Devices, methods and systems for renal denervation

Abstract

Renal nerve ablation techniques include methods and devices for generating one or more gas bubbles to at least partially fragment calcifications in a calcified region of a renal artery, and ablating one or more nerves near, within, or surrounding the calcified region of the renal artery after the calcifications have been at least partially fragmented. Other embodiments are also described and claimed.

Description

[Technical Field]

[0001] [Priority] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 378,328, filed October 4, 2022, entitled "Catheter with Pretreatment and Treatment Unit and Method of Use Thereof," and U.S. Provisional Patent Application No. 63 / 578,123, filed August 22, 2023, entitled "Catheter with Pretreatment and Treatment Unit and Method of Use Thereof," which applications are incorporated by reference in their entireties into this specification to provide continuity of disclosure.

[0002] [Technical field] This application relates generally to minimally invasive apparatus, devices, systems and methods for providing energy delivery to targeted anatomical locations in a subject, and more particularly to catheter-based intraluminal apparatus and systems configured to deliver ultrasound energy to treat tissue, such as neural tissue. [Background technology]

[0003] High blood pressure, also known as hypertension, commonly affects adults. If left untreated, hypertension can lead to kidney disease, arrhythmias, heart failure, and stroke. In recent years, treatment of hypertension has focused on interventional approaches to deactivate the renal nerves surrounding the renal arteries. Autonomic nerves tend to follow blood vessels toward the organs they innervate. Intraluminal devices, such as catheters, can reach specific structures, such as renal nerves, that are proximal to the body cavity through which the catheter passes. Thus, a catheter-based system can provide renal denervation therapy within the body cavity to deactivate the renal nerves around the blood vessel walls.

[0004] The present disclosure is defined in the independent claims. Further embodiments of the present disclosure are defined in the dependent claims. Methods, apparatus and systems are provided herein.

[0005] A tissue treatment system for renal denervation is provided, comprising: a bubble generating device configured to generate one or more bubbles to at least partially fragment calcifications in a calcified region of a renal artery; and an ablation device configured to ablate one or more nerves near, within, or surrounding the calcified region of the renal artery after the calcifications have been at least partially fragmented.

[0006] A tissue treatment system configured to ablate one or more nerves near, within, or surrounding a calcified region of a renal artery is provided, the tissue treatment system comprising a non-transitory computer-readable memory storing instructions, and one or more processors configured to execute the stored instructions to cause the tissue treatment system to detect a calcification condition in the renal artery within a target region and to decrease a default acoustic input power setting and increase an ablation duration setting based on the detected calcification condition.

[0007] Further provided is a tissue treatment system comprising: an ablation device configured to ablate one or more nerves innervating a kidney; a non-transitory computer-readable memory storing instructions; and one or more processors configured to execute the stored instructions to cause the tissue treatment system to detect calcification scores at one or more target locations along a main renal artery and one or more target locations along at least one of an accessory renal artery or a renal artery branch, determine whether the calcification score is lower at the one or more target locations along the main renal artery or one or more target locations along an accessory renal artery or a renal artery branch, and prompt a user using a graphical user interface to perform ablation at the one or more target locations along the main renal artery or one or more target locations along an accessory renal artery or a renal artery branch based on whether the calcification score is lower at the one or more target locations along the main renal artery or one or more target locations along an accessory renal artery or a renal artery branch.

[0008] A method for renal denervation is provided, comprising delivering a catheter to a calcified region of a cavity wall, the catheter including a proximal balloon, an intermediate balloon, and a distal balloon attached to a catheter shaft, the catheter including a laser fiber disposed on a surface of the intermediate balloon, generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region of the cavity wall, and ablating one or more nerves near, within, or surrounding the calcified region of the cavity wall after the calcified region is at least partially fragmented.

[0009] A further method for renal denervation is provided, comprising delivering a catheter to a calcified region of a cavity wall, the catheter including a barbell-shaped balloon attached to a catheter shaft, the catheter including a laser fiber disposed on a surface of a middle region of the barbell-shaped balloon, inflating the barbell-shaped balloon so that the middle region is longitudinally aligned with the calcified region and the calcified region is longitudinally located between a proximal region and a distal region of the barbell-shaped balloon, generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region of the cavity wall, and ablating one or more nerves near, within, or surrounding the calcified region of the cavity wall after the calcified region is at least partially fragmented.

[0010] A further method for renal denervation is provided, comprising delivering a catheter to a calcified region of a cavity wall, the catheter including a proximal balloon and a distal balloon attached to a catheter shaft, the catheter including a laser fiber disposed on a surface of the proximal balloon, generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region of the cavity wall, and ablating one or more nerves near, within, or surrounding the calcified region of the cavity wall after the calcified region is at least partially fragmented.

[0011] Some features of the present disclosure have been broadly described in the section entitled "Detailed Description" so that they may be better understood and the contributions of the present technology may be better appreciated. Additional features of the present disclosure are described below. In this respect, the present disclosure is not limited in its implementation to the details of the components or steps described herein or illustrated in the several figures of the drawings. Such components or steps may be implemented in various ways. Also, the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.

[0012] A renal denervation system is also presented. The renal denervation system includes a bubble generating device configured to generate one or more bubbles to at least partially fragment calcifications in a calcified region of a renal artery, and an ablation device configured to ablate one or more nerves near, within, or surrounding the calcified region of the renal artery after the calcifications have been at least partially fragmented. The system may further include an imaging device. The system may further include a controller or controller system and a memory that stores a computer program product, which may include program code portions for performing any of the steps of the methods presented herein when the computer program is executed by the controller or controller system. The system may be configured as a catheter device, such as an ablation catheter.

[0013] Also provided is a computer program product comprising program code portions for performing the steps of any of the methods presented herein when the computer program is executed by a processing device, which may be constituted by a controller or a controller system.

[0014] The foregoing description is summary and limited in detail. The foregoing and other aspects, features, and advantages of the present technology are described below in connection with various embodiments, with reference to the accompanying drawings. [Brief explanation of the drawings]

[0015] [Figure 1] FIG. 1 is a diagram illustrating a perspective view of a general ultrasound-based ablation system according to one embodiment of the present disclosure.

[0016] [Figure 2]FIG. 2 illustrates a detailed cutaway cross-sectional view of the distal end of the generic ultrasound-based ablation system shown in FIG. 1, according to one embodiment of the present disclosure.

[0017] [Figure 3] FIG. 3 illustrates a cutaway perspective view of a catheter device for preparing and treating an anatomical structure, according to one embodiment of the present disclosure.

[0018] [Figure 4A] FIG. 4A illustrates a side view of a catheter device for preparing and treating an anatomical structure, according to one embodiment of the present disclosure.

[0019] [Figure 4B] FIG. 4B illustrates a side view of a catheter device for preparing and treating an anatomical structure, according to one embodiment of the present disclosure.

[0020] [Figure 4C] FIG. 4C illustrates a side view of a catheter device for preparing and treating an anatomical structure, according to one embodiment of the present disclosure.

[0021] [Figure 4D] FIG. 4D illustrates a side view of a catheter device for preparing and treating an anatomical structure, according to one embodiment of the present disclosure.

[0022] [Figure 5] FIG. 5 is a schematic diagram illustrating a catheter device for preparing and treating an anatomical structure, according to one embodiment of the present disclosure.

[0023] [Figure 6] FIG. 6 is a flow diagram illustrating a method of manufacturing a catheter device for preparing and treating an anatomical structure according to one embodiment of the present disclosure.

[0024] [Figure 7] FIG. 7 is a flow diagram illustrating a method for preparing and treating an anatomical structure via a catheter device according to one embodiment of the present disclosure.

[0025] [Figure 8] FIG. 8 is a flow diagram illustrating a method for preparing and treating renal nerves according to one embodiment of the present disclosure.

[0026] [Figure 9A] FIG. 9A illustrates a side view of a catheter device with proximal and distal balloons in a deflated state for blocking debris after preparing a renal nerve according to an embodiment of the present disclosure.

[0027] [Figure 9B] FIG. 9B illustrates a side view of a catheter device with proximal and distal balloons inflated for blocking debris after preparing a renal nerve according to an embodiment of the present disclosure.

[0028] [Figure 10] FIG. 10 illustrates a side view of a catheter device with a cone-shaped balloon at its distal portion to block debris after preparing the renal nerve, according to an embodiment of the present disclosure.

[0029] [Figure 11] FIG. 11 illustrates a side view of a catheter device with a barbell-shaped balloon for blocking debris after preparing the renal nerve according to an embodiment of the present disclosure.

[0030] [Figure 12] FIG. 12 illustrates a side view of an embodiment of a catheter device with a scoop to collect debris after preparing the renal nerve, according to an embodiment of the present disclosure.

[0031] [Figure 13] FIG. 13 is a diagram showing the main renal artery and the accessory renal artery that extends parallel to the main renal artery.

[0032] [Figure 14] FIG. 14 is a diagram showing the main renal artery and renal artery branches that extend non-parallel to the main renal artery.

[0033] [Figure 15] FIG. 15 shows exemplary details of a controller, according to one embodiment.

[0034] [Figure 16] FIG. 16 is a diagram illustrating a cross section of a transducer according to one embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0035] The illustrated embodiments are merely examples and are not intended to limit the present disclosure. The schematic diagrams are drawn to illustrate features and concepts and are not necessarily drawn to scale.

[0036] [Detailed explanation] The foregoing description is brief and limited in detail. The foregoing and other aspects, features, and advantages of the present technology will be described in conjunction with various embodiments. The inclusion of the following embodiments is not intended to limit the disclosure to those embodiments. Rather, it is intended to enable one skilled in the art to make and use the contemplated invention. Other embodiments are possible, and changes may be made without departing from the spirit or scope of the subject matter presented herein. The aspects of the disclosure described and illustrated herein can be arranged, combined, changed, and designed in a variety of different forms, all of which are expressly contemplated and form part of this disclosure.

[0037] Any (any) system, apparatus, device, product-by-process, composition of matter, process, technique, or method described herein is useful in the health, medical, or surgical fields, including oncological treatments, procedures, and surgeries. However, the subject matter of this disclosure may be extended or applied to other conditions or fields outside of health, medicine, or surgery. Such extensions or implementations are also encompassed by this disclosure. Any (any) system, apparatus, device, product-by-process, composition of matter, process, technique, or method described herein encompasses techniques applicable to health, medical, or surgical procedures for any other anatomical region that would benefit from the use of a catheter to facilitate access to the interior of an animal body, such as a human body.

[0038] Various systems, apparatus, devices, process products, compositions of matter, processes, techniques, or methods are described below. When described, examples thereof are provided in accordance with some embodiments of the present disclosure. None of the embodiments described below limit the claimed embodiments, and any claimed embodiment may include systems, apparatus, devices, process products, compositions of matter, processes, techniques, or methods that may differ from the examples described below but are encompassed by the present disclosure. Claimed embodiments are not limited to any one or any combination of any systems, apparatus, devices, process products, compositions of matter, processes, techniques, or methods described below.

[0039] Furthermore, this detailed description sets forth numerous specific details in order to provide a thorough understanding of the various embodiments described throughout this disclosure. Although the embodiments described herein may be practiced without these specific details, in other instances, well-known methods, techniques, procedures, or components are not described in detail so as not to obscure the embodiments described herein.

[0040] Approximately one-third of patients typically respond poorly or fail to respond to renal denervation therapy, e.g., a decrease in daytime ambulatory systolic blood pressure (dASBP) of less than about 5 mm of mercury (Hg). Calcification or calcium deposits in the renal arteries may be the cause.

[0041] Calcification includes calcium buildup or calcium deposits that can increase arteriosclerosis and be a secondary cause of hypertension. Even when calcification is not severe enough to be a secondary cause of hypertension, it can still prevent renal denervation surgery. Calcification within the arterial wall of the renal artery can interfere with ultrasound treatment by an ultrasound therapy device because ultrasound signals tend to reflect off the calcium deposits. Similarly, when using radiofrequency (RF) devices, calcification in the arterial wall can disadvantageously block the conductive heating required to treat nerves associated with renal structures. Furthermore, when using RF devices, achieving proper electrode apposition (adhesion) to the vessel wall can be difficult due to calcification in the vessel wall. Furthermore, calcification can alter the shape of the lesion, resulting in inconsistent ablation and treatment.

[0042] Therefore, a need exists for a method for imaging a calcified region, fragmenting at least a portion of the imaged calcified region, and ablating tissue surrounding the imaged calcified region, as well as a need for an apparatus for use in performing the method.

[0043] To address at least the aforementioned challenges, the present disclosure generally includes catheter devices and methods for preparing and treating anatomical structures, such as renal arteries, to treat medical conditions. The present disclosure relates to catheters and methods for fragmenting calcifications from calcified regions and ablating nerves around the renal arteries to treat medical conditions. Additionally, the present disclosure includes catheter devices and methods for identifying calcified regions and verifying their removal prior to ablation therapy.

[0044] Renal artery calcification (also known as renal vascular calcification) refers to deposits of calcium and other minerals found on or within the walls of the renal arteries (or their branches). Renal artery calcification is considered present when the density of mineral deposits detected by CT is 130 Hounsfield units or greater.

[0045] Renal artery calcification is generally the result of vascular smooth muscle cell transformation into osteoblasts, and is due to, among other factors, phosphate retention, hypercalcemia, previous dialysis treatment, administration of active vitamin D, or lack of anti-calcification drugs.

[0046] Calcification can occur in the intima, media, or both layers of the renal artery. In atherosclerosis, the intima becomes severely inflamed, thickens, and calcifies. Meanwhile, medial arterial calcification is primarily associated with hypertension, diabetes, and / or chronic kidney disease. Medial calcification is associated with arterial stiffness, cardiovascular events, and mortality.

[0047] The Peripheral Artery Calcium Scoring System (PACSS) can be used to assess the degree and / or severity of calcification: Grade 0: no visible calcification in the area mentioned; Grade 1: unilateral calcification less than 5 cm in greatest diameter; Grade 2: unilateral calcification ≥ 5 cm in greatest diameter; Grade 3: bilateral calcification less than 5 cm in greatest diameter; Grade 4: bilateral calcification ≥ 5 cm in greatest diameter. Calcified renal arteries may be hard, dense, tubular, and associated with white, solid plaque.

[0048] Imaging of renal artery calcification can be performed using x-ray, ultrasound, non-contrast CT, PET scan, extravascular ultrasound, intravascular ultrasound, MRI, or angiography. The appearance of calcification with ultrasound is that of hyperechoic lesions obtained by acoustic shadowing.

[0049] Calcified regions may be found within the wall of the renal artery and may extend over the longitudinal distance of the renal artery. Calcified regions may also be found within the lumen of the arterial wall. Calcified regions may require high pressure (possibly 10-15 atmospheres or even 30 atmospheres) to fragment (fracture). Calcified regions may create variable distances from the ablation transducer or ablation electrode of the ablation catheter to the nerve. As a result, renal denervation may not be uniformly effective throughout the calcified region.

[0050] Referring to FIG. 1, this figure illustrates a perspective view of a generic ablation system according to one embodiment of the present disclosure. System 100 may be implemented in any one or more embodiments of the present disclosure, such as a catheter device, e.g., catheter device 200 (FIGS. 3A-7). System 100 includes a catheter 12 having a proximal end 20 and a distal end 22. Catheter 12 includes a catheter shaft 12a, an expandable member 14, e.g., a balloon or medical balloon, and a tip member 18. System 100 further includes an electrical coupler 31 positionable at the proximal end of catheter shaft 12a and configured to couple system 100 to a power source or generator (not shown). The generator may be a source of high-voltage pulses for the decalcification electrodes (FIGS. 4A-7). There may be a high-voltage switch (not shown) that can be set to control the duration of the pulses. The pulse duration depends on the surface area of ​​the decalcification electrode and is long enough to generate bubbles at the surface of the decalcification electrode, causing the plasma arc of current to jump over the bubbles, creating bubbles that rapidly expand and contract. This generates mechanical shock waves within the expandable member 14. These shock waves can be as short as a few microseconds. Shock waves are very large localized pressure fluctuations. Shock waves often have pressures of hundreds to thousands of bars and have a pulsed pressure profile. In some embodiments, the system 100 further includes a catheter device (e.g., catheter device 200 of FIGS. 3A-7). The catheter device can be comprised of at least one unit, each unit having at least one ablation device, such as a transducer 16 (e.g., at least one ultrasound transducer positionable within the expandable member 14).

[0051] As described below, system 100 may also include alternative components for generating gas bubbles and / or shock waves to break down calcifications. System 100 may include a laser source for generating and transmitting a laser to the treatment area. The laser may be a pulsed laser including pulses of light spaced apart in time. Energy from the laser may be absorbed by fluids in the treatment area, resulting in the formation of vapor microbubbles. The microbubbles collapse, generating mechanical shock waves that break down calcifications.

[0052] 1 , the expandable member 14 is positionable between the catheter shaft 12a and the tip member 18. The expandable member 14, e.g., a balloon, is further configured to be positioned along the distal end 22 of the catheter 12. The expandable member 14 includes at least one of a medically compatible balloon, a medically semi-compatible balloon, and a medically non-compatible balloon. The expandable member 14 is composed of at least one of the following materials: nylon, polyimide, polyimide film, thermoplastic elastomer (e.g., PEBAX® thermoplastic elastomer), medical-grade thermoplastic polyurethane elastomer (e.g., PELLETHANE® thermoplastic polyurethane elastomer), pellethane, isotane, any other suitable polymer, or any combination thereof.

