Systems and methods for diode laser-induced calcium fractures

Abstract

Apparatus, systems and methods for fracturing calcium in an artery of a patient. Certain embodiments include a diode laser light source, an optical fiber coupled to the laser light source, an expandable member coupled to the optical fiber, and a control system. The control system can be configured to control operating parameters, including a pulse repetition rate. In specific embodiments, the pulse repetition rate can be controlled at a frequency between 1 kHz and 100 kHz. Certain embodiments include a plurality of electromagnetic energy emitters separated by a distance configured to provide motion-enhanced intravenous lithotripsy during use.

Description

[0001] SYSTEMS AND METHODS FOR DIODE LASER-INDUCED CALCIUM FRACTURES

[0002] CROSS-REFERENCE TO RELATED APPLICATION

[0003] This application claims benefit of priority to U.S. Provisional Patent Application No. 63 / 672,610 filed July 17, 2024, the entire contents of which is hereby incorporated by reference.

[0004] BACKGROUND INFORMATION

[0005] Coronary and peripheral artery calcification (CPAC) complicates percutaneous coronary intervention (PCI) by reducing vessel compliance, interfering with device delivery, impairing balloon expansion, and potentially providing uneven drug distribution in the arterial wall. Further, CPAC causes damage to the drug-eluting polymer, thus resulting in more treatment failures. Decreased vessel compliance also reduces the ability of implanted stents to expand, causing stent under-expansion sometimes resulting in complications such as stent thrombosis and restenosis. Calcium localization (superficial or deep), distribution (focal, circumferential or longitudinal extension) and thickness also adversely impacts procedural time and success. CPAC has been an independent predictor of lower survival rate post PCI and is strongly correlated to major adverse cardiovascular events (MACE) after PCI.

[0006] Solutions currently used clinically to increase vessel compliance and deal with excessive calcium include high pressure balloon inflation and calcium scoring with cutting balloons. However, these approaches are often unsuccessful because of inability to completely cut calcium, and only applicable to superficial calcium. Coronary atherectomy with both rotational atherectomy systems (e.g., Rotablator™) and orbital atherectomy are suited for removing luminal superficial calcium. However, these approaches do not address deeper calcium and therefore do not always increase vessel compliance sufficiently to assure full stent expansion. These techniques are technically complex, time consuming and can increase risk since they release cut debris into the micro-circulation which can result in myocardial infarction during the procedure from no-reflow. Thus, dealing with the calcium burden of atherosclerosis in a safe and efficacious manner is a major clinical challenge for interventional cardiologists. Intravascular lithotripsy (IVL) techniques have been developed using electrical wires, electrodes, to deliver electrical energy inside a balloon catheter. The electric current discharge creates a vapor bubble formation which during collapse (‘micro-cavitation’) generates ultrasonic pressure waves that travels through soft vascular tissue but can selectively fracture calcium in the vessel wall. The high difference in density and mechanical sonic wave impedance properties between calcium and soft tissue allows the sonic pressure to fracture calcium while leaving soft tissue intact. However, the use of electrical current discharge limits the amount of delivered energy available and the ability to control spatially and temporally the delivery of energy to vaporize the fluid and induce calcium fracture. The electrical current discharge approaches also result in large voltage spikes that can pace the left ventricle with each delivered electric pulse, which is not ideal. There have been multiple cases reported of ventricular fibrillation, and case reports of atrial fibrillation / flutter because the delivered shocks are not timed with the endogenous pacemaker of the heart. Also, the size of the electrodes and wires limit miniaturization of the device. As a result, electric IVL devices are often larger in diameter than the residual lumen of many calcified lesions. As a result, there are many instances where rotational or orbital atherectomy are used simply to deliver the electric IVL device across the calcified lesion. The current electrical current discharge IVL devices are 12 mm in length while most coronary arteries are 100 mm in length. Development of longer balloons for electric IVL would require the addition of more wires and electrodes, further increasing the diameter of the device. Accordingly, systems and methods are desired that overcome these and other limitations associated with existing electrical IVL systems and methods.

[0007] SUMMARY

[0008] An urgent need is recognized for the ability to effectively fracture intravascular calcium for treatment of patient conditions, including atherosclerosis and other coronary diseases. Similarly, a need to decalcify heart valves, and the aorta is also recognized. A catheter apparatus is described herein for vascular insertion that employs diode laser sources that can be coupled into small diameter optical fibers to generate cavitation bubbles in a biocompatible fluid that upon collapse generates shock waves that can propagate into the walls of an artery. The optical fibers can be comprised of polymer and / or glass - unlike catheters that use near infrared light that are constructed of a glass material. An important element of our catheter apparatus is the diode laser / biocompatible fluid combination that allows the generation of large pressure-amplitude shock waves (50 atmospheres (atm) or more). Indocyanine green is an FDA-approved biocompatiblc fluid that absorbs strongly at diode laser emission wavelengths, c.g., 700 - 1000 nanometers (nm). This particular diode laser / biocompatible fluid combination provides numerous practical advantages. First, the radiant brightness of diode laser sources in the 700nm - lOOOnm spectral range allows the delivery of large pulse energies into small diameter optical fibers (100 - 400 micrometers (um) ) that can be positioned inside arteries with small lumen diameters. Second, the large pulse energy propagating down the optical fiber does not generate any non-specific electric al / magnetic fields that can interfere with cardiac function. Third, diode lasers that emit light in the 700nm - lOOOnm spectral range can propagate through polymer optical fibers and allow more design flexibility for optical emission elements in the catheter. Fourth, diode laser sources that emit in the 700nm - lOOOnm spectral range can be directly electric-current pulsed to provide precise control over the light emission time. Fifth, because ICG can absorb in the 700- lOOOnm spectral range, diode laser sources allow incorporation of numerous emission wavelengths that can be coupled into a small diameter optical fiber with multiple optical emission emitting elements. Moreover, the multiple optical emission elements can each be controlled by individually sized and timed electric -current pulses. More specifically, we disclose specific diode laser emission wavelengths, pulse durations, and formulations of ICG (concentrations and compositions) that when combined together unexpectedly generate large amplitude shock waves that can fracture calcium in the walls of coronary arteries.

[0009] Although near infrared pulsed lasers have been applied for decades to generate shock waves in saline due to cavitation bubble generation and / or collapse, these lasers are typically expensive, bulky and can generate shock waves with limited pressure magnitude. Diode laser sources can provide a number of practical advantages in numerous medical therapeutic systems. Diode lasers provide photons at high economic value - the economic cost per radiant watt is less than competing sources and has been decreasing exponentially over the last few decades and is expected to continue decreasing in the future. Generation of shock waves for fracturing calcium in arteries using diode laser sources can provide a number of important advantages. First, the radiant brightness of diode laser sources allows the delivery of large pulse energies into small diameter (lOOum - lOOOum) optical fibers that can be positioned inside arteries with a small lumen diameter. Second, the large pulse energy propagating down the optical fiber does not generate any non-specific electrical / magnetic fields that can interfere with cardiac function. More specifically, the electric fields associated with large pulse energies are confined to the optical fiber and do not extend outside the catheter and thus do not interfere with surrounding tissues such as the heart. Third, diode lasers emit light that can propagate through polymer and / or glass optical fibers and allow more design flexibility for optical emission elements. Fourth, diode laser sources can be directly electric-current pulsed to provide light emission allowing precise temporal control over the light emission time and pulse duration. Precise temporal control over the light emission allows control over the generation / collapse of generated cavitation bubbles and the corresponding shock wave pressure magnitudes and direction of travel. Fifth, diode laser sources allow selection of numerous emission wavelengths that can be matched to the specific absorption profiles of candidate biocompatible fluids and directed to one or more of the multiple optical emission emitting elements in the fiber catheter that can also be controlled by specific electric-current pulsing for the selected diode emission element(s).

[0010] Previously an apparatus using a diode laser source to generate shock waves in a biocompatible fluid and propagate into a biological tissue had not been realized. The fluid must be safe even if injected directly into a human coronary artery (mitigating the risk of balloon rupture which can and does happen). Preferably, the biocompatible fluid is already approved by a regulatory agency (e.g., US Food and Drug Agency) for injection into coronary arteries. In previous work, saline was the primary biocompatible fluid contemplated for generating shock waves inside an artery. In existing electrical-source embodiments for generating shock waves, saline is the biocompatible fluid contemplated in use. In existing light-source embodiments for generating shock waves in arteries, near infrared laser sources that emit in the 1.9-2.1 um spectral range and are strongly absorbed by water have been applied. The use of near infrared laser sources to generate shock waves has a number of limitations. For example, if multiple shock wave emitters are desired, a multiplexing approach is employed where light from one laser source is sequentially spatio-temporally multiplexed into multiple optical fibers. What is needed is a device that can employ economic diode laser sources that can be coupled into a small diameter optical fiber catheter and a biocompatible fluid that when a short pulse of light is injected into the biocompatible fluid a cavitation bubble is generated and collapses creating a shock wave.

[0011] Exemplary embodiments of the present disclosure include an intravascular lithotripsy apparatus comprising: a diode laser light source; an optical fiber coupled to the laser light source; an expandable member coupled to the optical fiber; and a control system configured to control operating parameters of the diode laser light source, where: the operating parameters of the diode laser light source comprise a pulse repetition rate; and the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 1 kHz and 1 MHz.

[0012] In certain embodiments the expandable member contains a fluid at a pressure greater than 1 bar. In particular embodiments the expandable member comprises a fluid at a pressure between 1 bar and 20 bar. In some embodiments the expandable member comprises a fluid at a pressure between 2 bar and 8 bar. In specific embodiments the expandable member comprises a fluid at a pressure between 3 bar and 7 bar. In certain embodiments the expandable member comprises a fluid at a pressure between 4 bar and 6 bar. In particular embodiments the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 10 kHz and 90 kHz. In some embodiments the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 20 kHz and 80 kHz. In specific embodiments the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 30 kHz and 70 kHz.

[0013] In certain embodiments the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 40 kHz and 60 kHz. In particular embodiments the operating parameters of the diode laser light source comprise a pulse duration; and the control system is configured to control the pulse duration between 500 nanoseconds (ns) and 20 microseconds (ps). In some embodiments the control system is configured to control the pulse duration between 1 ps and 15 ps. In specific embodiments the control system is configured to control the pulse duration between 2 ps and 10 ps. In certain embodiments the control system is configured to control the pulse duration between 3 ps and 8 ps. In particular embodiments the control system is configured to control the pulse duration between 4 ps and 6 ps. In specific embodiments the fluid comprises a mixture of a plurality of components. In certain embodiments the plurality of components comprise indocyanine green (ICG), water, a contrast agent, and / or human serum albumin (HSA). In particular embodiments the plurality of components comprise the indocyanine green (ICG), the water and the contrast agent are contained in pre-filled syringes prior to being contained in the expandable member. Exemplary embodiments of the present disclosure may comprise an identification element; and a reading system, where the identification element and the reading system are configured to identify and read parameters of the intravascular lithotripsy apparatus. In certain embodiments the identification clement and the reading system comprise Radio Frequency Identification (RFID) tag and reader. In particular embodiments the identification element and the reading system comprise a barcode or quick response (QR) code. In specific embodiments the identification element and the reading system identify parameters of the diode laser light source. In some embodiments the identification element and the reading system identify parameters of the optical fiber. In certain embodiments the identification element and the reading system identify parameters of the expandable member.

[0014] In exemplary embodiments of the present disclosure the diode laser light source is coupled to the optical fiber via a sterile coupling. In certain embodiments the sterile coupling is a singleuse coupling. In particular embodiments the sterile coupling is a sterile optical connector. In some embodiments the optical fiber is a taper fiber, index gradient fiber, photonic crystal fiber or polymer fiber. In specific embodiments the apparatus has a profile of 355-400um. In certain embodiments the intravascular lithotripsy apparatus can maintain shockwave repetition at 10 kHz or higher.

