Systems, devices and methods for laser-assisted targeted endovascular therapy

Abstract

Systems and methods are disclosed that facilitate the local therapy of tissue within the body. In some example embodiments, infrared laser pulses are locally delivered, via optical fiber, to an intracorporal target tissue region and are provided with pulse conditions suitable for causing local tissue disruption and liquification, leading to fine tissue disruption, tissue homogenization, and removal of vasculature and interstitial fluid channels, and enabling passage of the distal tip of the optical fiber into the target tissue region without substantial tissue deformation and damage along a preferred surgical pathway. When optical fiber emitting such pulses is employed to penetrate tumor tissue, the resulting reduction of interstitial fluid pressure facilitates the subsequent injection of a drug into the tumor, enabling the drug to remain localized within the tumor with reduced diffusion. The tumor disruption and subsequent drug delivery may be performed using an integrated optical and fluidic delivery device.

Description

SYSTEMS, DEVICES AND METHODS FOR LASER-ASSISTED TARGETED ENDOVASCULAR THERAPYCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 746,781 , titled “SYSTEMS, DEVICESAND METHODS FOR LASER-ASSISTED TARGETED ENDOVASCULAR THERAPY” and filed on January 17, 2025, the entire contents of which is incorporated herein by reference.BACKGROUND

[0002] The present disclosure relates to systems and methods for treating vascular disorders within the body.

[0003] Atherosclerosis, the buildup of plaque in arteries, is the leading cause of peripheral artery disease (PAD). The accumulation of plaques within the arterial walls leads to narrowing and stiffening of the arteries, reducing blood flow and resulting in ischemic conditions. In severe cases, this can progress to acute limb ischemia (ALI), characterized by a sudden and critical reduction in blood flow to a limb, and gangrene, a condition where tissue death occurs due to prolonged ischemia.

[0004] Beyond PAD, atherosclerosis is a significant contributor to other vascular occlusive conditions. Plaques may rupture or erode, exposing their contents to the bloodstream and triggering thrombosis — the formation of blood clots. Thrombosis can exacerbate arterial blockages, leading to severe complications such as myocardial infarction (heart attack) and ischemic stroke. These events arise when blood clots obstruct coronary or cerebral arteries, respectively, cutting off oxygen supply to vital tissues.

[0005] Thrombosis is not restricted to atherosclerotic arteries; it can also occur in veins, leading to conditions like deep vein thrombosis (DVT). DVT may result in venous occlusion, which carries the risk of pulmonary embolism (PE) if the clot dislodges and travels to the lungs. Pulmonary embolism is a life-threatening condition characterized by blockage of pulmonary arteries, impairing oxygen exchange.

[0006] Current treatment options for arterial occlusions caused by atherosclerosis, thrombosis, and other related conditions include mechanical and laser-based endovascular atherectomy devices, which remove plaque to restore blood flow. However, restenosis, or the re-narrowing of arteries post-procedure, remains a prevalent issue. Restenosis is often linked to damage to the arterial wall during plaque removal, triggering a biological response that leads to tissue proliferation and scar formation.

[0007] Despite advances, the management of atherosclerosis, thrombosis, and related vascular occlusions remains challenging. Hence, innovative therapeutic strategies that addressboth mechanical and biological factors underlying these vascular disorders are critical for improving patient outcomes.

[0008] Atherosclerotic plaques are primarily composed of lipids, calcium, fibrous connective tissue, and various cells. There are several stages of plaque development in which the proportional composition of constituents varies. The clinically problematic plaques include fatty atheroma (type IV), fibroatheromas (type Va), calcific atheroma (type Vb), and fibrotic atheroma (type Vc).

[0009] Various instruments are employed to resolve atherosclerosis, including directional, rotational, and laser devices. Directional atherectomy allows precise excision of diseased tissue while minimizing collateral damage to the vessel lumen. Orbital atherectomy is advantageous for precise and narrow areas, such as in-stent restenosis (ISR), while minimizing vessel wall damage even in tortuous areas.

[0010] Existing laser atherectomy devices, particularly those using ultraviolet (UV) lasers, address some of the problems associated with purely mechanical approaches. Existing ultraviolet (UV) laser atherectomy devices operate via photochemical and photomechanical mechanisms, but they carry risks of ionizing radiation, leading to inflammatory and mutagenic effects. While UV lasers excel in precision, their adoption in atherectomy and chronic total occlusion (CTO) crossing has been limited.SUMMARY

[0011] Systems and methods are disclosed that facilitate the local therapy of tissue within the body. In some example embodiments, infrared laser pulses are locally delivered, via optical fiber, to an intracorporal target tissue region and are provided with pulse conditions suitable for causing local tissue disruption and liquification, leading to fine tissue disruption, tissue homogenization, and removal of vasculature and interstitial fluid channels, and enabling passage of the distal tip of the optical fiber into the target tissue region without substantial tissue deformation and damage along a preferred surgical pathway. When optical fiber emitting such pulses is employed to penetrate tumor tissue, the resulting reduction of interstitial fluid pressure facilitates the subsequent injection of a drug into the tumor, enabling the drug to remain localized within the tumor with reduced diffusion. The tumor disruption and subsequent drug delivery may be performed using an integrated optical and fluidic delivery device.

[0012] Various embodiments of the present disclosure may thus be employed to solve the problem of the need to treat intravascular accumulations, such as intravascular occlusions, without causing substantial trauma to the surrounding vessel, thereby enabling treatment of intravascular accumulations with improved overall clinical efficacy and potentially improved long term outcomes. Moreover, the embodiments of the presentdisclosure provide a novel means of energy delivery during passage through an intravascular accumulation with substantially reduced shear forces and thereby a substantial reduction in friction, enabling passage through and crossing of complex and heterogeneous intravascular occlusions that are difficult to treat with conventional approaches.

[0013] Accordingly, in a first aspect, there is provided a system for performing ablative removal of an intravascular accumulation, the system comprising:an optical fiber microcatheter comprising:an elongate sheath; andan optical fiber extending through the elongate sheath;a steering mechanism operatively coupled to the elongate sheath, the steering mechanism being externally controllable for steering a distal portion of the elongate sheath; anda laser system in optical communication with a proximal end of the optical fiber for coupling laser pulses into the optical fiber, the laser system and the optical fiber being configured such that the laser pulses are delivered by a distal end of the optical fiber with properties comprising:a wavelength selected such that absorption of the laser pulses by a laser- irradiated volume of the intravascular accumulation, when the intravascular accumulation is positioned adjacent to a distal end of the optical fiber, is predominantly due to excitation of vibrational modes of one or more constituents of the intravascular accumulation;a pulse duration that is shorter than a first time duration required for thermal diffusion out of the laser-irradiated volume and shorter than a second time duration required for a thermally driven expansion of the laser-irradiated volume;a pulse fluence and the pulse duration resulting in a peak pulse intensity below a threshold for ionization-driven tissue disruption to occur within the laser-irradiated volume;the pulse fluence being sufficiently high to cause local ablative disruption and liquification of the laser-irradiated volume of the intravascular accumulation.

[0014] In some example implementations of the system, the laser system and optical fiber are configured such that the pulse fluence is sufficiently high to generate a disrupted volume, due to expansion of the laser-irradiated volume, that is larger, in a lateral direction, than an outer diameter of the optical fiber microcatheter, thereby facilitating extension of the optical fiber microcatheter through the intravascular accumulation during delivery of the laser pulses.

[0015] In some example implementations of the system, the steering mechanism comprises pull cables extending through the elongate sheath to the distal portion of the elongate sheath.

[0016] In some example implementations, the system further comprises an outer tube housing at least a portion of the optical fiber microcatheter, wherein the distal portion of the optical fiber microcatheter extendable beyond a distal end of the outer tube for steering the distal portion of the optical fiber microcatheter.

[0017] The laser system and the optical fiber may be configured such that the disrupted volume, due to expansion of the laser-irradiated volume, is larger, in a lateral direction, than an outer diameter of the outer tube, thereby facilitating extension of the outer tube through the intravascular accumulation during or after delivery of the laser pulses.

[0018] The steering mechanism may be a concentric tube-based steering mechanism comprising the outer tube, and wherein at least a distal portion of the elongate sheath is formed from a memory metal having a pre-defined curved shape, such that the distal portion of the optical fiber microcatheter is steerable by varying extension of the elongate sheath relative to a distal end of the outer tube.

[0019] The pre-defined curved shape may be defined such that the elongate sheath is laterally extendable by 7 cm when the elongate sheath is longitudinally extended from the distal end of the outer tube.

[0020] In some example implementations of the system, an outer diameter of the outer tube is between 500 and 1000 microns.

[0021] In some example implementations of the system, the outer diameter of the elongate sheath is between 300 and 1000 microns.

[0022] In some example implementations of the system, the outer diameter of the elongate sheath is between 300 and 600 microns.

[0023] In some example implementations, the system further comprises a force sensor configured to measure an opposing force applied to the distal portion of the optical fiber microcatheter during longitudinal translation of the optical fiber microcatheter.

[0024] The system may further comprise control circuitry operatively coupled to the force sensor, wherein the control circuitry is configured to employ a force signal obtained from the force sensor to provide feedback for controlling advancement of the optical fiber microcatheter.

[0025] The control circuitry may be configured to display, on a user interface, qualitative or quantitative feedback indicative of the force signal.

[0026] The control circuitry may be configured to provide haptic feedback to a user based on the force signal.

[0027] The control circuitry may be configured to provide haptic feedback to the user when the opposing force exceeds a force threshold.

[0028] In some example implementations, the system further comprises a motorized translation mechanism operably coupled to the control circuitry, the motorized translation mechanism capable of actuating longitudinal translation of the optical fiber microcatheter, the controlcircuitry being configured to control the motorized translation mechanism according to feedback provided by the force signal, such that longitudinal translation of the optical fiber microcatheter is dependent on the opposing force.

[0029] The control circuitry may be configured to control the motorized translation mechanism such that longitudinal translation of the optical fiber microcatheter is prevented when the opposing force exceeds a force threshold.

[0030] The control circuitry may be configured to control the motorized translation mechanism such that the optical fiber microcatheter is retracted when the opposing force exceeds a force threshold.

[0031] In some example implementations of the system, the optical fiber is operably coupled to the laser system through a fiber optic rotary to facilitate rotation of the elongate sheath.

[0032] In some example implementations of the system, the laser pulses have a pulse energy between 0.3-3 mJ, a pulse duration between 0.5-5 ns, a wavelength between 2750 - 3100 nm, and a repetition rate between 0.1-5 kHz.

[0033] In some example implementations of the system, the laser pulses have a pulse energy between 1mJ - 10mJ, a pulse duration between 10-50 ns, a wavelength between 1890- 1950 nm, and a repetition rate between 0.1-3 kHz.

[0034] In some example implementations, the system further comprises a delivery catheter, wherein the elongate sheath is extendable through a lumen of the delivery catheter.

[0035] In some example implementations, the system further comprises a delivery catheter, wherein the outer tube and the optical fiber microcatheter are extendable through a lumen of the delivery catheter.

[0036] The delivery catheter may comprise an anchoring means for anchoring the delivery catheter within a vessel while permitting extension of the elongate sheath beyond a distal end of the delivery catheter.

[0037] In some example implementations of the system, the delivery catheter may further comprise an endoscopic imaging subsystem comprising an optical camera capable of acquiring images of a distal region residing beyond a distal end of the delivery catheter, and an illumination source capable of illuminating the distal region.

[0038] In some example implementations of the system, the delivery catheter may further comprise an irrigation lumen connectable to an external irrigation source.

[0039] In another aspect, there is provided a method for providing intravascular laser therapy to an intravascular accumulation, the method comprising:providing the system described above, and positioning the optical fiber microcatheter such that the distal end of the optical fiber microcatheter resides adjacent to the intravascular accumulation; andas the optical fiber microcatheter is steered and longitudinally translated into the intravascular accumulation, delivering the laser pulses such that a disrupted volume, due to expansion of the laser-irradiated volume, is larger, in a lateral direction, than an outer diameter of the optical fiber microcatheter, such that longitudinal translation of the optical fiber microcatheter within the intravascular accumulation occurs with an opposing force that is lower than an opposing force that would occur in the absence of delivery of the laser pulses.

[0040] The laser pulses may be delivered, as the optical fiber microcatheter is steered and longitudinally translated within the intravascular accumulation, such that a channel is formed within the intravascular accumulation, the channel having a sufficient cross- sectional area to permit longitudinal advancement of the optical fiber microcatheter through the intravascular accumulation.

[0041] In some example implementations of the method, the laser pulses are delivered, as the optical fiber microcatheter is steered and longitudinally translated within the intravascular accumulation, such that the disrupted volume has a sufficiently large size to permit steering of the distal portion of the optical fiber microcatheter.

[0042] In some example implementations of the method, the intravascular accumulation is an intravascular occlusion, and the optical fiber microcatheter is employed to cross the intravascular occlusion while delivering the laser pulses.

[0043] In some example implementations of the method, an outer tube, housing at least a portion of the optical fiber microcatheter, may be extended with the optical fiber microcatheter during crossing of the intravascular occlusion, and wherein the distal portion of the optical fiber microcatheter is extended beyond a distal end of the outer tube to facilitate steering the distal portion of the optical fiber microcatheter via the steering mechanism.

[0044] In some example implementations, the method further comprises, after crossing the intravascular occlusion: withdrawing the optical fiber microcatheter from the outer tube while maintaining the outer tube across the intravascular occlusion; extending a guidewire through the outer tube, such that the guidewire crosses the intravascular occlusion; withdrawing the outer tube; and employing the guidewire to facilitate the positioning of a medical device for treatment of the intravascular occlusion.

[0045] In some example implementations of the method, the steering mechanism is a concentric tube-based steering mechanism that includes the outer tube, and wherein at least a distal portion of the elongate sheath is formed from a memory metal having a pre-defined curved shape, such that the distal portion of the optical fiber microcatheter is steerable by varying extension of the elongate sheath relative to a distal end of the outer tube.

[0046] In some example implementations of the method, the steering mechanism includes pull cables extending through the elongate sheath to the distal portion of the elongate sheath.

[0047] In some example implementations of the method, an outer diameter of the outer tube is between 500 and 1000 microns.

[0048] In some example implementations of the method, the outer diameter of the elongate sheath is between 300 and 1000 microns.

[0049] In some example implementations of the method, the outer diameter of the elongate sheath is between 300 and 600 microns.

[0050] In some example implementations, the method further comprises employing a force sensor to measure an opposing force applied to the distal portion of the optical fiber microcatheter during longitudinal translation of the optical fiber microcatheter within the intravascular accumulation.

[0051] The method may further comprise employing feedback generated from the force sensor to control longitudinal translation of the optical fiber microcatheter.

[0052] In some example implementations of the method, longitudinal translation of the optical fiber microcatheter is prevented when the opposing force exceeds a force threshold.

[0053] In some example implementations of the method, the laser pulses have a pulse energy between 0.3-3 mJ, a pulse duration between 0.5-5 ns, a wavelength between 2750 - 3100 nm, and a repetition rate between 0.1-5 kHz.

[0054] In some example implementations of the method, the laser the laser pulses have a pulse energy between 1mJ - 10mJ, a pulse duration between 10-50 ns, a wavelength between 1890- 1950 nm, and a repetition rate between 0.1-3 kHz.

[0055] In some example implementations of the method, a delivery catheter is employed to facilitate positioning of the optical fiber microcatheter proximal to the intravascular accumulation, wherein the elongate sheath is extendable through a lumen of the delivery catheter.

[0056] In some example implementations of the method, the delivery catheter is anchored, via an anchoring mechanism, such that the elongate sheath is extendable beyond a distal end of the delivery catheter.

[0057] In some example implementations of the method, an endoscopic imaging subsystem of the delivery catheter is employed to facilitate steering of the distal portion of the optical fiber microcatheter prior to entry of the optical fiber microcatheter into the intravascular accumulation.

[0058] A further understanding of the functional and advantageous aspects of the disclosure can be realized by reference to the following detailed description and drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0059] Embodiments will now be described, by way of example only, with reference to the drawings, in which:

[0060] FIG. 1 plots the threshold fluence, as a function of wavelength, for ionization and for disruption and liquification via the Pulsed InfraRed Laser (PIRL) impulsive heat deposition tissue disruption mechanism. Pulse durations may be controlled, depending on material composition, to achieve energy confinement to drive ablative disruption.

[0061] FIG. 2 schematically illustrates an example system for performing ablation of intravascular accumulations via the delivery of PIRL pulses by a steerable optical fiber microcatheter system.

[0062] FIG. 3A illustrates an example optical fiber microcatheter assembly that employs an integrated tendon-based steering mechanism.

[0063] FIG. 3B illustrates an example optical fiber microcatheter assembly that employs a concentric-tube-based steering mechanism.

[0064] FIG. 3C shows an example optical fiber microcatheter assembly that employs a concentric-tube-based steering mechanism, where a delivery catheter 130 is employed to facilitate positioning of the concentric tube assembly that includes the optical fiber microcatheter.

[0065] FIG. 3D illustrates an example embodiment of a hydraulically steerable hollow-core optical fiber microcatheter.

[0066] FIG. 3E shows suitable core liquids and properties for an example hydraulically steered microcatheter.

[0067] FIG. 3F shows suitable cladding catheter materials for an example hydraulically steered microcatheter.

[0068] FIG. 4A illustrates how a catheter embedded in a solid intravascular accumulation experiences opposing forces that prevent continuous movement in advancing degrees of freedom. Meanwhile shear forces cause damage due to deformation beyond the elastic limit.

[0069] FIG. 4B illustrates how PIRL pulses, with pulse parameters configured to produce ablation via the IHD process, leads to single pulse vaporization that relieves the opposing forces that would otherwise prevent continuous movement via translational and rotational degrees of freedom.

[0070] FIG. 4C shows a photograph of a vapour bubble generated as a result of PIRL-based ablation of water.

[0071] FIG. 5 shows an example delivery catheter for positioning the optical fiber microcatheter relative to an intravascular accumulation.

[0072] FIG. 6 illustrates an example implementation of an optical fiber microcatheter system that is capable of performing ablation of an intravascular accumulation via the IHD process.

[0073] FIG. 7 plots the absorption spectra of fat and muscle.

[0074] FIG. 8 shows a schematic of a single-fiber-based reflection test apparatus.

[0075] FIG. 9 plots reflection spectra of fat tissue at different sample distances. The curve for a sample distance of zero is offset from the remainder of the curves, which descend in order from the 0.13” curve.

[0076] FIG. 10 plots the intensity of laser reflection for different tissues at two different wavelengths as a function of distance.

[0077] FIG. 11 shows a schematic of an example Raman spectroscopy apparatus.

[0078] FIG. 12 shows a photograph of an example Raman spectroscopy apparatus.

[0079] FIG. 13 shows example Raman spectra for skin, muscle and fat.

[0080] FIGS. 14A, 14B, 14C, 14D, 14E, 14F and 14G illustrate an example method of crossing a chronic total occlusion via the delivery of PIRL pulses by a steerable optical fiber microcatheter.

[0081] FIG. 15 shows a photograph of an apparatus employed to measure the sound power emitted during PIRL ablation of water as a function of the laser fluence, and determine IHD fluence threshold in liquid water.

[0082] FIG. 16 shows a representative spectrum of the sound during ablation of liquid water by PIRL pulse delivery.

[0083] FIG. 17 plots a dependence of relative acoustic signal on fluence for ablation of liquid water by PIRL pulse delivery.

[0084] FIG. 18 plots the observed bubble size along with a theoretical fit based on an efficiency of about 0.65.

[0085] FIG. 19 plots the dependence of efficiency on pulse FWHM for a 1 mJ pulse.

[0086] FIG. 20 plots a comparison of cavitation bubble size vs intensity for a 200um fiber optic at 2.75um wavelength and an array of fiber optic sizes at 1.92um wavelength with 50ns pulses and different pulse energies.

[0087] FIG. 21 shows a photograph of an experimental apparatus for measuring the temperature rise of a fixed volume of water during PIRL pulse delivery.

[0088] FIG. 22 plots the temporal rise of temperature of the water as the laser energy is absorbed, based on experiments performed using the apparatus shown in FIG. 21.

[0089] FIG. 23 shows (A) the maximum force measured at the tip of the optical fiber when the laser was turned on and off, (B) the maximum force measured at different fiber advancement speeds, and (C) a maximum force comparison at full laser output and half laser output.

[0090] FIG. 24 shows (A-C) snapshots of angioscopic feedback provided for the user, for identifying (A) the plaque cap, (B) the initial crossing attempt with a guidewire, and (C) ablating the plaque with PIRL pulses. Panel D shows a microCT image of the plaque post-PIRL ablation.

[0091] FIG. 25 schematically illustrates an example system for performing ablation of intravascular accumulations within the neurovasculature via the delivery of PIRL pulses by a hydraulically steerable optical fiber microcatheter system.DETAILED DESCRIPTION

[0092] Various embodiments and aspects of the disclosure will be described with reference to details discussed below. The following description and drawings are illustrative of the disclosure and are not to be construed as limiting the disclosure. Numerous specific details are described to provide a thorough understanding of various embodiments of the present disclosure. However, in certain instances, well-known or conventional details are not described in order to provide a concise discussion of embodiments of the present disclosure.

[0093] As used herein, the terms “comprises” and “comprising” are to be construed as being inclusive and open ended, and not exclusive. Specifically, when used in the specification and claims, the terms “comprises” and “comprising” and variations thereof mean the specified features, steps or components are included. These terms are not to be interpreted to exclude the presence of other features, steps or components.

[0094] As used herein, the term “exemplary” means “serving as an example, instance, or illustration,” and should not be construed as preferred or advantageous over other configurations disclosed herein.

[0095] As used herein, the terms “about” and “approximately” are meant to cover variations that may exist in the upper and lower limits of the ranges of values, such as variations in properties, parameters, and dimensions. Unless otherwise specified, the terms “about” and “approximately” mean plus or minus 25 percent or less.

[0096] It is to be understood that unless otherwise specified, any specified range or group is as a shorthand way of referring to each and every member of a range or group individually, as well as each and every possible sub-range or sub-group encompassed therein and similarly with respect to any sub-ranges or sub-groups therein. Unless otherwise specified, the present disclosure relates to and explicitly incorporates each and every specific member and combination of sub-ranges or sub-groups.

[0097] As used herein, the term "on the order of', when used in conjunction with a quantity or parameter, refers to a range spanning approximately one tenth to ten times the stated quantity or parameter.

[0098] As used herein, the phrase “microcatheter” refers to a catheter for which a distal region thereof has a diameter less than 1 mm.

[0099] As used herein, the phrase “intravascular accumulation” refers to any substance, material, or obstruction present within a blood vessel that is not part of the normal anatomical structure of the vessel. Non-limiting examples of intravascular accumulations include plaque, thrombus, embolus, calcified deposits, lipids, proteinaceous material, cellular debris, and tissue overgrowth associated with restenosis. Intravascular accumulations may vary in size, composition, and effect on blood flow. For example, thrombi, emboli, instent restenotic lesions, or chronic total occlusions may completely block blood flow, while plaques, calcified deposits, or abnormal tissue proliferation associated with restenosis may allow partial or near-normal blood flow but still pose risks such as embolization, localized vascular injury, or progressive occlusion. Intravascular accumulations as contemplated by the present disclosure include both soft and hard materials that may arise from pathological processes, such as atherosclerosis, thrombosis, embolism, or restenosis, and that may benefit from direct or adjunctive treatment to remove, reduce, or otherwise modify the accumulation.Challenges with use of Lasers in Conventional Minimally Invasive Intravascular Procedures

[0100] Although fiber optic delivered laser pulses have been used previously in vascular surgery, previous approaches have failed to consider and address the impact of laser energy on the surrounding vascular tissue. Indeed, lasers have become indispensable in many surgical fields due to their precision and versatility, but their application in delicate vascular surgeries remains limited by several technical challenges. One of the primary concerns is the delivery of excessive heat to surrounding tissues. Some lasers operate by focusing high-power light onto targeted areas, can generate significant thermal energy. While this heat can be useful for coagulating blood and sealing vessels, it often spreads beyond the intended target, damaging adjacent tissues. In delicate vascular structures, this unintended thermal spread can lead to necrosis, weakening of vessel walls, or even perforation, complicating the healing process and increasing the risk of complications such as hemorrhage or thrombosis.

