Devices and methods for expansion of tubular anatomy

Abstract

A method and apparatus for dilating a tubular anatomical structure is described. The devices and methods may be used to draw blood clots in an artery of a mammal by using an ultraviolet (UV) laser beam transmitted by an optical fiber to concentrically irradiate an inner wall of the occluded artery. When a UV laser is projected as a ring beam onto the inner wall of the artery, expansion is caused by photophysical generation and release of nitric oxide from cells lined with the wall of the artery.

Description

Background Art

[0001] The present invention relates to dilation of tubular anatomical structures using ultraviolet (UV) laser light to photophysically stimulate the release of nitric oxide from smooth muscle cells on the inner wall of tubular anatomical structures, such as tubes or tubules, arteries, bronchioles, ureters, blood vessels, etc., resulting in relaxation (radial enlargement) of the structures. More specifically, the present invention relates to an optical fiber having a tapered tip for directing an annular UV beam to the inner surface of a tubular anatomical structure.

[0002] There are four types of approaches currently used to treat occlusive disorders. These include: (1) Use of high-intensity pulsed lasers to disrupt thrombi or emboli by ablation or photoacoustic shock (direct ultrasound is also used); (2) catheterization, angioplasty, and stenting to physically expand the lumen of blood vessels that have been constricted by atherosclerosis; (3) administration of thrombolytic or thrombolytic agents to chemically dissociate the clot, usually followed by administration of platelet inhibitors (also called antiplatelet agents) to prevent re-thrombus formation; and (4) Thrombectomy, in which the occlusive clot is removed by mechanical extraction, thereby restoring blood flow.

[0003] Each of these currently available methods is associated with potential deleterious effects on the vessel wall. For example, endothelial injury is currently unavoidable during thrombectomy and, in some cases, can render the outcome poor or the quality of recovery questionable.

[0004] There are two approaches that are now considered adequate for removing blood vessel obstructions in specialized clinical settings: (1) aspiration, in which negative pressure is applied proximal to the clot, and (2) Removal by a stent retriever (stentriever), in which a mesh-like network of expanded filaments is deployed within the clot, resulting in the clot being directly integrated into the mesh as the retriever is withdrawn, thereby removing the clot.

[0005] Either aspiration or stent retriever approaches may damage the arterial endothelium and arterial wall layers in different but unique ways, portending future negative effects on arterial structure and function. To this point, the primary focus has been on rapid clot removal by these mechanical means, with less consideration given to local or peripheral damage, especially to the normally thrombogenic endothelium. All improvements to these approaches have been strictly limited to mechanical improvements in aspiration efficiency, or the integrability of the stent retriever with the clot in an attempt to remove the entire clot with a single application (pass) of the device. Despite the recent apparent success of thrombectomy in removing arterial occlusions, these current procedures are imperfect. During clot extraction, the arterial endothelium may be damaged by mechanical friction. Vessel rupture is a known risk of any of the currently used interventional procedures (such as aspiration catheters or stent retrievers), and arterial wall perforation may occur during catheter insertion, especially when entering the entrance of a branch artery. In addition, patient recovery after current thrombectomy procedures is not optimal, especially in terms of behavior. Approximately 50% of patients show signs of residual injury, but this has not been an area of ​​concern until recently, as practitioners’ main concern has been the technicality of clot extraction. In this context, if the extraction is inefficient (requiring up to five passes, thus more mechanical interactions with the vessel wall), recovery is compromised.

[0006] Methods for addressing the damage and risk problems caused by previously known procedures have been proposed. For example, U.S. Pat. No. 6,539,944 describes the use of ultraviolet (UV) lasers (with or without additional agents) to dissolve occlusive thrombi in arteries. In other words, the UV laser itself is used to promote the dissolution of thrombi by means of its photophysical production of a thrombin inhibitor, nitric oxide (NO), which is a free radical that destabilizes adjacent platelet aggregates into individual platelets when secreted from irradiated smooth muscle cells in the arterial wall. This patent is incorporated herein by reference in its entirety.

[0007] There is a need in the art for a device and method for dilating a tubular anatomical structure containing smooth muscle cells during treatment of a patient while reducing and minimizing damage to the anatomical structure and reducing the risk of subsequent harm to the patient while undergoing a medical procedure. This can be accomplished by an expansion system according to the present invention. Preferably, the system of the present invention can minimize contact between the mechanical device of the system and the anatomical structure being dilated, thereby providing a minimal contact expansion system. For example, when prepared with such a system, thrombectomy using an aspiration catheter, stent retriever, or other mechanical thrombus extractor can be more easily achieved and with less endothelial damage, where UV laser rather than mechanical pressure directly causes dilation of the occluded artery. Preparing the artery for a subsequently deployed thrombectomy device in this manner helps to reduce friction and chemical bonding, and therefore less mechanical damage to the arterial wall before, during, and after clot removal. Summary of the invention

[0008] The present invention is particularly useful for dilating arteries using an optical fiber that can deliver UV light in the form of a ring-shaped laser beam to the arterial wall to reverse vasospasm consistent with hemorrhagic stroke, or to facilitate the removal of blood clots (thrombi) from the vasculature. A method of dilating a tubular anatomical structure using an optical fiber with a tapered tip to create a ring shape and deliver a laser beam to the inner wall of the tubular anatomical structure is also part of the present invention.

[0009] The device and method can be particularly useful in thrombectomy procedures performed on partially or completely occluded arteries for the treatment of stroke, myocardial infarction and other vascular occlusive disorders, particularly thrombi formed within the vasculature of the brain. It can also be useful for dissolving distal microvascular thrombi known to occur in hemorrhagic stroke as a manifestation of "early brain damage".

[0010] Thus, the present invention includes a fused silica optical fiber for carrying UV laser light, wherein the optical fiber has a distal end, wherein the distal end is configured as an inverted cone (i.e., a negative cone lens) or an everted cone, both of which are capable of emitting UV laser light as a cone-shaped beam. The emitted cone-shaped UV laser beam impinges on the inner wall of a tubular anatomical structure in an annular or ring-like configuration.

[0011] The tapered distal end of the optical fiber may be provided as a tip that is separate from the optical fiber itself, i.e., not part of the optical fiber, but optically coupled and preferably physically coupled and connected to the distal end of the optical fiber so that the tip is in optical communication with the optical fiber. Preferably, the tip is configured to have a distal end formed as an everted cone capable of emitting UV laser light as a tapered beam.

[0012] Preferably, the optical fiber of the present invention or the tip coupled thereto may include diamond at its distal end to optimize the emission of a conical beam, for example, the size, shape, emission angle or intensity of the beam may be modified and even improved by using diamond as the material of the tip or using a diamond-like material such as zirconium oxide. Alternatively, the tip may be made of a UV-transparent polymer material, such as a specialty plastic with a high refractive index.

[0013] Preferred embodiments of the fiber tip of the present invention are in the shape of an inverted cone (e.g., a negative axicon) capable of emitting an annular beam into water at an emission angle β up to 56° from the central longitudinal axis of the fiber. An everted conical tip may emit light at an angle β up to 71.5°. These angles are necessarily approximate, as the natural angular spread of a laser beam may exceed the critical angle for total internal reflection, thereby reducing some portion of the beam power.

[0014] The greater the angle allowed by Snell's law, the thinner the projection of the ring beam onto the irradiated surface, with a corresponding increase in laser intensity. Preferably, the inverted tapered tip is capable of emitting an annular "ring" beam into the water at an emission angle β ranging from 20° to 56° from the central longitudinal axis of the fiber; the limit of the emission angle range is 71.5° for the outer cone. With such emission angles, the ring-shaped fiber or tip of the present invention is capable of emitting an annular beam of maximum allowed intensity onto the inner wall of a tubular anatomical structure.

[0015] The present invention further relates to an expansion system comprising a thrombectomy catheter modified to a system that uses an optical fiber to carry a UV laser, the optical fiber having a distal end or including a tip at its distal end, wherein the optical fiber or the tip is configured in a conical shape for emitting the UV laser as a beam having a conical trajectory. An expansion system comprising the optical fiber of the present invention can configure the distal end or tip of the optical fiber as an inverted (inwardly protruding) cone or an externally convex cone. An expansion system comprising the optical fiber of the present invention can be employed in conjunction with an aspiration thrombectomy catheter or a stent retriever. Preferably, the expansion system of the present invention minimizes physical contact with the expanded anatomical structure, but still allows the UV laser to impinge on the structure. Because the impingement and resulting expansion can be continuous (>1 day), a preferred embodiment of the present invention is referred to as a "minimal contact continuous expansion system." Therefore, a preferred embodiment of the system includes a "minimal contact continuous expansion system."

