Systems and methods for laser-induced calcium fracturing

Abstract

Apparatus, systems, and methods for disrupting calcium in an artery of a patient. Certain embodiments include an expandable member, a laser light source, and an optical fiber coupled to the laser light source. The optical fiber may include one or more emission points configured to emit electromagnetic energy from the laser light source. The electromagnetic energy may be transmitted through a fluid in the expandable member to disrupt the calcium.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 63 / 124,357, filed on December 11, 2020, the entire content of which is incorporated herein by reference.

Background Art

[0002] Background Information Atherosclerotic coronary artery disease is the most common type of cardiovascular disease, causing hundreds of thousands of deaths each year in the United States. Calcium in atherosclerosis is common in coronary artery disease (CAD) and poses problems during coronary intervention. Calcium can reduce arterial compliance, impair cardiac output, and complicate cardiovascular intervention. For example, calcium can prevent complete stent deployment, which can lead to stent thrombosis (heart attack) with high mortality, increasing the complexity of the treatment.

[0003] Solutions currently used clinically to increase vascular compliance and address excess calcium include high-pressure balloon inflation and calcium scoring with cutting balloons. However, these approaches are often unsuccessful for various reasons. Both rotational atherectomy systems (e.g., Rotablator®) and orbital atherectomy are suitable for removing calcium from the surface of the lumen. However, these approaches cannot address deeper calcium and therefore do not always provide sufficient increase in vascular compliance to ensure complete stent deployment. These techniques are also technically complex, time-consuming, and can carry increased risks, as cutting debris can introduce it into the microcirculation, potentially causing myocardial infarction during the procedure. Thus, addressing the calcium challenges of atherosclerosis in a safe and effective manner, including the placement of fully deployed stents, is a major clinical challenge for cardiovascular health and treatment.

[0004] An endovascular lithotripsy technique based on kidney stone treatment is being developed using electrodes inside a balloon catheter. The electrodes vaporize the fluid inside the balloon, generating sound pressure waves that travel through the soft tissue of the blood vessels, selectively fragmenting calcium within the vessel wall. The large difference in density and mechanical properties between calcium and soft tissue makes it possible to fragment calcium with sound pressure while leaving the soft tissue undamaged. However, the use of electrodes limits the amount of energy available and the ability to spatially and temporally control the delivery of energy to vaporize the fluid and induce calcium fragmentation. The electrical approach also results in large voltage spikes, requiring cardiac pacing with each electrical pulse delivered, which is not ideal.

[0005] Therefore, systems and methods that overcome these and other limitations associated with existing systems and methods are desired. [Overview of the project]

[0006] overview There is an urgent need to recognize the potential for effectively disrupting intravascular calcium to treat patient conditions, including atherosclerosis and other coronary diseases. Similarly, the need to decalcify heart valves and aorta is also recognized.

[0007] Exemplary embodiments of this disclosure offer unique advantages over existing systems and methods. For example, it is conceivable that a more effective treatment can be provided by generating sound pressure within an expandable member such as a balloon using electromagnetic energy (including, for example, laser energy). The pressure amplitude generated by the laser is an order of magnitude larger than the pressure generated by the electrodes. In addition, laser irradiation allows for flexible temporal and spatial control of shock wave generation. The advantages of pressure amplitude, as well as temporal and spatial control, can be utilized to provide larger and more efficient calcium fracturing.

[0008] In addition, laser shock wave generation offers the advantage of more precise spatial and temporal control of cavitation or bubble formation in the fluid contained within the balloon, which generates pressure. By varying the duration of the laser pulse, specific bubble shapes with pre-set arrival times can also be formed, which may enable more predictable and improved calcium disruption. Furthermore, the laser approach enables time generation of secondary pulses, which may offer therapeutic benefits. While existing techniques may use optical imaging to verify the effectiveness of calcium disruption after treatment, exemplary embodiments of this disclosure can provide imaging during calcium disruption to monitor the effectiveness of calcium disruption in real time. Specific embodiments of this disclosure may be used to treat calcified aortic stenosis to decalcify the valve leaflets and delay the need for aortic valve replacement (AVR) or transcatheter aortic valve replacement (TAVR). The approach described herein may also be used to induce calcium fracturing in the aorta, which improves elastic rebound in various disease conditions and thus improves blood supply to the microcirculation during diastole.

[0009] Exemplary embodiments include: an expandable member; a laser light source; and an optical fiber connected to the laser light source, the optical fiber comprising one or more emission regions configured to emit electromagnetic energy from the laser light source from the optical fiber, wherein the emission of electromagnetic energy from the one or more emission regions is configured to cause fragmentation in coronary calcium. In certain embodiments, the expandable member comprises a fluid, and the emission of electromagnetic energy from the emission regions is configured to cause fragmentation in coronary calcium by generating ultrasound in the fluid. In particular embodiments, the one or more emission regions are configured as conical reliefs within the optical fiber. In some embodiments, the optical fiber is a first optical fiber; the device further comprises a plurality of optical fibers; and each of the plurality of optical fibers comprises one or more emission regions configured to emit electromagnetic energy from each optical fiber in a radial pattern. In specific embodiments, the expandable member is a balloon.

[0010] In certain embodiments, the expandable member is configured to be expandable via a fluid contained within the expandable member. Certain embodiments further comprise a first port configured to deliver fluid to the expandable member. Some embodiments further comprise a second port configured to drain fluid from the expandable member. In specific embodiments, the fluid is configured to absorb electromagnetic energy from an optical fiber, generate acoustic waves, and propagate to calcium. In certain embodiments, the fluid is saline fluid. In certain embodiments, the optical fiber is configured to emit electromagnetic energy in a radial pattern. In some embodiments, the electromagnetic energy is emitted at a wavelength of approximately 2 μm. In specific embodiments, the electromagnetic energy is emitted at a wavelength of 1.5 μm to 2.5 μm. Certain embodiments further comprise an intravascular imaging device. In certain embodiments, the intravascular imaging device is an intravascular ultrasound (IVUS) device. In some embodiments, the intravascular imaging device is an optical coherence tomography (OCT) device.

[0011] An exemplary embodiment is a method for fragmenting calcium in an artery, comprising the steps of: inserting a catheter into an artery; and emitting electromagnetic energy from the catheter, wherein the calcium is located in an artery, the catheter comprises a laser light source and an optical fiber, a fluid surrounds the optical fiber, the electromagnetic energy is generated by the laser light source, and the electromagnetic energy absorbed in the fluid surrounding the optical fiber generates acoustic waves that enter the arterial wall and fragment the calcium.

[0012] In certain embodiments, the catheter comprises an expandable member, and the method further comprises a step of extending the expandable member. In certain embodiments, the expandable member is extended after the catheter has been inserted into the artery and before electromagnetic energy is emitted from the catheter. In some embodiments, the expandable member is extended to conform to the surface of calcium located in the artery. In specific embodiments, the expandable member is extended via a fluid contained within the expandable member. In certain embodiments, the electromagnetic energy emitted from the catheter is absorbed by the fluid surrounding the optical fiber and propagates into the calcium. In certain embodiments, the electromagnetic energy emitted from the catheter causes cavitation in the fluid contained within the expandable member. In some embodiments, the cavitation generates ultrasound in the fluid contained within the expandable member. In specific embodiments, the ultrasound causes fragmentation in the calcium located in the artery. In certain embodiments, the calcium is heterogeneous, and the fragmentation is formed along the heterogeneity in the calcium. In certain embodiments, the step of fragmenting the calcium increases arterial compliance. In some embodiments, electromagnetic energy is emitted at a wavelength of approximately 2 μm. In specific embodiments, electromagnetic energy is emitted at a wavelength of 1.5 μm to 2.5 μm. Certain embodiments further comprise a step of imaging the arteries during calcium fragmentation, and certain embodiments further comprise a step of imaging the arteries before calcium fragmentation.

