomy more specifically in that the renal nerves 220 extending longitudinally along the renal artery 200, are located generally within, or just outside the adventitia, of the outer portion of the artery. Arteries are typically composed of three layers: the first is the intimal, the second is the media, and the third is the adventitia. The outer layer, the adventitia, is a fibrous tissue which contains blood vessels and nerves. The renal nerves are generally postganglionic sympathetic nerves although there are some ganglia which exist distal to the takeoff from the aorta such that some of the nerve fibers along the renal artery are in fact pre-ganglionic. By the time the fibers reach the kidney, the majority of the fibers are post-ganglionic.
  • Energy generators 900 deliver energy to the renal nerves accompanying the renal artery, depositing energy from multiple directions to target inhibition of the renal nerve complex. The energy generators can deliver ultrasound energy, ionizing radiation, light (photon) therapy, or microwave energy to the region. The energy can be non-focused in the case where a pharmaceutical agent is targeted to the region to be ablated or modulated. Preferably, however, the energy is focused, being applied from multiple angles from outside the body of the patient to reach the region of interest (e.g. sympathetic nerves surrounding blood vessels). The energy transducers 900 are placed in an X-Y-Z coordinate reference frame 950, as are the organs such as the kidneys. Once in the coordinate reference frame, cross-sectional imaging using MRI, CT scan, and/or ultrasound is utilized to couple the internal anatomy to the energy transducers. The transducers 900 in this embodiment are focused on the region of the renal nerves at the level of the renal blood vessels, the arteries and veins.
  • When applying ultrasonic energy across the skin to the renal artery region, energy densities of potentially over 1 MW/cm2 might be required so as to reach the region of interest. The energy may be pulsed across the skin in an unfocused manner; however, for application of heat, the transducers must be focused otherwise the skin and underlying tissues will receive too much heat. Under imaging with MRI, temperature can be measured with the MRI image. When low energy ultrasound is applied to the region, energy densities in the range of 50 mW/cm2 to 500 mW/cm2 may be applied. Low energy ultrasound may be enough to stun or partially inhibit the renal nerves. High intensity ultrasound applied to the region with only a few degrees of temperature rise may have the same effect and this energy range may be in the 0.5 kW/cm2 to the 500 kW/cm2 range. In some of the embodiments, cooling may be applied to the skin if the temperature rise is deemed too large to be acceptable. Alternatively, the ultrasound transducers can be pulsed or can be alternated with another set of transducers to effectively spread the heat across the surface of the skin.
  • In one method of altering the physiologic process of renal sympathetic excitation, the region around the renal arteries is imaged using CT scan, MRI, thermography, infrared imaging, optical coherence tomography (OCT), photoacoustic imaging, pet imaging, SPECT imaging, or ultrasound, and the images are placed into a three dimensional coordinate reference frame. Energy transducers which can deliver ultrasound, light, radiation, ionizing radiation, or microwave energy are placed in the same three-dimensional reference frame as the renal arteries at which time an algorithm can determine how to direct the transducers to deliver energy to the region of the nerves. The algorithm consists of a targeting feature (planning feature) which allows for prediction of the position and energy deposition of the energy leaving the transducer. Once the three dimensional coordinate reference frames are linked or coupled, the planning and prediction algorithm can be used to precisely position the energy beams at a target in the body.
  • The original imaging utilized to locate the renal sympathetic region can be used to track the motion of the region during treatment. For example, the imaging technology used at time zero is taken as the baseline scan and subsequent scans at time t1 are compared to the baseline scan. The frequency of updates can range from a single scan every few seconds to many scans per second. With ultrasound as the imaging technology, the location might be updated at a frame rate greater than 50 Hz and up to several hundred Hz or thousand Hz. With MRI as the imaging modality, the imaging refresh rate might be closer to 30 Hz. In other embodiments, internally placed fiducials transmit positional information at a high frequency and this information is utilized to fuse the target with an initial external imaging apparatus. Internal fiducials might be one more imageable elements including doppler signal, regions of blood vessels, ribs, kidneys, blood vessels other than the target (e.g. vena cava). These fiducials can be used to track the region being treated and/or to triangulate to the region to be treated.
  • A test dose of energy can be applied to the renal sympathetic region and then a test performed to determine if an effect was created. For example, a small amount of heat can be delivered to the region of the sympathetic nerves and then a test of sympathetic activity such as microneurometry (detection of sympathetic nerve activity around muscles and nerves which correlate with the beating heart) can be performed. Past research and current clinical data have shown that the sympathetic nerves to the peripheral muscles are affected by interruption of the renal afferent nerves. The temperature rise with the small degree of heat can be determined through the use of MRI thermometry and the temperature rise can be determined or limited to an amount which is reversible.
  • Alternatively, ultrasonic imaging can be utilized to determine the approximate temperature rise of the tissue region. The speed of ultrasonic waves is dependent on temperature and therefore the relative speed of the ultrasound transmission from a region being heated will depend on the temperature, therefore providing measureable variables to monitor. In some embodiments, microbubbles are utilized to determine the rise in temperature. Microbubbles expand and then degrade when exposed to increasing temperature so that they can then predict the temperature of the region being heated. A technique called ultrasound elastography an also be utilized. In this embodiment, the elastic properties of tissue are dependent on temperature and therefore the elastography may be utilized to track features of temperature change. The microbubbles can also be utilized to augment the therapeutic effect of the region being targeted. For example, the microbubbles can be utilized to release a pharmaceutical when the ultrasound reaches them.
  • In another embodiment, a test may be performed on the baroreceptor complex at the region of the carotid artery bifurcation. After the test dose of energy is applied to the renal artery complex, pressure can be applied to the carotid artery complex; typically, with an intact baroreceptor complex, the systemic blood pressure would decrease after application of pressure to the carotid artery. However, with renal afferent nerves which have been inhibited, the baroreceptors will not be sensitive to changes in blood pressure and therefore the efficacy of the application of the energy to the renal nerves can be determined.
  • Other regions of the autonomic nervous system can also be affected directly by the technology in this invention by applying energy from one region to another. For example, FIG. 4 illustrates a system in which external energy 1020 is applied to a portion of the autonomic nervous system, the carotid body complex 1000, through the internal jugular vein 1005, and to the carotid body 1000 and/or vagus nerve 1020 region. Ablative energy or electrical stimulation energy can be utilized to affect the transmission of signals to and from these nerves. The transmission in this complex can be augmented, interrupted, inhibited with over-stimulation, or a combination of these effects via energy (e.g. ultrasound, electrical stimulation, etc.)
  • A catheter 1010 is advanced into the internal jugular vein 1005 and when in position, stimulation or ablative energy 1020 is directed toward the autonomic nerves, the vagus nerve, and the carotid sinus from the catheter positioned in the venous system. A similar type of catheter can be inserted into the region of the renal arteries or renal veins to stimulate or inhibit the renal nerves from the inside of the vessel. For example, a catheter delivering unfocused ultrasound energy in the range of 50 mW/cm2 to 50 W/cm2 can be placed into the renal artery and the energy transmitted radially around the artery to the nerves.
  • This therapy can be delivered on an acute basis such as for example in an ICU or critical care setting. In such a case, the therapy would be acute and intermittent, with the source outside the patient and the catheter within the patient as shown in FIG. 4. The therapy can be utilized during times of stress for the patient such that the sympathetic system is slowed down. After the intensive care admission is nearing a close, the catheter and unit can be removed from the patient.
  • FIGS. 5 a-b illustrates the eye in close up detail with sympathetic nerves surrounding the posterior of the eye. In the eye, glaucoma is a problem of world-wide importance. The most commonly prescribed medication to treat glaucoma is timoptic, which is a non-selective β1 and β2 (adrenergic) antagonist. Compliance with this pharmaceutical is a major problem and limits its effectiveness in preventing the complications of glaucoma, the major complication being progression of visual dysfunction.
  • Ultrasound, or other energy transducers 7000, can be applied to focus energy from an external region (e.g. a distance from the eye in an external location) anterior to the eye or to a region posteriorly behind the eye 2500 on the sympathetic 2010 or parasympathetic ganglia, all of which will affect lowering of intra-ocular pressure. The energy transducers 700 apply ablative or near ablative energy to the adventitia of the blood vessel. In some embodiments, the energy is not ablative but vibratory at frequencies and penetration depths sufficient to inhibit the function of the nerves which are responsible for intra-ocular pressure.
  • FIG. 5 b depicts the anatomy behind the eye. In this illustration, a catheter 2000 is tunneled through the vasculature to the region of the sympathetic nerves surrounding the arteries of the eye 2010 and utilized to ablate, stun, or otherwise modulate the efferent and/or afferent nerves through the wall of the vasculature.
  • FIG. 6 illustrates an overall schematic of the renal artery, renal vein, the collecting system, and the more distal vessels and collecting system within the renal parenchyma. The individual nerves of the autonomic nervous system typically follow the body vasculature and they are shown in close proximity 3000 to the renal artery as the artery enters the kidney 3100 proper. Any one or multiple of these structures can influence the function of the kidney. Ablative or non-ablative energy can be applied to the renal vein, the renal artery, the aorta or the vena cava, the renal hilum, the renal parenchyma, the renal medulla, the renal cortex, etc.
  • In one embodiment, selective lesions, constrictions or implants 3200 are placed in the calyces of the kidney to control or impede blood flow to specific regions of the kidney. Such lesions or implants can be placed on the arterial 3010 or venous sides 3220 of the kidney. In some embodiments, the lesions/implants are created so as to selectively block certain portions of the sympathetic nerves within the kidney. The lesions also may be positioned so as to ablate regions of the kidney which produce hormones, such as renin, which can be detrimental to a patient in excess. The implants or constrictions can be placed in the aorta 3210 or the renal vein 3220. The implants can be active implants, generating stimulating energy chronically or multiple ablative or inhibitory doses discretely over time.
  • In the renal vein, the implants might cause an increase in the pressure within the kidney which will prevent the downward spiral of systolic heart failure described above. That is, once the pressure in the kidney is restored or artificially elevated by increased venous pressure, the relative renal hypotension signaling to retain electrolytes and water will not be present any longer and the kidney will “feel” full and the renal sympathetic stimulation will be turned off. In one embodiment, a stent which creates a stenosis is implanted using a catheter delivery system 3000. In another embodiment, a stricture is created using heat delivered either externally or internally. In one embodiment, an implant is placed between girota's fascia and the cortex of the kidney.
  • FIG. 7 a depicts at least partial ablation of the renal sympathetic nerves 4400 to the kidney using an imaging system such as an MRI machine or CT scanner 4000. The MRI/CT scan can be linked to a focused ultrasound (HIFU) machine to perform the ablations of the sympathetic nerves 4400 around the region of the renal artery 4500. The MRI/CT scan performs the imaging 4010 and transmits data (e.g. three dimensional representations of the regions of interest) to the ultrasound controller which then directs the ultrasound to target the region of interest with low intensity ultrasound (50-1000 mW/cm2) heat (>1000 mW/cm2), cavitation, or a combination of these modalities and/or including introduction of enhancing agents locally or systemically (sonodynamic therapy). Optionally, a doppler ultrasound or other 3D/4D ultrasound is performed and the data pushed to the MRI system to assist with localization of the pathology; alternatively, the ultrasound data are utilized to directly control the direction of the energy being used to target the physiologic processes and CT/MRI is not obtained. Using this imaging and ablation system from a position external to a patient, many regions of the kidney can be treated such as the internal calyces, the cortex, the medulla, the hilum and the region near to the aorta.
  • Further parameters which can be measured include temperature via thermal spectroscopy using MRI or ultrasound thermometry/elastography; thermal imaging is a well-known feature of MRI scanners; the data for thermal spectroscopy exists within the MRI scan and can be extrapolated from the recorded data in real time by comparing regions of interest before and after or during treatment. Temperature data overlaid on the MRI scan enables the operator of the machine to visualize the increase in temperature and therefore the location of the heating to insure that the correct region has indeed been ablated and that excessive energy is not applied to the region. Having temperature data also enables control of the ablation field as far as applying the correct temperature for ablation to the nerves. Furthermore, other spectroscopic parameters can be determined using the MRI scan such as oxygenation, blood flow, or other physiologic and functional parameters. In one embodiment, an alternating magnetic field is used to over-stimulate or inhibit an autonomic nerve (e.g. to or from the kidney).
  • Elastography is a technique in which the shear waves of the ultrasound beam and reflectance are detected. The tissue characteristics change as the tissue is heated and the tissue properties change. An approximate temperature can be assigned to the tissue based on elastography and the progress of the heating can be monitored.
  • MRI scanners 4000 generally consist of a magnet and an RF coil. The magnet might be an electromagnet or a permanent magnet. The coil is typically a copper coil which generates a radiofrequency field. Recently, permanent magnets have been utilized to create scanners which are able to be used in almost any setting, for example a private office setting. Office based MRI scanners enable imaging to be performed quickly in the convenience of a physicians offices as well as requiring less magnetic force (less than 0.5 Tesla) and as a consequence, less shielding. The lower tesla magnets also provides for special advantages as far as diversity of imaging and resolution of certain features. Importantly, the permanent magnet MRI scanners are open scanners and do not encapsulate the patient during the scan.
  • In one embodiment, a permanent magnet MRI is utilized to obtain an MRI image of the region of interest 4010. High intensity focused 4100 ultrasound is used to target the region of interest 4600 identified using the MRI.
  • Image 4010 is monitored by a health care professional to ensure that the region of interest is being treated and can stop the therapy if the region is not being treated. Alternatively, an imaging algorithm can be initiated in which the region of interest is identified and then subsequent images are compared to the initial demarcated region of interest.
  • Perhaps, most importantly, with MRI, the region around the renal arteries can be easily imaged as can any other region such as the eye, brain, prostate, breast, liver, colon, spleen, aorta, hip, knee, spine, venous tree, and pancreas. The imaging from the MRI can be utilized to precisely focus the ultrasound beam to the region of interest around the renal arteries or elsewhere in the body. With MRI, the actual nerves to be modified or modulated can be directly visualized and targeted with the energy delivered through the body from the ultrasound transducers. One disadvantage of MRI can be the frame acquisition (difficulty in tracking the target) rate as well as the cost of introducing an MRI machine into the treatment paradigm.
  • FIG. 7 b depicts a method of treating a region with high intensity focused ultrasound (HIFU). Imaging with an MRI 4520 or Doppler ultrasound 4510 (or preferably both) is performed. MRI can be used to directly or indirectly (e.g. using functional MRI or spectroscopy) to visualize the sympathetic nerves. T1 weighted or T2 weighted images can be obtained using the MRI scanner. In addition to anatomic imaging, the MRI scanner can also obtain temperature data regarding the effectiveness of the ablation zone as well as the degree to which the zone is being heated and which parts of the zones are being heated. Other spectroscopic parameters can be added as well such as blood flow and even nerve activity. Ultrasound can be used to add blood flow to the images using Doppler imaging. The spectroscopic data can be augmented by imaging moieties such as particles, imaging agents, or particles coupled to imaging agents which are injected into the patient intravenously, or locally, and proximal to the region of the renal arteries; these imaging moieties may be visualized on MRI, ultrasound, or CT scan. Ultrasound can also be utilized to determine information regarding heating. The reflectance of the ultrasonic waves changes as the temperature of the tissue changes. By comparing the initial images with the subsequent images after heating, the temperature changes can be determined.
  • In one embodiment, the kidneys are detected by a cross-sectional imaging modality such as MRI, ultrasound, or CT scan. Next, the imaging data is placed into a three dimensional coordinate system which is linked to one or more ultrasound (e.g. HIFU) transducers which focus ultrasound onto the region of the renal arteries in the coordinate frame. The linking, or coupling, of the imaging to the therapeutic transducers is accomplished by determining the 3 dimensional position of the target by creating an anatomic model. The transducers are placed in a relative three dimensional coordinate frame as well. For example, the transducers can be placed in the imaging field during the MRI or CT scan such that the cross-sectional pictures include the transducers.
  • Alternatively, in another embodiment, ultrasound is utilized and the ultrasound image can be directly correlated to the origin of the imaging transducer. The therapeutic transducer in some embodiments is the same as the imaging transducer and therefore the therapeutic transducer is by definition coupled in a coordinate reference once the imaging transducer coordinates are known. If the therapeutic transducer and the imaging transducer are different devices, then they can be coupled by knowledge of the relative position of the two devices. The region of interest (ROI) is highlighted in a software algorithm . . . for example, the renal arteries, the calyces, the medullary region, the cortex, the renal hila, the celiac ganglia, the aorta, or any of the veins of the venous system as well. In another embodiment, the adrenal gland, the vessels traveling to the adrenal gland, or the autonomic nerves traveling to the adrenal gland are targeted with focused ultrasound and then either the medulla or the cortex of the adrenal gland or the nerves and arteries leading to the gland are partially or fully ablated with ultrasonic energy.
  • The targeting region or focus of the ultrasound is the point of maximal intensity. In some embodiments, targeting focus is placed in the center of the artery such that the walls on either side receive equivalent amounts of energy or power and can be heated more evenly than if one wall of the blood vessel is targeted. In some embodiments in which a blood vessel is targeted which has a closely surrounding vein (e.g. the renal artery/vein pedicle), the center of the focus might be placed at the boundary of the vein and the artery.
  • Once the transducers are energized after the region is targeted, the tissue is heated 4560 and a technique such as MRI thermography 4570 or ultrasound thermography is utilized to determine the tissue temperature. During the assessment of temperature, the anatomic data from the MRI scan or the Doppler ultrasound is then referenced to ensure the proper degree of positioning and the degree of energy transduction is again further assessed by the modeling algorithm 4545 to set the parameters for the energy transducers 4550. If there is movement of the target, the transducers may have to be turned off and the patient repositioned.
  • Ablation can also be augmented using agents such as magnetic nanoparticles or liposomal nanoparticles which are responsive to a radiofrequency field generated by a magnet. These particles can be selectively heated by the magnetic field. The particles can also be enhanced such that they will target specific organs and tissues using targeting moieties such as antibodies, peptides, etc. In addition to the delivery of heat, the particles can be activated to deliver drugs, bioactive agents, or imaging agents at the region at which action is desired (e.g. the renal artery). The particles can be introduced via an intravenous route, a subcutaneous route, or a percutaneous route.
  • The addition of Doppler ultrasound 4510 may be provided as well. The renal arteries are (if renal arteries or regions surrounding the arteries are the target) placed in a 3D coordinate reference frame 4530 using a software algorithm with or without the help of fiducial markers. Data is supplied to ultrasound transducers 4540 from a heat modeling algorithm 4545 and the transducers are energized with the appropriate phase and power to heat the region of the renal artery to between 40 degrees C. and 90 degrees C. within a time span of several minutes. The position within the 3D coordinate reference is also integrated into the treatment algorithm so that the ultrasound transducers can be moved into the appropriate position. The ultrasound transducers may have frequencies below 1 megahertz (MHz), from 1-20 MHz, or above 30 Mhz. The transducers may be in the form of a phased array, either linear or curved, or the transducers may be mechanically moved so as to focus ultrasound to the target of interest. In addition, MRI thermography 4570 can be utilized so as to obtain the actual temperature of the tissue being heated. These data can be further fed back to the system to slow down or speed up the process of ablation 4560 via the transducers 4550.
  • Aside from focused ultrasound, ultrasonic waves can be utilized directly to either heat an area or to activate pharmaceuticals in the region of interest. There are several methodologies to enhance drug delivery using focused ultrasound. For example, particles can release pharmaceutical when they are heated by the magnetic field. Liposomes can release a payload when they are activated with focused ultrasound. Ultrasound waves have a natural focusing ability if a transducer is placed in the vicinity of the target and the target contains an activateable moiety such as a bioactive drug or material (e.g. a nanoparticle sensitive to acoustic waves). Examples of sonodynamically activated moieties include some porphyrin derivatives.
  • So as to test the region of interest and the potential physiologic effect of ablation in that region, the region can be partially heated with the focused ultrasound to stun or partially ablate the nerves. Next, a physiologic test such as the testing of blood pressure or measuring norepinephrine levels in the blood can be performed to ensure that the correct region was indeed targeted for ablation. Depending on the parameter, additional treatments may be performed.
  • In another embodiment, a fiducial is utilized to demarcate the region of interest. A fiducial can be intrinsic (e.g. part of the anatomy) or the fiducial can be extrinsic (e.g. placed in position). For example, the fiducial can be an implanted fiducial, a fiducial or device placed in the blood vessels, or a device placed percutaneously through a catheterization or other procedure. The fiducial can also be a bone, such as a rib, or another internal organ, for example, the liver. In one embodiment, the fiducial is a beacon or balloon or balloon with a beacon which is detectable via ultrasound. In one embodiment, the blood flow in the renal arteries, detected via Doppler or B-mode imaging, is the fiducial and its relative direction is determined via Doppler analysis. Next, the renal arteries, and specifically, the region around the renal arteries are placed into a three dimensional coordinate frame utilizing the internal fiducials. A variant of global positioning system technology can be utilized to track the fiducials within the artery or around the arteries. The three dimensional coordinate frame is transmitted to the therapeutic ultrasound transducers and then the transducers and anatomy are coupled to the same coordinate frame. At this point, the HIFU is delivered from the transducers, calculating the position of the transducers based on the position of the target in the reference frame.
