WO2015066311A1

WO2015066311A1 - Systems and methods for neuromodulation and treatment of abnormal growths

Info

Publication number: WO2015066311A1
Application number: PCT/US2014/063130
Authority: WO
Inventors: Paul Walinsky; Arye Rosen
Original assignee: Thomas Jefferson University
Priority date: 2013-10-30
Filing date: 2014-10-30
Publication date: 2015-05-07

Abstract

Systems and methods for the treatment of an abnormal growth and neuromodulation of patients are disclosed. In some embodiments, the system includes an applicator, a positioning mechanism, and at least one signal generator. The applicator is configured to be disposed at or adjacent a target site and to impart a first electromagnetic energy having a first frequency to modulate at least one nerve tissue. The applicator is further configured to impart a second electromagnetic energy having a second frequency to treat an abnormal growth at or adjacent one or more of the target sites. The positioning mechanism is configured to retain the applicator in a position relative to the target site. The at least one signal generator is operatively coupled to the applicator and is configured to supply the first electromagnetic energy and the second electromagnetic energy to the applicator.

Description

SYSTEMS AND METHODS FOR NEUROMODULATION AND

TREATMENT OF ABNORMAL GROWTHS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 61/897,572, filed October 30, 2013, which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present disclosure relates to methods, systems, and apparatuses generally for intravascular neuromodulation and for treatment of tumors. More specifically, the present invention provides methods, systems, and apparatuses for using microwave and radio frequencies to modulate nerve tissue and treat abnormal growths.

BACKGROUND

[0003] Pancreatic cancer has one of the highest mortality rates of any malignancy, and the 5- year-survival rate of patients is 4%. It has been reported that approximately 28,000 patients with pancreatic cancer are diagnosed each year, and nearly all patients will die of their disease. This is caused in part by the poor response to current therapeutic methods. For example, the structure of the pancreas may inhibit resection of abnormal growths therein. Abnormal growths such as tumors may be unresectable because the tumor has grown around one or more blood vessels and/or around one or more nerves. Even if the abnormal growth does not envelop a blood vessel or nerve, resection may be inhibited because of a density of blood vessels and/or nerves that practicably occludes the tumor from resection.

[0004] Afferent nerve fibers transmit impulses which convey the sensation of pain. The invasion of these nerve fibers in the abdomen by a tumor may cause severe and constant pain. Pain may also occur when there is invasion of the celiac plexus by tumor. Treatment of pain is difficult because of the location of the nerve fibers and/or the celiac plexus. Modalities currently employed include radiation therapy and/or injection of local anesthetic either percutaneously, laparoscopically, or endoscopically.

[0005] Therefore, it would be useful to provide a system to treat abnormal growths and to modulate nerve tissue responsible for causing pain.

SUMMARY

[0006] According to some embodiments, a system for treatment of an abnormal growth and neuromodulation of at least one patient includes an applicator, a positioning mechanism, and at least one signal generator. The applicator is configured to be disposed at or adjacent at least one target site. The applicator is further configured to impart a first electromagnetic energy having a first frequency to modulate at least one nerve tissue at or adjacent one or more of the at least one target sites. The applicator is yet further configured to impart a second electromagnetic energy having a second frequency to treat an abnormal growth at or adjacent one or more of the at least one target sites. The positioning mechanism is configured to retain the applicator in a position relative to the at least one target site. The at least one signal generator is operatively coupled to the applicator, the at least one signal generator configured to supply the first electromagnetic energy and the second electromagnetic energy to the applicator.

[0007] According to some embodiments, a method for treatment of an abnormal growth and neuromodulation of at least one patient includes positioning a catheter within at least one vas using a guide wire; positioning an applicator at or adjacent at least one target site using the catheter; applying, using the applicator, a first electromagnetic energy having a first frequency to modulate at least one nerve tissue at or adjacent one or more of the at least one target sites; and applying, using the applicator, a second electromagnetic energy having a second frequency to treat the abnormal growth at or adjacent one or more of the at least one target sites.

[0008] According to some embodiments, an applicator is configured to be disposed within a vas of at least one patient at or adjacent a target site for treatment of an abnormal growth and neuromodulation. The applicator includes a radio-frequency probe and a microwave- frequency antenna. The radio-frequency probe is configured to heat a first target tissue by transferring a radio-frequency electromagnetic energy from the radio-frequency probe to a dispersive electrode spaced a distance from the applicator. The radio-frequency electromagnetic energy has a frequency between about 3 KHz and about 300 MHz. The microwave-frequency antenna is configured to heat a second target tissue by transmitting a microwave-frequency electromagnetic energy to the second target tissue. The microwave- frequency electromagnetic energy has a frequency above about 300 MHz. The applicator is configured to be retained at a position within the vas by a positioning mechanism.

[0009] According to some embodiments, a system for treatment of at least one patient includes an applicator, a positioning mechanism, and at least one signal generator. The applicator is configured to be disposed at or adjacent at least one target site. The applicator is further configured to treat a first condition by imparting a first electromagnetic energy having a first frequency and to treat a second condition by imparting a second electromagnetic energy having a second frequency. The positioning mechanism is configured to retain the applicator in a position relative to the at least one target site. The at least one signal generator is operatively coupled to the applicator. The at least one signal generator is configured to supply the first electromagnetic energy and the second electromagnetic energy to the applicator.

