Intraluminal electrical tissue characterization and tuned rf energy for selective treatment of atheroma and other target tissues

IS 2 380 487 T3

DESCRIPTION

Characterization of intraluminal electrical tissue and adjusted RF energy for the selective treatment of atheroma and other target tissues

BACKGROUND OF THE INVENTION

[0001] 1. Field of the invention

[0002] The present invention relates generally to systems for the analysis and remodeling of a vessel wall of a blood vessel. In exemplary embodiments, the invention provides a catheter-based diagnosis and / or treatment of luminal diseases, especially for atheroma plaque, hot or vulnerable plaque, and the like. The structures of the invention allow for eccentrically guided analysis, remodeling and / or removal of atherosclerotic material often employing both electrical diagnostic signals and electrosurgical energy.

[0003] Physicians use catheters to access and repair interior tissues of the body, particularly within the lumens of the body, such as blood vessels. For example, balloon angioplasty and other catheters are often used to open arteries that have narrowed due to atherosclerotic disease.

[0004] Balloon angioplasty is often effective in opening an occluded blood vessel, but the trauma associated with balloon dilation can lead to significant injury, so the benefits of balloon dilation may be time-limited. . Stents are commonly used to extend the beneficial opening of the blood vessel.

[0005] Stenting, in combination with balloon dilation, is often the preferred treatment for atherosclerosis. In stenting, a folded metal frame is mounted on a balloon catheter that is inserted into the body. The stent is manipulated at the site of occlusion and deployed in situ by dilation of the underlying balloon. Stenting has gained wide acceptance, and in many cases produces acceptable results. Along with treating the blood vessels (particularly the coronary arteries), stents can also be used in the treatment of many other tubular obstructions within the body, such as the treatment of reproductive, gastrointestinal, and pulmonary obstructions.

[0006] Restenosis or posterior narrowing of the body lumen after stenting has occurred in a significant number of cases. More recently, drug-coated stents (eg, Johnson and Johnson's Cypher ™ stent, with the corresponding drug provided by Sirolimus ™) have shown a markedly reduced rate of restenosis, and alternative drug-eluting stents are being developed and commercialized by others. In addition, work has begun on the administration of systemic drugs (intravenously or orally), which can also improve the success rates of angioplasty procedure.

[0007] While drug-eluting stents appear to hold significant promise for the treatment of atherosclerosis in many patients, there remain many cases in which stents either cannot be used or have significant disadvantages. Generally, the stent leaves an implant in the body. These implants can present risks, including mechanical fatigue, corrosion, and the like, particularly when removing the implant is difficult and involves invasive surgery. The Stent may have additional disadvantages for treating diffuse arterial disease, for treating bifurcations, for treating areas of the body susceptible to collapse, and for treating arteries subjected to torsion, lengthening, and shortening.

[0008] A variety of modified restenosis treatments or restenosis-inhibiting occlusion treatment modalities have also been proposed, including intravascular radiation, cryogenic treatments, ultrasonic energy, and the like, often in combination with balloon angioplasty and / or stent. While these and different approaches show different expectations for decreasing subsequent degradation in blood flow after angioplasty and stenting, the trauma initially imposed on tissues by angioplasty remains problematic.

[0009] Many alternatives to balloon angioplasty and stenting have also been proposed in order to open stenosed arteries. For example, a wide variety of atherectomy devices and techniques have been described and tested. Despite the drawbacks and limitations of angioplasty and stenting, atherectomy has not achieved the widespread use and success rates of dilation-based approaches. More recently, even more disadvantages of dilation have appeared. These include the existence of vulnerable plaque, which can rupture and release materials that can cause myocardial infarction or heart attack.

In view of the foregoing, it would be advantageous to provide new devices, systems, and procedures for the diagnosis, characterization, remodeling, and / or removal of atherosclerotic material and occlusions from the lumens of the body, and particularly from blood vessels. Furthermore, it would be desirable to avoid significant cost or complexity by providing structures that could both characterize and reshape or remove plaques and other occlusive materials without resorting to dilation trauma, and allow opening of blood vessels and

ES 2 380 487 T3 other body lumens that are not suitable for stenting. It would also be helpful if the diagnostic and treatment systems could provide some feedback on the progress of treatment.

[0011] US 4,587,975 describes a dilatation catheter for use in performing transluminal angioplasty techniques. The catheter comprises an elongated tubular member having an inelastic expansion element near its distal end. The expansion element is adapted to be inflated and deflated through the introduction of a suitable fluid into the lumen of the tubular member. Arranged on either side of the expander member are sets of electrodes, preferably ring electrodes. Associated with each electrode is a conductor that runs along the catheter from a ring electrode associated with the proximal end of the catheter where these conductors are connected to circuits to perform impedance plethysmography.

US 6,036,689 describes an ablation device for the treatment of atherosclerotic tissues of a patient. The device comprises a catheter shaft and an inner catheter having an electrode deployment means. The electrode deployment means comprises a plurality of preformed metal basket elements deployable at the distal end of the inner catheter. The electrode means are adapted to contact atherosclerotic tissues and to apply RF current to the tissues for therapeutic purposes. Alternatively, a plurality of deployable metal basket elements can be wrapped on and around a balloon of an ablation device system.

BRIEF SUMMARY OF THE INVENTION

The present invention is set forth in the appended claims. Enhanced devices, systems, and procedures for treating body lumen diseases are described herein. The embodiments may allow analysis and / or treatment of materials along these body lumens, optionally allowing plaque and other lesions to be characterized using a variable frequency electrical signal or power source. By radially deploying an electrode support matrix basket (for example) within a blood vessel, and by controlling the electrical characteristics (and particularly the frequency, impedance phase angle, and impedance magnitude) of circuits formed using Selected array electrodes can be locally analyzed for plaque, hot or vulnerable fibrous plaques, healthy tissues, treated tissues, and / or the like throughout the blood vessel. The same electrodes can be used (and often eccentrically) to selectively treat tissues by analysis results.

[0014] Embodiments of the invention may employ electrical energy to selectively heat target tissues and / or other structures. For example, the electrical energy waveform, application cycles, potential, delivery systems, and the like can be adapted to help apply therapeutic energy directly to atheroma and other diseased vessel tissues, inhibiting the sometimes injury to collateral tissue structures. As the electrical characteristics of at least some diseased tissues (and in particular their impedances relative to those of the surrounding tissues) may tend to apply treatment energy to adjacent healthy tissues, this tailor-made adaptation may improve the efficacy of luminal therapies and / or reduce collateral damage to tissues. Some examples of treatment systems and procedures for physical application (for example, axial and / or radial targeting of occlusive tissues from within a blood vessel) and / or frequency targeting may make use of disease location information (e.g. example, from intravascular imaging, impedance measurement, or the like) and optionally they can employ cooling to protect at least some tissues along a luminal wall.

[0015] Described herein is a catheter system for reshaping and / or reducing material from or adjacent to a body lumen of a patient. The system comprises an elongated flexible catheter body having a proximal end and a distal end with a shaft between them. At least one power supply surface is arranged near the distal end. A power source is electrically coupled to the power supply surface (s). The energy source activates the energy supply surface (s) with a form of electrical energy that helps the energy heat the material and inhibits collateral tissue damage.

[0016] A method for analyzing a vessel wall of a blood vessel is described herein. The method comprises connecting the vessel wall to an electrode of a probe, and energizing the electrode with a variable frequency power source. A power supply frequency is varied, and a wall target plate is characterized by tracking a frequency-dependent characteristic of an electrical circuit. The electrical circuit comprises the power source, the electrode, and the connected vessel wall.

[0017] Optionally, the probe is radially deployed within the blood vessel so as to engage a plurality of electrodes against the vessel wall. The extended probe electrodes generally define a circumferentially distributed array of electrodes, and the array electrodes may be supported by associated probe arms. The arms can extend elastically and independently within the blood vessel in order to couple the matrix to the vessel wall within non-circular lumens. An eccentric subset of the array (optionally a single electrode or an adjacent pair of electrodes) adjacent to the target plate can be energized to characterize tissues locally, and / or eccentrically remodel the target plate.

ES 2 380 487 T3 characterized using a remodeling electrical potential. Feedback information about remodeling can be obtained by monitoring the electrical circuit characteristic while applying a suitable variable frequency signal, either during remodeling or by stopping the remodeling at least temporarily.

[0018] In exemplary embodiments, the characterized target board can comprise a vulnerable board, and remodeling can be stopped in response to the electrical characteristics of the circuit. For example, remodeling can be arrested in response to a change in a tissue signature signal (e.g., a phase angle and impedance magnitude at a selected frequency or selected frequency range), particularly when the change is associated with the heating the lipids of the vulnerable plaque to 85 ° C or more. More generally, the target plate can be characterized by tissue signature and / or tissue signature profiles, the signature profiles comprising curves or data sets representing a plurality of tissue signature measurements at different frequencies throughout. of a frequency range. The target plate can be characterized by comparing a measured tissue signature profile with at least one profile from another tissue signature, and can allow identification of the measured signature profile as being associated with at least one healthy tissue, a calcified plaque, or a vulnerable plaque, with some embodiments capable of identifying at least two of these. Some beneficial embodiments may allow differentiation between plaques and other tissues that have not been treated, that have been partially treated, and that have been appropriately treated, optionally by checking for changes from a subset of tissue signature measurements of the profiles of signature (such as at a suitable frequency or the like).

[0019] Many embodiments will be suitable for the characterization of a plurality of localized materials distributed axially and / or eccentrically in the blood vessel, and, optionally, to selectively treat the different characterized materials with the different remodeling treatments using the electrodes. Tissue Signature Profiles can be standardized and / or referenced from known patient tissue (such as healthy tissue identified using intravascular ultrasound or other known techniques), and target plaques can be characterized using relative slopes of the profiles. tissue signature profiles or offsets between tissue signature profiles (and preferably both). The frequency range of the profiles will often extend below 50 KHz, typically from below about 50 KHz to more than 1 MHz, and in some embodiments from about 4 Hz to about 2 MHz.

