WO2010019773A2

WO2010019773A2 - Smart stent

Info

Publication number: WO2010019773A2
Application number: PCT/US2009/053716
Authority: WO
Inventors: Timothy Robertson
Original assignee: Proteus Biomedical, Inc.
Priority date: 2008-08-13
Filing date: 2009-08-13
Publication date: 2010-02-18
Also published as: WO2010019773A3

Abstract

Smart stent systems and methods of using the same to evaluate fluid flow through a stent are provided. Systems according to various aspects of the invention include a stent having a coil configured as a resonant circuit and a reader. During use, an oscillation is produced in the coil of the stent by applying an RF field to the stent. Then, a parameter associated with the oscillation is obtained to evaluate fluid flow through the stent. The systems and methods may be used in a variety of applications, such as detecting the occurrence of re-stenosis.

Description

SMART STENT

CROSS-REFERENCE TO RELATED APPLICATIONS

Pursuant to 35 U. S. C. § 119 (e), this application claims priority to the filing date of United States Provisional Patent Application Serial No. 61/088,349 filed on August 13, 2008: the disclosure of which application is herein incorporated by reference.

INTRODUCTION

Estimated seven million Americans suffer from coronary artery disease, which causes 1.5 million myocardial infarctions (e.g., heart attacks) and over half a million deaths annually at a cost of over $100 billion. Coronary artery disease results from atherosclerosis, a complex process in which fatty and other deposits (e.g., cellular intimal and mineral additives, engrained proteinaceous or clotting/platelet debris, etc.) build up in the walls of arteries, resulting in blockages and reduced blood flow. This process leads to the formation of a plaque of atherosclerotic material that can be comprised of various cells, lipids (e.g., fats or cholesterol), and collagen (e.g., fibrous tissue). This process progresses over a number of years and may eventually result in the formation of a blockage (e.g., stenosis) in the coronary artery. If the artery is sufficiently narrowed, the reduction of blood flow (e.g., ischemia), chest pain (angina pectoris), heart attack, or sudden death may follow. In addition to the narrowing of the artery produced by atherosclerosis, plaques may also rupture, resulting in the formation of a thrombus or blood clot on the plaque surface, leading to an abrupt cessation of blood flow to the heart. The plaque rupture plays a key role in most cases of heart attack and stroke.

In 1977, Dr. Andreas Gruentzig from Switzerland introduced a novel method for treating coronary artery stenosis, which he termed "Percutaneous Transluminal Coronary Angioplasty" (PTCA), also commonly known as balloon angioplasty. Over 500,000 coronary angioplasties (e.g., where the term angioplasty is derived from angio, which refers to a blood vessel, and plasty, which means to reshape) were performed in the U.S., surpassing the number of coronary bypass operations. The advantage of this technique is that it can be performed using minimally invasive catheter procedures. Using special x-ray equipment and contrast dye to visualize the arteries, the cardiologist advances a guide catheter (e.g., of a hollow tube) through a vascular access sheath and up the aorta to the origin of the coronary arteries. Using this catheter as a track to the coronary artery, a long, fine guidewire (e.g., 0.014 inch in diameter) is negotiated across the stenosis. A catheter with a deflated balloon on the far end is then advanced over the guidewire to the narrowed arterial segment. At this point the balloon is inflated, and the occluding plaque is compressed to the arterial wall.

In conventional PTCA, the occluding plaque is simply compressed and no material is removed. In about one-third of cases, re-narrowing of the treated segment may occur over a period of several months, necessitating a repeat procedure or coronary artery bypass surgery. This re-narrowing is termed "restenosis" and appears to be distinct from the process of atherosclerosis. Despite intense research efforts and numerous drug trials, a solution to this problem remains elusive.

In order to reduce the re-stenosis rate and improve blood flow, stents may be routinely inserted into arteries after PTCA. A stent is a wire mesh tube usually made of metal that is expanded within the artery to form a scaffold that keeps the artery open. The stent stays in the artery permanently, holds it open, improves blood flow to the heart muscle, and relieves symptoms (e.g., chest pain).

After placement, the stent may be covered with epithelium over the course of several weeks. In the case of in-stent re-stenosis, this tissue growth process continues. The hyperproliferation of normal cells may result in the obstruction of the flow of blood through the stented vessel. Thus, even with stents, the re-stenosis rate can be as high as 25%.

