Systems and methods for ultrasound and photoacoustic guidance of coronary procedures

Abstract

Disclosed herein are devices, systems, and methods for ultrasound and photoacoustic guidance of coronary artery procedures. A specific embodiment includes a first catheter equipped with an ultrasound transmitter / receiver and a second catheter having a proximal end and a distal end, with a photoacoustic excitation light transmitter disposed at the distal end of the second catheter. The photoacoustic excitation light transmitter can be configured to emit excitation light in a conical pattern with a specific pulse duration. The second catheter can be configured to detect photoacoustic signals resulting from absorption of the excitation light emitted by the photoacoustic excitation light transmitter. TIFF2023546323000005.tif93128

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 63 / 078,096, filed on September 14, 2020, the entire content of which is incorporated herein by reference.

Background Art

[0002] Background Information Coronary atherosclerotic heart disease is the most common type of cardiovascular disease and causes 370,000 American deaths each year. Percutaneous coronary intervention (PCI) techniques that utilize intravascular devices and stent placement provide effective and minimally invasive treatment options for many patients with severe coronary atherosclerotic heart disease, but their use for treating chronic total occlusion (CTO) remains difficult and controversial. CTO is seen in 20% of patients undergoing angiography for coronary atherosclerotic heart disease [1], and existing treatment options are sub - optimal and are associated with increased morbidity and mortality [2, 3]. Current CTO treatment options include coronary artery bypass graft or CABG (30%), medical management (60%), and PCI (10%) [1, 4]. CABG is effective in reducing morbidity and mortality, but this technique is expensive, not practical for elderly or frail patients, and requires a relatively long recovery time. Another important limitation of CABG is that most bypass grafts utilize veins, which fail early because the venous graft is reused from a low - pressure environment to a high - pressure environment. The increase in arterial pressure in the reused venous graft leads to persistent endothelial cell injury and early onset of atherosclerotic heart disease. As a result, 50% of venous grafts become occluded within 10 years after CABG.

[0003] Pharmaceutical management of CTOs does not address the underlying disease mechanism and often fails to reduce the number of major adverse cardiac events (MACE), resulting in minimal improvement in patient outcomes. PCI, on the other hand, has been shown to significantly improve patient outcomes by reducing angina and MACE [5,6]. Despite being highly effective and minimally invasive, PCI is used in only 10% of CTO cases because the procedure is complex and technically difficult, and can only be performed by a small number of interventional cardiologists [4]. The difficulty in treating CTOs with PCI lies in the challenge of navigating a maneuverable wire to cross the hard fibrous calcified material containing the lesion. Current CTO crossing techniques involve advancing the wire around the plaque and into the subintima of the vessel wall and then re-entering the true lumen. Risks of subintima crossing include vessel wall perforation and side branch occlusion, leading to tamponade and myocardial infarction. Furthermore, in subintimal crossings, final stent placement within the vessel wall via re-entry is associated with an increased risk of restenosis and stent thrombosis compared to true lumen CTO crossings and stent placement [7-11].

[0004] Conventional PCI techniques used for non-CTO stenotic lesions of the coronary arteries involve navigating a wire through the narrowed lumen of the affected artery

[12] . Once the wire is successfully navigated across the atherosclerotic plaque, a stent or atherectomy device can be deployed to further open the narrowed passage and restore normal blood flow. When applied to coronary CTOs, these conventional PCI techniques generally fail because the coronary artery is 100% occluded for a length of 1-2 centimeters, making it nearly impossible for most interventional cardiologists to pass the wire through the CTO while leaving the true lumen intact. The challenges of true lumen PCI include safely puncturing the hard fibrous calcified CTO cap while simultaneously avoiding unintended misdirection of the wire into the subintima, which carries the risk of perforation of the vessel wall and loss of arterial collaterals.

[0005] An alternative method is a technique known as subintima-crossing, which attempts to intentionally guide a wire to the side of a hard fibrous calcified CTO cap. The subintima-crossing method involves advancing a wire through the vessel wall surrounding the CTO lesion. The vessel wall is a three-layered structure consisting of a thin endothelial layer (intima), an intermediate layer (media), and an outer layer. Atherosclerotic disease thickens all three layers. In subintima-crossing, the wire is looped and intentionally advanced across the CTO in either an antegrade and / or retrograde direction within the space between the atherosclerotic plaque and the outer layer of the vessel wall. After advancing the wire through the vessel wall across the CTO, a stent is deployed in the vessel wall or subintima to re-establish blood flow. Once across the CTO, the wire must be returned from the subintima to the true lumen of the coronary artery. Because safely returning the wire to the true lumen is a difficult process, specialized devices such as Stingray balloons and knuckle wires, which can spontaneously re-enter at vascular bifurcations, are used.

[0006] Pharmacological applications can be used to treat angina pectoris in patients with CTOs, but these are not always successful in eliminating angina symptoms. Medical interventional procedures are used to provide CTO treatment when drug therapy is unsuccessful. Two major existing procedures for addressing CTOs are coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). CABG is an invasive surgical procedure in which a healthy artery or vein is transplanted across an occluded coronary artery. The transplanted vessel bypasses the occluded area of ​​the coronary artery, providing a pathway for blood to flow to the myocardium. CABG is a relatively expensive procedure, has a longer patient recovery time, and is more traumatic for the patient compared to PCI.

[0007] PCI procedures typically involve advancing a folded stent into the occluded area and expanding the stent to provide a passage through the previously occluded vessel. Such procedures generally involve guiding a guidewire through the occluded area to allow stent placement. However, in the case of CTOs, it is often not possible to guide a guidewire through a completely occluded area. In such cases, treatment options include guiding a guidewire or other components through or around the occlusion, including through the vessel wall. Specifically, many typical treatment options require guiding components through the subintima-intimal space within the vessel.

[0008] Such treatment options present significant challenges to physicians, partly due to limited available space and associated risks. One of the main challenges is guiding mechanical components beyond the occlusion without inadvertently perforating the vascular wall. Such perforation of the vascular wall can lead to serious complications such as cardiac tamponade, and therefore, avoiding such risks is highly desirable when treating patients with vascular occlusion.

[0009] Furthermore, such procedures can require a considerable amount of time to perform, typically up to three hours. Completing the procedure requires the physician to maintain extreme concentration for an extended period while performing highly precise manipulations. This can lead to physician fatigue and increase the risk of inadvertently perforating the vessel wall. Therefore, few cardiologists are able to perform or willing to perform PCI procedures for CTOs. The extended time required for such procedures also results in the reallocation of resources (both equipment and personnel) normally available for other procedures.

[0010] Due to the technical difficulties and complexity of the procedure, only a small number of highly specialized interventional cardiologists perform subintimal crossing. Furthermore, since the day Antonio Columbo, MD first reported subintimal crossing in 2003, the procedure has been controversial due to the increased risk of serious complications, such as vascular wall perforation [13,14]. Vascular wall perforation results in rapid loss of blood to the pericardium, which usually leads to shock. Rapid blood loss must be stopped immediately by either intravascular placement of a metal coil or deployment of a covered stent at the perforation site. Placement of a metal coil stops the bleeding but induces a localized blood clot that leads to downstream infarction. By deploying a covered stent against the vessel wall, the perforation can be sealed, but the rate of restenosis is high. Another serious risk associated with subintimal crossing PCI procedures is side branch perforation and / or occlusion. During subintimal crossing, the wire may encounter and perforate an arterial side branch, causing myocardial infarction.