[0053] 1, the catheter 12 has a handle 13 that can be positioned near or at the proximal end of the catheter shaft 12a. The system 100 includes at least one electrical coupler 31 configured to couple the catheter system 100 to at least one external electrical conductor (not shown), which is in electrical communication with external electronics (not shown). The at least one external electrical conductor can comprise at least one of at least one wire, at least one cable, and at least one flexible printed circuit (FPC).

[0054] Continuing with FIG. 1 , the catheter 12 has at least one lumen, e.g., at least one electrical lumen (not shown). Each of the at least one electrical lumen extends from the at least one electrical coupler 31 along the longitudinal length of the catheter shaft 12a toward the distal end of the catheter shaft 12a. Each of the at least one electrical lumen is configured to receive and hold at least one conductor carrier (not shown), which is configured to hold at least one electrical conductor. The at least one electrical conductor may be in electrical communication with external electronics via the at least one electrical coupler 31 and the at least one external electrical conductor. When an electrical conductor carrier holds multiple electrical conductors, the electrical conductor carrier has an electrically insulating jacket (not shown). When the electrical conductor is comprised of a single electrical conductor, the electrical conductor includes an electrical insulator disposed thereon, whereby the electrical insulator functions as the electrical conductor carrier.

[0055] Continuing with FIG. 1 , the handle 13 optionally includes at least one fluid port (e.g., fluid ports 34a, 34b) for connecting the catheter 12 to a conduit (not shown). A suitable conduit may comprise at least one of a tube, a hose, and any hollow member. The conduit facilitates fluid communication between the at least one fluid port and a fluid source (not shown). The fluid source may comprise at least one of a pump, a tank, a reservoir, and a container. The catheter shaft 12a may include at least one fluid lumen (not shown). Each of the at least one fluid lumen facilitates fluid communication with each of the at least one fluid port and may be positioned along the length of the catheter shaft 12a toward the distal end of the catheter shaft 12a. Additionally, some lumens may be in fluid communication with a corresponding pump or other fluid transmission device (not shown) via ports 34a, 34b, such as via a luer fitting or other standard or non-standard coupling.

[0056] 1 , the handle 13 optionally includes at least one guidewire port (not shown) configured to receive at least one guidewire (not shown). The catheter shaft 12a optionally includes at least one guidewire lumen (not shown) configured to accommodate and retain the at least one guidewire. The at least one guidewire lumen extends along the length of the catheter shaft 12a toward the distal end 22 of the catheter shaft 12a. Each of the at least one guidewire lumen facilitates fluid communication with each of the at least one guidewire ports, and each of the at least one guidewire inserted into each of the at least one guidewire ports can be received within each of the at least one guidewire lumen.

[0057] 1 , in some embodiments, each of the at least one lumen is operable as at least one of a fluid lumen, a fluid conduit, a cable lumen, an electrical cable passageway, a guidewire lumen, etc. For example, the cable lumen is shaped, sized, and otherwise configured to receive an electrical cable (not shown), such as a coaxial cable, a wire, any other electrical conductor, etc. The electrical cable is configured to allow electrodes of an ultrasound transducer of system 100 to be selectively activated to radiate acoustic energy at a target in a subject.

[0058] 1 , in some embodiments, the fluid lumens are configured to transmit cooling fluid (e.g., water, saline, and any other cooling liquid or gas) to and from the expandable member 14 disposed at the distal end 22 of the catheter shaft 12a. In some embodiments, the catheter shaft 12a has at least two fluid lumens, one for delivering cooling fluid to the expandable member 14 and one for returning cooling fluid from the expandable member 14. However, the catheter shaft 12a may have at least one fluid lumen, as desired or required. The at least one fluid lumen may be located along any portion of the catheter shaft 12a, e.g., along the centerline or offset from the centerline, and / or may include any cross-sectional shape, e.g., circular, elliptical, rectangular or other polygonal, irregular, etc., as desired or required.

[0059] In some embodiments, the catheter device 200 includes a tissue collection unit (not shown) or a scraping unit (not shown). The scraping unit is located adjacent to the tissue collection unit, allowing calcified debris (also referred to as calcified dust or calcified fragments) to be scraped off and collected by the tissue collection unit, e.g., after or as an alternative to cavitation. In certain embodiments, for example, where the calcified condition is located within the lumen of the blood vessel itself, cavitation may not be necessary, and calcium may be scraped or otherwise removed from the vessel wall without the need for cavitation. In certain embodiments, calcified conditions within the intima and / or lumen of the vessel may be cavitated using a shockwave source, and calcified debris, e.g., cracked calcifications, may be removed using the tissue collection unit and / or the scraping unit and / or the vacuum catheter. In one embodiment, the scraping unit may be located between the tip member 18 and the expandable member 14. In another embodiment, the scraping unit can be located at the proximal end of the expandable member 14. The scraping unit can be a scoop-shaped cutting blade attached to the catheter device. In another embodiment, the scraping unit can be a rotary tissue perforator. The tissue collection unit can have an opening through which the calcified fragments / debris enter for removal from the body cavity by suction, such as a vacuum, or natural force. In one embodiment, the tissue collection unit is located posterior to the scraping unit, allowing the scraped calcified debris to flow into the collection unit after being scraped from the body cavity.

[0060] Referring to FIG. 2, this figure illustrates a detailed cutaway cross-sectional view of the distal end of a typical catheter system 100 including an expandable member 14, as shown in FIG. 1, according to one embodiment of the present disclosure. Alternatively, rather than system 100, device 200 (FIGS. 3-7) includes the expandable member 14. As desired or required by a given implementation, at least one unit including at least one transducer 16 (e.g., at least one ultrasound transducer) is configured to be positionable at at least one location, for example, within the expandable member 14 (e.g., within the internal cavity 14a of the expandable member 14) or external to the expandable member 14. In some embodiments, the outer wall of the expandable member 14, when expanded, is generally parallel to the wall of the at least one transducer 16, where, for example, the at least one transducer 16 is cylindrical in shape. When inflated, the expandable member 14 at least partially surrounds the transducer 16 and at least partially contacts the adjacent wall 37 of a body vessel, such as a blood vessel. The adjacent wall 37 of the blood vessel may be disposed adjacent to the nerve tissue 15 .

[0061] 2 , in some embodiments, one or more portions of the expandable member 14 are configured to avoid contact with the adjacent wall 37 of the blood vessel when expanded. In some embodiments, the transducer 16 is liquid-cooled along both its outer and inner electrodes, allowing coolant entering the expandable member 14 to pass through both the outer and inner surfaces of the transducer 16 and transfer heat outward from the transducer 16. In some embodiments, the coolant or other fluid directly contacts the outer and inner surfaces of the transducer 16. The transducer 16 may include a reflective interface (not shown), for example, along its inner surface, which may allow ultrasonic energy generated by the inner electrode to be reflected radially along the inner surface of, for example, a cylindrical transducer.

[0062] Referring to Figure 3, a cutaway perspective view, catheter device 200 is comprised of multiple units 401a, 401b. In some embodiments, catheter device 200 is comprised of three or more units. In certain embodiments, multiple units 401a, 401b include a cavitation transducer unit 401a and an ablation transducer unit 401b at distal end 22 (Figure 1) of catheter shaft 12a. Each of cavitation transducer unit 401a and ablation transducer unit 401b includes a transducer 16. Alternatively, cavitation and ablation may be provided using separate catheters, with one catheter including cavitation transducer unit 401a and another including ablation transducer unit 401b. In certain embodiments having both the cavitation transducer unit 401a and the ablation transducer unit 401b on a single catheter 200, the cavitation transducer unit 401a is located on the catheter 200 proximal to the ablation transducer unit 401b. After the cavitation procedure, the catheter 200 can be pulled proximal to the decalcified region and the ablation procedure can be performed. Moving the catheter from distal to proximal (i.e., from the kidney toward the aorta) can help prevent / minimize mechanical trauma to the renal artery. In certain embodiments, an imaging device is used to determine whether the cavitation procedure has sufficiently decalcified the region, e.g., whether the calcium score has been sufficiently reduced (e.g., whether the calcium score after cavitation is 50 or less), and / or whether the media-adventitia boundary is visible using intravascular ultrasound imaging, e.g., at a frequency of 20-50 MHz (e.g., 40 MHz).

[0063] Alternatively, the cavitation transducer unit 401 a can be positioned distal to the ablation transducer unit 401 b on the catheter 200, and the catheter can be pushed from proximal to distal. This can allow for ablation of proportionately more afferent renal nerves, which may be responsible for transmitting messages to the brain regarding pain during the ablation procedure. By ablating these nerves first, further ablations closer to the kidney can be perceived by the patient as less painful.

[0064] The cavitation transducer unit 401a and the ablation transducer unit 401b may be optimized for their respective functions. The wavelength and power of the cavitation transducer unit 401a may be optimized to generate cavitations in the blood that preferentially destroy calcified tissue in the lumen, intima, and / or media of the blood vessel based on the inelasticity of the calcified region, while sparing healthy, elastic vascular tissue. In certain embodiments, the cavitation transducer unit 401a has an operating frequency of 400 kHz to 3 MHz, e.g., 1 to 2 MHz or less than 3 MHz. The cavitation transducer unit 401a may have an operating frequency of 50 W / cm to generate shock waves at the calcifications to fragment them. 2 For example, 2 to 20 W / cm 2 Ultrasound may be delivered at a time-averaged intensity output of 100 Hz to 100 Hz. In certain embodiments, 10 to 100 short acoustic pulses of 10 μsec to 1 ms duration, each separated by 20 ms to 2 s (pulse repetition rate of 0.5 Hz to 50 Hz), are generated until the calcification is fragmented. In some embodiments, a vacuum catheter is used to remove debris.

[0065] In some embodiments, the ablation transducer unit 401b is optimized to ablate nerves, while the balloon 14 (FIG. 2) helps protect non-target tissue within the vessel wall from thermal damage (e.g., stenosis). In certain embodiments, during an ablation treatment, fluid flows through the balloon 14 at a rate of 10 ml / min to 45 ml / min. In certain embodiments, the balloon 14 is compliant. The inflation pressure can correspond to the flow rate of fluid circulating through the interior of the balloon 14. For example, fluid can be circulated at a flow rate of 15 to 35 ml / min (e.g., 25 to 35 ml / min) to inflate the balloon 14 to an inflation pressure of 10 psi, resulting in a first inflation diameter of 3 to 6 mm (e.g., 3.5 to 6 mm). When the compliant balloon 14 is inflated to a second inflation pressure of 30 psi, the balloon has a second inflation diameter of 8 mm to 9 mm. The inflation pressure can correspond to the flow rate of fluid circulated through the interior of balloon 14 between the inlet channel and the outlet channel (not shown). For example, fluid can be circulated at a flow rate of 35-50 mL / min (e.g., 40-45 mL / min) to inflate balloon 14 to an inflation pressure of 30 psi, resulting in a second inflated diameter of 8-9 mm. For example, the balloon can have a second inflated diameter of 8 mm at a second inflation pressure of 30 psi and a flow rate of 40-45 mL / min.

[0066] In certain embodiments, during calcium cavitation, the flow is stagnant or at a low rate, e.g., less than 2 ml / min. Thus, during calcium cavitation, the flow may be lower compared to during ablation therapy.

[0067] In certain embodiments, the ablation transducer unit 401b emits unfocused ultrasonic energy. As used herein, the term "unfocused" refers to an ultrasonic energy beam that does not increase in intensity in the direction of propagation of the beam away from the transducer. In some embodiments, the ablation transducer unit 401b is an air-backed ablation transducer. In some embodiments, the ablation transducer unit 401b is a water-backed ablation transducer. In certain embodiments, the ablation transducer unit 401b has an operating frequency between 7 MHz and 20 MHz, e.g., between 8.5 MHz and 15 MHz, or between 8.5 MHz and 9.5 MHz, or between 8.5 MHz and 13 MHz. In one embodiment, the ablation transducer unit 401b may be energized for a period of 5 seconds to 20 seconds. In one embodiment, the ablation transducer unit 401b may be energized for a period of 6 seconds to 10 seconds. In one embodiment, the ablation transducer unit 401b may be energized for a period of approximately 7 seconds. The amount of acoustic energy emitted by the ablation transducer unit 401b and entering the target tissue surrounding the body cavity in which the ablation transducer unit 401b is located is equal to the duration (T) for which the acoustic signal is emitted multiplied by the acoustic entry power. The acoustic entry power may be based on (and may depend on) various factors, including the output power level setting of the ablation unit excitation source (e.g., 1518a), the power efficiency of the system (including its components), the frequency of the acoustic signal emitted by the ablation transducer unit 401b, the duration (T) of the acoustic signal emitted by the ultrasound transducer, and the amount of attenuation caused by the medium between the ultrasound transducer and the body cavity wall.When the ablation transducer unit 401b is disposed within a balloon 14 through which a cooling fluid (e.g., water, sterile water, saline, or D5W) is circulated, the cooling fluid and the balloon material (and possibly folds in the balloon material) are the medium between the ablation transducer unit 401b and the wall of the body cavity. When the catheter is balloonless (i.e., has no balloon), blood passing through the body cavity is the medium between the ultrasound transducer and the wall of the body cavity. The catheter may include a centering mechanism configured to generally center the ultrasound transducer within the body cavity. In certain embodiments, the centering mechanism is provided by a compliant balloon. Alternatively or additionally, the centering mechanism may include, but is not limited to, one or more flexible, acoustically transparent baskets attached to the catheter shaft (e.g., 212) or other structures such as a helical spring.

[0068] In other words, the total energy (E eff ) is the acoustic ingress power (E O ) multiplied by the fraction (e.g., percent) of energy used for ablation at the target region, where the fraction (e.g., percent) of energy used for ablation at the target region depends on the degree of attenuation caused by the medium between the ultrasound transducer and the cavity wall. More specifically, E eff =β E O =(1-e -2αfd )P O T, a is the attenuation coefficient (neper / MHz / cm), β is the fraction (e.g., percent) of energy used for ablation in the target region, f is the acoustic frequency, and d is the desired outer lesion boundary (also called lesion depth). The total energy absorbed in the target region (E eff ) is the effective energy (E eff ) may also be called.

[0069] Acoustic approach power (E O ) is the total acoustic power delivered to the patient's tissue, such as through the balloon wall. As the acoustic waves propagate through the patient's tissue, the acoustic energy is attenuated and converted to heat, resulting in a temperature rise in the tissue. The acoustic penetration power (E O Only a portion (β) (e.g., a percentage) of the effective energy (E) is absorbed in the target area, while the remaining portion travels further and is absorbed in non-targeted patient tissue beyond the target area. As a reminder, energy is the product of power and time (duration). Therefore, the effective energy (E) eff ) (the fraction of acoustic energy absorbed by the target region) is a function of β and the acoustic ingress power (E O ), i.e., as stated above, E eff =β E O The value of β may depend on a variety of different parameters, including but not limited to the acoustic frequency f and the desired lesion depth d.

[0070] To maintain the same lesion boundary d (lesion depth), E eff must be kept constant. This statement applies when the treatment time (duration) T does not change significantly and when the effects of thermal conduction do not change significantly. It is noted that if the treatment time (duration) T is increased significantly to compensate for heat loss due to thermal conduction, more total or effective energy is generally required. Table 3 below shows the acoustic penetration power at various different ultrasound frequencies, assuming a desired lesion depth (d) of 4 mm and a treatment time (T) of 7 seconds. [Table 3] TIFF2025534449000002.tif33155

[0071] Table 4 below shows the acoustic entry power at various different ultrasound frequencies, assuming a desired lesion depth (d) of 6 mm and a treatment time (T) of 7 seconds. As can be seen from a comparison of Table 4 and Table 3, a higher acoustic entry power of 35.6 W should be used when it is desired to create a lesion depth of 6 mm (more distal, i.e., closer to the kidney, may be appropriate), compared to an acoustic entry power of 26.0 W that may be used if the desired lesion depth is 4 mm. [Table 4] TIFF2025534449000003.tif33155

[0072] Table 5 below shows the acoustic approach power at various different ultrasound frequencies, assuming a desired lesion depth (d) of 6 mm and a treatment time (T) of 10 seconds. As can be seen from a comparison of Table 5 and Table 4, a lower acoustic approach power of 24.2 W should be used when it is desired to create a lesion depth of 6 mm when the acoustic approach power is delivered for a duration of 10 seconds, compared to the acoustic approach power of 36.4 W that can be delivered for a shorter duration of 7 seconds to create the same desired lesion depth of 6 mm. [Table 5] TIFF2025534449000004.tif33155

[0073] In certain such embodiments, the frequency of the acoustic energy is about 9 MHz, the duration of the acoustic power delivery is about 7 seconds, and the acoustic ingress power is about 34.6 W.

