BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a medical device that can be used to evaluate in-stent restenosis. The present invention also relates to a combination electromagnetic wave excitation and ultrasound detection device that can be used to monitor occlusions inside implanted stents.

Description of Related Art An estimated seven million Americans suffer from coronary artery disease, which causes 1.5 million myocardial infarctions (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, and engrained proteinaceous or clotting/platelet debris) 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 (fats or cholesterol), and collagen (fibrous tissue). This process progresses over a number of years and may eventually result in the formation of a blockage (stenosis) in the coronary artery. If the artery is sufficiently narrowed, blood flow is reduced (ischemia), and chest pain (angina pectoris), heart attack, or sudden death may follow. In addition to the narrowing produced by atherosclerosis, plaques may also rupture, resulting in the formation of a thrombus (clot) on the plaque surface, leading to an abrupt cessation of blood flow to the heart. 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" (PICA), also commonly known as balloon

angioplasty. Over 500,000 coronary angioplasties (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 (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 (generally 0.014 inches 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 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 restenosis rate and improve blood flow, stents are now routinely inserted into arteries after PTCA. Stents are wire mesh tubes usually made of metal that are 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 (usually chest pain).

After placement, the stent will normally be covered with epithelium over the course of several weeks. In the case of in-stent restenosis, this tissue growth process continues. The hyperproliferation of normal cells results in the obstruction of the flow of blood through the stented vessel. Even with stents, the restenosis rate can be as high as 25%.

Restenosis within the stent can 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. Unfortunately this test typically cannot detect 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 (at rest or exercised). Unfortunately, this procedure requires injecting radioactive markers into the patient and the use of expensive gamma imaging cameras and requires above 70% blockage of blood flow to give a positive result. Stress Echo Cardiography and Thallium Stress Tests are expensive, and can subject a patient with a dysfunctional heart to exercise loads, which can be dangerous.

If preliminary test results are positive then a physician generally performs coronary angiography. In this procedure a catheter is inserted into the patient and x-ray contrast agent injected so that the blood flow can be imaged with x-rays. This is an invasive procedure requiring the use of an operating room and exposes the patient to x-ray radiation. The procedure is also very costly. In addition there is a finite risk that the patient will experience a stroke or other adverse event that is associated with the procedure, and this risk can extend long period after the angiography is performed.

Another emerging technique, referred to as"intravascular ultrasound" where a miniature ultrasound transducer is inserted by a catheter and the acoustic impedance of the blood vessel is monitored by external acoustic receivers is also being evaluated for efficacy. Unfortunately this is an invasive procedure.

Recently Spillman et al. (WO 00/56210) and Cimochowski et al. (WO 99/26530) described a novel stent design that incorporates a miniature sensor that can be used to measure flow or pressure and diagnose restenosis. Unfortunately, these devices require incorporating a sensor into the stent that could adversely affect the mechanical properties of the stent

Given the limitations of current techniques to diagnose restenosis, there is a need for a novel device that can safely, quickly and effectively detect restenosis after stenting. The present invention fulfills this need, and further provides related advantages.

SUMMARY OF THE INVENTION An object of the present invention is to provide a device and method to evaluate in-stent restenosis.

Another object of the present invention is to provide an endoluminal implant (or stent) that can be inserted into the body and excited by electromagnetic radiation to oscillate.

Another object is to provide an ultrasound transducer that detects the excited ultrasound oscillations for analysis to detect a change in the aperture (i. e., lumen) for blood flow within the stent.

Another object of the present invention is to provide an endoluminal implant (or stent) that can be inserted into the body and probed with high frequency (0.1 to 20 GHz) electromagnetic radiation (or microwaves) to determine a change in the aperture (i. e., lumen) for blood flow within the stent.

These and other objects will be apparent to those skilled in the art based on the disclosure herein.

For treating coronary occlusions, the endoluminal implant is generally a tubular shaped member having at least two configurations. Initially it has a compact configuration in which the member has a cross-sectional size smaller than the lumen at the treatment area. After placement it has an expanded configuration in which the member has a cross-sectional size comparable to the lumen of the treatment area. The implant includes at least a portion that is made of an electrical conducting material.

The endoluminal implant system further includes an external microwave transmitter and receiver for probing the endoluminal implant. The microwave transmitter can generate a wide frequency range of microwaves (e. g. , 0.1 to 20 GHz). The receiver detects the microwaves scattered, reflected and possibly

transmitted from the endoluminal implant. The received amplitude as a function of microwave frequency and polarization can be analyzed to determine the conditions within and around the endoluminal implant.

In one embodiment, the endoluminal implant is made of a high microwave scattering material (e. g. , conductive metal). In another embodiment the geometrical structure of the implant is designed to scatter (and/or reflect) microwaves within a narrower frequency range or lower frequency or specific polarization state.