  • In one embodiment, a virtual fiducial is created via an imaging system. For example, in the case of a blood vessel such as the renal artery, an image of the blood vessel using B-mode ultrasound can be obtained which correlates to the blood vessel being viewed in direct cross section (1700; FIG. 17C). When the vessel is viewed in this type of view, the center of the vessel can be aligned with the center of an ultrasound array (e.g. HIFU array 1600) and the transducers can be focused and applied to the vessel, applying heat to regions around the vessels 1680. With different positions of the transducers 1610 along a circumference or hemisphere 1650, varying focal points can be created 1620, 1630, 1640. The directionality of the transducers allows for a lesion which runs lengthwise along the vessel 1620, 1630, 1640. Thus, a longitudinal lesion can be produced along the artery to insure maximal inhibition of nerve function. In some embodiments, the center of the therapeutic ultrasound transducer is off center relative to the center of the vessel so that the energy is applied across the vessel wall at an angle.
  • In this method of treatment, an artery such as a renal artery is viewed in cross-section or close to a cross-section under ultrasound guidance. In this position, the blood vessel is substantially parallel to the axis of the spherical transducer so as to facilitate lesion production. The setup of the ultrasound transducers 1600 has previously been calibrated to create multiple focal lesions 1620, 1630, 1640 along the artery if the artery is in cross-section 1680.
  • In one embodiment, the fiducial is an intravascular fiducial such as a balloon or a hermetically sealed transmitting device. The balloon is detectable via radiotransmitter within the balloon which is detectable by the external therapeutic transducers. The balloon can have three transducers, each capable of relaying their position so that the balloon can be placed in a three dimensional coordinate reference.
  • Once the balloon is placed into the same coordinate frame as the external transducers using the transmitting beacon, the energy transducing devices can deliver energy (e.g. focused ultrasound) to the blood vessel (e.g. the renal arteries) or the region surrounding the blood vessels (e.g. the renal nerves). The balloon and transmitters also enable the ability to definitively track the vasculature in the case of movement (e.g. the renal arteries). In another embodiment, the balloon measures temperature or is a conduit for coolant applied during the heating of the artery or nerves.
  • Delivery of therapeutic ultrasound energy to the tissue inside the body is accomplished via the ultrasound transducers which are directed to deliver the energy to the target in the coordinate frame.
  • Once the target is placed in the coordinate frame and the energy delivery is begun, it is important to maintain targeting of the position, particularly when the target is a small region such as the sympathetic nerves. To this end, the position of the region of ablation is compared to its baseline position, both in a three dimensional coordinate reference frame. The ongoing positional monitoring and information is fed into an algorithm which determines the new targeting direction of the energy waves toward the target. In one embodiment, if the position is too far from the original position (e.g. the patient moves), then the energy delivery is stopped and the patient repositioned. If the position is not too far from the original position, then the energy transducers can be repositioned either mechanically (e.g. through physical movement) or electrically via phased array (e.g. by changing the relative phase of the waves emanating from the transducers). In another embodiment, multiple transducers are placed on the patient in different positions and each is turned on or off to result in the necessary energy delivery. With a multitude of transducers placed on the patient, a greater territory can be covered with the therapeutic ultrasound. The therapeutic positions can also serve as imaging positions for intrinsic and/or extrinsic fiducials.
  • In addition to heat delivery, ultrasound can be utilized to deliver cavitating energy which may enable drug delivery at certain frequencies. Cavitating energy can also lead to ablation of tissue at the area of the focus. A systemic dose of a drug can be delivered to the region of interest and the region targeted with the cavitating or other forms of ultrasonic energy. Other types of therapeutic delivery modalities include ultrasound sensitive bubbles or radiation sensitive nanoparticles, all of which enhance the effect of the energy at the target of interest.
  • Ultrasound may also be utilized to create tumor vaccines in vivo. In this embodiment, sub-ablative doses of energy is applied to a tumor to induce a stress response or to heat shock response to increase the anti-tumor or immune response to the tumor. The energy can be applied from an external position to and internal position or from an internal position to an external position.
  • FIG. 8 a depicts a percutaneous procedure 5000 and device 5010 in which the region around the renal artery 5030 is directly approached through the skin from an external position. A combination of imaging and ablation may be performed to ablate the region around the renal artery to treat hypertension, end stage renal disease, and heart failure. Probe 5010 is positioned through the skin and in proximity to the kidney 5030. The probe may include sensors which detect heat or temperature or may enable augmentation of the therapeutic energy delivery. Ablative, ionizing energy, heat, or light may be applied to the region to inhibit the sympathetic nerves around the renal artery using the probe 510. Ultrasound, radiofrequency, microwave, direct heating elements, and balloons with heat or energy sources may be applied to the region of the sympathetic nerves.
  • In one embodiment, the percutaneous procedure is performed under MRI, CT, or ultrasound guidance to obtain localization or information about the degree of heat being applied. In one embodiment, ultrasound is applied but at a sub-ablative dose. That is, the energy level is enough to damage or inhibit the nerves but the temperature is such that the nerves are not ablated but paralyzed or partially inhibited by the energy. A particularly preferred embodiment would be to perform the procedure under guidance from an MRI scanner because the region being heated can be determined anatomically in real time as well via temperature maps. As described above the images after heating can be compared to those at baseline and the signals are compared at the different temperatures.
  • In one embodiment, selective regions of the kidney are ablated through the percutaneous access route; for example, regions which secrete hormones which are detrimental to a patient or to the kidneys or other organs. Using energy applied external to the patient through the skin and from different angles affords the ability to target any region in or on the kidney or along the renal nerves or at the region of the adrenal gland, aorta, or sympathetic chain. This greater breadth in the number of regions to be targeted is enabled by the combination of external imaging and external delivery of the energy from a multitude of angles through the skin of the patient to the target. The renal nerves can be targeted at their takeoff from the aorta onto the renal artery, at their synapses at the celiac ganglia, or at their bifurcation point along the renal artery.
  • In a further embodiment, probe 5010 can be utilized to detect temperature or motion of the region while the ultrasound transducers are applying the energy to the region. A motion sensor, position beacon, or accelerometer can be used to provide feedback for the HIFU transducers. In addition, an optional temperature or imaging modality may be placed on the probe 5010. The probe 5010 can also be used to locate the position within the laparoscopic field for the ablations to be performed.
  • In FIG. 8 b, intravascular devices 5050, 5055 are depicted which apply energy to the region around the renal arteries 5065. The intravascular devices can be utilized to apply radiofrequency, ionizing radiation, and/or ultrasound (either focused or unfocused) energy to the renal artery and surrounding regions. MRI or ultrasound or direct thermometry can be further utilized to detect the region where the heat is being applied while the intravascular catheter is in place.
  • In one embodiment, devices 5050, 5055 apply ultrasound energy which inhibits nerve function not by heating, but by mechanisms such as periodic pressure changes, radiation pressure, streaming or flow in viscous media, and pressures associated with cavitation, defined as the formation of holes in liquid media. Heat can selectively be added to these energies but not to create a temperature which ablates the nerves, only facilitates the mechanism of vibration and pressure. In this embodiment, the ultrasound is not focused but radiates outward from the source to essentially create a cylinder of ultrasonic waves that intersect with the wall of the blood vessel. An interfacial material between the ultrasound transducer and the wall of the artery may be provided such that the ultrasound is efficiently transduced through the arterial wall to the region of the nerves around the artery. In another embodiment, the ultrasound directly enters the blood and propagates through the ultrasound wall to affect the nerves. In some embodiments, cooling is provided around the ultrasound catheter which protects the inside of the vessel yet allows the ultrasound to penetrate through the wall to the regions outside the artery. A stabilization method for the ultrasound probe is also included in such a procedure. The stabilization method might include a stabilizing component added to the probe and may include a range finding element component of the ultrasound. Imaging can be performed externally or internally in this embodiment in which a catheter is placed inside the renal ateries.
  • Alternatively, in another embodiment, the devices 5050, 5055 can be utilized to direct externally applied energy (e.g. ultrasound) to the correct place around the artery as the HIFU transducers deliver the energy to the region. For example, the intravascular probe 5050 can be utilized as a homing beacon for the imaging technology utilized for the externally delivered HIFU.
  • In another embodiment, the physiologic process of arterial expansion is targeted. In FIG. 9 a, an ultrasound transducer is 6005 is placed near the wall of an aneurysm 6030. Ultrasonic energy is applied to the wall 6030 of the aneurysm to thicken the wall and prevent further expansion of the aneurysm. In some embodiments, clot within the aneurysm is targeted as well so that the clot is broken up or dissolved with the ultrasonic energy. Once the wall of the aneurysm is heated with ultrasonic energy to a temperature of between 40 and 70 degrees, the collagen, elastin, and other extracellular matrix in the wall will harden as it cools, thereby preventing the wall from further expansion. In another embodiment, a material is placed in the aneurysm sac and the focused or non-focused ultrasound utilized to harden or otherwise induce the material in the sac to stick to the aorta or clot in the aneurysm and thus close the aneurysm permanently. In one embodiment therefore, an ultrasound catheter is placed in an aorta at the region of an aneurysm wall or close to a material in an aneurysmal wall. The material can be a man-made material placed by an operator or it can be material such as thrombus which is in the aneurysm naturally. Ultrasound is applied to the wall, or the material, resulting in hardening of the wall or of the material, strengthening the aneurysm wall and preventing expansion.
  • FIG. 9 b depicts a clot prevention device 6012 within a blood vessel such as the aorta or vena cava 6000. The ultrasound catheter 6005 is applied to the clot prevention device (filter) 6012 so as to remove the clot from the device or to free the device 6012 from the wall of the blood vessel in order to remove it from the blood vessel 6000.
  • FIG. 9 c depicts a device and method in which the celiac plexus 6020 close to the aorta 6000 is ablated or partially heated using heat or vibrational energy from an ultrasonic energy source 6005 which can apply focused or unfocused sound waves 6007 at frequencies ranging from 20 kilohertz to 5 Mhz and at powers ranging from 1 mW to over 100 kW in a focused or unfocused manner. Full, or partial ablation of the celiac plexus 6020 can result in a decrease in blood pressure via a similar mechanism as applying ultrasonic energy to the renal nerves; the ablation catheter is a focused ultrasound catheter but can also be a direct (unfocused) ultrasonic, a microwave transducer, or a resistive heating element.
  • FIG. 10 depicts a method 6100 to treat a patient with high intensity or low intensity focused ultrasound (HIFU or LIFU) 6230. In a first step, a CT and/or MRI scan and/or thermography and/or ultrasound (1D, 2D, 3D) is performed 6110. A fiducial or other marking on or in the patient 6120 is optionally used to mark and track 6140 the patient. The fiducial can be an implanted fiducial, a temporary fiducial, or a fiducial intrinsic to the patient (e.g. bone, blood vessel, arterial wall) which can be imaged using the CT/MRI/Ultrasound devices 6110. The fiducial can further be a temporary fiducial such as a catheter temporarily placed in an artery or vein of a patient or a percutaneously placed catheter. A planning step 6130 for the HIFU treatment is performed in which baseline readings such as position of the organ and temperature are determined; a HIFU treatment is then planned using a model (e.g. finite element model) to predict heat transfer, or pressure to heat transfer, from the ultrasound transducers 6130. The planning step incorporates the information on the location of the tissue or target from the imaging devices 6110 and allows placement of the anatomy into a three dimensional coordinate reference such that modeling 6130 can be performed.
  • The planning step 6130 includes determination of the positioning of the ultrasound transducers as far as position of the focus in the patient. X, Y, Z, and up to three angular coordinates are used to determine the position of the ultrasonic focus in the patient based on the cross sectional imaging 6110. The HIFU transducers might have their own position sensors built in so that the position relative to the target can be assessed. Alternatively, the HIFU transducers can be rigidly fixed to the table on which the patient rests so that the coordinates relative to the table and the patient are easily obtainable. The flow of heat is also modeled in the planning step 6130 so that the temperature at a specific position with the ultrasound can be planned and predicted. For example, the pressure wave from the transducer is modeled as it penetrates through the tissue to the target. For the most part, the tissue can be treated as water with a minimal loss due to interfaces. The relative power and phase of the ultrasonic wave at the target can be determined by the positional coupling between the probe and target. A convective heat transfer term is added to model heat transfer due to blood flow, particularly in the region of an artery. A conductive heat transfer term is also modeled in the equation for heat flow and temperature.
  • Another variable which is considered in the planning step is the size of the lesion and the error in its position. In the ablation of small regions such as nerves surrounding blood vessels, the temperature of the regions may need to be increased to a temperature of 60-90 degrees Celsius to permanently ablate nerves in the region. Temperatures of 40-60 degrees may temporarily inhibit or block the nerves in these regions and these temperatures can be used to determine that a patient will respond to a specific treatment without permanently ablating the nerve region. Subsequently, additional therapy can be applied at a later time so as to complete the job or perhaps, re-inhibit the nerve regions.
  • An error analysis is also performed during the treatment contemplated in FIG. 10. Each element of temperature and position contains an error variable which propagates through the equation of the treatment. The errors are modeled to obtain a virtual representation of the temperature mapped to position. This map is correlated to the position of the ultrasound transducers in the treatment of the region of interest.
  • During the delivery of the treatment 6260, the patient may move, in which case the fiducials 6120 track the movement and the position of the treatment zone is re-analyzed 6150 and the treatment is restarted or the transducers are moved either mechanically or electrically to a new focus position.
  • In another embodiment, a cross-sectional technique of imaging is used in combination with a modality such as ultrasound to create a fusion type of image. The cross-sectional imaging is utilized to create a three dimensional data set of the anatomy. The ultrasound, providing two dimensional images, is linked to the three dimensional imaging provided by the cross-sectional machine through fiducial matches between the ultrasound and the MRI. As a body portion moves within the ultrasound field, the corresponding data is determined (coupled to) the cross-sectional (e.g. MRI image) and a viewing station can show the movement in the three dimensional dataset. The ultrasound provides real time images and the coupling to the MRI or other cross-sectional image depicts the ultrasound determined position in the three dimensional space.
  • FIG. 11 depicts the treatment of another disease in the body of a patient, this time in the head of a patient. Subdural and epidural hematomas occur as a result of bleeding of blood vessels in the dural or epidural spaces of the brain, spinal column, and scalp. FIG. 11 depicts a CT or MRI scanner 7300 and a patient 7400 therein. An image is obtained of the brain 7000 using a CT or MRI scan. The image is utilized to couple the treatment zone 7100 to the ultrasound array utilized to heat the region. In one embodiment 7100, a subdural hematoma, either acute or chronic, is treated. In another embodiment 7200, an epidural hematoma is treated. In both embodiments, the region of leaking capillaries and blood vessels are heated to stop the bleeding, or in the case of a chronic subdural hematoma, the oozing of the inflammatory capillaries.
  • In an exemplary embodiment of modulating physiologic processes, a patient 7400 with a subdural or epidural hematoma is chosen for treatment and a CT scan or MRI 7300 is obtained of the treatment region. Treatment planning ensues and the chronic region of the epidural 7200 or sub-dural 7010 hematoma is targeted for treatment with the focused ultrasound 7100 transducer technology. Next the target of interest is placed in a coordinate reference frame as are the ultrasound transducers. Therapy 7100 ensues once the two are couple together. The focused ultrasound heats the region of the hematoma to dissolve the clot and/or stop the leakage from the capillaries which lead to the accumulation of fluid around the brain 7420. The technology can be used in place of or in addition to a burr hole, which is a hole placed through the scalp to evacuate the fluid.
  • FIG. 12 depicts a laparoscopic based approach 8000 to the renal artery region in which the sympathetic nerves 8210 can be ligated, interrupted, or otherwise modulated. In laparoscopy, the abdomen of a patient is insufflated and laparoscopic instruments introduced into the insufflated abdomen. The retroperitoneum is accessible through a flank approach or through a transabdominal approach. A laparoscopic instrument 8200 with a distal tip 8220 can apply heat or another form of energy or deliver a drug to the region of the sympathetic nerves 8210. The laparoscopic implement can also be utilized to ablate or alter the region of the celiac plexus 8300 and surrounding ganglia. The laparoscope can have an ultrasound transducer attached, a temperature probe attached, a microwave transducer attached, or a radiofrequency transducer attached. The laparoscope can be utilized to directly ablate or stun the nerves(e.g. with a lower frequency/energy) surrounding vessels or can be used to ablate or stun nerve ganglia which travel with the blood vessels. Similar types of modeling and imaging can be utilized with the percutaneous approach as with the external approach to the renal nerves.
  • FIG. 13 depicts an algorithm for the treatment of a region of interest. MRI and/or CT with or without a imaging agent 8410 can be utilized to demarcate the region of interest (for example, the ablation zone) and then ablation 8420 can be performed around the zone identified by the agent using any of the modalities above. This algorithm is applicable to any of the therapeutic modalities described above including external HIFU, laparoscopic instruments, intravascular catheters, percutaneous catheters, as well as any of the treatment regions including the renal nerves, the eye, the kidneys, the aorta, or any of the other nerves surrounding peripheral arteries or veins. Imaging 8430 with CT, MRI, ultrasound, or PET can be utilized in real time. At such time when destruction of the lesion is complete 8440, imaging with an imaging (for example, a molecular imaging agent or a contrast agent such as gadolinium) agent 8410 can be performed again. The extent of ablation can also be monitored by monitoring the temperature or the appearance of the ablated zone under an imaging modality. Once lesion destruction is complete 8440, the procedure is finished. In some embodiments, ultrasonic diagnostic techniques such as elastography are utilized to determine the progress toward heating or ablation of a region.
  • FIG. 14 depicts ablation in which specific nerve fibers of a nerve are targeted using different temperature gradients or temperatures 8500. For example, if temperature is determined by MRI thermometry or with another technique such as ultrasound, then the temperature can be kept at a temperature in which only certain nerve fibers are targeted for destruction or inhibition. Alternatively, part or all of the nerve can be turned off temporarily to then test the downstream effect of the nerve being turned off. For example, the sympathetic nerves around the renal artery can be turned off with a small amount of heat or other energy (e.g. vibrational energy) and then the effect can be determined. For example, norepinephrine levels in the systemic blood or renal vein can be assayed; alternatively, the stimulation effect of the nerves can be tested after temporary cessation of activity (e.g. skin reactivy, blood pressure lability, cardiac activity, pulmonary activity. Varying frequencies of vibration can be utilized to inhibit specific nerve fibers versus others. For example, in some embodiments, the efferent nerve fibers are inhibited and in other embodiments, the afferent nerve fibers are inhibited. In some embodiments, both types of nerve fibers are inhibited, temporarily or permanently.
  • FIG. 15 depicts treatment 8600 of a vertebral body or intervertebral disk 8610 in which nerves within 8640 or around the vertebral column 8630 are targeted with ultrasound 8625 waves. In one embodiment, nerves around the facet joints are targeted. In another embodiment, nerves leading to the disks or vertebral endplates are targeted.
  • FIG. 16 depicts a set of lesion types, sizes, and anatomies 8710 a-h which lead to de-innervation of the different portions of the sympathetic nerve tree. For example, the lesions can be annular, cigar shaped, linear, doughnut and/or spherical; the lesions can be placed around the renal arteries 8705, inside the kidney 8710, and/or around the aorta 8700. For example, the renal arterial tree 8700 comprises renal arteries 8705 and kidneys 8715. Lesions 8710 a-h are different types of lesions which are created around the aorta 8700 and vascular tree. Lesions can be placed in a spiral shape along the length of the artery.
  • FIG. 17 a depicts a multi-transducer HIFU device 1100 which applies a finite lesion 1150 along an artery 1140 (e.g. a renal artery) leading to a kidney 1130. The lesion can be spherical in shape, cigar shaped 1050, annular shaped 1050, or point shaped; however, in a preferred embodiment, the lesion runs along the length of the artery and has a cigar shaped. This lesion is generated by a spherical type of ultrasound array in a preferred embodiment. FIG. 17 c depicts the pathway of the spherical or cylindrical type of ultrasound array 1600. Ultrasound transducers 1610 are aligned along the edge of a cylinder aimed so that they intersect at one or more focal spots 1620, 1630, 1640. The transducers 1610 are positioned along the cylinder 1650 such that some are closer to one focus or the other so that a range of distances to the artery is created. The patient and artery are positioned such that their centers 1700 co-localize with the center of the ultrasound array 1600. Once the centers are co-localized, the HIFU energy can be activated to create lesions along the length of the artery wall 1640, 1620, 1630 at different depths and positions around the artery. The natural focusing of the transducers positioned along a cylinder as in FIG. 17 b is a lengthwise lesion, longer than in thickness or height, which will run along the length of an artery when the artery is placed along the center axis of the cylinder. When viewed along a cross section the nerve ablations are positioned along a clock face 1680 around the vessel.
  • Importantly, during treatment, a treatment workstation 1300 gives multiple views of the treatment zone with both physical appearance and anatomy 1050. Physical modeling is performed in order to predict lesion depth and the time to produce the lesion; this information is fed back to the ultrasound transducers 1100. The position of the lesion is also constantly monitored in a three dimensional coordinate frame and the transducer focus at lesions center 1150 continually updated.
  • In some embodiments, motion tracking prevents the lesion or patient from moving too far out of the treatment zone during the ablation. If the patient does move outside the treatment zone during the therapy, then the therapy can be stopped. Motion tracking can be performed using the ultrasound transducers, tracking frames and position or with transducers from multiple angles, creating a three dimensional image with the transducers. Alternatively, a video imaging system can be used to track patient movements, as can a series of accelerometers positioned on the patient which indicate movement.
  • FIG. 18 depicts a micro-catheter 8810 which can be placed into renal calyces 8820; this catheter allows the operator to specifically ablate or stimulate 8830 regions of the kidney 8800. The catheter can be used to further allow for targeting of the region around the renal arteries and kidneys by providing additional imaging capability or by assisting in movement tracking or reflection of the ultrasound waves to create or position the lesion. The catheter or device at or near the end of the catheter may transmit signals outside the patient to direct an energy delivery device which delivers energy through the skin. Signaling outside the patient may comprise energies such as radiofrequency transmission outside the patient or radiofrequency from outside to the inside to target the region surrounding the catheter.