[0013] Certain embodiments include an apparatus configured to disrupt coronary artery calcium, comprising: an intravascular imaging device; a stretchable member; a laser light source configured to emit electromagnetic energy; and an optical fiber connected to the laser light source, having a proximal and distal end, and configured to emit electromagnetic energy from the laser light source from the distal end of the optical fiber. In certain embodiments, the stretchable member comprises a fluid, and the electromagnetic energy from the distal end of the fiber is configured to cause disruption in coronary artery calcium by generating ultrasound in the fluid. In some embodiments, the stretchable member is a balloon. In specific embodiments, the stretchable member is configured to be stretchable via a fluid contained within the stretchable member. Certain embodiments further comprise a first port configured to deliver fluid to the stretchable member. Certain embodiments further comprise a second port configured to drain fluid from the stretchable member. In some embodiments, the second port is further configured to discharge vapor bubbles from the stretchable member. In a specific embodiment, the fluid is configured to absorb electromagnetic energy from an optical fiber, generate acoustic waves, and propagate them to calcium. In a certain embodiment, the fluid is indocyanine green (ICG). In a particular embodiment, the electromagnetic energy is emitted at a wavelength of 790–810 nanometers (nm). In a specific embodiment, the electromagnetic energy is emitted at a wavelength of approximately 793 nm.

[0014] In certain embodiments, the electromagnetic energy emitted from the optical fiber is less than 1.0 kilowatt (kW). In specific embodiments, the electromagnetic energy emitted from the optical fiber is approximately 0.6 kW. In some embodiments, the laser light source is a diode laser. In specific embodiments, the intravascular imaging device is an intravascular ultrasound (IVUS) device. In certain embodiments, the intravascular imaging device is an optical coherence tomography (OCT) device. In specific embodiments, the intravascular imaging device has an outer diameter of less than 2.0 millimeters (mm). In some embodiments, the intravascular imaging device has an outer diameter of approximately 1.2 millimeters (mm).

[0015] In the following disclosures, the term “coupled” is defined as “connected,” but the connection does not necessarily have to be direct or mechanical.

[0016] The use of the words “a” or “an” may mean “one” when used in conjunction with the term “comprising” in the claims and / or herein, but is not inconsistent with the meaning of “one or more” or “at least one.” The terms “about” and “approximately” generally mean plus or minus 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 alternative options or that the alternative options are mutually exclusive; however, this disclosure supports the definition of “and / or” referring only to alternative options.

[0017] The terms "comprise" (and any variations of "comprise" such as "comprises" and "comprising"), "have" (and any variations of "have" such as "has" and "having"), "include" (and any variations of "include" such as "includes" and "including"), and "contain" (and any variations 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 method step, 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 certain manner is configured at least in that manner, but may also be configured in ways not recited.