[0016] In use, the expansion system of the present invention can be used in a method for expanding a tubular anatomical structure in a patient. The method according to the present invention comprises the following steps: - providing a catheter housing containing a UV transparent balloon expanded with a UV transparent gadolinium-based contrast agent, into which is inserted an optical fiber for carrying a UV laser, wherein the optical fiber has a distal end or tip with a tapered configuration; and - UV laser energy is emitted as a circular beam of uniform intensity through the balloon (which is expanded by the gadolinium contrast agent so as to be adjacent to the inner wall of the tubular anatomical structure) onto the smooth muscle cells in the inner wall of the tubular anatomical structure. This will stimulate the release of nitrite (NO2 - ) stores, whereby nitric oxide (NO) causes relaxation of smooth muscle cells and dilation of tubular anatomical structures. Dilation can be achieved even if the endothelium is damaged; the NO photophysically generated by UV light exposure functionally reproduces the NO normally produced by the endothelial enzyme nitric oxide synthase.

[0017] The method may be adapted or applied to an endovascular thrombectomy procedure, further comprising the steps of: - positioning the UV fiber optic dilation system within about 1 to 10 vessel diameters of a clot within an artery containing the clot; - expanding the UV-transparent balloon catheter to the inner wall of the artery with a UV-transparent gadolinium contrast fluid, which is sufficient to stop blood flow but does not dilate the artery due to mechanical pressure, - Bursts of UV light energy are emitted as laser beams through the wall of the gadolinium-expanded balloon and onto the smooth muscle cells in the arterial wall to stimulate the production of nitrite (NO2 - ) produces NO from the reserve, thereby stimulating active dilation of the arteries and this active dilation can be observed; and - Mechanical removal of the clot (e.g., by thrombectomy), thereby restoring circulation to the arterial trunk and its branches (recirculation).

[0018] The UV-transparent balloon catheter is first deployed into the tubular structure so that the tapered tip of the inserted optical fiber is centered to ensure uniform irradiation intensity around the perimeter of the structure. The balloon can be expanded to the inner diameter of the tubular structure with UV-transparent gadolinium contrast to ensure visibility on x-ray examination. The UV irradiation is then conducted through the balloon fluid and into the wall.

[0019] The method of the present invention is preferably performed by directing UV light onto the vessel wall within about 1 and about 4 vessel diameters away from the clot. The method can be performed using continuous UV light emission or UV light emission that is acousto-optically Q-switched (pulsed) at high frequency (5 to 25 kHz) with a pulse width greater than 40 nanoseconds (to ensure transmission through silica optical fiber due to minimization of two-photon absorption), or as a quasi-continuous beam with a picosecond pulse width, such as pulsed at 100 MHz with a pulse width >10 picoseconds, or as a square wave lasting at least 2 to 15 seconds. In a preferred embodiment, the UV light is emitted at a wavelength of about 180 to 400 nm, more preferably at a wavelength of about 300 to 400 nm. A preferred embodiment emits the UV light using a frequency tripled Nd:YAG laser that emits light at 355 nm (close to the absorption maximum of NO-releasing substances (e.g., S-nitrosothiol)). The preferred incident intensity of the UV light is between about 3 watts per square centimeter and about 20 watts per square centimeter.

[0020]

[00136] Based on the methods described herein, it will be appreciated that the thrombectomy catheter used in a thrombectomy procedure may be an aspiration catheter or a catheter through which a stent retriever is inserted.

[0021] It is an object of the present invention to provide a less invasive or traumatic method for extracting thrombus from an artery of a mammal by non-mechanically opening a larger diameter path for invasive interventional devices and passage of the extracted thrombus. This and other objects of the present invention are provided by one or more of the embodiments described herein.

[0022] The present invention aims to optimize arterial integrity during and after thrombectomy by reducing frictional or chemical bonding resistance to mechanical extraction of an occlusive clot. The apparatus and methods of the present invention comprise providing UV laser irradiation of appropriate intensity to the inner wall of the artery proximal to the clot when an aspiration catheter is used or distal to the clot when a stent retriever is used (although simultaneous distal and proximal irradiation may be advantageous) while performing a thrombus extraction technique. UV laser irradiation by an annular beam whose axis is co-linear with the artery will cause significant dilation of the arterial wall within seconds, wherein the dilation effect will propagate proximally and distally to weaken or release friction and / or chemical bonding of the clot to the wall.

[0023] Another object of the present invention is to provide an aspiration catheter or stent retriever, which further includes an optical fiber capable of transmitting UV light to the distal end or tip of the catheter, wherein the UV light can be emitted for a short period of time, such as 2 to 15 seconds, during saline flushing or balloon catheter expansion to clear blood from the vessel wall (but without mechanical dilation of the artery), and is thus directed to the smooth muscle cells that constitute the vessel wall. A specific embodiment introduces the laser beam through an optical fiber deployed within the blood vessel, which includes a protruding (external) conical tip that can actually act as a diverging lens for the beam through one reflection and one refraction (in fact, a negative axicon). This design will produce a circumferential irradiation pattern as an expanding conical ring, thereby producing a ring-shaped laser beam on the wall of the tubular anatomical structure to which the beam is directed. The protruding conical output tip is preferably made of a UV transparent material with a refractive index n higher than fused silica, such as diamond, zirconium oxide, or a customized polymer material with n>2 that can be optically coupled to silica. As the exit angle β increases, the beam intensity and arterial dilation efficiency also increase, while the width of the beam projected along the arterial wall decreases because the annular area irradiated is also reduced. Any projected length along the arterial wall will cause dilation if the intensity criteria are met, but a larger beam exit angle favors greater intensity and therefore more efficient use of the beam.

[0024] The intensity of the UV ring beam around the circumference of the artery is intended to be constant to ensure reproducibility of the procedure. This is facilitated by centering the optical fiber with a UV transparent balloon catheter. If the structure is an artery, the expansion balloon will occlude blood flow but will not itself expand the artery. The arterial wall is then irradiated through the balloon wall with minimal contact with the artery.

[0025] These same considerations apply to the inverted tapered tip, but in diamond the maximum emission angle (e.g., about 56°) will be less than that of the outer tip (e.g., 71.5°). The intent is to provide two different ways to produce an expanded ring shaped beam, the relative benefits of which have been described above and can be evaluated for clinical application.

[0026] In another embodiment of the present invention, an optical fiber for emitting UV laser light is provided in a guidewire used in an arterial catheter. Preferably, this embodiment includes a guidewire formed as a hollow tube so that an axial cavity or lumen is formed through the entire length of the guidewire. An optical fiber with an external, inverted or etched (diffractive optical element-DOE) tapered tip according to the present invention as described herein can be arranged in the cavity of the hollow guidewire. The optical fiber can be attached to the cavity of the guidewire or can be removed from the cavity. In one embodiment, the optical fiber can be manually configured to a "locked position", whereby it is attached to the guidewire, and manually configured to an "unlocked position", thereby allowing the guidewire and the optical fiber to operate independently and separately from each other. It can be advantageous to arrange the optical fiber in combination in the guidewire by eliminating certain steps of the catheter insertion process. The combined guidewire and optical fiber can have a distal end configured to emit a conical UV laser beam.

[0027] In one embodiment, the distal end of the combined guidewire and optical fiber is configured as an outer cone. In another embodiment, the distal end of the combined guidewire and optical fiber is configured as an inverted cone capable of emitting a conical UV laser beam. In yet another embodiment, the combined guidewire and optical fiber includes a flat distal end on which concentric circular grooves (DOEs) are etched that serve as negative axicon lenses.

[0028] The distal end of the combination guidewire and optical fiber may include a separate tip in optical communication with the optical fiber. The separate tip in optical communication with the optical fiber may be diamond, zirconium oxide, or a polymer material (eg, plastic).

[0029] One aspect of the present invention relates to a method for reperfusing an arterial blood vessel distal to a thrombus, wherein the method comprises the following steps: i) providing optical fiber capable of carrying UV laser; ii) extending the optical fiber through the thrombus; iii) emitting UV laser light from an optical fiber distal to the thrombus to dilate the arterial blood vessel distal to the thrombus; and iv) Removal of blood clots; This allows blood to flow to the dilated arterial capillaries and reperfuse them.

[0030] In one embodiment, the method includes the steps of emitting UV laser light from an optical fiber proximal to the thrombus before extending the optical fiber through the thrombus. In another embodiment, after emitting UV laser light from an optical fiber distal to the thrombus, the optical fiber may be withdrawn to a position proximal to the thrombus, and then UV laser light may be emitted proximal to the thrombus. In one embodiment, the method may include emitting UV laser light from an optical fiber proximal to the thrombus before and after extending the optical fiber through the thrombus. In one embodiment, the method includes the thrombus being an occlusive thrombus.