  • In one method, a micro catheter is delivered to the renal arteries and into the branches of the renal arteries in the kidney. A signal is generated from the catheter into the kidney and out of the patient to an energy delivery system. Based on the generated signal, the position of the catheter in a three dimensional coordinate reference is determined and the energy source is activated to deliver energy to the region indicated by the microcatheter. The microcatheter may be utilized to place a flow restrictor inside the kidney (e.g. inside a renal vein) to “trick” the kidney into thinking its internal pressure is higher than it might be. In this embodiment, the kidney generates signals to the central nervous system to lower sympathetic output to target organs.
  • Alternatively, specific regions of the kidney might be responsible for hormone excretion or other factors which lead to hypertension or other detrimental effects to the cardiovascular system. The microcatheter can generate ultrasound, radiofrequency, microwave, or X-ray energy. The microcatheter can be utilized to ablate regions in the renal vein or intraparenchymal venous portion as well. In some embodiments, ablation is not required but vibratory energy emanating from the probe is utilized to affect, on a permanent or temporary basis, the mechanoreceptors or chemoreceptors in the location of the hilum of the kidney.
  • FIG. 19 depicts the application of acoustic waves to the region of the renal artery 8910 and kidney 8920 using physically separated transducers 8930, 8931. In contrast to the delivery method of FIG. 17, FIG. 19 depicts delivery of ultrasound transverse to the renal arteries and not longitudinal to the artery. The direction of energy delivery is the posterior of the patient because the renal artery is the first vessel seen when traveling from the skin toward the anterior direction facilitating delivery of the therapy. In one embodiment, the transducers 8930, 8931 are placed under, or inferior to the rib of the patient or between the ribs of a patient; next, the transducers apply an ultrasound wave propagating forward toward the anterior abdominal wall and image the region of the renal arteries and renal veins, separating them from one another. In some embodiments, such delivery might be advantageous, if for example, a longitudinal view of the artery is unobtainable or a faster treatment paradigm is desirable. The transducers 8930, 8931 communicate with one another and are connected to a computer model of the region of interest being imaged (ROI), the ROI based on an MRI scan performed just prior to the start of the procedure and throughout the procedure. Importantly, the transducers are placed posterior in the cross section of the patient, an area with more direct access to the kidney region. The angle between the imaging transducers is
  • In another embodiment, an MRI is not performed but ultrasound is utilized to obtain all or part of the view in FIG. 19. For example, 8930 might contain an imaging transducer as well as a therapeutic energy source (e.g. ionizing energy, HIFU, low energy focused ultrasound, etc.).
  • FIG. 20 depicts an alternative method 9000 and device to ablate the renal nerves 9015 or the nerves leading to the renal nerves at the aorta-renal artery ostium 9010. The intravascular device 9020 is placed into the aorta 9050 and advanced to the region of the renal arteries 9025. Energy is applied from the transducer 9020 and focused 9040(in the case of HIFU, LIFU, ionizing radiation) to the region of the takeoff of the renal arteries 9025 from the aorta 9050. This intravascular procedure can be guided using MRI and/or MRI thermometry or it can be guided using fluoroscopy, ultrasound, or MRI. Because the aorta is larger than the renal arteries, the HIFU catheter can be placed into the aorta directly and cooling catheters can be included as well. In addition, in other embodiments, non-focused ultrasound can be applied to the region around the renal ostium or higher in the aorta. Non-focused ultrasound in some embodiments may require cooling of the tissues surrounding the probe using one or more coolants but in some embodiments, the blood of the aorta will take the place of the coolant; HIFU, or focused ultrasound, may not need the cooling because the waves are by definition focused from different angles to the region around the aorta. The vena cava and renal veins can also be used as a conduit for the focused ultrasound transducer to deliver energy to the region as well. In one embodiment, the vena cava is accessed and vibratory energy is passed through the walls of the vena cava and renal vein to the renal arteries, around which the nerves to the kidney travel. The veins, having thinner walls, allow energy to pass through more readily.
  • FIG. 21 depicts an eyeball 9100. Also depicted are the zonules 9130 and ultrasound transducer 9120. The transducer 9120 applies focused ultrasound energy to the region surrounding the zonules, or the zonules themselves, in order to tighten them such that a presbyopic patient can accommodate and visualize object up close. Similarly, heat or vibration to the ciliary muscles, which then slows down the outflow of aqueous humor at the region of interest so that the pressure within the eye cannot build up to a high level. The ultrasound transducer 9120 can also be utilized to deliver drug therapy to the region of the lens, ciliary body, zonules, intravitreal cavity, anterior cavity, posterior cavity, etc.
  • In some embodiments (FIG. 21 b), the ultrasonic transducers 9170 are focused on the particular region of the eye so that tissues along the path of the ultrasound are not damaged by the ultrasound and the focus region and region of effect is the position where the waves meet in the eye. In one embodiment, the transducers are directed through the pars plana region of the eye to target the macula 9180 at the posterior pole 9175 of the eye. This configuration might allow for heat, vibratory stimulation, drug delivery, gene delivery, augmentation of laser or ionizing radiation therapy, etc. In certain embodiments, focused ultrasound is not required and generic vibratory waves are transmitted through the eye at frequencies from 20 kHz to 10 MHz. Such energy may be utilized to break up clots in, for example, retinal venous or arterial occlusions which are creating ischemia in the retina. This energy can be utilized in combination with drugs utilized specifically for breaking up clots in the veins of the retina.
  • FIG. 22 depicts a peripheral joint 9200 being treated with heat and/or vibrational energy. Ultrasound transducer 9210 emits waves toward the knee joint to block nerves 9260 just underneath the bone periostium. Although a knee joint is depicted, it should be understood that many joints can be treated including small joints in the hand, intervertebral joints, the hip, the ankle, the wrist, and the shoulder. Unfocused or focused ultrasonic energy can be applied to the joint region to inhibit nerve function reversibly or irreversibly. Such inhibition of nerve function can be utilized to treat arthritis, post-operative pain, tendonitis, tumor pain, etc.
  • FIG. 23 a-b depicts closure of a fallopian tube 9300 of a uterus 9320 using externally applied ultrasound 9310 so as to prevent pregnancy. MRI or preferably ultrasound can be utilized for the imaging modality. Thermometry can be utilized as well so as to see the true ablation zone in real time. The fallopian tube 9300 can be visualized using ultrasound, MRI, CT scan or a laparoscope. Once the fallopian tube is targeted, external energy 9310, for example, ultrasound, can be utilized to close the fallopian tube to prevent pregnancy.
  • In other embodiments, ultrasound is applied to the uterus or fallopian tubes to aid in pregnancy by improving the receptivity of the sperm and/or egg for one another. This augmentation of conception can be applied to the sperm and egg outside of the womb as well, for example, in a test tube.
  • In 23 b a method is depicted in which the fallopian tubes are visualized 9340 using MRI, CT, or ultrasound. HIFU 9350 is applied under visualization with MRI or ultrasound. As the fallopian tubes are heated, the collagen in the wall is heated until the walls of the fallopian tube close off. At this point the patient is sterilized 9360. During the treating time, it may be required to determine how effective the heating is progressing. If additional heat is required, then additional HIFU may be added to the fallopian tubes until there is closure of the tube and the patient is sterilized 9360.

Claims (13)

1) A method to inhibit the function of a renal nerve comprising:
a. Introducing an intravascular catheter into a renal artery;
b. Applying vibrational energy, from the catheter, in an unfocused manner, to at least a portion of the circumference of the artery sufficient to at least inhibit a partial function of a renal nerve.
2) A method to at least partially inhibit the function of a renal nerve comprising:
a. Introducing an intravascular catheter into a renal artery;
b. Stabilizing the catheter in the renal artery;
c. Determining the size of the renal artery;
d. Modeling the transfer of vibrational power from the catheter inside the artery to the region outside the artery and determining the appropriate power required to the catheter to reach a level outside the artery to inihibit nerve function;
e. Applying vibrational power from inside the artery to the region outside the artery at the appropriate pre-determined power level.
3) The method of claim 2 wherein the vibrational power outside the artery is in the range from 20 mW/cm2 to 500 W/cm2.
4) The method of claim 1 further comprising: stabilizing the catheter within the artery and approximating the distance to the renal nerves outside the artery based on one of: angiography, ultrasound, CT scan, MRI.
5) The method of claim 1 further comprising introducing a cooling lumen or independent cooling catheter into the artery.
6) The method of claim 1 wherein the energy transmitting element does not contact the arterial wall.
7) A method to inhibit the function of a renal nerve comprising:
a. Introducing an intravascular catheter into an aorta;
b. Applying energy, from the catheter, in an unfocused manner, to at least a portion of the circumference of the aorta to affect the function of nerves traveling to the kidney.
8) The method of claim 7 further comprising cooling the region immediately adjacent the intravascular catheter during inhibition of the renal nerve function.
9) The method of claim 7 wherein the intravascular catheter is placed into the ostium of at least one of the renal arteries.
10) A method to stimulate or inhibit the function of a nerve traveling to or from the kidney comprising:
a. Identifying an acoustic window at the posterior region of a patient in which the renal arteries can be visualized;
b. transmitting a first energy through the skin of a patient from the posterior region of the patient;
c. imaging an arterial region using the first transmitted energy;
d. applying a second transmitted energy to the arterial adventitia by coupling the imaging and the second transmitted energy.
11. The method of claim 10 further comprising: tracking the image created by the first transmitted energy.
12. A method to locate the position of a blood vessel in the body of a patient comprising:
Applying a first wave of ultrasound, from a first direction, to a region of a blood vessel from outside of the patient and detecting its return signal;
Comparing the applied first wave and its return signal;
Simultaneously, or sequentially, applying a second wave of ultrasound from a second direction to the blood vessel and detecting a its return signal;
Integrating the return signals from the first wave and the return signals from the second wave to determine the position, in a three dimensional coordinate reference, of the blood vessel.
13. The method of claim 12 further comprising the step of instructing a therapeutic ultrasound transducer to apply energy to the position of the blood vessel.
US12/725,450 2009-10-12 2010-03-16 External Autonomic Modulation Abandoned US20110118600A1 (en)

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US12/725,450 US20110118600A1 (en) 2009-11-16 2010-03-16 External Autonomic Modulation
JP2012533385A JP5794580B2 (en) 2009-10-12 2010-10-11 Nerve regulation by energy
EP10810835.8A EP2344039B1 (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
KR1020157004249A KR101567285B1 (en) 2009-10-12 2010-10-11 Energetic Modulation of Nerves
CN201080002316.4A CN102164542B (en) 2009-10-12 2010-10-11 Neural energy adjustment
US12/902,135 US20110092880A1 (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
CN201080052675.0A CN102740925B (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
EP15196135.6A EP3005944A1 (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
KR1020127012159A KR101545775B1 (en) 2009-10-12 2010-10-11 Energetic Modulation of Nerves
BR112012008538A BR112012008538A2 (en) 2009-10-12 2010-10-11 energy modulation of nerves
RU2012119540/14A RU2523129C2 (en) 2009-10-12 2010-10-11 Energy neuromodulation
MYPI2012001623A MY160595A (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
CA2777228A CA2777228A1 (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
PCT/US2010/052197 WO2011046880A2 (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
EP10823909.6A EP2488250B1 (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
CN201510013394.9A CN104800973A (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
AU2010307029A AU2010307029B2 (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
CN201510013395.3A CN104771138A (en) 2009-10-12 2010-10-11 External autonomic modulation
US12/902,133 US9174065B2 (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
PCT/US2010/052193 WO2011046879A1 (en) 2009-10-12 2010-10-11 Energetic modulation of nerves
CN201510014506.2A CN104856731A (en) 2009-10-12 2010-10-11 Energy modulation of nerves
US12/966,962 US8556834B2 (en) 2009-10-12 2010-12-13 Flow directed heating of nervous structures
US12/966,954 US20110172528A1 (en) 2009-10-12 2010-12-13 Systems and methods for treatment using ultrasonic energy
US12/966,943 US20110172527A1 (en) 2009-10-12 2010-12-13 Systems for externally delivered energy to modulate neural structures
US13/019,273 US8374674B2 (en) 2009-10-12 2011-02-01 Nerve treatment system
US13/048,830 US8517962B2 (en) 2009-10-12 2011-03-15 Energetic modulation of nerves
US13/048,842 US8469904B2 (en) 2009-10-12 2011-03-15 Energetic modulation of nerves
US13/048,837 US8986231B2 (en) 2009-10-12 2011-03-15 Energetic modulation of nerves
US13/048,844 US8986211B2 (en) 2009-10-12 2011-03-15 Energetic modulation of nerves
US13/091,116 US9119951B2 (en) 2009-10-12 2011-04-20 Energetic modulation of nerves
US13/111,837 US9005143B2 (en) 2009-10-12 2011-05-19 External autonomic modulation
US13/228,366 US20110319765A1 (en) 2009-10-12 2011-09-08 Energetic modulation of nerves
US13/246,775 US20120016226A1 (en) 2009-10-12 2011-09-27 Energetic modulation of nerves
US13/246,763 US20120022409A1 (en) 2009-10-12 2011-09-27 Energetic modulation of nerves
HK11110882.7A HK1156491A1 (en) 2009-10-12 2011-10-13 Energetic modulation of nerves
US13/417,194 US9358401B2 (en) 2009-10-12 2012-03-09 Intravascular catheter to deliver unfocused energy to nerves surrounding a blood vessel
IL219083A IL219083A (en) 2009-10-12 2012-04-05 Energetic modulation of nerves
US13/487,135 US9579518B2 (en) 2009-10-12 2012-06-01 Nerve treatment system
US13/487,121 US20120238918A1 (en) 2009-10-12 2012-06-01 Methods for delivering energy to modulate neural structures
US13/487,118 US20120245494A1 (en) 2009-10-12 2012-06-01 Methods for treatment using ultrasonic energy
US13/523,835 US8992447B2 (en) 2009-10-12 2012-06-14 Energetic modulation of nerves
US13/535,070 US8512262B2 (en) 2009-10-12 2012-06-27 Energetic modulation of nerves
US13/717,401 US20130190716A1 (en) 2009-10-12 2012-12-17 Nerve treatment system
US13/751,133 US9352171B2 (en) 2009-10-12 2013-01-27 Nerve treatment system
US13/896,247 US9199097B2 (en) 2009-10-12 2013-05-16 Energetic modulation of nerves
US13/896,252 US20130253381A1 (en) 2009-10-12 2013-05-16 Energetic modulation of nerves
US13/904,853 US20140058188A1 (en) 2009-10-12 2013-05-29 Energetic modulation of nerves
US13/960,743 US20140039479A1 (en) 2009-10-12 2013-08-06 Energetic modulation of nerves
US13/966,212 US20130331739A1 (en) 2009-10-12 2013-08-13 Energetic modulation of nerves
US14/015,331 US20140074076A1 (en) 2009-10-12 2013-08-30 Non-invasive autonomic nervous system modulation
US14/099,834 US9125642B2 (en) 2009-10-12 2013-12-06 External autonomic modulation
US14/207,516 US20140194785A1 (en) 2009-10-12 2014-03-12 Methods and devices for thermally induced hepatic neuromodulation
US14/207,526 US20140336497A1 (en) 2009-10-12 2014-03-12 Non-invasive or minimally invasive paraspinal and pre-aortic sympathetic ablation for the treatment of hypertension
US14/207,511 US20140194784A1 (en) 2009-10-12 2014-03-12 Methods and devices for thermally induced hepatic neuromodulation
US14/207,642 US20140194786A1 (en) 2009-10-12 2014-03-13 Method and system for tissue modulation
US14/562,477 US20150202466A1 (en) 2009-10-12 2014-12-05 Energetic modulation of nerves
JP2015082029A JP5943441B2 (en) 2009-10-12 2015-04-13 Nerve regulation by energy
IL238653A IL238653A0 (en) 2009-10-12 2015-05-06 An apparatus for energy delivery into a patient
US14/939,670 US20160059044A1 (en) 2009-10-12 2015-11-12 Energy delivery to intraparenchymal regions of the kidney to treat hypertension
US15/662,179 US10772681B2 (en) 2009-10-12 2017-07-27 Energy delivery to intraparenchymal regions of the kidney
US16/412,379 US11154356B2 (en) 2009-10-12 2019-05-14 Intravascular energy delivery
US17/486,826 US20220202483A1 (en) 2009-10-12 2021-09-27 Intravascular energy delivery

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US13/048,830 Continuation-In-Part US8517962B2 (en) 2009-10-12 2011-03-15 Energetic modulation of nerves
US13/048,842 Continuation-In-Part US8469904B2 (en) 2009-10-12 2011-03-15 Energetic modulation of nerves
US13/091,116 Continuation-In-Part US9119951B2 (en) 2009-10-12 2011-04-20 Energetic modulation of nerves