[0018] [Invention 1001] Extendable member and; Laser light source and; An optical fiber connected to the laser light source, It comprises one or more emission regions configured to emit electromagnetic energy from the laser light source through the optical fiber, and The optical fiber is configured such that the emission of electromagnetic energy from one or more emission regions causes fragmentation in coronary artery calcium. <00>00082> A device equipped with the following features, configured to break up coronary artery calcium. [Invention 1002] The extendable member contains a fluid, and The emission of electromagnetic energy from the emission region is configured to generate ultrasound in the fluid, thereby causing fragmentation in coronary artery calcium. Apparatus according to Invention 1001. <000009> Any of the above-mentioned devices of the present invention, wherein one or more emission regions are configured as conical reliefs within an optical fiber. [Invention 1004] Optical fibers are the first optical fibers; <00001>00> The device further comprises multiple optical fibers; and Each of the plurality of optical fibers comprises one or more emission regions configured to emit electromagnetic energy in a radial pattern from each optical fiber. Any of the above-described apparatuses of the present invention. [Invention 1005] Any of the above-described devices of the present invention, wherein the expandable member is a balloon. [Invention 1006] Any of the above-described devices of the present invention, wherein an extendable member is configured to be extended via a fluid contained within the extendable member. [Invention 1007] The apparatus of the present invention 1006 further comprises a first port configured to deliver fluid to an extendable member. [Invention 1008] The apparatus of the present invention 1007 further comprises a second port configured to drain fluid from an extendable member. [Invention 1009] The apparatus of the present invention 1007, wherein a second port is further configured to discharge vapor bubbles from an extendable member. [Invention 1010] An apparatus according to any of the inventions 1006 to 1008, wherein a fluid is configured to absorb electromagnetic energy from an optical fiber, generate acoustic waves, and propagate them to calcium. [Invention 1011] An apparatus according to any of the present invention 1006 to 1010, wherein the fluid is physiological saline fluid. [Invention 1012] Any of the above-described devices of the present invention, wherein the optical fiber is configured to emit electromagnetic energy in a radial pattern. [Invention 1013] Any of the above-described devices of the present invention, wherein electromagnetic energy is emitted at a wavelength of approximately 2 μm. [Invention 1014] Any of the above-described devices of the present invention, wherein electromagnetic energy is emitted at a wavelength of 1.5 μm to 2.5 μm. [Invention 1015] Any apparatus of the present invention further comprising an intravascular imaging device. [Invention 1016] The apparatus of the present invention 1015, wherein the intravascular imaging device is an intravascular ultrasound (IVUS) device. [Invention 1017] The apparatus according to the present invention 1015, wherein the intravascular imaging device is an optical coherence tomography (OCT) device. [Invention 1018] A method for breaking up calcium in an artery, comprising the following steps: The step of inserting a catheter into an artery; and In the step of releasing electromagnetic energy from the catheter, Calcium is located within the artery, The catheter comprises a laser light source and an optical fiber, The fluid surrounds the optical fiber, The electromagnetic energy is generated by the laser light source, and The step involves the electromagnetic energy absorbed in the fluid surrounding the optical fiber entering the artery wall and generating acoustic waves that break down the calcium. [Invention 1019] The method of the present invention 1001, wherein the step of emitting electromagnetic energy includes generating a series of laser pulses. [Invention 1020] The method of the present invention 1019, wherein a series of laser pulses are tuned by selecting a specific combination of pulse duration and power to optimize calcium fragmentation. [Invention 1021] The catheter is equipped with an extendable member, and The method further includes the step of extending the extendable member, The method of the present invention 1018. [Invention 1022] The method of the present invention 1021, wherein an extendable member is extended after the catheter has been inserted into an artery and before electromagnetic energy is released from the catheter. [Invention 1023] The method of the present invention 1021 or 1022, wherein an extendable member is extended to conform to the surface of calcium located within an artery. [Invention 1024] A method according to any one of the present invention 1021 to 1023, wherein an extendable member is extended via a fluid contained within the extendable member. [Invention 1025] The method of the present invention 1024, wherein electromagnetic energy emitted from a catheter is absorbed by a fluid surrounding an optical fiber and propagates into calcium. [Invention 1026] The method of the present invention 1025, wherein electromagnetic energy emitted from a catheter causes cavitation in a fluid contained within an expandable member. [Invention 1027] Cavitation forms vapor bubbles within the expandable member, and The method further includes the step of discharging the vapor bubbles from the expandable member, The method of the present invention 1026. [Invention 1028] In the step of releasing subsequent electromagnetic energy from the catheter after discharging vapor bubbles from the extendable member, The subsequent electromagnetic energy is generated by a laser light source, and The subsequent electromagnetic energy absorbed in the fluid surrounding the optical fiber generates subsequent acoustic waves that enter the artery wall and break down calcium, in a stepwise manner. The method of the present invention 1027, further comprising the above. [Invention 1029] The method of the present invention 1026, wherein cavitation generates ultrasound in a fluid contained within an expandable member. [Invention 1030] The method of the present invention 1029, wherein ultrasound causes fragmentation in calcium located within an artery. [Invention 1031] Calcium possesses heterogeneity, and The crushing is formed along the heterogeneity in the calcium, The method of the present invention 1030. [Invention 1032] A method according to any of the present invention 1018-1031, wherein the step of crushing calcium increases arterial compliance. [Invention 1033] A method according to any of items 1018 to 1032 of the present invention, wherein electromagnetic energy is emitted at a wavelength of approximately 2 μm. [Invention 1034] A method according to any of items 1018 to 1033 of the present invention, wherein electromagnetic energy is emitted at a wavelength of 1.5 μm to 2.5 μm. [Invention 1035] Any method of the present invention 1018 to 1034, further comprising the step of imaging the arteries during calcium lithotripsy. [Invention 1036] Any method of the present invention 1018 to 1035, further comprising the step of imaging the arteries before calcium fragmentation. [Invention 1037] Intravascular imaging devices; Extendable member and; A laser light source configured to emit electromagnetic energy; An optical fiber connected to the laser light source, It has a proximal end and a distal end, and An optical fiber configured to emit electromagnetic energy from the laser light source from the distal end of the optical fiber, A device equipped with the following features, configured to break up coronary artery calcium. [Invention 1038] The extendable member contains a fluid, and The electromagnetic energy from the distal end of the fiber is configured to generate ultrasound in the fluid, thereby causing fragmentation in the coronary artery calcium. Apparatus according to Invention 1037. [Invention 1039] The apparatus of the present invention 1037 or 1038, wherein the expandable member is a balloon. [Invention 1040] An apparatus according to any one of the present invention 1037 to 1039, wherein an extendable member is configured to be extended via a fluid contained within the extendable member. [Invention 1041] The apparatus of the present invention 1040 further comprises a first port configured to deliver fluid to an extendable member. [Invention 1042] The apparatus of the present invention 1041 further comprises a second port configured to drain fluid from an extendable member. [Invention 1043] The apparatus of the present invention 1042, wherein a second port is further configured to discharge vapor bubbles from an extendable member. [Invention 1044] An apparatus according to any of the present invention 1040 to 1043, wherein a fluid is configured to absorb electromagnetic energy from an optical fiber, generate acoustic waves, and propagate them to calcium. [Invention 1045] An apparatus according to any of invention 1040 to 1043, wherein the fluid is indocyanine green (ICG). [Invention 1046] An apparatus according to any of invention 1037 to 1045, wherein electromagnetic energy is emitted at a wavelength of 790 to 810 nanometers (nm). [Invention 1047] An apparatus according to any of invention 1037 to 1045, wherein electromagnetic energy is emitted at a wavelength of approximately 793 nm. [Invention 1048] An apparatus according to any of inventions 1037 to 1047, wherein the electromagnetic energy emitted from the optical fiber is less than 1.0 kilowatt (kW). [Invention 1049] An apparatus according to any of the invention 1037 to 1048, wherein the electromagnetic energy emitted from the optical fiber is approximately 0.6 kW. [Invention 1050] An apparatus according to any of the present invention 1037 to 1049, wherein the laser light source is a diode laser. [Invention 1051] An apparatus according to any of the present invention 1037 to 1050, wherein the intravascular imaging device is an intravascular ultrasound (IVUS) device. [Invention 1052] An apparatus according to any of the present invention 1037 to 1050, wherein the intravascular imaging device is an optical coherence tomography (OCT) imaging device. [Invention 1053] An intravascular imaging device having an outer diameter of less than 2.0 millimeters (mm), according to any of the inventions 1037 to 1052. [Invention 1054] An intravascular imaging device having an outer diameter of approximately 1.2 mm, according to any of the devices described in invention 1037 to 1053. Other objects, features, and advantages of the present invention will become apparent from the following detailed description. However, it should be understood that the following detailed description and examples, while illustrating specific aspects of the present invention, are provided only as examples, as it will be apparent to those skilled in the art from this detailed description that various changes and modifications within the spirit and scope of the invention will become apparent from this detailed description. [Brief explanation of the drawing]

[0019] The following drawings form part of this specification and are included herein to further illustrate certain aspects of the disclosure. The present invention may be better understood by referring to one of these drawings in combination with the detailed description of the specific embodiments presented herein.

[0020] [Figure 1] A schematic diagram of an artery with a guidewire for use with a device based on an exemplary embodiment is shown. [Figure 2] A schematic diagram of an exemplary embodiment based on this disclosure during the initial stages of use is shown. [Figure 3] A schematic diagram of a portion of the configuration shown in Figure 1 during use is provided. [Figure 4] A schematic diagram of a portion of the configuration shown in Figure 1 during use is provided. [Figure 5] A schematic end view of an exemplary embodiment based on this disclosure is shown. [Figure 6] A schematic diagram of a portion of the configuration shown in Figure 5 during use is provided. [Figure 7] A schematic diagram of a portion of the configuration shown in Figure 5 during use is provided. [Figure 8] A schematic diagram of a portion of the configuration shown in Figure 5 during use is provided. [Figure 9] A schematic diagram of a portion of the configuration shown in Figure 5 during use is provided. [Figure 10] An end view of an exemplary embodiment based on this disclosure is shown. [Figure 11] An illustrative dimension diagram of the embodiment shown in Figure 10 is provided. [Figure 12] The graphs show the peak amplitude of pressure as a function of the fluence rate for various techniques. [Figure 13] A graph of the pressure vs. volume compliance curve measured during a test of an exemplary embodiment of this disclosure is shown. [Figure 14] A graph of the pressure vs. volume compliance curve measured during a test of an exemplary embodiment of this disclosure is shown. [Figure 15] The image shows a pre-treatment optical coherence tomography (OCT) image of an artery based on an exemplary embodiment of the present disclosure. [Figure 16] The image shows an optical coherence tomography (OCT) image of an artery after treatment according to an exemplary embodiment of the present disclosure. [Figure 17] A graph showing molar extinction coefficient versus wavelength, based on exemplary embodiments of this disclosure, is shown. [Figure 18] A graph showing pressure vs. joules per pulse, based on exemplary embodiments of this disclosure, is shown. [Figure 19] A graph showing molar extinction coefficient versus wavelength, based on exemplary embodiments of this disclosure, is shown. [Figure 20] A graph showing absorbance versus wavelength, based on exemplary embodiments of this disclosure, is shown. [Figure 21] A graph showing nanorod optical density versus wavelength, based on exemplary embodiments of this disclosure, is shown. [Figure 22] A schematic diagram of an exemplary embodiment of the present disclosure in use is shown. [Figure 23] A cross-sectional view of the embodiment shown in Figure 22 is displayed. [Figure 24] A schematic diagram of one embodiment of the optical fiber shown in Figure 22 is shown. [Figure 25] The images show ex vivo OCT images of human arteries before and after laser-guided lithotripsy. [Figure 26] Images of different subjects before and after laser-guided lithotripsy are shown. [Figure 27] The images show ex vivo microCT images of human arteries before and after laser-guided lithotripsy, illustrating the procedure. [Figure 28] This graph shows pressure vs. energy for different pulse durations in different fluids used in laser-guided lithotripsy procedures. [Figure 29] This shows stenosis in a rabbit model and laser-guided shock wave fracturing in ex vivo human arteries. [Figure 30] This shows one embodiment of a laser light source comprising multiple diode lasers. [Figure 31] The graphs show the absorption coefficient versus wavelength for indocyanine green (ICG) saline solutions of different concentrations. [Figure 32] The graphs show the absorption coefficient versus wavelength for ICG at the same concentration in different solutions. [Modes for carrying out the invention]