[0074] In some embodiments, calcium may be present in the media of a blood vessel, making it difficult to adequately fragment and / or remove. In some embodiments, decalcification is omitted despite the presence of calcification. Calcification may be detected by the user and / or processor based on calcium scores and / or an indication that the media-adventitial boundary is not visible or unclear. To compensate for the calcification, the generator may increase (lengthen) the ablation duration, increase the cooling fluid flow rate, and / or decrease the cooling fluid temperature while decreasing the acoustic inlet power. For example, the acoustic inlet power may be reduced by 30% from the default setting (i.e., the setting used in the absence of calcification and / or a setting not specifically configured to compensate for calcification), while the treatment duration (T) is increased by 35-45% from the default setting. In some embodiments, the flow rate is increased, for example, by 5% or more from the default setting. The increased flow rate removes power from the system. This power needs to be compensated for by the system by increasing the treatment time (T) disproportionately (ie, more) relative to the acoustic ingress power.

[0075] Alternatively or additionally, regions free of calcification or regions less severely affected by calcification may be targeted (if available). For example, regions with lower calcium scores (e.g., calcium scores between 0 and 50) may be prioritized over regions with higher calcium scores (e.g., calcium scores above 50). In one embodiment, the renal artery may be imaged prior to the ablation procedure to provide a calcium score map, i.e., calcium scores at multiple locations along the renal artery. In one embodiment, the renal artery may be imaged concurrently with, during, and / or after the ablation procedure, e.g., using an imaging transducer on the treatment catheter 200, to provide a calcium score map. The map may be provided to the physician / user via user interface 1516 (FIG. 15).

[0076] In certain embodiments where a secondary artery, branch, or vein is non-calcified, less calcified, or has more easily treatable calcification (hence, is a less diseased vessel) and runs parallel to a calcified vessel, nerves extending outside the calcified vessel can be targeted by sonicating for a longer time in the less diseased vessel, and the length (depth) of the lesion can be increased to reach those nerves. For example, as shown in FIG. 13, an accessory renal artery 1100b runs parallel to the main renal artery 1100a. For example, if the calcification score at one or more target locations along the main renal artery 1100a is higher than the calcification score at one or more target locations along the accessory artery 1100b (after a decalcification / cavitation procedure or if a decalcification procedure is not performed), an ablation procedure can be performed from within the accessory artery 1100b, which has a lower calcification score. On the other hand, if the calcification score at one or more target locations along the main renal artery 1100a is lower than the calcification score at one or more target locations along the accessory artery 1100b (after a decalcification / cavitation procedure or if no decalcification procedure is performed), an ablation procedure can be performed from within the main renal artery 1100a where the calcification score is lower. The ablation lesion 1103 can extend from approximately 1 mm outside the accessory artery 1100b to approximately 1 mm outside the main renal artery 1100a. In certain embodiments, this can be accomplished by creating a longer-than-average ablation lesion between the two vessels. For example, the ablation lesion is approximately 5 mm long on average. To extend the ablation lesion from one vessel to another, a 7 mm ablation lesion can be created. For example, the flow rate and acoustic penetration power for treatment in the less diseased vessel may be held constant while the treatment duration (T) is increased from 7 seconds to 10 seconds to create a lesion that reaches the outer wall of the parallel more diseased vessel. In another example, the treatment duration (T) for treatment in the less diseased vessel may be held constant while the acoustic penetration power is increased to create a lesion that reaches the outer wall of the parallel more diseased vessel.In another example, the acoustic ingress power for treatment in the less diseased vessel may be reduced and the treatment duration (T) may be increased to create a lesion that reaches the outer wall of the parallel, more diseased vessel, while still compensating for calcification in the less diseased vessel. As shown in FIG. 16 , an ablation transducer unit 401b with multiple focal depths (e.g., with different wall thicknesses activated at different optimal frequencies) may be used. In other embodiments, an array of transducers with different optimized frequencies may be used to achieve an ablation lesion that reaches the more diseased vessel while simultaneously ablating the less diseased vessel from within the lumen of the less diseased vessel. While the ablation lesion between two vessels may be longer than the average ablation depth, the ablation transducer unit 401b may target an average or near-average ablation depth in other target areas around the less diseased vessel / vessel with the lower calcification score.

[0077] A transducer with multiple focal depths (e.g., with different wall thicknesses activated at different optimal frequencies) or an array of transducers with different optimized frequencies can be rotated to focus on a target to ablate nerves that run non-parallel (e.g., at an angle) from less diseased vessels to more diseased vessels. As a result of the varying thickness of the ablation transducer unit 401b, the direction in which the acoustic signal travels from the ablation transducer unit 401b changes in response to changes in the frequency of the applied alternating current. This change in direction results from the different efficiencies of the ablation transducer unit 401b at different applied alternating current frequencies. In general, the thickness of the portion of the ablation transducer unit 401b that generates the acoustic signal is inversely proportional to the frequency of the alternating current applied to the ablation transducer unit 401b. As a result, the frequency of the applied alternating current can be adjusted, the portion of the ablation transducer unit 401b that generates the acoustic signal can be adjusted, and the direction in which the acoustic signal travels away from the ablation transducer unit 401b can be adjusted accordingly. In certain embodiments, portions (thicker portions) of the ablation transducer unit 401b that activate at lower frequencies are used to target deeper regions (e.g., 4 mm to 10 mm from the lumen of the blood vessel). Portions (thinner portions) of the ablation transducer unit 401b that activate at higher frequencies are used to target closer regions (e.g., 0.5 mm to 4 mm from the lumen of the blood vessel).

[0078] Figure 16 has an arrow A representing the direction in which the acoustic signal travels from the ablation transducer unit 401b. The direction in which the acoustic signal travels away from the ablation transducer unit 401b may be represented by an angle θ, where θ is measured relative to a measurement line, such as measurement line S in Figure 16. Examples of suitable measurement lines include, but are not limited to, a line of symmetry of the outer surface of the transducer. In some cases, the measurement line extends through the center of the outer surface of the transducer, the center of gravity of the outer surface of the transducer, and / or the center of gravity of the transducer.

[0079] 16 also includes a graph of an exemplary power distribution of acoustic signal A. The power distribution shows the power levels of acoustic signal A from angle θ denoted by R to angle θ denoted by Q. The angle θ (representative angle) associated with acoustic signal A may be selected to represent the direction in which acoustic signal A moves away from the transducer. For example, the representative angle associated with acoustic signal A may be located at the maximum of the power distribution, the average value of the power distribution over the angle range θ, or the average value of the power distribution weighted by power and obtained over angle ranges of 30°, 90°, or 180°.

[0080] To illustrate the steerable nature of the acoustic signals, FIG. 16 also includes arrows B and C. Arrows A, B, and C each represent a different acoustic signal direction away from the ablation transducer unit 401b. The acoustic signal represented by arrow A occurs when a higher AC frequency ("first frequency") than the acoustic signal represented by arrow B is applied to the ablation transducer unit 401b. The acoustic signal represented by arrow B occurs when a higher AC frequency ("second frequency") than the acoustic signal represented by arrow C is applied to the ablation transducer unit 401b. The acoustic signal represented by arrow C occurs when a lower AC frequency ("third frequency") than the acoustic signal represented by arrow B or arrow A is applied to the ablation transducer unit 401b. Thus, different angles are associated with different AC frequency levels.

[0081] Measurement line S in FIG. 16 is a line of symmetry. In one embodiment, a first region of ablation transducer unit 401b on one side of the line of symmetry has the same thickness as a second region of the transducer on the other side of the line of symmetry. As a result, ablation transducer unit 401b can simultaneously output identical acoustic signals from both regions of the ablation transducer unit 401b. For example, the transducer of FIG. 16 can simultaneously output acoustic signals A and A' at equal powers at a first frequency, acoustic signals B and B' at equal powers at a second frequency, or acoustic signals C and C' at equal powers at a third frequency. As a result, a single AC frequency level can be associated with multiple angles θ.

[0082] The ablation transducer unit 401b of Figure 16 can be modified so that when the ablation transducer unit 401b has multiple different regions of the same thickness, the region from which the acoustic signal is output can be selected. Figures 12A-17 and paragraphs

[0167] -

[0226] of U.S. patent application Ser. No. 18 / 451,044, filed Aug. 16, 2023, which are incorporated by reference, disclose further ablation transducer units 401b capable of targeting tissue in specific directions.

[0083] Referring to FIG. 3, as the length of the transducer 16 decreases, the number of lobes corresponding to the output from the transducer 16 may also decrease. For example, a transducer 16 having a length ranging from about 2.5 mm to about 3 mm and operating at a frequency of about 9 MHz may generate an output corresponding to a single lobe. In certain embodiments, each of the transducers 16 is optimized for ablation as described herein, and the transducer cavitation unit 401a is replaced with a second transducer ablation unit 401b. In this example, one or more electrode cavitation units on the expandable member 14 can be positioned between the lobes corresponding to the output from different transducers 16. For example, one or more electrode cavitation units on the expandable member 14 can be positioned on a component of the catheter 12 located between adjacent transducers 16.

[0084] The device 200 optionally includes at least one flexible feature 402, such as a bridge portion 113 having an increased flexibility region that does not extend below the transducers 16. Alternatively, each bridge portion 113 disposed within the catheter 12 may include at least one increased flexibility region L that extends between two transducers 16 and below at least one transducer 16. S Includes:

[0085] 3, a fluid lumen 40 is disposed relative to the catheter shaft 12a. The fluid lumen 40 has a fluid port (not shown) that allows fluid to be exchanged between the fluid lumen 40 and the interior of the expandable member 14. As a result, the fluid lumen 40 and the interior of the expandable member 14 are in fluid communication. Thus, the fluid lumen 40 provides fluid communication between the interior of the expandable member 14 and one of several conduits (not shown). The catheter system 100 (FIG. 1) can be configured to pump fluid into the interior of the expandable member 14 through the fluid lumen 40 and / or to withdraw fluid from the interior of the expandable member 14 through the fluid lumen 40. As a result, the fluid can be used to inflate and deflate the expandable member 14. Alternatively, the catheter shaft 12a can have several fluid lumens 40, each opening into the interior of the expandable member 14. The catheter system 100 can be configured to pump fluid into the interior of the expandable member 14 through a first selection of the plurality of fluid lumens 40 and to withdraw fluid from the interior of the expandable member 14 through a second selection of the plurality of fluid lumens 40. The relative flow of fluid into and out of the expandable member 14 can be varied to inflate the expandable member 14, to deflate the expandable member 14, or to maintain a steady level of inflation of the expandable member 14.

[0086] 3, the catheter shaft 12a includes an electrical lumen (not shown). The electrical lumen has a first conductor carrier (not shown) and a second conductor carrier. The first conductor carrier extends through the wall of the catheter shaft 12a into the interior of the expandable member 14. The first conductor carrier includes a first electrical conductor (not shown) configured to couple with the backing member 42. The conductive backing member 42 and the conductive spacing element provide electrical communication between the inner electrode 36 and the first electrical conductor. Furthermore, the first electrical conductor is in electrical communication with electronics (not shown) via one of an electrical coupling (not shown) and an external electrical conductor.

[0087] 3, at least a portion of the bridge portion 113 of the backing member 42 extending between adjacent transducers 16 may include one or more regions of increased flexibility 114. The one or more regions of increased flexibility 114 may be selected to increase the flexibility of the backing member 42 and, correspondingly, the catheter 12. Suitable regions of increased flexibility 114 include, but are not limited to, a plurality of openings through the wall of the backing member 42 arranged in a pattern, such as a backing member 42 having a grid pattern.

[0088] 3 , the enhanced flexibility region 114 includes an opening 116 extending through the wall of the backing member 42. The opening 116 spirals around the longitudinal axis of the backing member 42 for the portion of the backing member 42 located between adjacent transducer assemblies 32. As a result, at least one enhanced flexibility region 114 of the backing member 42 has a helical or substantially helical configuration for a portion of the longitudinal length of the backing member 42. In some cases, the enhanced flexibility region 114 does not extend into any of the multiple transducer assemblies 32 within the expandable member 14.

[0089] 3, the helical rate may be measured in degrees that the helix turns about the longitudinal axis of the backing member 42 per unit length of the longitudinal axis. The helical rate may determine the degree of flexibility of the enhanced flexibility region 114 of the backing member 42. For example, increasing the helical rate may provide more flexibility to the backing member 42, while decreasing the helical rate may provide more stiffness to the backing member 42. Suitable helical rates (pitch numbers) include, but are not limited to, rates of about 0° / mm or greater, and may span an angular range of about 360° or greater, or may span an angular range of greater than 720°.

[0090] 3, the connecting portion 96 of the backing member 42 extends from the transducer 16 to at least a portion of the catheter shaft 12a of the catheter 12. Although the connecting portion 96 is shown as excluding one or more regions of increased flexibility 114, the connecting portion 96 may optionally include one or more regions of increased flexibility 114. Although the catheter device 200 is shown as including two units 401a, 401b disposed within a single expandable member 14, such as a balloon, the expandable member 14 may contain more than two units 401, each including a transducer 16, for example.

[0091] 3 , when the catheter device 200 includes at least three units 401 (e.g., each including three transducers 16), the backing member 42 includes a plurality of bridge portions 113. At least one bridge portion 113 of the plurality of bridge portions 113 includes at least one region of increased flexibility 114. In some cases, the number of transducer assemblies 32 (e.g., each including a transducer 16 disposed within an expandable member 14) ranges from about 2 to about 20. In one example suitable for use in treating renal arteries, the number of units 401 (e.g., each including a transducer 16 disposed within an expandable member 14) illustratively ranges from about 2 to about 5.

[0092] 3, although electrodes are not shown as disposed on the expandable member 14, the expandable member 14 can be configured to selectively accommodate at least two electrodes. When the expandable member 14 selectively accommodates at least two electrodes, a second conductor carrier provides electrical communication between any two electrodes and external electronics. When the expandable member 14 selectively accommodates at least two electrodes, at least some of the transducers 16 are associated with different selections of the at least two electrodes.

[0093] Additionally, the external electronics can independently activate each of the at least two electrode selections such that the external electronics can deliver ultrasonic energy from a selection of the expandable member 14 and electromagnetic energy from at least two electrodes associated with at least two portions of the expandable member 14 at that selection of the expandable member 14.

[0094] The cavitation transducer unit 401a and the ablation transducer unit 401b can be configured in many shapes, such as cylindrical (eg, tubular) or flat (eg, flat rectangular or disc-shaped).

[0095] 4A-5, these schematic diagrams illustrate various embodiments of a catheter device 200 for preparing and treating an anatomical structure, according to one embodiment of the present disclosure. Referring to FIG. 5, the catheter device 200 includes multiple units 600. As shown in FIGS. 4A-4D, the multiple units may include one or more ablation and / or decalcification transducers 500, one or more decalcification and / or ablation electrodes 510, and one or more imaging transducers 520. In certain embodiments, the catheter 200 may be configured for chemical ablation. In certain embodiments, the catheter 200 may be configured to ablate renal fibers innervating the kidney using direct current heating, cryogenics, intravascular or extracorporeal focused ultrasound, microwave heating, laser heating, induction heating, radiation, or mechanical methods. 4A-4D, multiple electrodes 510 and one or more imaging transducers 520 may be interspersed along the catheter shaft 12a among multiple transducers 500 in a variety of non-limiting configurations. In one embodiment, an imaging transducer 520 having a frequency in the range of 30-45 MHz is used to provide high resolution intravascular images.

[0096] In some embodiments, catheter 200 includes multiple units 600. The multiple units 600 include a decalcification unit configured to prepare at least one anatomical structure by at least partially decalcifying the at least one anatomical structure, and an ablation unit configured to treat the at least one anatomical structure by ablating at least one nerve associated with the at least one anatomical structure. At least one of the multiple units may be configured to be disposed within catheter 12. The length of the decalcification or ablation transducer 500 depends on various factors, such as the treatment site. However, in some embodiments, the length of the cylindrical decalcification or ablation transducer 500 may be between 0.9 mm and 30 mm. In some embodiments, the length of each cylindrical decalcification or ablation transducer 500 may be between 1 mm and 10 mm. In some embodiments, the length of each cylindrical decalcification or ablation transducer 500 may be between 5 mm and 6 mm. In some embodiments, the length of each demineralization or ablation transducer 500 may be between 0.5 and 2 mm.

[0097] In certain embodiments described herein, the demineralization or ablation transducer 500 may have an outer diameter of approximately 1.3 mm and an operating frequency of 11-15 MHz. The ultrasound transducer 500 may be configured to deliver sufficient acoustic energy during sonication to, for example, thermally induce modulation of nerve fibers surrounding blood vessels sufficient to improve measurable physiological parameters corresponding to a diagnosed patient condition. In one embodiment, the generator may be configured to energize the demineralization or ablation transducer 500 for a time period between 5 and 20 seconds, at a frequency between 11 and 15 MHz, or under both conditions. In one embodiment, the generator may be configured to energize the demineralization or ablation transducer 500 for a time period between 6 and 10 seconds, at a frequency between 12 and 14 MHz, or under both conditions. In one embodiment, the generator may be configured to energize the demineralization or ablation transducer 500 for a time period of about 7 seconds, at a frequency of about 13 MHz, or under both of these conditions. The demineralization or ablation transducer 500 may be energized by the generator to raise the temperature of the demineralization or ablation transducer 500 by up to 50°C. The demineralization or ablation transducer 500 may be energized by the generator to raise the average surface acoustic intensity to between 20 and 150 W / cm. 2In one embodiment, the demineralization or ablation transducer 500 may be energized for a time period between 5 and 20 seconds at a frequency between 11 and 15 MHz, or both. In one embodiment, the piezoelectric component may be energized for a time period between 6 and 10 seconds at a frequency between 12 and 14 MHz, or both. In one embodiment, the piezoelectric component may be energized for a time period between about 7 seconds at a frequency of about 13 MHz, or both. In one embodiment, energizing the piezoelectric component may increase the temperature of the piezoelectric component by up to 50°C. In one embodiment, energizing the piezoelectric component may increase the average surface acoustic intensity by 20 to 150 W / cm. 2 At 15 MHz, most of the delivered energy is delivered to distances of 6 mm or less (65% compared to 46% at 9 MHz), improving the specificity and safety of energy targeting. Comparing the heating power profiles of demineralization or ablation transducers 500 operating at 12 MHz and 15 MHz, the 12 MHz transducer has higher heating power at distances less than about 6 mm and lower heating power at distances greater than about 6 mm.