According to another aspect, the invention provides a system for the analysis of a vessel wall of a blood vessel. The system comprises a vascular probe having a proximal end, a distal end, and an electrode disposed near the distal end to engage the wall of the vessel. A variable frequency power source can be coupled to the electrode in such a way that, when the electrode is coupled to the vessel wall, an electrical circuit is established (including the power source, the electrode, and the vessel wall involved). . A processor is coupled with the variable frequency power source, the processor configured to characterize a vessel wall target plate by monitoring a frequency dependent characteristic of the electrical circuit.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1A illustrates diffuse atherosclerotic disease in which a substantial length of multiple blood vessels has limited their effective diameters.

[0022] Figure 1B shows vulnerable plaque within a blood vessel.

[0023] Figure 1C illustrates the sharp bends or tortuosity of some blood vessels.

[0024] Figure 1D illustrates atherosclerotic disease at a bifurcation.

[0025] Figure 1E illustrates a lesion associated with atherosclerotic disease of the extremities.

[0026] Figure 1F is an illustration of a stent fracture or corrosion.

[0027] Figure 1G illustrates a dissection within a blood vessel.

[0028] Figure 1H illustrates a circumferential measurement of an artery wall around a healthy artery.

[0029] Figure 1I illustrates the circumferential distribution of atheroma over a restenosed artery.

[0030] Figure 2 schematically illustrates an atherosclerotic material catheter system in accordance with the present invention.

[0031] Figure 3 schematically illustrates a catheter system for remodeling of atherosclerotic material, the system including, the catheter of Figure 2.

IS 2 380 487 T3

[0032] Figure 4 illustrates an extended basket and associated electrode array of the catheter system of Figure 2.

Figures 5 and 6 illustrate an example of a basket structure having axially staggered offset electrodes in a circumferential array.

Figures 7A-E illustrate an example of a remodeling and / or removal procedure for atherosclerotic material using the catheter system of Figure 2.

Figures 8-10 schematically illustrate the controllers for selectively energizing the electrodes in the system of Figure 2.

Figures 11 illustrate an alternative controller for selectively energizing the electrodes in the system of Figure 2.

[0037] Figures 12A-12H illustrate an alternative basket structure formed with independent arms having an improved localized width for use as an electrode surface, along with the components thereof.

[0038] Figure 13 is a schematic cross-sectional view showing the application of different power levels across different electrodes to eccentrically remodel atherosclerotic materials.

[0039] Figures 14A-14E are sectional side views through a body lumen showing additional aspects of treatment procedures and apparatus described herein.

[0040] Figures 14F-14H are cross-sectional views taken through a body lumen and treatment device to show additional aspects of eccentric treatment devices and procedures.

Figures 15A and 15B illustrate an eccentric treatment device and procedure in a gelatin artery model.

[0042] Figure 16 is a perspective view of an example catheter assembly.

[0043] Figure 17A shows physical targeting within the container by longitudinal movement.

[0044] Figure 17B shows physical targeting within the container by activation of the radial electrode.

[0045] Figure 17C shows the physical targeting by activation of the radial and longitudinal electrode combinations.

[0046] Figure 18 shows the electrical impedance as a function of the frequency characteristics of diseased and non-diseased tissues.

[0047] Figure 19 illustrates the shielding of high impedance tissues from electrical current by passing through low impedance tissue.

[0048] Figure 20 illustrates electrical impedance measurement using multiple radially spaced electrodes.

[0049] Figure 21 shows variations of multiple frequency therapy.

[0050] Figure 22 illustrates the use of the physical characteristics of the fabric from external sources. combined with electrical impedance measurements to determine a desired or optimal power setting.

[0051] Figure 23 illustrates a four electrode measurement system distributed across multiple electrodes to measure contact and tissue impedance.

[0052] Figure 24 illustrates flooding the container with nonionic fluid to direct energy to the vessel wall and surrounding tissue, reducing native fluid losses.

[0053] Figure 25 illustrates one embodiment of a closed loop monitoring system for automatically diagnosing and treating injuries within a container using tissue information from an external source such as an IVUS.

[0054] Figure 26A illustrates the switching mechanism in an external control box.

[0055] Figure 26B illustrates the switch mechanism at the distal end of the catheter.

[0056] Figure 26C illustrates the switching mechanism at the proximal end of the catheter.

IS 2 380 487 T3

[0057] Figure 27 illustrates selective plaque treatment.

[0058] Figures 27A-27C illustrate tissue spectral correlations, as can be used to analyze or characterize plaques.

[0059] Figures 28A-28C illustrate laboratory remodeling of tissue using a model of animal fat treated with an exemplary embodiment of the catheter system.

[0060] Figures 29A and 29B illustrate intravascular imaging and eccentric remodeling with an exemplary embodiment of the catheter system.

[0061] Figure 30 is a simplified schematic illustrating the components of the system of Figure 2 that can be used for analysis and characterization of intraluminal tissue and other materials.

Figures 31A-31J graphically illustrate the relationships between phase angles and impedance over a frequency range, as can be used to electrically analyze and characterize materials coupled and disposed between the electrodes of the Figure 2 system.

[0063] Figures 32 illustrate a variety of tissues for characterization and selective treatment using the system of Figure 2.

[0064] Figures 32A-32C illustrate changes in a relationship between phase angle and impedance over a frequency range associated with treating a tissue, along with histological images of the tissue before and after treatment.

DETAILED DESCRIPTION OF THE INVENTION

[0065] This document describes devices, systems and procedures for analyzing and / or treating luminal tissue. These will be particularly useful for characterizing and reshaping materials along a partially occluded artery in order to open the lumen of the artery and increase blood flow. Reshaping may involve the application of electrosurgical energy, typically in the form of RF and / or microwave electrical potentials, to power supply surfaces such as electrodes, antennas, and the like. This energy will optionally be controlled to limit a temperature of the target and / or collateral tissues, for example, by limiting the heating of a fibrous layer of a vulnerable plaque or the intima layer of an artery structure to a maximum temperature in a range from about 50 to about 60 ° Celsius. In many embodiments, the energy is controlled to limit the maximum temperature of an outer or adventitial layer of the blood vessel to no more than about 63 ° Celsius. Limiting heating of a lipid-rich volume of a vulnerable plaque sufficiently to induce fusion of the lipid volume while inhibiting heating of other tissues (e.g., an intimal layer or fibrous layer) below a temperature in a range about 50 to about 60 degrees centigrade can inhibit an immune response that might otherwise lead to restenosis, or the like. Many embodiments can apply sufficient thermal energy to heat lipids to about 85 ° C or more while inhibiting collateral damage through the selective application of heating energy. Relatively low heating energies may be sufficient to denature and shrink atherosclerotic material during treatment, immediately after treatment, and / or after more than an hour, more than a day, more than a week or even a month after treatment. through a tissue healing response to treatment in order to provide a larger vessel lumen and improved blood flow.

[0066] In some embodiments, atherosclerotic plaque remodeling may comprise the use of high energies to ablate and remove occlusive material from within lumens of the body, and particularly to remove atherosclerotic material from a blood vessel in order to improve blood flow. Ablation debris can be generated by this ablation for example, and ablation debris can be thrombolytic or non-thrombolytic. When thrombolytic debris is generated by ablation, these debris can be immobilized, captured, and / or evacuated from the treatment area. Non-thrombolytic debris produced by ablation may not be immobilized in and / or evacuated from the vessel. The analysis and / or treatment region of the body lumen may be at least partially (or fully effective) isolated for ablation or other remodeling treatments to allow the treatment environment to be modified (for example, by cooling the lumen and / or alteration of the electrical characteristics of fluid within the lumen using cold fluid irrigation, non-isotonic fluid irrigation and / or the like), to limit the release of any remodeling residue, and the like. The techniques of the invention will often provide suitable electrosurgical, sensing or imaging capabilities for measuring atheromas and / or vascular walls, and / or an embolism inhibitor. As atherosclerosis can be eccentric with respect to a blood vessel axis more than 50% of the time, possibly in (or even more) 75% of cases, the devices and methods of the present invention will often be particularly well suited to direct treatment eccentrically, often in response to detection or monitoring of circumferential atherosclerotic material. Although the procedures and devices described herein allow for these eccentric treatments, the devices can also be used to

ES 2 380 487 T3 treatment of radially symmetric atherosclerosis by selectively directing energy in a radially symmetric pattern around a catheter shaft or the like.

[0067] Therefore, remodeling of atherosclerotic materials can comprise ablation, removal, contraction, fusion, and the like of atherosclerotic plaques and other plaques. Optionally, atherosclerotic material within the layers of an artery can be denatured in order to improve blood flow so that debris will not necessarily be generated. Similarly, the atherosclerotic materials within the arterial layers can be fused and / or the treatment can involve shrinkage of the atherosclerotic materials within the arterial layers, again without necessarily generating treatment debris. Particular advantages can be provided for treating vulnerable plaques or blood vessels where vulnerable plaque is a problem. These vulnerable plates may comprise eccentric lesions, and the present invention may be particularly well suited for identifying an orientation (as well as axial location) of the vulnerable plate structure. Applications can be found to target the cap structure for gentle heating (to induce cap growth and make the plate less vulnerable to rupture) and / or heat the lipid-rich volume of the vulnerable plate (thus as to reshape, denature, melt, contract, and / or redistribute lipid-rich volume).

[0068] The devices, systems and procedures described can be used in combination with stenting and / or balloon dilation, and are especially suitable for increasing the open diameter of blood vessels in which stenting and balloon angioplasty are not a viable option. Potential applications include the treatment of diffuse disease, in which atherosclerosis extends along a significant length of an artery rather than being localized. They may also offer advantages in treating vulnerable plaque or blood vessels where vulnerable plaque is a problem, both by being able to identify and avoid treating vulnerable plaque with a choice of eccentric and / or axial treatments. separated from the vulnerable plate, and by intentional ablation and aspiration of the lid and lipid-rich volume of the vulnerable plaque within a controlled surrounding area or region within the lumen of the blood vessel. They may also find advantageous use in treating tortuous or sharply-curved vessels, since a stent does not need to be advanced or extended in the tight curves of the various blood vessels. Even more advantageous applications include treatment along bifurcations (where lateral branch block can be a problem) and in peripheral extremities such as the legs, feet, and arms (where crushing and / or failure of the fracture stents can be problematic).