[0021] Detailed explanation of illustrative aspects Exemplary embodiments of this disclosure include apparatus and methods for disrupting arterial calcium, including, for example, calcium in the coronary arteries. An overview of exemplary apparatus and methods of use is shown first with reference to Figures 1-4. For clarity, not all features shown in each drawing are numbered in each drawing. In Figure 1, a guidewire 200 is inserted into a coronary artery 250, and calcium 270 is located within the artery 250. In Figure 2, a catheter apparatus 100 is inserted into the artery 250 on the guidewire 200. In the illustrated embodiment, the apparatus 100 comprises an extendable member 110 (e.g., a balloon) and an optical fiber 120 connected to a laser light source 130. In the illustrated embodiment, the optical fiber 120 comprises one or more emission points 140 configured to emit electromagnetic energy 150 (shown in Figure 3) from the laser light source 130 in a radial pattern from the optical fiber 120. In certain embodiments, the emission points 140 may be configured as conical reliefs or ends of the optical fiber 120. In other embodiments, the emission point 140 may be configured as a chamfered, angled, or flat relief or end of the optical fiber 120. In the embodiment shown in the figure, the apparatus 100 comprises a control system 135 configured to control operating parameters of the apparatus 100, including, for example, the operation of the laser light source 130 (e.g., laser pulse duration, frequency, amplitude, etc.).

[0022] In the embodiment shown in Figure 3, the expandable member 110 is expanded within the artery 250 via a pressurized fluid 115 (e.g., saline fluid) within the expandable member 110. In the embodiment shown in the figure, the expandable member 110 is expanded after the device 100 has been inserted into the artery 250 and before electromagnetic energy 150 is released from the device 100. The electromagnetic energy 150 causes cavitation 155 (e.g., bubbles) in the fluid 115, which generates ultrasound 125 from the formation and collapse of the bubbles 155 in the fluid 115. In certain embodiments, the expandable member 110 may be configured as a large balloon configured for distal aortic treatment to increase aortic compliance in elderly patients with treatment-resistant systolic hypertension and to increase elastic rebound during diastole to improve blood flow to the microcirculation.

[0023] As shown in Figure 4, the ultrasound 125 propagates through the fluid 115, causing fragmentation 275 only in the calcium 270 without damaging the vessel wall; this is because the vessel wall is more elastic than the calcium plaque. In exemplary embodiments, fragmentation 275 occurs along the heterogeneity in the calcium 270 and / or within the calcium-hard tissue-soft tissue interface. Fragmentation of the calcium 270 increases the compliance of the artery 250, allowing the artery 250 to expand and contract more easily in response to pressure changes.

[0024] Next, referring to Figures 5-11, another embodiment of the present disclosure in use is shown. This embodiment is similar to the previously described embodiment but includes multiple optical fibers. Not shown in Figures 5-11, but understood to include the components shown in Figures 1-4, such as the laser light source 130 and the control system 135.

[0025] First, referring to Figure 5, an end view of the apparatus 100 is shown with four optical fibers 120. Although four optical fibers 120 are shown in the illustrated embodiment, it should be understood that other embodiments may have more or fewer optical fibers than the four shown in this embodiment.

[0026] In Figure 6, the device 100 is inserted into an artery 250 containing calcium 270. It is understood that a guidewire (not shown) may be used to position this embodiment in a manner similar to the embodiments illustrated and described in Figures 1-4. In Figure 7, a pressurized fluid 115 extends the extendable member 110 within the artery 250 to match the contours of the artery 250 and the calcium 270. In Figure 8, a laser light source (e.g., an equivalent of the light source 130 shown in Figure 2) is activated so that electromagnetic energy 150 is emitted from the emission point 140. As shown in Figure 9, the electromagnetic energy 150 causes cavitation 155 (e.g., bubbles) in the fluid 115, which generates ultrasound 125 from the formation and collapse of bubbles in the fluid 115.

[0027] Next, referring to Figure 10, a schematic cross-sectional end view of a specific embodiment further comprising additional ports, as will be described later, is shown. Figure 10 illustrates one embodiment of the device 100, comprising an expandable member 110 connected to a catheter 114 via a weld (e.g., ultrasonic welding) 112. In the embodiment shown in the figure, the device 110 comprises fluid ports 122 and 124 configured to deliver fluid (e.g., saline fluid) to the expandable member 110, and a vent or drain port 126 configured to discharge fluid, for example, to reduce the cross-sectional diameter and volume of the expandable member 110 before removing the device from the artery. In addition, port 126 may be configured to vent or remove air bubbles from the expandable member 110 after the delivery of electromagnetic energy 150.

[0028] The accumulation of bubbles from the expandable element (balloon) after the laser light source is activated is difficult to control, and their removal is extremely important. The accumulation of one or more bubbles originating from the preceding laser activation can alter the direction of electromagnetic energy during subsequent laser shots (resulting in unfocused delivery), which can lead to complications such as damage to the blood vessel wall.

[0029] The illustrated embodiment also comprises a port 128 configured to receive the optical fiber 120. In the illustrated embodiment, the optical fiber 120 is located within the conduit 121. In certain embodiments, the conduit 121 may be configured as a capillary, and in a specific embodiment, the conduit 121 is a Polymicro Flexible Fused Silica Capillary Tubing with an inner diameter of 200 μm and an outer diameter of 350 μm, available from Molex®. The optical fiber 120 may provide real-time imaging of the procedure (including, for example, optical coherence tomography [OCT] imaging) to provide the user with visual feedback on the degree of calcium fracturing and to enable more precise control of the apparatus 100.

[0030] In certain embodiments, OCT imaging may be used for other purposes, in addition to or instead of calcium fragmentation detection. For example, in certain embodiments, OCT imaging may be used for navigation, identification and sizing of calcium plaques (e.g., to provide more precise treatment) for identifying treatment regimens, and laser control.

[0031] Figure 11 shows an end dimension diagram with dimensions for one specific embodiment of a catheter 114, which includes fluid supply ports 122 and 124, a vent or drain port 126, and a port 128 for an optical fiber. It is understood that other embodiments may have configurations with dimensions different from those shown in Figure 11.