[0098] The demineralization or ablation transducer 500 may be configured to resonate at a frequency between 200 kHz and 1 MHz. Optionally, the demineralization or ablation transducer 500 may be configured to resonate at a frequency between 500 kHz and 1 MHz. Alternatively, the demineralization or ablation transducer 500 may be configured to resonate at a frequency between 600 kHz and 900 kHz. In some embodiments, the ablation transducer 500 may be configured to resonate at a frequency between 10.0 and 90.0 Watts / cm. 2 It can be activated at an intensity of 100 Hz for a duration between 5 and 20 seconds at a frequency of 8.5 MHz to 15 MHz.

[0099] In certain embodiments, no demineralization is performed and / or the calcification is only partially fragmented. As provided herein according to certain embodiments, calcification can also be compensated for in other ways.

[0100] 4A, which illustrates in side view one embodiment of a catheter device 200 for preparing and treating an anatomical structure, such as a blood vessel, in accordance with one embodiment of the present disclosure. For example, the catheter device 200 includes one transducer 500 disposed about the catheter shaft 12a and two ablation electrodes 510 disposed about the catheter shaft 12a, one in front of and one behind the transducer 500.

[0101] 4B, this figure shows in side view another embodiment of a catheter device 200 for preparing and treating an anatomical structure, in accordance with an embodiment of the present disclosure. For example, the catheter device 200 includes two transducers 500 disposed about the catheter shaft 12a and three ablation electrodes 510 disposed about the catheter shaft 12a and separating the transducers 500. More specifically, a middle ablation electrode 510 may be disposed longitudinally between the two transducers 500, and a proximal ablation electrode 510 and a distal ablation electrode 510 may be disposed on either side (anterior and posterior) of the two transducers 500.

[0102] 4C, this figure shows in side view another embodiment of a catheter device 200 for preparing and treating an anatomical structure, in accordance with an embodiment of the present disclosure. For example, the catheter device 200 includes one transducer 500 disposed around the catheter shaft 12a, two ablation electrodes 510 disposed around the catheter shaft 12a, one in front of and one behind the transducer 500, and a step 521 connecting one of the two ablation electrodes 510 to the transducer 500.

[0103] 4D, which illustrates in side view another embodiment of a catheter device 200 for preparing and treating an anatomical structure, in accordance with an embodiment of the present disclosure. For example, the catheter device 200 includes two transducers 500 disposed about the catheter shaft 12a, three ablation electrodes 510 disposed about the catheter shaft 12a and separating the transducers 500, and an imaging transducer 520 disposed about the catheter shaft 12a and positioned between one of the ablation electrodes 510 and one of the two transducers 500.

[0104] Injecting bubbles adjacent to or into the calcified region may depend on the distance between the expandable member 14 (e.g., balloon) and the inner surface of the blood vessel (e.g., renal artery). A short distance between the balloon and the inner surface of the renal artery may increase the likelihood of cavitation bubbles forming near and / or at the inner surface of the renal artery. In other words, the deflated balloon is advanced and positioned adjacent to or at the calcified region, and then the balloon is expanded. The fluid within the balloon may act as a coupler to facilitate efficient energy transfer of the pressure wave from the decalcification electrode 510 into the surface of the blood vessel to reach the calcified region.

[0105] Referring to FIG. 5 , in system 100, the decalcification unit includes a decalcification transducer 500 and / or at least one of a plurality of decalcification electrodes 510. In some embodiments, the decalcification transducer is configured to perform decalcification in a frequency range of about 400 kHz to about 3 MHz. The plurality of decalcification electrodes are configured to generate bubbles in the liquid to generate cavitation, which affects the cavitation and thereby detaches calcifications from the at least one anatomical structure such that the at least one anatomical structure is not substantially damaged. The plurality of decalcification electrodes may be configured in an array. The plurality of decalcification electrodes includes at least one ring electrode. At least one electrode of the plurality of decalcification electrodes is configured to be disposed at at least one of the distal end of the catheter, proximal to at least one of the plurality of units 600, and on at least one of the plurality of units 600.

[0106] 5, in system 100, the ablation unit includes at least one of an ablation transducer 500 or a plurality of ablation electrodes 510. In some embodiments, the ablation transducer is configured to perform nerve ablation at a frequency of about 9 MHz. The plurality of ablation electrodes includes at least one radio frequency electrode configured to perform at least one of ablation, confirmation, or mapping of at least one nerve.

[0107] Continuing with reference to FIG. 5 , in some embodiments of the system 100, either the plurality of units 600 or the ablation unit further includes an imaging unit 602. The imaging unit 602 can have an imaging transducer (not shown) configured to identify calcification and / or the media-adventitial boundary. The imaging transducer is configured to image at a frequency of approximately 20 MHz to 60 MHz. In some embodiments, the imaging transducer is made of a piezoelectric material. Suitable materials for the imaging transducer include, but are not limited to, piezoelectric materials including piezoelectric ceramics, piezoelectric crystals, and piezoelectric polymers, and acoustic microelectromechanical system (MEMS) transducers such as piezoelectric micromachined ultrasound transducers (PMUTs) and capacitive micromachined ultrasound transducers (CMUTs). Examples of suitable piezoelectric materials include, but are not limited to, lead zirconate titanate (PZT), CMUTs, and PMUTs. The imaging transducer can have rectangular elements, the size of which is determined by the field of view. The transducer elements can be formed in an array, or the transducer can have a single element. The element can be positioned on a stepped portion of the transducer 500, or the element can be positioned remotely from the transducer 500. The array elements can have dimensions of 0.3 mm to 1.5 mm in height and 0.5 to 2 wavelengths in width. The array can be a single cylindrical array or a multi-row cylindrical array. A multi-row cylindrical array helps reduce the thickness of the image slice and achieve better contrast resolution. To reduce the number of cables, the elements can be individually controlled for transmission and reception by ASIC circuitry. The array size can be 8 to 256 elements. The imaging unit 403 can be positioned between the tip member 18 and the expandable member 14, or at the proximal end of the expandable member 14. The imaging depth can be up to 12 mm. The imaging unit 403 can be used to measure blood vessel size and image anatomical structures and pathologies, including blood vessel walls, plaque, calcifications, tissue layers, and nerves.

[0108] 5, the catheter device 200 further includes at least one of an expandable member 603 and a porous member (not shown). The expandable member 603 and at least one of the porous member are configured to be disposed at the distal end of the catheter 12, such as the distal end 22 of the catheter shaft 12a (FIG. 1). The expandable member 603 includes at least one of the following materials: polyamide, polyimide film, polyethylene terephthalate, thermoplastic elastomer, nylon, PEBAX® thermoplastic elastomer, medical-grade thermoplastic polyurethane elastomer, PELLETHANE® thermoplastic polyurethane elastomer, pellethane, isotane, and any other suitable polymer, or any combination thereof.

[0109] In certain embodiments, the catheter device 200 further comprises a flexibility feature 402 (FIG. 3A) configured to separate each unit 600 of the plurality of units 600 from the other units 600. At least a portion of the flexibility feature 402 is configured to be disposed within the catheter 12. The flexibility feature 402 is configured to facilitate navigation of the catheter 12 through at least one anatomical structure. The distance between any of the transducer 500 and the decalcification electrode 510 may aid in catheter flexibility due to the gap separating them from one another.

[0110] 5, in catheter device 200, each unit of multiple units 600 is configured to selectively operate in at least one of an independent mode (e.g., independent of the mode of any other unit of the one or more units) and a dependent mode (e.g., its function depends on the mode of the other units). Each unit of multiple units 600 is configured to selectively operate in at least one of an ultrasound mode of a focused mode and a non-focal mode. In some embodiments, first decalcification electrode 510 and second decalcification electrode 510 may be connected in series, such that activating first decalcification electrode 510 also activates second decalcification electrode 510. This may allow decalcification electrode 510 to generate up to two shock waves using one generator.

[0111] 5, in catheter device 200, the plurality of decalcification electrodes includes at least one shock wave electrode. The plurality of decalcification electrodes is constructed of at least one metal, such as stainless steel, tungsten, nickel, iron, steel, etc. Catheter device 200 is suitable for use in at least one anatomical structure including at least one vascular system, the at least one vascular system including at least one of a renal vein and a renal artery.

[0112] 5, a catheter device 200 is provided and configured to prepare a renal artery by at least partially removing calcium deposits from the arterial wall and / or ablating nerves to treat conditions such as hypertension, arrhythmia, heart failure, chronic kidney disease, atrial fibrillation, end-stage renal disease, myocardial infarction, anxiety, diabetes, metabolic disorders, insulin resistance, etc. Once the catheter device 200 is positioned near a calcified region, a user can begin with low-energy shock waves and increase the energy as needed to at least partially fragment the calcifications in the calcified region. The shock waves can be conducted through the fluid, through the expandable member 14, through the blood and the vessel wall, and to the calcified region, where the energy can destroy / fragment the calcified region without the expandable member 14 applying undue pressure to the vessel wall. In some embodiments, the catheter device 200 is further configured to identify calcified plaque before applying ablation therapy and to verify that the plaque has been removed, e.g., after applying ablation therapy. For example, such identification of calcified plaque and / or verification of plaque removal may be performed and / or confirmed using an imaging unit / device. Intravascular imaging may be performed using either intravascular ultrasound or optical coherence tomography to define calcium density and determine cavitation parameters. In one embodiment, the imaging unit / device used to identify the calcified region and the imaging unit / device used to determine whether the calcification has at least partially fragmented from the calcified region may be the same. In another embodiment, there may be separate imaging units / devices for identifying the calcified region and determining whether the calcification has at least partially fragmented from the calcified region.

[0113] In certain embodiments, a high-resolution intravascular ultrasound imaging transducer is used to detect the media-adventitial border. The one or more processors 1512 may determine that the media-adventitial border cannot be detected using intravascular ultrasound imaging because a user inputs this determination into the user interface 1516, or because the one or more processors 1512 are configured to determine that the image input to the controller 1500 does not contain a media-adventitial border (e.g., by using a machine learning model implemented by at least one of the one or more processors, or more generally, by using artificial intelligence). If the processor 1512 determines that the media-adventitial border cannot be detected, the processor 1512 may determine that cavitation / decalcification is necessary or that alternative treatment parameters (e.g., reduced power, longer duration, and / or increased flow rate) are warranted and / or an alternative treatment location is recommended. If the media-adventitial boundary is detectable using the imaging transducer, the processor may determine that the cavitation operation can be skipped, that ablation therapy can be initiated, and / or that the processor can save the location as a candidate for treatment. The user may input a calcium score at a given location based on an image provided by the intravascular ultrasound imaging transducer. Alternatively, the processor may be configured to determine the calcium score directly from the input image. Calcified regions / plaques should have (and be treated as) calcium scores in the low to moderate range. A low calcium score ranges from 0 to 50, and a moderate calcium score ranges from 50 to 1000. If the calcium score is lower, decalcification may be more effectively and / or more easily compensated for by modifying treatment parameters (e.g., reduced power, longer duration, and / or increased flow rate). This improves the effectiveness of ablation of one or more nerves within and / or surrounding the decalcified region of the blood vessel.If the calcium score is too high, the processor 1512 may determine whether treatment should be avoided at this location or whether an alternative treatment strategy should be implemented (e.g., ablation of an adjacent nerve from another location, as shown in Figures 13 and 14).

[0114] In certain embodiments, the imaging operation is omitted and the cavitation procedure is performed regardless of the calcium score of the location.

[0115] In one embodiment, impedance (e.g., blood impedance) is used to determine calcification without the need for an imaging device. If the impedance indicates calcification, the area is cavitated and the impedance is tested again to determine whether the target location has been sufficiently decalcified.

[0116] With further reference to FIG. 5 , system 100, in some embodiments, is configured to operate as an ultrasound renal denervation (uRDN) system. In some embodiments, catheter device 200 includes a first transducer unit 500, such as an ablation transducer unit, optimized for denervation therapy. In some embodiments, as shown in FIG. 4A , the ablation transducer unit includes an ablation transducer (e.g., a non-focusing transducer) operable at a frequency of about 9 MHz or a frequency in the range of about 6 MHz to about 20 MHz. In some embodiments, as shown in FIG. 4C , catheter device 200 further includes a second transducer unit 520, such as an imaging transducer unit, optimized for imaging. In one embodiment including an imaging transducer unit, the imaging transducer unit includes an imaging transducer including a piezoelectric material. The piezoelectric material may have an operating frequency of, for example, about 40 MHz. The operating frequency may be configured to identify calcium deposits, for example, by material selection.

[0117] In some embodiments, as shown in FIG. 4D, the catheter device 200 includes a third transducer unit 530, such as a demineralization transducer unit optimized for disrupting / fragmenting calcifications. The demineralization transducer unit includes a demineralization transducer (e.g., a focal transducer) having an operating frequency within a range of about 400 kHz to about 3 MHz. The operating frequency of the demineralization transducer is configured to induce cavitation and form microcracks within the calcified plaque without substantially damaging the arterial wall.

[0118] 4A-4D , in some embodiments, instead of or in addition to the third transducer unit 530, the catheter device 200 includes multiple electrodes. For example, at least one array of electrodes 510 (e.g., decalcification electrodes) is configured to generate steam bubbles and subsequent cavitation to crack calcifications from the arterial wall without substantially damaging the arterial wall. The decalcification electrodes are comprised of at least one ring electrode coupled to the catheter (e.g., distal and / or proximal sides of the transducer unit) and housed within an insulating balloon to protect the patient from electric shock. In one embodiment, the ring electrode is located on the transducer itself (e.g., on one or more operating or recessed portions of the transducer) to minimize the space occupied by the ring electrode. In another embodiment, one ring electrode can be located distally or proximally of the transducer unit 500, and another ring electrode can be located between two transducer units 500. 4B, the catheter device 200 includes two transducer units 500 optimized for nerve ablation therapy, with ring electrodes 510 that can be distributed in various configurations around the transducer units. In an alternative embodiment, the catheter device 200 includes a telescoping transducer that slides over the ring electrodes after applying shock therapy.

[0119] 5, in one embodiment, the catheter device 200 includes a set of treatment verification / neural mapping electrodes (e.g., attached to the balloon), such as neural mapping electrodes, which may be located elsewhere, may be constructed of ultrasound transparent material, and may be positioned on the catheter so as not to interfere with the sonication process.

[0120] Continuing with reference to FIG. 5, in one embodiment, an RF ablation electrode is provided in place of the ablation transducer. The RF ablation electrode is operable to perform treatment confirmation / neural mapping. The RF ablation electrode can be positioned proximal and / or distal to the insulating balloon and / or attached to the balloon surface. In one embodiment, a distal balloon or basket prevents emboli from migrating into the renal artery and / or distal branches of the kidney. The captured emboli can then be removed by suction toward the proximal end.

[0121] Referring to Figure 6, a flow diagram illustrates a method 700 of manufacturing a catheter device 200 for preparing and treating at least one anatomical structure according to one embodiment of the present disclosure. The method 700 comprises providing a plurality of units 600, including providing a decalcification unit configured to prepare at least one anatomical structure by decalcifying the at least one anatomical structure, providing an ablation unit configured to treat the at least one anatomical structure by ablating at least one nerve associated with the at least one anatomical structure, as depicted at block 710, and providing an imaging unit configured to detect calcification, as depicted at block 720. At least one of the plurality of units is configured to be disposed within a catheter.

[0122] Continuing with FIG. 6 , in method 700, providing a demineralization unit (block 710) includes providing at least one of a demineralization transducer and a plurality of demineralization electrodes. Method 700 further includes configuring the demineralization transducer to perform demineralization in a frequency range of about 400 kHz to about 3 MHz. Method 700 further includes configuring the plurality of demineralization electrodes to generate gas bubbles in a liquid to generate cavitation, thereby causing the cavitation to detach calcifications from the at least one anatomical structure without substantially damaging the at least one anatomical structure. Method 700 further includes configuring the plurality of demineralization electrodes in an array. In some embodiments, providing the plurality of demineralization electrodes includes providing at least one ring electrode.

[0123] Continuing with reference to FIG. 6, method 700 further includes configuring at least one electrode of the plurality of decalcification electrodes to be positioned at least one of the distal end of the catheter, proximal to at least one unit of the plurality of units 600, on at least one unit of the plurality of units 600, on at least one stepped portion (or setback) of at least one unit of the plurality of units 600, between two units of the plurality of units 600, proximal to the expandable member, and in a location that does not interfere with (prevent) sonication.