[0015] Exemplary embodiments of the present disclosure include a method of treating a patient having coronary artery calcification, where the method comprises: a. delivering the intravascular lithotripsy (IVL) apparatus of any one of claims 1 -29 to a calcified segment within a coronary artery of the patient; b. positioning an expandable portion of the IVL apparatus adjacent to the calcified segment; and c. activating the IVL apparatus to generate cavitation shockwaves to fracture the coronary artery calcification. In particular embodiments, the calcified segment has a length of up to 100mm.

[0016] Certain embodiments include a method of treating a patient having coronary artery calcification, where the method comprises: a. inserting the intravascular lithotripsy (IVL) apparatus of any one of claim 1-29 into a blood vessel of the patient; b. advancing the IVL apparatus to a calcified segment within a coronary artery; c. expanding the expandable member of the IVL apparatus to appose the optical fiber or plurality of emitters against the calcified segment; d. delivering electrical pulses to the optical fiber or plurality of emitters to generate a plurality of cavitation shockwaves, thereby fracturing the calcified segment; and e. retracting the expandable member. In particular embodiments, the calcified segment has a length of up to 100mm.

[0017] Exemplary embodiments include a method of introducing a fluid into an expandable member of an intravascular lithotripsy apparatus, where the method comprises: providing a first container comprising a first specified amount of indocyanine green (ICG); providing a second container comprising a second specified amount of water; providing a third container comprising a third specified amount of contrast agent; mixing the first specified amount of ICG and the second specified amount of water to form a dissolved ICG water mixture; mixing the dissolved ICG water mixture and the third specified amount of contrast agent to form a final fluid mixture; and introducing the final fluid mixture into the expandable member.

[0018] In certain embodiments at least one of the first container, the second container, and the third container is a syringe. In particular embodiments the dissolved ICG water mixture has an ICG concentration of approximately 10 mg / mL. In some embodiments the final fluid mixture has an ICG concentration of 5 mg / mL.

[0019] Exemplary embodiments of the present disclosure include an apparatus comprising a diode laser light source and an optical fiber, where the optical fiber comprises: a polymer optical core; a cladding surrounding the polymer optical core; and a laser light emission element. In certain embodiments the laser light emission clement is a first laser light emission clement in a plurality of laser light emission elements. In particular embodiments each of the plurality of laser light emission element is configured to emit light at an equivalent wavelength range. In some embodiments each of the plurality of laser light emission elements is configured to emit light at equivalent power.

[0020] In specific embodiments a first laser light emission element of the plurality of laser light emission elements is configured to emit light at a first wavelength range, a second laser light emission element of the plurality of laser light emission elements is configured to emit light at a second wavelength range, where the first wavelength range is different than the second wavelength range. In certain embodiments an optical grating within the optical fiber comprises the plurality of laser light emission elements. In particular embodiments the plurality of laser light emission elements emit light radially from the optical fiber. In some embodiments the plurality of laser light emission elements is configured as a line of scattering centers along the polymer optical core of the optical fiber. In specific embodiments the plurality of laser light emission elements is configured as scattering centers located at positions offset from the polymer optical core and placed at equivalent angles near the cladding. In certain embodiments the plurality of laser light emission elements is configured as one or more photonic crystal lattices comprising a plurality of scatting centers in the polymer optical core.

[0021] In particular embodiments the plurality of laser light emission elements comprises N number of laser light emission elements, and wherein laser light emission elements are positioned radially around the optical fiber such that there are 360 / N degrees between each laser light emission element in the plurality of laser light emission element. In some embodiments the plurality of laser light emission elements emit light radially 360 degrees around the optical fiber. In specific embodiments the diode laser light source is configured to emit laser light at a wavelength between approximately 690 nanometers (nm) and 900 nm. In certain embodiments the diode laser light source can provide a pulse of light between 50 nanoseconds and 150 microseconds. In particular embodiments radiant power propagating in the optical fiber is between 100 watts (W) and 100 kilowatts (kW). In some embodiments the polymer optical core comprises poly (methyl methacrylate) (PMMA), poly dimethylsiloxane (PDMS), polyacrylamide (PAM) or a transparent amorphous fluoropolymer. In specific embodiments the polymer optical core comprises a transparent thermoplastic. In certain embodiments the transparent thermoplastic is poly (methyl methacrylate). In particular embodiments the polymer optical core comprises a silicon-based organic polymer. In some embodiments the silicon-based organic polymer is polydimethylsiloxane. In specific embodiments the polymer optical core comprises a transparent amorphous fluoropolymer. In certain embodiments the polymer optical core comprises a synthetic polymer.

[0022] Particular embodiments further comprise an expandable member. In some embodiments the expandable member comprises a lumen configured to receive the optical fiber. In specific embodiments the expandable member contains a fluid. In certain embodiments the fluid surrounds the optical fiber and wherein the fluid absorbs light emitted by the diode laser light source. In particular embodiments the fluid comprises indocyanine green (ICG). In some embodiments the fluid comprises a solvent, and in specific embodiments the concentration of the ICG to the solvent is between 5 milligrams / milliliter (mg / ml) and 25 mg / ml. Tn certain embodiments the solvent comprises water, saline or dextrose.

[0023] Particular embodiments further comprise a control system configured to control an operational parameter of the diode laser light source. In some embodiments the operational parameter is a pulse duration, a wavelength frequency, multiple varying wavelength frequencies, or a wavelength amplitude of the diode laser light source. In specific embodiments the control system is configured to provide a first laser light emission and a second laser light emission from the diode laser light source. In certain embodiments the first laser light emission is configured to generate a bubble in the fluid in the expandable member. In particular embodiments the control system is configured to provide the second laser light emission from the diode laser light source when the bubble in the fluid in the expandable member collapses.

[0024] In specific embodiments the optical fiber comprises an imaging element, and in certain embodiments the imaging element is configured to provide intravascular ultrasound (IVUS) or optical coherence tomography (OCT) imaging data. In certain embodiments the diode laser light source is a first diode laser light source in a plurality of diode laser light sources, and the optical fiber is a first optical fiber in a plurality of optical fibers. In particular embodiments each diode laser light source in the plurality of diode laser light sources is coupled to a separate optical fiber in the plurality of optical fibers. In some embodiments an optical fiber in the plurality of optical fibers comprises a conical distal end.

[0025] In specific embodiments the plurality of optical fibers are coupled via a tapered fiber coupler. In certain embodiments the plurality of optical fibers are coupled via a side-coupling region. In particular embodiments the plurality of optical fibers are coupled via sleeve coupling elements and at least one of the plurality of optical fibers comprises an angled polished end coated with a dielectric reflector.

[0026] Exemplary embodiments include an apparatus comprising: a diode laser light source and an optical fiber, where the optical fiber comprises: an optical core; a cladding surrounding the polymer optical core; and a plurality of laser light emission elements, where the laser light emission elements are configured as emission centers in the optical core. In particular embodiments the plurality of laser light emission elements is configured as a line of scattering centers along the optical core of the optical fiber. In some embodiments the plurality of laser light emission elements is configured as scattering centers located at positions offset from the optical core and placed at equivalent angles near the cladding. In specific embodiments the plurality of laser light emission elements is configured as one or more photonic crystal lattices comprising a plurality of scatting centers in the optical core. In certain embodiments the optical core is a polymer optical core, and in particular embodiments the optical core is a glass optical core.

[0027] In specific embodiments the diode laser light source is a first diode laser light source in a plurality of diode laser light sources, and the optical fiber is a first optical fiber in a plurality of optical fibers. In particular embodiments each diode laser light source in the plurality of diode laser light sources is coupled to a separate optical fiber in the plurality of optical fibers. In some embodiments an optical fiber in the plurality of optical fibers comprises a conical distal end.

[0028] In specific embodiments the plurality of optical fibers are coupled via a tapered fiber coupler. In certain embodiments the plurality of optical fibers are coupled via a side-coupling region. In particular embodiments the plurality of optical fibers are coupled via sleeve coupling elements and at least one of the plurality of optical fibers comprises an angled polished end coated with a dielectric reflector.

[0029] Exemplary embodiments include a method of fracturing calcium in an artery, where the method comprises: inserting an optical fiber into an artery, where the optical fiber is coupled to a diode laser light source, and the optical fiber comprises a polymer optical core, a cladding surrounding the polymer optical core, and a laser light emission element; inserting an expandable member into the artery; expanding the expandable member via a fluid in the expandable member; emitting electromagnetic energy from the laser light emission element, where the electromagnetic energy generates a pressure wave in the fluid contained within the expandable member; and fracturing the calcium in the artery via the pressure wave in the fluid.

[0030] In certain embodiments the laser light emission element is a first laser light emission element in a plurality of laser light emission elements. In particular embodiments each of the plurality of laser light emission elements is configured to emit light at an equivalent wavelength range. In some embodiments each of the plurality of laser light emission elements is configured to emit light at equivalent power. In certain embodiments a first laser light emission element of the plurality of laser light emission elements is configured to emit light at a first wavelength range; a second laser light emission clement of the plurality of laser light emission elements is configured to emit light at a second wavelength range; and the first wavelength range is different than the second wavelength range. In particular embodiments a grating structure within the optical fiber comprises an element of each laser light emission element. In some embodiments the plurality of laser light emission elements emits light radially from the optical fiber. In specific embodiments the plurality of laser light emission elements comprises N number of laser light emission elements, and wherein laser light emission elements are positioned radially around the optical fiber such that there are 360 / N degrees between each laser light emission element in the plurality of laser light emission element.

[0031] In certain embodiments the plurality of laser light emission elements emits light radially 360 degrees around the optical fiber. In particular embodiments the diode laser light source is configured to emit laser light at a wavelength between approximately 690 nanometers (nm) and 900 nm. In some embodiments the diode laser light source can provide a pulse of light between 50 nanoseconds and 150 microseconds. In specific embodiments radiant power propagating in the optical fiber is between 100 watts (W) and 100 kilowatts (kW). In particular embodiments the polymer optical core comprises a synthetic polymer. In some embodiments the polymer optical core comprises poly(methyl methacrylate) (PMMA), polydimethylsiloxane (PDMS), polyacrylamide (PAM) or a transparent amorphous fluoropolymer. In specific embodiments the polymer optical core comprises a transparent thermoplastic. In certain embodiments the transparent thermoplastic is poly (methyl methacrylate). In particular embodiments, the optical fiber has a high numerical aperture (NA) so that for a required etendue (or optical throughput) the diameter of the fiber is less. The use of high NA fibers allows the device diameter to be reduced and provides advantages for navigating highly stenotic arteries.

[0032] In particular embodiments the polymer optical core comprises a silicon-based organic polymer, and in some embodiments the silicon-based organic polymer is polydimethylsiloxane. In specific embodiments the polymer optical core comprises a transparent amorphous fluoropolymer. In certain embodiments of the method, the fluid comprises indocyanine green (ICG). In particular embodiments the fluid comprises a solvent, and in some embodiments the concentration of the ICG to the solvent is between 5 milligrams / milliliter (mg / ml) and 25 mg / ml. In specific embodiments the solvent comprises water, saline or dextrose.

[0033] In certain embodiments the expandable member comprises a lumen, and the optical fiber extends through the lumen of the expandable member. In particular embodiments of the method the optical fiber comprises an imaging element. In some embodiments the imaging element is configured to provide intravascular ultrasound (IVUS) or optical coherence tomography (OCT) imaging. In specific embodiments the imaging element provides imaging data while: inserting the optical fiber into the artery; inserting the expandable member into the artery; expanding the expandable member via a fluid in the expandable member; emitting electromagnetic energy from the laser light emission element; or fracturing the calcium in the artery via the pressure wave in the fluid. In certain embodiments the imaging element provides imaging data after fracturing the calcium in the artery via the pressure wave in the fluid.