In normal use to treat and monitor coronary occlusions, a physician inserts the endoluminal implant (stent) into the patient using a balloon catheter.

After the procedure is completed or, e. g. , within about a month, the patient is placed in proximity to the microwave transmitter and receiver apparatus and a detailed measurement of the reflected and scattered microwave amplitude as a function of microwave frequency and polarization angle is performed. Typical stents are hollow metal wire mesh cylinders that can be approximated as a cylindrical waveguide. The microwave scattering cross-section on this cylinder has peaks at frequencies characteristic of the resonance frequencies of the waveguide.

This data is collected and recorded to provide a baseline frequency response around the frequencies of natural resonance of the stent for the patient with no restenosis.

In subsequent months the patient visits the doctor's office and a new frequency response is measured. The new frequency response is compared to the baseline frequency response and any previous measurements to identify possible restenosis.

When the change in the frequency response exceeds some predetermined limit, the doctor can be advised to perform additional tests including angiography.

In an alternative embodiment of the device, the patient is provided with a compact device that can be used at home to measure the scattering amplitude over a narrow range of frequencies in the vicinity of the implant resonance. In the simplest form the compact device measures the scattered microwave amplitude at two frequencies one at the implant resonance and one off resonance. The off resonance amplitude can be used to normalize the scattered amplitude and correct differences

in the positioning of the device from use to use. If the measured scattered resonance amplitude changes then it is likely due to plaque formation. In this case the patient can visit the doctor for a more detailed measurement over the full microwave frequency range.

A change in the resonance frequency of the implant occurs because the dielectric properties of plaque differ significantly from that of blood (for example near 10 GHz, the relative permittivity (dielectric constant) 0 El of blood is about 64 times larger than plaque).

There are several studies documenting the loss tangent versus frequency for tissue, blood, bone, etc. Typically the attenuation in the microwave range increases with increasing frequency from 0.1 to tens of GHz, and therefore optimal performance is achieved at the lowest eigen-frequency of the stent. The minimal H- mode eigen-frequency for a metal cylinder of radius a is given by Blood has a high relative permittivity O and 1 ; ~8, for f < lOGhz. Therefore, a blood filled cylinder with a=0. 1 cm gives f-11 GHz. As plaque or a thrombus forms on the stent, the dielectric constant inside the resonator changes by & resulting in an increase in its resonance frequency. The frequency shift is given by Here E is the electric field distribution for the lowest H mode and 56 is the change of dielectric constant within the plaque and h is the thickness of the plaque. Given the difference between plaque and blood, frequency shifts of several percent are possible.

When plaque starts to form in the stents, the eigenfrequency of the stent will increase shifting the scattering peak position to higher frequencies. The amount of the frequency shift can be used to determine the extent of restenosis.

The exact value of the resonance-frequency will depend in detail on the exact shape of the stent and can be slightly different from (1) due to the environment and the finite size of the cylinder. The value of the scattering peak is determined by the convolution of the coupling of the incident electromagnetic wave with the field inside the cylinder and Eigen mode damping. For example, the up shift in frequency due to the finite length of the cylinder L is given by <BR> <BR> <BR> <BR> (I + k2 2<BR> <BR> <BR> <BR> f 6. 8 L This shift is less than the shift expected from plaque build up within the stent as approximated by equation (2) and most importantly will not change with time.

In order to minimize the background signal due to reflection and scattering from the skin and other parts of the body, the intraluminal implant can be designed to have enhanced reflectivity at a specific polarization angle. For example using linearly polarized fields even for a simple conducting cylinder with the electric field polarized along the axis of the cylinder will generate current along the axis only and thus the scattered magnetic field intensity along the axis is zero.

Similarly, an incident wave with its magnetic field vector polarized along the cylinder axis yields a scattered wave with no electric field component along the cylinder axis. Thus, simple linear polarization of the incident field yields large discrimination. Rotating the polarization and detecting versus phase rotation can also be used to increase signal to noise. A more general solution is provided for the case of an infinite cylinder and incident wave E-polarized along the axis to obtain the scattering cross section (defined as the total scattered power divided by the Poynting vector in 3D) whereas a B-polarized incident wave would produce

where J is Bessel's function of the first kind, N is Neumann function, J'N'is the first derivative of J, N, k is the wave vector in the medium of propagation, and a is the radius of the cylinder.

Some embodiments will use stents currently used in the field without modification. However the 11 GHz resonance frequency of typical stents is in a region of the microwave spectrum where the absorption in tissue is quite high. And so in other embodiments, the material or geometry will be modified to enhance the microwave scattering or to lower the resonance frequency of the stent. Current stents such as that shown in Figure 2 would function as described above. To enhance the Q or the signal produced through buildup of plaque, the stent geometry can be modified. As one example, the cylindrical symmetry of the stent can be broken. Even in these cases polarization will improve discrimination. Figure 3 shows possible embodiments for scatterers with broken symmetry. In these cases the change in dielectric constant due to restenosis changes the resonant frequency in two ways. First the frequency changes due to the effect described above. In addition, because the E-field is concentrated at the gap, a very small change in dielectric constant near the gap (a very small degree of restenosis) can be detected.