[0124] 6 , in method 700, providing an ablation unit includes providing at least one of an ablation transducer and a plurality of ablation electrodes. Method 700 further includes configuring the ablation transducer to perform nerve ablation at a frequency of approximately 13 MHz. Method 700 further includes configuring the ablation transducer to perform nerve ablation in a frequency range of approximately 9 MHz to approximately 15 MHz. Providing a plurality of ablation electrodes includes providing at least one radio frequency electrode. Method 700 further includes configuring the at least one radio frequency electrode to perform at least one of ablation (of calcifications), confirmation (of ablation), and mapping of at least one nerve.

[0125] 6 , in method 700, providing one of the plurality of units 600 and the ablation unit further includes providing an imaging unit 602, as indicated at block 720. Providing the imaging unit 602 includes providing an imaging transducer configured to identify calcifications. Method 700 further includes configuring the imaging transducer to image at an optimal frequency of about 40 MHz. The range frequency is about 20 MHz to about 60 MHz, or about 30 MHz to 45 MHz. In some embodiments, providing the imaging transducer includes providing a piezoelectric material.

[0126] 6 , the method 700 further includes providing at least one of an expandable member 603 and a porous member (not shown), as indicated at block 730. The method 700 further includes configuring the at least one of the expandable member 603 and the porous member to be disposed at a distal end of the catheter 12. The method 700 further includes configuring the expandable member 603 to block at least one embolus, thereby allowing the at least one embolus to be removed from the at least one anatomical structure. The method 700 further includes configuring the porous member to capture at least one embolus, thereby allowing the at least one embolus to be removed from the at least one anatomical structure. In some embodiments, the porous member may include a stentriver, a basket, a net, or the like. Alternatively or additionally, suction may be used to capture the at least one embolus.

[0127] Continuing with reference to FIG. 6, in method 700, providing the expandable member 603 includes providing at least one material of polyamide, polyimide film, polyethylene terephthalate, thermoplastic elastomer, nylon, PEBAX® thermoplastic elastomer, medical grade thermoplastic polyurethane elastomer, PELLETHANE® thermoplastic polyurethane elastomer, pellethane, isotane, and any other suitable polymer, or any combination thereof.

[0128] 6, the method 700 further includes providing flexible features 402 (FIGS. 3A-3C) configured to separate each unit from the other units of the plurality of units 600. At least a portion of the flexible features 402 are configured to be disposed within the catheter 12. The flexible features 402 are configured to facilitate navigation of the catheter 12 through at least one anatomical structure.

[0129] 6, method 700 further comprises configuring each unit of the plurality of units 600 to selectively operate in at least one of an independent mode (independent of the mode of any other unit of the one or more units) and a slave mode (whose functionality is dependent on the mode of the other units). Method 700 further comprises configuring each unit of the plurality of units 600 to selectively operate in at least one of a focused mode and a non-focused ultrasound mode.

[0130] 6 , in method 700, providing a plurality of decalcification electrodes includes providing at least one shockwave electrode. Providing a plurality of decalcification electrodes includes providing an electrode formed of at least one of stainless steel, tungsten, nickel, iron, and steel. In method 700, the at least one anatomical structure includes at least one vasculature, and the at least one vasculature includes at least one of a renal vein and a renal artery.

[0131] Referring to FIG. 7 , a flow diagram illustrates an embodiment of a method 800 for preparing and treating at least one anatomical structure via a catheter device 200, in accordance with an embodiment of the present disclosure. As indicated at block 810, the method 800 includes providing a catheter device 200 including a unit 600, the unit 600 including a decalcification unit configured to prepare the at least one anatomical structure by decalcifying the at least one anatomical structure, and an ablation unit configured to treat the at least one anatomical structure by ablating at least one nerve associated with the at least one anatomical structure. The unit is configured to be disposed within the catheter and to operate the catheter device 200 within the at least one anatomical structure such that the at least one anatomical structure is not substantially damaged. As indicated at block 820, the method 800 further includes providing an imaging unit 602 configured to detect calcification. The method 800 further includes providing an expandable member 603 configured to be disposed at the distal end of the catheter 12, as shown at block 830. Providing the imaging unit 602 includes providing the imaging unit to either the unit or the ablation unit.

[0132] 7, as shown in block 840, operating the catheter device 200 includes the following steps: using the imaging unit 602 to detect whether calcification is present in the at least one anatomical structure; if calcification is present, expanding the expandable member 603 to allow apposition (close contact) of the expandable member 603 with at least one wall of the at least one anatomical structure; using a decalcification unit to break up / fragment the calcification; further expanding the expandable member 603 against the at least one wall of the at least one anatomical structure; using the imaging unit 602 to detect whether the calcification is successfully broken up in the at least one anatomical structure; and if the calcification is successfully broken up in the at least one anatomical structure, using an ablation unit to denervate the at least one anatomical structure so that it is not damaged. In certain embodiments, a calcification is determined to be successfully disrupted if the media-adventitial boundary is detectable, indicating that ultrasound can penetrate beyond the calcification into the adventitia.

[0133] 7 , in method 800, providing an expandable member 603 further includes positioning the expandable member 603 at the distal end of the catheter 12, as indicated at block 840. Actuating the catheter device 200 further includes blocking at least one calcified region using the expandable member 603, as indicated at block 840. Method 800 further includes removing at least one calcified region by aspirating at least one anatomical structure. In method 800, the at least one anatomical structure includes at least one vasculature, and the at least one vasculature includes at least one of a renal vein and a renal artery. In some embodiments, a renal nerve ablation method can include advancing the catheter device 200 from an entry site in a patient to a target region of a blood vessel (e.g., a renal artery having a calcified region). The catheter device 200 may include an ablation and / or decalcification transducer 500, an ablation and / or decalcification electrode 510, and an imaging transducer 520 along the catheter shaft 12a, and may further include an expandable member 14. Once within the blood vessel, the calcified region may be identified using an imaging device. The imaging device may be configured for intravascular ultrasound (IVUS) imaging of the calcified region. The imaging device may be configured to identify the calcified region of the renal artery. After the location and calcified region have been identified and the catheter device 200 is positioned adjacent the calcified region, the expandable member 14 may be inflated with a fluid. The decalcification electrode 510 may be activated to generate one or more gas bubbles adjacent the calcified region to fragment the calcified region. Depending on the size of the calcified region, at least two decalcification electrodes 510 may be activated to generate one or more gas bubbles to fragment the calcified region. The progress of fragmentation can be monitored using an imaging device. If fragmentation is adequate, ablation of one or more nerves within and / or around the calcified region is performed. After ablation is complete, the expandable member 14 is retracted and the catheter device 200 is removed from the blood vessel.The imaging device may be separate from or connected to the catheter 12. For example, the imaging device may be a separate system used in combination with the renal denervation catheter 12.

[0134] In some embodiments, a renal denervation method may include advancing a catheter device 200 from an entry site in a patient to a target region of a blood vessel (e.g., a renal artery having a calcified region). The catheter device 200 may include an ablation and / or decalcification transducer 500, an ablation and / or decalcification electrode 510, and an imaging transducer 520 along a catheter shaft 12a, and may further include an expandable member 14. Once within the blood vessel, calcified and non-calcified regions may be identified using the imaging device. The imaging device is configured for intravascular ultrasound (IVUS) imaging of the calcified and non-calcified regions. The intravascular location, calcified, and non-calcified regions are identified. The catheter device 200 may then be positioned adjacent to the calcified region, and the expandable member 14 may be inflated with a fluid. The decalcification electrodes 510 are activated to generate one or more gas bubbles adjacent to the calcified region, fragmenting the calcified region. Depending on the size of the calcified region, at least two decalcification electrodes 510 may be activated to generate one or more gas bubbles, fragmenting the calcified region. The progress of fragmentation may be monitored using an imaging device. If fragmentation is adequate, ablation of one or more nerves around the renal artery is performed. After ablation is complete, the expandable member 14 is deflated and the catheter device 200 is removed from the blood vessel.

[0135] In some embodiments, a renal denervation method may include selecting a patient for treatment, e.g., a patient with hypertension and one or more calcified regions associated with a renal artery. A catheter device 200 is advanced from an entry site in the patient to a target region of a blood vessel (e.g., a renal artery having a calcified region). The catheter device 200 may include an ablation and / or decalcification transducer 500, an ablation and / or decalcification electrode 510, and an imaging transducer 520 along the catheter shaft 12a, and may further include an expandable member 14. Once within the blood vessel, calcified and non-calcified regions may be identified using an imaging device. The imaging device is configured for intravascular ultrasound (IVUS) imaging of the calcified and non-calcified regions. The decalcification electrode 510 is activated to generate one or more gas bubbles in the calcified region, fragmenting the calcified region. The progress of fragmentation may be monitored using the imaging device. If fragmentation is adequate, ablation of one or more nerves within the identified non-calcified region of the renal artery, one or more nerves surrounding the identified non-calcified region of the renal artery, or both, is performed. After ablation is complete, the expandable member 14 is deflated and the catheter device 200 is removed from the blood vessel.

[0136] 4A-7, in some embodiments of the present disclosure, the catheter device 200 can operate as a denervation device to identify and disrupt / fragment calcified plaques located in arterial walls, verify that the plaques have been removed, and apply ablation therapy. In some embodiments, the catheter device 200 can operate as a uRDN ​​catheter. The catheter can include an imaging transducer that images at an optimal frequency of about 40 MHz, with a range frequency of about 20 MHz to about 60 MHz. The catheter device 200 can be configured to identify calcium deposits.

[0137] 4A-7, in some embodiments of the present disclosure, a catheter device 200 includes an imaging unit configured for intravascular ultrasound (IVUS) imaging, where acoustic reflection or scattering from calcifications is significant, making calcifications more readily detectable in ultrasound images than otherwise possible with related art devices. In one embodiment, one or more stepped (or recessed) portions of the ablation transducer are used for imaging.

[0138] 4A-7, in one embodiment of the present disclosure, the catheter device 200 is operable as a uRDN ​​catheter. The catheter device 200 further includes multiple shock wave electrodes located distal and / or proximal to the transducer and spaced about 3 mm to about 20 mm apart (e.g., about 5 mm, 6.7 mm, 7 mm, or 10 mm apart). The number of decalcification electrodes 510 along the catheter shaft 12a can vary depending on the geometry of the targeted calcified region. For example, if it is intended to decompose / fragment a calcified region along a long vessel segment, a greater number of decalcification electrodes 510 can be used along the length of the catheter shaft 12a. On the other hand, if it is intended to fragment a calcified region within a shorter vessel segment, the catheter device 200 can include a fewer number of decalcification electrodes 510 along the length of the catheter shaft 12a.

[0139] The decalcification electrode 510 may have a thickness of about 0.001 inch to about 0.01 inch, e.g., 0.002 inch, and may be attached along the catheter shaft 12a. An insulating layer may be present, made of any material with a high breakdown voltage, such as Kapton, ceramic, polyimide, or Teflon. The insulating layer may be about 0.001 inch to about 0.006 inch, e.g., 0.0015 inch or 0.0025 inch, and may have an opening that may be aligned over the decalcification electrode 510. In one embodiment, a second decalcification electrode 510 may be present. The second decalcification electrode 510 may have a thickness of about 0.001 inch to about 0.015 inch, e.g., 0.0025 inch or 0.004 inch. The total thickness of the shock wave electrode assembly may be about 0.002 inch to about 0.03 inch, e.g., 0.005 inch, 0.007 inch, or 0.008 inch. The required voltage ranges from about 100 volts to about 10,000 volts, depending on the size of the gap between the electrodes. In one embodiment, the generator may apply a voltage pulse such that the potential difference between the first demineralization electrode 510 and the second demineralization electrode 510 is high enough to form a plasma arc between them, generating bubbles and creating shock waves.

[0140] In one embodiment, the electrodes are constructed of metals such as stainless steel, tungsten, nickel, iron, or steel, and are configured to withstand high voltage levels and the high mechanical forces generated during use (e.g., in the range of about 1000 psi to about 2000 psi, or about 20 atm to about 200 atm for several microseconds). The electrodes have a small surface area, resulting in high current densities, and therefore the generation of vapor bubbles upon application of high voltage. The formation, growth, and collapse of these bubbles results in cavitation and shock waves that disrupt / fragment calcifications. The direction of the pressure pulse waves generated by cavitation can be controlled based on the circumferential orientation of the electrode where the cavitation occurs. In one embodiment, the electrodes include two ring electrodes, each including an inner electrode, an insulating layer disposed over the inner electrode, and an outer electrode sheath disposed over the insulating layer, with an opening in the insulating layer aligned with the inner electrode and an opening in the outer electrode sheath coaxially aligned with the opening in the insulating layer. In one embodiment, a shock wave generator, e.g., a decalcification electrode 510, can be coupled via an electrical cable to a high voltage source at the proximal end of the catheter device 200. When an expandable member 14, such as a balloon, is positioned adjacent to a calcified region of a blood vessel, such as a renal artery, a low voltage is applied across the decalcification electrodes 510 for approximately 2 milliseconds (ms) to ensure that no arcing occurs across the decalcification electrodes 510. During this 2 ms period, a gas bubble is generated above one of the decalcification electrodes 510. The size of the bubble can be controlled by the amount of current and the length of time the low current is applied. After a period of 2 ms, a narrow pulse (500 nanoseconds (ns)) of high voltage of 3,000 volts is applied across the decalcification electrode 510 .

[0141] 4A-7, in one embodiment of the present disclosure, the electrodes include two simple electrodes (+ and -) distal and proximal to the ablation transducer (or ablation transducer / imaging transducer) added to the ablation system 100. Voltage can be precisely adjusted based on distance to introduce an electric arc, generating high temperatures (localized) and vapor bubbles within the fluid. In certain embodiments, multiple electrodes (arrays) can be used. The electrodes 510 can be spaced a controlled distance apart on the catheter shaft 12a to generate a reproducible arc for a given voltage and current. The electric arc between the electrodes 510 within the fluid can be used to generate shock waves within the fluid. The generator can be a variable high-voltage pulse generator configured to supply a pulse stream to the decalcification electrode 510 to generate a shock wave stream within the expandable member 14 and the treated blood vessel. The magnitude of the shock waves can be controlled by controlling the magnitude(s) of the pulse voltage, current, duration, and repetition rate.

[0142] 3-7, in one embodiment of the present disclosure, the expandable member, e.g., balloon, comprises an electrically insulating material such as polyamide, polyethylene terephthalate, or a thermoplastic elastomer. In certain embodiments, the expandable member includes, but is not limited to, nylon, polyimide film, thermoplastic elastomer (such as those bearing the registered trademark "PEBAX"), medical grade thermoplastic polyurethane elastomer (such as those bearing the registered trademark "PELLETHANE"), pellethane, isotane, other suitable polymers, or any combination thereof. The length of the balloon can vary depending on the number of demineralization electrodes 510 present.

[0143] 4A-7, in one embodiment of the present disclosure, electrical power is applied to generate a gas bubble on the surface of the electrode, causing a plasma arc of electrical current to cross the bubble, thereby creating a gas bubble that rapidly expands and contracts, resulting in the generation of mechanical shock waves within the balloon. The shock waves mechanically propagate through the fluid and through the expandable member, exerting a mechanical force or pressure to disrupt / fragment any calcified plaque on or within the vessel wall. In some embodiments, the shock waves can radiate outward from the decalcification electrode 510, pass through the expandable member 14, and reach the vessel where the decalcification electrode 510 can fragment the calcified region. In some embodiments, the first and second decalcification electrodes 510 can be positioned radially apart from each other so that the shock waves generated by each electrode propagate in opposite directions. The shock waves generated by each of the decalcification electrodes 510 can propagate outward with an angular spread of approximately 180 degrees. In some embodiments, decalcification electrodes 510 may generate shock waves that propagate from the left and right longitudinal sides of the catheter shaft 12a, and other decalcification electrodes 510 may generate shock waves that propagate from the top and bottom longitudinal sides of the catheter shaft 12a.

[0144] In some embodiments, the decalcification electrode 510 may generate pairs of shock waves that propagate outward from positions at 0 and 180 degrees around the circumference of the catheter shaft 12a. In some embodiments, the decalcification electrode 510 may generate pairs of shock waves that propagate outward from positions at 60 and 240 degrees around the circumference of the catheter shaft 12a. In some embodiments, the decalcification electrode 510 may generate pairs of shock waves that propagate outward from the same position around the circumference of the catheter shaft 12a but different positions along the length of the catheter shaft 12a.

[0145] 4A-7, in one embodiment of the present disclosure, intermittent acoustic waves emitted by the electrodes include a series of pulses having multiple cycles, e.g., about 8 to about 12 cycles, at a fixed pulse repetition rate, e.g., 1 pulse per second (pulse duration dependent on the surface area of ​​the electrode), to generate acoustic pressure waves that create a circumferential field effect to fragment calcifications. Prior to applying the shock waves, the expandable member is inflated to a pressure, e.g., 1 atm or 4 atm, to achieve apposition (contact) against the arterial wall. Once the calcifications are fragmented (fractured), the expandable member can be inflated to a higher pressure.

[0146] 5A-7, in one embodiment of the present disclosure, a 50 / 50 ratio of saline and contrast agent is used for the expansion of the expandable member during shock wave penetration. Other conductive liquids may be used instead of saline. The ultrasound transducer may or may not be insulated from the fluid. The conductivity of the fluid may be adjusted to promote the formation of bubbles (cavitation). In certain embodiments, saline includes a salt content of between about 0.9 weight percent (wt.%) and about 5 wt.%. The higher the salt content of the conductive fluid, the higher the conductivity of the fluid, thereby requiring less energy to raise the temperature of the fluid and induce bubble formation. In certain embodiments, contrast agents may be avoided by using an imaging transducer unit.