[0101] Another limitation arises from the photochemical and ionization effects associated with certain laser wavelengths and intensities. Lasers such as excimer or tripled YAG can induce photochemical reactions with their ultraviolet wavelengths, altering the molecular structure of proteins and other cellular components in unintended ways. Additionally, at high intensity, some lasers may cause ionization, creating plasma and free radicals that can damage the DNA and cellular integrity of surrounding tissues. These effects are particularly problematic in vascular surgery, where precision and preservation of endothelial integrity are critical. Damaging the endothelial layer can disrupt the normalfunction of blood vessels and impair their ability to heal, potentially leading to long-term complications like vascular stenosis or aneurysm formation. Consequently, while lasers offer powerful capabilities, their side effects such as heating, shock-wave generation and ionization necessitate careful selection of parameters and limit their widespread use in highly sensitive vascular applications.

[0102] The use of high intensity lasers inside chronic total occlusions (CTOs) and occluded vessels presents unique and significant risks due to the complex nature of these pathologies and the challenges posed by laser-tissue interactions. CTOs are characterized by heavily calcified or fibrotic plaques that completely block the blood vessel lumen, often making them difficult to penetrate or revascularize using conventional methods. Lasers are sometimes employed in such cases to vaporize or ablate the occluding material, but the inherent risks of thermal and photomechanical damage can limit their utility and safety. Lasers which are inefficient result in accumulation of significant heat as they interact with the occlusive material, which can inadvertently transfer to surrounding tissues. This heat can weaken or perforate the vessel wall, particularly in areas where the tissue is already compromised by chronic inflammation or prior interventions.

[0103] Another major concern is the risk of perforation or rupture caused by photomechanical effects. High-energy laser pulses can create shock waves or large cavitation bubbles when interacting with occluded vessels, in fluid-filled environments. These effects can exert mechanical stress on the vessel wall, potentially causing tears or complete rupture. In smaller or fragile vessels, the likelihood of catastrophic vessel injury is even higher. In these situations, pulse duration and efficiency are critical to minimize the delocalization of photomechanical effects. Parameters such as those used in laser lithotripsy, can result in pieces of hard tissue debris after laser fragmentation which can result in distal embolization, and lead to ischemic complications.

[0104] Finally, laser energy can exacerbate endothelial damage within the vessel, impairing the vessel’s natural healing response. This can increase the risk of restenosis or thrombus formation at the treatment site. The endothelium plays a critical role in maintaining vascular homeostasis, and laser-induced injury may disrupt this balance, triggering inflammatory or thrombotic cascades. Thus, while lasers offer potential advantages in dealing with CTOs, their use must be approached with caution, balancing the risks of thermal, mechanical, and biological damage against the potential benefits of successful revascularization.

[0105] Accordingly, the present inventors set out in search of a laser-based intravascular delivery solution that would solve the aforementioned problem and provide efficient disruption of awide range of types of intravascular accumulations while minimizing thermal or ionization damage to surrounding vascular tissue.

[0106] The present inventors also determined that a viable solution to this problem, when implemented using an optical fiber for laser pulse delivery, would need to avoid or reduce the forces that would be applied during extension of the optical fiber through an intravascular accumulation. Such forces can have a deleterious impact on safety, effectiveness and long term outcomes. For example, excessive forces can cause breakage of a distal portion of an optical fiber, presenting significant risk to the subject and / or requiring complex salvage procedures. Excessive forces can also impair the ability to steer a laser catheter along a path suitable for achieving a desired outcome, such as crossing a chronic total occlusion without dissection of the arterial wall and / or the inability to achieve re-entry into the true vessel lumen after entering a false lumen. Finally, excessive force can cause local trauma to the vessel tissue and can lead to poor outcomes, such as inflammation and restenosis. The present inventors therefore sought a solution that could reduce friction during extension of an optical-fiber-based laser ablation catheter, such that a reduction is achieved in the frictional forces applied to the distal optical fiber tip and in the shear forces applied to the outer surface of the catheter sheath during extension.

[0107] As described in detail below, the present inventors realized that the forces applied during advancement of the optical-fiber-based laser ablation microcatheter into an intravascular occlusion could be reduced if the laser ablation catheter could be adapted such that the lateral extent of the ablation zone - also referred to herein as the disrupted volume - exceeds the outer diameter of the distal region of the laser ablation catheter, such that the distal region of the optical microcatheter can fit inside (the somewhat elastic) channel it is creating via the repeated delivery of PIRL laser pulses during extension of the optical fiber microcatheter, and can be extended / translated longitudinally / axially without or with reduced likelihood of tearing or exceeding the elastic limit of the surrounding vascular tissue. With such an extended laser disrupted volume (disruption zone), the laser ablation catheter would be able to pass substantially unhindered into or further within an intravascular accumulation.

[0108] The present inventors also understood, based on numerous discussions with clinical experts with deep experienced in performing minimally invasive intravascular procedure, that it can be clinically useful to be able to steer a microcatheter or guidewire when attempting to cross or penetrate an intravascular lesion such as a chronic total occlusion. Accordingly, it was understood by the present inventors that high clinical utility would be realized by the inclusion of a steering mechanism that would facilitate, for example, intraprocedural navigation when crossing total chronic occlusions of arteries and fornavigating arterial blockages in tortuous vessels, such as those in the peripheral vasculature, coronary vasculature, cranial vasculature and / or neuro vasculature.

[0109] In summary, the present inventors identified the following four criteria as being relevant for improving intravascular laser ablation catheter technology to solve current problems in the intravascular therapy art:a) the capability to ablate a wide variety of types of intravascular accumulations;b) the ability to deliver laser radiation that achieves local disruption while reducing or limiting collateral damage to surrounding vascular tissue; c) the ability to perform steering through intravascular accumulations residing within tortuous portions of the vasculature; andd) the capability to produce a disruption zone that exceeds that lateral extent of the distal portion of the catheter to facilitate low-friction catheter extension.Steerable Optical Fiber Microcatheter for Delivering PIRL Laser Pulses for Ablation via Impulsive Heat Deposition

[0110] The present inventors understood that these criteria could be satisfied by a new system design that employs a steerable optical fiber microcatheter (an optical fiber surrounded by a thin elongate microcatheter sheath having an outer diameter less than 1 mm) coupled to a laser system capable of delivering infrared laser pulses with pulse conditions that have properties suitable for ablating an intravascular accumulation via the impulsive heat deposition (IHD) process. Accordingly, as will be described in further detail below, the example systems and methods described herein employ an optical fiber microcatheter system that is capable of performing ablation of an intravascular accumulations via the IHD process while driving and steering the microcatheter in a forward direction through the intravascular accumulation within very low friction. The optical fiber microcatheter system is configured to deliver pulsed infrared laser (PIRL) pulses that achieve highly localized laser disruption to reduce or minimize the piercing force when advancing the optical fiber microcatheter through the intravascular occlusion while limiting collateral damage. With this reduction in the forces during forward motion of the microcatheter, an integrated steering mechanism can be employed to not only guide and position the distal end of the optical microcatheter, but to also control the pose the distal portion of the optical fiber microcatheter to conform with the curvature of the tissue structures, (e.g. arteries, veins and blood vessels) so as to minimize uncontrolled forces that can traumatize the elastic tissue while also overcoming the challenges of continuum navigation through dense tissue of non-uniform or inhomogeneous mechanical properties.

[0111] The impulsive heat deposition (IHD) process, as described in United States Patent No. US 8,029,501 , efficiently localizes laser energy to ablate, vaporize, or emulsify solid tissue while minimizing collateral damage to surrounding tissue from thermal, acoustic, or ionization effects. The IHD process involves the delivery of infrared laser pulses with a wavelength selected such that absorption of the laser pulses by a material is predominantly due to excitation of vibrational modes of one or more constituents of the material. For example, in the case of water, the wavelength of the infrared laser pulses can be selected to target vibrational absorption of interstitial water within an intravascular accumulation to create highly localized tissue disruption due to the extremely strong absorption of infrared in the OH-stretching region, with absorption 1 / e depths on the order of 1 - 10 microns, which is smaller than a single cell dimension.

[0112] The infrared laser pulses are sufficiently short to drive disruption and liquification of the material faster than the timescales associated with thermal and acoustic transport, thus avoiding damage due to heat and shock wave formation, while also being sufficiently long to avoid the ionizing radiation effects of plasma formation.

[0113] A pulsed infrared laser system that is configured for the delivery of laser pulses having pulse conditions suitable for performing disruption of a material according to the IHD mechanism is henceforth referred to as a “PIRL” (pulsed infrared laser) system. Likewise, infrared laser pulses having wavelengths, pulse durations and energies suitable for performing disruption and liquification of a material according to the aforementioned mechanism are henceforth referred to as a “PIRL” pulses. It will be understood that a PIRL pulse is not limited to a picosecond pulse, as preferred pulse durations for some wavelengths extend into the tens of nanosecond range, as described below.

[0114] The IHD process has been described and implemented as involving the selection of appropriate laser wavelengths, pulse durations, and minimal pulse energies to achieve efficient, and local ablation of tissue. For example, US Patent No. 8,029,501 teaches the use of the IHD process for the ablation of various tissue types. The present inventors, however, realized that the IHD method could also be employed to facilitate the ablation of intravascular accumulations that would not be classified as tissue per se. Indeed, although various types of intravascular accumulations, such as arterial plaques, are formed at least in part from non-tissue materials / components, they can still contain a significant fraction of proteins and interstitial water that have vibrational levels that can be targeted for absorption by PIRL laser pulses suitable for performing ablation via the IHD process.

[0115] Accordingly, as will be described in detail below, in various example embodiments of the preset disclosure, local disruption of an intravascular accumulation is achieved using a pulsed infrared laser system that is configured to generate PIRL pulses that selectivelytarget vibrational absorption in the material forming the intravascular accumulation, and to deliver the PIRL laser pulses through a steerable optical fiber microcatheter such that the laser pulses are delivered to the intravascular accumulation with a pulse duration and fluence suitable for performing ablation via the IHD process. Accordingly, the PIRL laser pulses are delivered to the intravascular accumulation such that the absorption of laser energy is directly coupled to mechanical ablation of the intravascular accumulation over a sufficiently fast timescale to avoid the transfer of energy beyond the irradiated volume, thereby avoiding substantial collateral damage to surrounding vascular tissue.

[0116] Without intending to be limited by theory, it is believed by the inventors that the nucleation process and bubble formation occurs in a spatially distributed manner, corresponding to the energy distribution deposited in the intravascular accumulation by the fast conversion of absorbed infrared radiation into thermal motions. These nucleation sites merge at longer times (>10-100 ns) and create shock waves, and this process is highly localized through the initial uniform homogeneous nucleation that occurs with the PIRL process. Ultrasound imaging has shown these uniformly generated nucleation sites to be very effective generating a very fine dispersion that effectively liquefies the intravascular accumulation. Moreover, this process is cumulative locally. One can deliberately control the number of pulses to drive additional energy into the exposed volume to achieve thermal disruption which disperses to increase the volume of disruption. Accordingly, in some example implementations, trains of pulses of varying lengths can be employed to increase the disrupted volume in a controlled manner to extend the disruption volume beyond the single pulse limit of a few 10s of microns and to control the degree of heating as desired.

[0117] Non-limiting example suitable wavelength ranges for PIRL laser pulses can be employed that target various components of the materials forming intravascular accumulations such as sclerotic plaques and thrombotic occlusions, comprised in general of a heterogeneous mixture of water, lipids, proteins, calcium deposits, and other biomolecules, each with distinct vibrational absorption peaks. For example, the PIRL laser pulse wavelength may be selected to overlap with, or reside proximal to, a strong peak in the vibrational spectrum of a constituent of the intravascular accumulation such as:(i) water, which constitutes a significant portion of occluded tissues, exhibits strong absorption in the 2.7-3.3 pm range due to O-H stretching vibrations, as well as at 5.9-6.1 pm from H-O-H bending and the vibrational overtone mode near 1.92 pm;(ii) lipids, a major component of atheromatous plaques, show characteristic absorption peaks in the 2.7-3.3 pm range (due to C-H stretching in aliphatic chains) and around 5.75 pm (C=O stretching of ester carbonyls);(iii) proteins, including fibrin and other structural molecules in thrombi, absorb strongly at 6.06-6.49 pm, corresponding to amide I and amide II bands arising from C=O and N-H vibrations in peptide bonds; and(iv) calcified deposits, such as calcium hydroxyapatite, display phosphate (PO43-) stretching and bending vibrations between 9-11 pm. Such vibrational modes quickly absorb the electromagnetic radiation and may effectively localize optical energy to micron scale deep sections.

[0118] In the case of water, maximum absorption for vibrational modes occurs between about 2.7-3.33 pm, where broad peaks, > 10 cm-1, in the absorption spectrum, correspond to the short lived, sub-picosecond to picosecond, relaxation of the OH-stretching vibrational modes of liquid water molecules to energize the surroundings. The spectrum also shows the resonance conditions between the OH-stretch and other vibrational modes such as the OH bend and intermolecular modes. Other absorption peaks, for example, at approximately 1 ,9pm or approximately 6 pm, may alternatively be employed, as described in further detail below.

[0119] Therefore, as per the conditions associated with the IHD process, PIRL pulses are generated and delivered to an intravascular accumulation such that when a given volume of an intravascular accumulation is irradiated, the pulse duration is shorter than:(i) the time duration required for thermal diffusion out of the laser-irradiated volume; and(ii) the time duration required for a thermally driven expansion of the laser-irradiated volume.

[0120] The skilled artisan will be able to determine a suitable pulse duration for PIRL pulses for a given pulse wavelength and absorption depth in a typical intravascular accumulation (e.g., in one or more components that are known to make up various types of intravascular accumulation). In general, for a given PIRL laser pulse wavelength that is selected according to the aforementioned criterion (absorption of the laser pulses by an intravascular accumulation is predominantly due to excitation of vibrational modes of one or more constituents of the intravascular accumulation), estimated properties of the intravascular accumulation, such as the absorption depth of the laser pulses, thermal diffusion constant, and the speed of sound, may be employed to calculate a suitable PIRL pulse duration that satisfies criteria (i) and (ii) above. Alternatively, or additionally, experiments may be performed to determine a suitable laser pulse duration that satisfies criteria (i) and (ii) for various types of intravascular accumulations.

[0121] For example, in the case of disruption and liquifying an intravascular accumulation formed from a mix of calcified material, lipids, and connective tissue, with water content of about50% with a laser wavelength of 2.95 .m, for which the absorption depth is approximately 1.4 pm, the maximum pulse duration can be calculated based on the ratio of absorption depth to speed of sound in the hard plaque, ~1600 m / sec, i.e. t= a / v = 1.4 10-6m / 1600 m / s = 8.75 x 1O'10sec, giving approximately 875 ps.

[0122] Different types of intravascular accumulations will have different absorption depths at a given wavelength. Around the OH-stretching band, the absorption of many types of intravascular accumulations is expected to be dominated by the interstitial water content along with additional absorption from lipids. In general, the absorption depth will be longer than pure water. At a wavelength of 2.95 pm, the absorption depth of pure water is close to 0.7 pm, and given the variance in the high concentration of water in different types of intravascular accumulations, along with other OH-stretching modes, the absorption depth may be approximately 1-2 pm at this wavelength. If the wavelength of the laser is shifted, e.g., to a wavelength of 2.75 pm, then the absorption depth of the light increases by a factor of about 3 according to the change in the absorption spectrum of the OH-stretch. (See, for example, Diaci, J., J. Laser and Health Acad. 2012, 1-13 (2012).

[0123] In another example in which an intravascular occlusion is disrupted and liquified using a laser wavelength of 6 pm, for which the absorption depth is dominated by water and certain organic molecular vibrations, such as the C=O stretching mode of carbonyl groups and other molecular bonds present in lipids, proteins, and connective tissue. The absorption coefficient for water at 6 pm is approximately 1 ,000 cm-1. This dominates in areas of plaque with high water content. Lipids have lower absorption at 6 pm compared to water, typically with around 50-150 cm-1depending on the exact lipid structure. While calcified material does not absorb strongly in this range and has negligible contributions compared to water and lipids. For a mixed sclerotic plaque with about 35-50% water content the effective absorption coefficient at 6 pm would likely fall in the range of 500- 700 cm-1, considering a weighted average of the absorption contributions of water, lipids, and calcification. This corresponds to an absorption depth of 10 - 20 urn, the pulse duration can be chosen as shorter than 10 pm / 1.6x103= 6.25 ns (while being sufficiently long to avoid ionization, as explained below). Likewise, an absorption depth of about 100 pm is expected to occur for a laser wavelength of 1940 nm. Accordingly, a suitable pulse duration for PIRL pulses will depend on the pulse wavelength. In some example implementations, a suitable pulse duration for PIRL pulses may range from 100 ps to 100 ns, depending on the selected wavelength and light intensity dependent changes in absorption depths due to saturation of the absorption at a given wavelength.

[0124] The pulse duration and pulse fluence may therefore also be selected such that a peak pulse intensity is below a threshold for ionization-driven ablation to occur within the laser-irradiated volume. For example, for a given pulse duration, a suitable upper limit of the pulse fluence may be determined to avoid the threshold for ionization-driven ablation. In the example case of sclerotic plaque, at a laser wavelength 3 pm, the maximum fluence values for avoiding ionization-driven ablation are higher than for pure water due to the lower water content, for pulse durations of 10 ps, 500 ps, and 1 ns, in pure water, the ionization thresholds are approximately 1.5 J / cm2, 5.5 J / cm2, and 17 J / cm2, respectively, as shown in the FIG. 1.

[0125] Furthermore, in order to achieve PIRL-based disruption and liquification of intravascular accumulations for laser pulses that satisfy the preceding criteria involving wavelength, pulse duration and pulse fluence, the laser pulses should be delivered at the distal end of the optical fiber of the optical fiber microcatheter with a sufficient pulse fluence to achieve a threshold energy density for PIRL tissue disruption and liquification, as shown, for example, by the tissue disruption and liquification threshold identified in FIG. 1. For example, the pulse fluence that is delivered to the tissue should be sufficiently high so that the energy deposited in the irradiated volume is sufficient to heat the contents of the volume up to its vaporization temperature including the enthalpy of vaporization.

[0126] For example, if an optical fiber having a 200 pm core diameter fiber ablates a volume of ~1 pm deep X TT(100 pm)2, the mass of the ablated volume is 3.1x10-8g in the case of water and 3.72x10-8g in the case of plaque (which has an average density of 1.2 g / cm3). The energy required to raise the temperature of this volume of plaque, with similar heat capacity to water and similar latent heat of vaporization, from 20 to 100°C and then vaporize the volume is approximately 96 pJ of energy, which corresponds to a fluence of 0.30 J / cm2for a 200 pm spot. This fluence defines the threshold for impulsive heat deposition to drive the phase transition without loss due to acoustic transport or thermal diffusion out of the excited zone. To ensure the ensuing tissue disruption and liquification process occurs in this limit, for highly scattering medium such as tissue which effectively decreases the incident intensity, typical excitation conditions used are 1 J / cm2. The determination of a sufficient fluence for PIRL tissue disruption and liquification can be made experimentally by varying the applied fluence, examining the resulting tissue disruption and liquification, and selecting an applied fluence value that provides a sufficient amount or degree of tissue disruption and liquification. The subsequent process in the confined volume, defined by the unexcited tissue and the fiber tip, leads to disruption of the tissue to cellular levels and removal of pressure gradients.

[0127] In another example implementation, PIRL laser pulses for achieving IHD based ablation of an intravascular accumulation are provided with a 0.3-3mJ pulse energy, 0.5-5 ns pulse duration, a wavelength of 2750 - 3100 nm, and a 0.1-5 kHz repetition rate. In yet anotherexample implementation, PIRL laser pulses for achieving IHD based ablation of an intravascular accumulation are provided with a 1mJ - 10mJ pulse energy, a 10-50 ns pulse duration, a wavelength of 1890- 1950 nm, and a 0.1 -3kHz repetition rate.

[0128] Accordingly, as described below, various example embodiments of the present disclosure can be employed to enable the delivery of intense mid infrared (MIR) PIRL pulses from a laser source to be guided towards an intravascular region of interest, for example, in the lower extremities, heart, and / or cranial vasculature for minimally invasive surgical procedures.Example System for Ablation of Intravascular Accumulations via PIRL Pulse Delivery from Steerable Optical Fiber Microcatheter

[0129] Referring now to FIG. 2, an example system for performing PIRL-based ablative removal of an intravascular accumulation is schematically illustrated. The example system shown in the figure includes several components and subsystems, including a laser source 300 capable of delivering PIRL pulses, a control and processing subsystem 200, a user interface (console 290), and a steerable optical fiber microcatheter, schematically shown at 100 and described and illustrated in further detail below. The optical fiber microcatheter 100 serves as a conduit for infrared light (within the bounds mentioned earlier) from the source to the target intravascular accumulation within the vasculature of the subject. For example, the optical fiber microcatheter (optionally assisted by one or more additional components, such as, for example, a delivery catheter 130 and / or an introducer / cannula, can access intravascular regions of interest via a main entry point such as the radial artery and the femoral artery. From these entry points, the distal region of the optical fiber microcatheter can be maneuvered towards the intravascular accumulation by an experienced user at which point pulsed MIR laser light can be administered for therapeutic purposes.

[0130] PIRL laser pulses are generated by the PIRL laser source 300, which is optically coupled to (e.g. via delivery optical fiber 305) the optical fiber 110 of the microcatheter assembly 100. The optical fiber 110 is mechanically supported by an elongate sheath (tube, conduit) 120. A delivery catheter 130 may optionally be employed to facilitate insertion and positioning of the optical fiber microcatheter within the vasculature. In some example implementations, the optical fiber 110 is optionally extendable from the distal end of the sheath 120. The optical fiber microcatheter is insertable into the vasculature of a subject to position the distal end of the optical fiber 110 adjacent to an intravascular accumulation 20. In some example implementations, the distal portion of the optical fiber 110 is extendable relative to the elongate sheath 120. In other example implementations, the distal portion of the optical fiber 110 is fixed relative to the elongate sheath 120.

[0131] The laser source 130 is operatively coupled or connectable to the control and processing hardware 200 for control thereof. The example control and processing hardware 200 may include a processor 210, a memory 215, a system bus 205, one or more input / output devices 220, and a plurality of optional additional devices such as communications interface 225, external storage 230, and a data acquisition interface 235. In one example implementation, a display (not shown) may be employed to provide a user interface for facilitating input to control the operation of the system 200. The display may be directly integrated into a control and processing device (for example, as an embedded display), or may be provided as an external device (for example, an external monitor).

[0132] The PIRL source is a laser that produces infrared light with wavelength between 1.5 urn and 10 urn which meet the conditions of the thermal and stress confinement of the IHD process. These conditions are achievable at and near various material absorption peaks found within tissue and atherosclerotic tissue. In one non-limiting example of suitable PIRL laser pulse properties, PIRL pulses are delivered with a wavelength tuned to the OH stretch of interstitial water at 2950 nm, a pulse length less than 0.8 nanoseconds, and a pulse fluence at the distal aperture, 200um diameter, of the optical fiber of at least > 80 uJ, with the pulse fluence and pulse length being selected to avoid ionization. In another non-limiting example of suitable PIRL laser pulse properties, PIRL pulses are delivered with a wavelength tuned off-peak relative to the OH-stretch, for example, at a wavelength of 2750 nm, having a pulse length less than 5 nanoseconds, and a pulse fluence at the distal aperture of the optical fiber of at least > 320 uJ, with the pulse fluence and pulse length being selected to avoid ionization. In another non-limiting example of suitable PIRL laser pulse properties, PIRL pulses are delivered with a wavelength tuned to the OH stretch overtone at 2 urn region, for example, at a wavelength of 1920 nm, having a pulse length less than 50ns nanoseconds, and a pulse fluence at the distal aperture of the optical fiber of at least > 1.3 mJ, with the pulse fluence and pulse length being selected to avoid ionization.