[0010] Additional aspects of the invention will be apparent to those of ordinary skill in the art in view of the detailed description of various embodiments, which is made with reference to the drawings, a brief description of which is provided below.

BRIEF DESCRIPTION OF THE FIGURES

[0011] FIG. 1A illustrates a system for treatment of a tumor and neuromodulation of a target nerve tissue within a patient, according to an embodiment.

[0012] FIG. IB illustrates a system for treatment of a tumor and neuromodulation of a target nerve tissue within a patient, according to another embodiment.

[0013] FIG. 2 illustrates an applicator for use in the system of FIGS. 1A-B according to an embodiment.

[0014] FIG. 3A illustrates an applicator for use in the system of FIGS. 1A-B according to another embodiment.

[0015] FIG. 3B illustrates an applicator for use in the system of FIGS. 1A-B according to yet another embodiment.

[0016] FIG. 3C illustrates an applicator for use in the system of FIGS. 1A-B according to still yet another embodiment.

[0017] FIG. 3D illustrates an applicator for use in the system of FIGS. 1A-B according to a further embodiment.

[0018] FIG. 4A illustrates the distal end of a catheter and guide wire disposed within a blood vessel, according to an embodiment.

[0019] FIG. 4B illustrates the distal end of the catheter of FIG. 4A with a removable conductor, according to an embodiment.

[0020] FIG. 5A illustrates an applicator for use in the system of FIGS. 1A-B with a positioning mechanism, according to an embodiment.

[0021] FIG. 5B illustrates a cross-sectional view of the catheter of FIG. 5 A.

[0022] FIG. 6 illustrates a simplified cross sectional view of the catheter of FIG. 5 A with the positioning mechanism having a first metallized portion and a second metallized portion. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0023] The present disclosure relates to methods, systems, and apparatuses generally for neuromodulation and for treatment of abnormal growths in patients. Neuromodulation is achieved using electrically- and/or thermally-induced neuromodulation of a target nerve tissue such as tissue within a nerve or nerve fibers. This results in reducing or eliminating function of the target nerve tissue to relieve pain suffered by the patient. Abnormal growths (e.g. tumors) are treated using electrically- and/or thermally-induced necrosis. This treatment results in inhibiting further growth of the tumor and reduces adverse risks to the patient including complications associated with attempted resection of the tumor. More particularly, aspects of the present disclosure relate to systems and apparatuses configured to deliver a first electromagnetic energy having a first frequency to at least one target nerve tissue and deliver a second electromagnetic energy having a second frequency to an abnormal growth near a vas, as well as methods of using the same. Beneficially, delivery of the first electromagnetic energy and the second electromagnetic energy allow for tailoring treatment based on patient- specific conditions at the time of operation by providing therapeutically high temperatures in at least one target tissue while allowing for adjustment of ablation volumes and/or ablation times.

[0024] The first electromagnetic energy and the second electromagnetic energy are delivered using at least one applicator and can be radio-frequency energy and/or microwave-frequency energy. As used herein, radio frequencies are frequencies that range from about 3 KHz to about 300 MHz. Also as used herein, microwave frequencies are frequencies that range from about 300 MHz to about 300 GHz. The particular frequency of the electromagnetic energy to be delivered is selected based on factors such as the distance of the target from the vas, the composition of tissue and/or fluids between the vas and the target, the composition of tissue and/or fluids within the target, the desired amount of energy to deliver to the target, the desired time period for delivering the energy, the desired pulse duration, the volume of the target, and/or the surface area of the target. The electromagnetic energy is selected to deliver a therapeutic amount of heat to a target tissue. In some aspects, the therapeutic amount of heat causes necrosis of the target tumor.

[0025] Beneficially, microwave-frequency energy can provide therapeutic heating of tissue with a heating profile that is generally uniform across a volume of a target tissue. The microwave-frequency energy provides volumetric heating of the target tissue, which is accomplished generally by dielectric heating. The dielectric heating increases the temperature of the target tissue to therapeutically high temperatures and ultimately leads to cell death in the tissue. The microwave-frequency energy is transmitted from an antenna and induces an alternating electric field that permeates the tissue. Molecules within the tissue that have a positive charge at one end and a negative charge at the other end, such as water molecules, are known as electric dipoles. These dipoles generate frictional heating by rotating to align with the alternating field. This heating is particularly efficient with liquid water molecules, which have a relatively high dipole moment.

[0026] Additionally, microwave-frequency energy can provide therapeutic heating of a target tissue that is spaced a distance from the vas while limiting heat-damage to non-target tissue. The depth of penetration of the microwave-frequency energy through the tissue is frequency dependent where relatively higher microwave frequencies provide relatively shallower tissue penetration and relatively lower microwave frequencies provide relatively deeper tissue penetration. This allows delivery of therapeutic amounts of heat to the target tissue while reducing heat damage to non-target tissue beyond the target tissue when the frequency is selected to penetrate the target tissue, but not substantially penetrate non-target tissue beyond the target tissue. Further, tissue types with relatively low water content, such as adipose tissue, do not absorb the microwave-frequency energy as efficiently as other types of tissue. This allows delivery of therapeutic amounts of heat to the target tissue while reducing heat damage to non-target tissue disposed between the applicator and the target tissue when the non-target tissue has a lower water content than the target tissue.