Embodiments can measure the impedance of a circuit, and in particular a circuit that includes an electrode coupled to a luminal wall or other tissue. These measurements of impedance of alternating current (AC) circuits typically include a measurement of a real part or magnitude of the impedance, and an imaginary part or phase angle of the impedance. The magnitude of the impedance and the phase angle generated at an appropriate frequency by a tissue coupled to the electrode can provide a tissue signature. To improve the accuracy of tissue signature measurements, a plurality of individual measurements (often three or more) can be averaged. By measuring tissue signatures at a plurality of different frequencies (for example, at about 100 different frequencies) within a range of frequencies, a signature profile for the tissue can be generated, the signature profiles optionally comprising a curve or an approximation by curve of phase angles and magnitudes over a whole range of frequencies. In some embodiments, tissue signature signal measurements can be compared, and / or a smaller number (2-10 or 5-50) of these measurements can be included in a tissue signature profile. Tissue signature measurements may depend on the measurement conditions (including the coupling configuration between electrodes and tissue), in particular when measurements are made by transmitting bipolar sensing currents in the tissue between two electrodes that are supported. by a flexible and / or radially extensible support structure. Nevertheless, the relative and / or signature tissue signature profiles (in particular the relative offsets between the signature profiles, the relative slopes of the signature profiles, and the like) of different tissues from different patients will often be sufficiently consistent to allow tissue signatures and signature profiles to be used to distinguish between healthy tissue, calcified plaque, fibrous plaque, lipid-rich plaques, untreated fabric, partially treated fabric, fully fully treated fabric, and the like.

[0070] Optionally, baseline measurements of the tissues (which can be characterized via intravascular ultrasound, optical coherence tomography, or the like) can be taken to help differentiate adjacent tissues, as tissue signatures and / or signature profiles may vary between people. In addition, tissue signatures and / or profile signature curves can be normalized to facilitate identification of corresponding slopes, offsets, and the like, between different tissues. Once sufficient correlations have been established between tissue signatures (including impedance magnitude, phase angle, and frequency) and different tissue signature profiles for different patients and measurement conditions, characterization of tissue from at least some patients without having to resort to other tissue characterization methodologies with different rationales.

[0071] Diffuse disease and vulnerable plaque are illustrated in Figures 1A and 1B, respectively. Figure 1C illustrates vascular tortuosity. Figure 1D illustrates atherosclerotic materials in a bifurcation, while Figure 1E shows a lesion that can result from atherosclerotic disease of the extremities.

IS 2 380 487 T3

[0072] Figure 1F illustrates a fracture of the stent structural element that can result from corrosion and / or fatigue. Stents can be, for example, designed for an implant life of ten years. As the population of stent recipients lives longer, it becomes increasingly likely that at least some of these stents will remain in place longer than their designed lifespan. As with any metal in a corrosive body environment, material degradation can occur. As the metal weakens with corrosion, the stent can fracture. As metal stents corrode, they can also generate foreign body rejection and by-products that can irritate adjacent body tissues. This scar tissue can, for example, lead to eventual reengagement or restenosis of the artery.

[0073] Arterial dissection and restenosis can be understood with reference to Figures 1G to 1I. The artery comprises three layers, an endothelial layer, a middle layer, and an adventitial layer. During angioplasty, the inner layer may delaminate or partially separate from the wall to form a dissection, as illustrated in Figure 1G. These dissections divert and can obstruct blood flow. As can be understood by comparison between Figures 1H and 1I, angioplasty is a relatively aggressive procedure that can damage blood vessel tissue. In response to this injury, the presence of a stent, and / or the continued progression of the original atherosclerotic disease, the open artery may subsequently be thinned or decreased in diameter, as illustrated in Figure 1I. Although drug-eluting stents have been shown to reduce restenosis, the efficacy of these new structures has not been studied several years after implantation, and furthermore, these drug-eluting stents are not applicable in many blood vessels.

[0074] In general, the present invention provides a catheter that is relatively quick and easy for the physician to use. The catheter system of the present invention can allow arteries to open at least 85% of their native or nominal artery diameter. In some embodiments, the arteries can be about 85% open, and / or the acute openings can be less than 85%. Rapid removal of occlusive material can be accomplished using enough energy to locally heat tissues to greater than about 100 ° C as well as to vaporize the tissues, or gentler reshaping can also be employed.

[0075] In some embodiments, the desired aperture diameters can be achieved immediately after treatment with the catheter system. Alternatively, a gentler ablation can be applied, for example, providing a native diameter of no more than 50% when treatment is completed, although it can still provide up to 80 or even 85% or more opening of the native diameters of the vessels. after completion of a subsequent healing process, due to resorption of luminal injured tissues analogously to left ventricular ablation for arrhythmia and transurethral prostate treatments. In these embodiments at least some occlusive tissue can be heated to a temperature in a range of about 55 ° C to about 80 ° C. In some embodiments, the occlusive tissues can be heated to a maximum temperature in a range between about 93 and 95 ° C. In other embodiments described herein, heating can be controlled to provide fabric temperature in a range between about 50 and 60 ° C, and with some embodiments benefiting from maximum fabric temperatures of about 63 ° C. Others Treatments can benefit from treatment temperatures of approximately 90 ° C. Advantageously, the catheter systems and procedures of the invention can be used without balloon angioplasty, avoiding dissections and potentially limiting restenosis. Optionally, the tissue treatments described herein can be repeated during a single surgical session, or after a month or more (even after a year or more) if appropriate to provide or maintain the desired lumen opening.

[0076] An example catheter system 10 is schematically illustrated in Figures 2 and 3. A reshaping and / or ablation catheter 12 includes a catheter body 14 having a proximal end 16 and a distal end 18. The body of Catheter 14 is flexible and defines a catheter shaft 20, and includes an aspiration lumen 22 and an irrigating lumen 24 (see Figure 3). Still more lumens can be provided for a guidewire, for an imaging system, or the like, as described below. Lumen 22 can be used for atheroma detection and / or imaging, as well as for aspiration.

[0077] Catheter 12 includes a radially extendable structure 26 adjacent to distal end 18 and a housing 28 adjacent to proximal end 16. A distal tip 30 may include an integral tip valve to seal suction lumen 22 and allow passage of guide wires, imaging and / or restenosis-inhibiting catheters, and the like.

[0078] Proximal housing 28 includes a first connector 32 in fluid communication with aspiration lumen 22. Aspiration lumen 22 may have an aspiration port within extendable structure 26 to allow aspiration or aspiration of debris and gases from inside the extensible structure. Aspiration lumen 22 may also be used as an access lumen for guide wires, intravascular imaging catheters, and / or intravascular distal radiation treatment catheters or restenosis inhibitor drugs. Thus, connector 32 can selectively accommodate an imaging catheter 34 having an atherosclerotic material detector 36 moveable within catheter body 14 adjacent to, and / or beyond distal end 18, the frequency detector often comprising an intravascular ultrasound transducer, an optical coherent tomography sensor, an MRI antenna, or the like. A 38 catheter image connector

ES 2 380 487 T3 image 34 transmits image signals that allow circumferential measurement of atherosclerotic thicknesses around axis 20 to a screen 39.

The connector 32 also accommodates a restenosis inhibition treatment catheter 40, the treatment catheter comprising an intravascular radiation catheter. This radiation catheter may include a radiation source 42 that can again be advanced distally into catheter body 14 or past extendable frame 26.

[0080] A second connector 44 of proximal housing 28 is in fluid communication with irrigation lumen 24 (see FIG. 4). The second connector 44 may be coupled to a source of irrigation fluid for the introduction of conductive or non-conductive liquids, gases, or the like, ideally for the introduction of gas or heparinized saline. Both the first and second connectors 32, 44 may optionally comprise a standard connector such as a Luer-Loc ™ connector. In Figure 3 the connector 44 is shown schematically coupled to a vacuum aspiration source / infusion fluid source 45.

[0081] Referring now to Figures 2, 3, and 4, proximal housing 28 also accommodates an electrical connector 46. Connector 46 includes a plurality of electrical connections, each electrically coupled to an electrode 50 via a Dedicated conductor 52. This allows a subset of the electrodes 50 to be easily energized, the electrodes often being powered with bipolar or monopolar radio frequency energy. Therefore, the electrical connector will often be coupled 46 to an RF generator via a controller 47, which controller will allow energy to be selectively directed to an eccentric portion of a connected luminal wall. When monopolar radio frequency energy is employed, the mass of the patient can (for example) be provided by an external electrode or an electrode on the catheter body 14. A processor 49 can manipulate the signals from an image catheter 34 to generate an image on screen 39, can coordinate aspiration, irrigation, and / or treatment, and can automatically record the treatment with the image.

Processor 49 will typically comprise hardware and / or software, and will often include one or more programmable processor units that execute program instructions or computer-readable code for the application of some or all of the procedures described herein. The code will often be included on a readable medium such as a memory (optionally a read-only memory, a random access memory, a non-volatile memory, or the like) and / or a recording medium (such as a floppy disk, a hard drive, CD, DVD, memory stick, or the like). The code and / or associated data and signals can also be transmitted to or from the processor over a network connection (such as a wireless network, Ethernet, the Internet, an intranet, or the like), and some or all of the Code may also be transmitted between components of catheter system 10 and within processor 49 via one or more buses, and appropriate standard or proprietary communications cards, connectors, cables, and the like will be included in the processor. Processor 49 will often be configured to perform the calculations and signal transmission steps described herein at least in part by programming the processor with software code, which can be written as a single program, a series of subroutines. separate or related programs, or the like. The processor may comprise standard or proprietary analog signal processing hardware, software and / or firmware, and will typically have sufficient processing power to perform the calculations described herein during patient treatment, the processor optionally comprising a personal computer, a laptop, a tablet PC, a proprietary processing unit, or a combination of these. It can also include standard or proprietary input devices (such as a mouse, keyboard, touch screen, joystick, etc.) and output devices (such as a printer, speakers, display, etc.) associated with modern computer systems, and processors having a plurality of processing units (or even independent computers) can be employed in a wide range of centralized or distributed data processing architectures. Therefore, any or all

[0083] Extendable structure 26 is illustrated in more detail in Figure 4. Extendable structure 26 may elastically extend when released from within a containment sheath, or it may be extended by pulling tip 30 toward distal end 18 ( see FIG. 2), optionally using a bias wire, inner catheter body 58, or the like. The extendable structure 26 here comprises a perforated structure or a basket having a series of arms or structural elements 54 with openings or perforations 56 therebetween. The perforations 56 may be formed, for example, by cutting elongated slits in a flexible tube material, or the basket may be formed by braiding elongated cables or ribbons or the like.