[0011] Alternatively, if a stent is deployed in the subintima to restore blood flow to the coronary arteries, the side branches may be occluded by stent expansion, as shown in panels B and C of Figure 1. This is a common complication of branch occlusion during ballooning, where a CTO subintima crossing in one artery leads to cessation of blood flow in the side branches.

[0012] Along with the need for highly specialized interventional cardiologists, these serious risks and potential complications limit the application of subendocardial crossing procedures, meaning that only about 10% of CTO patients benefit from PCI.

[0013] Most patients with calcified CTOs undergoing PCI are currently treated using subintima-crossing procedures, but recent studies have demonstrated that true lumen approaches actually result in better patient outcomes

[15] . Restenosis rates, stent thrombosis rates, and patient mortality are improved with true lumen approaches compared to subintima-crossing

[15] . As a result, a number of endovascular devices have been developed and clinically tested for use in performing true lumen CTO crossing

[16] . These endovascular devices include fiber-optic delivered excimer or mid-infrared laser radiation for CTO ablation, radiofrequency ultrasound (HIFU), acoustic wires, wire centering devices, and mechanical rotablators with side-view OCT imaging. All of these devices have failed clinical trials for crossing coronary artery CTOs

[16] . Excimer laser devices have failed in coronary arteries due to inefficient calcium ablation, inadequate guidance, and nonspecific residual thermal damage. Mid-infrared laser devices can readily cut through rigid fibrous calcified CTO caps

[17] , but these devices have failed due to inadequate guidance and nonspecific thermal damage. HIFU devices have failed due to nonspecific thermal damage and large device size for the most distal coronary artery segments. Acoustic wires have failed because the bending of the wire required to navigate tortuous coronary arteries leads to undesirable contact with the vessel wall, delivering nonspecific acoustic energy and causing vascular damage

[16] . Wire-centering devices do not assist in puncturing calcified fibrous caps. Rigid mechanical cutting devices, such as OCT lateral view rotablators for peripheral circulation, lack the flexibility to safely navigate tortuous coronary arteries, carry a risk of vessel wall perforation, and are too large for use in coronary arteries. Interventional cardiologists do not have readily available access to safe and robust PCI devices capable of true lumen CTO crossover, so there is a recognized opportunity to develop a device that could extend the benefits of PCI procedures to 90% of CTO patients currently being treated with drugs or CABG.

[0014] Therefore, systems and methods that overcome these and other limitations associated with existing systems and methods are desired. [Overview of the Initiative]

[0015] overview There is a recognized urgent need for new endovascular systems and methods that simplify PCI, make the procedure accessible to all interventional cardiologists, and increase the number of CTO patients that can be treated sequentially by PCI rather than CABG or pharmaceuticals. Illustrative embodiments of this disclosure include systems and methods that can treat vascular occlusion (e.g., restore blood flow through the occluded area of ​​a vessel) and address the shortcomings of existing treatment options. Specific embodiments include systems and devices that cross the true lumen of a vessel.

[0016] Previous attempts to develop PCI true lumen catheter devices and procedures for crossing CTOs within coronary arteries have contained drawbacks that hinder successful implementation. For example, such systems incorporated oversized catheter devices that were inflexible or unmaneuverable. Furthermore, such systems did not provide real-time guidance and did not incorporate navigation systems. For instance, while optical coherence tomography (OCT) guidance systems are incorporated into mechanical atherectomy devices, their large size and inflexible tips limit the clinical application of these devices to peripheral arteries of the lower extremities and make them unsuitable for use in smaller coronary arteries with greater curvature and tortuosity. When guidance systems are combined with atherectomy or cutting devices, the size of the catheter increases, making maneuverability and navigation more difficult.

[0017] Several potential CTO guidance imaging systems have been identified, including ultrasound, photoacoustic imaging, optical coherence tomography (OCT), and radiographic imaging. However, each of these candidate guidance systems has potential limitations related to ranging depth, spatial resolution, device size, and biocompatibility. Ultrasound has excellent ranging depth and is biocompatible, but its spatial resolution may be limited by array size or the need for a rotating catheter. Photoacoustic imaging, similar to ultrasound, has excellent ranging depth, good biocompatibility, and tissue specificity, but incorporates both an excitation source and an ultrasound receiver, which can increase catheter size. OCT provides good spatial resolution, but has limited ranging depth (typically around 2 mm) and utilizes a rotating catheter, which increases the size of the CTO device. Radiographic imaging can meet both ranging depth and resolution requirements, and the X-ray source can be placed outside the body. However, radiographic imaging may be limited by biocompatibility in dose measurement and by inadequate imaging of highly curved and tortuous occluded coronary arteries. Furthermore, while only calcium in the arterial wall and luminal plaque allows for X-ray identification of coronary arteries, outer layer calcium and luminal calcium cannot be distinguished by conventional X-ray approaches.

[0018] An exemplary embodiment of the present disclosure includes a CTO guidance and treatment system that provides high-resolution imaging and a small, maneuverable catheter that crosses the CTO using pulsed laser radiation. In certain embodiments, the guidance system combines both ultrasound and photoacoustics using intracardiac echocardiography (ICE) (e.g., located in either the right atrium or right ventricle) to free up space and reduce the size of the crossing catheter.

[0019] Exemplary embodiments using ultrasound / photoacoustic guidance systems and laser CTO catheters can potentially substantially improve outcomes for patients with coronary CTO by successfully introducing a true lumen PCI approach with a small catheter that has superior guidance capabilities.

[0020] A particular embodiment includes an apparatus configured for guidance on the treatment of chronic total occlusion, comprising a first catheter equipped with an ultrasonic transceiver, a second catheter including a proximal and distal end, and a photoacoustic excitation light transmitter located at the distal end of the second catheter, wherein the photoacoustic excitation light transmitter emits excitation light in a conical pattern, the photoacoustic excitation light transmitter emits excitation light with a pulse duration of 50 femtoseconds (fs) to 1 microsecond (μs), and the second catheter is configured to detect a photoacoustic signal resulting from the absorption of excitation light emitted by the photoacoustic excitation light transmitter.