[0027] Beneficially, radio-frequency energy can provide therapeutic heating of a target tissue with a focused heat profile. The focused, point heating of tissue is accomplished generally by resistive heating of a target tissue. The resistive heating increases the temperature of the target tissue by passing a current through the tissue from a radio-frequency probe to a dispersive electrode. The transfer of radio-frequency energy between a radio-frequency probe and the contacted tissue causes the formation of a thermal lesion in the tissue. The thermal lesion penetrates deeper into the tissue using thermal conduction. The conducted heat ultimately leads to cell death extending from the contact point to a depth within the lesion. The duration of heating and the power applied affect properties of the thermal lesion such as the size and the heat profile of the lesion.

[0028] As will be described in more detail with reference to FIGS. 1A-6, an applicator can deliver at least two frequencies of electromagnetic energy to the patient. Alternatively, multiple applicators can be used to deliver at least two frequencies of electromagnetic energy to the patient with each applicator delivering at least one of the frequencies. The applicator can include at least one microwave-frequency antenna, at least one radio-frequency probe, or combinations thereof.

[0029] According to aspects of the present disclosure, the first electromagnetic energy modulates at least one nerve tissue using a first microwave frequency and the second electromagnetic energy treats an abnormal growth using a second microwave frequency. In some embodiments, the applicator includes a first antenna to deliver the first electromagnetic energy at the first microwave frequency and a second antenna to deliver the second electromagnetic energy at the second microwave frequency. In other embodiments, the applicator includes a multi-band antenna to deliver both the first electromagnetic energy at the first microwave frequency and the second electromagnetic energy at the second microwave frequency. As used herein, an antenna may be any of a single-band antenna, dual-band antenna, or multi-band antenna. The use of one microwave-frequency energy for neuromodulation and another microwave-frequency energy for treatment of an abnormal growth allows for therapeutic heating of two relatively large volumes of tissue at different tissue depths while limiting heat-related damage to non-target tissue adjacent the target tissue.

[0030] According to aspects of the present disclosure, the first electromagnetic energy modulates at least one nerve tissue using a first radio frequency and the second electromagnetic energy treats an abnormal growth using a second radio frequency. In some embodiments, the applicator includes a radio frequency probe to deliver the first electromagnetic energy at the first radio frequency and a radio frequency probe to deliver the second electromagnetic energy at the second radio frequency. In other embodiments, the applicator includes a single radio-frequency probe to deliver both the first electromagnetic energy at the first radio frequency and the second electromagnetic energy at the second radio frequency. The use of radio-frequency energy for neuromodulation allows for point heating of a small volume of nerve tissue generally adjacent the radio-frequency probe without heating a large volume of tissue. The use of radio-frequency energy for treatment of an abnormal growth allows for point heating of a small volume of target tissue generally adjacent the radio-frequency probe without heating a large volume of tissue.

[0031] According to aspects of the present disclosure, the first electromagnetic energy modulates at least one nerve tissue using a radio frequency and the second electromagnetic energy treats an abnormal growth using a microwave frequency. In some embodiments, the applicator includes a radio-frequency probe to deliver the first electromagnetic energy at the radio frequency and an antenna to deliver the second electromagnetic energy at the microwave frequency. In other embodiments, the radio-frequency probe and the antenna are integral components. The use of radio-frequency energy for neuromodulation allows for point heating of a small volume of nerve tissue generally adjacent the radio-frequency probe without heating a large volume of tissue. The use of microwave-frequency energy for treatment of an abnormal growth allows for delivery of therapeutic amounts of heat in a generally uniform profile across a relatively large volume of tissue.

[0032] According to aspects of the present disclosure, the first electromagnetic energy modulates at least one nerve tissue using a microwave frequency and the second electromagnetic energy treats an abnormal growth using a radio frequency. In some embodiments, the applicator includes an antenna to deliver the first electromagnetic energy at the microwave frequency and a radio-frequency probe to deliver the second electromagnetic energy at the radio frequency. In other embodiments, the radio-frequency probe and the antenna are integral components. The use of microwave-frequency energy for neuromodulation allows for delivery of therapeutic amounts of heat in a generally uniform profile across a relatively large volume. This can be used to modulate at least one nerve tissue spaced a distance from the antenna and/or to treat a relatively large volume of nerve tissue such as a bundle of nerves or nerve fibers. The use of radio-frequency energy for treatment of an abnormal growth allows for point heating of a small volume of target tissue generally adjacent the radio-frequency probe without heating a large volume of tissue.