[0031] The optical fiber can extend through the thrombus preferably to a distance suitable for the UV irradiation distal field, in which the reperfusion can be enhanced by dilation. Any emission or pulse of the UV laser in the process described herein can be repeated to produce the desired arterial dilation effect. The arterial blood vessels that dilate and undergo reperfusion are preferably arterioles. The nitric oxide produced by the interaction of the emitted UV laser with smooth muscle cells can also dissociate (by dethrombosis) or decompose the platelet clots formed in the arteries or arterioles distal to the thrombus, because nitric oxide inhibits thrombin, which is required for the strong intraplatelet binding via fibrinogen.

[0032] In the method for reperfusing an arterial vessel distal to a thrombus as described herein, an optical fiber may be provided in combination with a hollow guidewire as described above.

[0033] In the method for establishing recirculation or reperfusion in an occluded arterial vessel according to the present invention, the step of removing the thrombus is preferably performed using a thrombectomy device. The thrombectomy device for removing the thrombus may be a stent retriever or an aspiration catheter.

[0034] Another embodiment of the present invention is directed to a method for enhancing reperfusion (i.e., restoring circulation) in a small artery branch distal to a thrombus that cannot be directly treated by thrombectomy, wherein the method comprises the following steps: i) providing optical fiber capable of carrying UV laser; ii) extending the optical fiber through the thrombus occluding the aortic trunk; iii) emitting UV laser light from an optical fiber distal to the thrombus to dilate small branch arteries distal to the thrombus; and iv) removing the thrombus, Blood is thereby allowed to flow through the aortic trunk (ie, recirculation) and through dilated and dethrombosed distal arterioles and arteriolar branches, such as arterioles (which cannot be treated directly by thrombectomy), to establish reperfusion.

[0035] In one embodiment, the method includes the steps of emitting UV laser light from an optical fiber proximal to the thrombus before extending the optical fiber through the thrombus. In another embodiment, after emitting UV laser light from an optical fiber distal to the thrombus, the optical fiber may be withdrawn to a position proximal to the thrombus, and then UV laser light may be emitted proximal to the thrombus. In one embodiment, the method may include emitting UV laser light from an optical fiber proximal to the thrombus before and after extending the optical fiber through the thrombus. In one embodiment, the method includes the thrombus being an occlusive thrombus.

[0036] Any emission or pulse of the UV laser in the process described herein can be repeated to produce the desired arterial dilation effect. The arterial vessels that dilate and undergo reperfusion are preferably branch arteries and arterioles. The UV laser can also be emitted to destabilize the platelet clot formed in the artery or arteriole distal to the thrombus (by dethrombosis).

[0037] In the methods for reperfusing small artery branches distal to a thrombus as described herein, an optical fiber may be provided in combination with a hollow guidewire as described above.

[0038] In the method for reperfusing the small artery branch distal to the thrombus according to the present invention, it is preferred to use a thrombectomy device to perform the step of removing the thrombus from the aortic trunk. The thrombectomy device for removing the thrombus can be a stent retriever or an aspiration catheter. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1A The upper half of the z-plane cross section of a laser ring beam (generated by an optical fiber with an external tapered tip having a cone half angle α) with a Gaussian intensity distribution G0 is shown, which produces an extended Gaussian beam profile G when impinging on the inner wall of an artery with a radius R. w It should be noted that the beam has a 2θ w The polar angular spread of the ring beam is cylindrically symmetric about the optical axis, with its central maximum emitted at an angle β. The intensity profile of G0 is plotted at a scale of 1 / 9. G at point "p" w The intensity is r w =(z–z o )sinβ, and also (z 2 +R 2 ) 1 / 2 function.

[0040] Figure 1B Figure 1 shows the axial ray tracing of a laser in a protruding (external or everted) tapered tip fiber. The dashed line (OO*) traces the path of an ideal laser ray at the output end of a silica fiber with a tapered tip (total apex angle = 2α). As long as the incident angle θ1 is greater than the critical angle θ at the silica / water interface crit (64.653°) (and hence by checking α < 90° – θ crit ), the light beam will follow total internal reflection at point P, and then enter the water-based medium from point Q, θ crit=64.653°. The locus of points defined by O* produces a ring-shaped beam when rotated about the optical axis. N1 and N2 are the normals to the top and bottom surfaces of the cone. From the figure, it is checked that α+θ1=90° and ω=180°-2θ1, so δ=3θ1-180°=90°-3α. It is also checked that the ring beam trajectory is a conical surface defined by the angle β(α)=θ1-α-γ(α). γ(α) is expressed as sin -1 {(n1 / n2)cos 3α}. According to Snell's law, β(α) can now be determined from the half angle α of the fiber's tapered tip.

[0041] Figure 2A An externally tapered tip machined on a 36° full apex taper angle (2α) fused silica optical fiber in accordance with an embodiment of the present invention is shown.

[0042] Figure 2B Shown by Figure 2A Figure 1 shows a UV laser ring beam in water produced by an external tapered tip as shown in Figure 2. Table 1 shows the values ​​of α, β(α) and the angles of reflection and refraction for pure silica fibers, and Table 2 shows β(α) when the tip is optically coupled diamond. The range and value of β(α) for diamond (up to 71.5°) is significantly increased compared to silica itself (up to 48.4°).

[0043] Figure 3 Optical properties of inverted tapered tip fibers are shown, showing the path of reflected and refracted laser light (entering from the right) in a fused silica fiber with an inverted tapered tip or a tip made of diamond, where the beam enters water (saline) to the inner wall of an artery. The maximum emission angle β (α) of diamond into water is about 56°, which is far greater than the maximum emission angle from silica alone (25.4°); see Table 3.

[0044] Figure 4A , Figure 4B and Figure 4C Fiber optic tip placement and intravascular UV irradiation in the basilar artery (BA) of three dogs are shown. The dilation induced by UV irradiation is semilocal; for a basilar artery of length ~40 mm, the dilation can extend even up to 60 mm from the trajectory of ring beam irradiation of the adjacent (vertebral) artery.

[0045] Figure 5The initial deployment of a balloon catheter over a guidewire (dark grey) inserted near an arterial occlusion (thrombus) prior to UV laser-facilitated thrombectomy is shown. The balloon is partially inflated. When the balloon is inflated or nearly inflated, the guidewire will effectively be centered in the artery. At this point, the guidewire can be withdrawn and replaced with a UV emitting fiber in order to dilate the obstructing tortuosity (if present) to reduce resistance to further insertion of the guidewire in order to further track the optimal route of the UV emitting fiber and subsequent thrombectomy device through the artery.

[0046] Figure 6 Shows Figure 5 The balloon catheter is fully inflated over a centered guidewire, and the guidewire is withdrawn and replaced by an optical fiber (white line) that emits UV laser light from a tapered tip that is synthesized to produce a ring beam (elliptical slash track) at the desired angle β near the occlusion (thrombus). The output end of the fiber can be placed as close to the thrombus as the balloon allows, but UV ring beam irradiation will cause continued arterial dilation starting at <4 diameters up to 40 diameters from the thrombus. At 3 to 20 W / cm 2 At a beam intensity of 100 nm, expansion will occur within seconds and extend into the thrombus segment. The optical fiber is then withdrawn, and the thrombectomy device is then mounted over the deflated balloon. In this configuration, an aspiration catheter will be introduced to extract the thrombus, as the occluded arterial segment is dilated and there is now less frictional resistance. To deploy the stent retriever, the guidewire must penetrate the thrombus (possibly near the edge) and deploy the balloon thereon, and the other steps are performed as described. Here, expansion distal to the thrombus will allow the stent retriever to be deployed at a larger diameter, ensuring that the thrombus can be maximally intercepted and completely extracted with less fragmentation as long as the integrability of the stent retriever is retained. Similarly, given the possibility of fragmentation, aspiration procedures may benefit from distal irradiation as well as proximal irradiation because the suction force is not evenly distributed along the thrombus.

[0047] Figure 7 A pictorial overview of the application of UV laser-induced dilation in thrombectomy to minimize wall damage due to mechanical friction is provided.

[0048] Fig. 8A It refers to a combination of a hollow guidewire and an optical fiber, wherein the optical fiber is arranged inside the hollow guidewire.

[0049] Figure 8B Represents a combined hollow guidewire and optical fiber, wherein the optical fiber disposed within the hollow guidewire has an external tapered tip.

[0050] Figure 8C Represents a combined hollow guidewire and optical fiber, wherein the optical fiber disposed within the hollow guidewire has an inverted tapered tip.