US13/111,837 Continuation US9005143B2 (en) 2009-10-12 2011-05-19 External autonomic modulation
US13/487,135 Continuation-In-Part US9579518B2 (en) 2009-10-12 2012-06-01 Nerve treatment system
US13/523,835 Continuation-In-Part US8992447B2 (en) 2009-10-12 2012-06-14 Energetic modulation of nerves
US13/535,070 Continuation-In-Part US8512262B2 (en) 2009-10-12 2012-06-27 Energetic modulation of nerves
US13/751,133 Continuation-In-Part US9352171B2 (en) 2009-10-12 2013-01-27 Nerve treatment system
US14/099,834 Continuation US9125642B2 (en) 2009-10-12 2013-12-06 External autonomic modulation

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Cited By (102)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080161801A1 (en) * 2003-09-12 2008-07-03 Minnow Medical, Inc. Selectable Eccentric Remodeling and/or Ablation of Atherosclerotic Material
US20100152626A1 (en) * 2006-08-22 2010-06-17 Schwartz Donald N Ultrasonic treatment of glaucoma
US8364237B2 (en) 2005-03-28 2013-01-29 Vessix Vascular, Inc. Tuned RF energy for selective treatment of atheroma and other target tissues and/or structures
US8396548B2 (en) 2008-11-14 2013-03-12 Vessix Vascular, Inc. Selective drug delivery in a lumen
US8401667B2 (en) 2008-11-17 2013-03-19 Vessix Vascular, Inc. Selective accumulation of energy with or without knowledge of tissue topography
US8496653B2 (en) 2007-04-23 2013-07-30 Boston Scientific Scimed, Inc. Thrombus removal
US8551096B2 (en) 2009-05-13 2013-10-08 Boston Scientific Scimed, Inc. Directional delivery of energy and bioactives
US20130310823A1 (en) * 2012-04-24 2013-11-21 Mark Gelfand Endovascular Catheters and Methods for Carotid Body Ablation
US20130324987A1 (en) * 2012-06-01 2013-12-05 Mark Leung Methods and Devices for Cryogenic Carotid Body Ablation
US20140148735A1 (en) * 2012-11-28 2014-05-29 Covidien Lp Device and method for salvaging myocardium following heart attack
US8845629B2 (en) 2002-04-08 2014-09-30 Medtronic Ardian Luxembourg S.A.R.L. Ultrasound apparatuses for thermally-induced renal neuromodulation
US8880185B2 (en) 2010-06-11 2014-11-04 Boston Scientific Scimed, Inc. Renal denervation and stimulation employing wireless vascular energy transfer arrangement
US8920414B2 (en) 2004-09-10 2014-12-30 Vessix Vascular, Inc. Tuned RF energy and electrical tissue characterization for selective treatment of target tissues
US20150005756A1 (en) * 2011-09-27 2015-01-01 Koninklijke Philips N.V. High intensity focused ultrasound enhanced by cavitation
US8951251B2 (en) 2011-11-08 2015-02-10 Boston Scientific Scimed, Inc. Ostial renal nerve ablation
US8974451B2 (en) 2010-10-25 2015-03-10 Boston Scientific Scimed, Inc. Renal nerve ablation using conductive fluid jet and RF energy
US9005143B2 (en) 2009-10-12 2015-04-14 Kona Medical, Inc. External autonomic modulation
US9023034B2 (en) 2010-11-22 2015-05-05 Boston Scientific Scimed, Inc. Renal ablation electrode with force-activatable conduction apparatus
US9028485B2 (en) 2010-11-15 2015-05-12 Boston Scientific Scimed, Inc. Self-expanding cooling electrode for renal nerve ablation
US9028472B2 (en) 2011-12-23 2015-05-12 Vessix Vascular, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9050106B2 (en) 2011-12-29 2015-06-09 Boston Scientific Scimed, Inc. Off-wall electrode device and methods for nerve modulation
US9060761B2 (en) 2010-11-18 2015-06-23 Boston Scientific Scime, Inc. Catheter-focused magnetic field induced renal nerve ablation
US9079000B2 (en) 2011-10-18 2015-07-14 Boston Scientific Scimed, Inc. Integrated crossing balloon catheter
US9084609B2 (en) 2010-07-30 2015-07-21 Boston Scientific Scime, Inc. Spiral balloon catheter for renal nerve ablation
US9089350B2 (en) 2010-11-16 2015-07-28 Boston Scientific Scimed, Inc. Renal denervation catheter with RF electrode and integral contrast dye injection arrangement
US9119600B2 (en) 2011-11-15 2015-09-01 Boston Scientific Scimed, Inc. Device and methods for renal nerve modulation monitoring
US9119632B2 (en) 2011-11-21 2015-09-01 Boston Scientific Scimed, Inc. Deflectable renal nerve ablation catheter
US9125667B2 (en) 2004-09-10 2015-09-08 Vessix Vascular, Inc. System for inducing desirable temperature effects on body tissue
US9155589B2 (en) 2010-07-30 2015-10-13 Boston Scientific Scimed, Inc. Sequential activation RF electrode set for renal nerve ablation
US9162046B2 (en) 2011-10-18 2015-10-20 Boston Scientific Scimed, Inc. Deflectable medical devices
US9173696B2 (en) 2012-09-17 2015-11-03 Boston Scientific Scimed, Inc. Self-positioning electrode system and method for renal nerve modulation
US9186210B2 (en) 2011-10-10 2015-11-17 Boston Scientific Scimed, Inc. Medical devices including ablation electrodes
US9186209B2 (en) 2011-07-22 2015-11-17 Boston Scientific Scimed, Inc. Nerve modulation system having helical guide
US9192435B2 (en) 2010-11-22 2015-11-24 Boston Scientific Scimed, Inc. Renal denervation catheter with cooled RF electrode
US9192790B2 (en) 2010-04-14 2015-11-24 Boston Scientific Scimed, Inc. Focused ultrasonic renal denervation
US9220558B2 (en) 2010-10-27 2015-12-29 Boston Scientific Scimed, Inc. RF renal denervation catheter with multiple independent electrodes
US9220561B2 (en) 2011-01-19 2015-12-29 Boston Scientific Scimed, Inc. Guide-compatible large-electrode catheter for renal nerve ablation with reduced arterial injury
US9265969B2 (en) 2011-12-21 2016-02-23 Cardiac Pacemakers, Inc. Methods for modulating cell function
US9277955B2 (en) 2010-04-09 2016-03-08 Vessix Vascular, Inc. Power generating and control apparatus for the treatment of tissue
US9283033B2 (en) 2012-06-30 2016-03-15 Cibiem, Inc. Carotid body ablation via directed energy
US9297845B2 (en) 2013-03-15 2016-03-29 Boston Scientific Scimed, Inc. Medical devices and methods for treatment of hypertension that utilize impedance compensation
WO2016058963A1 (en) * 2014-10-17 2016-04-21 Koninklijke Philips N.V. An ultrasound patch for ultrasound hyperthermia and imaging
US9326751B2 (en) 2010-11-17 2016-05-03 Boston Scientific Scimed, Inc. Catheter guidance of external energy for renal denervation
US9358365B2 (en) 2010-07-30 2016-06-07 Boston Scientific Scimed, Inc. Precision electrode movement control for renal nerve ablation
US9364284B2 (en) 2011-10-12 2016-06-14 Boston Scientific Scimed, Inc. Method of making an off-wall spacer cage
US9398930B2 (en) 2012-06-01 2016-07-26 Cibiem, Inc. Percutaneous methods and devices for carotid body ablation
US9408661B2 (en) 2010-07-30 2016-08-09 Patrick A. Haverkost RF electrodes on multiple flexible wires for renal nerve ablation
US9420955B2 (en) 2011-10-11 2016-08-23 Boston Scientific Scimed, Inc. Intravascular temperature monitoring system and method
US9433760B2 (en) 2011-12-28 2016-09-06 Boston Scientific Scimed, Inc. Device and methods for nerve modulation using a novel ablation catheter with polymeric ablative elements
US9463062B2 (en) 2010-07-30 2016-10-11 Boston Scientific Scimed, Inc. Cooled conductive balloon RF catheter for renal nerve ablation
US9486270B2 (en) 2002-04-08 2016-11-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for bilateral renal neuromodulation
US9579030B2 (en) 2011-07-20 2017-02-28 Boston Scientific Scimed, Inc. Percutaneous devices and methods to visualize, target and ablate nerves
US9649156B2 (en) 2010-12-15 2017-05-16 Boston Scientific Scimed, Inc. Bipolar off-wall electrode device for renal nerve ablation
US9668811B2 (en) 2010-11-16 2017-06-06 Boston Scientific Scimed, Inc. Minimally invasive access for renal nerve ablation
US9687166B2 (en) 2013-10-14 2017-06-27 Boston Scientific Scimed, Inc. High resolution cardiac mapping electrode array catheter
US9693821B2 (en) 2013-03-11 2017-07-04 Boston Scientific Scimed, Inc. Medical devices for modulating nerves
US9707036B2 (en) 2013-06-25 2017-07-18 Boston Scientific Scimed, Inc. Devices and methods for nerve modulation using localized indifferent electrodes
US9713730B2 (en) 2004-09-10 2017-07-25 Boston Scientific Scimed, Inc. Apparatus and method for treatment of in-stent restenosis
US9770606B2 (en) 2013-10-15 2017-09-26 Boston Scientific Scimed, Inc. Ultrasound ablation catheter with cooling infusion and centering basket
US9770593B2 (en) 2012-11-05 2017-09-26 Pythagoras Medical Ltd. Patient selection using a transluminally-applied electric current
US9808300B2 (en) 2006-05-02 2017-11-07 Boston Scientific Scimed, Inc. Control of arterial smooth muscle tone
US9808311B2 (en) 2013-03-13 2017-11-07 Boston Scientific Scimed, Inc. Deflectable medical devices
US9827039B2 (en) 2013-03-15 2017-11-28 Boston Scientific Scimed, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9833283B2 (en) 2013-07-01 2017-12-05 Boston Scientific Scimed, Inc. Medical devices for renal nerve ablation
US9895194B2 (en) 2013-09-04 2018-02-20 Boston Scientific Scimed, Inc. Radio frequency (RF) balloon catheter having flushing and cooling capability
US9907609B2 (en) 2014-02-04 2018-03-06 Boston Scientific Scimed, Inc. Alternative placement of thermal sensors on bipolar electrode
US9925001B2 (en) 2013-07-19 2018-03-27 Boston Scientific Scimed, Inc. Spiral bipolar electrode renal denervation balloon
US9943365B2 (en) 2013-06-21 2018-04-17 Boston Scientific Scimed, Inc. Renal denervation balloon catheter with ride along electrode support
US9955946B2 (en) 2014-03-12 2018-05-01 Cibiem, Inc. Carotid body ablation with a transvenous ultrasound imaging and ablation catheter
US9956033B2 (en) 2013-03-11 2018-05-01 Boston Scientific Scimed, Inc. Medical devices for modulating nerves
US20180117363A1 (en) * 2012-03-08 2018-05-03 Medtronic Ardian Luxembourg S.A.R.L. Catheter-based devices and associated methods for immune system neuromodulation
US9962223B2 (en) 2013-10-15 2018-05-08 Boston Scientific Scimed, Inc. Medical device balloon
US9974607B2 (en) 2006-10-18 2018-05-22 Vessix Vascular, Inc. Inducing desirable temperature effects on body tissue
US10004557B2 (en) 2012-11-05 2018-06-26 Pythagoras Medical Ltd. Controlled tissue ablation
US10022182B2 (en) 2013-06-21 2018-07-17 Boston Scientific Scimed, Inc. Medical devices for renal nerve ablation having rotatable shafts
CN108472017A (en) * 2015-10-06 2018-08-31 爱视珍科技有限责任公司 Ultrasonic guidance cavitation process and system for eye treatment
US10085799B2 (en) 2011-10-11 2018-10-02 Boston Scientific Scimed, Inc. Off-wall electrode device and methods for nerve modulation
US10265122B2 (en) 2013-03-15 2019-04-23 Boston Scientific Scimed, Inc. Nerve ablation devices and related methods of use
US10271898B2 (en) 2013-10-25 2019-04-30 Boston Scientific Scimed, Inc. Embedded thermocouple in denervation flex circuit
US10321946B2 (en) 2012-08-24 2019-06-18 Boston Scientific Scimed, Inc. Renal nerve modulation devices with weeping RF ablation balloons
US10335280B2 (en) 2000-01-19 2019-07-02 Medtronic, Inc. Method for ablating target tissue of a patient
US10342609B2 (en) 2013-07-22 2019-07-09 Boston Scientific Scimed, Inc. Medical devices for renal nerve ablation
US10383685B2 (en) 2015-05-07 2019-08-20 Pythagoras Medical Ltd. Techniques for use with nerve tissue
US10398464B2 (en) 2012-09-21 2019-09-03 Boston Scientific Scimed, Inc. System for nerve modulation and innocuous thermal gradient nerve block
US10413357B2 (en) 2013-07-11 2019-09-17 Boston Scientific Scimed, Inc. Medical device with stretchable electrode assemblies
US10478249B2 (en) 2014-05-07 2019-11-19 Pythagoras Medical Ltd. Controlled tissue ablation techniques
US10549127B2 (en) 2012-09-21 2020-02-04 Boston Scientific Scimed, Inc. Self-cooling ultrasound ablation catheter
US10589130B2 (en) 2006-05-25 2020-03-17 Medtronic, Inc. Methods of using high intensity focused ultrasound to form an ablated tissue area containing a plurality of lesions
US10660698B2 (en) 2013-07-11 2020-05-26 Boston Scientific Scimed, Inc. Devices and methods for nerve modulation
US10660703B2 (en) 2012-05-08 2020-05-26 Boston Scientific Scimed, Inc. Renal nerve modulation devices
US10695124B2 (en) 2013-07-22 2020-06-30 Boston Scientific Scimed, Inc. Renal nerve ablation catheter having twist balloon
US10722300B2 (en) 2013-08-22 2020-07-28 Boston Scientific Scimed, Inc. Flexible circuit having improved adhesion to a renal nerve modulation balloon
US10835305B2 (en) 2012-10-10 2020-11-17 Boston Scientific Scimed, Inc. Renal nerve modulation devices and methods
US10945786B2 (en) 2013-10-18 2021-03-16 Boston Scientific Scimed, Inc. Balloon catheters with flexible conducting wires and related methods of use and manufacture
US10952790B2 (en) 2013-09-13 2021-03-23 Boston Scientific Scimed, Inc. Ablation balloon with vapor deposited cover layer
US11000679B2 (en) 2014-02-04 2021-05-11 Boston Scientific Scimed, Inc. Balloon protection and rewrapping devices and related methods of use
US11202671B2 (en) 2014-01-06 2021-12-21 Boston Scientific Scimed, Inc. Tear resistant flex circuit assembly
US11246654B2 (en) 2013-10-14 2022-02-15 Boston Scientific Scimed, Inc. Flexible renal nerve ablation devices and related methods of use and manufacture
JP2022169606A (en) * 2016-10-31 2022-11-09 ゼネラル・エレクトリック・カンパニイ Techniques for neuromodulation
US11678932B2 (en) 2016-05-18 2023-06-20 Symap Medical (Suzhou) Limited Electrode catheter with incremental advancement
US20230233282A1 (en) * 2022-01-24 2023-07-27 Siemens Healthcare Gmbh Therapeutic apparatus for ultrasonic treatment
JP7445232B2 (en) 2016-03-31 2024-03-07 トーマス・ジェファーソン・ユニバーシティ Tumor implant for multimodality treatment of risk tissue surrounding the resection cavity

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE532142C2 (en) * 2007-09-28 2009-11-03 Clinical Laserthermia Systems Device for determining a thermal property of a tissue
CA2770452C (en) 2009-08-17 2017-09-19 Histosonics, Inc. Disposable acoustic coupling medium container
WO2011028603A2 (en) 2009-08-26 2011-03-10 The Regents Of The University Of Michigan Micromanipulator control arm for therapeutic and imaging ultrasound transducers
CA2770706C (en) 2009-08-26 2017-06-20 Charles A. Cain Devices and methods for using controlled bubble cloud cavitation in fractionating urinary stones
US9144694B2 (en) 2011-08-10 2015-09-29 The Regents Of The University Of Michigan Lesion generation through bone using histotripsy therapy without aberration correction
WO2013166019A1 (en) 2012-04-30 2013-11-07 The Regents Of The University Of Michigan Ultrasound transducer manufacturing using rapid-prototyping method
WO2014055906A1 (en) 2012-10-05 2014-04-10 The Regents Of The University Of Michigan Bubble-induced color doppler feedback during histotripsy
US10076384B2 (en) 2013-03-08 2018-09-18 Symple Surgical, Inc. Balloon catheter apparatus with microwave emitter
CN105530869B (en) 2013-07-03 2019-10-29 希斯托索尼克斯公司 The histotripsy excitation sequence optimized is formed to bubble cloud using impact scattering
WO2015003154A1 (en) 2013-07-03 2015-01-08 Histosonics, Inc. Articulating arm limiter for cavitational ultrasound therapy system
WO2015027164A1 (en) 2013-08-22 2015-02-26 The Regents Of The University Of Michigan Histotripsy using very short ultrasound pulses
ES2948135T3 (en) 2015-06-24 2023-08-31 Univ Michigan Regents Histotripsy therapy systems for the treatment of brain tissue
CN105796330A (en) * 2016-03-10 2016-07-27 深圳市海德医疗设备有限公司 High blood pressure therapy machine with pressure waves
US11013938B2 (en) 2016-07-27 2021-05-25 The Trustees Of Columbia University In The City Of New York Methods and systems for peripheral nerve modulation using non ablative focused ultrasound with electromyography (EMG) monitoring
US11020617B2 (en) 2016-07-27 2021-06-01 The Trustees Of Columbia University In The City Of New York Methods and systems for peripheral nerve modulation using non ablative focused ultrasound with electromyography (EMG) monitoring
EP3509481A4 (en) * 2016-10-14 2020-08-19 Mark D. Noar Balloon structure with anchoring portions for anchoring in a bodily passage
CN109427065B (en) * 2017-08-31 2022-02-25 中国科学院微电子研究所 Guan mai recognition system based on thermal imaging
CN111655336A (en) 2017-11-17 2020-09-11 纽约州立大学研究基金会 Method for treating damaged peripheral nerves using x-ray microbeam radiation
CN109044307B (en) * 2018-09-17 2020-07-21 西安交通大学 Noninvasive blood pressure regulating and controlling system based on ultrasonic nerve stimulation
WO2020113083A1 (en) 2018-11-28 2020-06-04 Histosonics, Inc. Histotripsy systems and methods
WO2021155026A1 (en) 2020-01-28 2021-08-05 The Regents Of The University Of Michigan Systems and methods for histotripsy immunosensitization
CN112023284A (en) * 2020-09-01 2020-12-04 中国科学院声学研究所 Focus position real-time monitoring method for focused acoustic dynamic therapy

Citations (100)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3499437A (en) * 1967-03-10 1970-03-10 Ultrasonic Systems Method and apparatus for treatment of organic structures and systems thereof with ultrasonic energy
US4905672A (en) * 1985-12-14 1990-03-06 Dornier Medizintechnik Gmbh Thromboses formation by means of shock waves
US4913155A (en) * 1987-05-11 1990-04-03 Capistrano Labs, Inc. Ultrasonic transducer probe assembly
US5080102A (en) * 1983-12-14 1992-01-14 Edap International, S.A. Examining, localizing and treatment with ultrasound
US5178148A (en) * 1990-04-06 1993-01-12 Technomed International Method of automatically measuring the volume of a tumor or of a gland, in particular the prostate, a measuring device, and a method and apparatus constituting and application thereof
US5178135A (en) * 1987-04-16 1993-01-12 Olympus Optical Co., Ltd. Therapeutical apparatus of extracorporeal type
US5193527A (en) * 1989-10-03 1993-03-16 Richard Wolf Gmbh Ultrasonic shock-wave transducer
US5194291A (en) * 1991-04-22 1993-03-16 General Atomics Corona discharge treatment
US5290278A (en) * 1992-10-20 1994-03-01 Proclosure Inc. Method and apparatus for applying thermal energy to luminal tissue
US5383896A (en) * 1993-05-25 1995-01-24 Gershony; Gary Vascular sealing device
US5391140A (en) * 1993-01-29 1995-02-21 Siemens Aktiengesellschaft Therapy apparatus for locating and treating a zone in the body of a life form with acoustic waves
US5394877A (en) * 1993-04-01 1995-03-07 Axon Medical, Inc. Ultrasound medical diagnostic device having a coupling medium providing self-adherence to a patient