[0133] Non-limiting examples of suitable laser systems for the generation of PIRL laser pulses include a near-IR pumped optical parametric amplifier (e.g. emitting pulses with a duration in the hundreds of ps, such as 500 ps) tuned to a wavelength of approximately 2.95 urn, operating, for example, between 0.05-10 kHz with a pulse fluence greater than 0.1 mJ / pulse, delivered on target, for example, through a sapphire fiber optic (e.g. having a core diameter of 200 urn, where the parametric amplifier could include one or more bulk nonlinear crystal, such as Potassium Titanyl Arsenate (KTiOAsO4), or a periodically poled nonlinear crystal such as periodically poled such as PPKTP and is either CW or pulse seeded at the signal ~1 ,6um or idler wavelength 2.95 or seeded by a cascaded parametric process, such as optical parametric generation (OPG) at either wavelengththat using a portion of the same pump laser, and pumped with an amplified near-IR picosecond laser such as a Nd:YAG or Nd;YLF regenerative amplifier or Master Oscillator Power Amplifier and a Cr:ZnSe gain-switched laser, emitting ns pulses (e.g. 1.5 ns), tuned to a wavelength of approximately 2.7 urn, operating, for example, between 0.05-10 kHz, with a pulse fluence greater than >0.1 mJ / pulse and focused in free space into a beam delivery fiber, and alternatively an all fiber or hybrid laser system in which a fiber amplifier consisting of a gain material such as Erbium doped ZBLAN fiber is used to amplify pulses from a fiber laser, diode laser, or Q-switched microchip lasers and amplifies them to an output with wavelength approximately 2.8 urn, operating, for example, between 1-10 kHz, with a pulse energy greater than >0.1 mJ / pulse either coupled directly into a mid-IR transmitting output fiber or through free space into a beam delivery fiber incorporated into the microcatheter. In general, the pulse energy requirement regardless of the laser architecture is determined by the intensity at the output of whatever size fiber optic is chosen and the mechanical properties of the target material , from 50um to 1mm diameters intensity must be > 0.25J / cmA2. The average power is a function of the maximum advancement speed and the thermal properties of the target material, so >100 Hz for >0.5 mm / s speeds would be typical. The control and processing system 200 may include or be connectable to a console 290 that provides an interface for facilitating an operator to control the laser source 300. The console may include, for example, one or more input devices, such, but not limited to, a keypad, mouse, joystick, touchscreen, and may optionally include a display device.

[0134] Position sensing and guidance of the optical fiber microcatheter 100 can be facilitated by position sensing subsystem 330, which is interfaced with the control and processing system 200. Non-limiting examples of position sensing subsystems are described in detail in the position sensing / guidance section below.

[0135] In various example embodiments, the longitudinal position (extension) of the optical fiber microcatheter 100 and / or the steering (pose) of the distal portion of the optical fiber microcatheter 100 within the vasculature are variable and controllable in a manual, semiautomated or autonomous manner to facilitate positioning and orienting of the distal region of the optical fiber microcatheter relative to an intravascular accumulation of interest. Several example positioning mechanisms and steering mechanisms that can be integrated with or mechanically coupled to the optical fiber microcatheter are described below.

[0136] The longitudinal position (extension) of the optical fiber microcatheter 100 and / or the steering (pose) of the distal portion of the optical fiber microcatheter 100 may be autonomously or semi-autonomously controlled via actuation of one or more integrated actuators (e.g. motors). For example, actuation of one or more actuators can be controlledin a semi-automated manner via a user interface or other user input device, or in an autonomous manner, for example, based on signals received from a position sensing system and a pre-defined surgical plan / trajectory, to transmit appropriate control signals to the position and / or steering mechanism actuators. In some example implementations, user input provided through the user interface is relayed to the control and processing system, which in turn drives the motors of a position and / or orientation actuation assembly and optionally controls when PIRL laser pulses are permitted to be transmitted to the optical fiber microcatheter. In one example implementation, stepper motors push, pull, and rotate two concentric tubes of a concentric tube-based steering mechanism (e.g. a “tube robot”), thereby controlling the position and orientation of the distal portion of the optical fiber microcatheter (the elongate sheath of the optical fiber microcatheter may be an inner tube of such a steering device). By regulating the transmission of laser light through the apparatus the system effectively delivers MIR light to an intravascular region of interest in the lower extremities, coronary vasculature, cranial / neurovasculature, and other vascular regions of the body.

[0137] In some example embodiments, longitudinal extension (advancement) of the optical fiber microcatheter into and within an intravascular accumulation may be manually, semiautomated or automated based on feedback from a force sensor (a force feedback mechanism) that is capable of generating a signal indicative of a magnitude of a force applied to the distal end of the optical fiber microcatheter. Such force-feedback-based control can be employed to ensure safe navigation and to prevent excessive forces that could damage tissue and / or lead to possible breakage of the optical fiber. Examples of such force feedback mechanisms, and their use in providing force-based feedback during manual, semi-automated, or automated extension of the optical fiber microcatheter, are described below.

[0138] FIG. 2 also shows the optional inclusion of a pump 310 and hydraulic or pneumatic conduit 320, which may be employed, as described below, to facilitate hydraulic or pneumatic control of steering of the optical fiber microcatheter.

[0139] The methods described herein, such as methods for controlling the sequence of operations of the local PIRL-based laser disruption, optionally controlling the extension, retraction and / or steering of the optical fiber microcatheter, and other example methods described below, can be implemented via processor 210 and / or memory 215. As shown in FIG. 2, executable instructions represented as control module 250 are processed by control and processing hardware 200. Such executable instructions may be stored, for example, in the memory 215 and / or other internal storage.

[0140] The methods described herein can be partially implemented via hardware logic in processor 210 and partially using the instructions stored in memory 215. Someembodiments may be implemented using processor 210 without additional instructions stored in memory 215. Some embodiments are implemented using the instructions stored in memory 215 for execution by one or more microprocessors. Thus, the disclosure is not limited to a specific configuration of hardware and / or software.

[0141] It is to be understood that the example system shown in the figure is not intended to be limited to the components that may be employed in a given implementation. For example, the system may include one or more additional processors. Furthermore, one or more components of control and processing hardware 200 may be provided as an external component that is interfaced to a processing device. Furthermore, although the bus 205 is depicted as a single connection between all of the components, it will be appreciated that the bus 205 may represent one or more circuits, devices or communication channels which link two or more of the components. For example, the bus 205 may include a motherboard. The control and processing hardware 200 may include many more or less components than those shown.

[0142] Some aspects of the present disclosure can be embodied, at least in part, in software, which, when executed on a computing system, transforms an otherwise generic computing system into a specialty-purpose computing system that is capable of performing the methods disclosed herein, or variations thereof. That is, the techniques can be carried out in a computer system or other data processing system in response to its processor, such as a microprocessor, executing sequences of instructions contained in a memory, such as ROM, volatile RAM, non-volatile memory, cache, magnetic and optical disks, or a remote storage device. Further, the instructions can be downloaded into a computing device over a data network in a form of compiled and linked version.Alternatively, the logic to perform the processes as discussed above could be implemented in additional computer and / or machine-readable media, such as discrete hardware components as large-scale integrated circuits (LSI's), application-specific integrated circuits (ASIC's), or firmware such as electrically erasable programmable readonly memory (EEPROM's) and field-programmable gate arrays (FPGAs).

[0143] A computer readable storage medium can be used to store software and data which when executed by a data processing system causes the system to perform various methods. The executable software and data may be stored in various places including for example ROM, volatile RAM, nonvolatile memory and / or cache. Portions of this software and / or data may be stored in any one of these storage devices. As used herein, the phrases “computer readable material” and “computer readable storage medium” refers to all computer-readable media, except for a transitory propagating signal perse.

[0144] A PIRL-based intravascular treatment system, such as the example system shown in FIG.2, may offer distinct benefits over other intravascular treatment approaches. For example,one primary advantage of the present example systems and methods over ultraviolet (UV) laser systems is the use of wavelengths that avoids photochemical (sunburn-like) damage to adjacent tissues along with improved photomechanical cutting efficiency and reduced shock waves.

[0145] Moreover, intense ultra-short pulsed IR PIRL pulses, for example, with a wavelength around 2.9 urn, can be advantageous over mechanical or UV laser mechanisms for tissue disruption due to ultrafast photomechanical interaction to achieve disruption and microscopic fragmentation of mechanically resilient disease tissue, without the risk introduced by ionizing UV radiation. In example implementations involving PIRL pulses having a wavelength of 2850 nm, the absorption of water is approximately seven orders higher than at a wavelength of 308 nm. Accordingly, such a PIRL-based intravascular treatment system can potentially achieve comparable results to UV catheters with far less energy and thus fewer fibers resulting in increasingly versatile catheter assemblies.Image Guidance / Catheter Navigation

[0146] While the example implementation illustrated in FIG. 2 demonstrates the use of a positioning system for guidance (e.g. ultrasound-based or fluoroscopy-based), it will be understood that any suitable image guidance system, tracking system, or positioning system may be employed to facilitate guidance of the distal end of the microcannula to the target, optionally also providing surgical guidance based on intraoperative volumetric image data that is rendered in an intraoperative frame of reference and presented on a user interface.

[0147] As noted above, the position of the optical fiber 110, or distal optical waveguide (e.g. the optical fiber may be in optical communication with a distal optical waveguide), may be detectable by and displayed, optionally relative to pre-operative image data, via a surgical guidance or navigation system, which can include a positioning mechanism, manual or motorized, which guides the insertion of the distal end of the apparatus into the body towards a targeted volume of an intravascular accumulation to be disrupted by the PIRL laser pulses within and / or during traversal of the intravascular accumulation. The position of the distal end of the optical fiber, can be determined, for example, using a position sensor in conjunction with spatial imaging such as an ultrasound, x-ray or MRI.

[0148] The path of the optical fiber microcatheter to the intravascular occlusion can be tracked in real time with minimal tissue deformation during passage to ensure absolute targeting of the desired tissue, or precise location. The distal region of the optical fiber microcatheter can be guided and adjusted in real time with one or more imaging methods such as, but not limited to, ultrasound imaging, magnetic resonance imaging, fluoroscopy, computed tomography, angioscopy and electromagnetic position sensing, optionally employing oneor more detectable markers residing on the microcannula and / or optical fiber, and optionally also providing surgical guidance based on intraoperative volumetric image data that is rendered in an intraoperative frame of reference and presented on a user interface.

[0149] In some example embodiments, the optical fiber tip may be detected and localized by ultrasound imaging of a photoacoustic signal generated by the local disruption of tissue by the PIRL pulses. For example, ultrasound imaging may be employed to detect shock waves that enable localization of the distal tip of the optical fiber. Such an embodiment may be beneficial in providing an improvement of localization accuracy over what is achievable based on the detection of ultrasound echoes from the tip region of a sapphire optical fiber, as ultrasound artifacts can arise due to the high reflectance due to the acoustic property difference of 10 (v_sapphire = 10x speed of sound in water and >1 Ox for speed of sound in tissue), as a high reflectance to low reflectance boundary leads to constructive interference that can impair visualization of the precise location of the tip. By superimposing ultrasound imaging with photoacoustic imaging, the active region at the distal end region of the fiber can be imaged to high accuracy. If ultrasound imaging is employed with a sufficiently high frequency, it can be possible in some cases to also image an intravascular accumulation.

[0150] The use of ultrasound imaging is limited in depth resolution by acoustic attenuation that varies quadratically with frequency. To have sufficient spatial resolution to image the fiber position, ultrasound wavelengths of approximately 30 MHz (or approximately 30 micron acoustic wavelengths) may be beneficial in enabling near diffraction limited resolution with current transducer technology. This frequency limits the imaging depth to approximately 1-2 cm. This depth can be extended to approximately 5 cm by employing lower frequencies, such as frequencies between 10-20 MHz.

[0151] In order to provide accurate position tracking and guidance deeper within the body cavity, other imaging modalities that have less contrast may be employed to identify the position of the fiber in the 3D space of the body cavity. For example, fluoroscope x-ray imaging or use of electromagnetic field gradients or MRI may be employed to image the optical fiber microcatheter and guide its position. Such imaging modalities may not have sufficient contrast to identify the fiber position relative to critical components within the body, to guide the fiber along the optimal, surgically relevant, pathway.

[0152] In such cases, as well as a general feature of imaging the fiber within the body, the position of the distal region of the optical fiber microcatheter can be uniquely determined by exploiting the large strain field generated by the PIRL process at the fiber tip. The action of PIRL in tissue disruption via the ultrafast thermal energy deposition in the 10 micron scale leads to thermally driven volume expansion with strain fields (delta V / V) of 10-2or larger. This strain field is orders of magnitude larger than that radiated bypiezoelectric transducers used for the ultrasound imaging. This extremely large strain can be detected by conventional photoacoustic detection to give an extremely bright acoustic point source or beacon to uniquely position the fiber in the body. The extremely large magnitude of the strain field means that the signal can be detected up to the desired 5-10 cm depth, or deeper, that would then effectively give unique photoacoustic location of the fiber anywhere in the body. This acoustic beacon, which is inherently generated through the action of the PIRL pulses emitted by the fiber in the act of disruption to make a pathway or for deliberate disruption, can be superimposed on other previously generated images such as CT scans, MRI, or use of position sensing devices (e.g. electrostatic location of the fiber tip). In the latter case, a pick-up coil can be used to map and display the fiber position relative to a 3D CT scan or other reference pre-operative volumetric image (provide that the preoperative image can be represented in the intraoperative reference frame, for example, by the use of stereotactic patient tracking devices, such as optical tracking systems, and / or via intraoperative image fusion, such as ultrasound to CT image fusion). The photoacoustic beacon thus provides a means of locating the fiber tip and its relation to the planned intravascular route to the region of interest.

[0153] Once the distal end of the optical fiber is positioned proximal to or within an intravascular accumulation of interest, the optical fiber may be employed to transmit PIRL pulses with sufficient energy to disrupt a desired volume, for example, via one or more pulses, optionally with timed intervals suitable to achieve a desired volume of disruption.It will be understood that the skilled artisan may perform experiments with real or simulated intravascular accumulation (e.g. a phantom) to determine a suitable pulse energy, number of pulses, and or pulse repetition rate to achieve a suitable level of PIRL- based disruption and / liquification, and / or thermal therapy induced ablation. For example, in the case of PIRL pulses tuned to the OH stretch water resonance at a wavelength of include 2.7-3.3 pm, each pulse interaction above the threshold fortissue disruption has been found to disrupt and liquify approximately 10 - 100 micron depth profile (depending on the chosen wavelength and the mechanical properties of the type of intravascular accumulation) from the optical fiber exit face.Examples of Steering Mechanisms

[0154] It will be understood that the optical fiber microcatheter that is employed to delivery the PIRL laser pulses for the ablation of an intravascular accumulation and while facilitating low-friction extension and steering of the microcatheter within the intravascular accumulation may be configured to be steerable according to a wide variety of steering mechanisms, thereby enabling criterion (c) above to be satisfied.

[0155] Traditional catheters and guidewires may encounter limitations when maneuvering through tortuous vessels, potentially leading to increased procedure time or risk of vesselinjury. By incorporating continuum robotic principles, devices such as steerable catheters and robotic-assisted endovascular tools can achieve enhanced flexibility and control. For instance, the adaptation of conventional catheters to include steering mechanisms based on continuum robotics can facilitate precise steering and positioning within the vasculature, improving the efficacy of interventions such as angioplasty or stent deployment.

[0156] Continuum robotics is a specialized field that focuses on the design and control of robots with continuously deformable structures, distinguishing them from traditional robots composed of rigid links and discrete joints. These robots draw inspiration from biological organisms such as snakes and octopuses, which exhibit fluid and adaptable movements through continuous bending. By employing flexible backbones or "continuums," continuum-robot-based steering mechanisms can achieve smooth and precise navigation within confined and complex environments. This capability makes them particularly suitable for applications requiring high degrees of dexterity and adaptability, such as minimally invasive medical procedures. Continuum robotics can be beneficially applied to endovascular medical devices by enhancing their ability to navigate the complex and delicate pathways of the human vascular system.

[0157] One type of steering mechanism suitable for endovascular applications is the tendon- driven steering mechanism, which employs a flexible backbone structure actuated by tendons extending along its length. The backbone is a central, flexible component made from superelastic materials such as nitinol, providing the necessary flexibility and resilience to allow for continuous bending without permanent deformation. This backbone is distinct from the catheter sheath and serves as the internal structural core within the catheter assembly. The catheter sheath encases the backbone and tendons, providing a smooth outer surface for safe navigation through blood vessels but does not contribute to the actuation mechanism.

[0158] Tendons, constructed from high-tensile-strength materials like stainless steel wires or polymer fibers, are strategically positioned around the circumference of the backbone. Each tendon is anchored at the distal end of the backbone and extends proximally to an actuation mechanism located outside the patient's body. The actuation of the tendons is achieved by applying controlled tension through external actuators, which may consist of motorized reels or linear actuators. By selectively increasing the tension in a specific tendon or combination of tendons, the backbone is induced to bend toward the side where the tension is applied. This bending occurs because the tightened tendon exerts a pulling force on the backbone, causing it to flex in the direction of the applied tension due to the differential forces along its length.

[0159] The magnitude and direction of the bending can be precisely controlled by adjusting the tension in the tendons, allowing the robot to assume complex three-dimensional configurations. This enables the clinician to steer the device with high precision through the vascular system, navigating tortuous pathways and accessing target sites with minimal trauma to vascular tissues. The tendon-driven actuation mechanism enhances the maneuverability and control of the endovascular device, improving procedural efficacy and patient outcomes.

[0160] FIG. 3A illustrates an example optical fiber microcatheter assembly that employs an integrated tendon-based steering mechanism. The example optical fiber microcatheter assembly includes an optical fiber 110 having an outer jacket (elongate sheath, 120A and 120B). The optical fiber 110 has a proximal end 150 that is connectable to the PIRL laser source. The optical fiber microcatheter formed from the optical fiber 110 and the jacket is extended through an optional delivery catheter 130 to facilitate insertion and navigation of the distal portion 112 of the optical fiber microcatheter to the region of interest within the vasculature, for example, proximal to an intravascular accumulation that is to be ablated by PIRL pulses. Tendon wires 140 are integrated into and extend along the jacket and are connected to tendon anchors 148 within a distal region 112 of the optical fiber microcatheter, where the jacket 120A is less rigid than a more rigid proximal portion of the jacket 120B. Steering of the distal region 112 of the optical fiber microcatheter is achieved via applying appropriate tension to the tendons by a tendon tension control mechanism, such as rotatable spools 145 and 146 shown in the figure. This actuation results in bending of the distal region 112 of the optical fiber microcatheter where the jacket 120A is less rigid and prone to bending.

[0161] Another type of steering mechanism suitable for endovascular applications is the concentric tube steering mechanism (also commonly called a tube robot), which consists of at least one pre-curved elastic tubes nested within one another more rigid tube. The tubes can be rotated and translated relative to one another, and the combined elastic interaction between the tubes results in complex three-dimensional shapes. The ability to adjust the curvature and orientation of each tube enables the robot to conform dynamically to the anatomy of the vascular system. This type of robot is particularly advantageous for accessing hard-to-reach areas, such as distal branches of the arterial or venous network, by providing enhanced maneuverability without increasing the device's overall diameter.

[0162] FIG. 3B illustrates an example optical fiber microcatheter assembly that employs a concentric-tube-based steering mechanism. The example optical fiber microcatheter assembly includes an optical fiber 110 having an elongate sheath 120, where at least a distal portion of the elongate sheath 120 is formed from a memory metal such as a nitinolalloy and is pre-bent to have a curved profile. The optical fiber 110 has a proximal end 150 that is connectable to the PIRL laser source. The optical fiber microcatheter, formed from the optical fiber 110 and the elongate sheath 120, is slidably extendable from the lumen of an outer tube (conduit) 160, such that a distal region of the optical fiber microcatheter is extendable relative to distal end of the outer tube 160.

[0163] As can be seen in the figure, extension of the distal region 112 of the optical fiber microcatheter relative to the distal end of the outer tube 160 causes the degree of deflection (pose) of the optical fiber microcatheter to vary, with the distal end of the optical fiber microcatheter moving both longitudinally and laterally, exposing the pre-determined curve profile of the memory-metal elongate sheath 120. In both the curved and the straightened states, the optical fiber microcatheter can be rotated relative to the outer tube 160, thereby facilitating three-dimensional steering of the distal region 112 of the optical fiber microcatheter. In some example implementations, both the optical microfiber microcatheter and outer tube 160 can be longitudinally (axially) translated, separately or in unison. For example, it may be beneficial to translate the outer tube 160 relative to the optical fiber microcatheter such that the outer tube 160 extends over the optical fiber microcatheter after employing the optical fiber microcatheter to perform ablative crossing of an intravascular occlusion (e.g. a CTO), so that the outer tube 160 establishes a conduit across the occlusion through which a guidewire can be extended after withdrawal of the optical fiber microcatheter from the lumen of the outer conduit 160.

[0164] In one example implementation, a steerable microcatheter system is provided with a 200 pm sapphire-tipped fiber, embedded in concentric memory alloy tubes with a pre-set bending radius that lies within the range of 10-40 mm. Such a steerable optical fiber microcatheter system allows for precise manipulation of the optical fiber relative to the outer tube of the concentric tube steering mechanism, enabling targeted treatment of diseased tissues while leaving healthy vascular tissues substantially unharmed.

[0165] In some example implementations, a delivery catheter may be provided to facilitate insertion and navigation of the distal portion 112 of the optical fiber microcatheter to the region of interest within the vasculature, for example, proximal to an intravascular accumulation that is to be ablated by PIRL pulses. FIG. 3C illustrates such an example case, where a delivery catheter 130 is employed to facilitate positioning of the concentric tube assembly that includes the optical fiber microcatheter.

[0166] Another example steering mechanism that can be integrated with the optical fiber microcatheter is a pneumatic or hydraulic steering mechanism. In some example embodiments, a pneumatic or hydraulic actuated fluid-core optical fiber microcatheter integrates pneumatic navigation with a liquid-core or air-core optical waveguide (“optical fiber”) for laser energy transmission.

[0167] Liquid-core waveguide catheters have been used in laser angioplasty and ablation of arterial plaque, where they demonstrated the use of fluid-core optical catheters for delivering laser energy to intravascular targets. These catheters utilize iodinated radiographic contrast materials as the core fluid, enabling efficient transmission of high- peak-power visible laser pulses. These catheters are engineered to navigate the vasculature's tortuous pathways, utilizing biocompatible fluids to transmit laser energy effectively.

[0168] Moreover, robotic catheters with pneumatic actuation have been employed in robotic catheter systems to enhance navigation through complex vascular environments. Studies have explored path planning for robotic catheters driven by pneumatic artificial muscles, aiming to improve precision in navigating deformable vessels. These systems leverage pneumatic control to achieve smoother and more accurate catheter movement.

[0169] While liquid-core or air-core waveguide catheters and pneumatic guidance systems have been independently developed and utilized, the present example embodiment combines these two technologies into a single microcatheter system that advantageously uses the central microcatheter channel for both optical waveguiding and for pneumatic or hydraulic steering. The integration of pneumatic / hydraulic steering with a fluid-filled waveguide for laser energy transmission thus appears to provide a significant improvement for facilitating PIRL-based ablation of intravascular accumulations during endovascular interventions.