[0051] Fig.8D Represents a combined hollow guidewire and optical fiber, wherein the optical fiber disposed within the hollow guidewire has an etched tip that acts as a negative axicon lens (ie, a diffractive optical element - DOE).

[0052] Fig. 9A Shown is a front view of the distal end of an optical fiber etched into concentric rings of V-shaped grooves formed in the fiber to create a diffractive optical element (DOE) that acts as a negative axicon lens.

[0053] Fig. 9B Shows Fig. 9A A cross-sectional perspective view of an optical fiber. DETAILED DESCRIPTION

[0054] The present invention relates to a device and method for dilation of a tubular anatomical structure, such as an artery, wherein dilation is induced by directing an ultraviolet (UV) laser beam of appropriate intensity to the wall of the tubular anatomical structure without causing functional damage to the cells of the structure. The device, system or method of the present invention can be used on anatomical structures, such as anatomical tubes, tubes or tubules, blood vessels, such as arteries, bronchioles, ureters, vessels, etc.

[0055] The preferred embodiment employs a fused silica optical fiber including an inverted tapered tip. The tip preferably comprises a UV transparent material with a high refractive index in optical contact with the fused silica optical fiber. Preferred for the tip is a UV transparent and very hard material with a high refractive index, such as diamond (refractive index of 2.48 at 355nm) or zirconium oxide (refractive index of 2.3 at 355nm), or a custom designed high refractive index (n>2) polymer material. Such a tip can provide the ability to produce an exit angle (half-taper angle) of a UV ring beam up to 56° (using an inverted tapered tip) or 71.5° (using an everted tapered tip), both tips being made of diamond.

[0056] A preferred embodiment of the present invention relates to an optical fiber, preferably having a diameter of 10 to 100 um, more preferably 50 to 100 um, for transmitting UV laser light to the distal end or tip of the optical fiber and emitting a conical UV laser beam, which impinges on the inner wall of a tubular anatomical structure in the form of an expanding annular ring or annular beam. The optical fiber is preferably a solid fused silica optical fiber. In a preferred embodiment, the solid optical fiber used is not a hollow optical fiber, nor does the solid optical fiber include a hollow optical fiber as any part or extension thereof.

[0057] To achieve this annular beam formation, the distal end of the fused silica optical fiber can be formed into a tapered shape; for example, an external tapered shape (protruding outward), or it can be an inverted tapered shape (protruding inward). Figure 1AUsing a silica optical fiber with an external tapered tip 101 positioned within a microcatheter 104, the upper half of a z-plane cross-section of a laser ring beam is shown having a Gaussian intensity distribution G0 generated by the optical fiber with an external tapered tip having a cone half angle α. The distribution G0 impinges on the inner wall 102 of an artery with a radius R to produce an extended Gaussian beam profile G w 103. It should be noted that the beam has a 2θ w The ring beam is cylindrically symmetric about the optical axis, with its central maximum emitted at an angle β. G at point "P" w The intensity is r w =(z–z o )sinβ, and also (z 2 +R 2 ) 1 / 2 As shown, the optical fiber 101 is positioned proximal to the thrombus 105 (T) for use.

[0058] Figure 1B yes Figure 1A Detailed view of a fused silica fiber with an external tapered tip 101 shown in Figure 1, demonstrating laser axial ray tracing in a protruding (external) tapered tip fiber. The dashed line (OO*) traces the path of an ideal laser ray at the output end of a silica fiber with a tapered tip (total apex angle = 2α). As long as the incident angle θ1 is greater than the critical angle θ at the silica / water interface crit (64.653°) (and hence by checking α < 90° – θ crit ), the light beam will follow total internal reflection at point P, and then enter the water-based medium from point Q, θ crit =64.653°. The locus of points defined by O* produces a ring-shaped beam when rotated about the optical axis. N1 and N2 are the normals to the top and bottom surfaces of the cone. From the figure, it is checked that α+θ1=90° and ω=180°-2θ1, so δ=3θ1-180°=90°-3α. It is also checked that the ring beam trajectory is a conical surface defined by the angle β(α)=θ1-α-γ(α). γ(α) is expressed as sin -1 {(n1 / n2)cos 3α}. According to Snell's law, β(α) can now be determined from the half angle α of the fiber's tapered tip.

[0059] Figure 2A is a photograph of an optical fiber 200 according to the present invention, showing an externally tapered tip 201 on a 36° full apex taper angle (2α) fused silica optical fiber according to an embodiment of the present invention.

[0060] Figure 2B Shown by Figure 2A FIG. 2 is a diagram of a UV laser ring beam generated by an optical fiber with an external tapered tip in water within a glass container 205. The UV laser beam is converted into an expanded ring shape 210 as shown in FIG. Figure 2B , shown as a diffuse ring on fluorescent paper; the ring beam can then irradiate the inner circumference of the artery after blood displacement using saline injection or a UV-transparent balloon filled with UV-transparent gadolinium-based contrast agent.

[0061] Table 1 below provides the path extent of the beam in the fused silica outer tapered tip for the fiber half-taper angle α, and the angles associated with one total internal reflection and one refraction, resulting in the beam exiting the tip at an angle β(α). Ring beam cross section along the arterial wall (angular width 2θ w , see Figure 1A ) can vary from a Gaussian profile to a super-Gaussian "top hat" profile, i.e., the typical output pattern of a multimode fiber, which at maximum expression implies a substantially constant intensity over the ring width. These intensity patterns are not critical to the generation of the expansion, but they do affect the average and peak powers of the beam and their upper limits.

[0062] Figure 1A , Figure 1B 2 shows an external convex conical tip according to an embodiment of the present invention. A sharp external conical tip made of silicon dioxide (full apex angle <40°, half cone angle <20°; see FIGS. 1 and Figure 2A ) may break and / or become entangled due to intravascular obstructions (if any). A maximally passivated external silica tip (full apex angle of approximately 50°) is preferred (see Table 2). Breakage can be avoided with a tip made of a very hard material such as diamond, zirconia, or a high refractive index (n>2) polymer material (e.g., plastic), but entanglement may still be possible, depending on the complementary device array used. In practice, the optical fiber is introduced through a catheter, which provides isolation and therefore protection.

[0063] Alternatively, the tapered tip may be inverted (protruding inwardly) at the distal end of the optical fiber, such as Figure 3As shown. Preferably, the fused silica optical fiber 301 includes an inverted diamond conical tip 310, because this design can avoid being trapped by intravascular obstacles and is less likely to be damaged during insertion or deployment. Such a tip is capable of emitting an annular (ring-shaped) beam into water using an emission angle of up to 56° from the diamond tip (see Table 3). The inverted fused silica conical tip can produce an emission angle between 20° and 24° relative to the central longitudinal axis of the optical fiber (see Table 3). The efficiency of the beam intensity and expansion (and associated clot dissolution) process increases with the emission angle projection of the ring beam of UV light onto the inner wall of the tubular structure (i.e., the artery), so it is desirable to maximize the emission angle within the physical limits allowed by the UV transparent high refractive index optical fiber tip material (fused silica, diamond, zirconia or custom polymer material). The tip can be made of a UV transparent high refractive index (n>2) material coupled to a conventional optical fiber, wherein the coupled tip and optical fiber are optically connected to each other. The coupled tapered tip of the silica fiber can bulge outward from the distal end of the fiber and emit an unobstructed ring beam at an angle of up to about 48° relative to the longitudinal axis of the fiber (Table 1). If the tip is composed of diamond (Table 2), a wider emission angle range of up to about 71.5° can be achieved.

[0064] Optical fibers including tapered tips (bulging outward (everted) or bulging inward (inverted)) can be used in the minimal contact sustained dilation system of the present invention, for example as part of a subsequently deployed arterial thrombectomy catheter system. The width of the annular or ring beam emitted by the optical fiber of the present invention depends on the fiber radius and angle α of the tapered optical fiber. This feature can be advantageous because the dilation effect in any tubular anatomical structure (including arteries) is driven by the beam intensity and can occur very quickly (<1 second), depending on the concentration of photophysically produced nitric oxide (NO) in the cells lining the tubular anatomical structure (e.g., the arterial wall). Irradiation at a given intensity will cause a corresponding dilation, which itself can propagate proximally and distally from the area contacted by the annular beam via a transnitrosylation reaction.

[0065] In a preferred embodiment, an optical fiber including an inverted tapered tip or a blunt everted tapered tip can be used with a balloon catheter including a UV transparent balloon in conjunction with an aspiration thrombectomy catheter. Preferably, a guidewire introduced in a segment proximal to the occlusion can be centered by the UV transparent balloon catheter and expanded with a UV transparent gadolinium-based contrast agent, whereby the guidewire is replaced by the optical fiber.