US5492126A (en) * 1994-05-02 1996-02-20 Focal Surgery Probe for medical imaging and therapy using ultrasound
US5507744A (en) * 1992-04-23 1996-04-16 Scimed Life Systems, Inc. Apparatus and method for sealing vascular punctures
US5507790A (en) * 1994-03-21 1996-04-16 Weiss; William V. Method of non-invasive reduction of human site-specific subcutaneous fat tissue deposits by accelerated lipolysis metabolism
US5601526A (en) * 1991-12-20 1997-02-11 Technomed Medical Systems Ultrasound therapy apparatus delivering ultrasound waves having thermal and cavitation effects
US5609485A (en) * 1994-10-03 1997-03-11 Medsim, Ltd. Medical reproduction system
USD389574S (en) * 1996-11-27 1998-01-20 Eclipse Surgical Technologies, Inc. Finger grip device for a laser fiber optic delivery system
US5711058A (en) * 1994-11-21 1998-01-27 General Electric Company Method for manufacturing transducer assembly with curved transducer array
US5716374A (en) * 1995-10-10 1998-02-10 Symbiosis Corporation Stamped clevis for endoscopic instruments and method of making the same
US5720286A (en) * 1994-05-30 1998-02-24 Technomed Medical Systems Use of A-mode echography for monitoring the position of a patient during ultrasound therapy
US5720287A (en) * 1993-07-26 1998-02-24 Technomed Medical Systems Therapy and imaging probe and therapeutic treatment apparatus utilizing it
US5726066A (en) * 1994-03-10 1998-03-10 Lg Electronics Inc. Method for manufacturing an infrared sensor array
US5735796A (en) * 1995-11-23 1998-04-07 Siemens Aktiengesellschaft Therapy apparatus with a source of acoustic waves
US5738635A (en) * 1993-01-22 1998-04-14 Technomed Medical Systems Adjustable focusing therapeutic apparatus with no secondary focusing
US5873828A (en) * 1994-02-18 1999-02-23 Olympus Optical Co., Ltd. Ultrasonic diagnosis and treatment system
US5873845A (en) * 1997-03-17 1999-02-23 General Electric Company Ultrasound transducer with focused ultrasound refraction plate
US5879314A (en) * 1997-06-30 1999-03-09 Cybersonics, Inc. Transducer assembly and method for coupling ultrasonic energy to a body for thrombolysis of vascular thrombi
US5882302A (en) * 1992-02-21 1999-03-16 Ths International, Inc. Methods and devices for providing acoustic hemostasis
US5882328A (en) * 1995-01-13 1999-03-16 Qlt Phototherapeutics, Inc. Method to prevent transplant rejection
US5895356A (en) * 1995-11-15 1999-04-20 American Medical Systems, Inc. Apparatus and method for transurethral focussed ultrasound therapy
US6036650A (en) * 1998-09-15 2000-03-14 Endosonics Corporation Ultrasonic imaging system and method with ringdown reduction
US6039694A (en) * 1998-06-25 2000-03-21 Sonotech, Inc. Coupling sheath for ultrasound transducers
US6050943A (en) * 1997-10-14 2000-04-18 Guided Therapy Systems, Inc. Imaging, therapy, and temperature monitoring ultrasonic system
US6179831B1 (en) * 1999-04-29 2001-01-30 Galil Medical Ltd. Method of cryoablating benign prostate hyperplasia
US6182341B1 (en) * 1995-06-07 2001-02-06 Acuson Corporation Method of manufacturing an improved coupling of acoustic window and lens for medical ultrasound transducers
US6200539B1 (en) * 1998-01-08 2001-03-13 The University Of Tennessee Research Corporation Paraelectric gas flow accelerator
US6206843B1 (en) * 1999-01-28 2001-03-27 Ultra Cure Ltd. Ultrasound system and methods utilizing same
US6221015B1 (en) * 1986-02-28 2001-04-24 Cardiovascular Imaging Systems, Inc. Method and apparatus for intravascular two-dimensional ultrasonography
US20030009194A1 (en) * 2000-12-07 2003-01-09 Saker Mark B. Tissue tract sealing device
US6506171B1 (en) * 2000-07-27 2003-01-14 Insightec-Txsonics, Ltd System and methods for controlling distribution of acoustic energy around a focal point using a focused ultrasound system
US20030018255A1 (en) * 1997-10-31 2003-01-23 Martin Roy W. Method and apparatus for medical procedures using high-intensity focused ultrasound
US6514221B2 (en) * 2000-07-27 2003-02-04 Brigham And Women's Hospital, Inc. Blood-brain barrier opening
US6522926B1 (en) * 2000-09-27 2003-02-18 Cvrx, Inc. Devices and methods for cardiovascular reflex control
US20030050665A1 (en) * 2001-09-07 2003-03-13 Integrated Vascular Systems, Inc. Needle apparatus for closing septal defects and methods for using such apparatus
US20030060737A1 (en) * 1997-12-31 2003-03-27 Pharmasonics, Inc. Methods and systems for the inhibition of vascular hyperplasia
US20030069569A1 (en) * 2001-08-29 2003-04-10 Burdette Everette C. Ultrasound device for treatment of intervertebral disc tissue
US6548047B1 (en) * 1997-09-15 2003-04-15 Bristol-Myers Squibb Medical Imaging, Inc. Thermal preactivation of gaseous precursor filled compositions
US6551576B1 (en) * 1989-12-22 2003-04-22 Bristol-Myers Squibb Medical Imaging, Inc. Container with multi-phase composition for use in diagnostic and therapeutic applications
US20040002654A1 (en) * 2000-09-29 2004-01-01 New Health Sciences, Inc. Precision brain blood flow assessment remotely in real time using nanotechnology ultrasound
US6676601B1 (en) * 1999-05-26 2004-01-13 Technomed Medical Systems, S.A. Apparatus and method for location and treatment using ultrasound
US6682483B1 (en) * 1999-05-28 2004-01-27 Vuesonix Sensors, Inc. Device and method for mapping and tracking blood flow and determining parameters of blood flow
US6685639B1 (en) * 1998-01-25 2004-02-03 Chongqing Hifu High intensity focused ultrasound system for scanning and curing tumor
US20040030269A1 (en) * 2000-11-07 2004-02-12 Gerald Horn Method and apparatus for the correction of presbyopia using high intensity focused ultrasound
US20040030268A1 (en) * 1999-11-26 2004-02-12 Therus Corporation (Legal) Controlled high efficiency lesion formation using high intensity ultrasound
US6706892B1 (en) * 1999-09-07 2004-03-16 Conjuchem, Inc. Pulmonary delivery for bioconjugation
US20040054289A1 (en) * 1997-01-08 2004-03-18 Volcano Therapeutics, Inc. Method for manufacturing an intravascular ultrasound transducer assembly having a flexible substrate
US6709407B2 (en) * 2001-10-30 2004-03-23 Mayo Foundation For Medical Education And Research Method and apparatus for fetal audio stimulation
US6709392B1 (en) * 2002-10-10 2004-03-23 Koninklijke Philips Electronics N.V. Imaging ultrasound transducer temperature control system and method using feedback
US6716184B2 (en) * 1998-09-18 2004-04-06 University Of Washington Ultrasound therapy head configured to couple to an ultrasound imaging probe to facilitate contemporaneous imaging using low intensity ultrasound and treatment using high intensity focused ultrasound
US6719694B2 (en) * 1999-12-23 2004-04-13 Therus Corporation Ultrasound transducers for imaging and therapy
US6719699B2 (en) * 2002-02-07 2004-04-13 Sonotech, Inc. Adhesive hydrophilic membranes as couplants in ultrasound imaging applications
US20040078034A1 (en) * 2001-07-16 2004-04-22 Acker David E Coagulator and spinal disk surgery
US20040078219A1 (en) * 2001-12-04 2004-04-22 Kimberly-Clark Worldwide, Inc. Healthcare networks with biosensors
US6726627B1 (en) * 1999-08-09 2004-04-27 Riverside Research Institute System and method for ultrasonic harmonic imaging for therapy guidance and monitoring
US20040082978A1 (en) * 2000-09-28 2004-04-29 Harrison William Vanbrooks Systems and methods for modulation of circulatory perfusion by electrical and/or drug stimulation
US6846291B2 (en) * 2002-11-20 2005-01-25 Sonotech, Inc. Production of lubricious coating on adhesive hydrogels
US20050054955A1 (en) * 2002-01-15 2005-03-10 Lars Lidgren Device for non-invasive ultrasound treatment of an object
US20050065436A1 (en) * 2003-09-23 2005-03-24 Ho Winston Zonh Rapid and non-invasive optical detection of internal bleeding
US6875176B2 (en) * 2000-11-28 2005-04-05 Aller Physionix Limited Systems and methods for making noninvasive physiological assessments
US20050085793A1 (en) * 2001-03-30 2005-04-21 Glossop Neil D. Device and method for registering a position sensor in an anatomical body
US20050192638A1 (en) * 2002-04-08 2005-09-01 Mark Gelfand Methods and devices for renal nerve blocking
US20060052701A1 (en) * 1998-09-18 2006-03-09 University Of Washington Treatment of unwanted tissue by the selective destruction of vasculature providing nutrients to the tissue
US20070004984A1 (en) * 1997-10-31 2007-01-04 University Of Washington Method and apparatus for preparing organs and tissues for laparoscopic surgery
US20070004964A1 (en) * 2005-07-01 2007-01-04 Pentax Corporation Image capturing unit for endoscope
US7162303B2 (en) * 2002-04-08 2007-01-09 Ardian, Inc. Renal nerve stimulation method and apparatus for treatment of patients
US20070038115A1 (en) * 2005-08-12 2007-02-15 Quigley David P High intensity ultrasound apparatus methods and systems
US20070055155A1 (en) * 2005-08-17 2007-03-08 Neil Owen Method and system to synchronize acoustic therapy with ultrasound imaging
US20070055181A1 (en) * 2005-09-07 2007-03-08 Deem Mark E Apparatus for treating subcutaneous tissues
US20070066957A1 (en) * 2004-11-02 2007-03-22 Ardian, Inc. Methods and apparatus for inducing controlled renal neuromodulation
US20070135875A1 (en) * 2002-04-08 2007-06-14 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US20070265687A1 (en) * 2002-04-08 2007-11-15 Ardian, Inc. Apparatuses for renal neuromodulation
US20080025756A1 (en) * 2004-08-28 2008-01-31 Byung-Sun Ahn Developing unit having foldable handle and image forming apparatus having the same
US20080033292A1 (en) * 2006-08-02 2008-02-07 Insightec Ltd Ultrasound patient interface device
US20080039746A1 (en) * 2006-05-25 2008-02-14 Medtronic, Inc. Methods of using high intensity focused ultrasound to form an ablated tissue area containing a plurality of lesions
US20080045865A1 (en) * 2004-11-12 2008-02-21 Hanoch Kislev Nanoparticle Mediated Ultrasound Therapy and Diagnostic Imaging
US20080045864A1 (en) * 2002-09-12 2008-02-21 The Regents Of The University Of California. Dynamic acoustic focusing utilizing time reversal
US20080047325A1 (en) * 2006-07-17 2008-02-28 Kci Licensing, Inc., Legal Department, Intellectual Property Measurement of moisture vapor transfer rate
US20080058683A1 (en) * 2003-06-10 2008-03-06 Cierra, Inc. Method and apparatus for non-invasively treating patent foramen ovale using high intensity focused ultrasound
US20090012098A1 (en) * 2001-01-29 2009-01-08 Otsuka Pharmaceutical Co., 5-ht1a receptor subtype agonist
US7499748B2 (en) * 2005-04-11 2009-03-03 Cardiac Pacemakers, Inc. Transvascular neural stimulation device
US20090062873A1 (en) * 2006-06-28 2009-03-05 Ardian, Inc. Methods and systems for thermally-induced renal neuromodulation
US20090062697A1 (en) * 1999-10-25 2009-03-05 Therus Corporation Insertable ultrasound probes, systems, and methods for thermal therapy
US7510536B2 (en) * 1999-09-17 2009-03-31 University Of Washington Ultrasound guided high intensity focused ultrasound treatment of nerves
US20100022921A1 (en) * 2004-03-02 2010-01-28 Ralf Seip Ultrasound phased arrays
US20100023088A1 (en) * 2008-03-27 2010-01-28 Stack Richard S System and method for transvascularly stimulating contents of the carotid sheath
US20100042020A1 (en) * 2008-08-13 2010-02-18 Shmuel Ben-Ezra Focused energy delivery apparatus method and system
US7684865B2 (en) * 2003-03-14 2010-03-23 Endovx, Inc. Methods and apparatus for treatment of obesity
US20120065492A1 (en) * 2009-10-12 2012-03-15 Kona Medical, Inc. Energetic modulation of nerves
US8347891B2 (en) * 2002-04-08 2013-01-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen

Family Cites Families (320)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US385256A (en) 1888-06-26 eggers
US3274437A (en) 1963-11-20 1966-09-20 Thompson Ramo Wooldridge Inc High intensity radiant energy source
US3552382A (en) 1968-01-11 1971-01-05 Hoffmann La Roche Ultrasonic transducer assembly for biological inspections
US3927662A (en) 1971-12-08 1975-12-23 Hoffmann La Roche Ultrasonic transducer assembly
US3847016A (en) 1971-12-08 1974-11-12 Hoffmann La Roche Ultrasonic transducer assembly
US4167180A (en) 1975-05-01 1979-09-11 The Commonwealth Of Australia, Care Of The Department Of Health Method and apparatus for ultrasonic examination
US4059098A (en) 1975-07-21 1977-11-22 Stanford Research Institute Flexible ultrasound coupling system
US4197856A (en) 1978-04-10 1980-04-15 Northrop Robert B Ultrasonic respiration/convulsion monitoring apparatus and method for its use
US4206763A (en) 1978-08-01 1980-06-10 Drexel University Ultrasonic scanner for breast cancer examination
US4237901A (en) 1978-08-30 1980-12-09 Picker Corporation Low and constant pressure transducer probe for ultrasonic diagnostic system
US4273127A (en) 1978-10-12 1981-06-16 Research Corporation Method for cutting and coagulating tissue
US4469099A (en) 1980-10-02 1984-09-04 Western Clinical Engineering Ltd. Pneumatic torniquet
US4484569A (en) 1981-03-13 1984-11-27 Riverside Research Institute Ultrasonic diagnostic and therapeutic transducer assembly and method for using
US4479494A (en) 1982-01-05 1984-10-30 Western Clinical Engineering Ltd. Adaptive pneumatic tourniquet
DE3219271A1 (en) 1982-05-21 1983-11-24 Siemens AG, 1000 Berlin und 8000 München ULTRASONIC APPLICATOR
US4773899A (en) 1982-11-23 1988-09-27 The Beth Israel Hospital Association Method of treatment of artherosclerosis and balloon catheter the same
JPS59147508U (en) 1983-03-25 1984-10-02 株式会社東芝 Ultrasonic probe adapter
US4601296A (en) 1983-10-07 1986-07-22 Yeda Research And Development Co., Ltd. Hyperthermia apparatus
US5150712A (en) 1983-12-14 1992-09-29 Edap International, S.A. Apparatus for examining and localizing tumors using ultra sounds, comprising a device for localized hyperthermia treatment
USRE33590E (en) 1983-12-14 1991-05-21 Edap International, S.A. Method for examining, localizing and treating with ultrasound
US4605010A (en) 1984-05-17 1986-08-12 Western Clinical Engineering Ltd. Pressurizing cuff
US4702732A (en) 1984-12-24 1987-10-27 Trustees Of Boston University Electrodes, electrode assemblies, methods, and systems for tissue stimulation and transdermal delivery of pharmacologically active ligands
JPS61209643A (en) 1985-03-15 1986-09-17 株式会社東芝 Ultrasonic diagnostic and medical treatment apparatus
EP0195718A1 (en) 1985-03-22 1986-09-24 Commissariat A L'energie Atomique Artificial skull, prosthetic head built up from the skull and process for producing them
JPH0653120B2 (en) 1985-05-10 1994-07-20 オリンパス光学工業株式会社 Ultrasonic diagnostic equipment
GB8529446D0 (en) 1985-11-29 1986-01-08 Univ Aberdeen Divergent ultrasound arrays
US4784148A (en) 1986-02-21 1988-11-15 Johnson & Johnson Ultrasonic transducer probe expansion chamber
JPH074373B2 (en) 1986-10-16 1995-01-25 オリンパス光学工業株式会社 Ultrasound endoscopy
US4770175A (en) 1986-10-22 1988-09-13 Western Clinical Engineering Ltd. Occlusive cuff
US4883790A (en) 1987-01-20 1989-11-28 University Of British Columbia Wavelength-specific cytotoxic agents
DE3704909A1 (en) 1987-02-17 1988-08-25 Wolf Gmbh Richard DEVICE FOR SPACIOUS LOCATION AND DESTRUCTION OF INTERIOR OBJECTS WITH ULTRASOUND
US5181522A (en) 1987-04-03 1993-01-26 Abatis Medical Technologies Limited Tourniquet for sensing and regulation of applied pressure
US4773865A (en) 1987-06-26 1988-09-27 Baldwin Jere F Training mannequin
US4931047A (en) 1987-09-30 1990-06-05 Cavitron, Inc. Method and apparatus for providing enhanced tissue fragmentation and/or hemostasis
US4957481A (en) 1987-10-01 1990-09-18 U.S. Bioscience Photodynamic therapeutic technique
US4841979A (en) 1988-01-25 1989-06-27 Capistrano Labs, Inc. Ultrasonic prostate probe assembly
US4957099A (en) 1988-02-10 1990-09-18 Siemens Aktiengesellschaft Shock wave source for extracorporeal lithotripsy
US4858613A (en) 1988-03-02 1989-08-22 Laboratory Equipment, Corp. Localization and therapy system for treatment of spatially oriented focal disease
US5036855A (en) 1988-03-02 1991-08-06 Laboratory Equipment, Corp. Localization and therapy system for treatment of spatially oriented focal disease
US5522878A (en) 1988-03-25 1996-06-04 Lectec Corporation Solid multipurpose ultrasonic biomedical couplant gel in sheet form and method
US4966953A (en) 1988-06-02 1990-10-30 Takiron Co., Ltd. Liquid segment polyurethane gel and couplers for ultrasonic diagnostic probe comprising the same
US4938217A (en) 1988-06-21 1990-07-03 Massachusetts Institute Of Technology Electronically-controlled variable focus ultrasound hyperthermia system
US4938216A (en) 1988-06-21 1990-07-03 Massachusetts Institute Of Technology Mechanically scanned line-focus ultrasound hyperthermia system
US5211160A (en) 1988-09-14 1993-05-18 Interpore Orthopaedics, Inc. Ultrasonic orthopedic treatment head and body-mounting means therefor
US4929246A (en) 1988-10-27 1990-05-29 C. R. Bard, Inc. Method for closing and sealing an artery after removing a catheter
FR2643252B1 (en) 1989-02-21 1991-06-07 Technomed Int Sa APPARATUS FOR THE SELECTIVE DESTRUCTION OF CELLS INCLUDING SOFT TISSUES AND BONES WITHIN THE BODY OF A LIVING BODY BY IMPLOSION OF GAS BUBBLES
DE3922641A1 (en) 1989-07-10 1991-01-24 Wolf Gmbh Richard RUN FOR A LITHOTRIPSY DEVICE
EP0419729A1 (en) 1989-09-29 1991-04-03 Siemens Aktiengesellschaft Position finding of a catheter by means of non-ionising fields
DE69021158T2 (en) 1989-09-29 1995-12-07 Terumo Corp Ultrasonic coupler and manufacturing process.
US5585112A (en) 1989-12-22 1996-12-17 Imarx Pharmaceutical Corp. Method of preparing gas and gaseous precursor-filled microspheres
US5584853A (en) 1990-01-29 1996-12-17 Mcewen; James A. Tourniquet cuff apparatus
US5607447A (en) 1993-09-28 1997-03-04 Mcewen; James A. Physiologic tourniquet
US5556415A (en) 1990-01-29 1996-09-17 Mcewen; James A. Physiologic tourniquet for intravenous regional anesthesia
US5254087A (en) 1990-01-29 1993-10-19 Ivra Systems, Inc. Tourniquet apparatus for intravenous regional anesthesia
US5026387A (en) 1990-03-12 1991-06-25 Ultracision Inc. Method and apparatus for ultrasonic surgical cutting and hemostatis
US5263957A (en) 1990-03-12 1993-11-23 Ultracision Inc. Ultrasonic scalpel blade and methods of application
DE69123864T2 (en) 1990-03-24 1997-08-14 Toshiba Kawasaki Kk Device for medical treatment with ultrasound waves
FR2660732B1 (en) 1990-04-06 1992-09-04 Technomed Int Sa TRANSLATABLE END ARM AND THERAPEUTIC TREATMENT APPARATUS, INCLUDING APPLICATION.