[0033] FIG. 1A illustrates a system 100 for use in treatment of an abnormal growth and/or neuromodulation of at least one nerve tissue within a patient. The system 100 includes a guide wire (e.g., guide wire 318 described in more detail with reference to FIG. 4A), a catheter 102, a positioning mechanism 103, an applicator 104, an optional dispersive electrode 105, and a signal generator 106. The catheter 102 includes an elongate shaft having a distal end 108 and a proximal end 110. The elongate shaft also includes a lumen therethrough. The catheter 102 is generally flexible and configured to be navigated through vasa of a patient without causing damage to the vasa. The vas can be any vessel within the body including, but not limited to, a cardiac structure, a vascular structure, a gastrointestinal structure, a urologic structure, a gynecologic structure, a pulmonary structure, or a structure in the head, ear, nose, or throat. For example, the vas of the vascular structure can be a blood vessel such as an artery or vein.

[0034] The positioning mechanism 103 is configured to retain the applicator 104 at a position within a vas (e.g., blood vessel 306 described in more detail with reference to FIGS. 4A and 4B). The positioning mechanism 103 can be disposed on the catheter 102 or can be disposed on the applicator 104. As illustrated, in some aspects, the positioning mechanism 103 is an inflatable balloon. It is contemplated that other positioning mechanisms can be used such as a control wire that, when manipulated, deflects the applicator 104 from the axis of the blood vessel.

[0035] The signal generator 106 supplies electromagnetic energy to the applicator 104. It is contemplated that the signal generator 106 may include at least one radio-frequency energy source, at least one microwave-frequency energy source, or a combination thereof. In the illustrated embodiment, the signal generator 106 includes a radio-frequency energy source 118 and a microwave-frequency energy source 120. The radio-frequency energy source 118 is capable of producing electromagnetic energy at one or more radio frequencies. The microwave-frequency energy source 120 is capable of producing electromagnetic energy at one or more microwave frequencies.

[0036] The signal generator 106 is operatively coupled to the applicator 104 using a transmission line 122 and connectors 124, 126. A switch 128 is used to control delivery of the first electromagnetic energy and/or the second electromagnetic energy from the signal generator 106 to the applicator 104. In some embodiments, the switch 128 is a footplate configured to be selectively actuated by a practitioner. The delivered radiation can be delivered as a continuous wave or a pulse. In some aspects, an attenuator 130 can be used to reduce the power output of the signal generator 106 transferred to the applicator 104. A power level indicator 132 may also be included to indicate to a practitioner the power being delivered. The power level indicator 132 may indicate the power supplied to the applicator 104, the power output from the attenuator 130, the power output from the signal generator 106, the radio frequency source 118, and/or the microwave source 120, or combinations thereof. As recognized by those skilled in the art, the switch 128, the attenuator 130, and/or the power level indicator 132 may be integral with the signal generator 106.

[0037] The applicator 104 is slidably disposed within the lumen of the catheter 102. After the catheter 102 is disposed near the target site, the applicator 104 can be guided to or adjacent to the target site via the lumen of the catheter 102. In some aspects, the applicator 104 is fixed relative to the distal end 108 of the catheter 102.

[0038] The applicator 104 is configured to deliver electromagnetic energy to the target tissue. In the illustrated embodiment, the applicator 104 includes a coaxial cable having an inner conductor 112, an outer conductor 114, and an insulating layer 116 therebetween, as well as a helical antenna 134 that is operatively attached to the inner conductor 112. The helical antenna 134 extends from the inner conductor 112 and winds about the interior of the positioning mechanism 103. The helical antenna 134 is an omnidirectional antenna configured to emit at least one wavelength of microwave radiation generally evenly in all directions from the helical antenna 134. In some aspects, the helical antenna 134 is a dual- band antenna including at least two adjacent coils with a first spacing therebetween and another at least two adjacent coils having a second spacing therebetween configured to emit two wavelengths of microwave radiation. In an embodiment, the positioning mechanism 103 is disposed at the distal end 108 of the catheter 102 and the helical antenna 134 is disposed on the distal end of the applicator 104. The applicator 104 is fed through the lumen of the catheter 102 and the helical antenna 134 is then deployed within the positioning mechanism 103 of the catheter 102.

[0039] FIG. IB illustrates a system 100' for use in treatment of an abnormal growth and/or neuromodulation of at least one nerve tissue within a patient. The system 100' includes a guide wire (e.g., guide wire 318 described in more detail with reference to FIG. 4A), a catheter 102, a positioning mechanism 103, an applicator 104', an optional dispersive electrode 105, and a signal generator 106.

[0040] In the illustrated embodiment, the applicator 104' includes a coaxial cable having an inner conductor 112, an outer conductor 114, and an insulating layer 116 therebetween, as well as a helical antenna 134' that is operatively attached to the outer conductor 114. The helical antenna 134' is an omnidirectional antenna and winds about the exterior of the positioning mechanism 103. When emitting microwave-frequency electromagnetic energy, the helical antenna 134' is not in contact with the wall of the vas.

[0041] Advantageously, the helical antenna 134' can also function as a radio-frequency probe when the optional dispersive electrode 105 is disposed on the outer surface of the patient's body. To be used as a radio-frequency probe, the helical antenna 134' functions as an active electrode and is brought into contact with a surface of the vas. The contact can be formed, for example, by a portion of the helical antenna 134' abutting the wall of the vas. Electromagnetic energy is then supplied to the helical antenna 134'. The supplied radio- frequency electromagnetic energy is delivered from the helical antenna 134' to the dispersive electrode 105 through tissue of the patient. The transfer of the radio-frequency electromagnetic energy from the active electrode to the tissue heats the tissue and forms a thermal lesion extending a distance from the point of contact. The dispersive electrode 105 is a generally large-area electrode that provides a return path for the electromagnetic energy and reduces the current density at the electrode to inhibit or prevent unwanted heating and damage to the patient.