[0147] 4A-7, in some embodiments, a demineralization transducer unit is used in place of or in combination with the shock wave electrode. The demineralization transducer may include a third transducer unit optimized for inducing cavitation, such as a piezoelectric focused transducer having an operating frequency in the range of about 400 kHz to about 3 MHz. The third transducer unit is configured to disrupt / fragment calcium deposits from the arterial wall without substantially damaging the arterial wall. In one embodiment, there may be a series of ultrasound transducers that can be simultaneously activated to demineralize. In one embodiment, there may be a series of ultrasound transducers that can be independently activated to demineralize calcified regions. In some embodiments, the transducer 500 may be intermittently activated at relatively low and relatively high frequencies to perform cavitation and ablation, respectively. This may be achieved by operating the transducer 500 at a relatively low harmonic and a relatively high harmonic. Alternatively, this may be achieved by configuring different transducers 500 to have different resonant frequencies at the first harmonic. The amount of power supplied to each transducer 500 may be different, so that each transducer 500 delivers different amounts of demineralization and / or ablation energy. Thus, in some embodiments, the transducers 500 may be wired separately and differently. This may allow for individual energization of each transducer 500, providing the user with more control. In one embodiment, one or more transducers 500 may be configured to rotate using a rotation unit (not shown).

[0148] 4A-7, in some embodiments, a flexible post (such as the embodiment shown in FIGS. 3A-3C) can separate the non-focal ablation transducer unit and the focal demineralization transducer unit to facilitate delivery of the catheter device 200. In certain embodiments, the catheter device 200 can include an imaging transducer, an ablation transducer, a demineralization transducer, and a treatment verification electrode coupled to the balloon in a manner that does not interfere with the sonication of the transducers.

[0149] 8 is an example block diagram illustrating a process 900 for pre-treating a calcified region prior to ablation of one or more nerves surrounding the calcified region, as described above with reference to FIGS. 1-7, according to an embodiment of the present disclosure. Method 900 may optionally include selecting (910) a subject having one or more calcified regions associated with a renal artery. Method 900 may also optionally include identifying (920) the calcified region of the renal artery using an imaging device.

[0150] In some embodiments, method 900 may include, for example, generating one or more gas bubbles to at least partially fragment (fracture) calcifications in the calcified region of the renal artery, in operation 930. In some embodiments, steam bubbles may be generated. Various types of bubbles may be used, such as microbubbles, gas bubbles, steam bubbles, etc., as long as they have enough energy to fragment (fracture) the calcifications. Generating one or more gas bubbles may be performed using decalcification electrode 510 or decalcification transducer 500, as described above.

[0151] In some embodiments, method 900 may include determining whether the calcification is at least partially fragmented using an imaging device, for example, in operation 940. Alternatively, method 900 may be performed without determining whether the calcification is at least partially fragmented.

[0152] Once the calcified region has been at least partially fragmented, one or more nerves surrounding the calcified region of the renal artery may be ablated in operation 950. The nerves targeted for ablation may be within and / or around the calcified region, or may be located near the calcified region. If the nerve is located near the calcified region, the user may move the catheter device 200 to a different location along the renal artery after decalcification to ablate the nerve.

[0153] Calcifications, including their shape, location, content, and surrounding structures, are typically well visualized with ultrasound imaging devices, such as a separate or integrated IVUS transducer on an ablation catheter. When penetration is difficult with other techniques, such as OCT or ultra-high frequency (greater than 40 MHz) ultrasound imaging, visualization of the media-adventitia boundary using an imaging device can be a method used to confirm calcification / demineralization. In other words, if the media-adventitia boundary is not visible with the imaging device, a calcified area is most likely present. On the other hand, if the media-adventitia boundary is visible with the imaging device, a calcified area is most likely not present, or only a very thin layer of calcification is present.

[0154] In the foregoing description, pretreatment is performed by one or more demineralization units used to demineralize the anatomical structure. The demineralization unit may include, for example, a demineralization electrode 510 or a demineralization transducer 500. However, it will be understood that such examples do not limit the scope of demineralization units that may be incorporated into the foregoing method. For example, in one embodiment, pretreatment may be performed using a laser. More specifically, the demineralization unit may include a laser for demineralizing the calcified region prior to treatment with the transducer 16. The laser may include a holmium:yttrium-aluminum garnet (Ho:YAG) laser, a thulium fiber laser (TFL), or a thulium:yttrium-aluminum garnet (TrmYAG) laser.

[0155] In one embodiment, the laser may include a holmium:yttrium aluminum garnet (Ho:YAG) laser. The Ho:YAG laser can be used to demineralize calcified areas by vaporizing them. The 2100 nm wavelength of the holmium infrared laser is highly absorbed by water (water absorption coefficient: 3198 L / m). The energy absorbed by the water results in the formation of vapor microbubbles at the tip of the laser, which expand outward toward the target. Once the microbubbles reach the target, the density of water molecules in vapor is much lower than in the liquid state, allowing the laser beam to pass through the vapor and reach the target with little attenuation. The bubble formation can be initiated with very little energy, and the threshold for bubble formation and expansion (100-200 ms) is independent of pulse duration and residual energy. The Ho:YAG laser can produce smaller plaque fragments.

[0156] The laser pulses of the Ho:YAG system may have an average power of about 120-140 W, a pulse frequency of about 5-80 Hz (maximum 120 Hz), a pulse energy of about 0.2-6.0 J, a pulse width of about 50-1300 μs (can be adjustable (short, medium, long)), and a silica fiber of about 200 μm or longer.

[0157] In one embodiment, the laser may include a thulium fiber laser (TFL). A TFL can be used to decalcify calcified areas. Instead of a flash lamp used in a Ho:YAG laser, a TFL uses multiple electronically modulated laser diodes to excite thulium ions for laser pumping. The emitted laser beam may have a wavelength of 1940 nm and may be operated in continuous or pulsed mode. Compared to a Ho:YAG laser beam, the laser beam is more uniform and focused, allowing it to be delivered to a smaller-core fiber (50-150 mm). A TFL provides low pulse energies (e.g., around 0.025 J) to high pulse energies (e.g., around 6 J), at high pulse frequencies (up to 2400 Hz in the latest TFL devices), short to long pulse durations (200 μs to 50 ms), with peak powers of 500 W and average powers of 2-60 W. The TFL system may have an average power of about 2-60 W, a pulse frequency of about 1-2400 Hz, a pulse energy of about 0.025-6.0 J, a pulse width of about 200 μs-50 ms, a peak power of about 500 W, and a silica fiber of about 50 μm or larger.

[0158] In one embodiment, the laser can include a Tm:YAG laser. The Tm:YAG laser can be a solid-state laser and can be used to demineralize calcified areas through a photothermal mechanism. The Tm:YAG provides 120 W of power at a frequency of 1-200 Hz, with possible pulse energies ranging from approximately 0.1 J to 3 J. The Tm:YAG system can have an average power of approximately 120 W, a pulse frequency of approximately 1-200 Hz, a pulse energy of approximately 0.1-3 J, a peak power of approximately 200 W, and a silica fiber of approximately 400 μm.

[0159] In certain embodiments, the laser fibers disclosed herein can be used to ablate nerve fibers near, within, and / or surrounding a body cavity in addition to decalcifying areas. For example, the laser fiber can direct energy to the arterial wall to act in addition to or as an alternative to an ultrasound transducer. More specifically, the energy can ablate nerve fibers near, within, or surrounding calcifications. Further details of catheters incorporating lasers for decalcification and ablation are described below.

[0160] In one embodiment, the laser fiber 302 is positioned on the surface of the balloon, e.g., on the shoulder, bottom, top, front, back, or center of the balloon 14. The laser fiber 302 can fire in any direction, e.g., forward, back, top, bottom, center, or diagonally. More specifically, a forward-firing laser fiber can be oriented to emit laser radiation distally, e.g., parallel to the cavity wall. In contrast, a side-firing laser fiber can be oriented to emit laser radiation radially outward, e.g., perpendicular to the cavity wall. Reducing the warm-up time and circulating a cooling fluid adjacent to where the laser fiber 302 is located are ways to reduce the heat generated by the laser. The laser fiber 302 is energized by a power source, e.g., a generator.

[0161] In some of the embodiments described below, at least one laser fiber 302 is present on the balloon surface. For example, the laser fiber 302 may be attached to the surface of the balloon. When the balloon 14 is at least partially inflated, the laser fiber 302 may be located near the calcified region. For example, the distance between the laser fiber 302 and the lumen wall (e.g., arterial wall) may be within a range of approximately 0.1 to 1 mm. The laser fiber 302 may be positioned adjacent to (but not necessarily in contact with) the calcifications in the calcified region of the lumen wall prior to cavitation.

[0162] As mentioned above, the catheter 200 may include an imaging device. In one embodiment, the imaging device includes a laser fiber 302. More specifically, the laser fiber 302 may be used to image / visualize the calcified region and / or the arterial lumen. The laser fiber 302 may also be used to image / visualize the apposition (adhesion) of the balloon against the lumen wall. Changing the frequency allows the laser fiber 302 to be used for decalcification and / or imaging. In addition to generating one or more bubbles that cause cavitation to fragment the calcified region, the laser fiber 302 may have a lens for imaging. In one embodiment, the laser fiber 302 may be an optical illumination fiber for observing the catheter device 200 or the calcified region. For example, the laser fiber may include a fiber optic cable that transmits light that is reflected into a lens and returned to the imaging system for imaging. All portions of the interior of the balloon, including the balloon surface, may be completely or partially coated with a fluorescent material to illuminate the vessel wall. If the optical fiber / laser fiber 302 is used to inspect the blood vessel wall, the light source can be another laser fiber or a fluorescent light source. The illumination light can be monochromatic, and images can be observed using a corresponding laser fiber / camera. The corresponding laser fiber / camera can be separate from the catheter device 200 or can be attached to the catheter balloon. The laser fiber 302 extends from an energy source (e.g., a generator) through the catheter shaft 12a and is attached to the balloon 14. The laser fiber 302 can be attached to the surface of the balloon 14 by adhesive, such as bonding with a high-stretch flexible UV adhesive, or the laser fiber 302 can be embedded within the balloon 14 by lamination during the balloon blow-molding process.

[0163] In one embodiment, the laser fiber 302 may extend parallel to the balloon surface. The laser fiber 302 may be flexible to prevent breakage. Decalcification of calcified areas may be localized at or around the target area. In embodiments where there is only one laser fiber 302, the catheter device 200 may be rotated or twisted to inspect the body cavity for calcified areas. Rotating or twisting the catheter device 200 may be performed manually or by using a drive cable.

[0164] 9A illustrates a side view of one embodiment of a catheter device 200 having a deflated proximal balloon 14a and a distal balloon 14b for blocking debris after pretreatment. The balloons 14a, 14b, and 14c are separate balloons that are controlled independently of one another. For example, the interior of each of the balloons may be in fluid communication with a respective fluid lumen extending through the catheter shaft 12a. Thus, inflation fluid may be delivered through the fluid lumens to individually inflate or deflate the balloons.

[0165] The laser fiber 302 can be disposed on a surface of the expandable member 14C, such as a balloon. For example, the laser fiber 302 can be mounted such that the outlet (e.g., the port through which the laser is emitted from the laser fiber into the surrounding environment) is at the proximal shoulder or radially outer surface of the balloon. Such an arrangement can orient the outlet to emit the laser beam longitudinally forward in the direction of (along) the body cavity or radially outward toward the cavity wall of the body cavity.

[0166] A transducer 16 may be disposed within the balloon 14c. Imaging may be performed by the transducer 16 in addition to or instead of the laser fiber 302. More specifically, the transducer 16 may image or detect calcification, for example, as described above with respect to FIG. 5. Similarly, it will be understood that the laser fiber 302 may be incorporated into the above-described embodiments to perform such detection.

[0167] In one embodiment, the balloons 14a, 14b, and 14c are attached to the catheter shaft 12a. The balloons may be arranged sequentially (consecutively) on the catheter shaft. More specifically, the middle balloon 14c may be arranged longitudinally between the proximal balloon 14a and the distal balloon 14b. Thus, when the middle balloon 14c is longitudinally aligned with a calcification in a calcified region of a body lumen, the calcification may be located longitudinally between the proximal balloon 14a and the distal balloon 14b.

[0168] In one embodiment, catheter 200 includes a debris removal feature. Debris generated during the decalcification process, such as calcification fragments and stones, can cause embolism and endanger the patient. Therefore, catheter 200 can include a debris removal feature to capture and / or remove debris from the patient's anatomy. In one embodiment, the debris removal feature includes one or more holes 300 in catheter shaft 12a. Suction can be applied through holes 300 to draw debris into catheter shaft 12a. This allows the aspirated debris to be removed from the patient's anatomy without forming emboli that could pass distally beyond the treatment area and pose an embolism risk.

[0169] 9B illustrates a side view of an embodiment of the catheter device 200 with the proximal and distal balloons 14a, 14b inflated to block debris after pretreatment. In one embodiment, the imaging device may be separate from the catheter device 200. If the imaging device, such as IVUS or OCT, is separate from the catheter device 200, the imaging device may be inserted into the body cavity (BL) first to image the wall of the body cavity (e.g., the renal artery). Alternatively, the imaging device may be integrated with a laser fiber and / or incorporate a transducer, as described above. Whether integrated with or separate from the catheter 200, the imaging device allows the user to visualize the calcified region. Once the calcified region is detected, the imaging device is removed from the body cavity (if separate), and the catheter device 200 with the deflated balloons 14a, 14b, 14c is delivered adjacent to the calcifications in the calcified region of the body cavity wall. After positioning the catheter device 200 adjacent to the calcified area, suction is turned on via the generator. The suction draws or sucks fluid and debris within the fluid from the body cavity into the hole 300. The suction can be turned on and off at any time during the preparation process.

[0170] As shown in FIG. 9B, the proximal balloon 14a, the middle balloon 14c, and the distal balloon 14b may be inflated using circulating fluid. Once the balloons 14a, 14b, and 14c reach apposition, the laser fiber 302 may be energized. The laser emitted from the laser fiber may generate one or more bubbles to disrupt at least a portion of the calcified region. For example, energy absorbed by water in the blood at the treatment site may generate bubbles within a region 0.5 to 1.0 mm from the cavity wall. Generating bubbles within a region adjacent to the cavity wall may localize cavitation shock waves to loosen and / or fragment the calcifications. Some of the disrupted debris may remain within the cavity wall, for example, at the media-adventitia interface or within the media layer. Alternatively, some of the disrupted debris may be released into the cavity, for example, radially inward of the intima.

[0171] The proximal and distal balloons 14a, 14b can contain debris released into the area where the holes 300 are located to aspirate the debris away. The balloons 14a, 14b, 14c can be deflated and the catheter device 200 can be withdrawn from the body cavity.

[0172] After fragmentation and debris removal, the imaging device can be used again to image the calcified region. For example, another imaging device can be reinserted into the body cavity. Alternatively, a laser fiber can be used in imaging mode to capture images and / or reflected radiation, which can be analyzed to image / confirm that the calcified region has been properly decalcified. If it is determined that the calcified region was not properly fragmented, the above process can be repeated. On the other hand, if the imaging device confirms that the calcified region has been properly decalcified, the catheter device 200 can be used to ablate nerves near, within, or surrounding the calcified region.

[0173] Ablation may begin by reinserting, delivering, or otherwise positioning the catheter 200 within the body cavity so that the transducer 16 is positioned near the decalcified region. The balloon 14c may be inflated using circulating fluid to achieve apposition (fitting) with the cavity wall. Once apposition (fitting) is achieved, the transducer 16 may be energized to denervate the nerves surrounding the cavity. In another embodiment, the balloons 14a, 14b may be inflated first to block (occlude) the proximal and distal ends of the cavity. Then, the balloon 14c may be inflated to position the laser fiber 302 adjacent the calcified region for decalcification. The balloons 14a, 14b, 14c may be deflated simultaneously or individually.

[0174] In another embodiment, an imaging device may be integrated with the catheter device 200. In such an embodiment, the catheter device 200 is inserted into the body cavity, and the imaging device is used to locate the calcified region. The laser fiber 302 may also function as the imaging device. Once the calcified region is located, the balloons 14a, 14b, and 14c are inflated adjacent to the calcified region until they reach apposition with the cavity wall. During this process, suction may be turned on or off. Once the balloons 14a, 14b, and 14c reach apposition, the laser fiber 302 is energized to at least partially fragment the calcified region. The balloons 14a and 14b may be inflated first to block the proximal and distal ends of the body cavity, and the balloon 14c may be inflated last. The proximal and distal balloons 14a, 14b may prevent debris from becoming airborne. During decalcification, suction can be turned on through holes 300 to remove calcium debris contained by balloons 14a, 14b. In one embodiment, catheter shaft 12a has multiple lumens for wires, suction, and fluid flow. In one embodiment, inflation / deflation of balloons 14a, 14b, 14c can be independently controlled.