The extensible structure 26 generally includes a proximal portion 60, a distal portion 62, and an intermediate portion therebetween 64. Each electrode 50 is mounted on an associated basket element 54 along the intermediate portion64, with a conductor associated 52 extending proximally from the electrode. Electrodes 50 are distributed circumferentially around axis 20 like a string, preferably with adjacent electrodes axially offset, ideally staggered or staggered between proximal and distal axial locations. This allows bipolar energy to be directed between circumferentially (axially offset) adjacent electrodes, between adjacent distal electrodes, between adjacent proximal electrodes, and the like.

IS 2 380 487 T3

In the exemplary embodiment, the proximal and distal barriers 66, 68 extend radially with the proximal and distal portions 60, 62 of the extensible structure 26. The barriers 66, 68 prevent any ablation debris and generated gases adjacent to electrodes 50 travel into the body lumen past catheter 12. Barriers 66, 68 also allow a less partially isolated ablation environment to be established in the body lumen, for example, by replacing the blood within a blood vessel with a more advantageous fluid medium to limit charring of the electrodes and Similar. Alternative barriers may be provided in place of (or in combination with) barriers 66, 68, including one or more balloons axially offset from extendable member 26, elastic lips, or the like. In other embodiments remodeling can be accomplished without the generation of significant thermolytic ablation debris and / or a desired treatment environment can be provided with localized irrigation and / or aspiration flows such that some systems can dispense with the use of barriers.

[0086] An example of extensible structure 26 is formed by cutting grooves in a superelastic alloy tube such as a nickel-titanium alloy or a Nitinol ™ tube. As can be understood with reference to FIG. 6, the extensible structures 54 may have enlarged circumferential widths 80 adjacent to an electrode and / or an electrode mounting location 82. As can be seen in FIG. 5, the localized enlargement of the width 80 adjacent the electrode mounting pads 82 can be offset axially, as described above. The grooves that form the extensible members 54, and therefore the extensible members themselves can be, for example, 0.8 inches in length, with the extensible members having a circumferential width of about 0.25 inches.

[0087] With reference now to Figures 7A and 7B, side and end views of a collapsible cone-shaped extensible barrier can be seen. Barrier 66 here comprises a braided Nitinol ™ wire 84 coated with silicone, for example, by dipping a superelastic alloy braid such as Nitinol ™ in liquid silicone and allowing it to set. These cones can be mounted on the proximal and distal portions of the extensible frame. As noted above, a variety of alternative barrier membranes can be employed. Figure 7C illustrates a basket 75 with an integral barrier 77 directly overlying the basket. Barrier 77 comprises a polyurethane, which can be quite resistant to tearing. Alternative barrier membranes can comprise other materials, such as PTFE or the like.

[0088] With reference now to Figures 8 and 9, examples of electrodes 50 supported by polyimide alloy stretch members 54 can be coated with a high temperature polymer. Leads 52 extend proximally from electrodes 50 as previously described. High contrast radiopaque markers such as gold, platinum, platinum / iridium alloy, and the like can be attached to or near these arms. The markers could also be used as electrodes.

[0089] The use of catheter system 10 for remodeling and / or removal of eccentric atheroma from within a blood vessel can be understood with reference to Figures 7A through 7E. As seen in Figure 7A, access to a treatment site often involves advancing a GW guidewire into a V blood vessel, and more often distally beyond a target region of AM atherosclerotic material. . A wide variety of guide wires can be used. To access a vessel that is fully occluded, the GW Guide can comprise any commercially available guide suitable for crossing a total occlusion such as this, including the Safe-Cross ™ RF Guide System which has Forward View Optical Coherence Reflectrometry and radiofrequency ablation. When AM atherosclerotic materials do not result in total lumen occlusion, these capabilities need not be provided by GW guidewire, although other advantageous features can be provided. For example, the GW guidewire can include a distal balloon to hold the guidewire in place and further inhibit movement of ablation debris and the like. The GW Guide Wire can be positioned using fluoroscopy (or other) imaging.

[0090] Catheter 12 is advanced distally over the GW guide and positioned adjacent to the atherosclerotic material AM, often towards a distal portion of the occlusion as can be understood with reference to Figures 7A and 7B. The extensible structure 26 extends radially into the lumen of the blood vessel so that the electrodes 50 connect radially with the atherosclerotic material AM. The extensible structure 26 can be enlarged, for example, by pulling a bias wire extending through the catheter body 14 to the distal portion 62 coupled (directly or indirectly) of the extensible body 26 (see FIG. 4). Alternatively, an inner catheter body 58 may be moved proximally relative to the outer catheter body 14, with the inner catheter being reattached to the distal portion of the extensible body. Other alternatives are possible, including removing a cover from the entire extensible body and allowing the extensible body to flex radially outward. In at least some embodiments, whether actuated from the proximal end of catheter 12 or the extensible body is simply released, the structural members defining the extensible body may comprise elastic or superelastic materials treated to extend radially outward, such as by adjusting by Heat a superelastic metal of Nitinol ™, polyimide, or the like. In some embodiments, the GW guidewire can be removed after placement of the ablation catheter and / or extending the basket. As the atherosclerotic material AM is distributed eccentrically over catheter 12, some of the electrodes 50 directly engage a luminal wall W, as can be understood with reference to Figures 7B and 7C.

IS 2 380 487 T3

[0091] The imaging catheter 34 is positioned within a catheter lumen 12, so that the detector 42 extends adjacent to the AM atherosclerotic material. The imaging catheter operates within and / or through catheter 12 in order to measure a thickness of atherosclerotic material concentrically around catheter 12 as illustrated in Figure 7C with measurements often taken at a plurality of axial positions in order of measuring axial variation of the atherosclerotic AM material within the blood vessel, such measurements often progressing proximally. In many cases, the AM atherosclerotic material will be eccentrically distributed within the vessel wall, as shown in Figure 7C. It should be noted that no portion of the vessel wall needs to be completely covered by atherosclerotic material for the measurement distribution to indicate that the obstruction is eccentric, since a relatively thin layer of atheroma along a portion or part of the blood vessel may be very different from the thickness of a very thick layer of atherosclerotic material on an opposite side of the blood vessel V. In some procedures, reshaping and / or ablation of the entire atheroma along one side may result in the vessel wall engaging the electrode only after starting treatment.

[0092] In some cases, the imaging catheter 34 may allow the identification and / or characterization of materials, atherosclerotic plaques, tissues, lesions, and the like, within a blood vessel. For example, imaging catheter 34 can determine an axial and / or circumferential location of a target plate for treatment. When treatments target atherosclerotic plaques in order to increase blood flow through the lumen, the treatment can be tailored to provide short-term and / or long-term increases in lumen diameter and blood flow. When catheter 34 identifies a circumferentially and / or axially located vulnerable plaque, this vulnerable plaque can be treated appropriately to inhibit the release of noxious thrombolytic materials, often by thickening a fibrous layer of the vulnerable plaque, making the plaque less vulnerable to breakage, decreasing a size or danger of releasing a lipid-rich volume from the vulnerable plaque, or the like. Thus, catheter 34 can be used to provide information similar to that available by histology as well as to indicate a composition of an atheroma (by identifying and locating, for example, a fibrous cap, smooth muscle cells, a volume lipids, calcifications, and the like.). Intravascular ultrasound catheters may then be capable of such atheroma characterizations, and these characterizations can also be provided by intravascular optical coherence tomography catheters, intravascular magnetic resonance antennas, and other catheter-based imaging systems, or by imaging techniques. non-invasive imaging, such as MRI systems, and the like.

[0093] Some imaging catheters suitable for use in the catheter system of the present invention are commercially available from a wide variety of manufacturers. Suitable technology and / or catheters are available commercially for example from SciMed Life Systems and Jomed-Volcano Therapeutics (providers of intravascular ultrasound catheters), Light Lab ™ Imaging (which develop and market optical coherence tomography catheters of image intravascular), Medtronic CardioRhythm, and the like. There are still more alternative technologies that can be used, including ultra-fast magnetic resonance imaging (MRI), electrical impedance depth measurements of atheroma, optical coherence reflectrometry, and the like.

[0094] The systems, devices and procedures described herein may optionally employ imaging techniques and / or atherosclerotic material detecting devices that are at least in part (optionally totally) disposed outside the body lumen, optionally disposed outside the patient's body. Some non-invasive imaging modalities that may be employed include x-ray or fluoroscopy systems, magnetic resonance imaging systems, external ultrasound transducers, and the like. Optionally, external and / or intravascular atherosclerotic material detectors can also be used to provide temperature information. For example, a system having an MRI antenna can detect tissue temperature such that a graphical indication of treatment penetration can be displayed on the system screen. Tissue temperature information can also be obtained by ultrasound and / or optical coherence tomography systems, and temperature information can be used as feedback to direct ongoing treatments, for selection of tissues for treatment (e.g. , by identifying a hot or vulnerable plate), and the like.

As with GW guidewire placement and catheter 12 advancement, positioning of image catheter 34 sensor 30 can be facilitated by fluoroscopic imaging modalities or the like. The location of sensor 36 relative to extensible structure 26 may be facilitated by catheter radiopaque markers 34 adjacent to sensor 36, and by radiopaque structure (or corresponding radiopaque markers positioned on or near) extensible structure 26, and / or by the use of radiopaque electrodes.

[0096] By expanding the extensible structure 26 within the blood vessel V, the optional proximal and distal barriers 66, 68 (see Figure 4) can form an environment, at least partially, and preferably substantially isolated within the blood vessel. This environment can be adapted to enhance subsequent remodeling and / or ablation by aspirating blood from an aspiration lumen port 22 disposed between the proximal and distal barriers 66, 68, and by irrigating the isolated environment with a desired fluid, such as described above. When supplied, aspiration and / or irrigation can optionally be performed simultaneously,

ES 2 380 487 T3 to generate a flow within the controlled environment for removal of any vaporization gas, ablation debris, and the like.