[0042] FIG. 2 illustrates a slotted antenna 500 that can be used to deliver both microwave energy and radio-frequency energy. The slotted antenna 500 includes a plurality of metal bands 502a-d and a plurality of inflatable balloons 504a-e. Each of the plurality of metal bands 502a-d is operatively connected to the signal generator 106 in a similar fashion as described above. The width of each metal band 502a-d and the spacing therebetween is selected to allow emission of multiple wavelengths of microwave energy. In the illustrated example, the leftmost metal bands 502a,b are configured to emit electromagnetic energy at a first microwave frequency and the rightmost metal bands 502c,d are configured to emit electromagnetic energy at a second microwave frequency. The balloons 504a-e function as a positioning mechanism 103 and may be inflated individually or inflated in groups of two or more balloons 504a-e to dispose portions of the slotted antenna 500 at desired positions relative to the wall of the vas. When emitting microwave-frequency electromagnetic energy, the metal bands 502a-d are not in contact with the wall of the vas.

[0043] Advantageously, the slotted antenna 500 can also function as a radio-frequency probe when the optional dispersive electrode 105 is placed on the outer surface of the patient's body. To be used as a radio-frequency probe, one of the metal bands 502a-d or a metal tip 506 is operatively coupled to the radio-frequency energy source 118 using, for example the inner conductor 112 or the outer conductor 114 of the applicator 104. The coupled one of the metal bands 502a-d or metal tip 506 functions as the active electrode. The active electrode is brought into contact with a surface of the vas. The contact can be formed, for example, by a portion of the active electrode contacting the vas. In one nonlimiting example, each of the balloons 504a-e is shaped so that, when inflated each of the metal bands 502a-d and the metal tip 506 is brought into contact with the vas. When used as a microwave antenna, the balloons are either not inflated or are under-inflated to inhibit contact with the wall of the vas. In another nonlimiting example, the leftmost balloons 504a-c are shaped to dispose the leftmost metal bands 502a,b generally near the center of the vas when inflated and the rightmost balloons 504d,e are shaped to dispose a portion of the metal tip 506 generally against the wall of the vas when inflated.

[0044] Radio-frequency electromagnetic energy is then supplied from the radio-frequency energy source 118 to the active electrode (i.e., the coupled metal band 502a-d or the metal tip 506) in contact with the wall of the vas. The supplied radio-frequency electromagnetic energy is delivered from the active electrode to the dispersive electrode 105 through tissue of the patient. The transfer of the radio-frequency electromagnetic energy from the active electrode to the tissue heats the tissue and forms a thermal lesion extending a distance from the point of contact. The dispersive electrode 105 is a generally large-area electrode that provides a return path and reduces the current density at the dispersive electrode to inhibit or prevent unwanted heating and damage to the patient.

[0045] FIGS. 3A-3D illustrate applicators 104a-d according to aspects of the present disclosure. FIG 3 A shows an enlarged portion of an applicator 104a having an inner conductor 112, an outer conductor 114, and an insulating layer 116. In this embodiment, the inner conductor 112 protrudes from the insulating layer 116 and the insulating layer 116 protrudes from the outer conductor 114. The inner conductor 1 12 and the outer conductor 114 may be made of any material capable of carrying both a microwave-frequency and a radio-frequency signal. For example, the inner conductor 112 and outer conductor 114 may be a solid or braided metal including metals such as copper and/or aluminum. The insulating layer 116 may be any electrically insulating material such as dielectric materials. When used as a microwave-frequency antenna, the applicator 104a is retained in a position where the inner conductor 112 and the outer conductor 114 are not in contact with the wall of the vas. When used as a radio-frequency probe, the inner conductor 1 12 functions as the active electrode and can be brought into contact with the wall of the vas using any of the above-described methods or other suitable positioning methods.

[0046] FIG. 3B illustrates the applicator 104b according to another embodiment. In the illustrated embodiment, the applicator includes an inner conductor 112, an outer conductor 114, and an insulating layer 116. The applicator 104b also includes a disc-shaped plane surface 202 including a thin coating of metal 204. The metal 204 is in contact with inner conductor 112 and may be deposited in known fashion, such as by sputtering or vapor deposition, on surface 202. The applicator 104b includes efficient radiation characteristics and is suitable for catheter use because of a reduced likelihood of injury. When used as a microwave-frequency antenna, the applicator 104b is retained in a position where the inner conductor 112 and the outer conductor 114 are not in contact with the wall of the vas. When used as a radio-frequency probe, the inner conductor 112 functions as the active electrode and can be brought into contact with the wall of the vas using any of the methods described herein or other suitable positioning methods.