Alternatively the space between the shield and the stent can be filled with a high dielectric constant material to reduce the resonance frequency of the stent to the low GHz range where tissue absorption is lower (however the reflection at tissue interfaces is higher). Alternatively the stent can be constructed so that electrically it is a helical winding with n turns along its length. In this case the inductance of the stent increases approximately as n2 and so the resonance frequency decreases approximately as 1/n.

In a further embodiment of the invention the space between the azimuthal break has a microwave diode inserted. The non-linear response with microwave amplitude which results from the non-linear impedance of the diode generates harmonics of the fundamental microwave frequency which will be easier to measure against the scattering background from tissue interfaces which will all be at the fundamental frequency of the microwaves.

The use of low microwave power and energy makes this device safe for the patient and eliminates the need for unnecessary x-ray imaging. To increase the signal to noise, the device can include an acoustic modulator or detect on the natural rhythmic variations of the patient such as heart beat rate. These slight modifications are easily adapted into the device.

Additional background signal rejection can be achieved by time gating the return microwave signal to eliminate reflected microwaves from outside the area of interest For example, nanosecond pulses localize the detection to a few centimeters. For these embodiments, Q (which is related to the deadtime) will need to be low. While this is not a problem with some embodiments, others may need to have their Q spoiled or lowered through overcoupling. A very simple embodiment of a pulsed transmitter/receiver can be achieved through adding a pulse modulator and traveling wave tube on the output of the broad-band source, and switching on/off the detection/receiving arms to avoid saturation of the detectors during the microwave pulse.

If the stent is tuned with a high Q, this device might allow destruction of plaque buildup through the efficient channeling of microwaves into the stent cavity.

There are several possible approaches to detecting in-stent restenosis according to the present invention. Stent structures have characteristic resonant behavior in their interaction with electromagnetic and or acoustic energy. These resonance features are influenced by the dimensions, structure, materials of the stent, as well as other features of the stent itself, and the surrounding materials and structures. Thus electromagnetic and or acoustic energy may be utilized to determine the physical properties of the stent itself, and the materials surrounding and enclosed by the stent.

The approaches to determining the in-stent restenosis may include, but are not limited to, the following: 1. RF excitation, Probing RF resonant modes, Detecting RF radiation.

Using Radio Frequency EM energy to interrogate the stent, the frequency of the RF energy is scanned, and the response of the stent is detected, in reflection, absorption,

scatter, or other characteristic EM phenomena, by detecting the modified RF energy.

This includes the detection of shifted frequencies that are produced by modifications to the stent, e. g. , a printed circuit upon the surface of the stent. This may also include modifications to the stent structure to enhance sensitivity to restenosis material, and or to enhance the interaction with the RF energy. These modifications can include mechanical modifications, such as shapes, wire mesh patterns, such as fractal patterns, mechanical features, within cylindrical form, or extending out of a cylindrical and into the lumen. To enhance the measurement, stent materials may be coated, surface treated, or otherwise modified for insulative behavior. Additionally, active electronic devices may be incorporated, either integrated upon or in the stent, or added discretely to the stent.

2. RF excitation, within an RF resonant absorption, RF modulation at frequencies consistant with stent acoustic modes to search for resonant acoustic modes, Detection of acoustic energy. The stent acoustic modes may be excited through various phenomena, including Lorentz forces or ohmic heating. The stent may be modified, as previously mentioned, to enhance RF interaction, as well as and including modifications that enhance the sensitivity of the acoustic modes to restenosis, and or to the generation of acoustic energy.

3. Exciting the stent with RF energy that is modulated within an acoustic resonance of the structure, in order to enhance acoustic output of the stent, and scanning the RF carrier frequency to seek the characteristic RF modes of the stent, detecting the modes through the acoustic energy emission. As previously stated, the stent may be modified to enhance the acoustic and or EM interaction, and the sensitivity to restenosis.

4. Exciting the stent with RF energy, and directly detecting the acoustic energy of the stent modes. This is simply the limiting case of exciting acoustic modes whose frequency corresponds to the RF frequency. All the previously mentioned stent modifications may be employed. In this case the enhancements may be required to optimize the coincidence of optimal RF interaction with a frequency of optimal acoustic interaction, or vice versa.

For treating coronary occlusions, the endoluminal implant is generally a tubular shaped member having at least two configurations. Initially it has a compact configuration in which the member has a cross-sectional size smaller than the lumen at the treatment area. After placement it has an expanded configuration in which the member has a cross-sectional size comparable to the lumen of the treatment area. The implant includes at least a portion that is made of an electrical conducting material.