US5215680A (en) 1990-07-10 1993-06-01 Cavitation-Control Technology, Inc. Method for the production of medical-grade lipid-coated microbubbles, paramagnetic labeling of such microbubbles and therapeutic uses of microbubbles
WO1992014513A1 (en) 1991-02-13 1992-09-03 Interface Biomedical Laboratories Corp. Filler material for use in tissue welding
US5316000A (en) 1991-03-05 1994-05-31 Technomed International (Societe Anonyme) Use of at least one composite piezoelectric transducer in the manufacture of an ultrasonic therapy apparatus for applying therapy, in a body zone, in particular to concretions, to tissue, or to bones, of a living being and method of ultrasonic therapy
US5243988A (en) 1991-03-13 1993-09-14 Scimed Life Systems, Inc. Intravascular imaging apparatus and methods for use and manufacture
US5233994A (en) 1991-05-13 1993-08-10 Advanced Technology Laboratories, Inc. Detection of tissue abnormality through blood perfusion differentiation
JP3300419B2 (en) 1991-08-21 2002-07-08 株式会社東芝 Thrombolysis treatment device
US5348552A (en) 1991-08-30 1994-09-20 Hoya Corporation Laser surgical unit
US6875420B1 (en) 1991-09-17 2005-04-05 Amersham Health As Method of ultrasound imaging
US5649954A (en) 1991-09-30 1997-07-22 Mcewen; James A. Tourniquet cuff system
US5741295A (en) 1991-09-30 1998-04-21 James A. McEwen Overlapping tourniquet cuff system
US5312431A (en) 1991-09-30 1994-05-17 Abatis Medical Technologies Limited Occlusive cuff
US5524620A (en) 1991-11-12 1996-06-11 November Technologies Ltd. Ablation of blood thrombi by means of acoustic energy
US5230334A (en) 1992-01-22 1993-07-27 Summit Technology, Inc. Method and apparatus for generating localized hyperthermia
AU3727993A (en) 1992-02-21 1993-09-13 Diasonics Inc. Ultrasound intracavity system for imaging therapy planning and treatment of focal disease
WO1993019705A1 (en) 1992-03-31 1993-10-14 Massachusetts Institute Of Technology Apparatus and method for acoustic heat generation and hyperthermia
US5810810A (en) 1992-04-23 1998-09-22 Scimed Life Systems, Inc. Apparatus and method for sealing vascular punctures
US5230921A (en) 1992-08-04 1993-07-27 Blacktoe Medical, Inc. Flexible piezo-electric membrane
US5415657A (en) 1992-10-13 1995-05-16 Taymor-Luria; Howard Percutaneous vascular sealing method
US5391197A (en) 1992-11-13 1995-02-21 Dornier Medical Systems, Inc. Ultrasound thermotherapy probe
US5364389A (en) 1992-11-25 1994-11-15 Premier Laser Systems, Inc. Method and apparatus for sealing and/or grasping luminal tissue
US20020095164A1 (en) 1997-06-26 2002-07-18 Andreas Bernard H. Device and method for suturing tissue
US5573497A (en) 1994-11-30 1996-11-12 Technomed Medical Systems And Institut National High-intensity ultrasound therapy method and apparatus with controlled cavitation effect and reduced side lobes
DE4302538C1 (en) 1993-01-29 1994-04-07 Siemens Ag Ultrasonic therapy device for tumour treatment lithotripsy or osteorestoration - with ultrasonic imaging and ultrasonic treatment modes using respective acoustic wave frequencies
EP0683657B2 (en) 1993-02-10 2005-06-15 Siemens Aktiengesellschaft Apparatus for analgesic therapy and/or for influencing the vegetative nervous system
US5553618A (en) 1993-03-12 1996-09-10 Kabushiki Kaisha Toshiba Method and apparatus for ultrasound medical treatment
JP3578217B2 (en) 1993-04-15 2004-10-20 シーメンス アクチエンゲゼルシヤフト Treatment device for treating heart disease and blood vessels near the heart
US5626601A (en) 1995-10-27 1997-05-06 Gary Gershony Vascular sealing apparatus and method
US5716597A (en) 1993-06-04 1998-02-10 Molecular Biosystems, Inc. Emulsions as contrast agents and method of use
US5630837A (en) 1993-07-01 1997-05-20 Boston Scientific Corporation Acoustic ablation
WO1995002361A1 (en) 1993-07-15 1995-01-26 Zimmer Stevan D Doppler ultrasound trigger for use with mr
US5413550A (en) 1993-07-21 1995-05-09 Pti, Inc. Ultrasound therapy system with automatic dose control
US5445608A (en) 1993-08-16 1995-08-29 James C. Chen Method and apparatus for providing light-activated therapy
US5471988A (en) 1993-12-24 1995-12-05 Olympus Optical Co., Ltd. Ultrasonic diagnosis and therapy system in which focusing point of therapeutic ultrasonic wave is locked at predetermined position within observation ultrasonic scanning range
JPH07184907A (en) 1993-12-28 1995-07-25 Toshiba Corp Ultrasonic treating device
DE4443947B4 (en) 1994-01-14 2005-09-22 Siemens Ag endoscope
GB9408668D0 (en) 1994-04-30 1994-06-22 Orthosonics Ltd Untrasonic therapeutic system
AU2373695A (en) 1994-05-03 1995-11-29 Board Of Regents, The University Of Texas System Apparatus and method for noninvasive doppler ultrasound-guided real-time control of tissue damage in thermal therapy
US5454373A (en) 1994-07-20 1995-10-03 Boston Scientific Corporation Medical acoustic imaging
US5534232A (en) 1994-08-11 1996-07-09 Wisconsin Alumini Research Foundation Apparatus for reactions in dense-medium plasmas
US5807285A (en) 1994-08-18 1998-09-15 Ethicon-Endo Surgery, Inc. Medical applications of ultrasonic energy
US5503152A (en) 1994-09-28 1996-04-02 Tetrad Corporation Ultrasonic transducer assembly and method for three-dimensional imaging
US5453576A (en) 1994-10-24 1995-09-26 Transonic Systems Inc. Cardiovascular measurements by sound velocity dilution
US5920319A (en) 1994-10-27 1999-07-06 Wake Forest University Automatic analysis in virtual endoscopy
US5520188A (en) 1994-11-02 1996-05-28 Focus Surgery Inc. Annular array transducer
US5665073A (en) 1995-02-07 1997-09-09 Bulow; Christi Protective sheath and securement apparatus and method for surgical conduits
US5685307A (en) 1995-02-28 1997-11-11 Iowa State University Research Foundation, Inc. Method and apparatus for tissue characterization of animals using ultrasound
US5515853A (en) 1995-03-28 1996-05-14 Sonometrics Corporation Three-dimensional digital ultrasound tracking system
DE69634714T2 (en) 1995-03-31 2006-01-19 Kabushiki Kaisha Toshiba, Kawasaki Therapeutic ultrasound device
US5770801A (en) 1995-04-25 1998-06-23 Abbott Laboratories Ultrasound transmissive pad
US5558092A (en) 1995-06-06 1996-09-24 Imarx Pharmaceutical Corp. Methods and apparatus for performing diagnostic and therapeutic ultrasound simultaneously
US5755228A (en) 1995-06-07 1998-05-26 Hologic, Inc. Equipment and method for calibration and quality assurance of an ultrasonic bone anaylsis apparatus
US5902311A (en) 1995-06-15 1999-05-11 Perclose, Inc. Low profile intraluminal suturing device and method
US5655538A (en) 1995-06-19 1997-08-12 General Electric Company Ultrasonic phased array transducer with an ultralow impedance backfill and a method for making
US5810007A (en) 1995-07-26 1998-09-22 Associates Of The Joint Center For Radiation Therapy, Inc. Ultrasound localization and image fusion for the treatment of prostate cancer
US5855589A (en) 1995-08-25 1999-01-05 Mcewen; James A. Physiologic tourniquet for intravenous regional anesthesia
US5931853A (en) 1995-08-25 1999-08-03 Mcewen; James A. Physiologic tourniquet with safety circuit
US5638823A (en) 1995-08-28 1997-06-17 Rutgers University System and method for noninvasive detection of arterial stenosis
US5833647A (en) 1995-10-10 1998-11-10 The Penn State Research Foundation Hydrogels or lipogels with enhanced mass transfer for transdermal drug delivery
US5979453A (en) 1995-11-09 1999-11-09 Femrx, Inc. Needle myolysis system for uterine fibriods
US5598845A (en) 1995-11-16 1997-02-04 Stellartech Research Corporation Ultrasound transducer device for continuous imaging of the heart and other body parts
EP0864075A1 (en) 1995-11-28 1998-09-16 DORNIER MEDICAL SYSTEMS, Inc. Method and system for non-invasive temperature mapping of tissue
US6286989B1 (en) 1995-12-05 2001-09-11 Ronnald B. King Mixing device with vanes having sloping edges and method of mixing viscous fluids
US5824277A (en) 1995-12-06 1998-10-20 E. I.Du Pont De Nemours And Company Plasma oxidation of an exhaust gas stream from chlorinating titanium-containing material
US5935339A (en) 1995-12-14 1999-08-10 Iowa State University Decontamination device and method thereof
WO1997022015A1 (en) 1995-12-14 1997-06-19 Philips Electronics N.V. Method and device for heating by means of ultrasound guided by magnetic resonance imaging
US6332089B1 (en) 1996-02-15 2001-12-18 Biosense, Inc. Medical procedures and apparatus using intrabody probes
AU1983397A (en) 1996-02-29 1997-09-16 Acuson Corporation Multiple ultrasound image registration system, method and transducer
US6036687A (en) 1996-03-05 2000-03-14 Vnus Medical Technologies, Inc. Method and apparatus for treating venous insufficiency
JP3652791B2 (en) 1996-06-24 2005-05-25 独立行政法人科学技術振興機構 Ultrasonic diagnostic equipment
US5681339A (en) 1996-08-12 1997-10-28 Mcewen; James A. Apparatus and method for monitoring the patency of tubing in a pneumatic medical device
DE19635593C1 (en) 1996-09-02 1998-04-23 Siemens Ag Ultrasound transducer for diagnostic and therapeutic use
US5846517A (en) 1996-09-11 1998-12-08 Imarx Pharmaceutical Corp. Methods for diagnostic imaging using a renal contrast agent and a vasodilator
US20050182297A1 (en) 1996-10-04 2005-08-18 Dietrich Gravenstein Imaging scope
US5769790A (en) 1996-10-25 1998-06-23 General Electric Company Focused ultrasound surgery system guided by ultrasound imaging
US5827268A (en) 1996-10-30 1998-10-27 Hearten Medical, Inc. Device for the treatment of patent ductus arteriosus and method of using the device
US5827204A (en) 1996-11-26 1998-10-27 Grandia; Willem Medical noninvasive operations using focused modulated high power ultrasound
US6494848B1 (en) 1996-12-19 2002-12-17 St. Jude Medical Puerto Rico B.V. Measuring device for use with a hemostatic puncture closure device
US7789841B2 (en) 1997-02-06 2010-09-07 Exogen, Inc. Method and apparatus for connective tissue treatment
US5904659A (en) 1997-02-14 1999-05-18 Exogen, Inc. Ultrasonic treatment for wounds
US5788636A (en) 1997-02-25 1998-08-04 Acuson Corporation Method and system for forming an ultrasound image of a tissue while simultaneously ablating the tissue
IT1296010B1 (en) 1997-03-18 1999-06-04 Pavis Varese Srl TEXTILE MANUFACTURE FOR THE CLOSURE AND ELASTIC TENSIONING OF A GARMENT OR GARMENT
US6537246B1 (en) 1997-06-18 2003-03-25 Imarx Therapeutics, Inc. Oxygen delivery agents and uses for the same
US5922945A (en) 1997-04-16 1999-07-13 Abbott Laboratories Method and apparatus for noninvasively analyzing flowable products
US5906580A (en) 1997-05-05 1999-05-25 Creare Inc. Ultrasound system and method of administering ultrasound including a plurality of multi-layer transducer elements
DE69840444D1 (en) 1997-05-23 2009-02-26 Prorhythm Inc DISMISSABLE FOCUSING ULTRASOUND APPLICATOR OF HIGH INTENSITY
US6231507B1 (en) 1997-06-02 2001-05-15 Vnus Medical Technologies, Inc. Pressure tourniquet with ultrasound window and method of use
US5931786A (en) 1997-06-13 1999-08-03 Barzell Whitmore Maroon Bells, Inc. Ultrasound probe support and stepping device
US6042590A (en) 1997-06-16 2000-03-28 Novomedics, Llc Apparatus and methods for fallopian tube occlusion
US5957849A (en) 1997-06-30 1999-09-28 The Regents Of The University Of California Endoluminal ultrasound-guided resectoscope
US6652515B1 (en) 1997-07-08 2003-11-25 Atrionix, Inc. Tissue ablation device assembly and method for electrically isolating a pulmonary vein ostium from an atrial wall
EP1014857A4 (en) 1997-08-19 2006-10-25 John D Mendlein Multi-site ultrasound methods and devices, particularly for measurement of fluid regulation
US6037032A (en) 1997-09-02 2000-03-14 Lockheed Martin Energy Research Corp. Pitch-based carbon foam heat sink with phase change material
US6033506A (en) 1997-09-02 2000-03-07 Lockheed Martin Engery Research Corporation Process for making carbon foam
US5964782A (en) 1997-09-18 1999-10-12 Scimed Life Systems, Inc. Closure device and method
US6078831A (en) 1997-09-29 2000-06-20 Scimed Life Systems, Inc. Intravascular imaging guidewire
US6233477B1 (en) 1997-10-20 2001-05-15 Irvine Biomedical, Inc. Catheter system having controllable ultrasound locating means
US6071239A (en) 1997-10-27 2000-06-06 Cribbs; Robert W. Method and apparatus for lipolytic therapy using ultrasound energy
US5951476A (en) 1997-11-14 1999-09-14 Beach; Kirk Watson Method for detecting brain microhemorrhage
US6120453A (en) 1997-11-17 2000-09-19 Sharp; William A. Three-dimensional ultrasound system based on the coordination of multiple ultrasonic transducers
US6280388B1 (en) 1997-11-19 2001-08-28 Boston Scientific Technology, Inc. Aerogel backed ultrasound transducer
US5919139A (en) 1997-12-19 1999-07-06 Diasonics Ultrasound Vibrational doppler ultrasonic imaging
US6406759B1 (en) 1998-01-08 2002-06-18 The University Of Tennessee Research Corporation Remote exposure of workpieces using a recirculated plasma
US6562037B2 (en) 1998-02-12 2003-05-13 Boris E. Paton Bonding of soft biological tissues by passing high frequency electric current therethrough
US5997481A (en) 1998-02-17 1999-12-07 Ultra Sound Probe Covers, Llc Probe cover with deformable membrane gel reservoir
WO1999048621A2 (en) 1998-03-26 1999-09-30 Exogen, Inc. Arrays made from flexible transducer elements
US6246156B1 (en) 1998-03-27 2001-06-12 Ngk Insulators, Ltd. Piezoelectric/electrostrictive element
US5935144A (en) 1998-04-09 1999-08-10 Ethicon Endo-Surgery, Inc. Double sealed acoustic isolation members for ultrasonic
US6106463A (en) 1998-04-20 2000-08-22 Wilk; Peter J. Medical imaging device and associated method including flexible display
AU763551B2 (en) 1998-05-06 2003-07-24 Exogen, Inc. Ultrasound bandages
FR2778573B1 (en) 1998-05-13 2000-09-22 Technomed Medical Systems FREQUENCY ADJUSTMENT IN A HIGH INTENSITY FOCUSED ULTRASOUND TREATMENT APPARATUS
US5976092A (en) 1998-06-15 1999-11-02 Chinn; Douglas O. Combination stereotactic surgical guide and ultrasonic probe
US7686763B2 (en) 1998-09-18 2010-03-30 University Of Washington Use of contrast agents to increase the effectiveness of high intensity focused ultrasound therapy
US6277077B1 (en) 1998-11-16 2001-08-21 Cardiac Pathways Corporation Catheter including ultrasound transducer with emissions attenuation
US6254601B1 (en) 1998-12-08 2001-07-03 Hysterx, Inc. Methods for occlusion of the uterine arteries
US6213939B1 (en) 1998-12-10 2001-04-10 Mcewen James Allen Hazard monitor for surgical tourniquet systems
US6102860A (en) 1998-12-24 2000-08-15 Agilent Technologies, Inc. Ultrasound transducer for three-dimensional imaging
US6248124B1 (en) 1999-02-22 2001-06-19 Tyco Healthcare Group Arterial hole closure apparatus
US6270458B1 (en) 1999-03-05 2001-08-07 Barnev Inc. Cervix dilation and labor progression monitor
IL129461A0 (en) 1999-04-15 2000-02-29 F R A Y Project Dev Ltd 3-D ultrasound imaging system
US6259945B1 (en) 1999-04-30 2001-07-10 Uromed Corporation Method and device for locating a nerve
US6217530B1 (en) 1999-05-14 2001-04-17 University Of Washington Ultrasonic applicator for medical applications
US7534209B2 (en) 2000-05-26 2009-05-19 Physiosonics, Inc. Device and method for mapping and tracking blood flow and determining parameters of blood flow
US20040071664A1 (en) 1999-07-23 2004-04-15 Gendel Limited Delivery of an agent
US6361548B1 (en) 1999-08-20 2002-03-26 Mcewen James Allen Limb protection sleeve for matching tourniquet cuff
JP3848572B2 (en) 1999-09-10 2006-11-22 プロリズム,インコーポレイテッド Device for occluding anatomic tissue
US6231561B1 (en) 1999-09-20 2001-05-15 Appriva Medical, Inc. Method and apparatus for closing a body lumen
US6443894B1 (en) 1999-09-29 2002-09-03 Acuson Corporation Medical diagnostic ultrasound system and method for mapping surface data for three dimensional imaging
WO2001034018A2 (en) 1999-10-25 2001-05-17 Therus Corporation Use of focused ultrasound for vascular sealing
US8221402B2 (en) * 2000-01-19 2012-07-17 Medtronic, Inc. Method for guiding a medical device
US7706882B2 (en) 2000-01-19 2010-04-27 Medtronic, Inc. Methods of using high intensity focused ultrasound to form an ablated tissue area
US6409720B1 (en) 2000-01-19 2002-06-25 Medtronic Xomed, Inc. Methods of tongue reduction using high intensity focused ultrasound to form an ablated tissue area containing a plurality of lesions
US6595934B1 (en) 2000-01-19 2003-07-22 Medtronic Xomed, Inc. Methods of skin rejuvenation using high intensity focused ultrasound to form an ablated tissue area containing a plurality of lesions
US6520915B1 (en) 2000-01-28 2003-02-18 U-Systems, Inc. Ultrasound imaging system with intrinsic doppler capability
AU2001236731A1 (en) 2000-02-10 2001-08-20 Harmonia Medical Technologies Inc. Transurethral volume reduction of the prostate (tuvor)
US6633658B1 (en) 2000-03-17 2003-10-14 Senorx, Inc. System and method for managing intermittent interference on imaging systems
US7374538B2 (en) 2000-04-05 2008-05-20 Duke University Methods, systems, and computer program products for ultrasound measurements using receive mode parallel processing
US6905498B2 (en) 2000-04-27 2005-06-14 Atricure Inc. Transmural ablation device with EKG sensor and pacing electrode
AU2001249874A1 (en) 2000-04-27 2001-11-12 Medtronic, Inc. System and method for assessing transmurality of ablation lesions
US6599288B2 (en) 2000-05-16 2003-07-29 Atrionix, Inc. Apparatus and method incorporating an ultrasound transducer onto a delivery member
US6612988B2 (en) 2000-08-29 2003-09-02 Brigham And Women's Hospital, Inc. Ultrasound therapy
US7104958B2 (en) 2001-10-01 2006-09-12 New Health Sciences, Inc. Systems and methods for investigating intracranial pressure
IL138926A0 (en) 2000-10-06 2001-11-25 Notal Vision Ltd Method and system for detecting eye disease
US6524246B1 (en) 2000-10-13 2003-02-25 Sonocine, Inc. Ultrasonic cellular tissue screening tool
US6616624B1 (en) 2000-10-30 2003-09-09 Cvrx, Inc. Systems and method for controlling renovascular perfusion
US7022077B2 (en) 2000-11-28 2006-04-04 Allez Physionix Ltd. Systems and methods for making noninvasive assessments of cardiac tissue and parameters
US6447453B1 (en) 2000-12-07 2002-09-10 Koninklijke Philips Electronics N.V. Analysis of cardiac performance using ultrasonic diagnostic images
SE0100160D0 (en) * 2001-01-22 2001-01-22 Atos Medical Ab Method and apparatus for high energetic ultrasonic tissue treatment
ATE308922T1 (en) 2001-03-02 2005-11-15 Palti Yoram Prof DEVICE FOR DETECTING ARTERIAL STENOSIS
WO2002087692A1 (en) 2001-04-26 2002-11-07 The Procter & Gamble Company A method and apparatus for the treatment of cosmetic skin conditioins
US6576168B2 (en) 2001-05-22 2003-06-10 Poco Graphite, Inc. Process for making carbon foam induced by process depressurization
US6559644B2 (en) 2001-05-30 2003-05-06 Insightec - Txsonics Ltd. MRI-based temperature mapping with error compensation
JPWO2002100486A1 (en) 2001-06-07 2004-09-24 崇 岡井 Uterine fibroid treatment method and apparatus
US6735461B2 (en) 2001-06-19 2004-05-11 Insightec-Txsonics Ltd Focused ultrasound system with MRI synchronization
US6932771B2 (en) 2001-07-09 2005-08-23 Civco Medical Instruments Co., Inc. Tissue warming device and method
FR2827149B1 (en) 2001-07-13 2003-10-10 Technomed Medical Systems FOCUSED ULTRASOUND TREATMENT PROBE
US6682547B2 (en) 2001-08-14 2004-01-27 Mcewen James Allen Tourniquet cuff with identification apparatus
US6728566B1 (en) 2001-11-21 2004-04-27 Koninklijke Philips Electronics, N.V. Vessel tracking and tree extraction method and apparatus
US6780155B2 (en) 2001-12-18 2004-08-24 Koninklijke Philips Electronics Method and system for ultrasound blood flow imaging and volume flow calculations
SG114521A1 (en) 2002-01-21 2005-09-28 Univ Nanyang Ultrasonic treatment of breast cancers
EP1503685B1 (en) 2002-01-23 2012-10-31 The Regents of The University of California Implantable thermal treatment apparatus
US6755789B2 (en) 2002-02-05 2004-06-29 Inceptio Medical Technologies, Llc Ultrasonic vascular imaging system and method of blood vessel cannulation
US7128711B2 (en) 2002-03-25 2006-10-31 Insightec, Ltd. Positioning systems and methods for guided ultrasound therapy systems
US20030187371A1 (en) * 2002-03-27 2003-10-02 Insightec-Txsonics Ltd. Systems and methods for enhanced focused ultrasound ablation using microbubbles
US7617005B2 (en) 2002-04-08 2009-11-10 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US20070129761A1 (en) 2002-04-08 2007-06-07 Ardian, Inc. Methods for treating heart arrhythmia
US7620451B2 (en) 2005-12-29 2009-11-17 Ardian, Inc. Methods and apparatus for pulsed electric field neuromodulation via an intra-to-extravascular approach
US20030208101A1 (en) 2002-05-03 2003-11-06 Cecchi Michael D. Embryo-implanting catheter control system and method of the same
WO2003096883A2 (en) 2002-05-16 2003-11-27 Barbara Ann Karmanos Cancer Institute Combined diagnostic and therapeutic ultrasound system
CA2492140A1 (en) 2002-07-12 2004-01-22 Iscience Surgical Corporation Ultrasound interfacing device for tissue imaging
US7211045B2 (en) 2002-07-22 2007-05-01 Ep Medsystems, Inc. Method and system for using ultrasound in cardiac diagnosis and therapy
US7542793B2 (en) 2002-08-22 2009-06-02 Mayo Foundation For Medical Education And Research MR-guided breast tumor ablation and temperature imaging system
US20040054287A1 (en) 2002-08-29 2004-03-18 Stephens Douglas Neil Ultrasonic imaging devices and methods of fabrication
US20040122493A1 (en) 2002-09-09 2004-06-24 Kabushiki Kaisha Toshiba Ultrasonic irradiation apparatus
US7052463B2 (en) 2002-09-25 2006-05-30 Koninklijke Philips Electronics, N.V. Method and apparatus for cooling a contacting surface of an ultrasound probe
US7260250B2 (en) 2002-09-30 2007-08-21 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Computer-aided classification of anomalies in anatomical structures
US7697972B2 (en) * 2002-11-19 2010-04-13 Medtronic Navigation, Inc. Navigation system for cardiac therapies
US6831394B2 (en) 2002-12-11 2004-12-14 General Electric Company Backing material for micromachined ultrasonic transducer devices
US20040158154A1 (en) 2003-02-06 2004-08-12 Siemens Medical Solutions Usa, Inc. Portable three dimensional diagnostic ultrasound imaging methods and systems
US7783358B2 (en) 2003-03-14 2010-08-24 Endovx, Inc. Methods and apparatus for treatment of obesity with an ultrasound device movable in two or three axes
US20040254419A1 (en) 2003-04-08 2004-12-16 Xingwu Wang Therapeutic assembly
US20040220167A1 (en) 2003-05-02 2004-11-04 Nasrollah Samiy Methods of treating neuralgic pain
DE602004017248D1 (en) 2003-05-19 2008-12-04 Ust Inc Geometrically shaped hydrogel coupling bodies for high intensity focused ultrasound treatment
US8060197B2 (en) 2003-05-23 2011-11-15 Bio Control Medical (B.C.M.) Ltd. Parasympathetic stimulation for termination of non-sinus atrial tachycardia
US7738952B2 (en) 2003-06-09 2010-06-15 Palo Alto Investors Treatment of conditions through modulation of the autonomic nervous system
US7074218B2 (en) 2003-06-30 2006-07-11 Ethicon, Inc. Multi-modality ablation device
US8354773B2 (en) 2003-08-22 2013-01-15 Siemens Medical Solutions Usa, Inc. Composite acoustic absorber for ultrasound transducer backing material
US20050165298A1 (en) 2003-09-04 2005-07-28 Crum, Kaminski & Larson, Llc Treatment of cardiac tissue following myocardial infarction utilizing high intensity focused ultrasound
AU2004214572B2 (en) 2003-09-30 2010-04-29 Olympus Corporation Inserting shape detecting probe
US7285093B2 (en) 2003-10-10 2007-10-23 Imadent Ltd. systems for ultrasonic imaging of a jaw, methods of use thereof and coupling cushions suited for use in the mouth
US20050090104A1 (en) 2003-10-27 2005-04-28 Kai Yang Slurry compositions for chemical mechanical polishing of copper and barrier films
US20050096538A1 (en) 2003-10-29 2005-05-05 Siemens Medical Solutions Usa, Inc. Image plane stabilization for medical imaging
US20050119704A1 (en) 2003-11-13 2005-06-02 Peters Nicholas S. Control of cardiac arrhythmias by modification of neuronal conduction within fat pads of the heart
US7460906B2 (en) 2003-12-24 2008-12-02 Cardiac Pacemakers, Inc. Baroreflex stimulation to treat acute myocardial infarction
US7125383B2 (en) 2003-12-30 2006-10-24 General Electric Company Method and apparatus for ultrasonic continuous, non-invasive blood pressure monitoring
EP1718194A4 (en) 2004-01-20 2010-05-12 Topspin Medical Israel Ltd Mri probe for prostate imaging
CA2555473A1 (en) 2004-02-17 2005-09-01 Traxtal Technologies Inc. Method and apparatus for registration, verification, and referencing of internal organs
EP1742700A4 (en) 2004-03-02 2008-05-28 Cvrx Inc External baroreflex activation
US7854733B2 (en) 2004-03-24 2010-12-21 Biosense Webster, Inc. Phased-array for tissue treatment
US7654958B2 (en) 2004-04-20 2010-02-02 St. Jude Medical, Atrial Fibrillation Division, Inc. Method and apparatus for ultrasound imaging with autofrequency selection
WO2005107622A1 (en) 2004-05-06 2005-11-17 Nanyang Technological University Mechanical manipulator for hifu transducers
US20050261672A1 (en) 2004-05-18 2005-11-24 Mark Deem Systems and methods for selective denervation of heart dysrhythmias
WO2005122736A2 (en) 2004-06-10 2005-12-29 Imarx Therapeutics, Inc. Ultrasound device and method using same
US7806839B2 (en) 2004-06-14 2010-10-05 Ethicon Endo-Surgery, Inc. System and method for ultrasound therapy using grating lobes
US20090209862A1 (en) 2004-06-29 2009-08-20 Koninklijke Philips Electronics, N.V. Method and apparatus for medical ultrasound diagnostics
GB2445322B (en) 2004-08-13 2008-08-06 Stichting Tech Wetenschapp Intravasular ultrasound techniques
US8409099B2 (en) 2004-08-26 2013-04-02 Insightec Ltd. Focused ultrasound system for surrounding a body tissue mass and treatment method
US7393325B2 (en) 2004-09-16 2008-07-01 Guided Therapy Systems, L.L.C. Method and system for ultrasound treatment with a multi-directional transducer
MX2007003044A (en) 2004-09-16 2007-08-02 Univ Washington Acoustic coupler using an independent water pillow with circulation for cooling a transducer.