[0034] In the following disclosure, the term “coupled” is defined as connected, although not necessarily directly, and not necessarily mechanically.

[0035] The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and / or the specification may mean “one,” but it is also consistent with the meaning of “one or more” or “at least one.” The terms “about” and “approximately” mean, in general, the stated value plus or minus 5%. The use of the term “or” in the claims is used to mean “and / or” unless explicitly indicated to refer to alternatives only or the alternative are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and / or.”

[0036] 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 linking verbs. As a result, a method or device that “comprises,” “has,” “includes” or “contains” one or more steps or elements, possesses those one or more steps or elements, but is not limited to possessing only those one or more elements. Likewise, a step of a method or an element of a device that “comprises,” “has,” “includes” or “contains” one or more features, possesses those one or more features, but is not limited to possessing only those one or more features. Furthermore, a device or structure that is configured in a certain way is configured in at least that way, but may also be configured in ways that arc not listed.

[0037] Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will be apparent to those skilled in the ail from this detailed description.

[0038] BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0040] The following drawings form part of the present specification and arc included to further demonstrate certain aspects of the present disclosure. The invention may be better understood by reference to one of these drawings in combination with the detailed description of specific embodiments presented herein.

[0041] FIG. 1 shows a schematic view of an artery with a guidewire for use with an apparatus according to an exemplary embodiment.

[0042] FIG. 2 shows a schematic view of an exemplary embodiment according to the present disclosure during an initial stage of use.

[0043] FIG. 3 shows a schematic view of a portion of the embodiment of FIG. 1 during use.

[0044] FIG. 4 shows a schematic view of a portion of the embodiment of FIG. 1 during use.

[0045] FIG. 5 shows schematic end view of an exemplary embodiment according to the present disclosure.

[0046] FIG. 6 shows an emission element comprising a beveled surface in an optical fiber. FIG. 7 shows an emission element comprising an optical grating.

[0047] FIG. 8 shows an emission element comprising an embedded optical guide.

[0048] FIG. 9 shows emission elements configured as a line of scattering centers along a central region of a core in an optical fiber.

[0049] FIG. 10 shows emission elements 150 configured as scattering centers located at positions offset from a core and placed at equivalent angles near a cladding of an optical fiber.

[0050] FIG. 11 shows emission elements configured photonic crystal lattice comprising a plurality of scatting centers that are arranged in designed spatial configuration.

[0051] FIG. 12 shows a graph of pressure generated according to an exemplary embodiment according to the present disclosure.

[0052] FIG. 13 shows a prior art graph of molar extinction coefficient versus wavelength.

[0053] FIGS. 14-18 show graphs of molar extinction coefficient versus wavelength for different fluid combinations and concentrations of comprising indocyanine green ([ICG] according to exemplary embodiments of the present disclosure.

[0054] FIGS. 19-23 illustrate data obtained in ICG precipitation tests for different fluid combinations and concentrations of comprising indocyanine green ([ICG].

[0055] FIGS. 24-29 illustrate data from emitting a second pulse of electromagnetic energy and timed to occur at the collapse of a vapor bubble generated by a first pulse of electromagnetic energy.

[0056] FIG. 30 illustrates a block diagram of a system utilizing multiple diode lasers combined into a single fiber and then split into different fibers for each emitter.

[0057] FIG. 31 illustrates a block diagram of a system using a separate small core high NA fiber coupled to each diode and emitter. FIG. 32 illustrates an end section view of one embodiment of an IVL catheter comprising a plurality of optical fibers distributed around a central guide wire.

[0058] FIG. 33 illustrates optical fibers configured to redirect laser light emissions.

[0059] FIG. 34 illustrates an end section view of one embodiment of an IVL catheter comprising a plurality of optical fibers distributed around a central guide wire with an aperture in outer coil.

[0060] FIG. 35 illustrates schematic section views of an IVL catheter comprising a plurality of optical fibers within an expandable member.

[0061] FIG. 36 illustrates a partial section view of an embodiment of a tapered fiber coupler configured for use in an IVL catheter.

[0062] FIG. 37 illustrates a partial section view of an embodiment of a side-coupled fiber configured for use in an IVL catheter.

[0063] FIG. 38 illustrates a partial section view of an embodiment of inline reflectors created from dielectric film configured for use in an IVL catheter.

[0064] FIG. 39 illustrates a schematic view of an artery with a guidewire for use with an apparatus according to an exemplary embodiment.

[0065] FIG. 40 illustrates a schematic view of a test apparatus used to obtain data for an apparatus according to an exemplary embodiment.

[0066] FIG. 41 illustrates graphs of vapor bubble lifetime at different expandable member fluid pressure and pressure amplitude versus pulse repetition rate for the embodiment of FIG. 40.

[0067] FIGS. 42-46 illustrate graphs of pressure amplitude versus pulse repetition rate for the embodiment of FIG. 40.

[0068] FIG. 47 illustrates a schematic view of a test apparatus used to obtain data for an apparatus according to an exemplary embodiment. FIG. 48 illustrates a graph of pressure and laser voltage versus time for the embodiment of FIG. 47.

[0069] FIGS. 49-51 illustrate graphs of pressure amplitude versus pulse repetition rate for the embodiment of FIG. 47.

[0070] FIGS. 52-54 illustrate graphs of pressure amplitude versus time for the embodiment of FIG. 47.

[0071] FIG. 55 illustrates a schematic of an optimization methodology according to an exemplary embodiment.

[0072] FIG. 56 illustrates a side section view of an apparatus with cutting elements during use according to an exemplary embodiment.

[0073] FIG. 57 illustrates an embodiment of emitters that includes a hollow core fiber and features to minimize outside diameter while maintaining a high coupling efficiency to a laser.

[0074] FIG. 58 illustrates an embodiment of a lattice-based grating written inside a fiber core for light extraction.

[0075] FIG. 59 illustrates an embodiment of a hollow core fiber with photonic bandgap lattice in periphery.

[0076] FIG. 60 illustrates an embodiment of a photonic bandgap.

[0077] FIG. 61 illustrates a graph of a temperature rise along the longitudinal axis showing extraction efficiency of a high index polymer coating.

[0078] FIG. 62 illustrates a prior art embodiment using a segment of GRIN fiber to improve mode matching from step-index to hollow core fibers.

[0079] FIG. 63 illustrates experimental data using a Holmium: YAG laser in ex vivo human coronary arteries. FIG. 64 illustrates a graph of experimental data for molar extinction coefficient versus wavelength for different fluid media.

[0080] DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0081] Exemplary embodiments of the present disclosure include apparatus and methods for fracturing arterial calcium, including for example calcium in a coronary artery. Referring initially to FIGS. 1-4, an overview of an exemplary apparatus 100 and method of use are demonstrated. For purposes of clarity, not all features shown in each figure are labeled with reference numbers. In the embodiment shown, apparatus 100 comprises a diode laser light source 110 coupled to an optical fiber 120 and a control system 130. Control system 130 can be configured to control operational parameters of apparatus 100, including for example, the operation of diode laser light source 110 (e.g., laser pulse duration, frequency, amplitude et al.) during calcium fracturing procedures.

[0082] In FIG. 1, optical fiber 120 of apparatus 100 has been inserted into an artery 250 with calcium 270 located within artery 250. In FIGS. 1-4, artery 250 and the portion of optical fiber 120 are shown in a cross-sectional view. As will be discussed more fully below, optical fiber 120 comprises an optical core 121 and a polymer cladding 122 surrounding optical core 121. In addition, optical fiber 120 comprises one or more laser light emission elements 150. In exemplary embodiments of the present disclosure, optical fiber 120 is positioned within artery 250 such that laser light emission elements 150 arc proximal to calcium 270 (e.g., optical fiber 120 is inserted into artery 250 a sufficient distance until laser light emission elements 150 are generally aligned with calcium 270). In particular embodiments, optical fiber 120 may comprise an imaging element 123 to assist in the positioning of optical fiber 120. In specific embodiments, imaging element 123 may be configured to provide intravascular ultrasound (IVUS) and / or optical coherence tomography (OCT) imaging. In certain embodiments, polymer cladding 122 may comprise poly(methyl methacrylate) (PMMA), polydimethylsiloxane (PDMS), polyacrylamide (PAM) or a transparent amorphous fluoropolymer (e.g. Cytop™). It is understood that other embodiments of the present disclosure may comprise a polymer cladding with a different polymer than those listed herein.

[0083] In FIG. 2 an expandable member 300 (e.g. a balloon catheter) has been inserted into artery

[0084] 250. In certain embodiments, optical fiber 120 can function in a manner equivalent to a typical guidewire to allow for the insertion of expandable member 300. For example, in the embodiment shown, expandable member 300 comprises a lumen 310 configured to receive optical fiber 120 so that optical fiber 120 can be used to guide expandable member 300 into the desired location within artery 250. In addition, optical fiber 120 comprises a distal end 129 with a formable or shapeable portion 128. In particular embodiments, shapeable portion 128 may be formed from a nickel titanium alloy (e.g. Nitinol) wire or other suitable configurations, including for example, workhorse tips available from Asahi©. In exemplary embodiments distal end 129 can be coupled to optical fiber 120 via polyethylene micro tubing or other suitable structures. Existing imaging techniques can also be used to assist in the placement of expandable member 300. In particular embodiments, imaging element 123 can be used to assist in the positioning of expandable member 300 with respect to optical fiber 120 and calcium 270. Accordingly, expandable member 300 can be positioned within artery 250 in a manner that is familiar to surgeons to allow for accurate placement in the desired location proximal to calcium 270.

[0085] In the embodiment shown in FIG. 3, expandable member 300 has been expanded within artery 250 via a fluid 320 including, for example, a fluid comprising indocyanine green (ICG). In particular embodiments fluid 320 may comprise ICG and a solvent. In certain embodiments, the solvent may comprise a mixture of one or more of saline, dextrose and / or water. Expandable member 300 can be expanded by increasing the pressure of fluid 320 within expandable member 300.

[0086] In the embodiment shown in FIG. 3, expandable member 300 has been expanded after expandable member 300 has been inserted into artery 250 (as shown in FIG. 2) and prior to emitting electromagnetic energy 170 from laser light emission elements 150 (as shown in FIG. 4). As shown in FIG. 4, electromagnetic energy 170 creates cavitation (e.g. bubbles 330) in fluid 320 which generates ultrasonic waves 340 from the formation and collapse of the bubbles 330 in fluid 320. In certain embodiments a grating structure within optical fiber 120 comprises laser light emission elements 150. In certain embodiments, expandable member 300 can be configured as a balloon configured for treatment of the distal aorta in order to increase compliance of the aorta in elderly patients with resistant systolic hypertension, and to increase elastic recoil during diastole to improve blood flow to the microcirculation. As shown in FIG. 4, ultrasonic waves 340 propagate through fluid 320 and create fractures 280 only in calcium 270 without damaging the vessel walls of artery 250, since the vessel walls are more elastic than the calcium plaque. In exemplary embodiments, fractures 280 arc created along inhomogeneities in calcium 270 and / or in calcium-hard-soft tissue interfaces. Fracturing of calcium 270 increases compliance of artery 250, allowing artery 250 to more easily expand and contract with changes in pressure. In specific embodiments, imaging element 123 can be used to monitor the fracturing of calcium 270.

[0087] In particular embodiments elements of apparatus 100 are specifically selected to increase the ability to create fractures 280 in calcium 270 with reduced power requirements from diode laser light source 110 and reduced manufacturing costs for apparatus 100. For example, the laser light source 110 and fluid 320 can each be selected to maximize the amount of energy provided by ultrasonic waves 340 while minimizing the power requirements from diode laser light source 110. In particular embodiments, the operational parameters of laser light source 110 (e.g. the wavelength, pulse duration, etc. of electromagnetic energy 170) and the concentration of ICG in fluid 320 can be selected to optimize the efficiency of apparatus 100 (e.g. the ability to create fractures 280 in calcium 270 for a given power requirement of laser light source 110).