The endoluminal implant system further includes an external electromagnetic wave generator/transmitter and an ultrasound detector. A modulated EM wave generates a force as a result of the cross product of the induced azimuthal current and the longitudinal magnetic field. This JxB force induces a radial oscillation within the stent. The radial oscillations are a maximum when the frequency (or modulation frequency) of the EM wave is in resonance with the characteristic acoustic frequencies of the stent. In one embodiment the patient's chest is placed between a pair of coils or near an antenna and the stent excited over a range of EM wave frequencies and modulation frequencies. The EM wave range of frequencies is selected to effectively couple energy into the stent (e. g. , 100 MHz- 10 GHz). The modulation frequencies range is selected to cover the characteristic acoustic resonance frequencies of the stent (e. g. , 100 kHz-1 MHz). The ultrasound (or acoustic) detector measures the generated acoustic signal as a function of the EM wave frequencies. The measured acoustic spectrum will change when in-stent restenosis occurs.

During EM wave excitation the stent is also heated through resistive heating. The resulting heating causes thermal expansion of the stent, which also excites acoustic oscillations. The modulation frequency of the EM waves will control what acoustic frequencies are excited. In order to avoid an uncontrolled rise in temperature, the cooling time of the stent needs to be less than or comparable to the low modulation frequency of the EM wave. The cooling of the stent is controlled by thermal conduction and can be estimated by 7 &num X2/4D, where x is the stent wire thickness and D is the thermal diffusivity. For steel and x=50 microns,

=50 microseconds. Under these conditions the primary acoustic harmonic would be approximately 200 kHz. In order to increase the possible frequency the stent could have a thin high thermal conductivity coating (e. g. diamond) that would reduce the cooling time.

In another embodiment the natural blood flow through the stent is used to excite the resonant acoustic modes of the stent The measured blood pressure (and thus the measured force on the stent caused by forced blood flow) contains noise at frequencies much higher than the pulse frequency due to the complicated blood flow through the stent This noise spectrum will have a small component overlapping with the natural resonant acoustic mode of the stent. In addition to the pressure of the natural blood flow, there is a net magnetic flux through the stent.

This magnetic flux will also induce a current into a conducting stent, again causing a JXB force proportional to the amount of blood flow. This too will create a small acoustic excitation of the stent, which may be detected. In these cases the resonant acoustic signal would be detected without RF excitation.

The restenosis of a stent may be detected through the interrogation of the acoustic or electromagnetic properties of the stent, or an interrogation of a combination of the acoustic and EM properties. Because of the changes in the materials resident in, or flowing through the stent, the fundamental acoustic and EM modes of the stent change as the material loading changes.

The acoustic oscillations of the stent, excited directly by RF EM radiation, or modulation of an RF carrier, satisfy the wave equation 2 #r# + x2# = 0; x2 = #/S2-kz2; # # e-i#t+ikzz (1) where # is the sound frequency, s is the sound speed, and kz is the wavenumber.

The natural boundary condition is ##/#r= 0 at r=a. Here a is the stent radius and s is the sound speed. The localized solution of (6) is given by =AJn (X7) e ç (2)

where This the Bessel function of order n. The minimal value of X =1. 84/a is reached for n=O and for kz=0. The corresponding minimal sound frequency is 1. 84s o = (3) a For s=1550 m/sec (sound speed in blood) and the stent radius a=1 mm, the sound <BR> <BR> <BR> <BR> <BR> frequency v= #0 # 454kHz. This frequency and its harmonics are weakly attenuated<BR> <BR> <BR> zur in tissue and will therefore propagate through the surrounding tissue. The finite length of the cylinder increases the frequency by a value 6 (o , 50J a2 L The growth of tissue on the stent wall will produce a frequency shift 6Of equal to <BR> <BR> <BR> <BR> ##f ##s2#2dV #s2 h<BR> <BR> <BR> = # (4)<BR> <BR> <BR> # s2##2dV s2 a where h is the tissue thickness and bs2 is the difference of the squares of the sound speeds in plaque and blood. The difference in sound speed between blood and fat can be as high as 200 m/sec (15%). The resulting frequency shift can be as high as 80 kHz (20%) for 50% occlusions. The spectrum of the ultrasound generated by the stent will have a cut off at frequency wo with no sound generation below oo. Since stents currently in use have a variety of structures and geometries, the acoustic spectrum will generally exhibit multiple broad peaks.

Another technique that can enhance sensitivity when the acoustic frequency is different than the RF absorption frequency is to sweep the RF frequency past the EM resonant modes of the stent while detecting the acoustic response. Again the acoustic response is excited through modulation of the carrier.