[0021] In certain embodiments, the system further comprises a control module, which is coupled to a first catheter and a second catheter. In some embodiments, the ultrasonic transceiver is configured as a phased array. In certain embodiments, the ultrasonic transceiver comprises a plurality of transducers arranged in a circumferential row extending around the ultrasonic transceiver. In certain embodiments, the circumferential row is a first circumferential row, and the plurality of transducers are further arranged in a second circumferential row extending around the ultrasonic transceiver. In certain embodiments, the control module is configured to control the pulse duration of the excitation light. In certain embodiments, the second catheter comprises a photonic crystal fiber. In certain embodiments, the photonic crystal fiber is a double-clad photonic crystal fiber. In some embodiments, the double-clad fiber comprises a core and a cladding, and the photoacoustic excitation light transmitter is configured as a conical tip of the cladding at the distal end of the second catheter. In certain embodiments, the conical tip extends outward from the distal end. In certain embodiments, the conical tip extends inward from the distal end. In certain embodiments, the core is configured to provide illumination for close-range imaging of the region immediately in front of the distal end. In some embodiments, the photoacoustic excitation light transmitter is configured as a conical tip of a photonic crystal fiber at the distal end of the second catheter. In certain embodiments, the photonic crystal fiber has a multifaceted tip. In certain embodiments, the second catheter is configured to emit excitation light at a wavelength of 930 nanometers (nm). In certain embodiments, the second catheter is configured to emit excitation light at a wavelength of 1200 nm to 1240 nm. In some embodiments, the second catheter is configured to emit excitation light at a wavelength of 1210 nm. In certain embodiments, the second catheter is configured to emit excitation light at a wavelength of 1700 nm to 1740 nm.

[0022] In certain embodiments, the second catheter is configured to emit excitation light at a wavelength of 1720 nm. In certain embodiments, the second catheter is configured to emit excitation light at a first wavelength that is lipid-specific and a second wavelength that is blood-specific. In some embodiments, the second catheter is configured to emit excitation light at a first wavelength of 915 nm, 1210 nm, or 1720 nm, and a second wavelength of 532 nm, 980 nm, or 808 nm.

[0023] A particular embodiment is a method for imaging a blood vessel including a chronic total occlusion (CTO), comprising the steps of: guiding a first catheter equipped with an ultrasound transceiver into a region of the heart; guiding a second catheter into an artery including a chronic total occlusion (CTO); emitting photoacoustic excitation light from the distal end of the second catheter (wherein the photoacoustic excitation light is emitted in a conical pattern, the photoacoustic excitation light is emitted with a pulse duration of 50 fs to 1 us, and the photoacoustic excitation light generates a photoacoustic signal by light absorption in the tissue surrounding the artery or in the tissue within the CTO); and detecting the photoacoustic signal emitted from around the artery or CTO via the first catheter.

[0024] In certain embodiments, the artery is the right coronary artery, and the region of the heart to which the first catheter is led is the right atrium proximal to the right coronary artery. In some embodiments, the artery is the left anterior descending artery, and the region of the heart to which the first catheter is led is the right ventricle proximal to the left anterior descending artery. In certain embodiments, the artery is the left anterior descending artery, and the region of the heart to which the first catheter is led is the vein proximal to the left anterior descending artery. In certain embodiments, the artery is the left circumflex artery, and the region of the heart to which the first catheter is led is the right ventricle proximal to the left anteflex circumflex artery. In certain embodiments, the artery is the left circumflex artery, and the region of the heart to which the first catheter is led is the vein proximal to the left anteflex circumflex artery. In certain embodiments, the artery is the left anterior descending artery, and the region of the heart to which the first catheter is led is the left ventricle proximal to the left anterior descending artery. In certain embodiments, the artery is the left circumflex artery, and the region of the heart into which the first catheter is led is the left ventricle proximal to the left anterior circumflex artery. In certain embodiments, the photoacoustic excitation light is emitted at a wavelength of 930 nanometers (nm). In certain embodiments, the second catheter is configured to emit excitation light at a wavelength of 1200 nm to 1240 nm. In some embodiments, the second catheter is configured to emit excitation light at a wavelength of 1210 nm. In certain embodiments, the second catheter is configured to emit excitation light at a wavelength of 1700 nm to 1740 nm. In certain embodiments, the second catheter is configured to emit excitation light at a wavelength of 1720 nm.

[0025] Certain embodiments further include the steps of transmitting an ultrasonic signal from an ultrasonic transceiver and receiving the transmitted ultrasonic signal by the ultrasonic transceiver. In some embodiments, the photoacoustic signal and the transmitted ultrasonic signal are utilized to kinematically guide a second catheter. In certain embodiments, the kinematic guidance can include any combination of mechanical translation or reorientation. In certain embodiments, the first catheter and the second catheter are coupled to a control module, which is configured to control the pulse duration of the excitation light. In some embodiments, the second catheter comprises a photonic crystal fiber and the photoacoustic excitation light exits from the photonic crystal fiber. In certain embodiments, the photonic crystal fiber is a double-clad photonic crystal fiber. In certain embodiments, the double-clad fiber comprises a core and a cladding, and the photoacoustic excitation light exits from the conical tip of the cladding at the distal end of the second catheter. In certain embodiments, the conical tip extends outwardly from the distal end of the second catheter. In some embodiments, the conical tip extends inwardly from the distal end of the second catheter. Certain embodiments further include the step of illuminating a region immediately in front of the distal end of the second catheter through the core of the double-clad fiber.

[0026] In the following disclosure, the term "coupled" is defined as being connected, although not necessarily directly and not necessarily mechanically.

[0027] The use of the words “a” or “an” in the claims and / or specification in combination with the term “comprising” may mean “one,” but may also mean “one or more” or “at least one.” The terms “about” and “approximately” generally mean ±5% of the stated value. The use of the term “or” in the claims is used to mean “and / or” unless it is explicitly indicated that it refers only to substitutes or that the substitutes are mutually exclusive; however, this disclosure supports the definitions that refer only to substitutes and “and / or.”

[0028] The terms "comprise" (and any form of comprise such as "comprises" and "comprising"), "have" (and any form of have such as "has" and "having"), "include" (and any form of include such as "includes" and "including"), and "contain" (and any form of contain such as "contains" and "containing") are open-ended conjunctive verbs. As a result, a method or device that "comprises", "has", "includes" or "contains" one or more steps or elements has those one or more steps or elements, but is not limited to having only those one or more elements. Similarly, a step of a method or an element of a device that "comprises", "has", "includes" or "contains" one or more features has those one or more features, but is not limited to having only those one or more features. Further, a device or structure configured in a particular manner is at least configured in that manner, but may also be configured in manners not recited.

[0029] Other objects, features and advantages of the present invention will become apparent from the following detailed description. However, while the detailed description and specific examples show particular aspects of the present invention, it is to be understood that various changes and modifications within the spirit and scope of the present invention will be apparent to those skilled in the art from this detailed description and are given by way of illustration only.

Brief Description of the Drawings

[0030] The following drawings form part of this specification and are included to further illustrate certain aspects of this disclosure. The present invention may be better understood by referring to one of these drawings in conjunction with a detailed description of the particular embodiments presented herein.