Re-stenosis within the stent may be detected in several ways. If a patient is symptomatic with angina, several diagnostic procedures may be performed. Stress Echo Cardiography may be performed whereby the heart is imaged using ultrasound, and differences between the motion of the resting heart and the exercised heart are used to determine abnormalities that indicate restricted blood flow. However, this test may not be so effective in detecting a blockage less than 50%. A Thallium Stress Test may also be performed to indicate the degree of blood supply to the heart under differing load conditions (e.g., at rest or exercised). However, this procedure may require injecting radioactive markers into the patient and the use of expensive gamma imaging cameras. The procedure may also require above 70% blockage of blood flow for it to be effective. Further, Stress Echo Cardiography and Thallium Stress Tests are expensive, and can endanger a patient with a dysfunctional heart to exercise loads.

If preliminary test results of the diagnostic procedures are positive, then a physician generally performs coronary angiography. In this procedure a catheter is inserted into the patient, and an x-ray contrast agent is injected to image the blood flow with x-rays. This is an invasive procedure, which requires the use of an operating room and exposes the patient to x-ray radiation. The procedure is also costly and may subject the patient to a stroke or other adverse event that is associated with the procedure.

In another emerging technique known as "intravascular ultrasound," a miniature ultrasound transducer is inserted by a catheter to a blood vessel and the acoustic impedance of the blood vessel is monitored by external acoustic receivers. However, this, too, is an invasive procedure.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates an exemplary stent system. FIG. 2 illustrates another exemplary stent system.

FIGs. 3A-3D illustrate an exemplary operation of the stent systems. FIGs. 4 and 6 illustrate an exemplary stent with a four terminal device. FIG. 5 illustrates an exemplary stent with a two terminal. FIG. 7 illustrates an exemplary stent with conductive windows. FIGs. 8, 9, and 10 illustrate exemplary stents with different coil formations.

SUMMARY

DETAILED DESCRIPTION

Smart stent systems and methods of using the same to evaluate fluid flow through a stent are provided. Systems according to various aspects of the invention include a stent having a closed coil component and a reader, which may be external or implantable. During use, an oscillation is produced in the closed coil component of the stent, e.g., by applying a radio frequency (RF) field to the stent. Next, an oscillation parameter of the oscillation is detected in order to evaluate fluid flow through the stent. Also provided are kits made up of various components of the systems. The systems and methods may be used in a variety of applications, such as detecting the occurrence of re-stenosis.

The stent systems of the invention, hereinafter also referred to as a smart stent sensing system, provide in situ monitoring and measurement of re-stenosis within and around a stent. Using the smart stent innovation, in situ monitoring results can then be reported outside the body to relevant individuals, such as the patient and their caregivers, such as physicians.

FIG. 1 illustrates an exemplary stent system, according to one aspect of the invention. The stent system includes a stent 102 and a reader 104. The stent 102 is coupled to a coil 105 (e.g., a closed coil component 106) which enables the measurement of parameters indicative of changes in the status of the stent orifice, blood flow through it, and other pertinent clinical parameters. It is appreciated that the coil 105 may be one of many different configurations (e.g., an open coil, a closed coil, etc.). The reader 104 may be implanted or implemented external to the body of a subject. When implanted, the reader 104 may be incorporated into a pacing implant. When the reader 104 is outside the body, it may take a number of forms, such as a hand held reader. Alternatively, the reader can be in the form of a patch that can be worn on the skin or of any other form (e.g., a laptop, a handheld device, etc.) in close proximity to the stent 102.

In FIG. 1 , the closed coiled component 106 includes a capacitor 108 as well as a coil which makes up most of the closed coiled component 106. In one aspect, the stent 102 may provide a formed coil that runs longitudinally along the stent 102, as in the closed coil component 106. During fabrication, this coil is completed as a closed loop. This results in the coil becoming functionally a closed coil (e.g., the closed coil component 106). This simple, elegant design of the stent 102 may have special practicalities in construction and design, as well as in function. As illustrated in FIG. 1 , the reader 104 includes a signal source 1 10, a coil

1 12, and an amplifier 1 14. In one exemplary implementation, the signal source 110 is switched on to supply current to the coil 1 12. This produces an RF field 1 16 that couples to the coil of the closed coil component 106 of the stent 102. The coil of the stent 102 (e.g., a resonant circuit, such as a RC, RL, LC, or RLC circuit) may have an intrinsic oscillation frequency that comes from the capacitance of the capacitor 108, where the resonance comes from the inductance and the capacitance associated with the closed coil component 106. Then, one or more parameters associated with the oscillation may be detected using the reader 104 in order to evaluate fluid (e.g., blood) flow through the stent 102. FIG. 2 illustrates another exemplary stent system, according to one aspect of the invention. As illustrated in FIG. 2, the capacitance generated by a coil 205 (e.g., a closed coil component 206) is based on intrinsic, self-capacitance 208 of the coil. It is appreciated that the self-capacitance 208 may be built into the coil of the closed coil component 206 using the "chip skin" process, as taught in PCT Patent Application Serial No. PCT/US2007/009270, the disclosure of which is herein incorporated by reference. It is also appreciated that besides the nature of the capacitance, the stent system illustrated in FIG. 2, which includes components 202 through 214, may operate in a similar fashion as that of FIG. 1.