[0032] Exemplary embodiments of this disclosure offer numerous benefits and advantages through intravascular calcium fragmentation in the techniques disclosed herein. For example, the use of light (e.g., laser) energy has clear advantages over the use of electricity in generating appropriate sound waves. These advantages include a greater net energy delivered for a given shape factor of the catheter device. In addition, exemplary embodiments of this disclosure offer greater control over the interaction between the laser and water through pulse duration, pulse repetition rate, wavelength, and fluence / fluence rate. Furthermore, exemplary embodiments offer beam shaping, which enables the formation of conductive bubbles for a given desired sound wave propagation pattern. In addition, given the cost of optical fibers, exemplary embodiments may be provided for more economical catheters. Furthermore, the use of electricity requires pacing with each pulse, whereas light does not result in cardiac pacing.

[0033] Utilizing electromagnetic (e.g., laser) energy to generate sound pressure within a expandable member (e.g., a balloon) is thought to provide a more effective lithotripsy device for fragmenting arterial calcium in the blood vessel wall and increasing vascular compliance. Given the extremely high energy density possible with fiber-delivered laser pulses, for a given shape factor, the calculated and / or measured ultrasonic pressure is an order of magnitude greater than the pressure generated by electrodes. As illustrated in Figure 12, the peak pressure amplitude as a function of fluence rate indicates that a high value of 300 bar can be achieved by delivering radiation through a 200 μm fiber. In comparison, the maximum pressure amplitudes reported in several studies by other researchers (e.g., Shockwave Medical Inc., Santa Clara, CA) are in the range of approximately 40–50 bar. This suggests that using light can generate multiple shock waves in a single pass, or fragment larger calcium deposits, such as calcium nodules.

[0034] The larger amplitude of the pressure waves generated during laser-induced bubble formation and collapse may facilitate larger and more beneficial fracture within the calcium. Triggering with laser irradiation also offers the advantage of more precise temporal control over pressure-generating bubble creation compared to other techniques, including the use of current generated by electrodes. Temporal videography of laser-generated bubbles during testing of exemplary embodiments of this disclosure showed that, in contrast to electrically generated bubbles, laser formation was more uniform and controlled; this may be due to the higher noise levels in currents and the complex and sometimes disordered thermal-mechanical-electrical interactions.

[0035] While other techniques use imaging to verify post-procedure effectiveness, exemplary embodiments of this disclosure can provide real-time imaging feedback on the procedure. Such feedback is necessary to determine the laser dosimetry required to increase vascular compliance in arteries with complex calcification patterns. Exemplary embodiments of this disclosure can combine a high-intensity light source (e.g., a multiphoton light source including a two-photon light source) with imaging techniques on a single double-clad fiber. Such configurations demonstrate how optical coherence tomography (OCT) imaging can be incorporated into a catheter as feedback during laser lithotripsy to evaluate the effectiveness of the procedure. In addition, OCT can also guide the direction of the procedure by detecting calcium within the arterial wall, which allows for adjusting the acoustic effect of laser lithotripsy based on the location and load of calcium. In certain embodiments, OCT imaging can provide guidance not only by detecting calcified lesions or calcium plaques, but also by real-time calcium scoring using measurements of parameters such as thickness, length, and angle. Exemplary embodiments may include any of a number of options regarding the interaction between the laser and water. Water has absorption peaks at 1.3 μm, 1.94 μm, 2.07 μm, and 2.94 μm. Lasers readily available that correspond to these wavelengths are neodymium-yttrium-aluminum garnet (Nd:YAG), thulium (Tm), holmium-yttrium-aluminum garnet (Ho:YAG), and erbium (Er:YAG).

[0036] Referring next to Figure 22, an illustrative overview of an exemplary apparatus and method of use is illustrated. This embodiment is similar to the previously described embodiment and also comprises one or more intravascular imaging devices. For clarity, not all features shown in each drawing are numbered in each drawing. For example, apparatus 100 may comprise a laser light source and a control system configured to control operating parameters of apparatus 100, similar to the control system 135 and laser light source 130 shown in Figure 3; including, for example, the operation of the laser light source (e.g., laser pulse duration, frequency, amplitude, etc.).

[0037] In Figure 22, a guidewire 200 is inserted into a coronary artery 250, and calcium 270 is located within the artery 250. In this embodiment, a portion of the device 100 is inserted into the artery 250 on the guidewire 200. In the embodiment shown in the figure, the device 100 comprises an extendable member 110 (e.g., a balloon) and an optical fiber 120 connected to a laser light source (e.g., an equivalent of the laser light source 130 in Figure 3).

[0038] The apparatus 100 also comprises an intravascular imaging device 160. In a particular embodiment shown in the figure, the intravascular imaging device 160 is configured as an intravascular ultrasound (IVUS) device comprising an ultrasound transceiver 162, the ultrasound transceiver 162 comprising a plurality of transducers 164 extending around its outer circumference. In a certain embodiment, the transducers 164 are arranged circumferentially as one or more rows around the ultrasound transceiver 162. In an exemplary embodiment, the transducers 164 may be configured to provide imaging data from the entire inner circumference of the lumen (e.g., artery 250) into which the ultrasound transceiver 162 is inserted. In a specific embodiment, the ultrasound transceiver 162 may incorporate aspects of a commercially available system, such as the Eagle Eye Platinum digital intravascular ultrasound (IVUS) system available from Koninklijke Philips NV®.

[0039] An exemplary embodiment comprising transducers 164 extending around the outer circumference of the ultrasonic transceiver 162 can provide certain features not seen in other embodiments, such as embodiments incorporating an array of rotating transducers. For example, because the guidewire 200 extends through the interior of the ultrasonic transceiver 162, the photoacoustic signal is transmitted and received from multiple points around the circumference of the transceiver 162, so the guidewire 200 does not introduce artifacts. Therefore, (in contrast to a linear array of rotating transducers) the guidewire 200 does not block the transmission and reception of photoacoustic signals for each of the transducers 164 extending around the outer circumference of the ultrasonic transceiver 162, and thus does not introduce artifacts.

[0040] In addition, the configuration incorporating the circumferential transducer 164 allows for the transmission and reception of photoacoustic signals from multiple points around the circumference of the transceiver 162 without moving the transceiver 162. Therefore, it is not necessary to rotate the transceiver 162 to provide imaging data for the inner circumference of the artery 250. The ability to provide circumferential imaging data without rotating the transceiver 162 allows for a smaller diameter of the device 100 compared to configurations that require a mechanism for rotating the imaging device. Therefore, the device 100 shown in Figure 22 can be inserted into lumens with smaller diameters compared to coronary arteries, such as peripheral arteries.

[0041] In the embodiment shown in Figure 23 (a cross-sectional view along line AA in Figure 22), the device 100 has an outer diameter of approximately 1.5 millimeters (mm). The transceiver 162 has an outer diameter of approximately 1.2 mm, the optical fiber 120 has an outer diameter of approximately 0.32 mm, and the guidewire 200 has an outer diameter of approximately 0.23 mm. Both the guidewire 200 and the optical fiber 120 extend through the transceiver 162, which is located within the 1.5 mm diameter catheter of the device 100. It is understood that the diameters disclosed herein are illustrative of one embodiment only, and other embodiments may comprise components of different diameters. Although not shown in the figures for clarity, it is understood that the embodiments shown in Figures 22-23 may also comprise one or more fluid ports configured to deliver fluid to the expandable member 110, and a vent or drain port configured to discharge fluid from the expandable member 110, similar to those in the previously described embodiments.