[0031] [Figure 1] A schematic diagram of the device in an exemplary configuration during use is shown. [Figure 2] A schematic diagram of a part of the embodiment shown in Figure 1 is shown. [Figure 3] A schematic diagram of a part of the embodiment shown in Figure 1 is shown. [Figure 4] A schematic diagram of a part of the embodiment shown in Figure 1 is shown. [Figure 5] Schematic images and ultrasound images of exemplary embodiments of this disclosure are shown. [Figure 6] Schematic images and ultrasound images of exemplary embodiments of this disclosure are shown. [Figure 7] Images of photoacoustic excitation and phantom CTO vascular visualization in exvivota cardiac are shown. Exemplary embodiments of the present disclosure. [Figure 8] Images of photoacoustic excitation and calcified CTO right coronary artery visualization from a human heart are shown. [Figure 9] The image shows photoacoustic excitation, illustrating calcified CTO in the left anterior descending artery in an ex vivo heart. [Figure 10] This disclosure shows a catheter including an inflatable portion as an exemplary embodiment. [Figure 11] This shows the configuration of Figure 10 in use. [Figure 12] This shows the configuration of Figure 10 in use. [Figure 13] A schematic partial cross-sectional view of an exemplary apparatus equipped with a rotation sensor is shown. [Figure 14] A schematic partial cross-sectional view of an exemplary apparatus equipped with a circumferential sensor is shown. [Figure 15] A perspective view of an exemplary apparatus comprising two rows of circumferential sensors is shown. [Figure 16]A partial cross-sectional view of the embodiment shown in Figure 15 is displayed. [Figure 17] This paper presents a time-reversal algorithm that demonstrates the degradation of "circular" wall detection based on distance. [Figure 18] The experimental results of ultrasound and photoacoustic imaging of coronary artery phantoms are shown. [Figure 19] A perspective view of a first exemplary embodiment of the apparatus, comprising a photoacoustic excitation optical transmitting fiber having a multifaceted tip, is shown. [Figure 20] A perspective view of a second exemplary embodiment of the apparatus, comprising a photoacoustic-excited optical transmitting fiber having a multifaceted tip, is shown. [Figure 21] This disclosure demonstrates that a modified fiber tip shape can provide a ring of point output according to exemplary embodiments of this disclosure. [Figure 22] A simulated reconstruction is shown demonstrating the ability to complete all sides of a circle based on the output of the embodiment in Figure 21. [Figure 23] We will show a comparison between two cases: continuous (ring) excitations versus excitations that are a set of points completing the ring. [Figure 24] This shows the equipment used for the transvenous imaging approach in a rabbit model. [Figure 25] Figure 24 shows the results of the transvenous imaging approach in the rabbit model. [Figure 26] This disclosure demonstrates an exemplary embodiment of transvenous catheter placement in an in vivoboda heart. [Figure 27] A schematic diagram and imaging results illustrating exemplary embodiments of this disclosure are shown. [Figure 28] Ultrasonographic and photoacoustic images of the right coronary artery of a pig heart according to exemplary embodiments of this disclosure are shown. [Modes for carrying out the invention]

[0032] Detailed description of exemplary embodiments Exemplary embodiments of this disclosure include systems and methods for use in photoacoustic guidance for the treatment of chronic total occlusion in the coronary arteries. Referring first to Figures 1–4, an apparatus 100 configured for photoacoustic guidance for the treatment of chronic total occlusion (CTO) 150 is shown. In this embodiment, the apparatus 100 comprises a first catheter 110 and a second catheter 120 coupled to a control module 105. In certain embodiments, the first catheter 110 may be configured as an intracardiac echocardiographic photoacoustic ultrasound (ICE-PA) detection catheter, and the second catheter 120 may be configured as a chronic total occlusion (CTO) treatment catheter. Figure 1 shows a schematic diagram of the apparatus 100 in operation, having an ICE-PA detection catheter 110 inserted into a first artery 191 of the heart 190 and a second catheter 120 inserted into a second artery 192 containing the CTO 150. Figures 2–4 provide diagrams of specific parts of the apparatus 100, as will be described in more detail below.

[0033] In the illustrated embodiment, the first catheter 110 includes a proximal end 111 located near the control module 105 and a distal end 112. The ICE-PA first 110 also includes an ultrasonic transceiver 115 near the distal end 112. Furthermore, the second catheter 120 includes a proximal end 121 coupled to the control module 105 and a distal end 122. During operation of the device 100, the distal end 122 can be inserted into an artery of interest, for example, an artery including occlusion or other conditions for treatment. While the exemplary embodiments described herein refer to chronic total occlusion, it is understood that visualization and treatment of occlusions or conditions other than chronic total occlusion are also within the scope of this disclosure. In the illustrated embodiment, a photoacoustic excitation light transmitter 125 is located near the distal end 122 of the second catheter 120. In certain embodiments, the first catheter 110 can first be positioned at a desired cardiac location, and then the second catheter 120 can be guided toward the CTO 150, for example, via a guide catheter (not shown).

[0034] As will be described in more detail below, the first catheter 110 can be inserted into the first blood vessel 191 so that the ultrasound transceiver 115 is positioned at position 118 within the heart 190. The first catheter 110, and in particular the ultrasound transceiver 115, can receive photoacoustic signals 129 corresponding to the position of the distal end 122 of the second catheter 120. These signals can be used to help the user determine the position of the distal end 122 of the second catheter 120. The first catheter 110 can be positioned at different locations depending on which coronary artery contains the CTO 150. For example, the first catheter 110 can be guided to be positioned at position 118 in the right atrium or at position 119 in the right ventricle, based on the position 128 of the CTO 150. In some examples, the first 110 can be positioned at position 118 in the right atrium, close to the right coronary artery (RCA), allowing visualization of the second catheter 120 inside the RCA. In other examples, the first catheter 110 can be positioned at location 119 in the right ventricle to allow visualization of the second catheter 120 in the left circumflex (LCX) artery and the left anterior descending (LAD) artery. If the signal amplitude received by the first catheter is attenuated too much for the CTO in the left anterior descending (LAD) artery or the left circumflex (LCx) artery, the first catheter can be positioned in the left ventricle. Positioning the first catheter closer to the coronary arteries in the left ventricle increases the photoacoustic and ultrasound signal amplitude.

[0035] During the operation of the device 100, the photoacoustic excitation light transmitter 125 can emit excitation light 127 in a conical pattern 124 having a specific pulse duration. In certain embodiments, the photoacoustic excitation light transmitter 125 is a conical tip of a photonic crystal fiber 130. As shown in Figure 3, the photoacoustic excitation light transmitter 125 can be configured as a conical tip 133 extending outward from the distal end 122. In other embodiments, the photoacoustic excitation light transmitter 125 may be configured as a conical tip 133 extending inward from the distal end 122 (for example, a conical relief formed on the distal end 122), as shown in Figure 4. In certain embodiments, the photonic crystal fiber 130 may be a double-clad fiber having a core 131 and a cladding 131, and the conical tip 133 is formed on the fiber cladding 131. In certain embodiments, the core 131 can provide illumination for close-range imaging of the region immediately in front of the distal end 122.

[0036] In a particular embodiment, the control module 105 controls the photoacoustic excitation light transmitter 125 to emit excitation light 127 with a pulse duration of 50 femtoseconds (fs) to 1 microsecond (μs). The photoacoustic signal intensity is the fluence rate (W / m) of the excitation light 127 received by the lipid layer. 2 ) and the absorption coefficient at the excitation wavelength are determined. Specific embodiments utilize wavelengths of 930 nm, 1210 nm, and 1720 nm to contour the lipid layer considering dosimetry of radial fibers, and to achieve a suitable fluence rate for generating a strong photoacoustic signal intensity. The control module 105 maximizes the photoacoustic response by controlling the pulse duration coupled to the pulse energy (pulse energy of mJ in nanoseconds versus pulse energy of uJ in picoseconds). The first 110 may comprise one or more ultrasonic transceivers 115 configured to detect a photoacoustic signal 129 resulting from the absorption of excitation light 127 emitted by a photoacoustic excitation light transmitter 125. In the illustrated example, the photoacoustic signal 129 is generated at the boundary between lipid layers 151 surrounding the blood vessel wall 152.