FIGs. 3A-3D illustrate an exemplary operation of the stent systems, according to one aspect of the invention. It is appreciated that the operation illustrated in FIGs. 3A-3D is described in association with the stent system of FIG. 1. However, any similar stent systems, such as the one in FIG. 2, may be used to explain the operation. In operation of the stent system, the RF field 1 16 generates an oscillation in the closed coil component 106. Blood flow, which includes red blood cells bearing hemoglobin, transits through the internal fluid passageway of the stent 102. The coil 1 12 generates the oscillation field internally to the body, as illustrated in FIG. 3A. The RF field 1 16 then transfers energy into the closed coil component 106. The coil 1 12 is then turned off, and the oscillation in the closed coil component 106 may experience a decay, as illustrated in FIG. 3B.

As this field oscillates, the closed coil component 106 generates a magnetic field, functioning essentially as a solenoid. This produces an oscillating magnetic field. This oscillating magnetic field runs along the artery. Because the red blood cells have hemoglobin molecules in them, which contain iron, the magnetic field alternately polarizes and depolarizes the iron in the hemoglobin. This process results in magnetization, or a magnetic susceptibility. In a case where a stenosis forms on the stent 102, plaque may cover part of it. This may reduce the volume of blood that is inside the stent 102. As a result, the amount of iron that is available for polarization may decrease. Subsequently, the polarizability may decrease. These changes may manifest in one of two ways, either a change in the Quality factor (Q) of the closed coil component 106, that is the decay constant, or a change in the resonance frequency of the closed coil component 106, as the additional loading of the circuit by biologic media modifies the resonance. For example, FIG. 3C illustrates the decay when plaque is not present, while FIG. 3D illustrates the decay when plaque is present.

The signal source 1 10 on the reader 104 may have two functions. It may be used to read the status of the stent 102. The signal source 1 10 may be also used to apply the RF field 1 16, thus operating as an external transducer. Using the signal source 1 10, a strong AC field is applied, and subsequently turned off. Then, the stent 102 may track the field and gain energy.

Once the reader 104 is turned off, oscillation in the closed coil component 106 may begin to decay, as illustrated in FIG. 3B. There may be an envelope formed around this decaying oscillation. The decay time constant τ_dθCay of the decaying envelope may depend on the magnetization of the contents of the stent 102 (e.g., blood to plaque volume).

In general, more blood may result in more damping. As a result, the decay- time constant may get smaller. As the plaque displaces the blood during stenosis, the decay-time constant may be increased. In this manner, the quantitative measure of the amount of stenosis is achieved.

Changes in the decay-time constant of the stent 102 may be then read using the reader 104 of the stent system. The data gleaning is achieved because the reader 104 goes into an amplification mode where it would measure the voltage across the coil 112, where an induced signal on the reader 104 results. This signal tracks the decay. A measurement is made of the decay-time constant directly with the reader 104, which could be done through digitization and parametric fitting of the decaying waveform, or through an analog processing technique, as used in some nuclear magnetic resonance (NMR) systems. Because the signal received by the reader 104 may be much weaker than the driving signal, a blanking circuit may be employed to prevent the reader 104 from overloading, as indicated by the hatched period in FIG. 3B.

The detection can be accomplished and read by the reader 104 (e.g., in close proximity, in a doctor's office, in a remote location via a relay communication, etc.). In practice, the reader 104 (e.g., external reader) is placed close to the stent 102, and a measurement is made. These features can be built into a patch that is worn over the stent 102. Medication compliance functions associated with the stent can be integrated into the systems, such as those disclosed in PCT application Serial Nos. PCT/US2008/52845 and PCT/US2007/015547; the disclosures of which are herein incorporated by reference.