US7530958B2 (en) 2004-09-24 2009-05-12 Guided Therapy Systems, Inc. Method and system for combined ultrasound treatment
US20060082771A1 (en) 2004-10-14 2006-04-20 Agilent Technologies, Inc. Mount of optical components
AU2005307870A1 (en) 2004-11-15 2006-05-26 Christopher Decharms Stimulation of neural tissue with light
US7713210B2 (en) 2004-11-23 2010-05-11 St. Jude Medical, Atrial Fibrillation Division, Inc. Method and apparatus for localizing an ultrasound catheter
CN1814323B (en) 2005-01-31 2010-05-12 重庆海扶(Hifu)技术有限公司 Focusing ultrasonic therapeutical system
US7553284B2 (en) * 2005-02-02 2009-06-30 Vaitekunas Jeffrey J Focused ultrasound for pain reduction
CN103142251B (en) 2005-04-14 2015-04-29 维拉声学公司 Ultrasound imaging system with pixel oriented processing
EP1909908B1 (en) 2005-06-02 2011-03-30 Cancercure Technology AS Ultrasound treatment system
JP4686269B2 (en) 2005-06-22 2011-05-25 株式会社日立メディコ Ultrasonic therapy device
US20070016274A1 (en) 2005-06-29 2007-01-18 Boveja Birinder R Gastrointestinal (GI) ablation for GI tumors or to provide therapy for obesity, motility disorders, G.E.R.D., or to induce weight loss
EP1933941A2 (en) 2005-08-25 2008-06-25 Philip R. Houle Treatment systems for delivery of sensitizer solutions
US7430913B2 (en) 2005-08-26 2008-10-07 The Boeing Company Rapid prototype integrated matrix ultrasonic transducer array inspection apparatus, systems, and methods
US8167805B2 (en) 2005-10-20 2012-05-01 Kona Medical, Inc. Systems and methods for ultrasound applicator station keeping
US10716749B2 (en) 2005-11-03 2020-07-21 Palo Alto Investors Methods and compositions for treating a renal disease condition in a subject
AU2006315829B2 (en) 2005-11-10 2011-01-27 ElectroCore, LLC. Electrical stimulation treatment of bronchial constriction
US20070167806A1 (en) 2005-11-28 2007-07-19 Koninklijke Philips Electronics N.V. Multi-modality imaging and treatment
EP1962691A2 (en) * 2005-12-14 2008-09-03 Koninklijke Philips Electronics N.V. Method and apparatus for guidance and application of high intensity focused ultrasound for control of bleeding due to severed limbs
EP1962949B1 (en) 2005-12-20 2015-02-25 The Cleveland Clinic Foundation Apparatus for modulating the baroreflex system
US20070149880A1 (en) 2005-12-22 2007-06-28 Boston Scientific Scimed, Inc. Device and method for determining the location of a vascular opening prior to application of HIFU energy to seal the opening
US20080051767A1 (en) 2006-05-19 2008-02-28 Cvrx, Inc. Characterization and modulation of physiologic response using baroreflex activation in conjunction with drug therapy
US7871406B2 (en) 2006-08-04 2011-01-18 INTIO, Inc. Methods for planning and performing thermal ablation
CN100574829C (en) 2006-08-24 2009-12-30 重庆融海超声医学工程研究中心有限公司 A kind of high-strength focus supersonic therapeutic system of image documentation equipment guiding
US8287471B2 (en) 2007-02-20 2012-10-16 National Health Research Institutes Medical treatment using an ultrasound phased array
WO2008115830A2 (en) 2007-03-16 2008-09-25 Cyberheart, Inc. Radiation treatment planning and delivery for moving targets in the heart
WO2008144274A2 (en) 2007-05-14 2008-11-27 Sono Esthetx, Inc. Method, system, and apparatus for line-focused ultrasound therapy
US20080299177A1 (en) 2007-06-06 2008-12-04 Biovaluation & Analysis, Inc. Supramolecular Complexes for Use in Acoustically Mediated Intracellular Drug Delivery in vivo
JP5660890B2 (en) 2007-06-26 2015-01-28 バソノバ・インコーポレイテッドVasonova, Inc. Vascular access and guidance system
US8052604B2 (en) 2007-07-31 2011-11-08 Mirabilis Medica Inc. Methods and apparatus for engagement and coupling of an intracavitory imaging and high intensity focused ultrasound probe
EP2190532A1 (en) 2007-07-31 2010-06-02 M. Bret Schneider Device and method for hypertension treatment by non-invasive stimulation to vascular baroreceptors
US8824743B2 (en) 2007-08-23 2014-09-02 Verasonics, Inc. Adaptive ultrasound image reconstruction based on sensing of local media motion
US8251908B2 (en) 2007-10-01 2012-08-28 Insightec Ltd. Motion compensated image-guided focused ultrasound therapy system
US10035027B2 (en) 2007-10-31 2018-07-31 The Board Of Trustees Of The Leland Stanford Junior University Device and method for ultrasonic neuromodulation via stereotactic frame based technique
CA2706563C (en) 2007-11-21 2018-08-21 Focus Surgery, Inc. Method of diagnosis and treatment of tumors using high intensity focused ultrasound
CN101902971B (en) 2007-12-21 2013-03-13 皇家飞利浦电子股份有限公司 Systems and methods for tracking and guiding high intensity focused ultrasound beams
US20090221908A1 (en) * 2008-03-01 2009-09-03 Neil David Glossop System and Method for Alignment of Instrumentation in Image-Guided Intervention
US20090247911A1 (en) 2008-03-25 2009-10-01 Petr Novak Multiple-angle switched high intensity focused ultrasound
US20090264755A1 (en) 2008-04-22 2009-10-22 National Taiwan University High-Intensity Ultrasonic Vessel Ablator Using Blood Flow Signal for Precise Positioning
AU2009244058B2 (en) 2008-05-09 2015-07-02 Nuvaira, Inc Systems, assemblies, and methods for treating a bronchial tree
US20100010393A1 (en) 2008-07-08 2010-01-14 Medtronic Vascular, Inc. Treatment of Occlusions by External High Intensity Focused Ultrasound
CN103488870A (en) 2008-08-15 2014-01-01 皇家飞利浦电子股份有限公司 Model enhanced imaging
US8275442B2 (en) 2008-09-25 2012-09-25 Zeltiq Aesthetics, Inc. Treatment planning systems and methods for body contouring applications
US8808281B2 (en) 2008-10-21 2014-08-19 Microcube, Llc Microwave treatment devices and methods
US20100160781A1 (en) 2008-12-09 2010-06-24 University Of Washington Doppler and image guided device for negative feedback phased array hifu treatment of vascularized lesions
US8383671B1 (en) 2009-06-18 2013-02-26 Abbott Cardiovascular Systems Inc. Method of treating malignant solid tumors
KR101143645B1 (en) 2009-07-29 2012-05-09 주세은 Transcranial low-intensity ultrasound delivery device and non-invasive modulation of brain function
US8295912B2 (en) 2009-10-12 2012-10-23 Kona Medical, Inc. Method and system to inhibit a function of a nerve traveling with an artery
US9174065B2 (en) 2009-10-12 2015-11-03 Kona Medical, Inc. Energetic modulation of nerves
US8986231B2 (en) 2009-10-12 2015-03-24 Kona Medical, Inc. Energetic modulation of nerves
US20110118600A1 (en) 2009-11-16 2011-05-19 Michael Gertner External Autonomic Modulation
US9119951B2 (en) 2009-10-12 2015-09-01 Kona Medical, Inc. Energetic modulation of nerves
KR101673574B1 (en) 2009-10-30 2016-11-07 레코 메디컬, 인코포레이티드 Method and apparatus for treatment of hypertension through percutaneous ultrasound renal denervation
JP6042723B2 (en) 2009-10-30 2016-12-14 コナ メディカル, インコーポレイテッド Method and apparatus for non-invasive treatment of hypertension by ultrasonic renal nerve removal
US20110112400A1 (en) 2009-11-06 2011-05-12 Ardian, Inc. High intensity focused ultrasound catheter apparatuses, systems, and methods for renal neuromodulation
US20110251489A1 (en) 2010-04-07 2011-10-13 Physiosonics, Inc. Ultrasound monitoring systems, methods and components

Patent Citations (103)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3499437A (en) * 1967-03-10 1970-03-10 Ultrasonic Systems Method and apparatus for treatment of organic structures and systems thereof with ultrasonic energy
US5080102A (en) * 1983-12-14 1992-01-14 Edap International, S.A. Examining, localizing and treatment with ultrasound
US5080101A (en) * 1983-12-14 1992-01-14 Edap International, S.A. Method for examining and aiming treatment with untrasound
US4905672A (en) * 1985-12-14 1990-03-06 Dornier Medizintechnik Gmbh Thromboses formation by means of shock waves
US6221015B1 (en) * 1986-02-28 2001-04-24 Cardiovascular Imaging Systems, Inc. Method and apparatus for intravascular two-dimensional ultrasonography
US5178135A (en) * 1987-04-16 1993-01-12 Olympus Optical Co., Ltd. Therapeutical apparatus of extracorporeal type
US4913155A (en) * 1987-05-11 1990-04-03 Capistrano Labs, Inc. Ultrasonic transducer probe assembly
US5193527A (en) * 1989-10-03 1993-03-16 Richard Wolf Gmbh Ultrasonic shock-wave transducer
US6551576B1 (en) * 1989-12-22 2003-04-22 Bristol-Myers Squibb Medical Imaging, Inc. Container with multi-phase composition for use in diagnostic and therapeutic applications
US5178148A (en) * 1990-04-06 1993-01-12 Technomed International Method of automatically measuring the volume of a tumor or of a gland, in particular the prostate, a measuring device, and a method and apparatus constituting and application thereof
US5194291A (en) * 1991-04-22 1993-03-16 General Atomics Corona discharge treatment
US5601526A (en) * 1991-12-20 1997-02-11 Technomed Medical Systems Ultrasound therapy apparatus delivering ultrasound waves having thermal and cavitation effects
US5882302A (en) * 1992-02-21 1999-03-16 Ths International, Inc. Methods and devices for providing acoustic hemostasis
US5507744A (en) * 1992-04-23 1996-04-16 Scimed Life Systems, Inc. Apparatus and method for sealing vascular punctures
US5290278A (en) * 1992-10-20 1994-03-01 Proclosure Inc. Method and apparatus for applying thermal energy to luminal tissue
US5738635A (en) * 1993-01-22 1998-04-14 Technomed Medical Systems Adjustable focusing therapeutic apparatus with no secondary focusing
US5391140A (en) * 1993-01-29 1995-02-21 Siemens Aktiengesellschaft Therapy apparatus for locating and treating a zone in the body of a life form with acoustic waves
US5394877A (en) * 1993-04-01 1995-03-07 Axon Medical, Inc. Ultrasound medical diagnostic device having a coupling medium providing self-adherence to a patient
US5383896A (en) * 1993-05-25 1995-01-24 Gershony; Gary Vascular sealing device
US5720287A (en) * 1993-07-26 1998-02-24 Technomed Medical Systems Therapy and imaging probe and therapeutic treatment apparatus utilizing it
US5873828A (en) * 1994-02-18 1999-02-23 Olympus Optical Co., Ltd. Ultrasonic diagnosis and treatment system
US5726066A (en) * 1994-03-10 1998-03-10 Lg Electronics Inc. Method for manufacturing an infrared sensor array
US5507790A (en) * 1994-03-21 1996-04-16 Weiss; William V. Method of non-invasive reduction of human site-specific subcutaneous fat tissue deposits by accelerated lipolysis metabolism
US5492126A (en) * 1994-05-02 1996-02-20 Focal Surgery Probe for medical imaging and therapy using ultrasound
US5720286A (en) * 1994-05-30 1998-02-24 Technomed Medical Systems Use of A-mode echography for monitoring the position of a patient during ultrasound therapy
US5609485A (en) * 1994-10-03 1997-03-11 Medsim, Ltd. Medical reproduction system
US5711058A (en) * 1994-11-21 1998-01-27 General Electric Company Method for manufacturing transducer assembly with curved transducer array
US5882328A (en) * 1995-01-13 1999-03-16 Qlt Phototherapeutics, Inc. Method to prevent transplant rejection
US6182341B1 (en) * 1995-06-07 2001-02-06 Acuson Corporation Method of manufacturing an improved coupling of acoustic window and lens for medical ultrasound transducers
US5716374A (en) * 1995-10-10 1998-02-10 Symbiosis Corporation Stamped clevis for endoscopic instruments and method of making the same
US5895356A (en) * 1995-11-15 1999-04-20 American Medical Systems, Inc. Apparatus and method for transurethral focussed ultrasound therapy
US5735796A (en) * 1995-11-23 1998-04-07 Siemens Aktiengesellschaft Therapy apparatus with a source of acoustic waves
USD389574S (en) * 1996-11-27 1998-01-20 Eclipse Surgical Technologies, Inc. Finger grip device for a laser fiber optic delivery system
US20040054289A1 (en) * 1997-01-08 2004-03-18 Volcano Therapeutics, Inc. Method for manufacturing an intravascular ultrasound transducer assembly having a flexible substrate
US5873845A (en) * 1997-03-17 1999-02-23 General Electric Company Ultrasound transducer with focused ultrasound refraction plate
US5879314A (en) * 1997-06-30 1999-03-09 Cybersonics, Inc. Transducer assembly and method for coupling ultrasonic energy to a body for thrombolysis of vascular thrombi
US6548047B1 (en) * 1997-09-15 2003-04-15 Bristol-Myers Squibb Medical Imaging, Inc. Thermal preactivation of gaseous precursor filled compositions
US6050943A (en) * 1997-10-14 2000-04-18 Guided Therapy Systems, Inc. Imaging, therapy, and temperature monitoring ultrasonic system
US20030018255A1 (en) * 1997-10-31 2003-01-23 Martin Roy W. Method and apparatus for medical procedures using high-intensity focused ultrasound
US20070004984A1 (en) * 1997-10-31 2007-01-04 University Of Washington Method and apparatus for preparing organs and tissues for laparoscopic surgery
US20030060737A1 (en) * 1997-12-31 2003-03-27 Pharmasonics, Inc. Methods and systems for the inhibition of vascular hyperplasia
US6200539B1 (en) * 1998-01-08 2001-03-13 The University Of Tennessee Research Corporation Paraelectric gas flow accelerator
US6685639B1 (en) * 1998-01-25 2004-02-03 Chongqing Hifu High intensity focused ultrasound system for scanning and curing tumor
US6039694A (en) * 1998-06-25 2000-03-21 Sonotech, Inc. Coupling sheath for ultrasound transducers
US6036650A (en) * 1998-09-15 2000-03-14 Endosonics Corporation Ultrasonic imaging system and method with ringdown reduction
US20060052701A1 (en) * 1998-09-18 2006-03-09 University Of Washington Treatment of unwanted tissue by the selective destruction of vasculature providing nutrients to the tissue
US6716184B2 (en) * 1998-09-18 2004-04-06 University Of Washington Ultrasound therapy head configured to couple to an ultrasound imaging probe to facilitate contemporaneous imaging using low intensity ultrasound and treatment using high intensity focused ultrasound
US6206843B1 (en) * 1999-01-28 2001-03-27 Ultra Cure Ltd. Ultrasound system and methods utilizing same
US6179831B1 (en) * 1999-04-29 2001-01-30 Galil Medical Ltd. Method of cryoablating benign prostate hyperplasia
US6676601B1 (en) * 1999-05-26 2004-01-13 Technomed Medical Systems, S.A. Apparatus and method for location and treatment using ultrasound
US6682483B1 (en) * 1999-05-28 2004-01-27 Vuesonix Sensors, Inc. Device and method for mapping and tracking blood flow and determining parameters of blood flow
US6726627B1 (en) * 1999-08-09 2004-04-27 Riverside Research Institute System and method for ultrasonic harmonic imaging for therapy guidance and monitoring
US6706892B1 (en) * 1999-09-07 2004-03-16 Conjuchem, Inc. Pulmonary delivery for bioconjugation
US7510536B2 (en) * 1999-09-17 2009-03-31 University Of Washington Ultrasound guided high intensity focused ultrasound treatment of nerves
US20090062697A1 (en) * 1999-10-25 2009-03-05 Therus Corporation Insertable ultrasound probes, systems, and methods for thermal therapy
US20040030268A1 (en) * 1999-11-26 2004-02-12 Therus Corporation (Legal) Controlled high efficiency lesion formation using high intensity ultrasound
US6719694B2 (en) * 1999-12-23 2004-04-13 Therus Corporation Ultrasound transducers for imaging and therapy
US6506171B1 (en) * 2000-07-27 2003-01-14 Insightec-Txsonics, Ltd System and methods for controlling distribution of acoustic energy around a focal point using a focused ultrasound system
US6514221B2 (en) * 2000-07-27 2003-02-04 Brigham And Women's Hospital, Inc. Blood-brain barrier opening
US6522926B1 (en) * 2000-09-27 2003-02-18 Cvrx, Inc. Devices and methods for cardiovascular reflex control
US20040082978A1 (en) * 2000-09-28 2004-04-29 Harrison William Vanbrooks Systems and methods for modulation of circulatory perfusion by electrical and/or drug stimulation
US20040002654A1 (en) * 2000-09-29 2004-01-01 New Health Sciences, Inc. Precision brain blood flow assessment remotely in real time using nanotechnology ultrasound
US20040030269A1 (en) * 2000-11-07 2004-02-12 Gerald Horn Method and apparatus for the correction of presbyopia using high intensity focused ultrasound
US6875176B2 (en) * 2000-11-28 2005-04-05 Aller Physionix Limited Systems and methods for making noninvasive physiological assessments
US20030009194A1 (en) * 2000-12-07 2003-01-09 Saker Mark B. Tissue tract sealing device
US20090012098A1 (en) * 2001-01-29 2009-01-08 Otsuka Pharmaceutical Co., 5-ht1a receptor subtype agonist
US20050085793A1 (en) * 2001-03-30 2005-04-21 Glossop Neil D. Device and method for registering a position sensor in an anatomical body
US20040078034A1 (en) * 2001-07-16 2004-04-22 Acker David E Coagulator and spinal disk surgery
US20030069569A1 (en) * 2001-08-29 2003-04-10 Burdette Everette C. Ultrasound device for treatment of intervertebral disc tissue
US20030050665A1 (en) * 2001-09-07 2003-03-13 Integrated Vascular Systems, Inc. Needle apparatus for closing septal defects and methods for using such apparatus
US6709407B2 (en) * 2001-10-30 2004-03-23 Mayo Foundation For Medical Education And Research Method and apparatus for fetal audio stimulation
US20040078219A1 (en) * 2001-12-04 2004-04-22 Kimberly-Clark Worldwide, Inc. Healthcare networks with biosensors
US20050054955A1 (en) * 2002-01-15 2005-03-10 Lars Lidgren Device for non-invasive ultrasound treatment of an object
US6719699B2 (en) * 2002-02-07 2004-04-13 Sonotech, Inc. Adhesive hydrophilic membranes as couplants in ultrasound imaging applications
US8347891B2 (en) * 2002-04-08 2013-01-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen
US7162303B2 (en) * 2002-04-08 2007-01-09 Ardian, Inc. Renal nerve stimulation method and apparatus for treatment of patients
US20090036948A1 (en) * 2002-04-08 2009-02-05 Ardian, Inc. Renal nerve stimulation methods for treatment of patients
US20050192638A1 (en) * 2002-04-08 2005-09-01 Mark Gelfand Methods and devices for renal nerve blocking
US20070135875A1 (en) * 2002-04-08 2007-06-14 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
US20070265687A1 (en) * 2002-04-08 2007-11-15 Ardian, Inc. Apparatuses for renal neuromodulation
US20080045864A1 (en) * 2002-09-12 2008-02-21 The Regents Of The University Of California. Dynamic acoustic focusing utilizing time reversal
US6709392B1 (en) * 2002-10-10 2004-03-23 Koninklijke Philips Electronics N.V. Imaging ultrasound transducer temperature control system and method using feedback
US6846291B2 (en) * 2002-11-20 2005-01-25 Sonotech, Inc. Production of lubricious coating on adhesive hydrogels
US7684865B2 (en) * 2003-03-14 2010-03-23 Endovx, Inc. Methods and apparatus for treatment of obesity
US20080058683A1 (en) * 2003-06-10 2008-03-06 Cierra, Inc. Method and apparatus for non-invasively treating patent foramen ovale using high intensity focused ultrasound