[0037] The ultrasonic transceiver 115 can receive a photoacoustic signal 129, which can be used to determine the position of the photoacoustic excitation light transmitter 125, and consequently, the position of the distal end 122 of the second catheter 120 relative to the blood vessel wall 152. Thus, detection of the photoacoustic signal 129 can be used to assist in the treatment of the CTO 150 (e.g., material removal) without perforating the blood vessel wall 152. In certain embodiments, the second catheter 120 may include one or more additional lumens 140, 141 to perform additional functions (e.g., close-range imaging, vacuum lumens to assist in material removal, intermittent or pulsed injection of saline or CO2, etc., and temporary cooling of the CTO and artery in response to pulsed laser irradiation to prevent thermal damage that may lead to subsequent restenosis).

[0038] The first catheter 110 can be positioned in different locations depending on which coronary arteries contain the CTO 150 and therefore need to be visualized. For example, the first catheter 110 can be positioned at position 118 in the right atrium or at position 119 in the right ventricle, based on the position 128 of the CTO 150. In some examples, the first catheter 110 can be positioned at position 118 in the right atrium, close to the right coronary artery (RCA), enabling visualization of a second catheter 120 inside the RCA. In other examples, the first catheter 110 can be positioned at position 119 in the right ventricle to enable visualization of a second catheter 120 in the left circumflex artery (LCX) and the left anterior descending artery (LAD). Alternatively, the first catheter 110 can be positioned in the left ventricle to improve imaging of the LAD or LCX.

[0039] The radial / conical transmission of excitation light 127 allows for complete visualization of the cross-sectional region of artery 192 in response to a single photoacoustic excitation pulse. Given the high acoustic impedance mismatch between the vessel wall tissue 152 and the fiber 130, ultrasound imaging allows for the positioning of the fiber 130 via the ultrasound transceiver 115. The position of any cross-section of the fiber 130 can be determined by manipulating the ultrasound transceiver 115 of the first catheter 110 by rotation and bending to obtain a suitable cross-sectional or three-dimensional view. In certain embodiments, the ultrasound transceiver 115 may be a phased array or a single-element rotation / tilt ultrasound transducer. Thus, photoacoustic excitation from the fiber 130 within the lumen of the coronary artery 192 allows for the localization and visualization of CTO structures and luminal boundaries by imaging the lipid layer surrounding the artery or periarterial adipose tissue (PAAT).

[0040] Images obtained by embodiments of this disclosure demonstrate the success of the techniques described herein. Panel A of Figure 5 is an ultrasound (US) image of the periarterial adipose tissue (PAAT) surrounding an ex vivo human coronary artery with a calcified CTO, and panel B of Figure 5 shows that photoacoustic (PA) imaging can visualize blood vessels (BVs) even in calcified CTOs. Panel C of Figure 5 shows PA signals generated at different wavelengths for excitation light 127. In embodiments shown in panel C, the PA signal is maximum at 930 nm. In other embodiments, maximum photoacoustic signals can be obtained in the wavelength ranges of 1200–1240 nm (peaking at 1210 nm) and 1700–1740 nm (peaking at 1720 nm). Panel D of Figure 5 is a schematic diagram of the concepts described in Figures 1 and 2, and panel E shows a schematic diagram of a conical fiber providing radial illumination from the fiber. Panel F of Figure 5 shows a phased array ultrasound image of radial firing fibers inside an affected ex vivo human coronary artery ("x" indicates the fiber position). Finally, panel G of Figure 5 shows PA excitation, imaging, and visualization of the affected ex vivo human BV boundary using US phased array (simulating ICE-PA) (dashed lines depict the lumen wall).

[0041] In the upper schematic diagram of panel A in Figure 6, the upper and lower arrows indicate forward radial illumination from an optical fiber indicated by the central arrow. The optical fiber includes a glass surface shaped to achieve such an illumination spatial profile. The lower schematic diagram of panel A in Figure 6 shows a double-clad fiber having a central core that illuminates the tissue immediately ahead and a cladding that illuminates a forward conical profile for PA excitation. Panel B in Figure 6 shows an ultrasound (US) image of a catheter positioned inside a phantom CTO (indicated by the arrow). Panel C in Figure 6 shows that PA imaging can be used to visualize the phantom CTO vessel wall (BV), indicated by the arrow in panel C.

[0042] Referring to Figure 7, the additional results of PA excitation and phantom CTO vessel visualization placed in an exvivovota heart are shown. The left portion of Figure 7 shows the US imaging of the phantom CTO vessels placed in porcine myocardium. The right portion of Figure 7 shows the PA image of the wall of the phantom CTO vessels placed in porcine myocardium. The open rectangles in the left panel indicate the areas where the PA image was calculated in the right panel. In this case, the excitation light (wavelength 930 nm) is transmitted through a conical illumination fiber (indicated by the arrow in the left panel) placed inside the phantom CTO vessel, illuminating the radial cross-sectional area of ​​the phantom CTO vessel. The two arrows in the right panel highlight the contrast that visualizes the phantom CTO vessel wall.

[0043] Figure 8 shows PA excitation and calcified CTO right coronary artery (RCA) vascular visualization of ex vivo coronary arteries from a human heart that had previously undergone bypass grafting (CABG). All panels (A, B, C, D) are cross-sectional images of the RCA CTO coronary artery as the heart is translated within the field of view of the US / PA imaging system. In panels B and C (unlike panels A and D), lipid plaques are located inside the CTO (highlighted by arrows in the PA images of panels B and C, indicating areas where signs are visible inside the coronary artery, i.e., upward-pointing left arrows). Light is focused from the outside to the inside (from the top of the image to the 8-11 mm region highlighted by left-pointing horizontal arrows in the panel). In all cases, the contour of the lumen boundary can be clearly observed (the region is highlighted only in panels A and D with dashed white circles). The excitation wavelength is selected from the light source that provides the highest contrast in the image. As previously mentioned in Figure 5, excitation wavelengths can be 930 nm, 1200-1240 nm (peaking at 1210 nm), 1450-1470 nm, and 1700-1740 nm (peaking at 1720 nm) (panels F and G in Figure 5 are at 1720 nm).

[0044] Referring to Figure 9, PA excitation and visualization of the left anterior descending artery (LAD) vessel of a calcified CTO are shown in an ex vivo human heart. The left panel shows a US image of the LAD vessel in a human heart. The right panel shows a PA image (obtained with 930 nm excitation) showing the periarterial tissue surrounding the LAD. Light is focused from the outside to the inside (highlighted by the arrow on the right side of the panel, from 8 to 11 mm from the top of the image). The white rectangles in the left panel indicate the areas where the PA image was calculated in the right panel.