[0047] FIG. 3C illustrates the applicator 104c according to yet another embodiment. In the illustrated embodiment, the applicator includes an inner conductor 112, an outer conductor 114, and an insulating layer 116. The inner conductor 112 includes a rounded feature 206 at the tip of the inner conductor 112. The rounded feature 206 can be formed by, for example, silver soldering strands of the inner conductor 112 together. The rounded feature 206 increases the capacitance between the tip of the applicator 104c and its reference point (in this case, the distal end of the outer conductor 114), thereby increasing radiation efficiency across larger volumes. When used as a microwave-frequency antenna, the applicator 104c is retained in a position where the inner conductor 112 and the outer conductor 114 are not in contact with the wall of the vas. When used as a radio-frequency probe, the inner conductor 112 functions as the active electrode and can be brought into contact with the wall of the vas using any of the methods described herein or other suitable positioning methods.

[0048] FIG. 3D illustrates the applicator 104d according to still another embodiment. In the illustrated embodiment, the applicator 104d includes an inner conductor 112, an outer conductor 114, and an insulating layer 116. The applicator 104d also includes a conductive top cap 208. The top cap 208 increases the capacitance between the tip the applicator 104d and its reference point (in this case, the distal end of the outer conductor 114), thereby increasing radiation efficiency across larger volumes. The radiation effectiveness of the arrangement of FIG. 3D is generally superior to that of FIG. 3C, but is less suitable for use as a catheter because of the likelihood of injury to the patient. When used as a microwave- frequency antenna, the applicator 104d is retained in a position where the inner conductor 112 and the outer conductor 114 are not in contact with the wall of the vas. When used as a radio-frequency probe, the inner conductor 112 functions as the active electrode and can be brought into contact with the wall of the vas using any of the methods described herein or other suitable positioning methods.

[0049] FIGS. 4 A and 4B illustrate the distal end 304 of a catheter 302 disposed within a blood vessel 306, according to an embodiment. In this embodiment, the catheter 302 includes an elongate shaft 303 having an outer conductor 308, an inner conductor 310, and an insulator 312 therebetween. The inner conductor 310 is a tubular inner conductor having a lumen 314 therethrough. The lumen 314 extends from the distal end 304 toward the proximal end (not shown) of the catheter 302. In some aspects, the lumen 314 extends to the proximal end of the catheter 302. In other aspects, the lumen 314 forms an opening in a sidewall of the catheter 302 prior to reaching the proximal end. In some aspects, the catheter also includes a rounded end cap 316 to reduce the risk of injury to the blood vessel 306 during insertion of the catheter 302. Intravascular access to a desired location is well known in the art and is described in, for example, International Patent App. No. PCT/US2011/057729, filed October 25, 2011, which is incorporated herein by reference in its entirety.

[0050] FIG. 4A illustrates a guide wire 318 being used to guide the distal end 304 of the catheter 302 through the blood vessel 306. The guide wire 318 is inserted into the patient's cardiovascular system and navigated toward the target site through blood vessels. The guide wire 318 is generally made of a thin and flexible material to prevent damaging blood vessels while allowing access various sizes of blood vessels. After the guide wire 318 is disposed near the target site, the guide wire 318 is received by the lumen 314 and the catheter 302 is guided toward the target site by sliding over the guide wire 318. After the distal end 304 of the catheter 302 is disposed at or adjacent the target site, the guide wire 318 may be removed from the lumen 314.

[0051] FIG. 4B illustrates the distal end of the catheter with a removable conductor 320. After the guide wire 318 is removed, the removable conductor 320 is advanced through the lumen 314 to the distal end 304 of the catheter 302. The removable conductor 320 includes an exposed portion 322 that extends past the distal end 304 of the catheter 302. The removable conductor 320 is electrically coupled with the inner conductor 310 through, for example, protrusions that engage the inner conductor 310. Beneficially, the length of the exposed portion 322 can be changed dynamically to affect the transmitted frequencies of the electromagnetic energy. A tip 324 of the removable conductor 320 can be directed to contact the wall of the blood vessel using known methods such as those described herein. The tip 324 can also be used as an active electrode when contacting the wall to deliver a supplied radio-frequency electromagnetic energy to the dispersive electrode 105 through tissue of the patient.

[0052] FIGS. 5 A and 5B illustrate the applicator 104 with a positioning mechanism according to an embodiment. The positioning mechanism is configured to retain the applicator 104 at a position within the vas. In the illustrated embodiment, the positioning mechanism is a balloon 402 that is generally transparent to microwave frequencies. FIG. 5A illustrates the balloon 402 in an inflated condition. The balloon 402 can be inflated or deflated using gasses and/or liquids. The gasses and/or liquids can be transferred to the balloon 402 through the catheter 102 and/or the applicator 104 using, for example, the lumen or another lumen. The balloon 402 is generally spherical or generally cylindrical in shape and will retain the applicator 104 generally in the center of the vas. In some embodiments, the balloon 402 is asymmetrically shaped when inflated to retain the applicator 104 near or against a wall of the vas when inflated. [0053] In the illustrated embodiment, the balloon 402 also includes a metallized portion 404 that covers a portion of the interior of the balloon 402. As shown in FIG. 5B, microwave frequency radiation is not transmitted through the metallized portion 404. In some aspects, the metallized surface 404 is shaped to reflect the microwave radiation emitted by the applicator 104 in a desired direction, represented by arrows in FIG. 5B. The metallized portion may be formed by vapor deposition, electro deposition, etc.