[0066] Another preferred embodiment is a dilatation system of the present invention comprising an inverted tapered tip or a blunt everted tapered tip in combination with a balloon catheter and used in sequence with a stent retriever. In this embodiment, the guidewire makes the initial penetration, where it must be centered in the expanded balloon catheter, and is then replaced by the optical fiber so that the UV ring beam properly impinges on the inner wall with uniform circumferential intensity.

[0067] Another aspect of the present invention relates to a method for performing an endovascular thrombectomy procedure, wherein the method comprises the steps of: -Provide thrombectomy catheters compatible with UV-conducting optical fibers; - expanding the UV transparent balloon catheter to the inner wall of the artery with a UV transparent contrast fluid, which is sufficient to stop blood flow but does not dilate the artery due to mechanical pressure; - Positioning a UV fiberoptic thrombectomy catheter within one to four vessel diameters of a clot contained within the vessel; - emitting UV light energy as a ring beam onto smooth muscle cells in the inner wall of an artery to cause the formation and release of nitric oxide (NO) and thereby dilate the artery, regardless of whether the endothelium (a common source of NO) is intact and whether blood is present; and - Remove the clot.

[0068] The above procedures can be performed in preparation for the use of an aspiration catheter or stent retriever.

[0069] Figure 4A , Figure 4B and Figure 4C Deployment of our fiber optic device to achieve intravascular 355 nm UV laser irradiation in the basilar artery (BA) 401, 402, and 403 at baseline in three dogs, respectively (for each, the BA origin is indicated by an *). The dilation caused by the subsequent UV irradiation was semilocal; for a basilar artery of length ~40 mm, the dilation could extend to 60 mm ( Figure 4B and Figure 4C ). Figure 4B and Figure 4C This indicates that vertebral artery constriction prior to UV irradiation prevented the fiber tip from entering the basilar artery ostium. While for dog A, fiber tip 411 could be placed 22% distal to the BA origin, which was optimal, for dogs B and C, fiber tips 421 and 431 could only be placed within 52% and 34% of the respective BA length proximal to their origin (*). For 12 to 20 W / cm 2 With the irradiation intensity of 1.5 Å, the average dilation reached 94% of the baseline after starting from 78%, and although it decreased linearly over a 40 mm range, dilation was still observed at the end of the BA.

[0070] Figure 5 The initial deployment of a balloon catheter 510 over a guidewire 520 inserted near an arterial occlusion (thrombus) 530 is shown prior to UV laser-facilitated thrombectomy. The balloon is partially inflated (shown here as not contacting the inner wall of the artery 540). When the balloon is inflated or nearly inflated, the guidewire will effectively be centered in the artery. At this point, the UV emitting fiber can replace the guidewire and dilate the obstructing tortuosity (if present) to reduce resistance to the guidewire, and the guidewire can temporarily replace the UV fiber to further track the best route through the artery toward the thrombus, and then the UV fiber is reinserted, followed by the thrombectomy device.

[0071] Figure 6 Shows Figure 5 The balloon catheter 510 is fully inflated over the guidewire so that the guidewire is centered, and the guidewire has been replaced by an optical fiber 610 that emits UV laser light from a tapered tip that produces a ring beam 620 at the desired angle β. The output end of the fiber can be placed as close to the thrombus 530 as the balloon allows, but the UV ring beam irradiation will cause continued dilation, starting from <4 diameters away from the thrombus up to 40 diameters. At 3 to 20 watts / cm 2 At a beam intensity of 100 nm, expansion will occur within seconds and extend into the thrombus segment. The optical fiber is then withdrawn, and a thrombectomy device (e.g., an aspiration catheter) is then installed over the deflated balloon microcatheter, now with less frictional resistance due to the expansion of the occluded arterial segment. Alternatively, to deploy the stent retriever, a guidewire must penetrate the thrombus through the distal end and deploy a balloon thereon, and the other steps are performed as described. Here, the UV-induced expansion distal to the thrombus will allow the stent retriever to be deployed at a larger diameter, thereby ensuring maximum interception of the thrombus and complete extraction as long as the integrability of the stent retriever is preserved.

[0072] Figure 7 A pictorial overview of the steps taken by the present invention to apply ultraviolet laser-induced dilation to thrombectomy in order to minimize wall damage due to mechanical friction is provided. Figure 7 Demonstrated the use of Figure 5 and Figure 6 The steps of the method of the present invention are performed by the balloon catheter shown in Figure 7In step A of the device, a thrombus 701 is shown as being located in the middle cerebral artery 702 before the thrombectomy catheter of the present invention is deployed. A microguidewire 720, which is commonly used for balloon catheters, is introduced through the internal carotid artery 721 and positioned proximal to the thrombus 701 (step B). In step C, a UV transparent balloon 730 is then introduced over the microguidewire 720, as in normal use of the device, and is also positioned proximal to the thrombus 701. Step D shows that the balloon catheter is then inflated 740 to contact the inner wall of the blood vessel (artery) 721, so that blood flow is significantly or completely obstructed between the balloon and the vessel wall. The UV laser is deployed according to the method described herein, so that a ring beam is emitted to contact the inner wall of the blood vessel, and the blood vessel partially expands 722 (propagating in both directions from the area contacted by the UV laser ring beam). Using a stent retriever or an extraction procedure as shown by example only in step E, aspiration thrombectomy catheter 750 can be used in its conventional manner to extract thrombus 701, which is shown as being removed from middle cerebral artery 702 in step F. The dilation caused by UV laser irradiation can facilitate the removal step.

[0073] Advantageously, the dilation method may provide reduced mechanical friction, thereby minimizing damage to the arterial wall. Another advantage is that the platelet component of the clot will also dilate (see U.S. Patent 6,539,944), and the portion closest to the arterial wall will be partially degraded into single platelets (by dethrombosis) and therefore less adherent to the wall and thus less frictional resistance to the extraction process. No emboli will be generated.

[0074] In the method according to the invention, the UV light emission may be of very short duration, such as 2 to 15 seconds, preferably about 5 seconds, or may be repeated, as long as the light path is cleared of blood in either case by contact with the balloon or by saline injection. The laser irradiation intervals may be filled by a continuous wave laser beam, or by a beam which itself consists of a plurality of continuous MHz mode-locked pulses (with a width of about 10 picoseconds), which are referred to as quasi-continuous beams, or by a plurality of continuous 5 to 25 KHz pulses (with a width of up to 100 nanoseconds), which are referred to as acousto-optic Q-switched beams. The UV light is preferably directed directly onto the vessel wall within about 20 vessel diameters of the thrombus. More preferably, when a balloon is used, the UV light is directed directly onto the vessel wall within about 4 vessel diameters of the thrombus. In a preferred method, the vessel is an artery that is partially or completely occluded by a clot.

[0075] UV light is emitted at a wavelength of about 180 to 400 nm, and preferably at a wavelength of about 300 to 400 nm. In a preferred embodiment, a frequency tripled Nd:YAG laser emitting light at 355 nm is used to emit the UV light. (Other Nd-containing crystals exist, such as alexandrite.) NO production has been measured to reach a maximum at 350 nm; however, laser UV light at a wavelength of 350 nm is currently unavailable, and a wavelength of 355 nm can only be used with a slight decrease in efficiency. Newly developed lasers at 349 nm and 360 nm exist, but are not yet reliable enough for clinical use. Other UV-generating lasers that can be used with the present invention (but not to the extent of ablation) include XeF lasers (351 nm) and continuous wave (CW) argon ion lasers (351 nm, 364 nm). Any diode laser or dye laser can also be used as long as the output can be obtained in the UV range required for the non-ablative vasodilation effect. Currently, diode lasers cannot produce wavelengths in the optimal region. However, if the physical difficulties in manufacturing are overcome, diode lasers can also be used and will be much smaller than the lasers proposed above.In principle, any laser that emits UV radiation directly or as a result of frequency doubling or tripling can be used.

[0076] In the apparatus or method of the present invention, the average incident intensity of UV light is about 3 W / cm2 to about 20 W / cm2. 2 )between.

[0077] The device and method of the present invention can be used in conjunction with the prior administration of a pharmaceutically acceptable thrombolytic agent that aids in the lysis of (fibrinous) clots. The discharge of clot fragments is a concern, and our platelet-dethrombotic process can avoid the discharge of clot fragments. The preferred thrombectomy process is to remove the clot without the complications of debris caused by thrombolytic agents.