[0097] Referring now to Figures 7C and 7D, circular imaging often indicates that remodeling and / or ablation should be directed to an eccentric portion or R region of the wall of vessel W. To aid in targeting Engagement of the electrodes in the circumferential atheroma distribution, one arm of the extensible frame 26 has an identifiable image, allowing the arm to serve as a rotational alignment guide. Electrode fitting can be achieved using intravascular imaging such as intravascular ultrasound (IVUS), optical coherence tomography (OCT), intravascular MRI and / or the like, optionally employing external imaging, for example fluoroscopy, magnetic resonance imaging (MRI), or the like. Electronic registration can also be used. In response to this information, RF energy is directed to the electrodes within the R region. These actively energized electrodes define a subset of the total electrode array, and the selection of this subset of electrodes can be implemented using a controller as described below.

[0098] The mechanisms of ablation of atherosclerotic material within a blood vessel have been well described, including Slager et al. in an article titled, Vaporization of Atherosclerotic Plaque by Spark Erosion in J. of Amer. Cardiol. (June, 1985), on pp. 1382-6; and by Stephen M. Fry in Thermal and Disruptive Angioplasty: a Physician's Guide; Strategic Business Development, Inc., (1990). Some suitable vaporization procedures and devices for adaptation and / or use in the present system are also described in US Patents 5,098,431; 5,749,914; 5, 454, 809, 4, 682, 596, and 6, 582, 423, among other references.

[0099] Referring now to Figure 7E, as described above, it may not be necessary to completely remove all of the atheroma or atherosclerotic material from within the blood vessel. It may be sufficient to provide an open lumen having an effective diameter of at least 80 or 85% of a nominal native lumen diameter. Reshaping treatments can provide acute open effective diameters in a range of about 30% to about 50%. In some embodiments, damage caused to atherosclerotic material with energized electrodes or other energy-applying surfaces can result in subsequent resorption of lesions from damaged tissues in order to provide a greater opening of the vessel after termination. treatment as part of the healing process.

[0100] To promote long-term efficacy and inhibit restenosis of a treated region of blood vessel V, a restenosis inhibition catheter 40 can be advanced through a catheter lumen 12, such that a radiation source 42 irradiate the treated region of the blood vessel. Some suitable intravascular radiation catheters are commercially available from Novoste ™, Guidant and Johnson & Johnson and the like. Some restenosis inhibitor drugs similar to those now used in drug-eluting stents can also be advanced through a catheter lumen 12, optionally also while proximal and distal barriers help maintain a zone of controlled environment within the vessel. so that the administration of systemic drugs could be limited or avoided. In addition to the known restenosis inhibitor drugs used in drug-eluting stents, drugs that cause vasodilation can be used. Known drugs such as rapamycin ™ can also be used as restenosis inhibitors.

[0101] In some embodiments, the extensible structure 26 may remain extended against the wall of the vessel W and / or the atherosclerotic material AM, while the catheter 12 moves within the blood vessel, the catheter often being drawn proximally during or between the ablation treatments. An analogous movement of a radially extended perforated basket is employed, for example, when measuring blood vessel temperatures as well as for detecting vulnerable plaque in systems currently under development and / or marketed by Volcano Therapeutics. Alternatively, the basket may be repeatedly contracted, the axial movement of catheter 12 employed to reposition the basket, with subsequent expansion of the basket at each of a plurality of treatment sites along the AM atherosclerotic material. Intravascular imaging or other thickness measurements of atherosclerotic material circumferentially around catheter 12 may be employed repeatedly, temporarily interrupting remodeling and / or ablation in order to intermittently acquire an image during an ablation procedure. A final image can be taken to verify if the reshaping and / or ablation has been successful.

[0102] Referring now to Figures 8 and 9, alternative controllers 92a, 92b selectively energize catheter electrodes 12 with RF power supplied from RF generator 94. A wide range of RF energy types can be employed. , including 500 Khz bursts, different types of waveforms, and the like. At controller 92a, a simple dial 96 is turned to point to a pair of electrodes to be energized. A key electrode can be attached to the intravascular imaging system, either electronically or by providing an attached electrode, electrode support member, or marker, which presents a distinct image on the intravascular imaging screen. This simplifies the selection of one or more pairs of eccentric electrodes along the atheroma. Advantageously, catheter 12 does not need to be rotated into a suitable orientation for precise remodeling and / or ablation of eccentric atherosclerotic material.

ES 2 380 487 T3 desired. Controller 92b includes similar capabilities, but allows the operator to select multiple bipolar electrodes to conduct RF energy between them, providing greater flexibility by allowing multiple electrodes to be powered simultaneously. Monopole control arrangements similar to Figures 8 and 9 can also be employed, as can be understood with reference to Figure 10. Patient grounding can be accomplished by a patient grounding plate, a 2- to 5-cm ring electrode proximal to basket 26, or the like. Again, no rotation of the catheter is required to orient an active side of the catheter adjacent to the target atheroma since various eccentric ablation orientations can be selected by the electrode selection controller.

[0103] An alternative controller is illustrated in Figure 11. This controller allows an operator to select, for each electrode, if he wishes to keep that electrode inactive, electrically couple this electrode to a first pole (sometimes referred to as pole A) of a power source (such as an RF generator or the like), or electrically couple this electrode to a second pole or pole B of the power source. This controller allows a wide range of energized electrode configurations, including pseudo-monopolar modes where all but one electrode is connected to one pole of the power source (pole A) and one electrode is connected to the other pole (pole B). Each electrode (in this embodiment, up to eight electrodes) is electrically coupled to a 3-way switch numbered 1 through 8. A switch arranged in the middle position indicates that the electrode is not coupled to either pole, while a switch pushed to the plus sign indicates that the associated electrode is coupled to a red RF connector with the controller. Similarly, a switch pushed to the negative sign indicates that the associated electrode is electrically coupled to a black RF connector on the control box.

[0104] An example of a self-extending basket is illustrated in Figures 12A-12H. As can be understood from these drawings, the electrodes can be fabricated as part of the arms 172 from which the basket is formed, for example, using a radially outward-facing surface of a localized widening 174 of each arm disposed at the axially central portion of the arm, as can be seen in Figures 12B and 12E. Each arm may be formed from a piece of material, optionally comprising a shape memory nickel-titanium Nitinol ™ alloy, with the arms optionally laser cut from a nitinol ™ tube. The electrode / basket can be, for example, coated with a high temperature polymer, such as a polyimide. Electrodes 174 may be formed by inhibiting coating or removing coating from the desired portion of associated arm 172 (as illustrated in FIG. 12E) so that the electrode surface is exposed for contact with atherosclerotic material. At least the surfaces of the active electrodes can be coated with a highly conductive metal, such as gold, silver, a copper alloy, or the like, and the coating should preferably maintain and support the flexibility of the basket structure, with materials optionally rolled liner or the like. By limiting the conductive electrode to a suitable configuration (often radially outwardly facing), the electrical coupling between the electrode and blood or other conductive fluids within the lumen can be limited. The arms may be separated from each other and structurally supported by an insulating material such as a heat-cured or ultraviolet (UV) radiation-cured shrink sleeve, polyethylene, nylon ™, or the like, to form basket 170.

[0105] Each arm 172 can be used to conduct energy between the surface of electrode 174 and an electrical conductor extending proximally from the arm to a controller. These proximal pads for connecting these leads are illustrated in Figure 12C, while distal structural pads 178 are illustrated in Figure 12D. Adjacent electrodes 174 can be axially offset or staggered as can be seen in FIG. 12F. The insulating coating along each arm 172 may be inhibited or removed from an interior surface of proximal pads 176 to facilitate connection of an associated lead wire, such as by spot welding or the like. Alternative polymeric or non-polymeric insulating materials can also be used, including parylene coatings, employing alternative procedures for attaching arms 172 to a catheter body, including adhesive bonding using insulating UV curing, embedding the pad structures in polyethylene. , and the like.

[0106] Examples of structures for attachment of arms 172 of basket 170 to catheter body 180 are illustrated in FIG. 12G.

[0107] Referring now to Figures 12F and 12H, alternative indicia providing a distinguishable image can be understood to rotate the selected electrodes 174 of the basket of 170 to images or other measurements of atheroma materials. In this embodiment, an electrode 174i referenced as electrode 1 may have a radiopaque marker 182 disposed on the associated arm 172i. An arm 172ii that supports an associated second electrode 174ii that may have two radiopaque markers 182 that provide a circumferentially asymmetric count indicator that allows all electrodes to be referenced unambiguously. The shape of the electrodes 50 can vary, for example, the electrodes 174 can be wider than other portions of the arms 172 as illustrated in Figures 12A-G.

[0108] Reshaping will often be accomplished using irrigation and / or suction flows. In many embodiments, an irrigation port directs fluid, such as a saline solution, from an irrigation lumen into the basket. An aspiration port can provide fluid communication between a lumen of

ES 2 380 487 T3 suction and an interior of the basket. One or both of these fluid flows can be activated continuously, or alternatively, they can pulse before, during and / or after treatment. In some embodiments, the irrigation suction and / or flow may appear acutely or at the same time to circulate the fluid between the irrigation port and the aspiration port. Optionally, the flow can carry ablation debris to the aspiration port, where it can be evacuated through the aspiration lumen. There may be coordination between the irrigation system and the aspiration system such that the irrigation fluid can remain confined to an area closely adjacent to the basket as well as inhibit embolization of ablation debris as the basket extends into the vessel. blood. This coordination, for example, can inhibit distal movement of ablation residues, and / or can obviate the need for a distal and / or proximal barrier or membrane. In some embodiments, the flow of fluid between an irrigation port and a suction port can create an effective bloodless environment adjacent to the electrodes to facilitate remodeling and / or ablation, atherosclerotic tissue imaging, and the like.

[0109] With reference now to Figure 13, the controllers of the catheter systems described herein may allow the distribution of different power levels to the different pairs of electrodes. For example, in response to a circumferential distribution of AM atherosclerotic material such as that illustrated in Figure 13, a controller can direct 50 watts of power to a first electrode 230, 30 watts of power to a pair of second electrodes 232 and only 10 watts of power to a third electrode pair 234. Other electrodes may have no power at all, as described above. In some embodiments, a different power directed to different electrodes may be provided by duty cycle control, for example, with 50 watts provided for the activation of one or more electrodes 50% of the time, with 30 watts being provided by the activation of an electrode 30% of the time, and the like.