[0045] Certain aspects of this disclosure can be used to assist other procedures or techniques, such as the subintima-endarterial trace and re-entry (STAR) crossover to a CTO. Referring here to Figures 10–12, the STAR technique utilizes a catheter 200 having an inflatable flat portion 210. A commercially available embodiment of such a catheter is the Stingray® LP coronary system, available from Boston Scientific. As shown in Figure 11, the catheter 200 is inserted on a guidewire 240 that extends beyond the CTO 230 in the subintima-endarterial space 220 of an arterial vessel 205. The catheter 200 is positioned so that the flat portion 210 is located in the subintima-endarterial space 220 proximal to the CTO 230.

[0046] The flat portion 210 allows for self-orientation along the outer circumference of the arterial vessel 205. As shown in Figure 12, the guidewire 240 can exit the catheter 200 at a first position 241 located on one side of the flat portion 210, or at a second position 242 located on the opposite side of the flat portion 210. In a typical STAR procedure, trial and error is performed to determine which side of the vessel 205 the guidewire 240 must be punctured to achieve re-entry into the true lumen in order to restore blood flow.

[0047] An optical fiber (guidewire compatible) capable of transmitting two excitation wavelengths (lipid-specific (915nm, 1210nm, 1720nm) and blood-specific (532nm, 980nm, 808nm)) makes it easy to identify which side of re-entry corresponds to the blood (position 2 true lumen, blood-specific) and which side corresponds to the outer wall (position 1, lipid layer).

[0048] However, in certain aspects of this disclosure, the second catheter 120 may include an optical fiber (guidewire compatible) capable of transmitting two excitation wavelengths that are lipid-specific (e.g., 915 nm, 1210 nm, or 1720 nm) and blood-specific (e.g., 532 nm, 980 nm, or 808 nm). The lipid-specific and blood-specific wavelengths can be used to determine which side of the re-entry corresponds to the blood (e.g., position 242 corresponding to the true lumen) and which side corresponds to the outer wall (e.g., position 241 corresponding to the lipid layer).

[0049] Furthermore, certain embodiments of this disclosure can be used for guidance in procedures other than CTO procedures. For example, certain embodiments may be incorporated for use in the same way as conventional guidewires, but utilizing the OA-ICE principle for guidance rather than X-ray technology. Such “optical guidewires” can be used, for example, in cardiac catheter intervention (CCI) procedures in distal arteries.

[0050] Before performing a CCI procedure using conventional techniques, the guidewire is positioned correctly based on feedback from conventional X-rays, radiocomputed tomography (CT), and / or fluoroscopy. The guidewire is typically fabricated from a material that contrasts with the surrounding tissue and is easily detectable in X-ray images. However, such techniques can result in increased harmful X-ray radiation exposure to the patient during complex CCI procedures depending on the patient's coronary artery network.

[0051] The OA-ICE guidance utilized by aspects of this disclosure addresses the problem of X-ray exposure that may occur when using the prior art. In certain aspects of this disclosure, a single optical fiber having a conical tip can function as an optical guidewire instead of a conventional guidewire. Such an optical guidewire can be readily detected in intracardiac echocardiography (ICE) due to its high impedance mismatch with innate tissue. The photoacoustic (OA) image generated from this optical guidewire can produce contrast generated by blood and periarterial adipose tissue (PAAT), which typically surrounds the coronary arteries. For example, blood can be imaged via excitation at a wavelength of 532 nm, and PAAT can be imaged via excitation at wavelengths of 930 nm, 1210 nm, and / or 1720 nm. Such OA-ICE guidance can be used to guide the placement of such an optical guidewire within the anatomical structure of the coronary arteries.

[0052] Once the optical guidewire is positioned correctly, the appropriate CCI tool can be supplied along the optical guidewire to reach the location of interest. In certain embodiments, an X-ray contrast marker can also be added to the optical guidewire to position it within the X-ray fluoroscopy field.

[0053] In certain embodiments, the optical guidewire may include a cone-shaped end (as described above in this disclosure). It is understood that other embodiments may incorporate ends of different configurations.

[0054] During such a procedure, an ICE catheter phased array (e.g., a catheter having a photoacoustic excitation light transmitter located at its distal end, as described elsewhere in this disclosure) can be inserted at an appropriate location. In certain embodiments, the location may be the right atrium, right ventricle, or other location that can provide a broad "viewpoint" (e.g., photoacoustic excitation light transmission range) of the anatomical structures of the heart and the structures of interest. The derived OA-ICE signal can be used to guide the crossing of an "optical guidewire" before performing the desired (e.g., CCI) procedure.

[0055] Certain embodiments may also include a control system that includes an interface capable of manipulating, for example, the positioning of the optical guidewire (as defined by r, theta, and z cylindrical coordinates). In certain embodiments, the interface can control the positioning of the optical guidewire as it traverses the patient's coronary artery network to reach the appropriate area for the desired procedure.

[0056] After the optical guidewire is deployed, a suitable tool (e.g., one used in CCI procedures) can be supplied around the fiber, similar to a conventional guidewire. In certain embodiments, the optical guidewire can be controlled by a robotic feedback system to automate the guidewire deployment process. An example of such a robotic system is disclosed in Appl.Sci.2019,9(20),4305;https: / / doi.org / 10.3390 / app9204305. In contrast to the embodiments described above, embodiments of the optical guidewire do not incorporate features for traversing the CTO (e.g., Ho:YAG laser). However, certain examples of embodiments of the optical guidewire incorporate lipid / blood excitation light emitted conically from the optical guidewire to generate an OA-ICE signal to assist in guiding a CCI or other suitable tool to the desired position.

[0057] In certain embodiments, it may be desirable to insert the first catheter 110 into a vein proximal to the artery containing the CTO 150 (for example, instead of in the atrial or ventricular region). For example, if the location 128 of the CTO 150 (or any other condition being treated) is in the left anterior descending artery (LAD), it may be desirable to insert the catheter 110 into a vein proximal to the LAD artery (e.g., the AIV). Similarly, if the location 128 is in the left circumflex artery (CFX), it may be desirable to insert the catheter 110 into a vein proximal to the left CFX artery (e.g., the great cardiac vein).

[0058] For example, if sufficient detection sensitivity of the photoacoustic signal 129 cannot be obtained by placing the first catheter 110 in the atrial or ventricular region, it may be desirable to place the first catheter 110 in a proximal vein. Placing the first catheter 110 in a proximal vein may also be desirable, for example, if there is not enough space in the artery, including the CTO 150 (or other condition being treated), to insert both the first catheter 110 and the second catheter 120.

[0059] Placing the first catheter 110 in a vein proximal to position 128 can offer certain advantages in such situations. For example, reducing the distance between position 128 and the ultrasound transceiver 115 can increase the intensity or strength of the photoacoustic signal 129 detected by the ultrasound transceiver 115. This can improve the accuracy of position 128 detected by the first catheter 110. Furthermore, placing the first catheter 110 in a vein proximal to position 128 rather than in the artery being treated can provide greater space for the second catheter 120 to operate to remove the CTO 150 or otherwise address the treated condition in the artery.