In one exemplary implementation, an integrated system based on the stent system of FIG. 1 may be provided. Where a patient has the stent 102 installed with smart stent features, the patient is concomitantly put on an intelligent medicine program. With this dual capacity, for a patient who is taking their Plavix or other anticoagulant, the stent system may be used to measure properties, such as the restenosis, to give indications to doctors of the efficacy of a particular pharmaceutical regimen, and allow them more clarity when modifying such regimens.

In an additional implementation, the stent system may use a shift in Q, the decay-time constant, of the coil 105 to read out stenosis. Alternatively, a shift in frequency can be generated. This can be accomplished by tuning the coil 105 to a ferromagnetic resonance of the red blood cell. A shift in frequency is observed as that ferromagnetic resonance pulls the intrinsic resonance of the coil 105 in one direction or another. Shifts in frequency may be easier to measure than shifts in time constants. FIGs. 4 and 6 illustrate an exemplary stent 402 with a four terminal device

408, according to one aspect of the invention. It is appreciated that the stent 402 may comprise several features in common with the previously described stents (e.g., the stent 102, the stent 202, etc.). In this case, a coil 405 (e.g., a closed coil component 406) is attached to a chip (e.g., the four terminal device 408). Two terminals couple to each end of the coil, and a reader (e.g., similar to the reader 104) associated with the stent 402 may ring up the coil 405. This configuration may provide power for the chip very similar to how RFID is powered.

The second pair of terminals couple to a set of transducers 410, which could be pressure sensors, resistivity sensors, or electric field sensors as used in electromagnetic flow meter, e.g., as described in PCT Patent Application PCT/US2006/034258; the disclosures of which is herein incorporated by reference. These sensors may be positioned transversely across the blood vessel, as in FIG. 4, or longitudinally, as in FIG. 6. The chip (e.g., with an integrated circuit) may be powered by the coil 405 to measure one or more parameters detected by the transducer terminals that is related to a physiological quantity of interest such as stenosis, and then to modulate the impedance of the coil 405 to transmit that result back.

FIG. 5 illustrates an exemplary stent 502 with a two terminal device 508, according to one aspect of the invention. It is appreciated that the stent 502 may comprise several features in common with the previously described stents (e.g., the stent 102, the stent 202, the stent 402, the stent 602, etc.). In FIG. 5, there is a coil 505 (e.g., a closed coil component 506) attached to the two terminal device 508. In one exemplary implementation, the inductance or capacitance of the coil 505 may be modulated by a physiologic parameter of interest, such as stenosis. For example, the stent 502 may be provided with a membrane where its resonant frequency is modulated as plaque deposits on it. This approach is analogous to how a crystal monitor works in a thin film deposition system. The additional mass of deposited plaque may lower the resonant frequency. This change in resonant frequency may be detected using the read-out circuit, as illustrated in FIG. 3D.

FIG. 7 illustrates an exemplary stent 702 with conductive windows 708, according to one aspect of the invention. For example, in the stent 702, the resistance of a coil 705 (e.g., a closed coil component 706) may change during stenosis when the coil 705 is mostly insulated except for the conductive windows 708. These little conductive windows 708 may provide damping, so that a resistance can be formed on the coil 705 in response to a build-up of an overlaying material on the conductive windows 708. The degree of resistance may depend on whether the conductive windows 708 are covered with blood or plaque. The form of the overlying material may modulate the damping, changing in the decay constant of the coil 705. This change in the decay constant may be measurable.

In one aspect, as illustrated in FIG. 7, a set of loops may be provided in the coil 705 with its surface similar to the physical surface structure of Swiss cheese. That is, the structure may have little passages through it. Again, the electrical properties of the coil 705 may be modulated by whether blood or plaque is deposited on it.

These aspects may provide a qualitative signal indicating the type of substance in contact with the stent 702. This may be important for drug eluting stents, because the patient should remain anti-coagulated until tissue overgrows the stent 702. With this system, one would see a change in the Q of the coil 705 resulting from a change in the resistive shunting of the stent 702 as the substance in contact with it changes. A patient would be enrolled in a medication adherence program and prescribed an anti-coagulant until a signal indicating overgrowth is obtained. This may indicate that stopping anti-coagulant therapy is safe.