[0110] Many imaging modalities (including intravascular ultrasound, optical coherence tomography, intravascular MRI, and the like) can be at least partially blocked or degraded by positioning the image detection framework within such a metal framework. like a Nitinol ™ basket. Therefore, there may be advantages to producing alternative structures, such as extensible baskets comprising plastics or a polymer. Considering the heat generated by the electrodes of the systems described herein, it may be advantageous for these polymer basket structures to comprise a high temperature polymer, such as a polyimide. Alternative basket structures can comprise HDPE, PET, nylon ™, PEBAX ™, and the like. The basket can be formed by cutting arms from a tube of polymeric material.

[0111] Examples of treatment procedures are illustrated in Figures 14A-14H. In FIG. 14A, catheter system 260 includes a sheath covering basket 262 over atherosclerotic material detection and treatment catheter 264 as described above. In this embodiment, outer basket sleeve 262 radially restrains basket 266, which is caused to radially extend when released from the outer sleeve, as illustrated in FIG. 14B. In some embodiments, the basket may be extended after the outer sleeve is retracted, for example by pulling pull guides, by rotating one portion of the catheter relative to the other, or the like. Regardless, as the basket extends into the container V, the basket electrodes 50 engage the surrounding vessel wall. An image transducer near basket 266 of an imaging catheter disposed in a lumen of the treatment catheter assesses vessel V, and catheter detection / treatment system 264 is urged proximally along artery or vessel V.

[0112] When the imaging catheter detects AM atherosclerotic material as illustrated in FIG. 14C, an appropriate subset (possibly including only a single electrode 50) is activated to remodel the AM atherosclerotic material, as illustrated in FIG. Figure 14D, and the lumen size of the open vessel increases moderately during treatment. The catheter is pulled proximally to the next atheroma, which is again detected and treated. A cross section of the limited open lumen prior to treatment is schematically illustrated in Figure 14F, which also illustrates a saline or irrigating lumen 268 of catheter 264. Treatment energy and the moderate increase in open lumen diameter of vessel V it is schematically illustrated in cross section of FIG. 14G. As a healing response gradually increases the diameter of the open lumen, the longer term open lumen results can then be provided which is schematically illustrated in FIG. 14H.

[0113] With reference now to Figures 15A and B the removal of eccentric material in a jelly-like artery model 270 is presented. Prior to testing, the model artery includes a consistent lumen 272 as seen in Figure 15A. An eccentric test treatment catheter 274 having an extendable basket supporting a circumferential set of electrodes is inserted into lumen 272, with the extendable basket supporting the electrodes connected to the luminal wall. The selected electrodes of the test catheter 274 were energized in order to eccentrically treat the gelatinous artery model 274, thus applying the eccentric remodeling of the gelatin model, in this case by removing an eccentric volume 276 along one side. lumen 272. Orientation and amount of material removed was controlled by selective energization of the test catheter 274 electrodes.

IS 2 380 487 T3

[0114] With reference now to Figure 16, an example catheter system 280 is illustrated. In this embodiment, catheter body 282 includes only a single lumen, which is large enough to accommodate an imaging catheter in the same and also to be used as an irrigation lumen to carry irrigation fluid to irrigation ports 284. The lumen may decrease in diameter distal to the irrigation ports 284, with the reduced diameter portion 286 appropriately receiving the imaging catheter within the lumen thereof to direct the irrigation fluid radially outward through the plurality. of irrigation ports. This embodiment can be particularly useful in remodeling atherosclerotic materials using the procedures illustrated in Figures 14A-14H, in which gentle heating improves vessel size, optionally without the need for aspiration.

[0115] Catheter body 282 may include a braided shaft in which the conductive wires (eg copper wires or beryllium-copper wires) are coated with a high-resistance and / or high-temperature insulation material such as a layer of polyimide or the like. The braided wires can be sandwiched between layers of materials that form the axis of the catheter body 282. The shaft may, for example, comprise a plurality of layers of polyethylene, an inner layer of Teflon PTFE ™, an outer layer of nylon, and the like.

[0116] The wires of the shaft 282 may be twisted to inhibit capacitive losses between the cables when electrical currents pass through them. Capacitive losses can decrease when a wire carrying a current from a power source to an electrode in the catheter system and a wire carrying a current from an electrode back to the power source are not parallel, but form an angle. ideally perpendicular. This can be accomplished by braiding the wires with the appropriate pitch or a number of spikes per inch. The basket structure 170 of catheter system 280 may be included, with the basket structure being described in more detail with reference to Figures 12A-12H. Guide 286 may extend through basket 170 and may comprise a transparent material for the imaging catheter, optionally comprising HDPE, PET, or the like.

[0117] There are still other alternatives available. For example, another way to use RF energy for remodeling of atherosclerotic material may be to energize a plurality of adjacent electrodes with different radio frequency signals in order to use adjacent electrodes as a phase matrix. A phase matrix can direct or conduct an electromagnetic signal in a desired direction through constructive and destructive interference between signals from adjacent elements of the matrix. By controlling the phases of adjacent signals, an electrode phase array can provide a focused and / or steerable RF signal.

[0118] In conjunction with directional control, adjusting the phases of adjacent RF electrodes can allow the concentration of some or most of the radio frequency energy to a desired depth D within the atherosclerotic material while inhibiting RF energy delivery between electrode surfaces and depth D using constructive and destructive interference between signals. For example, such a system can be used to preserve the lid of a plate in order to reduce restenosis. Inhibiting lid heating while focusing energy to an internal portion of the plate can reduce an immune response to heat that could otherwise lead to restenosis. Therefore, cap heating inhibition can reduce restenosis.

[0119] In general, the present invention can make use of highly elastic extensible structures, in particular extensible structures formed from structural elements separated by perforations in order to define a basket. These structures can be adjusted to an artery diameter before, during and / or after removal of atherosclerotic material. This expandability allows direct contact of the electrodes with the atheroma, although the systems of the present invention can also make use of conductive fluid environments to complete an RF energy path, or conversely, the use of non-conductive fluid. to enhance energy directed through tissue. Multiple electrodes can be circumferentially distributed around an intermediate portion of the extensible structure, and a subset of these electrodes can be activated to allow remodeling and / or ablation of eccentric tissue.

[0120] Atheroma can be identified and selected by intravascular imaging, and these capabilities can be integrated into the remodeling and / or ablation catheter. Preferably, the intravascular imaging capabilities are implemented in a separate catheter that can be advanced into and removed from the ablation catheter. In general, this intravascular imaging capability allows therapy development to be monitored so that wall perforation can be avoided, ideally reducing the occlusion to no more than 15% of the overall native vessel diameter (either at the end of the treatment or subsequent tissue healing). The ablation catheter may further allow the use of localized radiation or drug delivery for anti-restenosis treatments. The ablation catheter may include a relatively large lumen allowing for selective use of an intravascular imaging system, radiation delivery or other catheter treatment, aspiration of debris, and vaporization gases, these uses often employing sequential. A guidewire can make use of this separate lumen, and the guidewire can be removed to allow access to the restenosis and / or imaging catheters.

IS 2 380 487 T3

[0121] The devices, systems and procedures described above are suitable for the application of adjusted electrical energy to tissues and materials along a body lumen.

[0122] The examples of catheter devices and procedures for use described herein are intended to be applied to the lumen of the vessels of the human anatomy. The anatomical structure in which the catheter is placed can be, for example, the esophagus, the oral cavity, the nasopharyngeal cavity, the Eustachian tube and the tympanic cavity, the brain sinus, the arterial system, the venous system, the heart , larynx, trachea, bronchi, stomach, duodenum, ileum, colon, rectum, bladder, ureter, ejaculatory duct, vas deferens, urethra, uterine cavity, vaginal canal , and the cervical canal.

[0123] As can be understood with reference to Figures 17A-17C, targeting eccentric disease can be achieved by placing electrodes by moving them longitudinally in the vessel until they are in proximity to target tissue. As illustrated schematically in FIG. 17A, axial movement of a distal end of catheter-shaped probe 302 within a lumen of body 304 allows different axial portions of the lumen wall to be subject to analysis and treatment. An additional method of physically targeting eccentric disease in a radial manner is to selectively apply bipolar energy to specific electrodes 306 in order to direct the energy through the target tissue, as can be understood with reference to FIG. 17B. In some embodiments, radial and longitudinal physical orientation can be effected by selective activation of electrodes distributed both radially and longitudinally on an extensible body 310, as illustrated in FIG. 17C

[0124] Tissue frequency targeting is illustrated in Figures 18 and 19. As graphically illustrated in Figure 18, different types of tissues have different electrical characteristic impedances that cause the tissue to absorb energy at certain frequencies or ranges. of frequencies more easily than others. By applying energy at the specific frequency or a range of frequencies in which the tissue is the most conductive, the energy penetrates the tissue more easily. In general, diseased tissue samples have been shown to exhibit greater impedance characteristics than healthy tissue samples. As illustrated in Figure 19, in the case where a diseased tissue of 312 is surrounded by relatively healthy tissue 314, it is likely that the healthy tissue protects the diseased tissue from the flow of electrical current due to the low impedance of the tissue. healthy. Thus, minimal (or less than desired) current flow 318 may pass through diseased tissue312, and higher current flow 320 may be seen in healthy low-impedance tissue 314 when bipolar current is transmitted between the electrodes. 316. Typically, the frequency ranges in which the tissue impedance varies to a useful degree occurs between 100 kilohertz and 10 megahertz.

[0125] Targeting often aims to deliver more energy to diseased tissue by determining the frequency or range of frequencies at which the impedance of diseased tissue is equal to or less than that of healthy tissue, such as by operation on or above a frequency threshold 322 as illustrated in Figure 18. Energy delivered at the specified frequency or range of frequencies will cause more heat dissipation in diseased tissue than energy delivered outside of those specific frequencies.