[0170] Indeed, by utilizing a fluid core waveguide instead of a solid core waveguide, improved flexibility can be achieved with a small cross-sectional footprint for the microcatheter tip. A fluid core can increase the minimum bend radius relative to that of a solid core waveguide. The pneumatic / hydraulic action takes advantage of this flexibility to achieve a small form-factor microcatheter design that has steering abilities either due to the pressurization of the waveguide channel, or additional parallel channels within regions of the soft catheter designed to enable pneumatic steering of the tip or other portions of the catheter assembly.

[0171] Steering of the fluid core microcatheter is achieved by varying the pressure within the fluid core. For example, when the catheter is ‘deflated’, it can be advanced through torturous portions of vessels and then ‘inflated’ selectively for steering or entirely upon reaching the target tissue to deliver the laser energy. In other words, pneumatic artificial muscles or channels allow controlled movements, enabling the catheter to navigate complex, deformable vascular structures smoothly and accurately. Hydraulic systems can provide dynamic tip steering and changes in stiffness, which enhances the catheter's ability to reach target areas that are otherwise challenging to access along. The ability to controlinflation and deflation of pneumatic segments ensures that the catheter can adapt to changes in vessel geometry without excessive force, reducing trauma to the vessel wall.

[0172] FIG. 3D illustrates an example embodiment of a hydraulically steerable hollow-core optical fiber microcatheter. The optical fiber in this case is cylindrical tubing 170 formed from a material having an index of refraction that, in combination with a central fluid 172, creates conditions of total internal reflection suitable for waveguiding optical energy (e.g. PIRL laser pulses) to a distal tip region 174. The distal tip region 174 includes a transparent window 176 of sufficient thickness such that it can be secured and sealed (e.g. using an adhesive such as glue or forming a thermal bond) to the inner or outer surfaces of the cylindrical tubing.

[0173] The distal portion 174 of the tubing is formed from a material and / or with a thickness that results in the distal portion 174 to have greater compliance / flexibility than the remaining proximal portion, such that the distal portion 174 can be inflated to a predefined shape (lower portion of FIG. 3D) and / or deflate (upper portion of FIG. 3D) to accommodate tight bends through tissue and thereby enable guidance of the catheter tip through torturous vasculature. Upon guidance to the target, the catheter would then be fully inflated for delivery of laser pulses efficiently through the fluid core waveguide.

[0174] The pressure inside the waveguide is controlled with a hydraulic system into which the laser is also coupled. For example, FIG. 3D shows a proximal fluid / optical coupling region 178 that includes a proximal optical coupling lens 180 and a seal 182 (which optionally permits rotation of the cylindrical tubing 170). The transparent window or ‘end-cap’ 176 allows the laser to irradiate the target without loss of the waveguide fluid up to some maximum pressure, sufficient to inflate and deflate the soft distal portion of the tubing while also achieving sufficient stiffness in inflation, or to maintain collapse of the soft tip during deflation. The system can be primed before use to eliminate any vacancies or airbubbles in the cylindrical tubing 170. The pressure of the fluid inside the system and hence the shape and stiffness could be controlled by a syringe pump for example. In other embodiments, multiple fluidic channels are used to control the shape of the tip or other regions of the catheter for additional degrees of freedom.

[0175] The hydraulic actuated fluid waveguide microcatheter may be constructed using materials optimized for flexibility, optical performance, and biocompatibility. The catheter includes soft, thin-walled tubing, for example, with inner diameters in the range of 50 to 200 micrometers, composed of materials such as, for example, medical-grade silicone, polyimide, polyethelyn, or polyurethane, providing biocompatibility, elasticity, and durability to navigate complex vascular pathways.

[0176] The transparent optical window 176 may be fabricated from a material such as, for example, sapphire, fused silica, or other high-strength, optically transparent materials,allowing efficient transmission of laser energy to the target tissue while withstanding thermal and mechanical stresses. The fluid core 172 of the waveguide may employ biocompatible liquids, such as iodinated contrast agents, saline solutions, or perfluorocarbon-based fluids, ensuring optimal optical transmission and compatibility with the mid-infrared wavelength range when necessary. For specific mid-IR wavelengths that are absorbed well in tissue, some of the material constraints make selection of suitable materials challenging. The tables shown in FIGS. 3E and 3F list examples of suitable core liquids and cladding materials that have the appropriate optical properties to form a >100 cm waveguide with sufficient transmission in the core and low absorption of evanescent waves in the cladding.

[0177] The example fluid / optical coupling region 178 shown in the figure consists of a sealed chamber with an optically transparent window or lens 180 that collects laser input from an external beam and couples through the liquid into the waveguide input which is also sealed in an unobstructed position relative to the optical window or lens input.

[0178] The figure also shows the inclusion of a pump (pressure applying) mechanism 184, shown in the example form of a syringe pump, forming a variable fluid reservoir 186 that is fluidically coupled to the optical / fluidic coupling component via fluidic conduit 188 for applying or removing pressure from the fluidic core of the cylindrical tubing 170.Pressurizing of the central fluidic lumen of the optical the cylindrical tubing 170 causes actuation of steering of the tip and also enables, upon inflation, the functional waveguiding with low or minimal absorption losses and high optical efficiency. The distal tip region 174 is constructed through varying stiffness or dimensions across opposing lengths of the lumen of the tip so that it forms a tight angle when deflated.

[0179] The flexibility and elasticity of the optical waveguide may be engineered by modifying the properties of the (e.g. polyethylene) cladding. Adjustments to molecular weight or the incorporation of softening agents create regions with varying stiffness along the waveguide. At the distal end, the cladding may be thinned or replaced with a softer material (e.g. softer polyethylene variant) to enhance flexibility. The tip may be configured to bend predictably under low pressure by incorporating anisotropic stress patterns during fabrication, such as localized stretching or heat treatment. Additional structural modifications, including embedded microchannels or corrugations, ensure precise directional bending to meet specific application requirements.

[0180] By hydraulic inflation, the radius of curvature of the distal tip region can be controlled, from the tightest angle to either straight or some desired angle. By controlling the pressure applied to the soft tip and rotating the optical fiber microcatheter, the optical fiber microcatheter can be guided into tortuous vascular geometries and then inflated fully upon reaching the target region of tissue to deliver the laser pulses.

[0181] While FIG. 3D shows a hydraulic pressure control device in the form of a syringe pump, but it will be understood that a wide variety of pump mechanisms may be employed in the alternative, in manual, automated, or semi-automated form. For example, FIG. 2 illustrates the inclusion of the pump 310 and optional reservoir 315, optionally connected to the control and processing system for autonomous or semi-automated control of the pump 310 for steering of the distal portion of the optical fiber microcatheter.

[0182] The hydraulic steering mechanism shown in FIG. 3D can be adapted to pneumatic embodiment utilizing pressurized gas, such as nitrogen or carbon dioxide, the catheter achieves controlled inflation and deflation, dynamically modifying its shape and internal waveguide structure to maintain the conditions necessary for total internal reflection or anti-resonant waveguiding. In this case the index of the gas is likely lower than the catheter cladding material, here the catheter tubing inner surface must be highly reflective or spatially confining, e.g. equivalent to hollow-core metal-coated fibers, omniguide fibers, or anti-resonant gas-filled waveguides.

[0183] Another type of steering mechanism employs magnetic materials into flexible structures to facilitate remote manipulation via external magnetic fields. Such magnetic steering mechanisms eliminate the need for onboard actuators and power sources, thereby reducing the device's complexity and size — a critical factor in endovascular applications where space is limited. By adjusting the strength and orientation of external magnetic fields, clinicians can steer the distal end of the microcatheter through the vascular system with high precision. This technology is particularly useful for navigating through highly tortuous or occluded vessels, where traditional mechanical steering mechanisms may be less effective.

[0184] Many types of steering mechanisms employ compliant, biocompatible materials that can safely deform within the body. For example, a steerable microcatheter may employ compliant materials such as shape memory alloys, dielectric elastomers, or embedded pneumatic channels to achieve movement. The high compliance of soft structures allows them to conform closely to the vascular anatomy, reducing the risk of vessel injury.Moreover, such materials can be beneficially employed to allow for the adjustment of the stiffness of the distal portion of microcatheter, thereby enhancing its stability during procedures, providing a balance between flexibility for navigation and rigidity for instrument support when necessary.

[0185] In some example implementations, a microcatheter assembly may include a hybrid steering mechanism that combines features from multiple types of steering mechanisms to facilitate performance for specific endovascular applications. For example, a hybrid steering mechanism may integrate tendon-driven actuation with soft materials to achieve both high dexterity and compliance. By leveraging the strengths of different continuumsteerable / robotic technologies, a steerable microcatheter can provide tailored solutions that address the unique challenges of navigating and operating within the vascular system, offering enhanced control, adaptability, and safety, thereby improving the overall effectiveness of endovascular interventions.

[0186] While conventional steerable microcatheters can facilitate control over the positioning and / or pose of a long flexible catheter within the vasculature, the limited force capability of such devices can be insufficient to perform operations involving movement within solid tissue. In particular, the flexibility of conventional steering mechanisms limits the amount of force that can be applied before buckling. Moreover, even if existing steering mechanisms were adapted to facilitate the application of more force and with less flexibility, this adaptation would only cause inelastic deformation of the intravascular accumulation due to the inability of conventional steering mechanism to penetrate and move through various types of intravascular accumulations without significant force and shear resistance. However, as described below, when combined with PIRL pulses that produce a disrupted volume exceeding the lateral size of the distal region of the steerable optical fiber microcatheter, these limitations can be overcome.PIRL Pulse Delivery for Low-Friction Advancement and Steering of Optical Fiber Microcatheter via Enhanced Disruption Volume

[0187] The PIRL-based intravascular treatment systems and methods described herein, which employ an optical fiber microcatheter to deliver PIRL pulses to intravascular accumulations, can ablate a wide variety of types of intravascular accumulations and deliver laser radiation that achieves local disruption without adversely impacting surrounding vascular tissue, thus addressing criteria (a) and (b) listed above for providing an improved intravascular laser ablation catheter that would solve current problems in the intravascular therapy arts.

[0188] However, a microcatheter system that delivers PIRL pulses to a local region of an intravascular accumulation, through an optical fiber inserted into the vasculature, also addresses criterion (d), namely the capability to produce a disruption zone that exceeds that lateral extent of the distal portion of the catheter to facilitate low-friction catheter extension. Indeed, when PIRL pulses are delivered to an intravascular accumulation with a sufficient fluence, the local disruption and liquification of the laser irradiated volume causes an explosive pressure increase that drives expansion of the laser irradiated volume to produce a disrupted volume that can exceed the lateral extent of the fiber optical microcatheter (i.e. exceeding the outer diameter of the microcatheter sheath / jacket surrounding and protecting a distal region of the optical fiber).

[0189] The term “disrupted volume”, as used herein in relation to the impact of PIRL pulses on an intravascular accumulation, refers to the volume of the void (ablation zone) caused by pressure-driven expansion of vapour generated by the IHD process as a consequence of PIRL pulse absorption within a laser irradiated volume. This disrupted volume may become filled with liquified material soon after the pressure-driven expansion process. When a lateral extent of the disrupted volume exceeds the outer lateral extent of the distal end or region of an optical fiber microcatheter that is employed to deliver PIRL pulses to an intravascular accumulation, extension, and in some cases, local steering, of the distal region of the optical microcatheter is facilitated, as described in further detail below. A lateral extent of the disrupted volume can be determined, or assessed, for example, by performing optical fiber microcatheter delivery of PIRL pulses to intravascular accumulations present in cadaverous or in-vitro vessel samples and observing the cross- sectional extent of the resulting disrupted volume, for example, by sectioning and optical microscopy.

[0190] The large disrupted volume caused by the delivery of PIRL pulses enables advancement of the distal tip of the optical fiber through the intravascular accumulation, which can result in a significant reduction in friction force relative to the force that would be experienced under advancement of the optical fiber microcatheter in the absence of PIRL pulse delivery. Accordingly, PIRL-based intravascular treatment systems and methods can be employed to provide a forward ablation mechanism that reduces (e.g. minimizes) the piercing force required to advance the optical fiber microcatheter into the lesion, avoiding or reducing the likelihood of fiber breakage, and also reduces the shear forces applied to the outer surface of the catheter sheath during extension, thereby reducing collateral damage to surrounding vascular tissue. Indeed, by reducing forces that impede catheter movement, the system allows precise positioning, reducing the likelihood of trauma to elastic tissues such as arteries and veins.

[0191] This aspect of the present disclosure is illustrated in FIGS. 4A and 4B. FIG. 4A illustrates several problems associated with attempts to cross a CTO using a conventional microcatheter: the microcatheter experiences a restoring force opposing its penetration into the occlusion and strong shear forces along its length, causing a zone of tissue damage and buckling of the microcatheter at a proximal location outside of the occlusion. The forces prevent the continuous movement and resist attempts to steer the microcatheter along a desired path. The shear forces also produce a torque that counteracts attempts to rotate the microcatheter during steering.

[0192] In stark contrast to FIG. 4A, FIG. 4B shows the utility of the increased disruption volume resulting from the explosive pressure increase caused by PIRL ablation. As shown in the figure, the delivery of PIRL pulses that are configured to produce ablation via the IHDprocess leads to single pulse disruption and liquification of the intravascular occlusion. The IHD ablation mechanism causes temporary vaporization of the PIRL laser-irradiated volume (the volume of tissue irradiated by PIRL laser pulses satisfying the IHD criteria), leading to expansion of the gas-filled cavity and subsequent collapse into liquification of an enhanced disruption volume that extends out beyond the initial laser-irradiated volume. This rapid volumetric expansion of PIRL ablation of water is illustrated in FIG. 4C. The figure shows the bubble created by the single laser pulse in which the maximum volume of the bubble corresponds proportional to the energy (above threshold) that is absorbed by the water. Upon absorption of the energy of the very short laser pulse, the molecules whose vibrational modes are resonant with the wavelength of the laser become excited and this vibrational energy is rapidly converted into lower frequency vibrational modes, intermolecular vibrations and eventually macroscopic motion and heating. Due to the ultrafast timescales of the energy input, this energy is localized to a volume of material of approximate thickness of the absorption depth of the light. Subsequently the material which has been rapidly heated up to the maximum temperature and beyond the enthalpy of vaporization to become hot vapour, in the case of liquid water this volume expands to form a bubble whose volume is proportional to the amount of energy absorbed from the laser above the vaporization threshold.

[0193] The portion of water that is vaporized expands until there is a balance of pressure inside and outside the bubble, at which point it collapses due to energy dissipation. The image is recorded using a stroboscopic camera which shows the bubble at a point in time where it is maximal. By comparing the observed volume of the bubble with the energy per pulse at the output of the fiber optic, the efficiency of energy conversion from light to mechanical disruption can be measured. It was found that this efficiency is maximum for the highest absorption peak and under IHD conditions. High efficiency for laser disruption is advantageous as it is accompanied with minimal mechanically ineffective thermal energy deposition. Similar phenomena occurs in tissue, but where the bubble size gets smaller as the stiffness of the tissue increases. Accordingly, as long as sufficient energy is absorbed to create a void large enough for the distal tip to pass deeper into the tissue either entirely into the voided cavity, or with a little elastic deformation of the surrounding material, the friction of advancing the distal tip will be minimized.

[0194] If the PIRL pulses are provided with a sufficiently high fluence, this enhanced disruption volume can exceed the lateral extent of the distal portion of the optical fiber microcatheter, relieving the opposing forces that would otherwise prevent continuous longitudinal extension, rotation and steering of the microcatheter. Indeed, as shown in the figure, the delivery of multiple PIRL pulses during extension of the optical fiber microcatheter can be employed to create a low-friction pathway that enables low-friction extension of themicrocatheter, reducing the likelihood of buckling, reducing axial forces applied to the distal end of the optical fiber microcatheter and reducing shear forces, thereby enabling the clinician to extend and steer the optical fiber microcatheter through the intravascular accumulation with control and without causing substantial injury to the surrounding vascular tissue. The present example PIRL-based intravascular treatment systems and methods can therefore be employed to achieve localized disruption / liquification of the intravascular accumulation while also permitting the optical fiber microcatheter to advance without substantial shear friction (analogous to a hot knife in butter), leading to efficient ablation and homogenization of at least a portion of the intravascular accumulation.

[0195] Accordingly, various example implementations of the present disclosure, laser-mediated fiber optic microcatheter adapted with integrated steering mechanism is employed clinical applications including, for example, the crossing of chronic total occlusions (CTOs) and the debulking of vascular lesions. The example embodiments disclosed herein, when configured to deliver PIRL pulses with a sufficiently high lateral disruption zone, facilitate a guided, frictionless cutting mechanism that allows for precise placement of a conventional guidewire through hardened occlusions while minimizing trauma to the arterial wall and surrounding tissue. Accordingly, the systems and methods disclosed herein addresses the need for a minimally invasive laser scalpel device, configured for guided intravascular tissue disruption, that incorporates motorized and vision-assisted systems for precise tissue fragmentation with reduced or minimal detrimental forces. In other words, various example systems and methods disclosed herein may be configured for frictionless forward cutting in intravascular procedures using a pulsed infrared laser (PIRL) system, where the laser technology reduces or minimizes piercing force and collateral damage to surrounding tissues, enhancing safety and effectiveness during arterial occlusion treatment, configured in the form of an intravascular optical fiber microcatheter that is configured to takes advantage of the above ablative mechanism to facilitate steering while penetrating the intravascular occlusions, thereby providing a capability to control and / or maintain pose of the distal operative end of the microcatheter and position the microcatheter while following the curvatures of arteries, veins, and blood vessels, while reducing or minimizing deformation and trauma to existing tissue structures.

[0196] These in combination present a novel approach to intravascular procedures by integrating frictionless forward cutting techniques with continuum robotics, which allow for precise guidance and positioning of the catheter while minimizing deformation and collateral damage to existing tissue structures. This innovation addresses critical limitations in existing methods, which often involve high piercing force and unintended dissection, by ensuring the device can naturally follow the curvature of blood vessels.

[0197] With sufficient fluence for a given material, as described above, a suitable rate for delivery of PIRL pulses to reduce opposing forces during advancement of the microcatheter is limited on the upper end by thermal accumulation, and at the lower end by advancement speed. Assuming that each pulse liquifies a few microns of the intravascular accumulation as it is advancing, then a suitable velocity of the distal tip of the optical fiber microcatheter is v = 1 urn x f, where f is the repetition rate of the laser (e.g. v( 250 Hz ) = 0.25 mm / s, v(1khz) = Imm / s . However, the velocity can also be determined experimentally based on measuring the force opposing the movement of the distal tip. The upper limit for the force may be determined by the microcatheter design, for example, a 200um diameter sapphire fiber tip can be broken if pushed into hard tissue with forces above ~400N. Furthermore, the optical fiber microcatheter, depending on its rigidity, will also have a buckling limit which may be below the breaking force limit of the tip. Lower forces will result in less damage to surrounding tissue, and a suitable force would be similar to the limitations of conventional guidewires, ~ 0.15 N @ 0.05 mm / sec. A practical speed range for advancement would be 0.02 mm / sec to 1 mm / sec and a force range of 0.1 N to 0.3N, which would be acceptable with ~0.14N as preferred. The present inventors have shown experimentally that in human plaque (see FIG. 23), an optical fiber based microcatheter delivering PIRL laser pulses can be advanced with forces between ~0.1N and 0.3N at speeds between 0.02 and 0.5 mm / s.

[0198] While many of the present example embodiments involve the delivery of PIRL pulses, via an optical fiber microcatheter, such that the lateral extent, relative to the local longitudinal axis of the distal region of the optical fiber microcatheter, of the disrupted volume resulting from vaporization and pressure-driven expansion, exceeds the outer diameter (e.g. outer jacket diameter) of at least the distal portion of the optical fiber microcatheter, in other example embodiments, the outer diameter (e.g. outer jacket diameter) of at least the distal portion of the optical fiber microcatheter may be equal to, or may slightly exceed, at one or more axial / longitudinal locations along the optical fiber microcatheter, the lateral extent of the disrupted volume, provided that at least one condition is met relating to facilitation of extension of the optical fiber microcatheter in the absence of significant friction (e.g. a friction force exceeding a pre-determined threshold friction), inelastic deformation of the surrounding material forming the intravascular occlusion and / or the vascular tissue surrounding the intravascular occlusion, and / or damage or inflammation of the surrounding vascular tissue that would result in restenosis following the procedure.

[0199] Indeed, in some example implementations, a nearly frictionless condition would allow for a slightly smaller volume of disruption, with the outer walls of the distal region of the microcatheter contacting and sliding relative to the inner surface of the disrupted volume, but with a sufficiently small applied shear force during extension of the optical fibermicrocatheter such that the distal portion of the optical fiber microcatheter can be extended through the intravascular accumulation with minimal compression of the surroundings. For example, the outer diameter of at least the distal portion of the optical fiber microcatheter may exceed, at one or more axial / longitudinal locations along the optical fiber microcatheter, the lateral extent of the disrupted volume by an amount less than 50 microns, less than 100 microns, less than 250 microns, less than 500 microns, between 50 microns and 100 microns, between 100 microns and 200 microns, or between 250 microns and 500 microns.

[0200] In some example implementations, it may be beneficial generate a sufficiently large disrupted volume such that, during extension of the optical fiber microcatheter while performing PIRL-pulse-based ablation of the intravascular occlusion, the resulting deformation of the unablated intravascular occlusion surrounding the optical fiber microcatheter, and / or the resulting deformation the vascular tissue surrounding the intravascular occlusion, remains below the elastic limit of the respective material such that a sufficiently small amount of friction is present that the surrounding material and / or vascular tissue is not substantially damaged. Such a nearly frictionless condition could be determined by observing an absence of microscopic tissue damage, through histology or other means, to the material surrounding the catheter and / or to the surrounding vascular tissue after advancement such that the borders of the catheters channel of travel are similar in damage to a completely frictionless condition as described above.Example Delivery Catheter with Imaging Capability

[0201] As noted above, in some example embodiments, a delivery catheter may be employed to facilitate positioning of the distal region of the microcatheter within the vasculature. In one example implementation, a delivery catheter includes a lumen for insertion and extension of the optical fiber microcatheter and also includes one or more components that provide endoscopic functionality. Such a delivery catheter may provide both imaging and irrigation to facilitate a clear field of view, which can be beneficial during a procedure involving PIRL-based ablation via the optical fiber microcatheter that is extended from and steered relative to the delivery catheter, within a field of view of the delivery catheter, at least during initial ablation. Such a configuration can potentially reduce procedure time and surgical complications. In particular, in some example implementations, images obtained via an endoscopic imaging system integrated with the delivery catheter can enable dynamic adjustments during the procedure, enhancing precision and reducing complications.

[0202] A non-limiting example intravascular ablation catheter system is shown in FIG. 5 and includes a multilumen imaging delivery catheter 500 that enables simultaneous irrigation,aspiration, and visualization via an integrated endoscope (borescope) with an imaging camera 510 (or alternatively an optical fiber bundle interfaced to a remote imaging camera) and illumination optical fiber 520, thereby enabling real-time image-based feedback of the local intravascular surgical field. As shown in the figure, an irrigation channel 560 may be employed to deliver an irrigation fluid (e.g. saline) to clear the field of view of the imaging camera, e.g. under manual, autonomous or semi-automated control of a pump in fluid communication with the irrigation lumen 560 and with a remote fluidic reservoir (not shown).

[0203] In the present example embodiment illustrated in the figure, the optical fiber microcatheter (an optical fiber 110 and an elongate sheath 120) is housed within an outer tube 160 to form a concentric tube steering mechanism that enables steering of the distal portion of the optical fiber microcatheter. It will be understood, however, that alternative steering mechanisms, such as those described above or variations / equivalents thereof, may be employed in the alternative.

[0204] As shown in the figure, the delivery catheter 500 may also include a steering mechanism that is separate and distinct from the steering mechanism of the optical fiber microcatheter, and may be a different type of steering mechanism than the steering mechanism employed to steer the optical fiber microcatheter. The figure illustrates a nonlimiting example implementation in which the steering mechanism is a 2-axis tendon based steering mechanism 540.