When the aspect of the stent 702 that couples a magnetic field to magnetic material in the blood is used, the stent 702 may measure the coil-iron content inside the coil 705. The geometry localizes the sensing to inside the coil 705 and not so much outside. The presumption here is that the magnetic susceptibility of blood is significantly different from that of plaque. What the coil 705 measures is the average magnetic susceptibility. As the fraction of blood relative to the fraction of plaque changes, that average susceptibility should change. There are other things that can change it. By example, theoretic hematocrit levels may in some cases be sufficiently deviant that a correction is warranted. If this is a doctor's office test, one could take a blood sample and calibrate hematocrit very precisely before making a final determination of re-stenosis levels. If the stenosis is stable, that is, there is no new stenosis after a long period of time, fluctuations in this parameter may be due to hematocrit. The device can then be employed as an in situ hematocrit sensor. FIGs. 8, 9, and 10 illustrate exemplary stents with different coil formations, according to various aspects of the invention. In FIG. 8, a coil 805 is formed around a stent 802. In FIG. 9, a coil 905 is integrated with a stent 902. In FIG. 10, a coil 1005 is formed inside of a stent 1002. It is appreciated that the stents illustrated in FIGs. 8-10 may function similar to the previous stents described in FIGs. 1-7. In an exemplary implementation, the coils used for the stents can be produced using a number of approaches. For instance, insulating various rungs of material may result in a functional coil. This approach may result in a spiral shaped form integrated in the existing stent form, e.g., where the closed coil component is integral with the stent component of the stent. In this case, the coil can be internal to the stent, as illustrated in FIG. 10.

Considerations such as usage parameters, periodicity of information query, temporary or permanent implant, medicated or unmedicated stents, ease of production, cost of materials, etc. may help guide the design and manufacture techniques of the stents. The coil of the stents according to various aspects of the invention can be external (e.g., as shown in FIG. 8), integrated (e.g., as shown in FIG 9), internal (e.g., as shown in FIG. 10), or a hybrid of these configurations. It could be integrally part of a laser production process as many current stents are typically laser cut. A cutting pattern can be designed that has an intrinsic spiral. Alternatively, a tube can be formed producing spiral around the outside of the entire construct. It is to be understood that this invention is not limited to particular aspects described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described.

All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. It is noted that, as used herein and in the appended claims, the singular forms

"a", "an", and "the" include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely," "only" and the like in connection with the recitation of claim elements, or use of a "negative" limitation. As will be apparent to those of skill in the art upon reading this disclosure, each of the individual aspects described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several aspects without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.

Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.

Accordingly, the preceding merely illustrates the principles of the invention. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the invention and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the invention and the concepts contributed by the inventors to furthering the art, and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and aspects of the invention as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. The scope of the present invention, therefore, is not intended to be limited to the exemplary aspects shown and described herein. Rather, the scope and spirit of present invention is embodied by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A device, comprising: a stent; and a coil configured as a resonant circuit, wherein the coil is coupled to the stent.

2. The device according to claim 1 , wherein the coil is separable from the stent.

3. The device according to claim 1 , wherein the coil is integrated with the stent.

4. The device according to claim 1 , wherein the coil is implemented internal to the stent.

5. The device according to claim 1 , wherein the coil is implemented external to the stent.

6. The device according to claim 1 , wherein the coil comprises a closed coil component.

7. The device according to claim 1 , wherein the resonant circuit is based on at least two of capacitance; resistance; and inductance built on the coil.

8. The device according to claim 1 , wherein the coil comprises a capacitor.

9. The device according to claim 1 , wherein the coil comprises at least one transducer.

10. The device according to claim 1 , wherein the coil comprises an insulated closed coil component forming a plurality of conductive windows therein.

1 1. A system comprising: a stent comprising a coil configured as a resonant circuit; and a reader.

12. The system according to claim 1 1 , wherein the coil comprises a closed coil component.

13. The system according to claim 1 1 , wherein the reader is configured to apply an RF field to a subject implanted with the stent.

14. The system according to claim 13, wherein the coil is configured to generate a magnetic field in response to the RF field based on a composition of a fluid flow via the stent.

15. The system according to claim 14, wherein the reader is configured to process the magnetic field.

16. A method for use with a medical device implanted in a subject, the medical device having a stent and a coil configured as a resonant circuit, the method comprising: producing an oscillation in the coil of the medical device; and detecting a parameter associated with the oscillation in the coil to evaluate a fluid flow through the stent.

17. The method according to claim 16, wherein the producing the oscillation comprises applying an RF field to the coil.

18. The method according to claim 16, wherein the parameter comprises a quality factor (Q) and a resonance frequency of the oscillation in the coil.

19. The method according to claim 16, further comprising determining an occurrence of re-stenosis based on the parameter associated with the oscillation.

20. The method according to claim 16, further comprising determining a response of the subject to a pharmaceutical regimen applied to the subject based on the parameter.