[0088] Furthermore, in particular embodiments optical fiber 120 may be formed from fibers with significantly lower costs than glass fibers. In specific embodiments, optical fiber 120 may be formed from fiber material that costs approximately $0.10 per meter, significantly reducing the manufacturing costs for apparatus 100.

[0089] A close-up view of one embodiment of distal end 129 is shown in the partial section schematic view of FIG. 5. As shown in the figure, shapeable portion 128 comprises a tapering core material 127. In certain embodiments, tapering core material 127 may be formed from a metal alloy of nickel and titanium (e.g. Nitinol). In addition, optical fiber 120 is shown with emission elements 150 that are radially arranged at both 90 degrees and 180 degrees from each other to provide for emission of electromagnetic energy around the circumference of optical fiber 120. It is understood that the configuration of emission elements shown in the figures are exemplary and other configurations of emission elements may be utilized according to embodiments of the present disclosure. For example, emission elements 150 may be arranged at 60, 45, 30 degrees (or other configurations as desired) around the circumference of optical fiber 120. In certain embodiments, emission elements 150 may be arranged to emit electromagnetic energy 360 degrees around the circumference of optical fiber 120.

[0090] Exemplary embodiments of the present disclosure may comprise emission elements 150 of one or more configurations. FIG. 6 illustrates a closer view of emission elements 150 illustrated in FIGS. 1-4. In the embodiment shown in FIG. 6, emission elements 150 comprise one or more beveled surfaces 151 in optical fiber 120. In certain embodiments, a radial emitting fiber comprises a single wedged surface that acts as both a reflector and refractive element as shown in FIG. 6. Wedged surfaces can be concatenated along the length of the optical fiber to realize multiple emitting elements.

[0091] In the embodiment shown in FIG. 7, optical fiber 120 includes emission element 150 comprising a fiber grating 152 and an optional lens element 153. In the embodiment shown in FIG. 8, emission element 150 comprises an optical guide 154 and an optical lens element 153. In exemplary embodiments, optical guide 154 has a refractive index that is higher than optical fiber 120. In certain embodiments, optical guide 154 may be configured as an orthogonal waveguide, and in particular embodiments optical guide 154 may be configured as an orthogonal waveguide. Optional lens 153 in FIGS. 7 and 8 can focus electromagnetic energy into biocompatible fluid in an expandable member surrounding optical fiber 120 (e.g. electromagnetic energy 170 into fluid 320 in expandable member 300 shown in FIG. 4). In certain embodiments, dielectric gratings may be written into fibers that are designed to couple light of selected wavelengths out of the fiber and into the surrounding biocompatible absorbing fluid. Waveguides can be written into a fiber to couple out radiation from the core by creating a region of higher refractive index. A waveguide region of higher refractive index can be created by first removing material from the fiber using a subtractive manufacturing process and then filling with a higher-index synthetic polymer.

[0092] In exemplary embodiments of the present disclosure, directing light from the optical fiber into the surrounding biocompatible absorbing fluid is accomplished using one or more emission elements configured as optical emitter(s) embedded into the optical fiber. Exemplary embodiments of optical emitter elements comprise a patterned refractive index gradient within the fiber-core guiding structure of the optical fiber. In particular embodiments, the function of the optical emitter elements is to couple to and direct light out of the fiber-core guiding structure and into the surrounding biocompatiblc absorbing fluid. The patterned refractive index gradient embedded within the fiber-core guiding structure can be of multiple forms and may comprise one or more of: (1) reflective surface; (2) refractive surface; (3) scattering center; (4) dielectric grating; (5) waveguide within the core; and / or (6) photonic crystal lattice.

[0093] In particular embodiments, the refractive index of selected regions in the core of an optical fiber can be modified (increased or decreased) by directing focused radiation into the core of the optical fiber to create a scattering center. The scattering center can have higher or lower refractive index compared to the surrounding core in specific embodiments. Referring now to FIG. 9, one exemplary embodiment comprises optical fiber 120 with a cladding 122 surrounding an optical core 121 with emission elements 150 configured as a line of scattering centers 155 along the central region of core 121 of fiber 120.

[0094] In the embodiment shown in FIG. 10, optical fiber 120 comprises cladding 122 surrounding an optical core 121 with emission elements 150 configured as scattering centers 156 located at positions offset from core 121 and placed at equivalent angles near cladding 122. As shown in the end section view on the left side of FIG. 10, in this embodiment six scattering centers 156 are equally spaced around the peripheral region of core 121 such that an angle A between the adjacent scattering centers 156 is approximately 60 degrees. While the embodiment shown in FIG. 10 comprises six radial locations scattering centers 156 arranged in a spiral or helix pattern along optical fiber 120, it is understood that other embodiments may comprise a different number of radial positions and / or a different arrangement along the length of optical fiber 120. For example, certain embodiments could comprise a different number of radial positions arranged linearly along the peripheral region of core 121.

[0095] In particular' embodiments, a photonic crystal lattice can be written into the core region of the optical fiber. Referring now to FIG. 11, emission elements 150 are configured as one or more photonic crystal lattice(s) 157 comprising a plurality of scatting centers 158 that are arranged in designed spatial configuration. A photonic crystal lattice 157 may be produced, for example, by a focused laser beam to induce a localized phase transition or scattering center in the core of the optical fiber to create a region of modified refractive index. By scanning the beam focus laterally and / or longitudinally, photonic crystal lattices 157 may be created at discrete longitudinal locations along the fiber core. For any of the patterned refractive index gradients embedded within the fibercore guiding structure a curved refractive surface may be fabricated onto the fiber or guidewire surface to focus light coupled out of the core into the surrounding biocompatible absorbing fluid.

[0096] In addition, the absorbing biocompatible fluid in the expandable member can be configured to efficiently fracture calcium with respect to the electromagnetic energy provided. As molar concentration of ICG increases in solution, the absorption coefficient also increases. However, this increase is not linear. Hence, if lx concentration is 1cm’1, lOOx is not necessarily 100cm’1. This is because of an "aggregation" effect of cyanine dyes. Cyanine dyes, including ICG, tend to aggregate at high concentration in aqueous solutions, which can reduce the absorption coefficient.

[0097] A lower aggregation implies lower power needed to generate the same pressure. While dimethyl sulfoxide (DMSO) can be used to avoid aggregation in ex vivo applications, it is not biocompatible. Accordingly exemplary embodiments of the present disclosure can comprise other techniques, including for example, dissolving the dye in liposome-type nano droplets. In addition, exemplary embodiments of the present disclosure can utilize dextrose, plasma, albumin and / or water in the solution to increase the absorption coefficient.

[0098] Data from one particular embodiment is shown in FIG. 12. In this embodiment diode laser light source 110 is configured to emit electromagnetic energy 170 at a wavelength of 787 nanometers (with a small spectral bandwidth of less than 5 nanometers [nm]) with a pulse duration of approximately 50 ps. In the embodiment shown, the pulse energy is less than 15 millijoule (mJ). When directed into a fluid containing ICG (and optionally a solvent, including for example, water, saline or dextrose) at ICG concentration of 25 milligrams / milliliter (mg / ml), the ultrasonic waves 340 generated a pressure of greater than 50 bars in the fluid.

[0099] FIG. 13 shows a prior art graph indicating molar extinction coefficient (a measure of how strongly a chemical species or substance absorbs light at a particular’ wavelength) versus wavelength according for different concentrations of ICG in water. The absorption at the laser wavelength (e.g., approximately 787 nm) is more than 10 times greater than the absorption of water at a laser wavelength of approximately 2 pm. In particular embodiments, diode laser light source 110 can be configured to emit electromagnetic energy at a wavelength near the maximum absorption coefficient for a specified concentration of an ICG formulation in expandable member 300. The use of diode lasers also provides for a compact configuration and flexible pulse profile. Accordingly, embodiments utilizing diode lasers can provide sufficient electromagnetic energy to an absorbing biocompatible fluid in an expandable member to effectively fracture calcium.

[0100] As previously noted, the contents of fluid 320 can be optimized to efficiently fracture calcium with respect to the electromagnetic energy provided. In FIGS. 14-18, data was obtained regarding the molar extinction coefficient versus wavelength according for five different ICG solvent combinations at different concentrations using a BioDrop® LITE+ spectrophotometer from BioChrom®. Specifically, the solvents included water, saline, water / saline (1:1), water / dextrose (1:1) and dextrose at ICG concentrations of 5, 12.5 and 25 mg / ml. As shown in the graphs, dextrose alone or in combination with water does not change the absorption peaks of ICG at concentrations of 5, 12.5 and 25 mg / ml.

[0101] Another factor for consideration when determining a desired ICG formulation is the extent to which ICG precipitates out of solution. FIGS. 19-23 illustrate data obtained in ICG precipitation tests for five different solvents at three different concentrations over time. Again, the solvents used to obtain the data in FIGS. 19-23 included water, saline, water / saline (1:1), water / dextrose (1 :1 ) and dextrose, respectively. The precipitation data in FIGS. 19-23 was obtained with concentrations of ICG in the solvents at 5mg / ml, 12.5 mg ml and 25 mg / ml at 37° Celsius at 15 minutes, 2 hours, 4 hours and 24 hours using an Invitrogen™ Countess™ II cell counter. The data in FIGS. 19-23 indicate that dextrose alone or in combination with water can be used to reconstitute ICG without causing precipitation within five hours of mixing.

[0102] Exemplary embodiments of the present disclosure may also be configured to provide sequential electromagnetic energy (e.g. laser light) emissions specifically time to maximize the ability of a pressure wave created in a fluid to fracture calcium in an artery. For example, certain embodiments can be configured to generate a first electromagnetic energy emission that generates a vapor bubble in a fluid (e.g. ICG), where the vapor bubble initially expands and then collapses. Particular embodiments can be configured to also generate a second electromagnetic energy emission that is emitted at approximately the same time as the bubble generated from the first electromagnetic energy emission collapses. By timing the emission of the second electromagnetic energy pulse to occur when the vapor bubble from the first electromagnetic energy emission is collapsing, a larger pressure pulse can be created and the ability to fracture calcium in an artery or other environment can be enhanced.

[0103] Referring now to FIGS. 24-29, data was collected from embodiments emitting a dual pulse of electromagnetic energy and compared to a similar embodiment emitting a single pulse of electromagnetic energy. Results were recorded for electromagnetic energy pulse duration of lOps, 20 s, and 5Ops from a NLight© 1500-watt fiber laser at 10 volts and 793 nm wavelength. Data was collected with a pressure sensor approximately 13.73 mm from the fiber tip in a chamber pressurized to 4 bars filled with a 50 / 50 mixture of ICG (5 mg / mL) and Visipaque™ solution.

[0104] The data for the single pulse was collected initially to determine the delay between the laser pulse and the vapor bubble collapse. The single pulse data was collected five times to determine an average delay between the laser pulse and the vapor bubble collapse and the amplitude of the shockwave pressure. The dual pulse data was collected by firing a second laser pulse at the average time delay observed in the single pulse between the laser pulse and the vapor bubble collapse. The data recorded for the lOps laser pulse is shown in FIGS. 24-25, while the 20ps laser pulse data is shown in FIGS. 26-27 and the 50ps laser pulse data is shown in FIGS. 28-29. As noted in each of the charts, the average pressure recorded for the dual pulse embodiments was greater than that generated in the single pulse embodiments. The pressure data was recorded in millivolts from the pressure transducer and converted to bars in the average calculation. Pressure data for the dual pulse embodiments was collected at 10kHz, 11 kHz and 11.68 kHz for the lOps embodiment, while data for the 20ps embodiment was collected at 10kHz and 11.36kHz, and collected at 10kHz, 11.6kHz and 11.16kHz for the 50ps embodiment. The most significant difference was noted in the lOps laser pulse embodiment at 11.68kHz, which provided an average pressure of 140.31 bars, as compared to 97.63 bars for the single pulse embodiment at lOps.