[0205] The lower portion of the figure shows a detailed view of the distal region of the delivery microcatheter 500 with the optical fiber microcatheter removed (and the outer tube of the concentric tube steering mechanism removed), showing the delivery lumen 530.

[0206] In one example implementation, a balloon anchoring mechanism 550 is integrated within the delivery catheter and can be remotely actuated for inflation to dynamically control the stiffness of the delivery catheter or to anchor its position. The inflatable balloon 550 provides stability and prevents the delivery catheter 500 from moving during laser ablation procedures, ensuring that the catheter remains in the correct position for precise tissue disruption. This feature is particularly useful when dealing with tortuous arteries, where maintaining catheter stability is crucial to avoid accidental vessel damage.

[0207] In some example implementations, the balloon anchoring mechanism can be designed with segmented chambers that allow selective inflation in different areas of the delivery catheter. This ensures localized stiffness control, allowing the clinician to adjust the flexibility of the catheter as needed during the procedure. In addition to controlling stiffness, the balloon could be embedded with sensors to monitor pressure inside the vessel, providing feedback to avoid excessive inflation, which could lead to vessel rupture.This mechanism also enables the catheter to maintain its position without needing external stabilization, reducing procedure time.

[0208] Incorporating imaging technology into the delivery catheter can be beneficial for achieving or facilitating precise entry positioning of the optical fiber microcatheter within a given intravascular accumulation. By employing real-time visual feedback, the imaging modality helps guide the catheter into the occluded area with accuracy, reducing the likelihood of incorrect placement. This can be very beneficial from a clinical perspective as improper positioning could lead to tissue damage or perforation. The inclusion of miniature cameras, such as a borescope, provides continuous video feedback to the clinician, allowing adjustments in real-time during the procedure.

[0209] In other example implementations, the delivery catheter may be adapted to include one or more additional or alternative imaging modalities, for example, to leverage high-resolution angioscopy or intravascular ultrasound (IVUS) to offer detailed insights into the vascular environment. By pairing this with advanced imaging techniques such as optical coherence tomography (OCT), clinicians could view the occlusion and surrounding tissue in three dimensions, which enhances both the precision of the catheter’s entry and its subsequent navigation through the tortuous anatomy.

[0210] In some example embodiments, one or more images can be employed to control the laser system to modify one or more pulse properties based on imaged lateral size of the disruption volume. For example , the pulse fluence can be increased until the imaged lateral size of the disruption volume is, in a lateral direction, equal, approximately equal, or larger than the outer diameter of at least a distal portion of the optical fiber microcatheter.Example Method of Crossing Chronic Total Occlusion

[0211] As noted above, the example PIRL-based intravascular treatment systems described herein may be employed for a wide variety of clinical intravascular procedures involving the ablation of an intravascular accumulation. One example clinical intravascular procedure is the crossing of a chronic total occlusion (CTO). A non-limiting example method of performing a CTO crossing using the example PIRL-based intravascular treatment systems described herein is presently described.

[0212] In an initial patient preparation step, the patient, presenting with calf pain and suspected arterial occlusions, undergoes imaging studies to locate the occlusion. Retrograde access is achieved via the superficial femoral artery, followed by the introduction of a guidewire to navigate to the occlusion. After extending a delivery catheter over the guidewire, the optical fiber microcatheter is inserted through a lumen of the delivery catheter (e.g. the guidewire lumen, after removal of the guidewire) and positioned at the site of occlusion. The delivery catheter may then be stabilized via the deployment of a balloon anchoringmechanism or some other anchoring mechanism such as deployable nitinol braces before final positioning, or some centering balloon or other mechanical mechanism for final positioning. The optical fiber microcatheter is then advanced to the occlusion and PIRL laser pulses are delivered through the optical fiber to cause local disruption (liquification) of the intravascular occlusion and to facilitate low-friction extension of the optical fiber microcatheter into the intravascular occlusion. The PIRL laser pulses are delivered, guided by real-time feedback, while extending the microcatheter at a controlled rate, such as a rate of 1 mm / s, and employing the integrated steering mechanism to appropriately steer the distal portion of the optical fiber microcatheter through the occlusion via image guidance (e.g. via fluoroscopy). After crossing the occlusion, an outer tube (which may be a component of a steering mechanism, such as an outer tube of a concentric tube steering mechanism) through which the optical fiber was initially extended, is left in place across the occlusion after withdrawal of the optical fiber microcatheter, a guidewire can be extended across the occlusion to facilitate the use of other medical devices during subsequent procedures, such as balloon angioplasty.Position and Force Feedback System

[0213] In some example embodiments, one or more force sensors are integrated into the microcatheter assembly to measure a signal related to the force applied to the distal tip of the optical fiber microcatheter during insertion of the optical fiber microcatheter into a vascular occlusion. There are many different ways in which a force sensor could be implemented for measuring a force applied to or by the microcatheter. Force sensors could be embedded directly into the distal region of the microcatheter using piezoelectric materials that generate a signal in response to applied force, or through thin-film strain gauges that measure strain-induced deformations. Capacitive or resistive sensors, for example, implemented as ultra-thin flexible circuits, could be wrapped around or laminated into the catheter walls. Signals from these distal-mounted force sensors would be externally accessible via electrically conductive paths (e.g. wires) residing on or within the elongate sheath of the microcatheter. Optical fiber-based force sensors, such as Fiber Bragg Gratings (FBG), could measure strain or deformation along the fiber, providing distributed sensing capabilities. Alternatively, the sensors could be positioned more proximally, transmitting mechanical interactions from the distal tip via a mechanical linkage or stress-transmitting material. For example, a force sensor could be mounted at the proximal end of the optical fiber microcatheter between the translating mechanics and a rigid fixture that holds the tubing of the microcatheter (the elongate sheath housing the optical fiber), where the tubing is rigid enough in compression that small forces at the tip are transmitted to the force. This sensor would also measure any internal frictions fromother concentric channels in which the tubing moves, but this can be subtracted to determine the distal tip forces alone. External force sensing could also be achieved through the incorporation of an external housing or guide that measures mechanical loads or strains during the insertion process. By exploring various modalities (e.g., capacitive, resistive, optical, piezoelectric) and locations (distal, proximal, external), a wide range of designs could be developed to balance precision with the physical constraints of a microcatheter assembly.

[0214] In one example implementation, a position and force feedback system could employ piezoelectric sensors or fiber optic sensors along at least a portion of the length of the optical fiber microcatheter to measure real-time strain and / or displacement. This data could be processed by the control and processing system (e.g. using a machine learning algorithm) to predict and prevent tissue dissection. Although various example algorithms could be employed to process the signals from such a sensor configuration, an example implementation would involve defining a force limit beyond which the system will prevent additional force from being applied. This would limit the device to operate under forces which are sufficient for laser mediated advancement, but would prevent dissection or damage to the device proximal tip. Another example implementation would be to control the speed of advancement of the microcatheter based on the sensed opposing force, such that under high force conditions, motion would be slowed down to reduce or minimize the forces, e.g. according to a maximum permitted advancement speed determined as inversely proportional to sensed force. Alternatively, a suitable laser power (or repetition rate) can be determined based on readings from the force sensor at a given speed where the power / repetition rate of the laser is increased to reduce the piercing force, or decreased if the force is already below a desired setpoint.

[0215] The force sensor can be connected (wired or wirelessly) to the control and processing system, such that the force signal can be received by and processed by the control and processing system to actively monitor the applied force. By providing real-time data, the system can alert the operator if excessive force is being exerted, which could lead to dissection or perforation of the surrounding vascular tissue, and potentially avoiding unintended damage during the procedure and enhancing the safety of the intervention. In some example implementations, the force signal is employed by the control and processing system as a feedback signal to autonomously control or limit the position of the optical fiber microcatheter, and / or a rate of axial / longitudinal translation of the optical fiber microcatheter into or within an intravascular accumulation. Additionally, haptic feedback could be provided to the clinician via the control interface, offering tactile resistance when excessive forces are detected.

[0216] For example, if the control and processing system is in electrical communication (wired or wireless) with a longitudinal translation mechanism (e.g. a motor coupled to a rack and pinion translation mechanism, lead screw / nut translation mechanism, or belt / pulley translation mechanism) that is mechanically coupled to the optical fiber microcatheter to control longitudinal translation of the optical fiber microcatheter, the control and processing system can control the longitudinal translation mechanism to arrest or reduce a rate of change of longitudinal translation of the optical fiber microcatheter based on the detected force signal. The system could also automatically retract the catheter if critical force thresholds are exceeded, thereby preventing accidental tissue damage. In some example implementations, a critical force threshold could be determined to be above the buckling or damage force of the microcatheter tip, for example, 0.1 -0.5 N for a sapphire fiber microcatheter.

[0217] The control and processing system may also or alternatively be connected (wired or wirelessly) to a position sensorthat provides a signal indicative of the position (e.g. relative position) and / or rate of change of longitudinal (axial) position of the optical fiber microcatheter. For example, when the measured longitudinal translation rate exceeds a pre-determined threshold known to result in the application of an excessive force, a warning can be communicated to a user.

[0218] In yet another example implementation, the control and processing system may be employed to control a rate of delivery of PIRL pulses and / or a pulse fluence based on a detected force signal and / or a detected rate of change of longitudinal position of the optical fiber microcatheter in order to ensure that the longitudinal advancement of the optical fiber microcatheter proceeds with a sufficiently low force and / or amount of collateral damage to the surrounding vascular tissue.

[0219] In yet another example embodiment, the control and processing system is employed to control the laser system to modify one or more pulse properties based on a detected force signal, where the modification is, for example, according to pre-determined criteria. For example, the pulse fluence can be increased until the force signal is reduced below a predetermined force threshold. In one example implementation, the pre-determined force threshold is determined based on reference experimental studies involving one or more types of intravascular accumulation types or compositions. For example the predetermined force threshold can corresponding to a force signal that was obtained when the disrupted volume, due to expansion of the laser-irradiated volume, was equal or approximately equal, or greater, in a lateral direction, to an outer diameter of sat least a distal portion of the optical fiber microcatheter.

[0220] In one example implementation, an optical fiber microcatheter system for controlled delivery of PIRL pulses for performing ablation of an intravascular accumulation mayinclude several of the components and features described above, for example, a delivery catheter having an integrated imaging modality for precise entry positioning of the optical fiber microcatheter, balloon anchoring for dynamic stiffness control, and real-time position and force feedback to prevent dissection. These features collectively reduce the risk of perforation and complications.Intraprocedural Optical Spectroscopy

[0221] In some example embodiments, the optical fiber employed for the delivery of PIRL pulses through the optical fiber microcatheter may be coupled to an external optical detection system that is configured to deliver, through the optical fiber, interrogating optical energy to the disrupted and liquified intravascular accumulation, and to collect optical energy that is responsively emitted by the disrupted and liquified intravascular accumulation. Nonlimiting example modalities for performing in-situ microbiopsy include spectroscopic methods such as Raman spectroscopy, fluorescence spectroscopy and frequency comb and laser induced breakdown spectroscopy. For example, Raman spectroscopy can be performed by employing the optical fiber used for PIRL disruption to also deliver excitation energy and collect backscattered Raman signals, which can be analyzed for biomarkers of disease or normal tissue. The very high excitation and thermal heating of tissue may also lead to light emission that provides a spectral signature or fingerprint of particular constituents of the tissue. Such an approach may be employed, for example, to determine whether or not the distal tip of the optical fiber resides within the intravascular accumulation region of interest, and such analysis may be performed, for example, before, during or after the delivery of PIRL pulses to perform ablation of the intravascular accumulation.

[0222] In one example embodiment, an optical fiber microcatheter system may integrate reflection spectrometry or a suite of other optical tissue differentiation technologies. These technologies enable real-time analysis of the reflected light from the tissue in front of the catheter's main fiber, allowing the system to detect whether it is facing a vessel wall, plaque, or open lumen. By analyzing variations in the optical properties, such as absorption, scattering, and reflectance, the catheter can be either manually or automatically adjusted, repositioning or have its treatment parameters modified, ensuring safe and precise interventions. FIG. 7 shows different absorption spectra of different example types of tissues. In some example implementations, the modification of treatment parameters can include modifying one or more pulse properties, based on a detected or inferred composition of an intravascular accumulations such that the laser pulses properties are sufficient to generate the disrupted volume, due to expansion of the laser- irradiated volume, that is larger, in a lateral direction, than an outer diameter at least adistal portion of the optical fiber microcatheter. For example, reference data can be predetermined that correlates suitable pulse properties (e.g. pulse fluence and / or pulse duration) with different compositions of an intravascular accumulation. In some example implementations, such reference data can be interpolated or otherwise processed to obtain an estimate of suitable pulse properties for a detected composition that does not match a reference composition.

[0223] The reflection spectrometry-guided catheter uses optical sensors positioned which share the main laser fiber or are included in a fiber bundle and which capture reflected light from the tissue surface into the distal catheter tip, shown schematically in FIG. 8. By comparing the spectral signatures of the reflection from different tissues, as shown, for example, in FIG. 9, the system can distinguish between tissue types in real-time according to the ratio between specific spectral peaks, as shown, for example, in FIG. 10. This allows for automated adjustments to laser power and position, reducing the risk of accidentally ablating healthy vessel walls or perforating delicate vascular structures.Additionally, the system could integrate other optical differentiation methods such as OCT, near-infrared spectroscopy (NIRS), breakdown spectroscopy or diffuse reflectance imaging, providing a comprehensive tissue analysis. The array of optical technologies can also alert the operator if the catheter tip is positioned too close to the vessel wall, prompting repositioning to prevent unintentional damage. This precise guidance ensures that ablation is directed only at pathological tissues, minimizing collateral damage and improving procedural outcomes. This embodiment enhances safety and control during complex vascular procedures, particularly in areas where precise navigation is critical to avoid perforation or unnecessary vessel trauma.

[0224] As noted above, in some example embodiments, a Raman-guided microcatheter system may be employed to allow for molecular fingerprinting of tissues by detecting vibrational modes specific to different tissue types. A non-limiting example of this embodiment is shown schematically in FIG. 11 and includes a 785nm Raman ‘pump’ source which is coupled optically into the optical fiber microcatheter fiber using dichroic mirrors or fiber multiplexers, and a spectrometer which is configured to receive back reflections from near the distal end of the catheter fiber. An example implementation of such an optical system is shown photographically in FIG. 12. This example system can produce Raman spectra which are easily classified in terms of constituent tissues, as shown in FIG. 13 which shows the different observed spectra for skin, muscle and fat. This technology is particularly beneficial when treating mixed plaques composed of lipids, calcium, and fibrous tissues, which require different approaches for effective removal. The catheter could share a single fiber optic for the Raman signal, or it could utilize a miniature fiberoptic Raman probe, relaying spectral data to a connected system for analysis. Based onthe molecular composition, the catheter can dynamically adjust treatment parameters, such as laser intensity or ablation depth, optimizing the procedure and minimizing collateral damage to healthy tissue. This precise guidance also reduces the risk of complications such as restenosis, which often occurs when damage to the vessel wall triggers new plaque formation.Ultrasound Cracking Catheter

[0225] In this embodiment, the catheter system integrates an ultrasound-generating laser or uses altered laser parameters to produce acoustic shockwaves. These shockwaves are directed at calcified plaques, cracking and disrupting them for easier removal or ablation. This method provides a non-invasive way to mechanically break apart hardened plaques without excessive force on the surrounding tissue, offering a safer alternative to traditional mechanical or purely laser-based atherectomy techniques.

[0226] The ultrasound cracking catheter operates by generating high-energy, short-duration laser pulses that produce localized acoustic shockwaves. These waves propagate through the catheter's tip and interact with calcified plaques, fracturing the rigid material. By targeting only the plaque, the surrounding soft tissues are preserved, reducing the risk of vessel injury. This technique is particularly advantageous in heavily calcified occlusions, where traditional ablation methods may be insufficient or pose a higher risk of vessel perforation. The ultrasound mechanism could be coupled with real-time feedback, allowing the system to adjust laser parameters based on plaque density or size. This embodiment effectively combines the precision of laser-based systems with the mechanical disruption of acoustic shockwaves, optimizing plaque removal for complex or hardened lesions.

[0227] To further enhance this example embodiment, the laser system could be designed to operate with specific parameters that optimize both the cutting and acoustic shockwave generation processes. For example, the catheter could utilize pulsed infrared laser (PIRL) technology at a wavelength of 2.9 pm for precise cutting of tissue, taking advantage of the high absorption in water-rich tissues. Once the plaque has been cut and partially ablated, a secondary mechanism could activate a longer-pulsed laser — either at the same 2.9 pm wavelength or at an alternate wavelength like 1920 nm.The longer-pulsed laser would operate beyond the acoustic confinement limit, producing localized acoustic shockwaves specifically designed to interact with the calcified portions of the plaque. These shockwaves, generated by pulses lasting several nanoseconds or microseconds, would efficiently fracture the calcified material, allowing for easier plaque removal. By tailoring the pulse duration to exceed the thermal and stress confinement limits, the system ensures that the shockwaves propagate without causing significant thermal damage to the surrounding tissue. The combination of short-pulse PIRL cuttingfollowed by longer-pulse acoustic disruption allows for a dual-mode intervention, providing both precision and mechanical effectiveness. The use of two complementary laser wavelengths or pulse regimes further ensures flexibility in treating plaques of varying composition and density, while keeping the procedure minimally invasive and reducing the risk of vessel perforation.Multipath Crossings

[0228] While many of the example embodiments disclosed herein relate to the steering of an optical fiber microcatheter into, and in some cases, through an intravascular occlusion for PIRL laser pulse based ablation, the advantages of such a method can be further leveraged for optional additional debulking of lesions and / or perforation of the occlusion along multiple parallel paths to reduce the density of the occlusion and enable less mechanical stress inducement during subsequent balloon angioplasty.Example Embodiment Without Delivery Catheter

[0229] Some example embodiments of the present disclosure employ a delivery catheter to facilitate insertion and guidance of the optical fiber microcatheter into the body. In other example embodiments, the optical fiber microcatheter may be positioned within the vasculature in the absence of a delivery catheter, to access and provide local therapy to an intravascular accumulation, with atraumatic fiber delivery, and accurate microcatheter steering, facilitated by the emission of PIRL pulses and the resulting disruption and liquification of tissue residing beyond the distal tip of the optical fiber.Example Clinical Applications

[0230] The example embodiments described above can be employed for a wide variety of clinical applications. Various example embodiments described herein provide surgical systems, devices and methods that can be employed to perform crossing and / or debulking of arterial occlusions with improved precision, and can facilitate re-cannulization of an artery without causing substantial damage to remaining tissue including the arterial walls, potentially reducing risk of restenosis. By limiting collateral damage, the risk of restenosis is significantly reduced, potentially offering a superior outcome compared to existing surgical techniques.

[0231] In particular, the delivery of ablative PIRL pulses results in a reduced piercing force when entering a vascular lesion, and when PIRL pulses are delivered such that the disruption volume extends laterally beyond the outer lateral extent of the optical fiber microcatheter, the resulting optical fiber microcatheter provides a near-frictionless cutting mechanism, requiring less force to navigate occluded vessels, thereby reducing tissue trauma.Moreover, the integration of a steering mechanism (e.g. a continuous steering mechanismsuch as those described above) facilitates fine control of the position and orientation (pose) of the distal region of the optical fiber microcatheter, enabling controlled and safe navigation through complex vascular structures, especially when performed in conjunction with a positioning / orientation guidance system.

[0232] It will be understood that the applications of the embodiment disclosed herein can extend beyond peripheral artery disease and apply to other vascular conditions such as chronic total occlusions in the cardiovascular system, stroke and blood clots and other veinous occlusions. Indeed, the aforementioned example therapeutic applications involving the crossing of a chronic total occlusion in are but one example implementation and are not intended to limit the scope of the present disclosure. It will be understood that the example embodiments may be employed for a wide variety of other applications, including, for example, the present example embodiments can be utilized in atherectomy, which includes bulk removal of intravascular tissue, and also for treatment of restenosis, where the re-narrowing of a vessel following stent placement or angioplasty requires precise and effective intervention. Similarly, the present example embodiments are well- suited for managing thrombi or emboli that obstruct blood vessels, necessitating removal or dissolution to restore perfusion to vital tissues. Thrombectomy and thrombolysis procedures, whether performed in the coronary arteries, peripheral vasculature, or cerebral arteries, are critical applications of these technologies.

[0233] Furthermore, the present embodiments can be adapted to address different anatomical regions, each with unique clinical challenges. In the cardiac vasculature, for instance, the present example embodiments can be employed for addressing coronary artery disease, ensuring precise navigation and treatment of occlusions, plaques, or calcified lesions. Peripheral vascular applications would include treating conditions like peripheral artery disease (PAD), critical limb ischemia, or arterial blockages in the lower extremities.Similarly, in the cranial and neurovasculature, the present example embodiments can aid in managing ischemic strokes caused by large vessel occlusions, providing tools for clot retrieval or vascular recanalization in a time-sensitive manner.

[0234] For example, in cranial / neuro clinical applications, in order to successfully navigate from the femoral artery to the hippocampal arteries, the microcatheter configured for PIRL laser pulse delivery may include the following properties: (a) minimum bend radius: the catheter should accommodate bends with radii as small as 5 mm; (b) catheter tip size: a microcatheter with an outer diameter of approximately 0.5 mm (1.5 Fr) is suitable to traverse the smallest cerebral vessels leading to the hippocampus; (c) flexibility: at least the distal portion of the microcatheter should have sufficient flexibility to allow advancing of the fiber without buckling while also enabling steering capability. Likely different lengths of the catheter may require different flexibilities, for example, the portion near the distal tipcould be more flexible to allow improved steering via tendons or other methods discussed here. This configuration can be beneficial in that the catheter can safely and effectively reach the target area for delivering the picosecond mid-infrared laser, facilitating minimally invasive access to various regions in the cranial vasculature, or more broadly, the neurovasculature.

[0235] A suitable microcatheter diameter and tip size may be determined by the diameter of the smallest vessels it must navigate. For example, the following examples provide suitable microcatheter diameters for navigation with various vessels: (a) Femoral Artery: Diameter of about 6-8 mm, accommodating larger guide catheters (up to 6-8 French); (b) Internal Carotid Artery: Diameter decreases to about 4-5 mm; (c) Middle Cerebral Artery (MCA): Further narrows to 2-3 mm; (d) Hippocampal Arteries: These are small perforating arteries with diameters ranging from 0.5 to 1 mm. For example, to reach the hippocampal arteries, a microcatheter with an outer diameter (OD) of 1.2-1.7 French (Fr) may be employed. Complementary guidewires / microwires with diameters of 0.25-0.36 mm can be used to navigate these small vessels.

[0236] Additional applications include addressing congenital vascular anomalies, repairing vascular dissections or aneurysms, and facilitating the placement of stent grafts or flowdiverting devices, for example Urethral stricture. These tools can also support the delivery of localized drug therapy, such as anti-proliferative agents to combat in-stent restenosis or chemotherapeutic agents for targeted oncological treatment. Ultimately, the example embodiments outlined here represent a versatile foundation for addressing a myriad of vascular pathologies and enhancing clinical outcomes in procedures across diverse anatomical and pathological contexts.Enumerated Embodiments

[0237] Embodiment 1. A system for performing ablative removal of an intravascular accumulation, the system comprising:an optical fiber microcatheter comprising:an elongate sheath; andan optical fiber extending through the elongate sheath;a laser system in optical communication with a proximal end of the optical fiber for coupling laser pulses into the optical fiber, the laser system and the optical fiber being configured such that the laser pulses are delivered by a distal end of the optical fiber with laser pulse properties comprising:a wavelength selected such that absorption of the laser pulses by a laser- irradiated volume of the intravascular accumulation, when the intravascular accumulationis positioned adjacent to a distal end of the optical fiber, is predominantly due to excitation of vibrational modes of one or more constituents of the intravascular accumulation;a pulse duration that is shorter than a first time duration required for thermal diffusion out of the laser-irradiated volume and shorter than a second time duration required for a thermally driven expansion of the laser-irradiated volume;a pulse fluence and the pulse duration resulting in a peak pulse intensity below a threshold for ionization-driven tissue disruption to occur within the laser-irradiated volume;the pulse fluence being sufficiently high to cause local ablative disruption and liquification of the laser-irradiated volume of the intravascular accumulation;wherein the laser system and the optical fiber are configured such that the pulse fluence is sufficiently high to generate a disrupted volume, due to expansion of the laser- irradiated volume, that is larger, in a lateral direction, than an outer diameter at least a distal portion of the optical fiber microcatheter, thereby facilitating extension of the optical fiber microcatheter through the intravascular accumulation during delivery of the laser pulses.