[0060] Certain embodiments may also include different configurations of the ultrasonic transceiver 115. In particular, certain embodiments of the ultrasonic transceiver 115 may include one (or more) transducers that rotate during use to scan the surrounding environment. Other embodiments of the ultrasonic transceiver 115 may include an array of transducers extending around or on the outer circumference of the ultrasonic transceiver 115. Figures 13 and 14 show embodiments of the ultrasonic transceiver 115 with a rotation sensor and a circumferential sensor, respectively. In the embodiment shown in Figure 13, a linear array 310 of transducers 300 is shown. During operation of the embodiment shown in Figure 13, the array 310 rotates around the central axis 117 of the first catheter 110. By rotating the array 310 around the axis 117, the transducers 300 can transmit and / or receive photoacoustic signals around the entire circumference of the lumen (e.g., artery or vein) into which the first catheter 110 is inserted. In the illustrated embodiment, the first catheter 110 is inserted using a guidewire 145. Embodiments utilizing guide wires and rotational sensor arrays may generate artifacts caused by the guide wires (for example, the guide wires may restrict the transmission or reception of photoacoustic signals by the transducers 300 of the linear array 310 during a portion of the rotation).

[0061] Referring here to Figures 15 and 16, a particular embodiment of the ultrasonic transceiver 115 includes a plurality of transducers 300 extending around the ultrasonic transceiver 115. Figure 15 shows a perspective view, and Figure 16 shows a partial cross-sectional view of the ultrasonic transceiver 115 in use. In this embodiment, the transducers 300 are arranged in a first circumferential row 301 and a second circumferential row 302 spaced apart from the first circumferential row 301. In a particular embodiment, the first and second circumferential rows 301, 302 can be configured to provide imaging data from different regions. For example, in one embodiment, the first circumferential row 301 can be configured to provide imaging data from an occluded region, and the second circumferential row 302 can be configured to provide imaging data from a lumen (e.g., an artery or a vein) into which the ultrasonic transceiver 115 is inserted.

[0062] Referring here to Figure 16, the transducers 300 are sequentially activated to transmit signals 310. In the diagram shown in Figure 16, the transducers 300 in the central part of the array are shown transmitting signals 310 toward the target 328. The reflected signals 320 are returned from the target 328 to the transducers 300. Certain embodiments may incorporate aspects of commercially available systems, such as the Eagle Eye Platinum digital intravascular ultrasound (IVUS) available from Koninklijke Philips NV®.

[0063] Embodiments incorporating transducers 300 extending around the ultrasonic transceiver 115 can offer certain features not found in embodiments incorporating a rotating array of transducers. For example, embodiments incorporating transducers 300 extending around the ultrasonic transceiver 115 do not generate guidewire artifacts because the photoacoustic signals are transmitted and received from multiple points on the outer periphery of the transceiver 115. Thus, the guidewire does not obstruct the transmission or reception of each photoacoustic signal from the transducers 300 extending around the ultrasonic transceiver 115 and does not generate artifacts (in contrast to linear rotating array transducers). Furthermore, embodiments incorporating circumferential transducers, as shown in Figures 15 and 16, typically include smaller apertures for the transducers (e.g., less than 1 mm compared to about 3 mm in the rotating array transducer embodiment). Furthermore, the circumferential transducer configuration may require a higher frequency laser in the kHz range, in contrast to the rotary transducer configuration which has a laser frequency of approximately 100 Hz.

[0064] Artifacts of limited field of view are commonly present in photoacoustic tomography images, for example, due to the actual geometric and physical constraints imposed by the imaging system. Near-field reconstruction provides a higher contrast-to-noise ratio (CNR), while image reconstruction for photoacoustic (OA) excitation at longer distances (e.g., beyond 50 mm) provides a lower CNR. This lower CNR can make it difficult to reconstruct images that include the entire circumference (e.g., of blood vessels). In addition to repositioning the ultrasound transceiver to improve the CNR (e.g., by positioning the ultrasound transceiver in a proximal vein of the area being investigated), other embodiments may include different photoacoustic excitation optical transmit fiber tip shapes. Such geometric shapes can provide improved CNR at longer OA excitation distances.

[0065] Longer distances can lead to limited field-of-view issues in photoacoustic reconstruction. In this scenario, the US probe aperture is typically a fraction of the distance from the US probe to the target structure to be detected and / or the relative size of the target to be detected. For example, if a 3mm linear array is placed 50mm away from a 3mm ring, it is difficult to isolate the entire curvature of the ring except for the curvature perpendicular to the US probe aperture. Figure 17 shows a time-reversal algorithm demonstrating the degradation of "circular" wall detection at millimeter-level distances from 15mm to 50mm. Figure 18 shows experimental results of US / OA images acquired with a 64-element probe using an arterial phantom, illustrating the effect.

[0066] However, by modifying the conical tip of the fiber to focus the light and generate a collection of points (Slide 3), it is possible to reconstruct the entire curvature of the blood vessel even over long distances such as 50-55 mm (Slide 4). Slide 5 shows a comparison of the two cases: continuous (ring) excitation versus excitation which is a collection of points that completes the ring. OA detection may be possible using point excitation, which is performed by modifying the tip of the fiber to emit a ring of discrete points or a collection of discrete points.

[0067] For example, in addition to the inward and outward conical tips shown in Figures 3 and 4, in certain embodiments, the photoacoustic-excited optical transmitting fiber 125 may have a polyfaceted tip 138 or 139, as shown in Figures 19 and 20, respectively. The polyfaceted tips 138 and 139 include multiple surfaces 137 that can generate additional output beams from the photoacoustic-excited optical transmitter 125. For example, the polyfaceted tip 138 can generate two output beams from the photoacoustic-excited optical transmitter 125, and the polyfaceted tip 139 can generate four output beams from the photoacoustic-excited optical transmitter 125. The multiple output beams can generate multiple response signals that can be combined and analyzed to improve the CNR at longer OA excitation distances. Other aspects (other than the fiber tip shape) in Figures 19 and 20 are equivalent to those described in Figures 3 and 4 and are not repeated here. Unless otherwise specified herein, the embodiments shown in Figures 19 and 20 will be understood to operate similarly to the embodiments described above.

[0068] As shown in Figure 21, the conical tip of the fiber is modified (for example, as shown in Figure 19 or Figure 20) to focus the light and generate a set of discrete points. By modifying the fiber tip shape, it is possible to provide a "ring" of point outputs, as shown on the left, instead of a continuous output, as shown on the right, relative to the conical tip. In the illustrated embodiment, four opposing output beams are provided, and the output on the left can be created using an adjustable angle between the beams.

[0069] Figure 22 shows a simulated reconstruction demonstrating the ability to complete all sides of a circle. As shown in Figure 22, it is possible to reconstruct all curvatures of blood vessels, even over long distances such as 50-55 mm.

[0070] Figure 23 shows that contouring of the vessel wall is possible on all sides (not just the top and bottom). Specifically, Figure 23 shows a comparison of two cases: continuous (ring) excitation on the right and excitation which is a set of points that complete the ring on the left.