[0175] Referring to Figure 10, a side view of a catheter device having a conical balloon is shown. A conical balloon 14e may be attached to the catheter shaft 12a of a catheter 200. The conical balloon 14e may be positioned at a distal portion of the catheter device 200 to block debris after pre-treatment. The conical balloon 14e may include an outer tapered surface 14d that slowly moves toward the lumen wall after the distal portion reaches apposition during inflation. More specifically, the surface 14d may be conically shaped such that the cross-sectional diameter of the distal end of the surface is larger than the cross-sectional diameter of the proximal end of the surface.

[0176] The catheter 200 can be deployed and used in a similar manner as described above with respect to Figures 9A and 9B. After the calcified region is fragmented with the laser fiber 302 (which can be attached to the balloon 14a, and the exit of the laser fiber can generate one or more bubbles near the lumen wall), debris from the calcified region can be contained. Capture of the debris can be achieved by aspirating fluid through the holes 300 in the catheter shaft 12a. This suction can cause the outer surface 14d of the conical balloon 14e to fold back and expand outward against the lumen wall. In other words, the distal portion of the conical balloon 14e prevents debris from migrating distally because it comes into apposition with the vessel wall, blocking the distal flow of debris as decalcification occurs. Towards or at the end of the decalcification operation, the conical balloon 14e is slowly inflated, moving the outer surface 14d of the balloon 14 closer to apposition against the cavity wall, thereby moving debris from the decalcification proximally and directing the debris towards the suction holes 300. Once the entire conical balloon 14e is in apposition, the debris is positioned closer to the suction holes 300, thereby reducing the risk of emboli flowing downstream within the cavity.

[0177] As shown in Figure 10, the laser fiber 302 may be positioned on the upper and lower surfaces of the proximal balloon 14a. More specifically, multiple laser fibers may be used, each with its exit at diametrically opposed (opposite) locations on the radially outer working length of the balloon 14a. The laser fiber 302 may also be positioned on the shoulder of the proximal balloon 14a. The laser fiber 302 may be positioned at different locations on the surface of the proximal balloon 14a. Inflation of the proximal balloon 14a and the conical balloon 14e may be independently controlled using circulating fluid moving through fluid lumens disposed within the catheter shaft 12a.

[0178] One method for pre-treatment / treatment (treatment) includes imaging the body cavity before pre-treatment and treatment (treatment), although this imaging step is optional. The imaging device can be separate from the catheter device 200. If the imaging device, such as IVUS or OCT, is separate from the catheter device 200, the imaging device can be inserted into the body cavity (BL) first to image the wall of the body cavity (e.g., the renal artery). Once a calcified region is detected, the imaging device is removed from the body cavity, and the catheter device 200 with the deflated balloons 14a, 14e is inserted into the body cavity. After positioning the catheter device 200 adjacent to the calcified region, a suction device is activated (switched on) via a generator. The suction is felt through the hole 300. However, the suction can be turned on and off at any time during treatment (treatment). As shown in FIG. 10 , the proximal balloon 14a and the conical balloon 14e can be inflated using circulating fluid flowing through a fluid lumen disposed within the catheter shaft 12a. Once the distal portion of the conical balloon 14e reaches apposition, the proximal balloon 14a is inflated to bring the laser fiber 302 closer to the calcified region. The laser fiber 302 is energized to at least partially fragment the calcified region, and the proximal balloon 14a is deflated. The proximal balloon 14a and the conical balloon 14e may contain debris within the area where the holes 300 are located to aspirate the debris. The balloons 14a, 14e may be deflated, the catheter device 200 may be withdrawn from the body cavity, and an imaging device may be reinserted into the body cavity to image / confirm that the calcified region has been adequately decalcified. If it is determined that the calcified region has not been adequately fragmented, the process described above may be repeated. On the other hand, if the imaging device confirms that the calcified region has been adequately decalcified, the catheter device 200 may be reinserted into the body cavity and positioned at the decalcified region. The proximal balloon 14a can be inflated using circulating fluid to achieve apposition with the cavity wall. Once apposition is achieved, the transducer can be energized to denervate the nerves surrounding the cavity.

[0179] In another embodiment, an imaging device may be integrated with the catheter device 200. In such an embodiment, one method for pre-treatment / treatment includes inserting the catheter device 200 into a body cavity. An integrated imaging device, such as a laser fiber 302, is used. Once the calcified region is located, the distal portion of the conical balloon 14e is inflated adjacent to the calcified region until it reaches apposition with the cavity wall. During this process, suction may be turned on or off. Once the distal portion of the conical balloon 14e reaches apposition, the proximal balloon 14a is inflated, bringing the laser fiber 302 closer to the calcified region. The laser fiber is then energized, at least partially fragmenting the calcified region. The proximal balloon 14a is slightly deflated, and the conical balloon 14e is slowly inflated proximally, pushing debris toward the hole 300 so that it can be suctioned at the proximal end. After debris is removed, the proximal balloon 14a is inflated to achieve apposition against the cavity wall. The transducer 16 is then energized to denervate the surrounding nerves. In one embodiment, the catheter shaft 12a has multiple lumens for wire, suction, and fluid flow.

[0180] Referring to Figure 11, a side view of a catheter device is shown. The catheter 200 includes a barbell-shaped balloon 14f attached to the catheter shaft 12a. The barbell-shaped balloon 14f may block debris after pre-treatment. The barbell-shaped balloon 14f is inflated at proximal and distal regions. The proximal and distal regions may be inflated before the middle region of the barbell-shaped balloon 14f is inflated. The middle region may surround the transducer 16.

[0181] In one embodiment, the barbell-shaped balloon 14f is the only balloon 14 of the catheter 200, and the imaging device may be separate from or integrated with the catheter device 200. The laser fiber 302 may be disposed on the surface of the barbell-shaped balloon 14f. One method for pre-treatment / treatment (treatment) includes inserting an imaging device into a body cavity (e.g., a renal artery) to image the wall of the cavity. Once a calcified area is detected, the imaging device is removed from the body cavity, and the catheter device 200 with the deflated barbell-shaped balloon 14f is inserted into the body cavity. After positioning the deflated barbell-shaped balloon 14f adjacent to the calcified area, a separate suction device 304 may be inserted into the body cavity near the area of ​​the laser fiber 302. Suction may be turned on and off at any time during treatment (treatment). As shown in FIG. 11 , the barbell-shaped balloon 14f may be inflated using a circulating fluid. The ends (e.g., the proximal and distal regions) of the barbell-shaped balloon 14f may reach apposition (close contact) first, followed by the central portion where the laser fiber 302 is located. As the laser fiber 302 approaches the body cavity wall, it may be energized. The laser fiber may emit laser energy to generate one or more bubbles, which may at least partially fragment or sever the calcified region. During this process, debris may be removed by the suction device 304. For example, the suction device may be an external tubular element disposed between the barbell-shaped balloon 14f and the body cavity wall. The inlet of the tubular element may be disposed within the volume defined between the body cavity wall and the balloon, for example, between the proximal and distal regions of the barbell-shaped balloon 14f in the longitudinal direction. The proximal and distal regions of the barbell-shaped balloon 14f may contain (contain) debris within the region where the opening of the suction device 304 is located. Thus, debris can be removed from the area and the risk of embolism can be reduced. Thereafter, the transducer 16 can be energized and the surrounding nerves can be denervated, as previously described.

[0182] The outer tubing element may be used in the previous embodiments. Similarly, the holes 300 described in the previous embodiments may be incorporated into the catheter 200 of Figure 11 to remove debris from the treatment site. Thus, it will be understood that features of the catheter systems described throughout this disclosure may be interchangeable in certain embodiments.

[0183] Referring to FIG. 12 , a side view of one embodiment of a catheter device having at least one laser fiber is shown. At least one fiber laser 302 may be disposed on the surface of the balloon 14. The catheter 200 may include a scoop 306 for collecting debris resulting from decalcification. The scoop 306 may be deployed in a distal region of the catheter device. The laser fiber 302 may be disposed on the surface of the balloon 14, as described above. For example, the laser fiber 302 may be disposed on the distal shoulder of the balloon 14 to direct energy into the body cavity such that one or more cavitation bubbles are generated near the cavity wall. The cavitation generates shock waves that disrupt the calcifications, and fragments of the calcified region may be released into the body cavity. In one embodiment, the scoop 306 collects debris within the body cavity (BL) before the transducer 16 denervates the surrounding area. The scoop 306 may collect debris as the catheter device 200 is pulled from a distal to a proximal direction. The imaging device may be separate from or integrated into the catheter device 200 shown in FIG.

[0184] One method of pre-treatment / treatment involves first inserting a separate imaging device into a body cavity (e.g., a renal artery) to image the wall of the body cavity. Once a calcified region is detected, the imaging device is removed from the body cavity, and the catheter device 200 is inserted into the body cavity. After positioning the catheter device 200 adjacent to the calcified region, the scoop 306 is deployed and the balloon 14 is inflated to position the laser fiber 302 adjacent to the calcified region. Once the laser fiber 302 is adjacent to the calcified region, the laser fiber 302 can be energized to cavitate the calcified region. The scoop 306 can capture debris, and the user can remove the catheter device 200 by pulling it proximally. The user can re-insert the imaging device and visualize whether the calcified region or the media-adventitia boundary is visible. If the media-adventitia boundary is visible or the calcified region is determined to be decalcified, the imaging device is removed and the catheter device 200 is reinserted to begin treatment. The user can reinsert the catheter device 200 adjacent the decalcified region, inflate the balloon, and energize the ultrasound transducer to ablate the nerves surrounding the region.

[0185] In one embodiment, an imaging device is integrated with the catheter device 200, and the laser fiber 302 can perform imaging and cavitation depending on the operating frequency. A user can insert the catheter device 200 into a body cavity and energize the laser fiber 302 to visualize the body cavity and / or calcified areas. Once a calcified area is found, the scoop 306 can be deployed, and the balloon 14 can be inflated to position the laser fiber 302 adjacent to the calcified area. The laser fiber 302 is then energized to cavitate the calcified area, and the scoop captures debris. Once it is determined via the imaging laser fiber 302 that the calcified area has been adequately decalcified, the ultrasound transducer 16 is energized to ablate the surrounding nerve. Once ablation is complete, the user can withdraw the catheter device 200.

[0186] Other embodiments for preventing fragments from causing embolism may also be employed. For example, an embolic protection device separate from catheter 200 may be used to provide distal vascular protection. The embolic protection device may include a separate balloon or filter basket attached to a wire. The embolic protection device may be advanced distal to the calcified region. Catheter 200 may be delivered to the calcified region, for example, via the wire of the embolic protection device, to fragment the calcified material and ablate neural tissue. The removed stone (calcification) may be captured and retrieved by the embolic protection device. Other embodiments for decalcifying the calcified region, such as rotational atherectomy, orbital atherectomy, cutting balloons, scoring balloons, or sculpting balloons, may also be employed.

[0187] In the aforementioned embodiment, the laser fiber 303 may be attached to one or more balloons of the catheter 200. The laser fiber may direct energy to an area surrounding the balloon, which may absorb some of the energy and heat up. In one embodiment, an insulating or reflective element may be used to protect the balloon material from heating. For example, an insulating sleeve may be placed over the surface of the balloon between the balloon and the exit of the laser fiber to insulate the surface from the laser energy. Similarly, a foil may be placed between the laser fiber exit and the balloon surface to reflect the laser radiation away from the balloon. This may insulate the balloon material and protect it from laser-generated heat that could damage (e.g., melt) the balloon material.

[0188] In some embodiments, a method of ablating a renal nerve of a subject using catheter device 200 may include emitting energy from a location within the renal artery to the renal nerve. The emitted energy may be acoustic energy, such as ultrasound. An imaging device, such as an x-ray, non-contrast CT scan, PET scan, extravascular ultrasound, intravascular ultrasound, MRI, OCT, IVUS, angiography, or the like, may be used to identify whether a calcified condition exists near and / or around the location within the renal artery. Ablation transducer 500 may ablate the renal nerve if the location is not calcified or if the calcium score at the location is low.

[0189] In some embodiments, a method of ablating a renal nerve of a subject using an ablation device may include emitting energy (e.g., acoustic energy) from a location within the renal artery to the renal nerve. Identifying whether a calcified condition exists near and / or around the location within the renal artery may be performed using an imaging device, such as imaging transducer 520. Decalcification occurs by generating one or more gas bubbles to at least partially fragment the calcification at the location. After the calcification is at least partially fragmented, an ablation transducer is used to ablate the renal nerve. In some embodiments, there may be a lack of calcification and decalcification will not occur. In this case, decalcification may be skipped and ablation may occur instead.

[0190] FIG. 15 is used to describe an exemplary implementation of controller 1500. With reference to FIG. 15, controller 1500 is shown as including one or more processors 1512, memory 1514, user interface 1516, ablation unit excitation source 1518, and demineralization unit excitation source 1520, but may include additional and / or alternative components. Although not specifically shown, processor 1512 may be located on a control board, or more generally, on a printed circuit board (PCB), along with additional circuitry for controller 1500. Processor 1512 is in communication with memory 1514, which may be a non-transitory computer-readable medium that stores instructions. Processor 1512 may execute the instructions to cause system 100 to perform the methods described herein. The user interface 1516 may interact with the processor 1512 to transmit electrical signals, for example at a selected operating frequency, to the ablation unit 401b via wires in a cable extending through the catheter shaft 12a. These wires electrically couple the controller 1500 to the ablation unit 401b, enabling the controller 1500 to transmit electrical signals to and receive electrical signals from the ablation unit 401b and the cavitation / decalcification unit 401a. The processor 1512 may control the ablation unit excitation source 1518 to control the amplitude and timing of the electrical signals, and may control the power level and duration of the ultrasound signal emitted by the ablation unit 401b. More generally, the controller 1500 may control one or more ultrasound treatment parameters used to perform the ultrasound treatment. In certain embodiments, the ablation unit excitation source 1518 may also detect electrical signals generated by the ablation unit 401b and communicate such signals to the processor 1512 and / or control board circuitry.Although the ablation unit excitation source 1518 in FIG. 15 is illustrated as part of the controller, the ablation unit excitation source 1518 can be external to the controller 1500 but controlled by the controller 1500 (more specifically, the processor 1512 of the controller 1500).

[0191] The processor 1512 may control the demineralization unit excitation source 1520 to control the amplitude and timing of the electrical signal, and may control the power level and duration of the ultrasonic signal emitted by the demineralization unit 401a. More generally, the controller 1500 may control one or more demineralization parameters used to perform cavitation. In certain embodiments, the demineralization unit excitation source 1520 may also detect electrical signals generated by the demineralization unit 401a and communicate such signals to the processor 1512 and / or control board circuitry. While the demineralization unit excitation source 1520 in FIG. 15 is illustrated as part of the controller, the demineralization unit excitation source 1520 may be external to the controller 1500 yet controlled by the controller 1500 (more specifically, the processor 1512 of the controller 1500). The user interface 1516 may include a touch screen, buttons, switches, etc., to allow an operator (user) to input patient data, select treatment parameters, view records stored in a storage / retrieval unit (not shown), and / or otherwise communicate with the processor 1512. The user interface 1516 may include a voice-activated mechanism for inputting patient data and may be capable of communicating with additional equipment such that control of the controller 1500 is via a separate user interface, such as a wired or wireless remote control. In some embodiments, the user interface 1516 is configured to receive operator-defined inputs, which may include, for example, duration of energy delivery, one or more other timing characteristics of the energy delivery pulses (e.g., frequency, duty cycle, etc.), power, lumen length, operating mode, patient parameters such as height and weight, and / or verification of arterial diameter, or a combination thereof. Exemplary modes of operation may include, but are not limited to, system activation and setup, catheter preparation, balloon inflation, balloon apposition verification, pre-cooling, sonication, post-cooling, balloon deflation, and catheter removal.In certain embodiments, user interface 1516 provides a graphical user interface (GUI) that instructs the user on how to properly operate system 100. User interface 1516 may also be used to display treatment data for viewing and / or downloading, allow software updates, etc.

[0192] The controller 1500 can also control a cooling fluid supply subsystem 1530, which may include a cartridge and reservoir, an alternative type of fluid pump, or the like. The cooling fluid supply subsystem 1530 is fluidly coupled to one or more fluid lumens 40 in the catheter shaft 12a, which are fluidly coupled to the balloon 14. The cooling fluid supply subsystem 1530 may be configured to circulate cooling fluid through the catheter 200 to the ablation unit 401b within the balloon 14. The cooling fluid supply subsystem 1530 may include elements such as a reservoir for holding cooling fluid, a pump (e.g., a syringe), a cooling coil, and the like, to provide a supply of cooling fluid to the interior space of the balloon 14 at a controlled temperature (preferably below body temperature). The processor 1512 interfaces with the cooling fluid supply subsystem 1530 to control the flow of cooling fluid into and out of the balloon 14. For example, the processor 1512 may control a motor controller coupled to a drive motor associated with a pump (e.g., a syringe) to control the operating speed of the pump. Such a motor controller may be used, for example, when the pump is a positive displacement pump, such as a peristaltic pump. Alternatively or additionally, the control circuit may include structures (not shown), such as controllable valves, connected within the fluid circuit to vary the circuit's resistance to fluid flow. The processor 1512 may monitor pressure measurements obtained by pressure sensors (e.g., P1, P2, P3) to monitor and control the flow of cooling fluid through the catheter 200 and balloon 14. The pressure sensors may also be used to determine whether a clog and / or leak exists in the catheter 200. While the balloon 14 is in an inflated state, the pressure sensors may be used to maintain a desired pressure within the balloon 14, for example, but not limited to, between 10 psi and 30 psi.