[0238] Embodiment 2. The system according to embodiment 1 further comprising a steering mechanism operatively coupled to the elongate sheath, the steering mechanism being externally controllable for steering a distal portion of the elongate sheath.

[0239] Embodiment 3. The system according to embodiment 2 wherein the steering mechanism comprises pull cables extending through the elongate sheath to the distal portion of the elongate sheath.

[0240] Embodiment 4. The system according to embodiment 2 further comprising an outer tube housing at least a portion of the optical fiber microcatheter, wherein the distal portion of the optical fiber microcatheter is extendable beyond a distal end of the outer tube for steering the distal portion of the optical fiber microcatheter.

[0241] Embodiment 5. The system according to embodiment 4 wherein the laser system and the optical fiber are configured such that the disrupted volume, due to expansion of the laser- irradiated volume, is larger, in the lateral direction, than an outer diameter of the outer tube, thereby facilitating extension of the outer tube through the intravascular accumulation during or after delivery of the laser pulses.

[0242] Embodiment 6. The system according to embodiment 4 wherein the steering mechanism is a concentric tube-based steering mechanism comprising the outer tube, and wherein at least a distal portion of the elongate sheath is formed from a memory metal having a predefined curved shape, such that the distal portion of the optical fiber microcatheter is steerable by varying extension of the elongate sheath relative to a distal end of the outer tube.

[0243] Embodiment 7. The system according to embodiment 6 wherein the pre-defined curved shape is defined such that the elongate sheath is laterally extendable by 7 cm when the elongate sheath is longitudinally extended from the distal end of the outer tube.

[0244] Embodiment 8. The system according to any one of embodiments 4 to 7 wherein an outer diameter of the outer tube is between 500 and 1000 microns.

[0245] Embodiment 9. The system according to any one of embodiments 2 to 8 wherein an outer diameter of the elongate sheath is between 300 and 1000 microns.

[0246] Embodiment 10. The system according to any one of embodiments 2 to 8 wherein an outer diameter of the elongate sheath is between 300 and 600 microns.

[0247] Embodiment 11. The system according to any one of embodiments 1 to 10 further comprising a force sensor configured to measure an opposing force applied to the distal portion of the optical fiber microcatheter during longitudinal translation of the optical fiber microcatheter.

[0248] Embodiment 12. The system according to embodiment 11 further comprising control circuitry operatively coupled to the force sensor, wherein the control circuitry is configured to employ a force signal obtained from the force sensor to provide feedback for controlling advancement of the optical fiber microcatheter.

[0249] Embodiment 13. The system according to embodiment 12 wherein the control circuitry is configured to display, on a user interface, qualitative or quantitative feedback indicative of the force signal.

[0250] Embodiment 14. The system according to embodiment 12 wherein the control circuitry is configured to provide haptic feedback to a user based on the force signal.

[0251] Embodiment 15. The system according to embodiment 14 wherein the control circuitry is configured to provide haptic feedback to the user when the opposing force exceeds a force threshold.

[0252] Embodiment 16. The system according to embodiment 12 wherein the control circuitry is configured such that the force signal is employed to control an average power or a repetition rate of the laser pulses.

[0253] Embodiment 17. The system according to embodiment 12 further comprising a motorized translation mechanism operably coupled to the control circuitry, the motorized translation mechanism being capable of actuating longitudinal translation of the optical fiber microcatheter, the control circuitry being configured to control the motorized translation mechanism according to feedback provided by the force signal, such that longitudinal translation of the optical fiber microcatheter is dependent on the opposing force.

[0254] Embodiment 18. The system according to embodiment 17 wherein the control circuitry is configured to control the motorized translation mechanism such that longitudinaltranslation of the optical fiber microcatheter is prevented when the opposing force exceeds a force threshold.

[0255] Embodiment 19. The system according to embodiment 17 wherein the control circuitry is configured to control the motorized translation mechanism such that the optical fiber microcatheter is retracted when the opposing force exceeds a force threshold.

[0256] Embodiment 20. The system according to embodiment 17 wherein the control circuitry is configured to control the laser system to modify or more properties of the laser pulses based on the force signal.

[0257] Embodiment 21. The system according to embodiment 20 wherein the control circuitry is configured to control the laser system to modify or more properties of the laser pulses such that the force signal satisfies pre-determined criteria.

[0258] Embodiment 22. The system according to embodiment 17 wherein the control circuitry is configured to control the motorized translation mechanism such that a speed of longitudinal translation of the optical fiber microcatheter is sufficient to limit thermal accumulation.

[0259] Embodiment 23. The system according to any one of embodiments 1 to 22 further comprising an optical detection system configured to deliver interrogating optical energy to the disrupted and liquified intravascular accumulation, and to collect emitted optical energy that is responsively emitted by the disrupted and liquified intravascular accumulation.

[0260] Embodiment 24. The system according to embodiment 23 further wherein the optical detection system comprises an additional optical fiber or optical fiber bundle configured to collect the emitted optical energy.

[0261] Embodiment 25. The system according to embodiment 23 wherein the optical detection system is operable coupled to the optical fiber and configured to employ the optical fiber for collection of the emitted optical energy.

[0262] Embodiment 26. The system according to any one of embodiments 23 to 25 wherein the system is further configured to analyze the emitted optical energy to perform tissue analysis.

[0263] Embodiment 27. The system according to embodiment 26 wherein the system is configured such that the tissue analysis is performed in real-time.

[0264] Embodiment 28. The system according to embodiment 26 or 27 wherein the system is configured to employ the tissue analysis to adjust at least one treatment parameter.

[0265] Embodiment 29. The system according to embodiment 26 or 27 wherein the system is configured to employ the tissue analysis to adjust one or more of the laser pulse properties, based on a detected or inferred composition of the intravascular accumulation, such that the laser pulse properties are sufficient to generate the disrupted volume, due toexpansion of the laser-irradiated volume, that is larger, in the lateral direction, than the outer diameter at least the distal portion of the optical fiber microcatheter.

[0266] Embodiment 30. The system according to embodiment 26 or 27 wherein the system is configured to employ the tissue analysis to generate an alert indicating that a distal end of the optical fiber microcatheter is positioned too close to a vessel wall.

[0267] Embodiment 31. The system according to embodiment 26 or 27 wherein the system is configured to employ the tissue analysis to determine whether the optical fiber microcatheter is facing a vessel wall, plaque, or an open lumen.

[0268] Embodiment 32. The system according to embodiment 26 or 27 wherein the system is configured to employ the tissue analysis to control the laser system such that ablation is only directed at pathological tissues.

[0269] Embodiment 33. The system according to any one of embodiments 23 to 32 wherein the optical detection system is an optical spectroscopy detection system.

[0270] Embodiment 34. The system according to any one of embodiments 23 to 33 wherein the optical detection system is configured to employ a detection modality selected from the group consisting of reflection spectroscopy, fluorescence spectroscopy, optical coherence tomography, near-infrared spectroscopy (NIRS), breakdown spectroscopy, Raman spectroscopy and diffuse reflectance imaging Raman spectroscopy.

[0271] Embodiment 35. The system according to any one of embodiments 1 to 34 wherein the optical fiber is operably coupled to the laser system through a fiber optic rotary to facilitate rotation of the elongate sheath.

[0272] Embodiment 36. The system according to any one of embodiments 1 to 35 wherein the laser pulses have a pulse energy between 0.3-3 mJ, a pulse duration between 0.5-5 ns, a wavelength between 2750 - 3100 nm, and a repetition rate between 0.1-5 kHz.

[0273] Embodiment 37. The system according to any one of embodiments 1 to 35 wherein the laser pulses have a pulse energy between 1mJ - 10mJ, a pulse duration between 10-50 ns, a wavelength between 1890- 1950 nm, and a repetition rate between 0.1-3 kHz.

[0274] Embodiment 38. The system according to any one of embodiments 2 to 37 further comprising a delivery catheter, wherein the elongate sheath is extendable through a lumen of the delivery catheter.

[0275] Embodiment 39. The system according to any one of embodiments 4 to 7 further comprising a delivery catheter, wherein the outer tube and the optical fiber microcatheter are extendable through a lumen of the delivery catheter.

[0276] Embodiment 40. The system according to embodiment 38 or 39 wherein the delivery catheter comprises an anchoring means for anchoring the delivery catheter within a vessel while permitting extension of the elongate sheath beyond a distal end of the delivery catheter.

[0277] Embodiment 41. The system according to any one of embodiments 38 to 40 wherein the delivery catheter further comprises an endoscopic imaging subsystem comprising an optical camera capable of acquiring images of a distal region residing beyond a distal end of the delivery catheter, and an illumination source capable of illuminating the distal region.

[0278] Embodiment 42. The system according to any one of embodiments 38 to 41 wherein the delivery catheter further comprises an irrigation lumen connectable to an external irrigation source.

[0279] Embodiment 43. A method for providing intravascular laser therapy to an intravascular accumulation, the method comprising:providing the system of embodiment 1;positioning the optical fiber microcatheter such that the distal end of the optical fiber resides adjacent to the intravascular accumulation; anddelivering the laser pulses as the optical fiber microcatheter is longitudinally translated into the intravascular accumulation.

[0280] Embodiment 44. The method according to embodiment 43 wherein the laser pulses are delivered, as the optical fiber microcatheter is longitudinally translated within the intravascular accumulation, such that a channel is formed within the intravascular accumulation, the channel having a sufficient cross-sectional area to permit longitudinal advancement of the optical fiber microcatheter through the intravascular accumulation.

[0281] Embodiment 45. The method according to embodiment 43 or 44 wherein the laser pulses are delivered, as the optical fiber microcatheter is longitudinally translated within the intravascular accumulation, such that the disrupted volume has a sufficiently large size to permit steering of the distal portion of the optical fiber microcatheter.

[0282] Embodiment 46. The method according to any one of embodiments 43 to 45 wherein the intravascular accumulation is an intravascular occlusion, and wherein the optical fiber microcatheter is employed to cross the intravascular occlusion while delivering the laser pulses.

[0283] Embodiment 47. The method according to embodiment 46 wherein an outer tube, housing at least a portion of the optical fiber microcatheter, is extended with the optical fiber microcatheter during crossing of the intravascular occlusion.

[0284] Embodiment 48. The method according to embodiment 47 wherein at least a distal portion of the elongate sheath is formed from a memory metal having a pre-defined curved shape, such that the distal portion of the optical fiber microcatheter is steerable by varying extension of the elongate sheath relative to a distal end of the outer tube.

[0285] Embodiment 49. The method according to embodiment 47 further comprising, after crossing the intravascular occlusion:withdrawing the optical fiber microcatheter from the outer tube while maintaining the outer tube across the intravascular occlusion;extending a guidewire through the outer tube, such that the guidewire crosses the intravascular occlusion;withdrawing the outer tube; andemploying the guidewire to facilitate the positioning of a medical device for treatment of the intravascular occlusion.

[0286] Embodiment 50. The method according to embodiment 46 further comprising employing the optical fiber microcatheter to cross the intravascular occlusion one or more additional times while delivering the laser pulses, each crossing occurring along a separate path through the intravascular occlusion.

[0287] Embodiment 51. The method according to embodiment 50 further comprising, after having reduced the density of the intravascular occlusion via multiple crossings, performing balloon angioplasty.

[0288] Embodiment 52. The method according to embodiment 43 wherein the system further comprises a steering mechanism operatively coupled to the elongate sheath, the steering mechanism being externally controllable for steering a distal portion of the elongate sheath.

[0289] Embodiment 53. The method according to embodiment 52 wherein the steering mechanism includes pull cables extending through the elongate sheath to the distal portion of the elongate sheath.

[0290] Embodiment 54. The method according to embodiment 47 wherein an outer diameter of the outer tube is between 500 and 1000 microns.

[0291] Embodiment 55. The method according to any one of embodiments 43 to 53 wherein an outer diameter of the elongate sheath is between 300 and 1000 microns.

[0292] Embodiment 56. The method according to any one of embodiments 43 to 53 wherein an outer diameter of the elongate sheath is between 300 and 600 microns.

[0293] Embodiment 57. The method according to any one of embodiments 43 to 56 further comprising employing a force sensor to measure an opposing force applied to the distal portion of the optical fiber microcatheter during longitudinal translation of the optical fiber microcatheter within the intravascular accumulation.

[0294] Embodiment 58. The method according to embodiment 57 further comprising employing feedback generated from the force sensor to control longitudinal translation of the optical fiber microcatheter.

[0295] Embodiment 59. The method according to embodiment 57 further comprising employing a force signal obtained from the force sensor to control an average power or a repetition rate of the laser pulses.

[0296] Embodiment 60. The method according to embodiment 57 wherein longitudinal translation of the optical fiber microcatheter is prevented when the opposing force exceeds a force threshold.

[0297] Embodiment 61. The method according to embodiment 57 wherein one or both of a detected force signal and / or a detected rate of change of longitudinal position of the optical fiber microcatheter is employed to control one or both of a rate of delivery of laser pulses and the pulse fluence in order to ensure that longitudinal advancement of the optical fiber microcatheter proceeds with a sufficiently low force and / or a sufficiently low amount of collateral damage to surrounding vascular tissue.

[0298] Embodiment 62. The method according to any one of embodiments 43 to 61 wherein an optical detection system is employed to deliver interrogating optical energy to the disrupted and liquified intravascular accumulation and to collect emitted optical energy that is responsively emitted by the disrupted and liquified intravascular accumulation.

[0299] Embodiment 63. The method according to embodiment 62 further wherein the optical detection system comprises an additional optical fiber or optical fiber bundle configured to collect the emitted optical energy.

[0300] Embodiment 64. The method according to embodiment 62 wherein the optical detection system is operable coupled to the optical fiber and configured to employ the optical fiber for collection of the emitted optical energy.

[0301] Embodiment 65. The method according to any one of embodiments 62 to 64 further comprising analyze the emitted optical energy to perform tissue analysis.

[0302] Embodiment 66. The method according to embodiment 65 wherein the tissue analysis is performed in real-time.

[0303] Embodiment 67. The method according to embodiment 65 or 66 further comprising employing the tissue analysis to adjust at least one treatment parameter.

[0304] Embodiment 68. The method according to embodiment 67 wherein the tissue analysis is employed to adjust one or more of the laser pulse properties, based on a detected or inferred composition of the intravascular accumulation, such that the laser pulse properties are sufficient to generate the disrupted volume, due to expansion of the laser- irradiated volume, that is larger, in the lateral direction, than the outer diameter at least the distal portion of the optical fiber microcatheter.

[0305] Embodiment 69. The method according to embodiment 65 or 66 further comprising employing the tissue analysis to generate an alert indicating that a distal end of the optical fiber microcatheter is positioned too close to a vessel wall.

[0306] Embodiment 70. The method according to embodiment 65 or 66 further comprising employing the tissue analysis to determine whether the optical fiber microcatheter is facing a vessel wall, plaque, or an open lumen.

[0307] Embodiment 71. The method according to embodiment 65 or 66 further comprising employing the tissue analysis to control the laser system such that ablation is only directed at pathological tissues.

[0308] Embodiment 72. The method according to any one of embodiments 62 to 71 wherein the optical detection system is an optical spectroscopy detection system.

[0309] Embodiment 73. The method according to any one of embodiments 62 to 72 wherein the optical detection system is configured to employ a detection modality selected from the group consisting of reflection spectroscopy, fluorescence spectroscopy, optical coherence tomography, near-infrared spectroscopy (NIRS), breakdown spectroscopy, Raman spectroscopy and diffuse reflectance imaging Raman spectroscopy.

[0310] Embodiment 74. The method according to any one of embodiments 43 to 73 wherein the laser pulses have a pulse energy between 0.3-3 mJ, a pulse duration between 0.5-5 ns, a wavelength between 2750 - 3100 nm, and a repetition rate between 0.1-5 kHz.

[0311] Embodiment 75. The method according to any one of embodiments 43 to 73 wherein the laser pulses have a pulse energy between 1mJ - 10mJ, a pulse duration between 10-50 ns, a wavelength between 1890- 1950 nm, and a repetition rate between 0.1-3 kHz.

[0312] Embodiment 76. The method according to any one of embodiments 43 to 75 further wherein a delivery catheter is employed to facilitate positioning of the optical fiber microcatheter proximal to the intravascular accumulation, wherein the elongate sheath is extendable through a lumen of the delivery catheter.

[0313] Embodiment 77. The method according to embodiment 76 wherein the delivery catheter is anchored, via an anchoring mechanism, such that the elongate sheath is extendable beyond a distal end of the delivery catheter.

[0314] Embodiment 78. The method according to embodiment 76 or 77 wherein an endoscopic imaging subsystem of the delivery catheter is employed to facilitate steering of the distal portion of the optical fiber microcatheter prior to entry of the optical fiber microcatheter into the intravascular accumulation.

[0315] Embodiment 79. The method according to any one of embodiments 43 to 77 further comprising controlling one or both of a speed of longitudinal extension of the optical fiber microcatheter to a rate of delivery of the laser pulses to limit thermal accumulation.

[0316] Embodiment 80. The method according to any one of embodiments 43 to 77 wherein the laser pulse properties are selected such that laser pulse absorption leads to expansion of a gas-filled cavity and subsequent collapse into liquification of the disrupted volume that extends out beyond the laser-irradiated volume.

[0317] Embodiment 81. The method according to any one of embodiments 43 to 77 wherein the optical fiber microcatheter is longitudinally advanced, through the intravascularaccumulation, while delivering the laser pulses, with forces between 0.100N and 0.300N at speeds between 0.02 and 0.5 mm / s.

[0318] Embodiment 82. A system for performing ablative removal of an intravascular accumulation, the system comprising:an optical fiber microcatheter comprising:an elongate sheath; andan optical fiber extending through the elongate sheath;a steering mechanism operatively coupled to the elongate sheath, the steering mechanism being externally controllable for steering a distal portion of the elongate sheath; anda laser system in optical communication with a proximal end of the optical fiber for coupling laser pulses into the optical fiber, the laser system and the optical fiber being configured such that the laser pulses are delivered by a distal end of the optical fiber with properties comprising:a wavelength selected such that absorption of the laser pulses by a laser- irradiated volume of the intravascular accumulation, when the intravascular accumulation is positioned adjacent to a distal end of the optical fiber, is predominantly due to excitation of vibrational modes of one or more constituents of the intravascular accumulation;a pulse duration that is shorter than a first time duration required for thermal diffusion out of the laser-irradiated volume and shorter than a second time duration required for a thermally driven expansion of the laser-irradiated volume;a pulse fluence and the pulse duration resulting in a peak pulse intensity below a threshold for ionization-driven tissue disruption to occur within the laser-irradiated volume;the pulse fluence being sufficiently high to cause local ablative disruption and liquification of the laser-irradiated volume of the intravascular accumulation.

[0319] Embodiment 83. An optical microcatheter system comprising:an optical fiber microcatheter comprising:an elongate sheath; andan optical fiber extending through the elongate sheath; andan outer tube housing at least a portion of the optical fiber microcatheter, wherein a distal portion of the optical fiber microcatheter is extendable beyond a distal end of the outer tube;wherein at least a distal portion of the elongate sheath is formed from a memory metal having a pre-defined curved shape, such that the distal portion of the optical fiber microcatheter is steerable by varying extension of the elongate sheath relative to a distal end of the outer tube.

[0320] Embodiment 84. The optical microcatheter system according to embodiment 83 further comprising a laser system in optical communication with a proximal end of the optical fiber for coupling laser pulses into the optical fiber.EXAMPLES

[0321] The following examples are presented to enable those skilled in the art to understand and to practice embodiments of the present disclosure. They should not be considered as a limitation on the scope of the disclosure, but merely as being illustrative and representative thereof.Example 1A: Implementation with Concentric Tube-Based Steering Mechanism and Delivery Catheter

[0322] The following example discusses one non-limiting example implementation of an optical fiber microcatheter system that is capable of performing ablation of an intravascular accumulation via the IHD process. The example system involves components shown in FIGS. 3B, 5 and 6. As shown in FIG. 5, the system includes a multichanneled flexible catheter 500, with irrigation, aspiration, vision, and ablation simultaneously. Ablation or tissue disruption is facilitated by a single ~200 urn sapphire tipped fiber 110 embedded in one or more thin memory alloy tubes (120, 160, shown in FIG. 3B) having a bend radius of 20-30 mm. By embedding the sapphire fiber 110 into one or more curved concentric tubes 120 and 160, and by translating and rotating each tube independently, a tube robot system provides a precise manipulation of the optical fiber 110 relative to the multichanneled flexible catheter 130. In this way it is possible to target diseased tissue while leaving healthy tissue substantially unharmed. Furthermore, it is possible to control not just position or orientation of the tip, but also the pose of the tube robot 690 to achieve minimal deformation to existing tissue structures by following the natural curvature of tissue such as arteries veins and blood vessels, enabling a more natural and less invasive approach compared to conventional rigid devices.

[0323] The addition of irrigation and aspiration, as per the example delivery catheter shown in FIG. 5, allow for the clearing of diseased tissue debris generated by the laser. A centering device 550 locates the distal end of the multichanneled catheter 500 within the vessel. Vision is achieved using an endoscope which is equipped with a miniature camera ~ 650 urn diameter 510. Where the endoscope allows the operator an intravascular view of the lesion effectively allowing for real time feedback of the optical fiber tip 110 position with respect to the vascular occlusion.

[0324] Referring again to FIG. 6 to consider this example implementation in more detail, the tube robot 690 allows for the transmission of MIR light from the PIRL laser source to the target area within the anatomy. It allows for the user to manipulate the position of the end effector of the tube robot 690 for targeted therapeutic application of the MIR light. In one embodiment, the end effector of the tube robot 690 is the distal tip of an optical fiber 110, for example, sapphire or any optical fiber compatible with MIR light transmission. In this example embodiment, the tube robot 690 consists of two concentric tubes 120 and 160 (see FIG. 3B) made of superelastic nitinol alloys where the distal 10-50 cm of the inner tube 120 is curved at 20-30 mm radius in the case of a 200 urn sapphire fiber. The outer tube 160 is not fixed to the inner tube so that the inner tube is free to slide independently of the outer tube and so that the outer tube can be removed when necessary. The inner and outer tubes have respective dimensions for the inside diameter (ID) and outside diameter (OD). The ID of the inner tube is 20-40 urn greater than the OD of the optical fiber 110 and the OD of the inner tube 120 is 100 urn greater than its ID. The ID of the outer tube is 50-100 urn greater than the inner tubes OD and outer diameter is no greater than 650 urn. These dimensions establish the flexibility of the tubes and ensure that the tube robot functions as intended.

[0325] During operation, the tube robot 690 manipulates the distal end of the optical fiber 110 along several degrees of freedom. For example, as can be seen in FIG. 3B, an inner tube 120 can be axially translated independently of the outer tube 160 over a stroke of 2- 10 cm. This allows it to be protruded and retracted in and out of the outer tube. As the inner tube protrudes past the outer tube, its curve is exposed and the fiber tip 110 moves laterally. When it is retracted back into the outer tube it is straightened and the fiber tip moves medially. In both the curved and the straightened states, the inner tube 120 can be rotated independently of the outer tube 160. Both the inner and outer tubes can be axially translated in unison over a stroke of 20-40 cm. With all degrees of freedom and strokes considered, the distal tip of the optical fiber 110 can be robotically driven about a cylindrical volume 25 cm in length and ~6.6 cm diameter.