[0071] result Referring here to Figure 24, a transvenous imaging approach in a rabbit model according to an exemplary embodiment of the present disclosure is shown. Panel A of Figure 24 shows a schematic cross-sectional end view of SwiftNINJA® showing a double-clad fiber (DCF) in a central lumen with a circumferential saline port. Panel B of Figure 24 shows a schematic cross-sectional side view showing the central lumen with a spacer centered on the DCF, allowing for the discharge of microliters of saline. In this embodiment, OA excitation light propagates from the DCF in a ring shape, and Tm laser light exits the central lumen forward to resect the CTO. As shown in panel C of Figure 24, this embodiment provides maneuverability of the Cold Laser Wire (CLW) via both deflection and translation. Panels D and E show a saline injector valve with a fast response time (milliseconds) demonstrating electronically triggered saline discharge, and panels F and G show a prototype assembly of the CLW. Panels H and I of Figure 24 show the micromovements possible with SwiftNINJA®(SN) during an in vivo rabbit femoral CTO experiment. Markers on EagleEye®(EE) placed on adjacent veins can be seen as it advances along the guidewire, and radiopaque markers on SwiftNINJA(SN) indicate the tip position relative to the axis of the 5Fr catheter.

[0072] Referring to Figure 25, Panel A shows contrast angiography performed before PCI intervention using CLW, showing occlusion by introduction of an acute CTO plug using thrombin (shown as an oval). Panel B shows the placement of SwiftNINJA® and EagleEye® in the femoral artery and adjacent vein, respectively. Panel C shows confirmation of the artery (upper left circle) using small bubbles injected into the proximal region of the femoral artery through SwiftNINJA® before CLW crossing. Panel D shows post-contrast angiography of the femoral artery (oval) after CLW (SwiftNINJA® + optical fiber) crossing. Panels E, F, and G show periodic images of the artery (upper left circle) using a transvenous imaging approach during PCI crossing, showing SwiftNINJA® and the optical fiber inside the switch during crossing. The diagrams in Panels E, F, and G were used to guide the direction of the CLW relative to the true lumen (upper left circle) during PCI crossing.

[0073] Panels A and B of Figure 26 demonstrate transvenous catheter placement in an in vivo vitreous heart according to exemplary embodiments of the present disclosure. Panel C shows a transvenous (lower circle) EagleEye® image of the CLW fiber tip (arrow) in the mid-LAD ​​(upper circle) in an ex vivo vitreous heart.

[0074] Panel A of Figure 27 shows the EagleEye® electronic scanning scheme, and Panel B shows the OA / US timing diagram showing the laser trigger and OA signal acquisition events. Panel C shows the Fast Fourier Transform (FFT) of the OA-beacon signal (OA source: 1064 nm triggered at OA frame rates of 500 Hz and 10 Hz synchronized with EagleEye®) obtained in the phantom using the EagleEye® catheter. In this embodiment, Panel D shows the results of a model-based transvenous reconstruction algorithm (TRA) using simulated EagleEye® data, showing improved lateral resolution (right) compared to a standard back projection (left).

[0075] Figure 28 shows the results using a 64-element Abbott ViewFlex® ICE transducer at 1205nm (OA amplifier: AMP128, Photosound® Inc., OA: approximately 10mJ / cm²). 2 The images show US (left) and OA (right) images of a pig heart RCA, where the blood vessel wall was detected using a radial firing fiber.

[0076] All devices, systems, and / or methods disclosed and claimed herein can be fabricated and performed without undue experimentation in light of this disclosure. While the devices, systems, and methods of the present invention have been described in relation to specific embodiments, it will be apparent to those skilled in the art that modifications can be applied to the devices, systems, and / or methods in steps or order of steps of the methods herein without departing from the concept, spirit, and scope of the invention. All such similar substitutions and modifications that are apparent to those skilled in the art are deemed to fall within the spirit, scope, and concept of the invention as defined by the appended claims.

[0077] References: The contents of the following references are incorporated herein by reference. TIFF2023546323000002.tif209150TIFF2023546323000003.tif230150TIFF2023546323000004.tif242150

Claims

1. a first catheter comprising an ultrasound transmitter and receiver; a second catheter including a proximal end and a distal end; and a photoacoustic excitation light transmitter disposed at the distal end of the second catheter; Equipped with the photoacoustic excitation light transmitter emits excitation light in a conical pattern; the photoacoustic excitation light transmitter emits excitation light with a pulse duration of 50 femtoseconds (fs) to 1 microsecond (μs); The first catheter is configured to detect a photoacoustic signal resulting from absorption of the excitation light emitted by the photoacoustic excitation light transmitter. A device configured for guidance for the treatment of chronic total occlusions.

2. The apparatus of claim 1 , further comprising a control module, the control module coupled to the first catheter and the second catheter.

3. The apparatus of claim 1 , wherein the ultrasonic transmitters and receivers are configured as a phased array.

4. 10. The apparatus of claim 1, wherein the ultrasonic transmitter / receiver comprises a plurality of transducers arranged in a circumferential array extending around the ultrasonic transmitter / receiver.

5. 5. The apparatus of claim 4, wherein the circumferential row is a first circumferential row, and the plurality of transducers are further disposed in a second circumferential row extending around the ultrasonic transmitter / receiver.

6. The apparatus of claim 2 , wherein the control module is configured to control the pulse duration of the excitation light.

7. The apparatus of claim 1 , wherein the second catheter comprises a photonic crystal fiber.

8. The apparatus of claim 7 , wherein the photonic crystal fiber is a double-clad photonic crystal fiber.

9. the double-clad fiber comprises a core and a cladding; the photoacoustic excitation light transmitter is configured as a conical tip of the cladding at the distal end of the second catheter; 9. The apparatus of claim 8.

10. The device of claim 9 , wherein the conical tip extends outwardly from the distal end.

11. The device of claim 9 , wherein the conical tip extends inwardly from the distal end.

12. The apparatus of claim 9 , wherein the core is configured to provide illumination for close-range imaging of an area just forward of the distal end.

13. The apparatus of claim 7 , wherein the photoacoustic excitation optical transmitter is configured as a conical tip of the photonic crystal fiber at the distal end of the second catheter.

14. The apparatus of claim 7 , wherein the photonic crystal fiber comprises a multi-faceted tip.

15. The apparatus of claim 1 , wherein the second catheter is configured to emit excitation light at a wavelength of 930 nanometers (nm).

16. 10. The apparatus of claim 1, wherein the second catheter is configured to emit excitation light at a wavelength between 1200 nm and 1240 nm.

17. 10. The apparatus of claim 1, wherein the second catheter is configured to emit excitation light at a wavelength of 1210 nm.

18. 10. The apparatus of claim 1, wherein the second catheter is configured to emit excitation light at a wavelength between 1700 nm and 1740 nm.

19. 10. The apparatus of claim 1, wherein the second catheter is configured to emit excitation light at a wavelength of 1720 nm.

20. 10. The apparatus of claim 1, wherein the second catheter is configured to emit excitation light at a first wavelength that is lipid-specific and a second wavelength that is blood-specific.

21. 10. The apparatus of claim 1, wherein the second catheter is configured to emit excitation light at a first wavelength of 915 nm, 1210 nm, or 1720 nm, and a second wavelength of 532 nm, 980 nm, or 808 nm.

Images