US20050065436A1 (en) * 2003-09-23 2005-03-24 Ho Winston Zonh Rapid and non-invasive optical detection of internal bleeding
US20100022921A1 (en) * 2004-03-02 2010-01-28 Ralf Seip Ultrasound phased arrays
US20080025756A1 (en) * 2004-08-28 2008-01-31 Byung-Sun Ahn Developing unit having foldable handle and image forming apparatus having the same
US20070066957A1 (en) * 2004-11-02 2007-03-22 Ardian, Inc. Methods and apparatus for inducing controlled renal neuromodulation
US20080045865A1 (en) * 2004-11-12 2008-02-21 Hanoch Kislev Nanoparticle Mediated Ultrasound Therapy and Diagnostic Imaging
US7499748B2 (en) * 2005-04-11 2009-03-03 Cardiac Pacemakers, Inc. Transvascular neural stimulation device
US20070004964A1 (en) * 2005-07-01 2007-01-04 Pentax Corporation Image capturing unit for endoscope
US20070038115A1 (en) * 2005-08-12 2007-02-15 Quigley David P High intensity ultrasound apparatus methods and systems
US20070055155A1 (en) * 2005-08-17 2007-03-08 Neil Owen Method and system to synchronize acoustic therapy with ultrasound imaging
US20070055181A1 (en) * 2005-09-07 2007-03-08 Deem Mark E Apparatus for treating subcutaneous tissues
US20080039746A1 (en) * 2006-05-25 2008-02-14 Medtronic, Inc. Methods of using high intensity focused ultrasound to form an ablated tissue area containing a plurality of lesions
US20090076409A1 (en) * 2006-06-28 2009-03-19 Ardian, Inc. Methods and systems for thermally-induced renal neuromodulation
US20090062873A1 (en) * 2006-06-28 2009-03-05 Ardian, Inc. Methods and systems for thermally-induced renal neuromodulation
US20080047325A1 (en) * 2006-07-17 2008-02-28 Kci Licensing, Inc., Legal Department, Intellectual Property Measurement of moisture vapor transfer rate
US20080033292A1 (en) * 2006-08-02 2008-02-07 Insightec Ltd Ultrasound patient interface device
US20100023088A1 (en) * 2008-03-27 2010-01-28 Stack Richard S System and method for transvascularly stimulating contents of the carotid sheath
US20100042020A1 (en) * 2008-08-13 2010-02-18 Shmuel Ben-Ezra Focused energy delivery apparatus method and system
US20120065492A1 (en) * 2009-10-12 2012-03-15 Kona Medical, Inc. Energetic modulation of nerves

Cited By (130)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10335280B2 (en) 2000-01-19 2019-07-02 Medtronic, Inc. Method for ablating target tissue of a patient
US9486270B2 (en) 2002-04-08 2016-11-08 Medtronic Ardian Luxembourg S.A.R.L. Methods and apparatus for bilateral renal neuromodulation
US10293190B2 (en) 2002-04-08 2019-05-21 Medtronic Ardian Luxembourg S.A.R.L. Thermally-induced renal neuromodulation and associated systems and methods
US8845629B2 (en) 2002-04-08 2014-09-30 Medtronic Ardian Luxembourg S.A.R.L. Ultrasound apparatuses for thermally-induced renal neuromodulation
US9186198B2 (en) 2002-04-08 2015-11-17 Medtronic Ardian Luxembourg S.A.R.L. Ultrasound apparatuses for thermally-induced renal neuromodulation and associated systems and methods
US9510901B2 (en) 2003-09-12 2016-12-06 Vessix Vascular, Inc. Selectable eccentric remodeling and/or ablation
US20080161801A1 (en) * 2003-09-12 2008-07-03 Minnow Medical, Inc. Selectable Eccentric Remodeling and/or Ablation of Atherosclerotic Material
US10188457B2 (en) 2003-09-12 2019-01-29 Vessix Vascular, Inc. Selectable eccentric remodeling and/or ablation
US9125666B2 (en) 2003-09-12 2015-09-08 Vessix Vascular, Inc. Selectable eccentric remodeling and/or ablation of atherosclerotic material
US8939970B2 (en) 2004-09-10 2015-01-27 Vessix Vascular, Inc. Tuned RF energy and electrical tissue characterization for selective treatment of target tissues
US9713730B2 (en) 2004-09-10 2017-07-25 Boston Scientific Scimed, Inc. Apparatus and method for treatment of in-stent restenosis
US9125667B2 (en) 2004-09-10 2015-09-08 Vessix Vascular, Inc. System for inducing desirable temperature effects on body tissue
US8920414B2 (en) 2004-09-10 2014-12-30 Vessix Vascular, Inc. Tuned RF energy and electrical tissue characterization for selective treatment of target tissues
US8364237B2 (en) 2005-03-28 2013-01-29 Vessix Vascular, Inc. Tuned RF energy for selective treatment of atheroma and other target tissues and/or structures
US9486355B2 (en) 2005-05-03 2016-11-08 Vessix Vascular, Inc. Selective accumulation of energy with or without knowledge of tissue topography
US9808300B2 (en) 2006-05-02 2017-11-07 Boston Scientific Scimed, Inc. Control of arterial smooth muscle tone
US10589130B2 (en) 2006-05-25 2020-03-17 Medtronic, Inc. Methods of using high intensity focused ultrasound to form an ablated tissue area containing a plurality of lesions
US8043235B2 (en) * 2006-08-22 2011-10-25 Schwartz Donald N Ultrasonic treatment of glaucoma
US20100152626A1 (en) * 2006-08-22 2010-06-17 Schwartz Donald N Ultrasonic treatment of glaucoma
US9974607B2 (en) 2006-10-18 2018-05-22 Vessix Vascular, Inc. Inducing desirable temperature effects on body tissue
US10413356B2 (en) 2006-10-18 2019-09-17 Boston Scientific Scimed, Inc. System for inducing desirable temperature effects on body tissue
US10213252B2 (en) 2006-10-18 2019-02-26 Vessix, Inc. Inducing desirable temperature effects on body tissue
US8496653B2 (en) 2007-04-23 2013-07-30 Boston Scientific Scimed, Inc. Thrombus removal
US8396548B2 (en) 2008-11-14 2013-03-12 Vessix Vascular, Inc. Selective drug delivery in a lumen
US9327100B2 (en) 2008-11-14 2016-05-03 Vessix Vascular, Inc. Selective drug delivery in a lumen
US8401667B2 (en) 2008-11-17 2013-03-19 Vessix Vascular, Inc. Selective accumulation of energy with or without knowledge of tissue topography
US8551096B2 (en) 2009-05-13 2013-10-08 Boston Scientific Scimed, Inc. Directional delivery of energy and bioactives
US9005143B2 (en) 2009-10-12 2015-04-14 Kona Medical, Inc. External autonomic modulation
US9277955B2 (en) 2010-04-09 2016-03-08 Vessix Vascular, Inc. Power generating and control apparatus for the treatment of tissue
US9192790B2 (en) 2010-04-14 2015-11-24 Boston Scientific Scimed, Inc. Focused ultrasonic renal denervation
US8880185B2 (en) 2010-06-11 2014-11-04 Boston Scientific Scimed, Inc. Renal denervation and stimulation employing wireless vascular energy transfer arrangement
US9084609B2 (en) 2010-07-30 2015-07-21 Boston Scientific Scime, Inc. Spiral balloon catheter for renal nerve ablation
US9358365B2 (en) 2010-07-30 2016-06-07 Boston Scientific Scimed, Inc. Precision electrode movement control for renal nerve ablation
US9408661B2 (en) 2010-07-30 2016-08-09 Patrick A. Haverkost RF electrodes on multiple flexible wires for renal nerve ablation
US9155589B2 (en) 2010-07-30 2015-10-13 Boston Scientific Scimed, Inc. Sequential activation RF electrode set for renal nerve ablation
US9463062B2 (en) 2010-07-30 2016-10-11 Boston Scientific Scimed, Inc. Cooled conductive balloon RF catheter for renal nerve ablation
US8974451B2 (en) 2010-10-25 2015-03-10 Boston Scientific Scimed, Inc. Renal nerve ablation using conductive fluid jet and RF energy
US9220558B2 (en) 2010-10-27 2015-12-29 Boston Scientific Scimed, Inc. RF renal denervation catheter with multiple independent electrodes
US9848946B2 (en) 2010-11-15 2017-12-26 Boston Scientific Scimed, Inc. Self-expanding cooling electrode for renal nerve ablation
US9028485B2 (en) 2010-11-15 2015-05-12 Boston Scientific Scimed, Inc. Self-expanding cooling electrode for renal nerve ablation
US9089350B2 (en) 2010-11-16 2015-07-28 Boston Scientific Scimed, Inc. Renal denervation catheter with RF electrode and integral contrast dye injection arrangement
US9668811B2 (en) 2010-11-16 2017-06-06 Boston Scientific Scimed, Inc. Minimally invasive access for renal nerve ablation
US9326751B2 (en) 2010-11-17 2016-05-03 Boston Scientific Scimed, Inc. Catheter guidance of external energy for renal denervation
US9060761B2 (en) 2010-11-18 2015-06-23 Boston Scientific Scime, Inc. Catheter-focused magnetic field induced renal nerve ablation
US9192435B2 (en) 2010-11-22 2015-11-24 Boston Scientific Scimed, Inc. Renal denervation catheter with cooled RF electrode
US9023034B2 (en) 2010-11-22 2015-05-05 Boston Scientific Scimed, Inc. Renal ablation electrode with force-activatable conduction apparatus
US9649156B2 (en) 2010-12-15 2017-05-16 Boston Scientific Scimed, Inc. Bipolar off-wall electrode device for renal nerve ablation
US9220561B2 (en) 2011-01-19 2015-12-29 Boston Scientific Scimed, Inc. Guide-compatible large-electrode catheter for renal nerve ablation with reduced arterial injury
US9579030B2 (en) 2011-07-20 2017-02-28 Boston Scientific Scimed, Inc. Percutaneous devices and methods to visualize, target and ablate nerves
US9186209B2 (en) 2011-07-22 2015-11-17 Boston Scientific Scimed, Inc. Nerve modulation system having helical guide
US10271890B2 (en) * 2011-09-27 2019-04-30 Koninklijke Philips N.V. High intensity focused ultrasound enhanced by cavitation
US20150005756A1 (en) * 2011-09-27 2015-01-01 Koninklijke Philips N.V. High intensity focused ultrasound enhanced by cavitation
US9186210B2 (en) 2011-10-10 2015-11-17 Boston Scientific Scimed, Inc. Medical devices including ablation electrodes
US10085799B2 (en) 2011-10-11 2018-10-02 Boston Scientific Scimed, Inc. Off-wall electrode device and methods for nerve modulation
US9420955B2 (en) 2011-10-11 2016-08-23 Boston Scientific Scimed, Inc. Intravascular temperature monitoring system and method
US9364284B2 (en) 2011-10-12 2016-06-14 Boston Scientific Scimed, Inc. Method of making an off-wall spacer cage
US9079000B2 (en) 2011-10-18 2015-07-14 Boston Scientific Scimed, Inc. Integrated crossing balloon catheter
US9162046B2 (en) 2011-10-18 2015-10-20 Boston Scientific Scimed, Inc. Deflectable medical devices
US8951251B2 (en) 2011-11-08 2015-02-10 Boston Scientific Scimed, Inc. Ostial renal nerve ablation
US9119600B2 (en) 2011-11-15 2015-09-01 Boston Scientific Scimed, Inc. Device and methods for renal nerve modulation monitoring
US9119632B2 (en) 2011-11-21 2015-09-01 Boston Scientific Scimed, Inc. Deflectable renal nerve ablation catheter
US9265969B2 (en) 2011-12-21 2016-02-23 Cardiac Pacemakers, Inc. Methods for modulating cell function
US9028472B2 (en) 2011-12-23 2015-05-12 Vessix Vascular, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9037259B2 (en) 2011-12-23 2015-05-19 Vessix Vascular, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9402684B2 (en) 2011-12-23 2016-08-02 Boston Scientific Scimed, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9592386B2 (en) 2011-12-23 2017-03-14 Vessix Vascular, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9072902B2 (en) 2011-12-23 2015-07-07 Vessix Vascular, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9174050B2 (en) 2011-12-23 2015-11-03 Vessix Vascular, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9186211B2 (en) 2011-12-23 2015-11-17 Boston Scientific Scimed, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9433760B2 (en) 2011-12-28 2016-09-06 Boston Scientific Scimed, Inc. Device and methods for nerve modulation using a novel ablation catheter with polymeric ablative elements
US9050106B2 (en) 2011-12-29 2015-06-09 Boston Scientific Scimed, Inc. Off-wall electrode device and methods for nerve modulation
US20180117363A1 (en) * 2012-03-08 2018-05-03 Medtronic Ardian Luxembourg S.A.R.L. Catheter-based devices and associated methods for immune system neuromodulation
US9757180B2 (en) * 2012-04-24 2017-09-12 Cibiem, Inc. Endovascular catheters and methods for carotid body ablation
US10219855B2 (en) * 2012-04-24 2019-03-05 Cibiem, Inc. Endovascular catheters and methods for carotid body ablation
US9393070B2 (en) * 2012-04-24 2016-07-19 Cibiem, Inc. Endovascular catheters and methods for carotid body ablation
US20130310823A1 (en) * 2012-04-24 2013-11-21 Mark Gelfand Endovascular Catheters and Methods for Carotid Body Ablation
US20170367749A1 (en) * 2012-04-24 2017-12-28 Mark Gelfand Endovascular catheters and methods for carotid body ablation
US10660703B2 (en) 2012-05-08 2020-05-26 Boston Scientific Scimed, Inc. Renal nerve modulation devices
US9398930B2 (en) 2012-06-01 2016-07-26 Cibiem, Inc. Percutaneous methods and devices for carotid body ablation
US9402677B2 (en) * 2012-06-01 2016-08-02 Cibiem, Inc. Methods and devices for cryogenic carotid body ablation
US9808303B2 (en) 2012-06-01 2017-11-07 Cibiem, Inc. Methods and devices for cryogenic carotid body ablation
US20130324987A1 (en) * 2012-06-01 2013-12-05 Mark Leung Methods and Devices for Cryogenic Carotid Body Ablation
US9283033B2 (en) 2012-06-30 2016-03-15 Cibiem, Inc. Carotid body ablation via directed energy
US10321946B2 (en) 2012-08-24 2019-06-18 Boston Scientific Scimed, Inc. Renal nerve modulation devices with weeping RF ablation balloons
US9173696B2 (en) 2012-09-17 2015-11-03 Boston Scientific Scimed, Inc. Self-positioning electrode system and method for renal nerve modulation
US10398464B2 (en) 2012-09-21 2019-09-03 Boston Scientific Scimed, Inc. System for nerve modulation and innocuous thermal gradient nerve block
US10549127B2 (en) 2012-09-21 2020-02-04 Boston Scientific Scimed, Inc. Self-cooling ultrasound ablation catheter
US10835305B2 (en) 2012-10-10 2020-11-17 Boston Scientific Scimed, Inc. Renal nerve modulation devices and methods
US10004557B2 (en) 2012-11-05 2018-06-26 Pythagoras Medical Ltd. Controlled tissue ablation
US9770593B2 (en) 2012-11-05 2017-09-26 Pythagoras Medical Ltd. Patient selection using a transluminally-applied electric current
US20140148735A1 (en) * 2012-11-28 2014-05-29 Covidien Lp Device and method for salvaging myocardium following heart attack
US9956033B2 (en) 2013-03-11 2018-05-01 Boston Scientific Scimed, Inc. Medical devices for modulating nerves
US9693821B2 (en) 2013-03-11 2017-07-04 Boston Scientific Scimed, Inc. Medical devices for modulating nerves
US9808311B2 (en) 2013-03-13 2017-11-07 Boston Scientific Scimed, Inc. Deflectable medical devices
US9827039B2 (en) 2013-03-15 2017-11-28 Boston Scientific Scimed, Inc. Methods and apparatuses for remodeling tissue of or adjacent to a body passage
US9297845B2 (en) 2013-03-15 2016-03-29 Boston Scientific Scimed, Inc. Medical devices and methods for treatment of hypertension that utilize impedance compensation
US10265122B2 (en) 2013-03-15 2019-04-23 Boston Scientific Scimed, Inc. Nerve ablation devices and related methods of use
US9943365B2 (en) 2013-06-21 2018-04-17 Boston Scientific Scimed, Inc. Renal denervation balloon catheter with ride along electrode support
US10022182B2 (en) 2013-06-21 2018-07-17 Boston Scientific Scimed, Inc. Medical devices for renal nerve ablation having rotatable shafts
US9707036B2 (en) 2013-06-25 2017-07-18 Boston Scientific Scimed, Inc. Devices and methods for nerve modulation using localized indifferent electrodes
US9833283B2 (en) 2013-07-01 2017-12-05 Boston Scientific Scimed, Inc. Medical devices for renal nerve ablation
US10660698B2 (en) 2013-07-11 2020-05-26 Boston Scientific Scimed, Inc. Devices and methods for nerve modulation
US10413357B2 (en) 2013-07-11 2019-09-17 Boston Scientific Scimed, Inc. Medical device with stretchable electrode assemblies
US9925001B2 (en) 2013-07-19 2018-03-27 Boston Scientific Scimed, Inc. Spiral bipolar electrode renal denervation balloon
US10342609B2 (en) 2013-07-22 2019-07-09 Boston Scientific Scimed, Inc. Medical devices for renal nerve ablation
US10695124B2 (en) 2013-07-22 2020-06-30 Boston Scientific Scimed, Inc. Renal nerve ablation catheter having twist balloon
US10722300B2 (en) 2013-08-22 2020-07-28 Boston Scientific Scimed, Inc. Flexible circuit having improved adhesion to a renal nerve modulation balloon
US9895194B2 (en) 2013-09-04 2018-02-20 Boston Scientific Scimed, Inc. Radio frequency (RF) balloon catheter having flushing and cooling capability
US10952790B2 (en) 2013-09-13 2021-03-23 Boston Scientific Scimed, Inc. Ablation balloon with vapor deposited cover layer
US11246654B2 (en) 2013-10-14 2022-02-15 Boston Scientific Scimed, Inc. Flexible renal nerve ablation devices and related methods of use and manufacture
US9687166B2 (en) 2013-10-14 2017-06-27 Boston Scientific Scimed, Inc. High resolution cardiac mapping electrode array catheter
US9770606B2 (en) 2013-10-15 2017-09-26 Boston Scientific Scimed, Inc. Ultrasound ablation catheter with cooling infusion and centering basket
US9962223B2 (en) 2013-10-15 2018-05-08 Boston Scientific Scimed, Inc. Medical device balloon
US10945786B2 (en) 2013-10-18 2021-03-16 Boston Scientific Scimed, Inc. Balloon catheters with flexible conducting wires and related methods of use and manufacture
US10271898B2 (en) 2013-10-25 2019-04-30 Boston Scientific Scimed, Inc. Embedded thermocouple in denervation flex circuit
US11202671B2 (en) 2014-01-06 2021-12-21 Boston Scientific Scimed, Inc. Tear resistant flex circuit assembly
US9907609B2 (en) 2014-02-04 2018-03-06 Boston Scientific Scimed, Inc. Alternative placement of thermal sensors on bipolar electrode
US11000679B2 (en) 2014-02-04 2021-05-11 Boston Scientific Scimed, Inc. Balloon protection and rewrapping devices and related methods of use
US9955946B2 (en) 2014-03-12 2018-05-01 Cibiem, Inc. Carotid body ablation with a transvenous ultrasound imaging and ablation catheter
US10478249B2 (en) 2014-05-07 2019-11-19 Pythagoras Medical Ltd. Controlled tissue ablation techniques
WO2016058963A1 (en) * 2014-10-17 2016-04-21 Koninklijke Philips N.V. An ultrasound patch for ultrasound hyperthermia and imaging
US11185720B2 (en) 2014-10-17 2021-11-30 Koninklijke Philips N.V. Ultrasound patch for ultrasound hyperthermia and imaging
US10383685B2 (en) 2015-05-07 2019-08-20 Pythagoras Medical Ltd. Techniques for use with nerve tissue
EP3359050A4 (en) * 2015-10-06 2019-06-12 Aleyegn Technologies LLC Ultrasound directed cavitational methods and systems for ocular treatments
CN108472017A (en) * 2015-10-06 2018-08-31 爱视珍科技有限责任公司 Ultrasonic guidance cavitation process and system for eye treatment
JP7445232B2 (en) 2016-03-31 2024-03-07 トーマス・ジェファーソン・ユニバーシティ Tumor implant for multimodality treatment of risk tissue surrounding the resection cavity
US11678932B2 (en) 2016-05-18 2023-06-20 Symap Medical (Suzhou) Limited Electrode catheter with incremental advancement
JP2022169606A (en) * 2016-10-31 2022-11-09 ゼネラル・エレクトリック・カンパニイ Techniques for neuromodulation
US20230233282A1 (en) * 2022-01-24 2023-07-27 Siemens Healthcare Gmbh Therapeutic apparatus for ultrasonic treatment
US11793595B2 (en) * 2022-01-24 2023-10-24 Siemens Healthcare Gmbh Therapeutic apparatus for ultrasonic treatment

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