[0054] FIG. 6 is a simplified cross sectional view of the applicator 104 with a balloon 402 having a first metallized portion 404a and a second metallized portion 404b. The metallized portions 404a,b are disposed opposite each other in the interior of the balloon 402. An opening 602 is formed between the first and second portions 404a,b that limits the radiation emitted to an annular ring extending generally radially from the vas.

[0055] In some aspects, more than one signal generator is used to supply electromagnetic energy. In one nonlimiting example, a first signal generator is used to produce the first electromagnetic energy and a second signal generator is used to produce the second electromagnetic energy.

[0056] In some aspects, the applicator 104 outputs the first electromagnetic energy at a first period of time and outputs the second electromagnetic energy at a second period of time. In other aspects, the applicator 104 outputs the first electromagnetic energy and the second electromagnetic energy simultaneously.

[0057] In some aspects, a heat sink is used to prevent detrimental heating of non-target tissue. In some embodiments, the heat sink is accomplished by allowing blood to flow through the blood vessel and around the catheter system. The flowing blood carries heat away from the blood vessel and surrounding tissue. In one non-limiting example, the balloon is under- inflated so that the blood vessel is not occluded and blood flows around the catheter. In some aspects, the heat sink is accomplished by using heat exchanger within the catheter. In one non-limiting example, open- or closed-circuit cooling is used to remove excess heat. Various methods, systems and apparatuses for active and open- and closed-circuit cooling have been described previously, for example, in U.S. Patent Application No. 13/279,205, filed October 21, 2011, and International Patent App. No. PCT/US2011/033491, filed April 21, 2011, both of which are incorporated herein by reference in their entireties.

[0058] While the preceding description has been made with reference to the pancreas and pancreatic tumors, it is contemplated that aspects described herein can be used on other portions of the body. Moreover, microwave and/or radio frequency energy applied using the systems and methods described herein may be applied to a patient for treatment of cancer, prostate enlargement, sleep apnea, and hypothermia, as well as other medical conditions.

[0059] Additionally, the above-described systems and methods provide benefits over prior-art devices such as needle probe devices for certain treatments. For example, proximity of blood vessels and nerve tissue to the target tissue or the type of intervening tissue may lead to the needle probe damaging non-target tissue during insertion or extraction. Systems and methods as described herein help to minimize both invasion of tissue and risk of damage to non-target tissue.

[0060] While the invention is susceptible to various modifications and alternative forms, specific embodiments and methods thereof have been shown by way of example in the drawings and are described in detail herein. It should be understood, however, that it is not intended to limit the invention to the particular forms or methods disclosed, but, to the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims.

Claims

CLAIMS What is claimed is:

1. A system for treatment of an abnormal growth and neuromodulation of at least one patient comprising:

an applicator configured to be disposed at or adjacent at least one target site, the applicator configured to impart a first electromagnetic energy having a first frequency to modulate at least one nerve or nerve tissue at or adjacent one or more of the at least one target sites and configured to impart a second electromagnetic energy having a second frequency to treat the abnormal growth at or adjacent one or more of the at least one target sites;

a positioning mechanism configured to retain the applicator in a position relative to the at least one target site; and

at least one signal generator operatively coupled to the applicator, the at least one signal generator configured to supply the first electromagnetic energy and the second electromagnetic energy to the applicator.

2. The system of claim 1 further comprising:

a guide wire for accessing the at least one target site in the at least one patient via a vas; and

a catheter including an elongate shaft having a distal end and a lumen therethrough, the guide wire being positioned within the lumen to guide the distal end to the at least one target site,

wherein the applicator is disposed at or adjacent the at least one target site via the lumen.

3. The system of claim 2 wherein the vas includes a cardiac structure, a vascular structure, a gastrointestinal structure, a urologic structure, a gynecologic structure, a pulmonary structure, or a structure in a head, ear, nose, or throat, the vascular structure including a blood vessel such as an artery or vein.

4. The system of claim 1 wherein the first frequency and the second frequency are radio frequencies between about 3 KHz and about 300 MHz, and wherein the system further includes a dispersive electrode disposed on the at least one patient when the radio frequency is applied.

5. The system of claim 1 wherein the first frequency is a radio frequency between about 3 KHz and about 300 MHz and the second frequency is a microwave frequency greater than about 300 MHz , and wherein the system further includes a dispersive electrode disposed on the at least one patient when the radio frequency is applied.

6. The system of claim 1 wherein the first frequency is a microwave frequency greater than about 300 MHz and the second frequency is a radio frequency between about 3 KHz and about 300 MHz, and wherein the system further includes a dispersive electrode disposed on the at least one patient when the radio frequency is applied.

7. The system of claim 1 wherein the first frequency and the second frequency are microwave frequencies greater than about 300 MHz.

8. The system of claim 1 wherein the applicator is at least two applicators.

9. The system of claim 1 wherein the at least one signal generator is a single signal generator.

10. The system of claim 1 wherein the applicator includes an inner conductor, an outer conductor, and an insulator therebetween.