[0042] In the embodiment shown in Figure 22, the expandable member 110 is extended within the artery 250 via a pressurized fluid 115 within the expandable member 110. In certain embodiments of this disclosure, the fluid 115 may be saline or indocyanine green (ICG), an FDA-approved solution that provides an absorption coefficient more than five times that of saline. It is understood that other embodiments disclosed herein may also comprise saline or ICG.

[0043] In this embodiment, the optical fiber 120 extends through the transceiver 162 into the interior of the expandable member 110. During operation, the optical fiber 120 may transmit electromagnetic energy 150 from its distal end 129. In certain embodiments, the distal end 129 is configured to transmit electromagnetic energy 150 in a specific direction toward the artery 250. For example, the distal end 129 may be configured to provide directional transmission of electromagnetic energy 150 (e.g., chamfered, tapered, faceted, or angled). The user can direct or target the electromagnetic energy 150 toward the calcium 270 by using an intravascular imaging device 160 to determine the location of the calcium 270 within the artery 250. In certain embodiments, the electromagnetic energy 150 is provided by a diode laser (793 nm, 0.6 kW, available from DILAS Coherent® Inc.). The 793 nm wavelength is suitable for an expandable member filled with ICG fluid that provides strong optical absorption in the range of 790–810 nm.

[0044] As mentioned above, the electromagnetic energy 150 causes cavitation 155 (e.g., bubbles) in the fluid 115, which generates ultrasound 125 from the formation and collapse of the bubbles 155 in the fluid 115. By directing the electromagnetic energy 150 toward the calcium 270, the cavitation 155 and ultrasound 125 are also directed toward the calcium 270 and not toward the portion of the artery 250 where calcium 270 is not deposited. Therefore, the portion of the artery 250 that does not contain calcium 270 deposition is not subjected to the forces associated with cavitation 155 and ultrasound 125, and is therefore less likely to be damaged by such forces. Since the calcium deposition 270 is not uniformly distributed, being able to acquire imaging data of the blood vessel 250 to determine the location of the calcium 270 and target the electromagnetic energy 150 to those locations may result in increased patient safety and reduced risk.

[0045] Certain embodiments may also incorporate other mechanisms for acquiring imaging data within the artery 250. For example, referring to Figure 24, in certain embodiments, the optical fiber 120 may be configured as a double-clad fiber (e.g., a DCF13 fiber available from Thorlabs Inc.) with a distributed refractive index (GRIN) lens 127 connected to its distal end 129. In such embodiments, the GRIN lens 127 may be used to acquire optical coherence tomography (OCT) image data beyond the distal end 129.

[0046] Referring now to Figure 30, one embodiment of a laser light source 130 is shown, comprising a power supply 131 electrically connected to a plurality of diode lasers 132. In the embodiment shown in the figure, the diode lasers 132 are connected to an optical fiber 120 via a fiber combiner 133 and an optical fiber 134. In a particular embodiment, the diode laser 132 may be a 793 nm or 808 nm laser emitting 100 watts, which emits electromagnetic energy at a wavelength close to the maximum absorption coefficient for a specified concentration of ICG formulation in a stretchable member (not shown in Figure 30) connected to the optical fiber 120. In a particular embodiment, the optical fiber 134 may be a 105 μm or 125 μm silica core fiber, or the optical fiber 134 may be a biocompatible 250 μm fiber.

[0047] This embodiment allows for the provision of higher levels of electromagnetic pulse energy coupled to an absorbent fluid medium at a lower cost by combining multiple diode lasers with a single power supply and fiber combiner. In a particular embodiment, 19 diode lasers may be coupled to a single power supply, while in other embodiments, a different number of diode lasers may be provided. The use of diode lasers also enables a compact configuration and a flexible pulse profile. Thus, embodiments utilizing multiple diode lasers can provide sufficient electromagnetic energy to an absorbent biocompatible fluid within a stretchable member for effective calcium fragmentation.

[0048] In addition, the absorbent biocompatible fluid within the expandable member may be configured to efficiently break down calcium with respect to the electromagnetic energy provided. As the molar concentration of ICG in the solution increases, the absorption coefficient also increases. However, this increase is not linear. Therefore, when the concentration of 1x is 1 cm³ -1 However, 100x does not necessarily mean 100 cm -1 No, that's not the case. This is due to the "aggregation" effect of cyanine pigments. Cyanine pigments, including ICG, tend to aggregate at high concentrations in aqueous solutions, which can reduce the absorption coefficient.

[0049] A lower degree of aggregation means that less power is required to generate the same pressure. Dimethyl sulfoxide (DMSO) can be used to avoid aggregation in ex vivo applications, but it is not biocompatible. Therefore, exemplary embodiments of this disclosure may include other techniques, such as dissolving cyanine dyes in liposome-type nanodroplets. In addition, exemplary embodiments of this disclosure may use plasma or albumin instead of water in the solution to increase the absorption coefficient.

[0050] Next, referring to Figure 31, the absorption coefficients of ICG as a function of wavelength are shown for different concentrations of ICG in physiological saline solution. ICG has an absorption coefficient of > 256 cm⁻¹ at 808 nm. -1 It has an absorption coefficient of , and the peak power requirement is reduced to one-fifth as aggregation is reduced (for example, a one-fifth cost reduction).

[0051] The absorption coefficient of ICG is also affected by the solution in which ICG is diluted. Referring to Figure 32, the absorption coefficient against wavelength is shown for the same concentration of ICG in different solutions. As shown in Figure 32, albumin yielded the highest absorption coefficient, while water yielded the lowest. The excimer wavelength of 308 nm corresponds to approximately 100 cm in serum albumin. -1It has an absorption coefficient of . ICG mixed in albumin has a higher absorption coefficient, and iodine contrast agents (such as those mixed with physiological saline for use in X-ray fluorescence fluoroscopy or X-ray angiography; e.g., OmniPaque® (iohexol), iobersol, etc.) have an absorption coefficient of approximately 400-500 cm in a 50 / 50 percent mixture. -1 That is the case.

[0052] Pure or 100% contrast agents are effective at 900-1000 cm⁻¹. -1 While this results in a certain absorption coefficient, 100% contrast agents are viscous and become extremely viscous in small lumens, making it difficult to flow the contrast agent into small lumens and fill intravascular balloons. However, mixing the contrast agent with water or saline in a 50 / 50 percent ratio makes it flow more easily. This mixture provides an easy flow to fill the balloon and generates the shock waves necessary to break up calcium. In addition, it has been found that when the contrast agent is mixed with blood or hemoglobin, the pressure from the shock waves increases while maintaining a constant flow to fill the intravascular balloon.

[0053] In summary, tests show that a stretchable material (e.g., a balloon) filled with 100 percent contrast agent can achieve a pressure of approximately 50 bar at an excimer wavelength of 308 nm. The blood / hemoglobin mixture inside the balloon and the 308 nm excimer wavelength can also reach a pressure of 50 bar. Therefore, by utilizing a contrast agent inside a balloon and illuminating the solution with a 308 nm excimer wavelength, a sufficient pressure amplitude can be achieved to induce calcium disruption.