[0078] One specific embodiment introduces the laser beam through an intravascularly deployed optical fiber that includes a protruding (external) conical tip that, by one reflection and one refraction, can effectively act as a diverging lens for the beam (i.e., a negative axicon lens). This design will produce a circumferential irradiation pattern as an expanding conical ring, thereby producing a ring-shaped laser beam on the wall of the tubular anatomical structure at which the beam is directed. The protruding conical output tip is preferably made of a UV transparent material with a higher refractive index than fused silica, such as diamond, zirconium oxide, or a custom polymer material with n>2 that can be optically coupled to silica (e.g., plastic). As the beam exit angle increases within the limits dictated by Snell's law, the beam intensity at the wall and the efficiency of arterial dilation increase because the distance to the wall, the width of the beam projected along the arterial wall, and therefore the area irradiated are all reduced.

[0079] These same considerations apply to the inverted tapered tip, but the maximum emission angle will be less than that of the outer tip.The intent is to provide two different ways to produce an expanding ring shaped beam, the relative benefits of which have been described above and can be evaluated for clinical application.

[0080] Preferred fiber tips include an inverted tip configuration ( Figure 3 ), the inverted tip configuration is less likely to obstruct during use, although its deployment via a guide catheter should avoid this possibility as well as the potential for arterial perforation.

[0081] Another embodiment is a fused silica optical fiber with an external convex tip ( Figure 1B ), its unobstructed maximum emission (half cone) angle is about 48.4° (see Table 2, but the limit is 50.3°). When the tip is sharp (full apex cone angle is less than 40°, see Figure 2A ), if a brittle material is used, the tip may be subject to breakage due to mechanical contact. This situation can be remedied by an externally tapered tip made of a very hard material with a high refractive index, such as diamond. An everted diamond tapered tip will allow beam exit angles up to 71.5°. Of course, as the bluntness increases (increase in the full cone apex angle), the external tip (including the silica itself) will be more resistant to mechanical damage.

[0082] UV light is activated by nitrite (NO2 -) is capable of photophysical release of nitric oxide (NO) at concentrations higher than those maintained by the endothelium during normal metabolism. This causes quasi-temporary (tens of minutes to hours) and semi-local dilation of the blood vessels. NO released from smooth muscle cells self-propagates through transnitrosylation reactions over local distances of up to several centimeters proximally and distally from the site irradiated with UV light. UV laser light is used to induce vasodilation in the vicinity of the occlusion, thereby reducing friction (or chemical bonding) with the arterial wall when a thrombectomy device is deployed to extract a blood clot. Thus, dilation of the blood vessel can facilitate separation of the clot from the vessel wall to which it is adhered, and facilitate easier and safer removal of the clot using a conventional aspiration catheter or stent retriever (by reducing the intensity and frequency of clot-vessel wall interactions). The present invention can advantageously reduce the late pathological and behavioral consequences of structural and functional damage to the endothelial and intimal structures of an occluded artery undergoing thrombectomy.

[0083] Dilation of the blood vessel increases the diameter of the vessel, which may also facilitate movement of the catheter into position, ie, allowing it to more easily navigate tortuosity (severe bends) or stenosis of the vessel.

[0084] To achieve the objects of the present invention, one novel aspect relates to an advantageous configuration for the tip of an optical fiber from or through which UV radiation is emitted. For example, it has been found that the use of an externally tapered tip constructed of a very hard but UV transparent material such as diamond can more easily provide an external (semi-conical) emission angle of up to 71.5° (relative to the fiber axis) and the resulting narrower projection of the ring beam of UV light on the inner wall of the artery. The preferred angle is preferably determined in conjunction with other components of the system (e.g., a UV transparent balloon expanded with a UV transparent gadolinium-based contrast agent).

[0085] In another embodiment of the present invention, the distal end of the optical fiber is covered with an inverted tapered tip. The inverted tapered tip is preferably composed of a UV transparent high refractive index material such as diamond, zirconium oxide, or a custom polymer material (e.g., plastic) and is capable of emitting a ring beam at an emission angle of up to 56° (from diamond) relative to the longitudinal axis of the optical fiber.

[0086] Another object of the present invention is to provide an optical fiber capable of transmitting UV light surrounded by a catheter, wherein the optical fiber is composed of an inverted tapered tip preferably composed of a UV transparent material high refractive index material such as diamond, zirconium oxide, or a customized polymer material (e.g., plastic) capable of emitting a ring beam for the cerebral arteries. The narrow beam width will concentrate the energy absorbed by the cells of the blood vessels so that even with a relatively low power laser, an effective amount of NO will be released for significant vasodilation to occur.

[0087] Another object of the present invention is to provide an expansion system which may include an aspiration catheter or a stent retriever in the final step, in front of which is a balloon catheter surrounding a fused silica optical fiber capable of transmitting UV light to the distal end of the optical fiber. Preferably, the expansion system comprises a fused silica optical fiber for UV irradiation, wherein a tapered tip is provided at the distal end of the optical fiber. Preferably, the tapered tip is made of a UV transparent material having a high refractive index, such as diamond, zirconium oxide, or a custom polymer material (e.g., plastic). More preferably, the tapered tip is an everted tapered tip configuration. Alternatively, the fused silica optical fiber component of the expansion system of the present invention comprises a thrombectomy aspiration catheter or a stent retriever system comprising an optically contacted inverted tapered tip made of a UV transparent high refractive index material, such as diamond, zirconium oxide, or a custom polymer material (e.g., plastic).

[0088] Yet another object of the present invention is to provide a UV transparent balloon catheter encasing a UV compatible optical fiber that is combined with an aspiration thrombectomy catheter as part of a single dilation system. Preferably, the UV compatible optical fiber combined with the aspiration thrombectomy catheter or stent retriever will incorporate a diamond or zirconia (or high refractive index polymer material) everted tapered tip at its distal end.

[0089] In a preferred embodiment, a UV transparent gadolinium-based contrast fluid can be used to expand the balloon catheter; the balloon wall then displaces blood, which provides an unobstructed path for the UV laser to travel to the inner wall of the artery. According to the present invention, the balloon is inflated for this purpose and also centers the tapered tip; it is not inflated to expand the inner diameter of the vessel wall. The gadolinium contrast agent is confined to the balloon and is therefore isolated from the blood flow. In this embodiment, the balloon material and contrast material are sufficiently transparent to UV light to allow the UV light to pass through the wrapped catheter and balloon unimpeded.

[0090] Another object of the present invention is a method of performing a thrombectomy procedure on a mammal in need thereof, wherein the method comprises the steps of: a) Providing an expansion system as described herein b) positioning the UV fiber optic balloon catheter within one to four vessel diameters of the clot within the occluded vessel; c) delivering square wave pulses of continuous or high repetition rate pulsed beam UV laser energy as a beam within a specified average intensity range onto smooth muscle cells lining the inner wall of a blood vessel to release NO from the cells and thereby cause dilation of the blood vessel; and d) Removal of the optical fiber and introduction of the thrombectomy device, e) and then remove the clot by mechanical extraction.

[0091] In one embodiment, the UV fiber expansion system preferably features a fused silica optical fiber with a diamond tapered tip that is capable of emitting a ring beam at an angle of up to 71.5° (for the outer tip) relative to the longitudinal axis of the optical fiber. For other known high refractive index materials such as zirconium oxide and custom polymer materials (e.g., plastics), this angle will be smaller.

[0092] The bursts of UV light energy in continuous or pulsed form may be emitted at an irradiation interval of about 2 to 20 seconds, preferably at least about 5 to 15 seconds, and more preferably about 8 to 12 seconds. A 10 second burst may be the most preferred emission duration of the UV beam for dilating a blood vessel to a sufficient diameter to reduce frictional interaction of the catheter with the vessel tortuosity or stenosis, or to promote local separation of a clot from the vessel wall.

[0093] In a preferred embodiment, the present invention comprises a dilation system comprising an aspiration catheter or stent retriever after a preparation period using a tapered tip optical fiber to supply an annular beam of UV irradiation. The tapered tip of the optical fiber may bulge inward or outward from the distal end of the optical fiber, depending on the desired emission angle and whether there are obstacles along the desired path.

[0094] In use, an optical fiber including a tapered tip can emit a tapered beam trajectory that irradiates a tubular anatomical structure as an annular or ring-shaped beam around the inner circumference of the tubular structure. Tubular anatomical structures that can be expanded with UV light are those that are lined with (smooth muscle) cells that are capable of storing nitric oxide (as nitrite) and releasing fully active nitric oxide (NO). Such expansion can be advantageously used to expand or dilate arteries near the location of a thrombus to facilitate easier and safer removal of the thrombus by reducing mechanical friction and chemical bonding to the thrombus. The thrombus can be an occlusive thrombus or a non-occlusive thrombus. Vascular expansion at or near the site of the thrombus within the blood vessel can at least partially loosen the adhesion of the thrombus to the vessel wall or separate the thrombus from the vessel wall, thereby facilitating the effective removal of the thrombus by conventional aspiration or stent thrombectomy catheter techniques currently used in the medical field. Peripheral damage to the occluded vessel should be minimized before, during and after extraction.