The exact value and shift of the RF eigen-frequency can be optimized by careful selection of the stent design. As an example of the sensitivity of the RF absorption frequency to restenosis, assume the stent is a cylinder of finite size resonating with

its characteristic minimal H-mode. The minimal H-mode eigen-frequency for a metal cylinder of radius a is given by <BR> <BR> <BR> <BR> f =1. 84 (1)<BR> <BR> 2V Blood has a high refractive index, l ; ~8, for f < 10 Ghz. Therefore, a blood filled cylinder with a=0. 1 cm gives f-11 GHz. As plaque or a thrombus forms on the stent, the dielectric constant inside the resonator changes by £ resulting in a shift in the eigen-frequency. The frequency shift is given by Here E is the electric field distribution for the lowest H mode and b ; F is the variation of dielectric constant within the stent. Given the difference between stenotic tissue and blood, frequency shifts of several percent are possible.

In one possible method to treat and monitor coronary occlusions, a physician inserts the endoluminal implant (stent) into the patient using a balloon catheter. After the procedure is completed or within a month, the patient is placed in proximity to the EM transmitter and the ultrasound transducer is positioned on the skin near the stent. The EM transmitter frequency is tuned to a frequency that is known, or has been measured, to deposit energy effectively in the stent under test.

The RF source is then modulated over a frequency range (e. g. , 100 kHz to 2 MHz), which encompasses the characteristic acoustic response that is affected by restenosis, and the ultrasound signal as a function of modulation frequency is measured. The ultrasound amplitude is sensitive to the stent geometry and therefore the signal will have a structure characteristic of the deployed stent. This data is collected and recorded to provide a baseline frequency response around the acoustic frequencies of natural resonance of the stent for the patient with no restenosis. In subsequent months the patient visits the doctor's office and a new frequency response is measured. The new frequency response is compared to the baseline frequency response and any previous measurements to identify possible restenosis. When the

change in the frequency response exceeds some predetermined limit, the doctor can be advised to perform additional tests including angiography.

In another possible method to treat and monitor coronary occlusions, a physician inserts the endoluminal implant (stent) into the patient using a balloon catheter. After the procedure is completed or within a month, the patient is placed in proximity to the EM transmitter and the ultrasound transducer is positioned on the skin near the stent. The EM transmitter frequency is tuned to a frequency that is known, or has been measured, to deposit energy effectively in the stent under test.

The RF source is then modulated at a frequency that is known to, or has been measured to, produce adequate acoustic signals. The RF frequency is then scanned, with fixed modulation, and the acoustic signal is recorded as a function of RF frequency. The RF scattered radiation is sensitive to the stent geometry and therefore the signal will have a structure characteristic of the deployed stent. This data is collected and recorded to provide a baseline frequency response around the RF frequencies of natural resonance of the stent for the patient with no restenosis.

In subsequent months the patient visits the doctor's office and a new frequency response is measured. The new frequency response is compared to the baseline frequency response and any previous measurements to identify possible restenosis.

When the change in the frequency response exceeds some predetermined limit, the doctor can be advised to perform additional tests including angiography.

Although this technique is applicable to existing metallic stents, alternative stent designs can enhance the RF/acoustic signal and exhibit a narrow resonance frequency that can be more sensitive to plaque formation. For example, the stent can have an imprinted resonance circuit tuned to a suitable RF frequency for easy coupling. In this case the resonant RF frequency of the stent will also change with restenosis formation due to the change in dielectric constant inside both the coil and near the fringe field of the patterned capacitors. Another approach to enhance the EM stent coupling is to manufacture the stent using a Fractal antenna design that can widen the frequency sensitivity of the stent. Another approach to enhance the EM stent coupling is to manufacture the stent with at least a core and

an outer layer. The inner core of the stent material is a conductive metal (e. g. , steel, titanium, Nitinol, gold, platinum) and the outer layer is an insulating dielectric (e. g., titanium oxide, silicon nitride, diamond, biocompatible polymers).

A combination of scanning RF frequency, and RF modulation, for the detection of acoustic modes and or EM modes of the stent, may provide additional and complimentary information for the determination of the characteristics of the stent, including degree of restenosis.

In order to improve the signal to noise, the simple ultrasound transducer can be replaced by an imaging ultrasound transducer that only collects ultrasound energy from the area near the stent This technique can be used to reduce acoustic oscillations generated due to thermal heating of tissue in other areas of the body.

The use of low power electromagnetic waves makes this device safe for the patient and eliminates the need for unnecessary x-ray imaging. To increase the signal to noise, the device can be synchronized to the natural rhythmic variations of the patient such as heart beat rate. These slight modifications are easily adapted into the device.