[0105] Particular embodiments of the present disclosure may also comprise a plurality of optical fibers, where each optical fiber is coupled to a separate diode laser. Such embodiments can provide increased flexibility with the operational parameters of the laser light emissions from the diode lasers. For example, the use of multiple separate optical fibers each coupled to an individual diode laser can allow a user to have increased spatio-temporal control by emitting light from the separate diode lascr / optical fiber units in a manner that may not be possible with a single laser (or multiple lasers) coupled to a single optical fiber.

[0106] Several considerations are made in the configuration of a diode laser IVL catheter incorporating multiple optical fibers. A diode laser emitter provides a specified radiance (W / (sr area)) or Watts per unit Etendue. A laser IVL catheter specification requires a number of emitters, and each emitter in a laser IVL catheter needs to provide some minimum radiant power density (Watts / Area) to generate a shockwave. For example, for 5mg / ml ICG a typical minimum radiant power density of approximately 2 kW / mm2is needed for shockwave generation. One challenge with laser IVL catheter design centers on the distribution of source radiance (W / Etendue) provided by diode laser emitters into catheter emitters. The optical etendue (capacity to carry light) of a fiber is proportional to the product of the core-area and solid angle (NA2).

[0107] IVL catheter design considerations include compatibility with existing guidewire (e.g. 0.014” wire / 350 pm) and minimizing the overall catheter diameter. For a laser IVL catheter, the diameter of each optical fiber contributes to the overall diameter of the laser IVL catheter. Accordingly, the use of small core diameter / high numerical aperture (NA) optical fibers provides a number of important advantages. For example, the small core diameter allows satisfying the overall design diameter constraint of the laser IVL catheter. In addition, fibers with a small core diameter provide increased radiant exitance (W / Area) at the fiber tip. Furthermore, fibers with high NA’s increase the etendue of the fiber, and for a given diode laser emitter allow more efficient coupling of diode laser radiant emission into the fiber and allow coupling of more wattage into each fiber.

[0108] The use of a separate optical fiber for each diode laser can also reduce or eliminate the need for passive splitters / combiners (e.g. used to split or combine light paths from one or more laser sources). A block diagram of a system utilizing multiple diode lasers combined into a single fiber and then split into different fibers for each emitter is shown in FIG. 30. Passive combiner / splitters can add cost and complexity to the system design, and configurations that do not use either a combiner / splitter can provide systems that are simpler, have lower loss, and are more cost effective. With the use of passive combiner / splitters, all emitters coupled to a laser source emit radiation at the same time, and triggered emission from individual emitters is not possible. Accordingly, the use of small core high NA fibers allows direct coupling of individual laser diodes to each emitter, and the use of small core diameter high etendue fibers allows efficient and fiber specific generation of shock waves while maintaining a small diameter laser IVL catheter. A block diagram of a system using a separate small core high NA fiber coupled to each diode and emitter is shown in FIG. 31. In certain embodiments, the small core high NA fibers can be biocompatible Optran® Ultra WFGE doped Si / Si fiber, with glass / glass / poly amide configuration for the core / clad / coating having a diameter of 50 / 60 / 70 pm.

[0109] Referring now to FIG. 32, an end section view of one embodiment of an IVL catheter 500 is shown comprising a plurality of optical fibers 501-507 distributed around a central guide wire 510. Optical fibers 501-507 and guide wire 510 are contained within an outer sheath or coil 511. In specific embodiments optical fibers 501-507 can have an outer diameter of 70 pm, while guide wire 510 may be approximately 0.004 inches in diameter and formed from stainless steel (e.g. 316, 304 or 302 stainless steel). In certain embodiments outer coil 511 may be approximately 0.002 inches thick with an overall diameter of approximately 0.0140 inches and can be configured to transmit torque to catheter 500. It is understood that the dimensions of components in this embodiment are merely exemplary, and other embodiments of the present disclosure may comprise similar’ components with different dimensions.

[0110] As shown in FIGS. 33-34, certain embodiments may also be configured to redirect laser light emissions 512 through one or apertures 513 in outer coil 511. In certain embodiments, an optical fiber (e.g. optical fiber 501) may comprise a distal end 515 that is conical, angled, tapered (or otherwise configured) to re-direct laser light emissions 512 via internal reflection. In certain embodiments, a conical distal end 515 can be configured to provide laser light emissions 512 that generate symmetric vapor bubbles when emitted in a fluid. The generation of symmetric vapor bubbles can maximize the amount of energy per vapor bubble volume transferred to coronary calcium during the subsequent collapse of the vapor bubble. In other embodiments, optical fiber 501 may direct laser light emissions 512 into a graded index (GRIN) lens 516 configured to direct laser light emissions 512 through aperture 513 (shown in FIG. 34). Referring now to FIG. 35, certain embodiments of the present disclosure may comprise configurations in which optical fibers arc located within an expandable member (e.g. a balloon catheter). In FIG. 35, schematic section views are shown at section lines A-A, B-B and C-C of IVL catheter 500. In this embodiment, IVL catheter 500 comprises optical fibers 501-507 contained within expandable member 520. In the embodiment shown, expandable member 520 is configured as a catheter balloon that can fold around central guide wire 510 and outer coil 511 when expandable member is in a deflated condition. This configuration can reduce the overall diameter of expandable member 520 and allow expandable member 520 to be more easily placed in the desired location within an artery or other lumen. The location of expandable member 520 can be verified via radiopaque markers 521 and 522 before expandable member 520 is expanded (e.g. inflated via fluid delivered by a fluid delivery channels 523 and 524 shown in Section A-A view).

[0111] In certain embodiments, optical fibers 501-507 can be configured to direct laser light emissions through aperture in outer coil 511 as described in previous embodiments (e.g. through an aperture via a GRIN lens or the configuration of the optical fiber as shown in FIGS. 33-34). In particular embodiments expandable member 520 can be tapered from approximately 0.55 mm to approximately 0.75 mm, or from approximately 0.65 mm to approximately 0.8 mm. As previously discussed, multiple optical fibers 501-507 provide for increased spatio-temporal control of the laser light emission. This can allow a user to sequentially time the emission from one fiber to coincide with the collapse of a vapor bubble generated by a laser light emission previously emitted from another fiber (or the same fiber the laser light source is capable of such emission). In addition, by distributing optical fibers circumferentially around a lumen into which the IVL catheter is inserted, a user can direct a specific fiber to provide laser light emissions in a desired radial direction to target specific locations of interest.

[0112] Certain embodiments of the present disclosure may comprise a tapered fiber coupler configured for use in an IVL catheter. Referring now to FIG. 36, a partial section view of an embodiment of a tapered fiber coupler 600 is located within a proximal end e.g. the end proximal to the IVL catheter operator) of a sheath 610 for an optical guidewire. In certain embodiments sheath 610 may be a steel sheath and tapered fiber coupler 600 may include a housing comprising a glass tubular member 605 with a tapered region 607. In the embodiment shown light 620 enters tapered fiber coupler 600 and is directed to optical output fibers 601-603. In the partial section view shown in FIG. 36 three output fibers arc shown in an embodiment comprising a total of seven output fibers. It is understood that other embodiments may comprise any number of output fibers within optical guidewire sheath 610. Each of the optical output fibers 601-603 comprises an emitter 613 (e.g. a side-firing reflector) configured to redirect laser light emissions 612 in an outwardly radial direction or other direction as desired.

[0113] Particular embodiments of the present disclosure may also comprise one or more side- coupled fibers in which an evanescent field in a primary fiber couples into one or more emitter fibers. Referring now to FIG. 37, a primary fiber 701 comprising a core 705 and a cladding 710 is coupled with an emitter fiber 702 via a side-coupling region 725. Side-coupling region 725 can be formed via a fused biconical taper (FBT) process or other suitable methods. Eight 721 propagates through primary fiber 701 via cladding 710 and via core 705. A portion of light 721 propagating via cladding 710 is directed to emitter fiber 702 as light 723 via side-coupling region 725. The fraction of light 721 that is transmitted to emitter fiber 702 as light 723 can be controlled by specifying the desired surface area within side-coupling region 725. For example, if more light 723 is desired, a configuration with a larger surface area in side-coupling region 725 can be specified. If less light 723 is desired, a configuration with a smaller surface area in side-coupling region 725 can be specified. Eight 723 propagates through emitter fiber 702 to an emitter 713 (e.g. a side-firing reflector) configured to redirect laser light emissions 712 in an outwardly radial direction or other direction as desired. While the embodiment shown in FIG. 37 illustrates one side-coupled fiber 702, it is understood that other embodiments may comprise additional side- coupled fibers.

[0114] Specific embodiments of the present disclosure may also comprise optical fibers with inline reflectors comprising dielectric films. Referring now to FIG. 38, a plurality of optical fibers 801- 804 are coupled via coupling elements 8O5In the embodiment shown, optical fibers 801-804 comprise an emitter 813 configured as a polished end that is tapered or angled (e.g. at 45 degrees in the embodiment shown) and coated with a dielectric reflector. Eight 820 propagates via fibers 801-804 and is redirected outwardly in a radial direction via emitters 813 as laser light emissions 812. In certain embodiments coupling elements 805 can be configured as transparent or translucent sleeves that function as lens elements configured to focus laser light emissions 812. Referring now to FIG. 39, exemplary embodiments of the present disclosure provide for automatic or manual rotation of the guidewire to direct or aim an emitter at a calcified nodule. Elements that are identified in FIG. 39 with reference numbers that are identical to those of previously-described embodiments are equivalent to the elements described in the previously- described embodiments. For sake of clarity, discussion of equivalent elements will not be repeated in the discussion of the embodiment shown in FIG. 39. The discussion of such elements in the previously-described embodiments is incorporated herein by reference.

[0115] In certain embodiments calcium 270 can be identified (e.g. by location, orientation and size) with intravascular optical coherence tomography (IV-OCT) or intravascular ultrasound (IVUS) prior to placement of the emitter guidewire. In particular embodiments, calcium 270 (e.g. a calcified nodule) can be identified with angiography as a round filling defect with contrast surrounding it. In specific embodiments, OCT could be placed within the emitter wire (e.g. optical fiber 120) to image the calcified nodule before placement of the expandable member (also referred to herein as a balloon) over the emitter wire.

[0116] Once calcium 270 is identified, the emitter wire can be identified with fluoroscopy via fiducial markers 322, while the calcified nodule will more easily identified with angiography (having been previously identified with OCT and / or IVUS). The emitter wire can be turned or rotated in the coronary artery either manually or with a torquing device 323 coupled to the wire to direct the emission element toward the calcified nodule or other desired target. Accordingly, the efficacy of the intravascular lithotripsy (IVL) treatment can be optimized by directing the pressure wave toward the target calcium and minimizing the effect on tissue not in the target area.

[0117] In the illustrated embodiment, expandable member 300 may also comprise cutting elements 324 (e.g. blades or wires) to score or cut calcium plates. During operation, the microcavitations (which create ultrasonic waves to fracture calcium plates) can have the fracturing force intensified at the location where the cutting elements 324 make contract with the calcified plates. The addition of cutting elements 324 can therefore increase the ability to fracture calcium 270 without increasing the energy generated by the micro-cavitations (e.g. vapor bubble collapse). It is understood that fiducial markers 322, torquing device 323 and cutting elements 324 (along with other features shown and described in FIG. 39) may not all be included in other embodiments of the present disclosure. Accordingly, exemplary embodiments may include any combination of these features, as well as other features shown and described in other embodiments disclosed herein.