11. The system of claim 1 further comprising a heat exchanger disposed within the lumen of the elongate shaft.

12. The system of claim 1 further comprising a temperature sensor disposed proximate the applicator.

13. The system of claim 1 wherein the positioning mechanism is an inflatable balloon.

14. The system of claim 1 wherein the applicator is capable of transmitting the first electromagnetic energy and the second electromagnetic energy simultaneously for a period of time.

15. A method for treatment of an abnormal growth and neuromodulation of at least one patient comprising:

positioning a catheter within at least one vas using a guide wire; positioning an applicator at or adjacent at least one target site using the catheter;

applying, using the applicator, a first electromagnetic energy having a first frequency to modulate at least one nerve or nerve tissue at or adjacent one or more of the at least one target sites; and

applying, using the applicator, a second electromagnetic energy having a second frequency to treat the abnormal growth at or adjacent one or more of the at least one target sites.

16. The method of claim 15 wherein the applicator includes a first applicator and a second applicator, the first electromagnetic energy being applied using the first applicator and the second electromagnetic energy being applied using the second applicator.

17. The method of claim 15 further comprising disposing a dispersive electrode on the at least one patient for application of radio-frequency electromagnetic energy, wherein the first frequency and the second frequency are radio frequencies between about 3 KHz and about 300 MHz.

18. The method of claim 15 further comprising disposing a dispersive electrode on the at least one patient for application of radio-frequency electromagnetic energy, wherein the first frequency is a radio frequency between about 3 KHz and about 300 MHz and the second frequency is a microwave frequency above about 300 MHz.

19. The method of claim 15 further comprising disposing a dispersive electrode on the at least one patient for application of radio-frequency electromagnetic energy, wherein the first frequency is a microwave frequency above about 300 MHz and the second frequency is a radio frequency between about 3 KHz and about 300 MHz.

20. The method of claim 15 wherein the first frequency and the second frequency are microwave frequencies above about 300 MHz.

21. The method of claim 15 wherein the positioning the applicator comprises:

positioning the applicator in a first position for applying the first electromagnetic energy; and

positioning the applicator in a second position for applying the second electromagnetic energy,

wherein the first position and the second position are different positions.

22. The method of claim 15 further comprising cooling non-target tissue using a heat sink.

23. The method of claim 22 wherein the heat sink is a heat exchanger disposed within the lumen of the elongate shaft.

24. The method of claim 15 wherein at least one of the applicator or the catheter includes a positioning mechanism configured to retain the applicator in a position within the vas.

25. The method of claim 15 wherein the applying the first electromagnetic energy and the applying the second electromagnetic energy are performed simultaneously for a period of time.

26. An applicator configured to be disposed within a vas at or adjacent a target site for treatment of an abnormal growth and neuromodulation of at least one patient, the applicator comprising:

a radio-frequency probe configured to heat a first target tissue by transferring a radio-frequency electromagnetic energy from the radio-frequency probe to a dispersive electrode spaced a distance from the applicator, the radio-frequency electromagnetic energy having a frequency between about 3 KHz and about 300 MHz; and

a microwave-frequency antenna configured to heat a second target tissue by transmitting a microwave-frequency electromagnetic energy to the second target tissue, the microwave-frequency electromagnetic energy having a frequency above about 300 MHz, wherein the applicator is configured to be retained at a position within the vas by a positioning mechanism.

27. The applicator of claim 26 wherein the first target tissue includes at least one nerve or nerve tissue and the radio-frequency electromagnetic energy is configured to modulate the at least one nerve or nerve tissue using a first frequency.

28. The applicator of claim 27 wherein the second target tissue includes the abnormal growth and the microwave-frequency electromagnetic energy is configured to treat the abnormal growth using a second frequency.

29. The applicator of claim 26 wherein the first target tissue includes the abnormal growth and the radio-frequency electromagnetic energy is configured to treat the abnormal growth using a first frequency.

30. The applicator of claim 29 wherein the second target tissue includes at least one nerve or nerve tissue and the microwave-frequency electromagnetic energy is configured to modulate the at least one nerve or nerve tissue using a second frequency.

31. The applicator of claim 26 wherein the applicator is capable of imparting the radio- frequency electromagnetic energy and the microwave-frequency electromagnetic energy simultaneously for a period of time.

32. A system for treatment of at least one patient comprising:

an applicator configured to be disposed at or adjacent at least one target site, the applicator further configured to treat a first condition by imparting a first electromagnetic energy having a first frequency and to treat a second condition by imparting a second electromagnetic energy having a second frequency;

33. The system of claim 32 wherein the first frequency is a radio frequency between about 3 KHz and about 300 MHz and the second frequency is a microwave frequency greater than about 300 MHz , and wherein the system further includes a dispersive electrode disposed on the at least one patient when the radio frequency is applied.

34. The system of claim 32 wherein the first frequency is a microwave frequency greater than about 300 MHz and the second frequency is a radio frequency between about 3 KHz and about 300 MHz, and wherein the system further includes a dispersive electrode disposed on the at least one patient when the radio frequency is applied.

35. The system of claim 32 wherein the first condition and the second condition are each selected from the group consisting of cancer, prostate enlargement, sleep apnea, and hypothermia.