The human body presents particular difficulties in the localization and distribution of RF electromagnetic energy. Because of the many surfaces and interfaces within the body, for example ribs, lungs, various other organs, fat and muscle layers, the distribution of RF energy tends to be very inhomogeneous. It may happen that very little intensity is incident upon the stent, while adjacent areas are well illuminated. To enhance the distribution of the radiation, a phased array antenna system may be used, such as a microstrip antenna, or patch type antenna, whereby the phases of the individual antenna components may be modified in order to target the electromagnetic energy onto the stent. This may be done in a time-averaged way, to uniformly illuminate all tissue in the vicinity of the targeted stent, or in a prescribed fashion in order to tailor the phases in a manner to optimize the intensity on the stent The feedback of the detected acoustic signal, or detected scattered or reflected RF, may be used to guide the phase given to each of the individual elements of the array. Alternatively, a phase plate, which may be

individually tailored, or pre-made, can be placed in front of a patient to place a phase front on the RF wavefront so as to enhance the RF upon the stent.

In a similar fashion, an index-matching interface may be placed upon the patient in order to effectively couple the RF into the patient, and out of the patient.

The layer materials, especially chosen for their index of refraction at the RF frequencies, and thickness, e. g. , quarter wave, as well as the number of layers, may be chosen to optimize the coupled RF. These and other objects will be apparent to those skilled in the art based on the teachings herein. Other objects and advantages of the present invention will become apparent from the following description and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated into and form part of this disclosure, illustrate embodiments of the invention and together with the description, serve to explain the principles of the invention.

Figure 1 is an illustration of one way the in-stent restenosis device would be used on a patient.

Figure 2 shows current stents that will function as microwave scattering devices.

Figure 3 shows a possible embodiment for scatterers with broken symmetry.

Figure 4 shows an alternative embodiment using a shield to block e-field penetration into the stent cavity.

Figure 5 shows an embodiment where a diode is placed in the gap.

Figure 6 is a schematic showing the key components in the microwave sensor electronics.

Figure 7 shows a flow chart illustrating the key elements of the system control software.

Figure 8 illustrates an embodiment of the system.

Figure 9 illustrates the basic concepts of an embodiment of the present invention.

Figure 10 shows how the excitation EM wave can be modulated to excite acoustic oscillations.

Figure 11 shows a stent design that incorporates simple RF LRC resonant circuit plated onto a dielectric stent.

DETAILED DESCRIPTION OF THE INVENTION An object of the present invention is to provide a device and method to evaluate in-stent restenosis. This invention utilizes a microwave device to monitor occlusions within implanted stents and provide information that can be used by the patient and the physician to determine the best course of treatment for the patient.

Figure 1 shows an embodiment of the present invention in normal use. A microwave transmitter/receiver 10 is placed near the chest of the patient 20 and transmits microwaves of selected frequency toward the implanted stent 30. A microwave receiver 10 detects the microwaves scattered from the stent 30. For purposes of this disclosure, the term"scattered"includes the term"reflected"as well as the term"scattered". In one embodiment, the microwave receiver may be separate from the transmitter so that it can be located either near the transmitter or moved around the patient to detect the scattering amplitude as a function of angle.

The control module 40 varies the transmitted microwave frequency over a selected range (e. g. , 0. 1-20 GHz) and records the detected scattered microwave signal. This information is processed by a microprocessor and displayed on a monitor 50. The control module can perform similar measurements for multiple microwave polarizations and for different transmitter-receiver orientations. The data collected with this system for each patient immediately after stent implant is stored by the microprocessor. On a regular basis (e. g. , every month) the patient returns to the doctor to have the complete set of microwave measurements repeated. The new measurements are compared by the microprocessor to the original measurements collected after stent implant. If the change in signal indicates a significant change the patient is scheduled for additional tests (e. g. , angiography).

Figure 2 shows currently used stents that will function as microwave scattering devices whose scattering frequency and amplitude will change with restenosis.

Although this technique is applicable to existing metallic stents, alternative stent designs can enhance the scattered signal and exhibit a narrow resonance frequency'that can be more sensitive to plaque formation. For example, Figure 3 shows a different stent design where the stent has a gap 300 along the cylindrical axis. This stent behaves as a high Q circuit simply through breaking the cylindrical symmetry. In this case the higher Q provides enhanced discrimination.

Further, because the electric field is highly concentrated at the gap, this embodiment will be ultra-sensitive to small changes in dielectric properties near the gap, and enables restenosis detection at a very early state.

For some embodiments the signal variation with the simple gap design shown in Figure 3 will be too large. In this case a shield 400 in Figure 4 can be used to block e-field penetration into the stent cavity. In an alternative embodiment the gap can be filled with dielectric material to tune the sensitivity of the system to plaque buildup. Also a filled gap reduces the risk of tissue herniating through the gap.

For some embodiments, the simple gap shown in Figure 5 will be replaced by a semi-conductor diode as shown. The non-linear response with microwave amplitude which results from the non-linear impedance of the diode generates harmonics of the fundamental microwave frequency which will be easier to measure against the scattering background from tissue interfaces which will all be at the fundamental frequency of the microwaves.