[0118] Referring now to FIG. 56, while acoustic energy that is generated within a fluid supports longitudinal waves (medium motion is parallel to wave propagation direction), fluids do not support shear waves (medium motion is perpendicular to wave motion). Fracture of hydroxyapatite deposits within the arterial wall can be accomplished with longitudinal and / or shear waves. In some cases, fracture of hydroxyapatite and other hard biological materials (e.g. bone) can be enhanced with the application of ultrasonic shear waves. Moreover, since shear wave velocity in hydroxyapatite is slower than longitudinal waves, resonance enhancement of shear wave amplitude generally occurs at lower ultrasonic frequencies in comparison to longitudinal waves. In some cases, lower ultrasonic frequencies may be produced with smaller and userpreferred guidewire and microcatheters designs. Thus, use of a cutting balloon can motivate microcatheter and guidewire designs that are smaller and easier to use.

[0119] The generation of shear waves at the surface of the balloon can be enhanced through use of a cutting balloon. When a longitudinal wave generated inside the balloon propagates across the fluid / arterial wall interface, a cutting structure on the balloon surface can effectively convert the incident longitudinal waves into shear waves inside the arterial wall. Both the geometry and surface texture of the cutting structure can impact the conversion of longitudinal wave energy into shear wave energy in the arterial wall. Both the geometry (i.e., aspect ratio) of cutting structure on the balloon and the surface texture of the cutting structure that interfaces with the arterial tissue can be varied. Higher aspect-ratio cutting structures (those that project deeper into the arterial wall for a given width) will provide relatively greater surface area in contact with the arterial wall to generate shear waves. Cutting structures with appropriate surface texture can enhance the conversion of incident longitudinal waves in the fluid to shear waves in the arterial wall.

[0120] The phenomenon of using acoustic or ultrasonic energy to increase the transport of pharmaceutical and related chemical species into tissues an effect sometimes referred to as sonoporation is an area of active research. The application of optically generated acoustic waves within the balloon can increase the permeability of an agent on the balloon surface into the arterial wall. Embodiments of the present invention allow a design configuration that can enhance the effect of sonoporation and optimize the transport of pharmaceutical and related chemical species into tissues.

[0121] When multiple light guides are used in the guidewire, a fiber-mode-converter can be employed proximally to the balloon. Fiber mode converters are photonic components known in the art that allow bidirectional conversion radiant energy in a single waveguide into multiple waveguides. For example, if each emitter in the guidewire is coupled to a single optical waveguide, a fiber mode converter can be utilized proximal to the balloon to couple radiant energy from a single parent waveguide into multiple daughter waveguides. In this configuration, the composite etendue of the daughter waveguides is less than or at most equal to the parent waveguide.

[0122] Exemplary embodiments of the present disclosure may also comprise pre-filled syringes to assure correct mix ratios in the IVL expandable member / balloon. In particular embodiments there are three components which can be mixed and contained within the IVL balloon. Specifically the IVL expandable member may comprise indocyanine green (ICG), radio-dense contrast used during angiography, and water to dilute these components. ICG is typically provided as a powder which needs to be reconstituted with water, with the two components provided separately and sterilely. The third angiographic contrast component can be provided in a third prefilled sterile syringe. Exemplary embodiments of the present disclosure may comprise Visipaque™ (lodixanol), Omnipaque1M(lohexol) or other suitable angiographic contrast agents which allow visualization of the expandable member during fluoroscopy or other visualization techniques. lodixanol may be preferred in certain embodiments because it shifts the maximal absorption of the diode laser closer to indocyanine green. In specific embodiments, ICG may be initially mixed with water to an ICG concentration 10 mg / mL. This mixture can then be further diluted 50:50 with the contrast agent to provide an ICG working concentration of 5 mg / mL.

[0123] Certain embodiments of the present disclosure may also an increased fluid pressure (e.g. a pressure above atmospheric pressure) within the expandable member and / or repeated (e.g. pulsed) laser emissions to improve the efficacy of the calcium lithotripsy. The use of higher ambient balloon pressures during vapor bubble generation can allow for the generation of substantially higher frequency ultrasonic energy. Vapor bubbles generated in fluids at a higher ambient balloon pressures have a shorter lifetime. For burst wave generation, the shorter bubble lifetime allows more rapid successive vapor bubble generation and collapse and consequently generation of higher shockwave pressures at higher burst frequencies. High pressure balloons are commonly used in the art, with balloons operating up to 40 atmospheres approved by various medical regulatory bodies. Experiments have been completed at ambient balloon pressures up to 10 atmospheres with burst wave frequencies up to 70KHz generating shockwave amplitudes in the 50-50 atmosphere range.

[0124] Specific embodiments can optimize the laser dosimetry (including for example, the pulse repetition rate [PRR] and pulse width or duration), the fluid pressure within the expandable member, and the emitter geometry to achieve improved lithotripsy at lower energy levels. For example, higher fluid pressures in the expandable member provide a smaller vapor bubble in the fluid resulting from a laser emission. In addition, higher fluid pressures result in the vapor bubble collapsing faster (e.g. a shorter period of time between vapor bubble formation and collapse). The shorter time period for the vapor bubble formation and collapse can provide for a higher PRR of the laser. In certain embodiments, the fluid pressure may be 2 bar, 3 bar, 4 bar, 5 bar, 6 bar, 7 bar, 8 bar, 9 bar or 10 bar 20 bar, 30 bar or 40 bar (or any value between the listed values) within the expandable member. As discussed below, optimizing parameters (including the laser PRR and fluid pressure within the expandable member) can provide for pressure waves with higher amplitude at lower laser energy levels as compared to single pulse lasers at lower fluid pressures within the expandable member. The use of higher ambient balloon pressures during vapor bubble generation can allow for the generation substantially higher frequency ultrasonic energy. Vapor bubbles generated in fluids at a higher ambient balloon pressures have a shorter lifetime. For burst wave generation, the shorter bubble lifetime allows more rapid successive vapor bubble generation and collapse and consequently generation of higher shockwave pressures at higher burst frequencies. High pressure balloons are commonly used in the art, with balloons operating up to 40 atmospheres approved by various medical regulatory bodies.

[0125] Reducing the energy level required to achieve effective lithotripsy can also reduce the cost of equipment needed to achieve such energy levels. In specific embodiments tested, a PCO-7121 Pulsed / CW Laser Diode Driver Module from IXYS / BNC Berkeley Nucleonics was utilized. In a specific embodiment, the specifications of the laser driver module include a risc / fall time of 8 nanoseconds (ns), a pulse duration: 50 ns-1 microsecond (us), a 4us, X -IKhz-lOOKhz PRR, and a frequency of SS-lMhz.

[0126] A schematic of an initial test apparatus is provided in FIG. 40, showing a flat cleaved 200 pm diameter fiber in a balloon with ICG at a concentration 5mg / mL in Visipaque™, with the pressure transducer approximately 60 mm from the vapor bubble. The laser used in this embodiment was a single element diode e24i from nLight. Referring now to FIG. 41, test data was obtained for vapor bubble lifetime at different expandable member fluid pressure (e.g. “Ambient pressure”) and the average pressure amplitude for a 32 burst 2 ps pulse at different fluid pressures.

[0127] FIG. 42 shows the average pressure amplitude for 2 ps and 4 ps pulses at 10 bar fluid pressure for different PRR and pulse-to-pulse time periods, respectively. As shown in the graphs, an optimal PRR exists (to maximize the pressure wave amplitude detected by the pressure transducer) for a specific laser dosimetry at a particular fluid pressure in the expandable member for the diode laser. FIGS. 43-46 show additional data for the average pressure amplitude versus PRR for different fluid pressure and pulse duration (also referred to herein as pulse width).

[0128] FIG. 47 illustrates a schematic of a second experimental setup testing a 1 diode laser system with optimized PRR and variable pulse duration to a system with 7 diode lasers (equivalent to the single diode laser used in the comparison) but configured to provide a single 10 ps pulse at 1500 W. In this setup the pressure transducer is approximately 75 mm from the vapor bubble . FIGS. 48-54 illustrate shockwave amplitude data obtained from the configuration shown in FIG. 47. As discussed further below, optimization the single laser system operating parameters (e.g. pulse rate, fluid pressure within the expandable member, etc.) can result in pressure wave amplitudes that exceeded the pressure wave amplitudes generated by the higher power multi laser system.

[0129] FIG. 48 illustrates the pressure sensor / transducer detects an increase in pressure after the laser is pulsed (the laser pulse is indicated by the peak voltage displayed in FIG. 48). This confirms that the pressure sensor is detecting a pressure increase after the laser pulse and that the cavitation event has started. The peaks detected by the pressure sensor are at the cavitation vapor bubble collapse, which releases a shockwave pressure as detected by the pressure sensor.

[0130] FIG. 49 illustrates the average amplitude of the vapor bubble pressure wave detected by the pressure sensor for 4, 8, and 10 atmosphere (atm) fluid pressure within the balloon. Data was collected for a 32 burst pulse at different pulse repetition rates (PRR) with a 4 ps pulse duration. As shown in the figure, the increase in pressure from 4 to 8 to 10 bar increased the PRR at which the maximum pressure amplitude was detected. FIGS. 50 and 51 illustrate the amplitude of the vapor bubble pressure wave detected by the pressure sensor for 2, 4, 6, 8, and 10 atm fluid pressure within the balloon. Data was collected for a at different pulse repetition rates (PRR) with a 4 ps pulse duration. In FIG. 50, the power setting for the diode laser was approximately 300 Watts, while in FIG. 51 the power setting for the diode laser was approximately 400 Watts. As shown in both figures, increasing the fluid pressure within the balloon resulted in an increased PRR for the peak vapor bubble shockwave pressure. However, it is noted that at the 300 W setting the maximum shockwave pressure was obtained at 10 atm balloon fluid pressure, while at the 400 W setting 6 and 8 atm balloon fluid pressures resulted in higher shockwave pressures than the 10 atm balloon fluid pressure.

[0131] FIGS. 52-54 illustrate a direct comparison of the 7 diode laser system at 1500 Watts with a 10 ps pulse in comparison to a single diode laser at 400 Watts that is pulsed (at varying frequencies between 10-100 kHz indicated by the different colors in the graph). At the lower balloon fluid pressures of 2 and 4 atm, the 7 diode laser system produced a maximum shockwave amplitude that was slightly greater than the single, pulsed laser, as shown in FIG. 52. However, as shown in FIGS. 53 and 54, as the balloon fluid pressure increased to 6, 8 and 10 atm, the single pulsed laser was able to generate pressure waves from the vapor bubble collapse that exceeded that of the seven laser system emitting a single pulse. Additional testing with a 105 micron diameter fiber provided similar results and indicated that the maximum shockwave amplitude was obtained at higher pulse repetition rates (e.g. approximately 100 kHz) in comparison to the 200 micron fiber used in the apparatus to obtain the results shown in FIGS. 48-54.

[0132] In summary, the higher ambient pressures (e.g. pressure of the fluid in the expandable member / balloon) resulted in smaller bubbles and a shorter vapor bubble lifetime e.g. the amount of time from bubble formation to bubble collapse). The optimum pulse repetition rate to maximize the pressure wave amplitude is related to the timing between the collapse of the vapor bubble and the laser pulse. Accordingly, the shorter vapor bubble lifetime can allow for systems to operate with a higher pulse repetition rate. In addition, the smaller vapor bubbles can allow for smaller diameter balloons, which improve access to target locations needed for IVL lithotripsy. In addition, the geometry of the emission element (e.g. the size and configuration of the fiber transmitting the laser pulse) can be specified to generate vapor bubble shapes (e.g. spherical, cylindrical, etc.) that are optimized for the balloon configuration and system parameters to limit the bubble interaction with the balloon.