[0126] The use of impedance measurements to determine a location and / or state of tissue can be generally understood with reference to Figure 20. First, impedance measurements can be used using an array of electrodes radially spaced within lumen 330 332 to analyze diseased tissue 334. Impedance measurements between the five electrodes in the array, and impedance measurements in particular between adjacent electrode pairs (and / or between separate electrode pairs), may differ when the current path passes through diseased tissue 334, and when it passes through the healthy tissues of the luminal wall. Therefore, impedance measurements between electrodes on either side of diseased tissue 334 may indicate injury, while measurements between other adjacent electrode pairs indicate healthy tissue. Impedance characterizes the molecular state of a tissue. The state of a tissue can be affected / changed by temperature: for example, lipids start to denature at 85 ° C and change state, to fatty acids, which can be 90% more compact in volume than the original lipids.

[0127] If the state change temperature for a tissue is known, and the impedance of the different tissue states, then by measuring the tissue impedance, it is possible to detect a state change, and / or estimate which is the temperature, thus making it possible to monitor the progress of the therapy. For example: If the impedance of lipids were 100 ohms and the impedance of fatty acids 90 ohms (in this case with hypothetical values), and knowing that lipids are converted into fatty acids around 85 ° C, then the Detecting a change in impedance shape from 100 Ohms to 90 Ohms indicates that lipids have been converted to fatty acids and therefore that the temperature should be around 85C. In the analysis of diseased luminal tissues, specific frequencies can be used to verify a type and condition of the tissue based on the measurement of electrical impedance. Normal use will include the discovery and characterization of diseased tissues using intraluminal ultrasound or other procedures. Measurement of tissue electrical impedances on radially spaced electrodes will allow verification of the existence of diseased tissue and knowledge of the location of the electrodes in relation to the specific tissue.

IS 2 380 487 T3

[0128] Multiple frequency therapies and signals are schematically illustrated in Figure 21. The therapy may consist of the application of electrical energy at a single frequency or at multiple frequencies. Depending on the composition of the target tissue and surrounding tissue, the optimal treatment may consist of directing a single frequency to a single tissue type, multiple frequencies to target multiple tissue types, or multiple frequencies applied to a single tissue type. Multiple bursts of the same frequency 336, variable frequencies, such as a continuous burst of variable frequency 338, bursts of multiple frequencies 340, and multiple overlapping frequencies (optionally in bursts 342) may be employed.

[0129] Multiple frequencies can be applied in any sequence of any combination of electrodes in contact with the target tissue or surrounding tissue. Multiple frequencies can be applied as discrete frequencies or as a frequency sweep over a range in a linear, logarithmic, or other manner.

[0130] An energy control arrangement is schematically illustrated in Fig. 22. In general, the impedance and physical characteristics of the tissue can be used to establish the output or treatment parameters. Geometry and tissue type can be determined as described herein using IVUS or other similar detection techniques. Multiple electrode electrode impedance measurements can be taken. A system processor algorithm can choose a correct starting rate, initial settings, and / or output ranges.

[0131] Regarding the adjustment of the correct initial dose, the shape and type of diseased tissue to be treated is generally diagnosed and characterized by intraluminal detection devices of the ultrasonic, optical or other type. Using the multiple electrode approach, electrical impedance measurements can be used to understand the electrical characteristics of atherosclerotic tissue of varying geometries and previously diagnosed types. Using these data, the initial dose adjustment of therapy can be optimized.

[0132] Regarding dosage control, the electrical impedance characteristics of tissues vary due to temperature variations and the molecular state of a tissue. Dynamic measurement of tissue electrical impedance during energy application can be used to monitor changes in tissue and progress of therapy. An implementation of the four electrode system would allow the measurement of electrical impedance at the electrode / tissue interface and therefore, measurement of the change in tissue temperature at the contact surface and at the tissue contact.

[0133] In terms of determining the appropriate dose during treatment, the energy distribution pattern can be a single pulse or multiple pulses of varying duration separated by rest periods of varying duration. Measurement of tissue and electrode electrical impedance at the tissue interface during energy delivery and between energy pulses can be used to determine optimal durations of energy delivery and rest periods. Bursts of pretreatment RF energy can be applied to condition the target tissue. Conditioning can be used to activate heat shock proteins (HSP) in healthy tissue prior to treatment for better protection of healthy tissue. Post-treatment bursts of RF energy can be applied to control tissue cooling time. Interim treatment bursts of RF signals can be used to monitor the temperature of the target and surrounding tissues between bursts of multiple therapy. Power can be delivered in any combination of amplitude and frequency from any combination of electrodes.

[0134] Multiple electrode impedance measurements can also be employed. When using a multiple electrode design, some of the electrodes are likely to come into contact with the lumen wall and others to become suspended in blood or other existing fluid or thrombus, or existing stents, or such foreign matter. Measurement of impedance at various radial locations allows one to determine which electrodes are in contact with the lumen wall and which are in contact with fluid such as blood. This contact determination can be used in combination with an intraluminal display device such as ultrasound to determine the physical orientation of the electrodes.

[0135] Using impedance measurements between multiple electrodes, determination of the contact status of each electrode with tissue or blood can be used to determine if the electrode carrying the mechanism (catheter) is in the proper location for therapy. . Impedance measurements between multiple electrodes can be used to determine the quality of electrode contact with tissue. Poor contact quality can cause excessive or unwanted localized heating or otherwise prevent optimal treatment. Contact quality determination can be used to minimize such problems.

[0136] In some situations, the choice of electrode can be determined by a combination of position and quality of contact. Impedance measurements between multiple electrodes can be used to better understand which electrodes are in best contact or position to treat a specific area or lesion.

IS 2 380 487 T3

[0137] In some situations, the determination of the energy level and frequency to be applied to the target can be based on the quality of the contact. Impedance measurements between multiple electrodes can be used to determine the optimal energy level and frequency.

[0138] In some situations energy may be applied to a single electrode pair, between multiple electrode pairs, or from a single multiple electrode electrode, or any combination thereof. Impedance measurements between multiple electrodes can be used to determine the optimal pattern.

[0139] Impedance measurement can be employed in different embodiments using two to four electrodes, as can be understood with reference to Figure 23. Four electrode systems have been used for electrical impedance measurement in many applications. Four electrode systems are inherently more accurate than two electrode systems due to inaccuracies created in the two electrode systems by excessive contact impedance and electrical polarization reactions created in the contact zone. In the four electrode system 344, energy is supplied to the target by two energy supply electrodes 346 and an impedance measurement is made between the other two high impedance electrodes 348 shown schematically in contact with tissue 350 in the path of Energy. In this multi-electrode application, either of the two electrodes can be used to supply power while either of the other two electrodes can be used for impedance measurement, thus forming a four-electrode measurement system. A probe or catheter 352 can be used, it can include a circumferential and / or longitudinally distributed set of electrodes to contact tissue, and any of the four electrodes of the catheter can be configured for power delivery or impedance measurement. Thus, the electrode assembly can be used as a two or four electrode system.

[0140] In many applications it is useful to know how much energy is being delivered to the target tissues and how much is dissipated at the interface between the electrodes and the tissue. By taking measurements as a two-electrode system and then as a four-electrode system, the electrode at the tissue interface can be characterized and this data can be used to determine how much energy is being dissipated at the electrode / tissue interface and how much is being dissipated. actually supplies the target tissue.

[0141] Measurement of electrical impedance in two or four electrode configurations can be performed statically using small excitation signals or can be measured dynamically during energy application at normal levels of therapy. Using this technique, the impedance of electrical tissue can be measured dynamically during energy application to determine the condition of the treated tissue and surrounding tissue.

[0142] The impedance measurement can optionally be carried out in mono-polar configuration. It is possible to use various electrode systems in a mono-polar configuration where the return electrode is an electrically conductive pad applied to the external surface of the patient or the like. In this configuration, impedance measurements can be made between any of the internally applied electrodes and the external return pad in the two-electrode mode or any of the internally applied electrodes can apply flowing energy to the external return pad while using either. another of the two internally applied electrodes to measure impedance.

[0143] As for temperature measurements, impedance measurements taken prior to therapy can be used to calculate a normalized value for use in further calculations to determine the change in temperature from said initial value. Dynamic monitoring of the electrical impedance of the target and surrounding tissue during therapy can be used to calculate the change in tissue temperature. In some embodiments, dynamic monitoring of the electrical impedance of the interface between the electrodes and the tissue can be used to prevent charring of the tissue or clotting of blood at the interface.

[0144] The change in temperature during treatment can be used to determine the effectiveness of the energy delivery setting and to determine the condition of the tissue being treated.

[0145] Temperature measurement can be performed by intraluminal ultrasound or other mechanism and verified with data derived from impedance measurements.

[0146] The use of the systems described herein with ionic and non-ionic liquid can be understood with reference to Figure 24. When the electric current flows in an ionic liquid such as blood that fills a lumen 356, at least a portion of current can pass through the blood when the electrodes 358 are energized. Even when the electrodes are arranged on either side of a target tissue 360, the heating of the target tissue can be reduced by current flow within the blood.

[0147] When used in a fluid-filled lumen such as an artery, this device can be used in combination with a non-ionic liquid that floods zone 362 to displace or partially displace native fluid to modify the conductivity of the surrounding medium of the tubes. electrodes. This action may be desirable in order to direct energy; in the form of an electric current 364, in the lumen walls rather than through the fluid

ES 2 380 487 T3 native, thus supplying energy to the surrounding wall tissues with minimal dissipation in the fluid filling the lumen.

[0148] A second objective of the nonionic or ionic fluid may be to provide cooling to the electrodes and tissue at the surface and just below the surface of the lumen wall.

[0149] Electrical impedance measurements at the electrodes can be used to determine the conductivity of the surrounding liquid, thus measuring the concentration of non-ionic liquid in the native fluid. This data can be supplied to the control system to allow adjustment of the ionic liquid concentration to optimize energy delivery to the target tissue and thus minimize unwanted effects to surrounding tissue.

[0150] The use of blood as a contact interface is also an option. Blood is an ionic conductive fluid that can be used as an interface between electrodes and tissue to ensure good electrode-tissue contact and low contact impedance.

[0151] A closed-loop control can be understood with reference to Figure 25. Impedance measurements in frequency ranges and across multiple electrodes can be used to verify electrode location relative to tissue reference points, optionally by correlation with intraluminal measuring devices used simultaneously such as an IVUS before and during therapy.