[0054] In summary, tests show that a stretchable material (e.g., a balloon) filled with 100 percent contrast agent can achieve a pressure of approximately 50 bar at an excimer wavelength of 308 nm. The blood / hemoglobin mixture inside the balloon and the 308 nm excimer wavelength can also reach a pressure of 50 bar. Therefore, by utilizing a contrast agent inside a balloon and illuminating the solution with a 308 nm excimer wavelength, sufficient pressure can be achieved to induce calcium disruption. [Examples]

[0055] result Figures 13-16 illustrate the results of the test described in more detail later. For this test, a Ho:YAG laser with a wavelength of 2.07 μm was selected, with a pulse duration of approximately 150 ms. Considering the known facts about the interaction between lasers and water, the best choice for laser dosimetry is considered to be a laser module with a shorter pulse duration (ns), higher water absorption coefficient, and higher energy density. This suggests Er:YAG (2.94 μm, with a higher water absorption coefficient). Er:YAG delivery fibers, such as germanium, are not biocompatible for implementation in one of these catheters. Therefore, the optimal choice is a thulium (1.94 μm) laser with a nanosecond pulse duration capable of delivering pulsed laser energies of 1 μJ to 5 J. However, considering the relative possibility of utilizing higher energy laser pulses at this wavelength, Ho:YAG, the closest option, was used in this test.

[0056] To test the ability of lasers to generate calcium-disrupting pressure waves, preliminary studies were conducted on fresh specimens of calcified human coronary arteries (n = 9). Arterial compliance was measured before and after holmium laser treatment, along with OCT imaging and histological examination.

[0057] Hearts were received from South Texas Blood and Tissue. Inclusion criteria for hearts included a history of CAD, or factors indicative of CAD and calcium load, namely advanced age, overweight, hypertension, history of bypass surgery, and diabetes. Coronary arteries were transected from the hearts. The left anterior descending artery (LAD), right coronary artery (RCA), and left circumflex artery (LCX) were all imaged by OCT. Intravascular calcium was identified using OCT. The location of calcium was marked on the outside of the vessels with dye so that compliance testing and laser treatment could be targeted to the same area where calcium was present.

[0058] Vascular compliance was measured after position identification. A balloon catheter was selected based on the size of the vessel. A vascular compliance curve was obtained by inflating the balloon using a manual balloon catheter pump (Endoflator®) and recording the balloon pressure in a given volume of added saline solution. This curve was repeated three times for each of four conditions: in air before and after other tests; and in the vessel before and after laser treatment; to measure the baseline compliance of the balloon and to ensure that there was no variation during the experiment due to balloon fatigue. The balloon position in the vessel was determined by the calcium position indicated by a dye.

[0059] For this trial, two holmium lasers were available: MOSES® Pulse 120H (Lumenis®, Yokneam, Israel) and Coherent Holmium:YAG (Lumenis®, Yokneam, Israel). These provided the energy source for the procedure through a cone-tipped optical fiber. Various pulse counts and patterns were tested for both lasers to determine the optimal treatment option. These lasers differed tenfold in the amount of pulse energy they could deliver. The aiming beam on the laser allowed for the treatment to be directed to an area marked with dye. After laser treatment, a second vascular compliance measurement and follow-up OCT images were recorded. These second OCT images were then aligned with the pre-test OCT images. The OCT images were analyzed for visible signs of calcium disruption; changes in lumen area could be calculated for quantitative characterization. The delta or increase in compliance of the compliance curve before and after laser treatment was used as an endpoint measure for procedure success.

[0060] Nine coronary arteries derived from four human hearts were tested. In each coronary artery, arterial compliance increased after laser treatment, leading to successful procedures. Figures 13 and 14 illustrate the recorded arterial compliance curves. Post-laser compliance (square markers) shows improvement compared to pre-laser compliance (round markers), while still being higher than the compliance with the balloon alone (solid line). If post-laser compliance is the same as that of a balloon in air, it would indicate that the coronary artery has extremely high compliance, suggesting possible damage to the arterial wall.

[0061] Figures 15 and 16 are optical coherence tomography (OCT) images of calcium-containing arteries before (Figure 15) and after (Figure 16) treatment using the method disclosed herein. As indicated by the white arrows in Figure 15, the calcium in the arteries is fragmented after treatment.

[0062] Next, referring to Figures 17 and 18, data from one exemplary embodiment are shown, involving a laser source emitting radiation in the 700–850 nm wavelength range and absorbed by indocyanine green (ICG). In this embodiment, ICG has an absorption spectrum in the 700–850 nm range, and the absorption peak can be tuned by the ICG concentration measured in micromolar units (see, for example, https: / / omlc.org / spectra / icg / ). For example, at 2.2 mg / mL (maximum concentration in liquid form, 2830 uM), the absorption coefficient can be as high as 240 cm⁻¹ at 755 nm and 311 cm⁻¹ at 700 nm. This is considerably higher than the absorption wavelength for saline / water for a holmium laser (for comparison, e.g., the local maximum at the absorption peak of water for a 1940 nm Tm laser is 119.83 cm⁻¹, and for a 2.09–2.10 u holmium laser it is about 30 cm⁻¹).

[0063] Using alternative fluids (instead of saline) for laser shock wave generation allows existing lasers to be used at approximately 755 nm, including, for example, Picosure (755 nm, 900 ps, ​​200 mJ, manufactured by Cynosure); GentleLase (755 nm, >1 ms, 25 J, manufactured by Candela); Alexandrite (750 nm, 5~10 ns, 150 mJ); and Laser Diode (793 nm, 1600W power, pulse duration: 100 ns~100 us, 500 us~CW, other options: 808 nm, 1600W).

[0064] The recorded shock wave pressure amplitude was 1000 psi (200 mJ, 900 ps). Figure 18 shows a graph of pressure as energy per pulse generated with ICG (approximately 2.2 mg / mL) using a Cynosure Picosure laser (755 nm, 900 ps).

[0065] Referring to Figure 19, data from another embodiment were obtained using a laser source with a wavelength range of 500-600 nm along with a blood / Hb fluid solution contained in a balloon. Blood has an absorption peak with an intensity of approximately 250 cm⁻¹ at 532 nm. The absorption of blood at 532 nm is several times higher than the absorption of water (approximately 30 cm⁻¹) at the emission wavelength of the holmium laser. Candidate fluids to fill the balloon to generate the pressure required to break up calcium in the blood vessel wall could be biocompatible hemoglobin or whole blood from the same patient.

[0066] Figures 20 and 21 show data for an embodiment in which a biocompatible nanoparticle solution is contained inside a balloon. In this embodiment, gold nanorods provide a tunable absorption spectrum. For example, nanorods produced by NanocomposiX and other manufacturers have an absorption peak at a wavelength of 980 nm (up to 230 cm⁻¹, up to 100 optical density [OD]). Numerous suppliers of 980 nm diode lasers are also available (delivered up to 570 W in 100 μm silica fiber). Other biocompatible nanorods / nanoparticles can also be manufactured and may be selected depending on the availability of laser sources (808 nm, 793 nm, 980 nm, 976 nm, 1210 nm, etc.) and the corresponding optical fiber delivery options.

[0067] It should also be noted that albumin (human serum albumin), when mixed with ICG, or on its own, has strong absorption at wavelengths within the ultraviolet (UV) spectrum. In certain embodiments, a UV laser (e.g., xenon monochloride [XeCl]) excimer or other UV laser diode may be used to generate shock waves within these albumin-filled balloons or albumin and ICG-filled balloons to disrupt calcium within the blood vessel walls.

[0068] Next, referring to Figure 25, Panel A shows an OCT image of an ex vivo human artery before undergoing laser-guided lithotripsy according to this disclosure. Panel B of Figure 25 shows an OCT image of the same artery after laser-guided lithotripsy has been performed. As shown in Panel B, fragments have formed within the calcium, and the cross-sectional area of ​​the artery has increased from 3.45 mm² before laser-guided lithotripsy. 2 (from) 5.48 mm 2 It increased to [a certain value].