[0095] When irradiation with UV light is performed within about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 25 or 30 vessel diameters of a thrombus, an artery in the region of the thrombus may dilate. As used herein, the term "vessel diameter" refers to the outer diameter of an artery. Preferably, the vessel is irradiated within about 10 vessel diameters of the thrombus. More preferably, the vessel is irradiated between about 1 to 4 vessel diameters away from the thrombus. The vessel may be irradiated proximally or distally of the thrombus.

[0096] Since the UV-induced vasodilation effect can propagate distally (as well as proximally), branch arterial vessels can also be dilated by irradiating the main vessel at a distance of about 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 25, or 30 vessel diameters from the main thrombus. This phenomenon may be particularly useful in situations where the thrombectomy surgeon does not have feasible access to the branch artery or arteriole containing the thrombus and can access the main artery proximally.

[0097] Preferably, the UV beam is directed onto the inner surface of a tubular anatomical structure (such as an artery) by means of a beam transmitted via an optical fiber placed inside the blood vessel by means of a catheter. After irradiation but almost immediately thereafter and no more than a few seconds after irradiation with the laser beam, the blood vessel first expands at the irradiated portion and then continuously propagates itself over a distance of several centimeters in the proximal and distal directions.

[0098] Under normal physiological conditions, dilation is mediated by nitric oxide (NO) produced by the endothelium. In contrast, UV laser-mediated photophysical generation of NO is mediated by nitrite (NO2 - Regardless of the severity of endothelial damage or even when the endothelium is absent (completely destroyed), local NO concentrations up to 10 μM can be generated.

[0099] Nitrite photolysis in smooth muscle cells produces NO, S-nitrosation of thiols (RSH), resulting in the formation of S-nitrosothiols (RNSO), and local dilation via NO or its release from thionitrates (RSNO); these denitrosate other thiols, propagating the dilation radially, distally and proximally, by releasing more NO. This is a self-perpetuating chain process.

[0100] Photophysically generated nitric oxide can stimulate dilation waves both proximally and distally. Therefore, at a certain portion of the clot length, the frictional resistance to clot removal may be reduced. Therefore, the clot may be extracted with less force and thus with less mechanical damage to the artery than currently observed, with fewer future complications at this site or distally or even proximally thereof.

[0101] The ultraviolet laser beam used to dilate the artery and thereby treat the occluded vessel can be either continuous or pulsed. The use of pulsed lasers can reduce heat accumulation and consequent damage in the target and surrounding tissues. If a non-ablative pulsed laser is used, such as a quasi-continuous or acousto-optic Q-switched laser, the pulse rate can be any rate consistent with delivering an appropriate time-averaged intensity of irradiation to the target tissue while avoiding individual pulses of such high intensity that they cause permanent damage in the target tissue or to the optical fiber, i.e., damage that is irreversible within a physiologically relevant time frame (e.g., a period of hours to weeks).

[0102] The wavelength of the UV light is preferably in the range of 180 to 400 nm. More preferably, the UV light is in the range of 300 to 400 nm. Even more preferably, the UV light is about 340 to 370 nm, and most preferably about 350 to 360 nm. A frequency tripled Nd:YAG laser emitting radiation at 355 nm is particularly preferred.

[0103] Other UV lasers that can be used with the present invention (while avoiding ablation) include XeF lasers (351 nm), CW argon ions (351 nm, 364 nm), or CW krypton ions (351 nm, 356 nm). Any diode laser or dye laser can also be used as long as a non-ablative output can be obtained in the UV range required for the vasodilation effect. In principle, any laser that emits UV radiation directly or as a result of frequency doubling or tripling can be used.

[0104] For 355 nm UV laser irradiation, at an intensity of 7 (intensity of 3 to about 20 W / cm 2 ) stimulates dilation over a wide dynamic range, resulting in a Gaussian beam shape. However, the dilation effect is independent of the beam shape. At the upper limit, vacuoles are formed in smooth muscle cells, but the function is not impaired. The dilation effect depends on the average intensity. For example, it can be achieved at 20 W / cm 2 A 100 nanosecond pulse train at 7 Hz and a peak power of 5 kW were used without causing functional damage.

[0105] The path of the laser beam can be cleared of blood, for example, by flushing a small amount of saline solution through the catheter opening where the beam emerges immediately prior to irradiating the vessel wall or thrombus.

[0106] The intensity of the UV irradiation is preferably adjusted to provide the minimum dose required to achieve the desired degree of vasodilation within the desired time frame prior to thrombectomy. For example, using a frequency tripled Nd-YAG laser, approximately 5 watts / cm 2 12 to 20 W / cm2 of incident light produces about 20% to 30% dilation in arterioles (this dilation can be reversed by NO inhibitor drugs).2 Higher intensity (equivalent to an energy flux of up to 1 J / cm per pulse at a pulse frequency of 20 Hz) 2 ) can produce a similar increase in the diameter of larger arteries (about 1.5 mm in diameter), but at more than 20 W / cm 2 The intensity of the injection may change the structure of the vessel wall (formation of small vacuoles in the smooth muscle tissue), but no functional impairment was observed.

[0107] You can then adjust the time in increments (e.g., 2 W / cm 2 or larger increments) until adequate dilation of the vessel is observed within a reasonable time (e.g., within 5 seconds). The irradiation periods may be continuous, i.e., continue until the dilatory effect stabilizes, or may be intermittent, in which case the duration of one or more irradiation periods may also be varied at a given incident intensity in order to obtain an adequate response; dilation already induced will be preserved and amplified. The appropriate vasodilatory response (i.e., the extent of dilation and its kinetics of onset and duration) may be determined by the user; however, many users generally consider a response in the range of 20% to 40% increase in vessel diameter within 5 to 10 seconds to be appropriate.

[0108] The methods of the present invention are suitable for treating various disease conditions involving arterial occlusion. Examples of such conditions include stroke, myocardial infarction, and occlusion or spasm of any peripheral artery (large or small).

[0109] In the method of using the suction catheter of the present invention, a balloon catheter can be introduced, and the suction catheter can then be introduced just above the catheter, below the balloon portion. As the balloon expands, a UV fiber can then be introduced into the balloon. When the UV transparent balloon expands to exceed the diameter of the suction catheter in front of the tortuous bend or stenosis, the UV fiber is then centered in the artery, and non-flowing blood is displaced from the projected light path. The UV beam can then flash for a few seconds to obtain enough expansion to allow the thrombectomy catheter used in the subject expansion system to pass. Here, the balloon does not push against the artery to expand it, but is simply a means to promote the displacement of blood away from the artery, while the laser ring beam follows an optically free path to non-mechanically expand the artery. Balloons are very common, but can damage tissue if over-inflated.

[0110] Once the UV light is emitted onto the wall of the vessel and absorbed, the vessel will dilate and propagate dilation regardless of the subsequent presence of blood or blood flow. This process can be used to more easily navigate tortuous bends or stenosis on the way to the clot. Thus, structural and endothelial damage is minimized from the entry point to the target site. Once the clot is reached, a final irradiation is performed, including an optional saline flush, and then the clot is extracted by a suction catheter.

[0111] For use in conjunction with the stent retriever, the guidewire penetrates the clot and moves just past the clot by one or several centimeters. The balloon catheter is then inserted and expanded just distal to the clot, and the guidewire is replaced with a UV fiber to irradiate the distal segment. The UV fiber is then withdrawn, and the stent retriever is passed through the balloon catheter to replace the UV fiber at the clot location. The balloon catheter can be withdrawn just proximal to the clot, and the stent retriever mesh expands spontaneously or in a controlled manner during catheter withdrawal to a diameter suitable for uniformly and symmetrically extracting the clot, which enables the stent retriever mesh to better capture the entire clot and ensure extraction efficiency.

[0112] Another benefit is the ability to use UV irradiation at locations where it is difficult to pass a catheter toward the target clot location; this will promote safer clot extraction. A catheter that appears to be too large for the artery at some unexpected point can still be used after UV dilation. If the catheter sizing error occurred at the outset, UV dilation can be used to dilate the artery without replacing the current catheter.