[0152] Impedance measurements using a closed loop treatment controller 366 using system processor hardware and / or software can facilitate treatment control. This control over frequency ranges and across multiple electrodes can be used to monitor and verify physical changes such as tissue contraction or tissue denaturation at the site of application. These data can be used to check the physical changes observed by other intraluminal observation techniques such as ultrasound.

[0153] Data from impedance measurements 368 combined with inputs from intraluminal measurement devices 370 such as ultrasound can be used to determine electrode selection from a predetermined set of rules of a controller or processor module 372. This type Control system could be used in automatic mode to diagnose and treat diseased intraluminal tissue.

[0154] A controller can utilize data on tissue status, optionally including temperature change, tissue electrode interface impedance, tissue impedance, tissue or blood electrode contact, and intraluminal geometry and tissue type to from ultrasound or other sources, such as inputs to a closed loop control system 366.

[0155] The electrode switching implementation can employ any of a wide variety of; selective energizing electrode circuits, switching types, switching locations, and the like, some of which are schematically illustrated in Figures 26A-26C.

[0156] The electrode switches may be located on an external instrument or external control box 374, such that an external connection point 376 is provided for each catheter catheter electrode 378, with one wire per electrode 380 extending in and / or along the catheter body. Alternatively, electrode switching mechanisms 386, 388 can be embedded in a catheter 382, ​​384, respectively, either near the proximal end of the catheter for external switching or near the distal end of the catheter for internal switching. A limited number (eg, 4) of leads 390 can run near the switch mechanism, while an electrode lead can extend distally through the switch mechanism. The connection of discrete electrodes to the RF generator or impedance measuring device can be accomplished with electromechanical or solid state means.

[0157] The provision of switch mechanisms at the distal end of the catheter can have advantages. If located on the catheter, the switch mechanism may be located at the distal end to decrease the number of wires in the catheter body or at the proximal end. In embodiments of the switch mechanism located at the distal end of the catheter the external control circuit optionally communicates with the switch mechanism via the same leads used for impedance measurements.

[0158] The switch mechanism can also be employed at the proximal end or any other site of the catheter. The switch mechanism can be located at the proximal end or elsewhere on the catheter if it provides performance or cost advantages.

[0159] Referring now to FIG. 27, the catheter systems and methods 418 described herein are often used to treat plaques having fibrous tissue 420. Fibrous tissue 420 can be heated as target tissue to a temperature in the range of 420. a range of about 90 to about 95 C, which can provide shrinkage of up to about 50%. Lipids 424 can be heated to target temperatures in a range of about 80-85 ° C, providing up to about 90% shrinkage. Damage to the adventitial layer 426 can be inhibited or the layer protected by limiting

ES 2 380 487 T3 heating to below about 62 C. These and other estimates of temperature and shrinkage can be determined by empirical tests or the like, from unpublished and / or published work, or from other sources. Referring to Figures 27A-27C, spectral correlations in diseased tissue may allow characterization of tissues using techniques such as those described in an article by Tjeerd J. Romer et al. entitled Histopathology of Human Coronary Atherosclerosis by Quantifying Its Chemical Composition with Raman Spectroscopy, Circulation 97: 878-885 (1998).

[0160] Referring now to Figures 28A-28D, the viability of tissue contraction can be seen in a laboratory experiment using a catheter system, such as that described herein. An animal fat tissue model 430 (shown prior to treatment in Figure 28A) can be treated by manually keeping the extensible structure and associated probe electrodes in contact with a tissue surface during tissue reshaping treatment with electrosurgical energy (see Figure 28B). After treatment, as seen in Figure 28C and the enlargement of Figure 28D, tissue contraction can be visually verified. The feasibility of using intravascular imaging with the procedures and systems described herein can be verified by the six individual electrode support arms 428 of the extensible catheter structure of Figure 29A, as well as by visualizing an eccentric vacuum. 430 that is created by focused guided benign remodeling energy in order to increase the effective diameter of the artery for better blood flow, as seen in Figure 29B.

[0161] Referring now to Figure 30, advantageous embodiments may employ aspects of electrical tissue discrimination techniques and apparatus described in US Patent 6,760,616 to Hoey et al. Entitled Tissue Discrimination and Applications in Medical Procedures. As described in more detail in this reference, the tissue identification system 510 includes a user-readable output device 512; a user input device 516, a processor 520, and a probe 522. The processor 520 includes a central processing unit (CPU) 514, a digital-to-analog converter (D / A), and an analog-to-digital converter (A / D) 518. Processor 520 can be included in processor 49 (see Figures 2 and 3), and probe 522 can comprise any of the catheter structures described herein, such that tissue identification system 510 can be included in system 10.

[0162] Referring now to Figures 30 and 31A, the tissue identification system 510 can apply a sliding or variable frequency electrical signal by activating the electrode with a variable frequency power source 524. Therefore, Power source 524, probe electrode 522, and connected patient tissue P can be included in a circuit and an electrical characteristic of the circuit can be measured at different frequencies. In exemplary embodiments, an impedance (phase angle and magnitude) of the circuit is measured at a plurality of frequencies within a frequency range of about 4KHz to about 2MHz. Each frequency / magnitude / phase angle point can represent a tissue signature measurement, with a series of individual data points often taken under similar conditions (for example, at a given frequency and without moving the electrodes) and averaged for greater precision. Tissue signature data points can be measured at a plurality of frequencies over a range of frequencies to generate frequency / phase angle / phase magnitude curves that represent a tissue signature profile or correlation 530, 532, or 534, which can be used to characterize the circuit fabric.

[0163] The signals used to obtain tissue signature profiles 530, 532, 543 will often be conducted between the electrodes of the catheters described herein. Conveniently, the tissue included in the circuit can be monitored by selecting different pairs of electrodes for verification, with or without repositioning of the electrodes. There can be significant differences from patient to patient (or even between different regions within the same patient) for individual tissue signature measurements, and these differences can, at least in part, be caused by different electrode configurations during verification. , different distances between the electrodes, and the like. However, the relationships (and in particular the relative slopes of the profile correlations, the shifts between the correlations, and the like will be consistent enough to allow tissue characterization, particularly when obtaining a reference tissue signature profile for the patient or tissue region using IVUs, OCTs, or the like. When a region of (for example) healthy tissue can be identified using IVUS and used to generate a reference tissue signature profile for the patient, other nearby tissue signature measurements or profiles can then be normalized to this reference in comparison with this reference, and / or the like. From the displacements, differences in slope, and the like, the tissue can be analyzed.

[0164] Referring now to Figures 31A-31J, the relationships between the tissue signature profile curves or the correlations can be used to analyze and characterize the tissues connected to the probe electrodes. For example, a correlation 530 associated with fibrous plaque (seen on the left side of the graph in Figure 31A) has both a significantly different slope and magnitude from a calcified plaque 534 (seen on the right side of the plotted data ) and from a 532 correlation associated with thrombi (generally between 530 and 534). The shifts between the correlations here encompass a phase difference for a given impedance, a difference in impedance for a given phase, or the like. As can be understood with reference to the graphical representations, the relationships between the correlations can be determined by curves fitted to the data, by statistical analysis, by lookup tables, or the like. In

ES 2 380 487 T3 exemplary embodiments, tissue signature measurements can be taken by (for example) a commercially available impedance vector meter such as Hewlett-Packard Model No. 4193A, and correlations can be captured using LabVIEW ™ software and plotted or manipulated with Microsoft Excel ™ spreadsheet, or similar. Once sufficient baseline data has been obtained and repeatability has been established in different probe configurations, characterization of tissues by electrical circuit measurements without comparative evaluation of each patient can avoid the expense of IVUS.

[0165] Referring now to Figure 31B, along with characterizing different tissues, the relationships can also be used as feedback on luminal wall treatments. A fibrous plaque correlation or profile before treatment (towards the right side of the graph) changes in magnitude during treatment for a post-treatment correlation or profile (towards the left side). This treatment involved 2 W of electrosurgical energy for 2 seconds, showing that moderate remodeling or partial treatments can be monitored, verified, and / or controlled by the electrical characteristics of the tissue circuit identification system 510. Advantageously, once an appropriate frequency or range of frequencies has been determined, it is not necessary to generate the entire tissue signature profile for analysis of tissue treatments and / or tissue characterization in progress, since the shifts may be easily identified. These measurements can, for example, make it possible to determine tissue temperatures, in particular when the temperature is a treatment temperature that alters a shift in tissue signatures. The energy of the electrical signals used for tissue analysis will typically be lower than that of remodeling treatments. A similar graph is shown in Figures 31C and 31D, here the post-treatment correlation after treatment being 2 W for 9 seconds and 1 W for 9 seconds, respectively.

[0166] Referring now to Figure 31E, the relationships between healthy tissue (on the right) and fibrous plaques (on the left) can be identified from their tissue signature profiles or associated correlations, which differ significantly both in slope and magnitude. Figure 31F shows the relationships between the correlations or profiles of fibrous tissue before treatment (left), fibrous tissue after treatment (right), and healthy tissue (center). Figures 31G-31J illustrate additional representations of the relationships between the profiles or correlations associated with fibrous tissues and fibrous tissues treated.

[0167] Referring to Figure 32, a severely diseased blood vessel can be seen with three basic categories of plaque: lipid-rich (fat) plaque, fibrous plaque, and calcified plaque or tissue. They can all be present in a sample, and they can also be present in diseased tissue from (or alongside) a lesion, making the lesion difficult to treat using conventional techniques. Through the tissue analysis techniques described here, the correct doses of energy can be directed and prescribed to effect a safe and appropriate (and often different) remodeling of the different categories or types of tissues, in the appropriate places of the constituent parts that make up each injury.

[0168] Referring now to Figure 32A, this graph shows the results of tissue signature and tissue profile measurements obtained from a human aorta specimen, with these fibrous plaque results obtained before and after treatment. Figures 32B and 32C show tissue histopathology slides. Visible cracks on each slide may be a product of the mounting process. However, the nucleation or voids shown in Figure 32C may indicate remodeling of the same tissue.

[0169] Although exemplary embodiments have been described in some detail, by way of example and for clarity of understanding, those skilled in the art will recognize that a variety of modifications, adaptations, and modifications may be employed. Therefore, the scope of the present invention should be limited only by the appended claims.