[0133] FIG. 55 illustrates one example of an optimization methodology according to an exemplary embodiment. As shown in the figure, a laser emitter geometry can be selected to generate vapor bubbles in a balloon. The laser emitters and vapor bubbles can then be imaged, and the ambient fluid pressure within the balloon optimized to minimize bubble interaction with the balloon (e.g. to ensure bubble non-interference with the balloon). In addition, the pulse repetition rate and pulse width can be optimized to generate the maximum pressure from the vapor bubble collapse.

[0134] Within the laser / diode apparatus described above there are a variety of system parameters in which it is desirable to adjust based on properties of the pairing patch cable and catheter apparatus. As previously stated, the diode laser source can be controlled in such a way as to provide precise light emission time and pulse duration. For parameters such as these as well as parameters like laser light wavelength and radiant power are just a few examples of values which could be adjusted based on the characteristics of the catheter apparatus connected. The characteristics of the catheter apparatus which could lead to varying laser / diode parameters include but are not limited to optical core polymer makeup, optical core size, and laser light emission element type. Therefore, in certain embodiments the laser / diode and patch cable apparatus can comprise an identification element and accompanying reading system. For each identification element, information pertaining to a specific catheter apparatus and its properties may be stored. The reading system would then have the ability to recognize the properties of the catheter and adjust the desired parameters of the laser / diode apparatus. There are a few common technologies utilized to achieve the functionality describe above. This first of these being Radio Frequency Identification (RFID) which is comprised of a tag and reader. In this configuration the reader sends radio signals to an RFID tag in which the tag will then respond with the identity and custom information. Within the RFID space there is a subset type of identification referred to as NFC. This technology functions the same as general RFID but from a much shorter distance at a higher frequency. Lastly an alternative identification technology is barcode or quick response (QR) code technology. This technology consists of a collection of lines or squares which when scanned with an associated reader can identity the item and other characteristics.

[0135] In the case of the catheter and laser / diode apparatus, any of the aforementioned technologies can be utilized to achieve the problem statement. In the case of utilizing an RFID / NFC system a tag would be stored on or within the catheter apparatus and contain all associated properties. The reader within the laser / diode apparatus therefore will read the information from the tag and adjust the parameters of the apparatus accordingly. Similarly in the case a barcode / QR code is utilized, the catheter apparatus will contain a code correlating to its specific characteristics. As for the laser / diode apparatus, a scanner will recognize the code and therefore adjust the parameters to match the catheter.

[0136] To achieve laser lithotripsy in a clinical setting, quick connection and disconnect will be desired in certain embodiments. In exemplary embodiments, a pulsed light source with high power can be used in these systems. Because the procedure is done in a sterilized environment, a sterile patch cord is needed to deliver the high-power laser from an external unsterile light source module to a sterile treatment device, namely the light emitter device. In certain embodiments, the sterile patch cord may be a single use patch cable. It is believed that existing systems do not utilize a sterile patch cord that is able to deliver high power multimode laser light.

[0137] In one embodiment of the present disclosure, light delivery is achieved by using a piece of multi-mode optical fiber. Specialized optical fibers such as taper fiber, index gradient fiber, photonic crystal fibers can be used. An outer layer of sheath or jacket can be added to the fiber for protection. An optical connection between the external light source and the patch cord, and between the patch cord and the emitter optical fiber can be realized by sterile optical connector design.

[0138] FIG. 57 illustrates emitters that include: 1. Hollow core fiber; 2. Bragg lattice in cladding; 3. High index coating; 4. Add retroreflector to double output; and 5. Splicing, modematching.

[0139] A significant percentage (-25%) of the light should be extracted from each emitter segment and each segment should be 5mm long or shorter to achieve high intensity. However, to deliver the light to the distal region in a tortuous anatomy (i.e. coronary artery), light must be tightly confined in a core of an optical fiber. As shown below, 8 emitters each transmit 12.5% of the power in two opposing directions. Alternately, those could be circular emitters, emitting 25% of the power. This disclosure will propose a method for circular emitters. Current Fiber Bragg gratings have been shown to be able to extract the light as well perform some focusing. However the extraction efficiency is relatively low, about 7 % per emitter.

[0140] FIG. 58 shows example of a lattice-based grating written inside the fiber core for light extraction. 4 sequential emitters are shown here.

[0141] Potential solution: Hollow core, photonic band gap fibers are commercially fabricated and arc in use in numerous applications, such as short-pulse continuum generation, pollution sensing applications and others. Hollow core fibers have the lowest (fastest light speed) index in the middle, which is the opposite of conventional fiber optics which place the highest index (lowest speed) in the center core to facilitate light guiding. Hollow core fibers use a novel photonic band gap formed by various schemes of hollow cores arranged to create wavelength regions where light will not be transmitted (the ‘band-gap’, following semiconductor nomenclature).

[0142] FIG. 59 shows a hollow core fiber, with photonic bandgap lattice in periphery. The current concept keeps only the hollow care, the rest is solid glass / silica with or without further modifications as described in the text.

[0143] FIG. 60 shows an example of a photonic bandgap. The white regions in the upper panel are the wavelengths regions where light can be transmitter. The gray areas are where light confinement to the core occurs. Photonic band gap fibers achieve light-guiding by transmitting light inside a band-gap region (shaded areas in figure 3). Without the band-gap structure, light will rapidly leave the fiber. In fact, a hollow core fiber will have among the fastest rates of light leakage possible.

[0144] In this case, a simple hollow core fiber without the photonic external structure will be used.

[0145] Once the light has left the core, it must also be extracted from the cladding layer. Several techniques can be used to increase the efficiency of cladding mode strippers; however they all rely on increasing the numerical aperture (NA) of the fiber. These techniques can include a high index region around the doped core, followed by a higher index polymer coating around the fiber. These have been shown to extract nearly all the light within just a few millimeters. The temperature profile below (high power laser example) shows that majority of the light is extracted within 4 mm (peak of the temp profile).

[0146] FIG. 61 shows extraction efficiency of a high index polymer coating. Another method to increase the NA would be the application of a fiber Bragg grating to increase the beam angle. Lattice-based (point-by-point) fiber gratings can be used to also focus the light into a tight ring around the fiber, increasing the power-density (intensity).

[0147] Splicing of hollow core fibers to standard fibers has been accomplished with good success (reference below). Techniques such as core expansion of the launching fiber to better match modes can also be used (diagram below, figure A). Several hollow core fibers can be stacked together to form an array.

[0148] As shown in Splicing Hollow-Core Photonic Bandgap Fibers to Step- Index Fibers Using an Arc Fusion Splicer, R. Thapa, K. L. Corwin, B. R. Washburn, Kansas State University, Department of Physics, 116 Cardwell Hall, Manhattan, KS 66506 email washburn@phys.ksu.edu, phone: 785-532-2263, fax: 785-532-6606

[0149] FIG. 62 shows using a segment of GRIN fiber to improve mode matching from step-index to hollow core fibers. In summary: 1) Use a hollow core fiber to initiate rapid light extraction from the core of the transmitting step-index fiber; 2) Use one or more of several techniques to increase the NA of the extracted light to enhance light extraction from the fiber and increase external intensity a. High index fiber clad and higher NA polymer coating; b. Fiber Bragg gratings inscribed in cladding (note that a hollow core might make this practically easier as a grating cannot be inscribed inside the hollow core, so precise control of grating location is somewhat simplified); c. Fiber Bragg grating acting also as a focusing element; d. Graded index design to create diverging light; 3) Use established techniques to splice hollow core fiber to transmitting fiber (i.e. step-index core fiber); 4) Use graded index fiber ahead of and behind each length of hollow core as shown above to enhance mode matching and minimize losses between regions; 5) Tailor extraction percentage by adjusting length of each hollow section; and 6) Add a retroreflector (i.e. metallic coating) at end of array to transmit light backwards to enhance extraction if needed.

[0150] As disclosed herein, coronary artery calcification (CAC) presents a major challenge for percutaneous coronary interventions (PCI) by reducing vessel compliance, impeding device delivery, and increasing the risk of restenosis and adverse clinical outcomes. [5,6] Over the past few decades, various strategies have been developed to address this issue by modifying calcified plaques. One such strategy is the use of cutting balloons — balloon catheters outfitted with microblades designed to “score” the plaque by creating shallow incisions [7], However, cutting balloons are difficult to deliver and ineffective against deeply embedded calcium. Atherectomy is another mechanical approach that removes only superficial calcified plaque using high-speed, diamond-coated rotating burrs. [8] While effective in shaving off calcified tissue, it carries a risk of distal embolization and the “no-reflow” phenomenon.

[0151] A more recent and notable innovation is electric intravascular lithotripsy (IVL), which uses electrical discharges to create cavitation bubbles within an electrolyte-filled balloon [9]. Shockwaves are produced through bubble expansion, which fracture both superficial and deep calcium in the arterial wall without generating calcium emboli. Despite its clinical value, electric IVL is constrained by a large profile (approximately 1,200 pm in diameter) due to electric wires and electrodes, limiting its ability to cross complex or heavily calcified lesions. About half of the operators fail to cross calcified lesions with a Shockwave IVL catheter up to 30% of the time. 32.7% of operators had problems crossing in 31%— 60% of cases, while the remaining 12% of clinicians had problems crossing in most of their cases

[0010] . Moreover, each high-cost IVL catheter (approximately $4,700 per unit) is limited to treating only a 12 mm segment of a typical 100-mm coronary artery, as the device’s shockwave emitters degrade rapidly and become prone to malfunction after a limited number of pulses (approximately 120). Electrically-based TVL systems have laid the groundwork for shockwave-based plaque modification but arc hindered by their large profile and rigidity, limiting their ability to cross severely calcified lesions. Their short treatment length also makes them suboptimal for long calcified segments, and adding emitters to extend coverage only increases device size, further reducing navigability. To overcome these challenges, we introduce a next-generation laser-based IVL platform engineered for flexibility, precision, and efficiency. With a dramatically reduced profile of just 355 pm — less than half the average lumen diameter of calcified plaques (approximately 800 pm) — exemplary embodiments of the present disclosure can traverse the tightest stenoses and treat an entire coronary artery segment with a single balloon, enabled by a more robust catheter and higher number of pulses. Results of experiments shown in FIG. 63 demonstrate that laser IVL significantly improves arterial compliance through multiple mechanisms beyond calcium fracture alone

[0011] , Exemplary embodiments of the present disclosure further incorporate ultrafast laser physics and cavitation dynamics, which underpins the system’s core performance. Exemplary embodiments of the present disclosure include additional innovations as further described below.

[0152] Efficient Shockwave Generation via Spectral Tuning of ICG

[0153] Exemplary embodiments of the present disclosure may utilize methods disclosed in the inventor’s prior published patent applications [12, 13] (incorporated herein by reference), to generate cavitation shockwaves within a balloon filled with Indocyanine Green (ICG) — an FDA- approved dye. Exemplary embodiments of the present disclosure may further comprise a blending of ICG with human serum albumin to precisely tune and stabilize its absorption peak, ensuring optimal energy absorption and highly efficient cavitation bubble formation. As a result, exemplary embodiments of the present disclosure can harness a compact, cost-effective pulsed diode laser for efficient shockwave generation.

[0154] In contrast to systems based on bulky, expensive Thulium fiber or Holmium: YAG lasers, exemplary embodiments disclosed herein deliver effective performance with a significantly smaller footprint and lower cost.

[0155] Exemplary embodiments of the present disclosure further provide broad patient applicability and long-segment treatment. Unlike electric IVL, which application is limited due to its bulky profile, exemplary embodiments disclose herein comprise a laser-based system featuring a low-profile (e.g. 355 pm) flexible catheter that can cross severely narrowed lesions and treat long segments (e.g. up to 100 mm) with a single, diode-laser-powered balloon.