Figure 6 is a block diagram showing the key components of the microwave transmitter and detection system. A broadband microwave source 600 passes through an isolator 610 and a small amount of power is split off 620 to monitor and stabilize the microwave source 600. The microwave source 600 is further split to bias detectors 630. The rest of the power is attenuated 640 and then transmitted to the patient 650. The power is focused on the patient with a

transmitter/receiver. The stent scatters the microwave field and the scattered intensity is collected by the transmitter/receiver. This scattered intensity is amplified initially with a GaAs FET preamplifier 660, detected with diodes biased into their linear range 630, differentially amplified 670, and then digitized 680 and stored on a computer 690 for processing. Microwave polarizers can be used to polarize the transmitted signal and detect the scattered intensity as a function of polarization. Output power for this Network system (20 dbm) may need to be enhanced with additional amplifier and associated components to isolate receiver and circulate signal. This detection sensitivity is-110 dbm.

Figure 7 shows a flow chart illustrating the key elements of the system control software. When first powered on (700) the system performs a self-test to verify that the system is operating correctly. If the system is operating correctly the computer asks the user for the stent type and patient ID (710) and whether a baseline reading for this patient already exists. The software then initiates a complete measurement (720) and records the data. The system then determines whether this is a first measurement or if previous data exists. If this is a baseline record (730), the software simply analyzes the data and verifies that signal levels and frequency range are suitable. If previous records exist 740 for this patient the software then performs an analysis 750 of all the data to determine whether a dangerous change or trend exists that indicates possible restenosis 760. The results of the analysis are presented (e. g. , to the doctor) (770) to enable interpretation of the data to provide a diagnosis. The data is saved and a report is generated 780.

The data collected by the system will be the scattered intensity as a function of frequency. In the analysis section the characteristic peaks in intensity are identified using standard peak detection algorithms well known in the art The frequency of the peaks will be compared to the baseline measurement to calculate the frequency shifts. It is the magnitude of these frequency shifts that determine the extent of restenosis. A shift of 1-5 % would indicate significant restenosis. If resonance peaks are broad then a full spectral comparison between baseline and

new data can be performed to calculate and difference index. Alternative analysis techniques could include neural networks that are trained with early clinical data.

In an alternative embodiment a compact microwave transmitter and receiver with reduced frequency range (or even single frequency) and options can be provided to the patient and used at home to monitor stent condition on a daily or weekly basis. This compact unit would be pretuned after the operation to operate near the resonant frequency of the stent. As restenosis occurs, the detected signal amplitude decreases and if it decreases below a preset amplitude an alarm would sound. The alarm signal level is a function of stent type and the shape of the patient. In another embodiment, a selected individual or group such as a health care professional or organization could be automatically notified by wireless or hardwired technology that the preset amplitude had been reached or exceeded.

In yet another embodiment modulated electromagnetic radiation are used to excite acoustic oscillations in the stent An ultrasound transducer that is placed in contact with the skin detects these acoustic oscillations. Existing ultrasound transducers or imaging systems could be used to detect the oscillations. By using pulsed or modulated EM radiation, and time gated ultrasound detection the signal to noise of the system can be significantly increased. Conventional lock-in amplifier techniques could also be employed to detect the ultrasound, which has the characteristic frequency of the modulated EM. For optimum detection the ultrasound will be in the range of 200 kHz to 2 MHz.

Although described for cardiovascular stents this technique can be applied to all applications where stents are used. This includes neurovascular stents, and stents used for urological applications.

Embodiments of the present invention utilize an electromagnetic wave (EM) transmitter (100 MHz-1 GHz) to excite acoustic oscillations in a stent that are then detected using an ultrasound transducer. Figure 8 shows the key components of an embodiment of the system. The system includes an electronic control unit 1030 that is connected through a cable 1040 to an electromagnetic wave transmitter 1050 and an ultrasound detector 1060. The electromagnetic wave is transmitted

through the chest of the patient 1010 and excites the implanted stent 1020. When excited the implanted stent 1020 generates acoustic waves that are detected by the ultrasound detector 1060. The control unit 1030 can generate electromagnetic waves over a wide frequency range that can be effectively coupled into the conductive stent 1020. The control unit 1030 can include a computer for data analysis, and archiving. A monitor 1070 is used to guide the user and display results.

Figure 9 illustrates the basic underlying concept of the present invention.

A modulated EM wave is transmitted through the patient and interacts with a stent 1020. The interaction of the EM wave with the stent generates a force as a result of the cross product of the induced azimuthal current and the longitudinal magnetic field. This JxB force induces a radial oscillation within the stent. The induced currents can also heat the metallic stent 1020 and induce thermal expansion of the stent, which also generates acoustic oscillations. The radial oscillations are a maximum when the frequency (or modulation frequency) of the EM wave is in resonance with the characteristic acoustic frequencies of the stent. The acoustic spectrum is sensitive to stent configuration and the properties of surrounding tissue.

The change in acoustic spectrum is used by the present invention to identify restenosis.