[0193] Advantages and benefits of embodiments of the present disclosure include, but are not limited to, removing calcifications that may interfere with sonication and contribute to arteriosclerosis and elevated blood pressure. By providing a catheter device 200, treatment is significantly faster and less traumatic.

[0194] In one embodiment, a tissue treatment system for renal denervation includes a bubble generating device and an ablation device. The bubble generating device is configured to generate one or more bubbles to at least partially fragment calcifications in a calcified region of a renal artery. The ablation device is configured to ablate one or more nerves near, within, or surrounding the calcified region of the renal artery after the calcifications have been at least partially fragmented.

[0195] In one embodiment, the tissue treatment system further comprises an imaging device configured to enable identification of the calcified region of the renal artery.

[0196] In one embodiment, the imaging device is configured to enable a determination of whether the calcification is at least partially fragmented based on an output of the imaging device.

[0197] In one embodiment, the imaging device is an imaging transducer.

[0198] In one embodiment, the gas bubble generating device comprises at least two demineralizing electrodes configured to generate the one or more gas bubbles.

[0199] In one embodiment, the gas bubble generating device comprises a demineralizing transducer configured to generate the one or more gas bubbles.

[0200] In one embodiment, the tissue treatment system further comprises a non-transitory computer-readable memory storing instructions and one or more processors configured to execute the stored instructions to cause the tissue treatment system to perform the following operations: identifying the calcified regions of the renal artery using the output of the imaging device; 2 and energizing the demineralization transducer with 10 to 100 pulses of 10 μsec to 1 ms duration spaced 20 ms to 2 seconds apart at a power intensity of 10 μsec to 1 ms.

[0201] In one embodiment, the tissue treatment system further comprises a first balloon, a non-transitory computer-readable memory, and one or more processors. The first balloon surrounds at least the bubble generation device. The non-transitory computer-readable memory stores instructions. The one or more processors are configured to execute the stored instructions to cause the tissue treatment system to fill the first balloon with fluid so that the first balloon is in apposition with the renal artery and maintain the first balloon at a constant pressure using a flow rate of 0-2 ml / min while the bubble generation device generates one or more bubbles.

[0202] In one embodiment, the gas bubble generator is configured to generate the one or more gas bubbles by applying a voltage of between 500 V / mm and 20 kV / mm across the at least two demineralizing electrodes for a period of time.

[0203] In one embodiment, a tissue treatment system configured to ablate one or more nerves near, within, or surrounding a calcified region of a renal artery includes a non-transitory computer-readable memory and one or more processors. The non-transitory computer-readable memory stores instructions. The one or more processors are configured to execute the stored instructions to cause the tissue treatment system to detect a calcification condition in the renal artery within a target region and to decrease a default acoustic input power setting and increase an ablation duration setting based on the detection of the calcification condition.

[0204] In one embodiment, the one or more processors reduce the acoustic input power by 30% and increase the treatment duration by 35-45%.

[0205] In one embodiment, the one or more processors additionally increase the flow rate by 5% or more based on the detected calcification state.

[0206] In one embodiment, a tissue treatment system includes an ablation device configured to ablate one or more nerves innervating a kidney, a non-transitory computer-readable memory, and one or more processors, the non-transitory computer-readable memory storing instructions. The one or more processors are configured to execute the stored instructions to cause the tissue treatment system to detect calcification scores at one or more target locations along the main renal artery and one or more target locations along at least one of the accessory renal arteries or renal artery branches, determine whether the calcification score is lower at the one or more target locations along the main renal artery or one or more target locations along the accessory renal artery or at least one of the renal artery branches, and prompt a user using a graphical user interface to perform ablation at the one or more target locations along the main renal artery or one or more target locations along the accessory renal artery or at least one of the renal artery branches based on whether the calcification score is lower at the one or more target locations along the main renal artery or one or more target locations along the accessory renal artery or at least one of the renal artery branches.

[0207] In one embodiment, the one or more processors are further configured to execute the stored instructions to cause the tissue treatment system to increase a default treatment duration while maintaining default flow rate and acoustic input power level settings to form a lesion from approximately 1 mm from the lumen of the main renal artery to approximately 1 mm from the lumen of the accessory renal artery or at least one of the renal artery branches.

[0208] In one embodiment, the one or more processors are further configured to execute the stored instructions to cause the tissue treatment system to decrease the acoustic input power below a default setting while increasing a treatment duration setting to form a lesion from approximately 1 mm from the lumen of the main renal artery to approximately 1 mm from the lumen of the accessory renal artery or at least one of the renal artery branches, while still compensating for calcification within the treated main renal artery or the accessory renal artery or at least one of the renal artery branches.

[0209] In one embodiment, a method for ablation of renal nerves comprises delivering a catheter to a calcified region of a cavity wall. The catheter includes a proximal balloon, an intermediate balloon, and a distal balloon attached to a catheter shaft. The catheter includes a laser fiber disposed on a surface of the intermediate balloon. The method further comprises generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region of the cavity wall. The method further comprises ablating one or more nerves near, within, or surrounding the calcified region of the cavity wall after the calcified region is at least partially fragmented.

[0210] In one embodiment, the method further comprises inflating the proximal and distal balloons to substantially align them with the cavity wall to prevent calcified fragments from embolizing.

[0211] In one embodiment, the method further comprises inflating the intermediate balloon to position the laser fiber adjacent the calcified region when generating the one or more bubbles.

[0212] In one embodiment, the method further comprises removing occluding calcified fragments using holes in the catheter shaft.

[0213] In one embodiment, a method for ablation of renal nerves comprises delivering a catheter to a calcified region of a cavity wall. The catheter includes a barbell-shaped balloon attached to a catheter shaft. The catheter includes a laser fiber disposed on a surface of a middle region of the barbell-shaped balloon. The method further comprises inflating the barbell-shaped balloon so that the middle region is longitudinally aligned with the calcified region and the calcified region is longitudinally located between a proximal region and a distal region of the barbell-shaped balloon. The method further comprises generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region of the cavity wall. The method further comprises ablating one or more nerves near, within, or surrounding the calcified region of the cavity wall after the calcified region is at least partially fragmented.

[0214] In one embodiment, the method further comprises delivering a suction device through the space between the cavity wall and the proximal region of the barbell balloon to remove fragments of the calcified region.

[0215] In one embodiment, the method further comprises inflating the proximal and distal regions of the barbell balloon to substantially align with the wall of the body cavity to prevent calcified fragments from embolizing.

[0216] In one embodiment, the method further comprises expanding the central region and positioning the laser fiber adjacent the calcified region when generating the one or more bubbles.

[0217] In one embodiment, a method for ablation of renal nerves comprises delivering a catheter to a calcified region of a cavity wall. The catheter includes a proximal balloon and a distal balloon attached to a catheter shaft. The catheter includes a laser fiber disposed on a surface of the proximal balloon. The method further comprises generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region of the cavity wall. The method further comprises ablating one or more nerves near, within, or surrounding the calcified region of the cavity wall after the calcified region is at least partially fragmented.

[0218] In one embodiment, the method further comprises inflating the distal balloon so that it lines up with the cavity wall to prevent calcified fragments from embolizing.

[0219] In one embodiment, the method further comprises passing a scoop proximally to remove fragments of the calcified region.

[0220] In one embodiment, a computer program product comprises program code portions for performing the operations of any of the above embodiments when the computer program is executed by a processing device, hi one embodiment, a controller or controller system comprises a memory for storing said computer program product.

[0221] In one embodiment, a method for renal denervation comprises identifying a calcified region of a renal artery using an imaging device. In one embodiment, the method further comprises blocking the renal artery. In one embodiment, the method further comprises delivering a laser fiber adjacent to the calcified region. In one embodiment, the method further comprises generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region. In one embodiment, the method further comprises removing the fragments of the calcified region. In one embodiment, the method further comprises ablating nerves surrounding the renal artery.

[0222] As used in this specification and claims, the singular forms "a," "an," and "the" include both singular and plural references unless the context clearly indicates otherwise. For example, the term "unit" can include, and is intended to include, multiple units. In places, the claims and this specification include terms such as "plurality," "one or more," "at least one," etc., but the absence of such terms does not mean that a "plurality" is not intended, and should not be interpreted as such. The terms "calcification" and "calcium" can both refer to calcification in a renal artery.

[0223] The terms "about" or "approximately," when used before a numerical designation or range (e.g., defining a length or pressure), indicate an approximation that may vary by (+) or (-) 5%, by (+) or (-) 1%, or by (+) or (-) 0.1%. All numerical ranges provided herein are inclusive of both the beginning and ending numerical values ​​recited. The term "substantially" refers to the majority (i.e., greater than 50%) or essentially all of a device, substance, or composition.

[0224] As used herein, the term "comprising" means that the devices, systems, and methods include the recited elements and may additionally include any other elements. "Consisting essentially of" means that the devices, systems, and methods include the recited elements and exclude other elements that are essential to the recited combination of purposes. Thus, a system or method consisting essentially of elements defined herein does not exclude other materials, features, or operations that do not materially affect the basic and novel characteristics of the claimed disclosure. "Consisting of" means that the devices, systems, and methods include the recited elements and exclude anything other than insignificant or insignificant elements or operations. Embodiments defined by each of these transition terms are within the scope of this disclosure.

[0225] The examples included herein illustrate, by way of illustration and not limitation, specific embodiments in which the inventive subject matter may be practiced. Other embodiments may be derived and utilized therefrom, and structural and logical substitutions and changes may be made without departing from the scope of the present disclosure. While such embodiments of the inventive subject matter may be referred to individually or collectively by the term "invention" for convenience, no attempt is made to intentionally limit the scope of this application to any single invention or inventive concept when multiple inventions or inventive concepts are actually disclosed. Thus, while specific embodiments are shown and described herein, any arrangements calculated (designed) to achieve the same purpose may be substituted for the specific embodiments shown. The present disclosure is intended to cover any and all adaptations or variations of the various embodiments. Combinations of the foregoing embodiments, as well as other embodiments not specifically described herein, will be apparent to those skilled in the art upon reviewing the foregoing description.

Claims

1. 1. A tissue treatment system for renal denervation, comprising: a bubble generating device configured to generate one or more bubbles to at least partially fragment calcifications in a calcified region of a renal artery; an ablation device configured to ablate one or more nerves near, within, or surrounding the calcified region of the renal artery after the calcification has been at least partially fragmented; A tissue treatment system comprising:

2. an imaging device configured to enable identification of the calcified region of the renal artery; 10. The tissue treatment system of claim 1, further comprising:

3. The imaging device is configured to enable a determination of whether the calcification is at least partially fragmented based on an output of the imaging device. The tissue treatment system of claim 2 .

4. The imaging device is an imaging transducer.

4. The tissue treatment system of claim 2 or 3.

5. The gas bubble generating device has at least two demineralizing electrodes configured to generate the one or more gas bubbles.

5. The tissue treatment system according to claim 1.

6. The bubble generating device includes a demineralizing transducer configured to generate the one or more bubbles.

5. The tissue treatment system according to claim 1.

7. a non-transitory computer-readable memory that stores instructions; Executing the stored instructions causes the tissue treatment system to deliver 1-50 W / cm at a frequency range of 400 kHz to 3 MHz. 2 one or more processors configured to energize the demineralization transducer with 10-100 pulses of 10 μsec-1 ms duration spaced 20 ms-2 sec apart, at a power intensity of 7. The tissue treatment system of claim 1, further comprising:

8. a first balloon surrounding at least the bubble generating device; a non-transitory computer-readable memory that stores instructions; one or more processors configured to execute the stored instructions to cause the tissue treatment system to fill the first balloon with fluid so that the first balloon is in apposition with the renal artery and maintain a constant pressure in the first balloon using a flow rate of 0-2 ml / min while the bubble generator generates one or more bubbles; 8. The tissue treatment system of claim 1, further comprising:

9. The bubble generator is configured to generate the one or more bubbles by applying a voltage of 500 V / mm to 20 kV / mm across the at least two demineralizing electrodes for a period of time.

9. The tissue treatment system of claim 5.

10. 1. A tissue treatment system configured to ablate one or more nerves near, within, or surrounding a calcified region of a renal artery, comprising: a non-transitory computer-readable memory that stores instructions; one or more processors configured to execute the stored instructions to cause the tissue treatment system to detect a calcification status within the renal artery in a target region and to decrease a default acoustic input power setting and increase an ablation duration setting based on the detected calcification status; A tissue treatment system comprising:

11. The one or more processors are configured to reduce the acoustic input power by 30% and increase the treatment duration by 35-45%. The tissue treatment system of claim 10 .

12. The one or more processors are additionally configured to increase the flow rate by 5% or more based on the detected calcification state. The tissue treatment system of claim 10 .

13. 1. A tissue treatment system comprising: an ablation device configured to ablate one or more nerves innervating the kidney; a non-transitory computer-readable memory that stores instructions; Executing the stored instructions to cause the tissue treatment system to: detecting a calcification score at one or more target locations along a main renal artery and at least one of an accessory renal artery or a renal artery branch; determining whether the calcification score is lower at one or more target locations along a main renal artery or at one or more target locations along at least one of an accessory renal artery or a renal artery branch; prompting a user using a graphical user interface to perform ablation at the one or more target locations along the main renal artery or the one or more target locations along the accessory renal artery or at least one of the renal artery branches based on whether the calcification score is lower at the one or more target locations along the main renal artery or the one or more target locations along the accessory renal artery or at least one of the renal artery branches; one or more processors configured to A tissue treatment system comprising:

14. The one or more processors are further configured to execute the stored instructions to cause the tissue treatment system to increase a default treatment duration while maintaining default flow rate and acoustic input power level settings to form a lesion from approximately 1 mm from the lumen of the main renal artery to approximately 1 mm from the lumen of at least one of the accessory renal artery or the renal artery branch.

14. The tissue treatment system of claim 13.

15. The one or more processors are further configured to execute the stored instructions to cause the tissue treatment system to decrease acoustic input power below a default setting while increasing a treatment duration setting to form a lesion from about 1 mm from the lumen of the main renal artery to about 1 mm from the lumen of the accessory renal artery or at least one of the renal artery branches, while still compensating for calcification within the treated main renal artery or the accessory renal artery or at least one of the renal artery branches.

14. The tissue treatment system of claim 13.

16. 1. A method of renal denervation, comprising: Delivering the catheter to the calcified area of ​​the body cavity wall. Equipped with The catheter includes a proximal balloon, an intermediate balloon, and a distal balloon attached to a catheter shaft; the catheter includes a laser fiber disposed on a surface of the intermediate balloon; The method further comprises: generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region of the cavity wall; ablating one or more nerves near, within, or surrounding the calcified region of the cavity wall after the calcified region has been at least partially fragmented; A method comprising:

17. inflating the proximal and distal balloons to substantially align with the cavity wall to prevent embolization of calcified fragments.

17. The method of claim 16, further comprising:

18. Inflating the intermediate balloon to position the laser fiber adjacent the calcified region when generating the one or more bubbles.

18. The method of claim 16 or 17, further comprising:

19. removing the obstructing calcified fragments using holes in the catheter shaft.

19. The method of any of claims 16 to 18, further comprising:

20. 1. A method of renal denervation, comprising: Delivering the catheter to the calcified area of ​​the body cavity wall. Equipped with the catheter includes a barbell-shaped balloon attached to a catheter shaft; the catheter includes a laser fiber disposed on a surface of a middle region of the barbell-shaped balloon; The method further comprises: inflating the barbell balloon so that the central region is longitudinally aligned with the calcified region and the calcified region is longitudinally located between the proximal and distal regions of the barbell balloon; generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region of the cavity wall; ablating one or more nerves near, within, or surrounding the calcified region of the cavity wall after the calcified region has been at least partially fragmented; A method comprising:

21. delivering a suction device through the space between the cavity wall and the proximal region of the barbell balloon to remove fragments of the calcified region.

21. The method of claim 20 further comprising:

22. inflating the proximal and distal regions of the barbell balloon to substantially align with the wall of the body cavity to prevent embolization of calcified fragments.

22. The method of claim 20 or 21, further comprising:

23. expanding the central region and positioning the laser fiber adjacent the calcified region when generating the one or more bubbles.

23. The method of claim 22 further comprising:

24. 1. A method of renal denervation, comprising: Delivering the catheter to the calcified area of ​​the body cavity wall. Equipped with The catheter includes a proximal balloon and a distal balloon attached to a catheter shaft; the catheter includes a laser fiber disposed on a surface of the proximal balloon; The method further comprises: generating one or more gas bubbles with the laser fiber to at least partially fragment the calcified region of the cavity wall; ablating one or more nerves near, within, or surrounding the calcified region of the cavity wall after the calcified region has been at least partially fragmented; A method comprising:

25. inflating the distal balloon so that it lines up with the cavity wall to prevent embolization of calcified fragments.

25. The method of claim 24 further comprising:

26. passing a scoop proximally to remove a fragment of the calcified region.

26. The method of claim 24 or 25, further comprising:

27. 1. A computer program product comprising: Program code portions for performing the operations of any of claims 16 to 26 when the computer program is executed by a processing device. A computer program product comprising:

28. A memory storing the computer program product of claim 27. A controller or controller system comprising:

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