[0069] Panels C and D of Figure 26 show images of Ultracal® 30 stones before and after fragmentation demonstrated under IVUS guidance using a flat 230 μm core fiber, respectively, in accordance with this disclosure. Panels E and F of Figure 26 show IVUS images before and after laser-guided lithotripsy fragmentation within a calcified coronary artery phantom (fragmentation is indicated by arrows in panels D and F). Panels G and H of Figure 27 show microCT images before and after ex vivo human arteries demonstrating laser-guided fragmentation (fragmentation is indicated by arrows in panel H). Figure 28 shows graphs of pressure (bars) against energy (joules) for different pulse durations in ICG (circles) and saline (squares); delivered in the fiber with pulse durations of 0.9 ns and 70 us. Scale bar is 1 mm.

[0070] Panels A–D of Figure 29 show in vivo fluoroscopy images of rabbit models exhibiting varying levels of stenosis from 25 percent to 100 percent. Panel E of Figure 29 shows hematoxylin-eosin (H&E) staining and von Kossa staining of the model arteries in the upper and lower rows, respectively, at 4x magnification. The brown areas in the von Kossa staining are calcium. Panels F and G of Figure 29 show laser-guided shock wave fracturing (black arrows in panel G) in ex vivo human arteries compared to a control (shown in panel F); the scale bar is 1 mm.

[0071] All devices, systems, and / or methods disclosed and claimed herein can be made and performed without excessive experimentation in light of this disclosure. While the devices, systems, and methods of the present invention have been described in terms of specific embodiments, it will be apparent to those skilled in the art that variations may be applied to the steps or sequence of steps of the devices, systems, and / or methods described herein without departing from the concept, spirit, and scope of the invention. All such similar substitutions and modifications, which are apparent to those skilled in the art, shall be deemed to be within the spirit, scope, and concept of the invention as defined by the appended claims.

[0072] References The contents of the following references are incorporated herein by reference. TIFF0007864712000001.tif180151

Claims

1. Extendable member and; With a laser light source; An optical fiber connected to the laser light source, It comprises a plurality of emission regions configured to emit electromagnetic energy from the laser light source through the optical fiber, The emission of electromagnetic energy from the plurality of emission regions is configured to cause fragmentation in coronary artery calcium, and The plurality of emission regions are configured as conical reliefs, beveled reliefs, or distributed refractive index (GRIN) lenses within the optical fiber, and A device equipped with the following features, configured to break up coronary artery calcium.

2. The extendable member contains a fluid, and The emission of electromagnetic energy from the emission region is configured to generate ultrasound in the fluid, thereby causing fragmentation in coronary artery calcium. The apparatus according to claim 1.

3. The optical fiber is the first optical fiber; The device further comprises multiple optical fibers; and Each of the plurality of optical fibers comprises one or more emission regions configured to emit electromagnetic energy in a radial pattern from each optical fiber. The apparatus according to claim 1 or 2.

4. The apparatus according to any one of claims 1 to 3, wherein the expandable member is a balloon.

5. The apparatus according to any one of claims 1 to 4, wherein an extendable member is configured to be extended via a fluid contained within the extendable member.

6. The apparatus according to claim 5, further comprising a first port configured to deliver fluid to an extendable member.

7. The apparatus according to claim 6, further comprising a second port configured to drain fluid from an extendable member.

8. The apparatus according to claim 6, wherein a second port is further configured to discharge vapor bubbles from an extendable member.

9. The apparatus according to any one of claims 5 to 7, wherein the fluid is configured to absorb electromagnetic energy from an optical fiber, generate acoustic waves, and propagate them to calcium.

10. The apparatus according to any one of claims 5 to 9, wherein the fluid is a physiological saline fluid.

11. The apparatus according to any one of claims 1 to 10, wherein the optical fiber is configured to emit electromagnetic energy in a radial pattern.

12. The apparatus according to any one of claims 1 to 11, wherein electromagnetic energy is emitted at a wavelength of approximately 2 μm.

13. The apparatus according to any one of claims 1 to 12, wherein electromagnetic energy is emitted at a wavelength of 1.5 μm to 2.5 μm.

14. The apparatus according to any one of claims 1 to 13, further comprising an intravascular imaging device.

15. The apparatus according to claim 14, wherein the intravascular imaging device is an intravascular ultrasound (IVUS) device.

16. The apparatus according to claim 14, wherein the intravascular imaging device is an optical coherence tomography (OCT) device.

17. With intravascular imaging devices; Extendable member and; A laser light source configured to emit electromagnetic energy; An optical fiber connected to the laser light source, It has a proximal end and a distal end, The electromagnetic energy from the laser light source is configured to be emitted from multiple emission regions near the distal end of the optical fiber, The plurality of emission regions are configured as conical reliefs, beveled reliefs, or distributed refractive index (GRIN) lenses within the optical fiber, and A device equipped with the following features, configured to break up coronary artery calcium.

18. The extendable member contains a fluid, and The electromagnetic energy from the distal end of the fiber is configured to generate ultrasound in the fluid, thereby causing fragmentation in the coronary artery calcium. The apparatus according to claim 17.

19. The apparatus according to claim 17 or 18, wherein the expandable member is a balloon.

20. The apparatus according to any one of claims 17 to 19, wherein an extendable member is configured to be extended via a fluid contained within the extendable member.

21. The apparatus according to claim 20, further comprising a first port configured to deliver fluid to an extendable member.

22. The apparatus according to claim 21, further comprising a second port configured to drain fluid from an extendable member.

23. The apparatus according to claim 22, wherein a second port is further configured to discharge vapor bubbles from an extendable member.

24. The apparatus according to any one of claims 20 to 23, wherein the fluid is configured to absorb electromagnetic energy from an optical fiber, generate acoustic waves, and propagate them to calcium.

25. The apparatus according to any one of claims 20 to 23, wherein the fluid is indocyanine green (ICG).

26. The apparatus according to any one of claims 17 to 25, wherein electromagnetic energy is emitted at a wavelength of 790 to 810 nanometers (nm).

27. The apparatus according to any one of claims 17 to 25, wherein electromagnetic energy is emitted at a wavelength of approximately 793 nm.

28. The apparatus according to any one of claims 17 to 27, wherein the electromagnetic energy emitted from the optical fiber is less than 1.0 kilowatt (kW).

29. The apparatus according to any one of claims 17 to 28, wherein the electromagnetic energy emitted from the optical fiber is approximately 0.6 kW.

30. The apparatus according to any one of claims 17 to 29, wherein the laser light source is a diode laser.

31. The apparatus according to any one of claims 17 to 30, wherein the intravascular imaging device is an intravascular ultrasound (IVUS) device.

32. The apparatus according to any one of claims 17 to 30, wherein the intravascular imaging device is an optical coherence tomography (OCT) device.

33. The apparatus according to any one of claims 17 to 32, wherein the intravascular imaging device has an outer diameter of less than 2.0 millimeters (mm).

34. The apparatus according to any one of claims 17 to 33, wherein the intravascular imaging device has an outer diameter of approximately 1.2 millimeters (mm).

35. The apparatus according to claim 1, wherein the laser light source is configured to emit electromagnetic energy at a wavelength of 790 to 810 nanometers (nm).

Images