[0156] In addition, exemplary embodiments disclosed herein provide calcified plaque-fibrotic tissue separation that not only fractures calcified plaques but also separates them from adjacent fibrotic tissue — a novel mechanism that further enhances arterial compliance and may improve long-term vessel remodeling.

[0157] By leveraging an optimized albumin-ICG medium and shockwave mechanism, specific embodiments of the present disclosure may utilize a compact, inexpensive (e.g. 790-nm pulsed diode) laser for efficient shockwave generation. The high energy conversion efficiency — from light to shockwave — lowers power requirements and system cost. This will enable the use of thinner optical fibers for a significantly reduced device profile, allowing access to even the most severely calcified coronary lesions, including distal calcified coronary branches in diabetics previously unreachable by current systems. These combined advantages — higher performance, smaller footprint, and lower cost — substantially increase the translational potential of this technology for widespread clinical use.

[0158] Accordingly, exemplary embodiments can optimize energy conversion and calcium fracturing mechanisms, for example, by tuning the composition of a specialized medium composed of ICG, human serum albumin, and Visipaque. ICG (an FDA-approved dye) is utilized to enhance the absorption of laser energy for highly efficient shockwave generation at the fiber optic emitters inside a balloon catheter. When ICG is in its monomeric form for a low concentration aqueous solution (e.g. less than 50 pg / mL), it exhibits a peak absorption at 790 nm, a wavelength for which high-power, cost-effective pulsed diode lasers are readily available. However, as the concentration of ICG increases — before reaching the FDA-allowed dosage limit of 5 mg / mL — it forms dimers, shifting the absorption peak to around 715 nm, which would reduce energy absorption at the desired laser wavelength, as shown in FIG. 64. To overcome this challenge, exemplary embodiments of the present disclosure leverage a unique property of ICG [14-16] showing that albumin can stabilize ICG in its monomeric form, increasing its absorption at 790 nm. The human serum albumin (HSA)-to-ICG ratio can be optimized for maximizing absorption at 790 nm. In addition, exemplary embodiments of the present disclosure may utilize an optimized concentration of Visipaquc — an FDA-approvcd X-ray contrast agent — to incorporate into the ICG solution, enabling real-time fluoroscopic visualization and precise tracking of when complete balloon catheter expansion has occurred within the coronary artery. Certain embodiments may also comprise a pressure sensor employed to measure the generated shockwave strength, allowing quantification of the light-to-shockwave energy conversion efficiency.

[0159] Referring back now to FIG. 63, results are shown for Laser IVL experiments using a Holmium: YAG laser in ex vivo human coronary arteries. A) Average lumen area before and after L-IVL increased (p=0.038). B) Spaghetti plot of ex vivo artery demonstrating increased compliance before and after L-IVL (p<0.05). C) Representative OCT images before IVL. D) OCT images after IVL (white arrows indicate calcium fractures). E) Representative micro-CT images before (El) and after (E2) IVL.

[0160] All of the apparatus, systems and / or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the apparatus, systems and methods of this invention have been described in terms of particular embodiments, it will be apparent to those of skill in the art that variations may be applied to the devices, systems and / or methods in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

[0161] REFERENCES:

[0162] The contents of the following references are incorporated by reference herein:

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[0164] 2. Ali et al, Optical Coherence Tomography Characterization of Coronary Lithoplasty for Treatment of Calcified Lesions, JACC Imaging, 2017

[0165] 3. Warisawa et al, Successful Disruption of Massive Calcified Nodules Using Novel Shockwave Intravascular Lithotripsy, Circ J, 2020

[0166] 4. Brinton et al, Feasibility of Shockwave Coronary Intravascular Lithotripsy for the Treatment of Calcified Coronary Stenoses, Circ J, 2019

[0167] 5. Hennessey, B., et al. Contemporary percutaneous management of coronary calcification: current status and future directions. Open Heart 10(2023).

[0168] 6. Riley, R.F., et al. SCAI Expert Consensus Statement on the Management of Calcified Coronary Lesions. J Soc Cardiovasc Angiogr Interv 3, 101259 (2024).

[0169] 7. Matsukawa, R., et al. Plaque modification using a cutting balloon is more effective for stenting of heavily calcified lesion than other scoring balloons. Cardiovasc Interv Ther 34, 325-334 (2019).

[0170] 8. Valdes, P.I., Nagalli, S. & Diaz, M.A. Rotational Atherectomy, in StatPearls (Treasure Island (FL) ineligible companies. Disclosure: Shivaraj Nagalli declares no relevant financial relationships with ineligible companies. Disclosure: Miguel Diaz declares no relevant financial relationships with ineligible companies., 2025).

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Claims

CLAIMS:

1. An intravascular lithotripsy apparatus comprising: a diode laser light source; an optical fiber coupled to the diode laser light source; an expandable member coupled to the optical fiber; and a control system configured to control operating parameters of the diode laser light source, wherein: the operating parameters of the diode laser light source comprise a pulse repetition rate; and the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 1 kHz and 1 MHz.

2. The intravascular lithotripsy apparatus of claim 1 wherein the expandable member contains a fluid at a pressure greater than 1 bar.

3. The intravascular lithotripsy apparatus of any one of claims 1-2 wherein the expandable member comprises a fluid at a pressure between 1 bar and 20 bar.

4. The intravascular lithotripsy apparatus of any one of claims 1-2 wherein the expandable member comprises a fluid at a pressure between 2 bar and 8 bar.

5. The intravascular lithotripsy apparatus of any one of claims 1-2 wherein the expandable member comprises a fluid at a pressure between 3 bar and 7 bar.

6. The intravascular lithotripsy apparatus of any one of claims 1-2 wherein the expandable member comprises a fluid at a pressure between 4 bar and 6 bar.

7. The intravascular lithotripsy apparatus of any one of claims 1-6 wherein the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 10 kHz and 90 kHz.

8. The intravascular lithotripsy apparatus of any one of claims 1-6 wherein the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 20 kHz and 80 kHz.

9. The intravascular lithotripsy apparatus of any one of claims 1-6 wherein the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 30 kHz and 70 kHz.

10. The intravascular lithotripsy apparatus of any one of claims 1-6 wherein the control system is configured to control the pulse repetition rate of the diode laser light source at a frequency between 40 kHz and 60 kHz.

11. The intravascular lithotripsy apparatus of any one of claims 1-10 wherein: the operating parameters of the diode laser light source comprise a pulse duration; and the control system is configured to control the pulse duration between 500 nanoseconds (ns) and 20 microseconds (ps).

12. The intravascular lithotripsy apparatus of any one of claims 1-11 wherein the control system is configured to control the pulse duration between I ps and 15 ps.

13. The intravascular lithotripsy apparatus of any one of claims 1-11 wherein the control system is configured to control the pulse duration between 2 p s and 10 ps.

14. The intravascular lithotripsy apparatus of any one of claims 1-11 wherein the control system is configured to control the pulse duration between 3 ps and 8 ps.

15. The intravascular lithotripsy apparatus of any one of claims 1-11 wherein the control system is configured to control the pulse duration between 4 ps and 6 ps.

16. The intravascular lithotripsy apparatus of any one of claims 1-11 wherein the control system is configured to control the pulse duration between 4 ps and 5 ps.

17. The intravascular lithotripsy apparatus of any one of claims 2-16 wherein the fluid comprises a mixture of a plurality of components.

18. The intravascular lithotripsy apparatus of claim 17 wherein the plurality of components comprise indocyanine green (ICG), water and a contrast agent.

19. The intravascular lithotripsy apparatus of claim 17 wherein the plurality of components comprise indocyanine green (ICG), water, human serum albumin (HSA), and a contrast agent.

20. The intravascular lithotripsy apparatus of claim 17 wherein the plurality of components comprise indocyanine green (ICG), water and human serum albumin (HSA).

21. The intravascular lithotripsy apparatus of claim 18 wherein the plurality of components comprise the indocyanine green (ICG), the water and the contrast agent are contained in pre- filled syringes prior to being contained in the expandable member.

22. The intravascular lithotripsy apparatus of any one of claims 1-21 further comprising: an identification element; and a reading system, wherein: the identification element and the reading system are configured to identify and read parameters of the intravascular lithotripsy apparatus.

23. The intravascular lithotripsy apparatus of claim 22 wherein the identification element and the reading system comprise Radio Frequency Identification (RFID) tag and reader.

24. The intravascular lithotripsy apparatus of claim 22 wherein the identification element and the reading system comprise a barcode or quick response (QR) code.

25. The intravascular lithotripsy apparatus of any one of claims 22-24 wherein the identification element and the reading system identify parameters of the diode laser light source.

26. The intravascular lithotripsy apparatus of any one of claims 22-25 wherein the identification element and the reading system identify parameters of the optical fiber.

27. The intravascular lithotripsy apparatus of any one of claims 22-26 wherein the identification element and the reading system identify parameters of the expandable member.

28. The apparatus of any one of claims 1-27 wherein the diode laser light source is coupled to the optical fiber via a sterile coupling.

29. The apparatus of claim 28 wherein the sterile coupling is a single-use coupling.

30. The intravascular lithotripsy apparatus of any one of claims 28-29 wherein the sterile coupling is a sterile optical connector.

31. The intravascular lithotripsy apparatus of any one of claims 1-29 wherein the optical fiber is a taper fiber, index gradient fiber, photonic crystal fiber or polymer fiber.

32. The intravascular lithotripsy apparatus of any one of claims 1-31, wherein the apparatus has a profile of 355-400um.

33. The intravascular lithotripsy apparatus of any one of claims 1-31, wherein the intravascular lithotripsy apparatus can maintain shockwave repetition at 10 kHz or higher.

34. A method of treating a patient having coronary artery calcification, the method comprising: a. delivering the intravascular lithotripsy (IVL) apparatus of any one of claims 1-31 to a calcified segment within a coronary artery of the patient;b. positioning an expandable portion of the IVL apparatus adjacent to the calcified segment; and c. activating the IVL apparatus to generate cavitation shockwaves to fracture the coronary artery calcification.

35. A method of treating a patient having coronary artery calcification, the method comprising: a. inserting the intravascular lithotripsy (IVL) apparatus of any one of claim 1-31 into a blood vessel of the patient; b. advancing the IVL apparatus to a calcified segment within a coronary artery; c. expanding the expandable member of the IVL apparatus to appose the optical fiber or plurality of emitters against the calcified segment; d. delivering electrical pulses to the optical fiber or plurality of emitters to generate a plurality of cavitation shockwaves, thereby fracturing the calcified segment; and e. retracting the expandable member.

36. The method of either claim 34 or 35, wherein the calcified segment has a length of up to 100mm.

37. A method of introducing a fluid into an expandable member of an intravascular lithotripsy apparatus, the method comprising: providing a first container comprising a first specified amount of indocyanine green (ICG); providing a second container comprising a second specified amount of water; providing a third container comprising a third specified amount of contrast agent; mixing the first specified amount of ICG and the second specified amount of water to form a dissolved ICG water mixture; mixing the dissolved ICG water mixture and the third specified amount of contrast agent to form a final fluid mixture; and introducing the final fluid mixture into the expandable member.

38. The method of claim 37 wherein the at least one of the first container, the second container, and the third container is a syringe.

39. The method of any one of claims 37-38 wherein the dissolved ICG water mixture has an ICG concentration of approximately 10 mg / mL.

40. The method of any one of claims 37-39 wherein the final fluid mixture has an ICG concentration of 5 mg / mL.

41. The method of any one of claims 37-40, wherein the intravascular lithotripsy (IVL) apparatus comprises the IVL apparatus of any one of claims 1-33.

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