The EM waves can be transmitted into the patient's chest using a pair of coils on either side of the patient, a single coil, fractal antenna, open dipole transmitter, patch antenna, or other antennas, which are common to the art.

In one embodiment of the present invention the EM wave is modulated to improve coupling. Figure 10 shows how the EM wave can be modulated to effectively excite acoustic oscillations using either sinusoidal or square wave modulation. The characteristic EM wave frequency fi is selected to effectively couple energy into the stent (typically 10 MHz to 10 GHz) whereas the low frequency modulationf2 is selected to be near the stent acoustic resonance frequency (typically 100 kHz to 2 MHz). In an alternative embodiment, the EM wave is continuous at a single frequency fi.

In one embodiment of the system, the control module 1030 varies the transmitted EM wave frequency and modulation frequency over a selected range that covers all possible stent resonance frequencies. The acoustic receiver 1060 detects the generated acoustic signal and the measured signal is digitized and recorded by the control module 1030. The recorded data is processed by the control module 1030 and displayed on a monitor 1070. The control module can perform similar measurements for multiple EM wave polarizations and for different transmitter-acoustic receiver orientations.

In another embodiment of the system, the EM wave frequency and/or modulation frequency can be fixed and the generated acoustic spectrum measured over a range of acoustic frequencies (e. g. , 100 kHz to 1 MHz). In another embodiment a short pulse (<1 nanosecond) EM pulse is used to gives the stent an impulse that generates broad-spectrum acoustic oscillations.

The data collected with the system for each patient immediately after stent implant is stored by the system in a data library for subsequent use. On a regular basis (e. g. , every month) the patient returns to the doctor to have the complete set of measurements repeated. The new measurements are compared by the system to the original measurements collected after stent implant If the change in signal indicates a significant change, the patient is scheduled for additional tests (e. g., angiography).

The approach of EM excitation and acoustic detection benefits from the fact that current ultrasound detectors have extreme sensitivity (Ultrasound in Medicine, Edited by F. A. Duck, A. C. Baker, H. C. Staritt, (1998) ) and when coupled with acoustic lenses can localize the area being probed. In addition, since the frequency being excited is controlled by the EM modulation frequency, lock-in detection techniques may be used to enhance the signal to noise.

Although this technique is applicable to existing metallic stents, alternative stent designs can enhance the RF/acoustic signal and exhibit a narrow resonance frequency that can be more sensitive to restenosis formation. For example, Figure 11 shows a different stent design where the stent has imprinted a

resonance circuit tuned to a suitable RF frequency for easy coupling. In this case the resonant RF frequency of the stent will also change with restenosis formation due to the change in dielectric constant inside both the coil and near the fringe field of the patterned capacitors. For the stent in Figure 11, the circuit resonance frequency is given by where Ci, 2 and L are the circuit capacitance and inductance respectively. Another approach to enhance the EM stent coupling is to manufacture the stent using Fractal antenna design that can widen the frequency sensitivity of the stent.

Circuit elements can also be employed to provide for harmonic generation of the RF excitation, such that a fundamental frequency may be employed to excite the imprinted circuit, where such fundamental is selected for advantageous absorption by the stent, or propagation to the stent, or interaction with the modes sensitive to restenosis, such that the imprinted circuit is capable of shifting the fundamental to another frequency, for example the second harmonic. The shifted frequency, for example a higher frequency, can thus provide for an enhanced interaction with features of the stent, or with those physical characteristic that are readily modified by restenosis. The shifted frequency is also more readily detected being easily filtered and detected with respect to the excitation.

Another embodiment of the invention uses the natural blood flow through the stent to excite the resonant acoustic modes stent. In such cases, the blood pressure and/or the magnetic flux through the stent excites the resonant acoustic modes of the stent, which would be detected without RF excitation. In addition, the RF excitation may be exchanged for acoustic excitation using pulsed or other noise reduction techniques to distinguish stent ringing over the excitation background.

In an alternative embodiment, a compact EM wave transmitter and acoustic receiver with reduced frequency range and options can be provided to the patient and used at home to monitor stent condition on a daily or weekly basis.

This compact unit would be pre-tuned after the implantation for operation near the

resonant frequency of the stent. As restenosis occurs, the detected signal amplitude decreases and if it decreases below an amplitude that has been pre-set, an alarm sounds. The alarm signal level is a function of stent type and the shape of the patient. In another embodiment, a selected individual or group such as a health care professional or organization could be automatically notified by wireless or hardwired technology that the preset amplitude had been reached or exceeded.

Although described for cardiovascular stents this technique can be applied to all applications where stents are used. This includes endovascular stents, neurovascular stents, and stents used for urological applications.

The above descriptions and illustrations are only by way of example and are not to be taken as limiting the invention in any manner. One skilled in the art can substitute known equivalents for the structures and means described. The full scope and definition of the invention, therefore, is set forth in the following claims.