[0326] The example delivery catheter is a seven French multichanneled tube 500 constructed out of PEBAX or some other low friction, biocompatible polymer. Two of the smaller lumens 530560 are 710 urn in diameter while the larger lumen has a diameter of 1.5 mm. Referring again to FIG. 5, the multichanneled delivery catheter 500 serves as both a housing for various subsystems (including the tube robot 690) and as a disposable barrier between the anatomy of the patient, and the subsystems housed in the catheter. One small lumen 530 contains the tube robot and also allows for aspiration of debris created during ablation. The second small lumen 560 is used for irrigation of saline to ensure continuous supply of aqueous media so that laser ablation occurs efficiently and debris iscleared away. The large lumen houses an angioscope (camera) 510 and illumination optical fibers 520. This subsystem provides continuous video feedback which is especially important during CTO crossing procedures where the ideal entry point into the occlusion by the tube robot must be determined. The angioscope 520 uses the OVM6948-RALA which is a camera cube chip of dimensions 650x650x1200 urn. The large lumen is also used for the transmission of pressurized air for inflation and deflation of a centering device 550 which is located approximately 8 cm from the distal end of the multichanneled catheter 500. The balloon serves as an anchor in the vasculature and is inflated once the multichanneled catheter has been navigated to the target anatomy. The distal 8 cm of the multichanneled catheter is more flexible than the rest of the catheter. This increased flexibility allows for the end of the catheter to be curved via steering tendon 530. Four stainless steel steering tendons 540 travel along the length of the catheter and are connected to two actuators 600 located in the actuation assembly, shown in FIG. 6. An actuated catheter body allows for the navigation of more complex vasculature.

[0327] The rotating optical fiber injection assembly (ROFI) 605 allows for the injection of MIR laser light into an appropriate optical fiber 110 while preserving a rotational degree of freedom in the tube robot 690. In the figure, the laser beam is incident on the first of three steering mirrors which direct the beam towards the fiber coupling lens. The tube robot with a fiber at its core is mounted onto a standard 1” lens tube 610 which contains a 40 mm focusing lens for focusing incoming MIR light onto the butt of the optical fiber 110. The lens tube 610 is mounted in a fixed ball bearing 615 at its distal end and a selfaligning ball bearing 620 at its proximal end, much like an axle. The combination of the two bearings minimizes precession in the ROFI 605 improving optical injection efficiency during operation. Both bearings are mounted in a bearing housing 625 which also features a mount for a stepper motor 630 which drives the rotation. Rotation is transferred from the stepper motor to the lens tube via spur gears 635.

[0328] The actuation assembly drives motion of the ROFI 605 which in turn drives motion in the tube robot 690. In addition to the aforementioned rotation stepper motor 630 it features two linear actuators 640 and 645, a force sensor 650, two antibuckling devices 655 and 660, a tube release assembly 665 and position feedback sensors 670. The ROFI 605 is mounted onto the small linear actuator 640. This stage drives the inner tube 120 of the tube robot 690 independently of the outer tube 160. The small linear actuator 640 in turn is mounted onto a low friction sliding carriage 675 which is linearly coupled to a force sensor 650. With this configuration the force experienced by the tip of the tube robot 110 can be relayed to the user interface. This feedback communicates to the user when toomuch force is being experienced by the tip, this can be used as a safety measure to prevent the optical fiber 110 from breaking.

[0329] The low friction sliding carriage 675 and force sensor 650 are mounted onto the main carriage 680 which is translated by the large linear actuator 645. The large linear actuator translates both the inner 120 and outer 160 tubes in unison. At the distal end of the large linear actuator 645, the catheter bracket 685 can be found. This part allows for the quick attachment and detachment of the multichanneled delivery catheter 500 from the system. It also holds the delivery catheter in a stationary position as the tube robot 690 is actuated through it. The tube robot’s outer tube 160 is also mounted onto the main carriage 680 via the tube release assembly 665. During CTO crossing, once an occlusion has been crossed, it is possible to activate the tube release mechanism 665 to decouple the tube robot 690 from its outer tube 160. In this way the outer tube can be left behind in the occlusion in a crossed state such that a guidewire can be introduced and additional hardware can be used. Between the ROFI 625 and the tube release assembly 665 the small antibuckling mechanism 655 is present to ensure that the inner tube 120 does not buckle as it is moved independently of the outer tube 160. The large antibuckling mechanism 660 is present between the tube release assembly 665 and the catheter bracket 685 ensuring that the entire tube robot 690 does not buckle as it is translated into and out of the catheter.Example 2 - Example Method of Crossing of a Chronic Total Occlusion

[0330] A patient presenting with calf pain and fatigue which resolves after rest is assumed to have one or more vascular occlusions in the lower extremities (occlusions and blockages can be used interchangeably). After conducting an ankle brachial index test this hypothesis is supported, and various imaging methodologies are used to find the location of the occlusion and asses it. If it is determined that there is severe occluding that a conventional guidewire cannot cross, then the MIR Beam Delivery System should be used. The patient is placed under anesthesia. Retrograde access is achieved via the superficial femoral artery via introducer sheath. Following this, a guidewire no greater than 27 thou is inserted through the introducer sheath and is navigated to the site of the occlusion. The catheter of the system is then navigated over the guidewire to the site of occlusion. In step 1, shown in FIG. 14A, the balloon is then inflated to anchor the catheter into place. The guidewire is removed. The tube robot is then carefully inserted into the right eye of the catheter until the butt end of the catheter can be coupled to the catheter bracket. The system is now completely set up.

[0331] Angioscopic feedback as well as preoperative imaging is used to determine the optimal entry point for the tube robot, as shown in step 2 in FIG. 14B. Any debris or bloodimpeding the video feed is cleared via irrigation and aspiration. The tube robot moves the fiber tip to the entry point. In steps 3 and 4, shown in FIGS. 14C and 14D, the tube robot is then advanced into the occlusion at a rate of Imm / s and simultaneously laser light is allowed to pass through the tube robot. Every 5 mm a contrast image is taken and compared to the original road map to determine the position and orientation of the tube robot. Tube robot pose is adjusted as needed to follow the curve of the artery. If at any time during crossing a force exceeding 400 g is detected the tube robot is retracted by 1mm and then advanced again. The tube robot is advanced until it has broken through the CTO. In step 5, shown in FIG. 14E, at this point, the tube release assembly is used to decouple the outer tube from the inner tube of the tube robot, the catheter is decoupled from the rest of the system and the entire tube robot (inner tube only) is withdrawn from the anatomy. In step 6, shown in FIG. 14F, the outer tube is left behind and a guide wire is inserted through it no bigger than 13 thou in diameter. Once the guide wire has been fully inserted through the outer tube, the outer tube can be removed and the next system can be introduced over the fully crossed guide wire, shown as step 7 in FIG. 14G.Example 3: Theoretical and Experimental Investigation of Material Disruption via IHD Process with PIRL Laser Pulses

[0332] The present example provides a concise theory of the mechanism of localization of tissue disruption in the IHD process, and which is employed in various example embodiments of the present disclosure to avoid damage of adjacent vascular tissue, while also achieving sufficient disruption of an intravascular accumulation to facilitate advancement of the microcatheter while reducing or minimizing the opposing force of translation through the intravascular accumulation. By using the combination of wavelength and pulse-durations defined by the IHD process (pulse conditions noted above) with the suitable fluence and system configuration, one can enable controlled steering of the distal portion of the optical fiber microcatheter, within the intravascular accumulations (e.g. occlusions) in curved and non-rectilinear arterial geometries.

[0333] For example, if one considers tuning the laser to a wavelength of 2900nm, very near the peak of the OH-stretch absorption in interstitial water present an intravascular accumulation, optical absorption in the intravascular accumulation ca be dominated by vibrational motions of biomolecules including interstitial liquid water. In the experiments and theory described below, pure liquid water is considered as a model system. Having stronger absorption and lower viscosity than solid tissue, one can nonetheless confirm the theory of IHD ablation. In the forthcoming analysis, the threshold for disruption is first determined by measuring at what fluence a sufficient amount of the laser pulse isabsorbed within the target material to achieve rapid heating and vaporization through vibrational excitation alone, rather than bulk heating or multiphoton ionization.

[0334] To estimate a threshold fluence for IHD in liquid water, the sound power emitted during PIRL ablation of water was measured as a function of the laser fluence with an experimental setup shown in FIG. 15. Here an optical fiber with a tip of 200 urn was immersed in water to a depth of 5 cm. An acoustic microphone was used to measure the resulting sound / ultrasound, and the spectra was recorded at different laser fluences.

[0335] A representative spectrum of the sound during ablation is shown in FIG. 16, which shows the sound power in dB from 0 to 40kHz. As can be seen in the figure, there is a clear structure of strong peaks separated by 1kHz (the laser repetition frequency).

[0336] For analysis purposes the strong peak at 24 kHz was chosen and its intensity was determined at all laser fluences, with FIG. 17 showing the results. Above a fluence of ~0.25 J / cm2the increase in sound power was roughly exponential with fluence. Below 0.25 J / cm2there is a sharp drop-off in sound power as the fluence is reduced.

[0337] The mass of water in the ablated disk with volume of ~1um deep x ir(100um)2is 3.1e-8 g.To raise the temperature of this water from 20 to 100 C and then vaporize it requires ~80pJ of energy, which corresponds to a fluence of 0.25 J / cm2, roughly the same fluence below which the sound power drops off quickly.

[0338] To estimate the efficiency of the process, one can quantify the effects of the laser by observing bubbles caused by the absorption and subsequent rapid expansion of the irradiated volume of water or transparent tissue using stroboscopic imaging.

[0339] Above the threshold fluence, for example at an above-threshold fluence of 350uJ, one can observe bubble formation where the bubble grows until the internal pressure equals the surrounding liquid pressure, after which it collapses. In this case the excess energy is approximately 350-80 uJ = 270uJ, and the work done to expand the bubble is W=PAV where P is approx, atmospheric pressure. Therefore AV = W / P = 270E-6J 1101325 Pa =2.6E-12 mA3 =2.6 pL, i.e., a bubble is formed with volume V = 2.6 pL. The radius of the maximal spherical volume, V, of the bubble is calculated as:R=(3V / 4TT )A1 / 3 = R=(3*2.6E-12 / (4*3.1415))A(1 / 3) =0.0000853 m = 853um, such that the predicted bubble diameter is approximate 1.7 mm. If one measures the bubble size as a function of the pulse energy using a fast or stroboscopic camera, then according to this theory, one can determine the efficiency of the IHD laser process.

[0340] FIG. 18 plots the observed bubble size along with a theoretical fit based on an efficiency of about 0.65. The observed bubble lifetime fits the expected Rayleigh collapse time

[0341] T = 0.915 • Ro* F

[0342] where Rois the initial radius, p is the density of water is 1000 and P is atmospheric pressure. (Brennen CE. Spherical Bubble Dynamics. In: Cavitation and Bubble Dynamics. Cambridge University Press; 2013:30-58.)

[0343] This efficiency result of approximately 0.65 (relative to unity) is significantly higher than what has been observed using long-pulsed Er:YAG laser disruption (having an efficiency of 0.03, as reported in Peter Gregorcie, Matija Jezersek, and Janez Mozina, Optodynamic energy-conversion efficiency during an Er: YAG-laser-pulse delivery into a liquid through different fiber-tip geometries, Journal of Biomedical Optics 17(7), 075006 (July 2012)), and also far more efficient than near infrared or visible femtosecond to picosecond laser systems which have efficiency less than 0.1 ( Hernandez-Rueda, Javier and Dries van Oosten. “Dynamics of Ultrafast Laser Ablation of Water.” arXiv: Applied Physics (2018): n. pag.). If the pulse duration is increased, there will be a loss of efficiency as described in US Patent Publication No. US20230113339A1, as shown in FIG. 19. The lower the efficiency, the more of the absorbed energy results in heat without the desired photomechanical effects.

[0344] Furthermore, the same trend of efficiency is expected at other wavelengths (and associated pulse conditions) in which IHD conditions can be achieved, such as at the absorption peak of water around 1.92 urn. For example, FIG. 20 presents a comparison of bubble size vs. fluence for a 200 urn core diameter optical fiber at a wavelength of 2.75 urn and for a set of different optical fiber core diameters at a wavelength of 1.92um, with 50 ns pulses, and different pulse energies.

[0345] Regardless of the efficiency advantages of IHD parameters, the total energy delivered results eventually in bulk heating. To observe this experimentally, the temperature rise of a fixed volume of water was measured as the laser pulses were delivered. The experimental setup is shown in FIG. 21 and includes a hollow polystyrene sphere that was filled with 2.4 ml of water. A thermocouple and an optical fiber with tip diameter of 200 urn were inserted through holes into the sphere. The optical fiber was positioned in the center of the sphere. The thermocouple was positioned halfway between the center and the edge of the sphere.

[0346] A laser power of 360 mW at 1 kHz was transmitted through the optical fiber and was absorbed by the water in the sphere. The temperature rise of the water was recorded for 250 seconds. The laser was then turned off and the temperature fall due to heat loss to the surroundings was measured.

[0347] The heat loss from the sphere to the surroundings was found to be:dT / dt = - AT / 1140 (deg. / s),

[0348] where AT is the temperature difference (in Kelvin) between the surroundings and the water and time is in units of seconds.

[0349] FIG. 22 shows the rise of temperature of the water as the laser energy is absorbed. The temperature rises in the first 50 seconds is roughly linear, but as the temperature difference relative to the surroundings increases, the heat loss to the surroundings becomes more significant, and the rise deviates from the expected linear increase with time.

[0350] Using this early linear rise, the rate of temperature (dT / dt) rise due to the laser is 0.0330K / S + / - 8%. Over the first 50 seconds, the average rate of heat loss to the surroundings is 0.0009 K / s, a minor correction. This compares to an expected rate of 0.0357 K / s for 2.4 g of water with a heat capacity of 4.2 J / g / K when heated by a 360 mW laser. Thus the amount of energy that does not end up increasing the temperature of the water (i.e. lost to sound, or other pathways) is less than 5%. It is clear from this experiment that choosing the most efficient laser parameters is important for practical conditions in which heat transfer creates a limit to the laser power density, i.e. rate of laser exposure, to prevent bulk heating from damaging the surrounding tissue during the laser exposure.

[0351] In a case in which an optical fiber is advanced through a material (an intravascular accumulation) at a given speed, local temperature rise as a function of speed can be estimated by considering a fixed volume of tissue and a given number of laser pulses. For an optical fiber that is positioned inside of a material such as liquid water, with heat capacity, c= 4.18J / g*K, the energy required to raise the temperature of 1 microliter = 1mmA3 = 1 mg of water by 1 degree K is only Q=m*c*AT = 1E-3g *4.18 J / g*K *1deg = 0.00418 J = 4.18 mJ assuming it is adiabatic. This result implies that that 1000 pulses, each having an energy of 350uJ, would raise the bulk temperature of the 1 microliter of the material to AT=.350 / (1 E-3g *4.18) = 83.7 K.

[0352] However, the model may be refined by considers heat diffusion assuming that that the 1 microliter pocket of water resides within surrounding water. The heat equation can be modeled in 1D (radial diffusion) as:and with the thermal conductivity of water k = 0.6W / m*K, the thermal diffusivity is calculated as follows:__A 10 TH1.44 X — - — .s2

[0353] For example, assuming that while passing through a small area of tissue, the cumulative energy of 1000 pulses at 500 Hz , Q = 350 mJ is diffused radially into a spherical volume defined by r= V4at, where t = 2s, r= V4 x 1.44 x 10 - 7 x 2 = 0.00107m (1.07 mm).

[0354] The mass of water affected is: m = ^npr3= 4.87 x 10-6kg and the temperature rise is AT = — me = - 4.87X10-6-X4180 17°C.

[0355] If however, one either reduces the repetition rate of the laser or decreases the speed of motion of the fiber tip (and hence reduce the power density in the tissue while delivering the same volumetric dose), e.g. 50 Hz instead of 500 Hz, then the same total energy (number of pulses) would be delivered in 20 sec instead and the temperature rise is determined using the same formula, with t = 20s, r = 0.0034m(3.4 mm). In such as case, the mass of water affected is m = 1.65 x w-4kg. and the temperature rise is reduced to AT = 0.5°C.

[0356] Considering that local temperatures above the limit of cell apoptosis will damage adjacent tissues and lead to wide spread damage from large temperature gradients, one can begin to estimate the advancement speed required to limit thermal effects. Opposing forces, however, must also be considered for advancement of a microcatheter into an intravascular accumulation (hard tissue).

[0357] To include the effect of stiffness in a tissue or intravascular accumulation (as opposed to water), one can consider that the pressure driving the bubble’s growth P =is proportional to the pulse energy E and inversely proportional to the bubble’s maximum volume Vmn= -nrm3where rmax is the maximum radius of a spherical bubble.^expansion = T"K, where E is pulse energy. However, we must also consider that the elastic forces of the surrounding material resist the bubble’s expansion. This elastic restoring pressure, Plastic Y ■rmax , is proportional to Young’s Modulus (Y) and the bubble’s maximum radius rmax. . At the maximum radius, these two pressures balance: — — a Y ■ rmIl LnUr. Solving for the maximum bubble radius we get rmlILnlrX a or atconstant pulse energy we can generalize to rmax<x - =.

[0358] Accordingly, expansion of bubbles in rigid environments is a competition between the pressure driving the growth of the bubble (proportional to the energy of the laser pulse) and the elastic restoring pressure of the surrounding material (related to the material’s stiffness). The result is that stiffer materials significantly limit the bubble's size, and the maximum bubble radius scales as the inverse fourth root of the material’s stiffness. In practical terms, water has a negligible Young’s modulus, Y ~ 0, and as a result the bubble can expand freely, achieving its maximum size against atmosphericpressure. For other materials Young’s modulus is non-negligible, e.g. brain tissue Ybrain= 1kPa or atherosclerotic plaque with a wide range from Ypiaque'\~'\00 kPa. To examine the change in bubble size as young’s modulus approaches zero and ultimately compare the maximum expected bubble size to the experimentally observed bubbles in water by considering that the bubble radius is determined by balance between the driving pressure inside the bubble, Pexpansion’ and the resisting pressure which combines the atmospheric pressure and the elastic restoring pressure rmaxa1a1in the case yof pure water, Peiastic is negligible. So the ratio of the maximum bubble radius can be expressed as> > t lsolution. This is a simplistic model that does not take into account inhomogeneities or nonlinearity of the tissue or other effects such as surface tension etc., but serves to illustrate that the viscosity acts to reduce the maximum size of the bubble.

[0359] Accordingly, the present inventors realized that as long as the zone of disruption is larger than the forward tip of the microcatheter (“the bow of the ship”), the advancement of the catheter will not be substantially impeded by opposing forces in the tissue, and will pierce through the intravascular accumulation (hard tissue) with a low friction. In FIG. 18, one can see that in pure water, a single 350uJ pulse from the tip of a 200 urn fiber creates a bubble with about 1 mm diameter, and a 1 mJ pulse creates a 1.75 mm diameter bubble, so in the case the microcatheter is moved through a stiffer tissue (or biological material) such as intravascular plaque, the bubble size can still be larger than the 200 urn fiber optic by some margin (depending on the nearby stiffness).

[0360] If the microcatheter includes a sheath that surrounds a distal portion of the optical fiber in close proximity to the distal tip of the optical fiber (or more generally, includes one or more additional elements through which light is not emitted), this ‘dark’ component will act as an anchor (or surface to which a restive / restoring shear forces is applied) during motion relative to the medium penetrated by the microcatheter, unless the additional “dark” component is dimensionally (i.e. has a lateral extent / dimensions) that is smaller than the disrupted zone of the medium (e.g. an intravascular accumulation). For this reason, an optical fiber material, e.g. sapphire or low OH glass, clad by a thin walled metallic tube, can be employed with low friction if sufficient pulse energy is delivered such that the disrupted zone is large enough to substantially prevent (overcome) the friction.

[0361] A nearly frictionless condition would allow for a slightly smaller volume of disruption in which the distal portion of the catheter can still fit with minimal compression of the surroundings. Here it is preferable to stay below the elastic limit of the material to minimize friction and damage to the surroundings. Such a nearly frictionless condition could be determined by observing an absence of microscopic tissue damage, through histology or other means, to the material surrounding the catheter after advancement such that the borders of the catheters channel of travel are similar in damage to a completely frictionless condition as described above.

[0362] These considerations were taken into account in an experiment in which the piercing force of an optical fiber (“laser”) microcatheter was measured. The optical fiber microcatheter consisted of a 200 urn sapphire fiber placed inside a 320 urn outer diameter blunt nitinol tube with the small distal gap between the fiber diameter and the tube filled with epoxy, as it is being translated inside sections of occluded atherosclerotic vessels in the presence of liquid water irrigation (M. Tahmasebi et al., "CathCam-Guided Picosecond Infrared Laser Ablation in Peripheral Artery Disease Revascularization," in IEEE Transactions on Biomedical Engineering, doi: 10.1109 / TBME.2024.3468889).

[0363] As can be seen in FIG. 23, a considerable drop in force appears with the laser on vs off at a fixed speed. Furthermore, the measurement of opposing force was found to vary with advancement speed of the optical fiber microcatheter. And lastly, the change in force vs advancement speed becomes saturated when the laser pulse is already at half power (0.5mJ in this case) as compared to full power, which implies that the zone of liquified / disrupted tissue created by the laser pulses was already wide enough at half power to accommodate the 320 urn diameter tip of the catheter assembly.

[0364] These ablation conditions resulted in a 350um ablated channel within the tissue, as can be seen in FIG. 24 (panel D) as would be expected from some combination. Using our previous expression for the ratio of the bubble size for these conditions where at pulse energy E= 500 uJ we expect a bubble of 1.3mm in water but in plaque we observe a channel of 325 urn which is 4 times smaller compared to the expected bubble size in pure water. We can solve the expression to determine Y for the tissue. In this casermax, wateris 13mm and atmospheric pressure about ~100kPa we find that- Y — o.325mm and thus Y must be approximately303 kPa which seems reasonable for stiff calcified tissue.

[0365] Conventional catheter-based interventions for treating peripheral artery disease use flexible guidewires to cross arterial plaques. Guidewires need to be flexible to allow for smooth tracking through the vasculature with minimal vessel wall injury, but the ability to apply force through a guidewire is an important part of crossing the plaque. It has beenshown that on average it is required to apply 0.43N to cross soft thrombotic plaques, 1.71 N to cross dense collagenous plaques, and greater than 20N to cross calcified plaques at a fixed displacement rate of 0.05mm / s [T. Roy et al., “Puncturing Plaques: Relating MRI Characteristics of Peripheral Artery Lesions to Guidewire Puncture Forces,” Journal of Endovascular Therapy, vol. 24, no. 1, pp. 35-46, Feb. 2017, doi:10.1177 / 1526602816671135.]. However, even the stiffest guidewire is rated to buckle at forces lower than 0.13N [1], Therefore, guidewires need catheter support to enable the delivery of sufficiently high forces to penetrate and cross even the softest plaques. Using the optical fiber microcatheter of the present disclosure (e.g. an “active guidewire”), is has been shown that calcified plaques can be penetrated while maintaining forces below the minimum force necessary in conventional procedures. The peak force applied during advancement has been found to be between 0.1 - 0.39N when the advancement speed is between 0.012 - 0.5mm / s [Tahmasebi M, Perez RR, Marques A, Soenjaya Y, Khoobani M, Keshavarz M, Kayssi A, Dueck A, Kraemer D, Demore C, Miller RJD, Wright G, Tavallaei MA. CathCam-Guided Picosecond Infrared Laser Ablation in Peripheral Artery Disease Revascularization. IEEE Trans Biomed Eng. 2024 Sep 26;PP. doi:10.1109 / TBME.2024.3468889.]. Laser parameters (1W Power, 1kHz Repetition Rate, 1mJ Energy) remained constant throughout the experiment. There is a complex relationship between laser power, pulse energy and advancement speed which can be optimized for different vascular scenarios.Example 4: Example Optical Fiber Design Parameters for Performing Intravascular IHD via Delivery of PIRL Pulses

[0366] To design the largest core size low-OH step-index (SI) fiber suitable for bending to a radius of 3-5 mm in catheter applications, a fiber with a 200 pm core diameter and a high numerical aperture (NA) of 0.37 is ideal. This large core allows for maximum light transmission and reduced bend losses, while the high NA ensures efficient light confinement despite tight bends. The cladding diameter would be approximately 220 pm, and with protective coatings, the overall diameter could reach around 500 pm, fitting within standard catheter sizes. The low-OH silica material minimizes attenuation at mid-IR wavelengths such as 1.9um, and the fiber's mechanical robustness, enhanced by suitable coatings, provides the necessary flexibility and durability for safe and effective use in catheter-based procedures.

[0367] For higher transmission at longer mid-infrared wavelengths (around 3-5 pm), fluoride glass fibers like ZBLAN are considered, which, despite being more brittle than conventional silica fibers, offer the best balance between transmission properties and mechanical feasibility within specified constraints for delivering picosecond mid-IR lasersbeyond 2.2 pm. Assuming a factor of 100 between the minimum bend radius and the core diameter, a bend radius of 5 mm corresponds to a 50 pm core diameter in ZBLAN fiber; from this core size, a cladding diameter of 70 pm and a total outer diameter with coating of <500 pm can be determined, achieving a minimum bend radius of less than 5 mm through design enhancements. Therefore, a ZBLAN fiber optimized for flexibility, with these specifications, is suitable for applications requiring tight bends and efficient mid-IR transmission within the specified constraints.

[0368] Energy Threshold goes with the square of the fiber output face diameter, for example, for a 200um fiber at 2950, <1 ns the threshold is 80uJ. For a 50um diameter fiber, the energy threshold for tissue disruption would be 16 x smaller. E.g. 5uJ for 2950nm, 500ps.Operating above the threshold can be advantageous for efficient tissue disruption, e.g. 2x or 4x threshold. 10uJ and 20uJ.

[0369] However, if the tip is polished at an angle, or tapered as a cone for example, to increase the surface are size, the energy would scale linearly with the new surface area at which the laser output occurs. It is critical that the intensity within the narrowest part of the fiber optic waveguide not exceed the optical damage threshold of the waveguide itself, while also being above the energy threshold fortissue disruption. For this reason, the very efficient disruption mechanisms, e.g. impulsive heat deposition, provide novel regimes in which the disruption threshold is far below the optical damage threshold of the waveguides that transmit well in the vibrational absorption bands of OH containing intravascular accumulations.Example 5: Treatment of Intravascular Occlusion in Cranial Vasculature

[0370] FIG. 25 shows an example optical fiber microcatheter system for treating a cerebral (neurovascular) accumulation via delivery of PIRL laser pulses, in the present example implementation, via a transfemoral path. The figure illustrates a percutaneous approach through the femoral or radial arteries utilizing microcatheter including small fiber optics to deliver picosecond mid-infrared laser pulses into the cerebral vasculature to ablate an intravascular accumulation. The distal portion 112 of the optical fiber microcatheter 100 is hydraulically steered (e.g. as per the example embodiment shown in FIG. 3D) and includes a proximal optical / fluidic coupling 178 that optically couples the PIRL pulses from the proximal delivery fiber 150 (e.g. via a lens relay) and the hydraulic steering fluid into the hollow core of the optical fiber microcatheter 100. In the present non-limiting example, steering is manually controlled by varying the volume of the fluid reservoir 186 via actuation of the syringe pump 310, which varies the pressure within the fluid core of the optical fiber microcatheter via the fluid delivery channel 188.

[0371] As illustrated in FIG. 25, after access to the femoral artery has been established, the catheter enters the femoral artery with advancement to the iliac artery, up the abdominal aorta, through the aortic arch to one of the carotid arteries, such that the distal end of the microcatheter is positioned adjacent to an intravascular occlusion. Advancement of the catheter can be visually monitored and guided by imaging methods such as fluoroscopy. Telescoping catheters may be used, where the largest and outermost goes from the femoral artery to the carotid artery in the neck; through this, a smaller and longer catheter is advanced to the base of the skull, and finally, the distal region 112 of the optical fiber microcatheter is advanced to the brain artery of interest, where the delivery of PIRL laser pulses can be employed to disrupt the intravascular accumulation (target region) 10.

[0372] One example implementation of an intravascular system may be provided as follows.Catheter Selection: an optical fiber microcatheter of 1.5 Fr (0.5 mm OD) would be suitable for accessing the hippocampal arteries without causing vessel trauma. The catheter should be made of materials like braided stainless steel or nitinol to provide the necessary flexibility and kink resistance while accommodating a fiber optic for laser mediated perforation. A hydrophilic surface reduces friction, facilitating smoother navigation through tortuous paths. Since the cerebral arteries, especially the small perforators like the lenticulostriate arteries, have tight curves with bend radii as small as 3 mm or even less, some practical requirements can be defined for the fiber optics size and bend radius. Assuming that the minimum allowable bend radius of a particular fiber optic waveguide is roughly proportional to the fiber's diameter. One can select a suitable diameter, for example, low OH Si glass can support a minimum bend radius that is approximately 20 times the fiber diameter.

[0373] The specific embodiments described above have been shown by way of example, and it should be understood that these embodiments may be susceptible to various modifications and alternative forms. It should be further understood that the claims are not intended to be limited to the particular forms disclosed, but rather to cover all modifications, equivalents, and alternatives falling within the spirit and scope of this disclosure.

Claims

1. CLAIMS1. A system for performing ablative removal of an intravascular accumulation, the system comprising:an optical fiber microcatheter comprising:an elongate sheath; andan optical fiber extending through the elongate sheath;a laser system in optical communication with a proximal end of theoptical fiber for coupling laser pulses into the optical fiber, the laser system and the optical fiber being configured such that the laser pulses are delivered by a distal end of the optical fiber with laser pulse properties comprising:a wavelength selected such that absorption of the laser pulses by a laser-irradiated volume of the intravascular accumulation, when the intravascular accumulation is positioned adjacent to a distal end of the optical fiber, is predominantly due to excitation of vibrational modes of one or more constituents of the intravascular accumulation;a pulse duration that is shorter than a first time duration required for thermal diffusion out of the laser-irradiated volume and shorter than a second time duration required for a thermally driven expansion of the laser-irradiated volume;a pulse fluence and the pulse duration resulting in a peak pulse intensity below a threshold for ionization-driven tissue disruption to occur within the laser-irradiated volume;the pulse fluence being sufficiently high to cause local ablative disruption and liquification of the laser-irradiated volume of the intravascular accumulation;wherein the laser system and the optical fiber are configured such that the pulse fluence is sufficiently high to generate a disrupted volume, due to expansion of the laser-irradiated volume, that is larger, in a lateral direction, than an outer diameter at least a distal portion of the optical fiber microcatheter, thereby facilitating extension of the optical fiber microcatheter through the intravascular accumulation during delivery of the laser pulses.

2. The system according to claim 1 further comprising a steering mechanism operatively coupled to the elongate sheath, the steering mechanism being externally controllable for steering a distal portion of the elongate sheath.

3. The system according to claim 2 wherein the steering mechanism comprises pull cables extending through the elongate sheath to the distal portion of the elongate sheath.

4. The system according to claim 2 further comprising an outer tube housing at least a portion of the optical fiber microcatheter, wherein the distal portion of the optical fiber microcatheter is extendable beyond a distal end of the outer tube for steering the distal portion of the optical fiber microcatheter.

5. The system according to claim 4 wherein the laser system and the optical fiber are configured such that the disrupted volume, due to expansion of the laser-irradiated volume, is larger, in the lateral direction, than an outer diameter of the outer tube, thereby facilitating extension of the outer tube through the intravascular accumulation during or after delivery of the laser pulses.

6. The system according to claim 4 wherein the steering mechanism is a concentric tubebased steering mechanism comprising the outer tube, and wherein at least a distal portion of the elongate sheath is formed from a memory metal having a pre-defined curved shape, such that the distal portion of the optical fiber microcatheter is steerable by varying extension of the elongate sheath relative to a distal end of the outer tube.

7. The system according to claim 6 wherein the pre-defined curved shape is defined such that the elongate sheath is laterally extendable by 7 cm when the elongate sheath is longitudinally extended from the distal end of the outer tube.

8. The system according to any one of claims 4 to 7 wherein an outer diameter of the outer tube is between 500 and 1000 microns.

9. The system according to any one of claims 2 to 8 wherein an outer diameter of the elongate sheath is between 300 and 1000 microns.

10. The system according to any one of claims 2 to 8 wherein an outer diameter of the elongate sheath is between 300 and 600 microns.

11. The system according to any one of claims 1 to 10 further comprising a force sensor configured to measure an opposing force applied to the distal portion of the optical fiber microcatheter during longitudinal translation of the optical fiber microcatheter.

12. The system according to claim 11 further comprising control circuitry operatively coupled to the force sensor, wherein the control circuitry is configured to employ a forcesignal obtained from the force sensor to provide feedback for controlling advancement of the optical fiber microcatheter.

13. The system according to claim 12 wherein the control circuitry is configured to display, on a user interface, qualitative or quantitative feedback indicative of the force signal.

14. The system according to claim 12 wherein the control circuitry is configured to provide haptic feedback to a user based on the force signal.

15. The system according to claim 14 wherein the control circuitry is configured to provide haptic feedback to the user when the opposing force exceeds a force threshold.

16. The system according to claim 12 wherein the control circuitry is configured such that the force signal is employed to control an average power or a repetition rate of the laser pulses.

17. The system according to claim 12 further comprising a motorized translation mechanism operably coupled to the control circuitry, the motorized translation mechanism being capable of actuating longitudinal translation of the optical fiber microcatheter, the control circuitry being configured to control the motorized translation mechanism according to feedback provided by the force signal, such that longitudinal translation of the optical fiber microcatheter is dependent on the opposing force.

18. The system according to claim 17 wherein the control circuitry is configured to control the motorized translation mechanism such that longitudinal translation of the optical fiber microcatheter is prevented when the opposing force exceeds a force threshold.

19. The system according to claim 17 wherein the control circuitry is configured to control the motorized translation mechanism such that the optical fiber microcatheter is retracted when the opposing force exceeds a force threshold.

20. The system according to claim 17 wherein the control circuitry is configured to control the laser system to modify or more properties of the laser pulses based on the force signal.

21. The system according to claim 20 wherein the control circuitry is configured to control the laser system to modify or more properties of the laser pulses such that the force signal satisfies pre-determined criteria.

22. The system according to claim 17 wherein the control circuitry is configured to control the motorized translation mechanism such that a speed of longitudinal translation of the optical fiber microcatheter is sufficient to limit thermal accumulation.

23. The system according to any one of claims 1 to 22 further comprising an optical detection system configured to deliver interrogating optical energy to the disrupted and liquified intravascular accumulation, and to collect emitted optical energy that is responsively emitted by the disrupted and liquified intravascular accumulation.

24. The system according to claim 23 further wherein the optical detection system comprises an additional optical fiber or optical fiber bundle configured to collect the emitted optical energy.

25. The system according to claim 23 wherein the optical detection system is operable coupled to the optical fiber and configured to employ the optical fiber for collection of the emitted optical energy.

26. The system according to any one of claims 23 to 25 wherein the system is further configured to analyze the emitted optical energy to perform tissue analysis.

27. The system according to claim 26 wherein the system is configured such that the tissue analysis is performed in real-time.

28. The system according to claim 26 or 27 wherein the system is configured to employ the tissue analysis to adjust at least one treatment parameter.

29. The system according to claim 26 or 27 wherein the system is configured to employ the tissue analysis to adjust one or more of the laser pulse properties, based on a detected or inferred composition of the intravascular accumulation, such that the laser pulse properties are sufficient to generate the disrupted volume, due to expansion of the laser-irradiated volume, that is larger, in the lateral direction, than the outer diameter at least the distal portion of the optical fiber microcatheter.

30. The system according to claim 26 or 27 wherein the system is configured to employ the tissue analysis to generate an alert indicating that a distal end of the optical fiber microcatheter is positioned too close to a vessel wall.

31. The system according to claim 26 or 27 wherein the system is configured to employ the tissue analysis to determine whether the optical fiber microcatheter is facing a vessel wall, plaque, or an open lumen.

32. The system according to claim 26 or 27 wherein the system is configured to employ the tissue analysis to control the laser system such that ablation is only directed at pathological tissues.

33. The system according to any one of claims 23 to 32 wherein the optical detection system is an optical spectroscopy detection system.

34. The system according to any one of claims 23 to 33 wherein the optical detection system is configured to employ a detection modality selected from the group consisting of reflection spectroscopy, fluorescence spectroscopy, optical coherence tomography, nearinfrared spectroscopy (NIRS), breakdown spectroscopy, Raman spectroscopy and diffuse reflectance imaging Raman spectroscopy.

35. The system according to any one of claims 1 to 34 wherein the optical fiber is operably coupled to the laser system through a fiber optic rotary to facilitate rotation of the elongate sheath.

36. The system according to any one of claims 1 to 35 wherein the laser pulses have a pulse energy between 0.3-3 mJ, a pulse duration between 0.5-5 ns, a wavelength between 2750 - 3100 nm, and a repetition rate between 0.1-5 kHz.

37. The system according to any one of claims 1 to 35 wherein the laser pulses have a pulse energy between 1mJ - 10m J, a pulse duration between 10-50 ns, a wavelength between 1890- 1950 nm, and a repetition rate between 0.1-3 kHz.

38. The system according to any one of claims 2 to 37 further comprising a delivery catheter, wherein the elongate sheath is extendable through a lumen of the delivery catheter.

39. The system according to any one of claims 4 to 7 further comprising a delivery catheter, wherein the outer tube and the optical fiber microcatheter are extendable through a lumen of the delivery catheter.

40. The system according to claim 38 or 39 wherein the delivery catheter comprises an anchoring means for anchoring the delivery catheter within a vessel while permitting extension of the elongate sheath beyond a distal end of the delivery catheter.

41. The system according to any one of claims 38 to 40 wherein the delivery catheter further comprises an endoscopic imaging subsystem comprising an optical camera capable of acquiring images of a distal region residing beyond a distal end of the delivery catheter, and an illumination source capable of illuminating the distal region.

42. The system according to any one of claims 38 to 41 wherein the delivery catheter further comprises an irrigation lumen connectable to an external irrigation source.

43. A method for providing intravascular laser therapy to an intravascular accumulation, the method comprising:providing the system of claim 1 ;positioning the optical fiber microcatheter such that the distal end of the optical fiber resides adjacent to the intravascular accumulation; anddelivering the laser pulses as the optical fiber microcatheter is longitudinally translated into the intravascular accumulation.

44. The method according to claim 43 wherein the laser pulses are delivered, as the optical fiber microcatheter is longitudinally translated within the intravascular accumulation, such that a channel is formed within the intravascular accumulation, the channel having a sufficient cross-sectional area to permit longitudinal advancement of the optical fiber microcatheter through the intravascular accumulation.

45. The method according to claim 43 or 44 wherein the laser pulses are delivered, as the optical fiber microcatheter is longitudinally translated within the intravascular accumulation, such that the disrupted volume has a sufficiently large size to permit steering of the distal portion of the optical fiber microcatheter.

46. The method according to any one of claims 43 to 45 wherein the intravascular accumulation is an intravascular occlusion, and wherein the optical fiber microcatheter is employed to cross the intravascular occlusion while delivering the laser pulses.

47. The method according to claim 46 wherein an outer tube, housing at least a portion of the optical fiber microcatheter, is extended with the optical fiber microcatheter during crossing of the intravascular occlusion.

48. The method according to claim 47 wherein at least a distal portion of the elongate sheath is formed from a memory metal having a pre-defined curved shape, such that the distal portion of the optical fiber microcatheter is steerable by varying extension of the elongate sheath relative to a distal end of the outer tube.

49. The method according to claim 47 further comprising, after crossing the intravascular occlusion:withdrawing the optical fiber microcatheter from the outer tube while maintaining the outer tube across the intravascular occlusion;extending a guidewire through the outer tube, such that the guidewire crosses the intravascular occlusion;withdrawing the outer tube; andemploying the guidewire to facilitate the positioning of a medical device for treatment of the intravascular occlusion.

50. The method according to claim 46 further comprising employing the optical fiber microcatheter to cross the intravascular occlusion one or more additional times while delivering the laser pulses, each crossing occurring along a separate path through the intravascular occlusion.

51. The method according to claim 50 further comprising, after having reduced the density of the intravascular occlusion via multiple crossings, performing balloon angioplasty.

52. The method according to claim 43 wherein the system further comprises a steering mechanism operatively coupled to the elongate sheath, the steering mechanism being externally controllable for steering a distal portion of the elongate sheath.

53. The method according to claim 52 wherein the steering mechanism includes pull cables extending through the elongate sheath to the distal portion of the elongate sheath.

54. The method according to claim 47 wherein an outer diameter of the outer tube is between 500 and 1000 microns.

55. The method according to any one of claims 43 to 53 wherein an outer diameter of the elongate sheath is between 300 and 1000 microns.

56. The method according to any one of claims 43 to 53 wherein an outer diameter of the elongate sheath is between 300 and 600 microns.

57. The method according to any one of claims 43 to 56 further comprising employing a force sensor to measure an opposing force applied to the distal portion of the optical fiber microcatheter during longitudinal translation of the optical fiber microcatheter within the intravascular accumulation.

58. The method according to claim 57 further comprising employing feedback generated from the force sensor to control longitudinal translation of the optical fiber microcatheter.

59. The method according to claim 57 further comprising employing a force signal obtained from the force sensor to control an average power or a repetition rate of the laser pulses.

60. The method according to claim 57 wherein longitudinal translation of the optical fiber microcatheter is prevented when the opposing force exceeds a force threshold.

61. The method according to claim 57 wherein one or both of a detected force signal and / or a detected rate of change of longitudinal position of the optical fiber microcatheter is employed to control one or both of a rate of delivery of laser pulses and the pulse fluence in order to ensure that longitudinal advancement of the optical fiber microcatheter proceeds with a sufficiently low force and / or a sufficiently low amount of collateral damage to surrounding vascular tissue.

62. The method according to any one of claims 43 to 61 wherein an optical detection system is employed to deliver interrogating optical energy to the disrupted and liquifiedintravascular accumulation and to collect emitted optical energy that is responsively emitted by the disrupted and liquified intravascular accumulation.

63. The method according to claim 62 further wherein the optical detection system comprises an additional optical fiber or optical fiber bundle configured to collect the emitted optical energy.

64. The method according to claim 62 wherein the optical detection system is operable coupled to the optical fiber and configured to employ the optical fiber for collection of the emitted optical energy.

65. The method according to any one of claims 62 to 64 further comprising analyze the emitted optical energy to perform tissue analysis.

66. The method according to claim 65 wherein the tissue analysis is performed in realtime.

67. The method according to claim 65 or 66 further comprising employing the tissue analysis to adjust at least one treatment parameter.

68. The method according to claim 67 wherein the tissue analysis is employed to adjust one or more of the laser pulse properties, based on a detected or inferred composition of the intravascular accumulation, such that the laser pulse properties are sufficient to generate the disrupted volume, due to expansion of the laser-irradiated volume, that is larger, in the lateral direction, than the outer diameter at least the distal portion of the optical fiber microcatheter.

69. The method according to claim 65 or 66 further comprising employing the tissue analysis to generate an alert indicating that a distal end of the optical fiber microcatheter is positioned too close to a vessel wall.

70. The method according to claim 65 or 66 further comprising employing the tissue analysis to determine whether the optical fiber microcatheter is facing a vessel wall, plaque, or an open lumen.

71. The method according to claim 65 or 66 further comprising employing the tissue analysis to control the laser system such that ablation is only directed at pathological tissues.

72. The method according to any one of claims 62 to 71 wherein the optical detection system is an optical spectroscopy detection system.

73. The method according to any one of claims 62 to 72 wherein the optical detection system is configured to employ a detection modality selected from the group consisting of reflection spectroscopy, fluorescence spectroscopy, optical coherence tomography, nearinfrared spectroscopy (NIRS), breakdown spectroscopy, Raman spectroscopy and diffuse reflectance imaging Raman spectroscopy.

74. The method according to any one of claims 43 to 73 wherein the laser pulses have a pulse energy between 0.3-3 mJ, a pulse duration between 0.5-5 ns, a wavelength between 2750 - 3100 nm, and a repetition rate between 0.1-5 kHz.

75. The method according to any one of claims 43 to 73 wherein the laser pulses have a pulse energy between 1mJ - 10m J, a pulse duration between 10-50 ns, a wavelength between 1890- 1950 nm, and a repetition rate between 0.1-3 kHz.

76. The method according to any one of claims 43 to 75 further wherein a delivery catheter is employed to facilitate positioning of the optical fiber microcatheter proximal to the intravascular accumulation, wherein the elongate sheath is extendable through a lumen of the delivery catheter.

77. The method according to claim 76 wherein the delivery catheter is anchored, via an anchoring mechanism, such that the elongate sheath is extendable beyond a distal end of the delivery catheter.

78. The method according to claim 76 or 77 wherein an endoscopic imaging subsystem of the delivery catheter is employed to facilitate steering of the distal portion of the optical fiber microcatheter prior to entry of the optical fiber microcatheter into the intravascular accumulation.

79. The method according to any one of claims 43 to 77 further comprising controlling one or both of a speed of longitudinal extension of the optical fiber microcatheter to a rate of delivery of the laser pulses to limit thermal accumulation.

80. The method according to any one of claims 43 to 77 wherein the laser pulse properties are selected such that laser pulse absorption leads to expansion of a gas-filled cavity and subsequent collapse into liquification of the disrupted volume that extends out beyond the laser-irradiated volume.

81. The method according to any one of claims 43 to 77 wherein the optical fiber microcatheter is longitudinally advanced, through the intravascular accumulation, while delivering the laser pulses, with forces between 0.100N and 0.300N at speeds between 0.02 and 0.5 mm / s.

82. A system for performing ablative removal of an intravascular accumulation, the system comprising:an optical fiber microcatheter comprising:an elongate sheath; andan optical fiber extending through the elongate sheath;a steering mechanism operatively coupled to the elongate sheath, the steering mechanism being externally controllable for steering a distal portion of the elongate sheath; anda laser system in optical communication with a proximal end of theoptical fiber for coupling laser pulses into the optical fiber, the laser system and the optical fiber being configured such that the laser pulses are delivered by a distal end of the optical fiber with properties comprising:a wavelength selected such that absorption of the laser pulses by a laser-irradiated volume of the intravascular accumulation, when the intravascular accumulation is positioned adjacent to a distal end of the optical fiber, is predominantly due to excitation of vibrational modes of one or more constituents of the intravascular accumulation;a pulse duration that is shorter than a first time duration required for thermal diffusion out of the laser-irradiated volume and shorter than a second time duration required for a thermally driven expansion of the laser-irradiated volume;a pulse fluence and the pulse duration resulting in a peak pulse intensity below a threshold for ionization-driven tissue disruption to occur within the laser-irradiated volume;the pulse fluence being sufficiently high to cause local ablative disruption and liquification of the laser-irradiated volume of the intravascular accumulation.

83. An optical microcatheter system comprising:an optical fiber microcatheter comprising:an elongate sheath; andan optical fiber extending through the elongate sheath; and an outer tube housing at least a portion of the optical fiber microcatheter, wherein a distal portion of the optical fiber microcatheter is extendable beyond a distal end of the outer tube;wherein at least a distal portion of the elongate sheath is formed from a memory metal having a pre-defined curved shape, such that the distal portion of the optical fiber microcatheter is steerable by varying extension of the elongate sheath relative to a distal end of the outer tube.

84. The optical microcatheter system according to claim 83 further comprising a laser system in optical communication with a proximal end of the optical fiber for coupling laser pulses into the optical fiber.

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