[0113] The external convex conical tip of the silica optical fiber (α = 18°, Figure 1A , Figure 1B and Figure 2A ) was designed for intravascular deployment via a microcatheter. Table 1. Launch angle β(α) (in degrees) of 355 nm light launched from a silica fiber (n1=1.475) with an external tapered tip into water (n2=1.333) or air (n2=1.00); α=half angle at the apex of the tapered tip; β(α)=π / 2-α-γ(α), δ=π / 2-3α, and γ(α)=sin -1 {(n1 / n2)cos 3α}. It should be noted that the limit of α is (90°-the critical angle between glass and water 64.653°)=25.347°.

[0114] To increase β (and thus reduce the area subtended by the ring beam on the arterial wall), a short (about 0.5 mm) everted tapered segment made of a UV-transparent material with a higher refractive index must be optically bonded to the silica fiber. The best choice is diamond, which has a refractive index of n d =2.48.

[0115] Table 2 presents the same calculations above for a beam launched from an external diamond tip into water. Table 2. Launch angle β(α) (in degrees) of 355 nm laser light launched from an external diamond-tipped silica fiber (n1 = 2.48) into water (n2 = 1.333) (see Figure 3 ); β(α)=90-α-γ(α), δ=90-3α, and γ(α)=sin -1 {(n1 / n2)cos 3α, where α = half angle at the apex of the cone tip. It should be noted that the critical angle of incidence for total internal reflection (diamond to water) is 32.51°.

[0116] Table 3 shows the path range of 355 nm laser light emitted into water (saline) from an inverted cone tip made of silica and diamond toward the arterial wall. The emission angle β is a function of the inverted cone half angle α (in Figure 3 ). Some practitioners may prefer a reverse tapered tip design because the tip is much less likely to become stuck on an obstruction (if any) than an external tapered tip. Table 3. Launch angle β in degrees calculated from Snell's law as a function of the inverted cone half angle α for silica and diamond tips for a ring beam launched into water toward the arterial wall ( Figure 3 ). α=90°-θ1, where θ1=θ g,d And g = glass (silicon dioxide), d = diamond, θ2 = θ 水 , and β=θ 水 -θ s,d .

[0117] The calculations are complementary to those for the external diamond conical tip and show that the emission angle β is even larger and therefore provides increased beam intensity at reduced distances from the external conical tip compared to the inverted conical tip (both are preferred over silica alone). However, β is very sensitive to α, which means that the input beam must be well collimated to minimize the polar angle spread 2θ w (See Figure 1A ), and the internal tapered tip must be ground very precisely to ensure high surface quality and thus minimize beam scatter. Here, θ crit =θ 金刚石 =32.51° and β =57.49°. If θ 金刚石 =32.50°, then θ 水 =88.44°, α=57.50° and β=55.94° (Table 3).

[0118] As an alternative to the tapered tip optical designs shown so far for generating ring beams, we propose the combination of diffractive optics with optical fibers. Diffractive optics involve etching a geometric pattern on a flat-ended optical fiber, the tip of which can be fused silica itself or other light-coupled UV-transparent high-refractive index (n>2) substances such as zirconia, diamond, or custom-designed polymer materials (e.g., plastics), by any of several methods (e.g., photolithography, electron beam evaporation) to obtain the desired diffraction phase profile. The pattern on the end of the fiber resembles a circularly symmetric bas-relief structure, that is, a series of concentric ring-like structures of variable depth and radius, because material must be precisely removed to form the desired diffraction phase profile. The desired output is a very sharp annular Bessel beam with minimal sidebands. For beams leaving the tip at angles β>40°, it is likely that a high-refractive index substance such as the last three substances (described previously) was used. To our knowledge, ring beams greater than β=15° have not yet been generated in any medium by this technique, but manufacturers of diffractive optics are willing to expand their capabilities. A flat-ended diffraction pattern mounted on a suitable high-refractive-index material, which may be the best form of the device, would consist of an end cap of a fused-silica optical fiber immersed in water.

[0119] Either the external or internal tapered tip can produce a ring beam over a range of angles to the arterial wall, with a practical upper limit of about 48° for silicon dioxide and about 71.5° for diamond for the external tip, but preferably near the maximum angle will be used. For the internal (inverted) diamond tapered tip, the range can be up to 56°, which is preferred. The direct benefit of firing the beam at the maximum acute angle is a reduction in the ring beam width, and therefore a higher laser intensity. Since the dilation process is entirely dependent on the beam intensity (between 3 and 20 watts / cm 2 ), so lower power (and potentially more compact) lasers can be used more efficiently. The internal tapered tip is designed for safety, as in previous work we noted that silica external tips can become damaged. Presenting a device that cannot be damaged by attachment to any other device or tissue component upon insertion is clearly beneficial, as jamming is avoided and the tip structure is preserved. However, these effects are less likely to occur in very hard materials such as diamond.

[0120] These and other embodiments and applications of the present invention will become apparent to those skilled in the art in view of the description provided herein. A common but intractable aspect of hemorrhagic stroke is vasospasm (narrowing) of the main cerebral arteries. Blood ejected from a ruptured aneurysm into the subarachnoid space (for example) migrates along the arteries, and hemoglobin from lysed red blood cells enters the arterial wall and scavenges nitric oxide, thereby causing spasm. This condition is currently untreatable; systemic dilator drugs can (and have) lowered blood pressure to the point of morbidity. Another currently untreatable aspect is early brain damage (i.e., preceding vasospasm) mediated by platelet occlusion of microvessels in the brain. Despite numerous animal studies, no drug will dissolve platelet thrombi in humans. The UV laser approach is intended to definitively treat both of these extremely difficult conditions. We have shown that vasospasm is reversed within three days in dogs with hemorrhagic stroke. We also show that platelet clots can indeed be dissolved by UV laser-induced nitric oxide because it inhibits thrombin, an enzyme required to maintain interplatelet fibrinogen / platelet GPIIb-IIIa crosslinks.

[0121] We propose that, in addition to arterial recirculation, UV irradiation of the trunk just proximal to the junction of the trunk to the feeding artery and its microvascular bed will also allow and enhance blood reperfusion to areas that cannot be treated directly by thrombectomy, due to the self-replication of nitric oxide at a certain distance and its associated vasodilation, thus increasing the possibility of tissue survival. For example, patients with ruptured cerebral aneurysms will be treated urgently by standard care interventional devices (such as coils and stents). After fixing the aneurysm, the neurointerventionalist can continue to position the microcatheter used for coiling to the more distal side of the aneurysm. The microcatheter can be replaced with a UV transparent balloon catheter, and the microguidewire can be replaced with an optical fiber. Distal UV irradiation will dissolve the microvessels occluded by platelet emboli in the vascular region, thereby enhancing reperfusion and improving the patient's clinical outcome. Three to twenty-one days after aneurysm treatment, cerebral vasospasm may cause vascular constriction. Again, using a UV transparent balloon catheter and optical fiber, UV irradiation proximal to the vascular constriction will dilate the artery and restore the artery to its original (or greater than original) diameter, thereby restoring blood circulation.

[0122] Atherosclerotic vascular disease may result in narrowing or stenosis (narrowing) of the arterial lumen due to the formation of plaque. Current approaches require enlargement of the lumen by balloon angioplasty followed by stent placement to secure the opening. Angioplasty and stent placement first require passing a microguidewire through the stenosis to gain distal access. When the stenosis is moderate to severe, it is difficult to safely pass the guidewire through the stenosis without dislodging the atherosclerosis. During stenting procedures for atherosclerotic disease, the passage of the guidewire and device through the plaque may be facilitated by dilating the artery with UV (given that existing scar tissue will allow such dilation). If the plaque is calcified, it may be very rigid and incompressible. In addition, balloon dilation may cause adjacent non-atherosclerotic segments to expand and stretch to the point of structural distortion. A common response to this trauma is hypertrophy, an abnormal healing response that is known to eventually occlude the opening created by the stent. We propose that non-mechanical dilation of arteries (even diseased arteries) through the nitric oxide pathway will significantly facilitate access to atherosclerosis from the distal side with intravascular devices. The NO pathway will also minimize vascular distortion and excessive manifestation of the healing response, and thus preserve the desired lumen and its service life. Endothelial damage to adjacent non-atherosclerotic segments will also be reduced. For example, for patients with severe carotid atherosclerosis, a UV-transparent balloon catheter can be positioned proximal to the stenosis with the aid of a microguidewire. The guidewire can be replaced with an optical fiber. Subsequent UV irradiation will expand the arterial wall and widen the narrow gap. The optical fiber can then be replaced with a microguidewire, and the guidewire can now more easily pass through the widened stenosis for distal access. The balloon catheter can then be removed and the plaque can be treated by a guidewire delivery device delivery system. The same system can usually be used to safely place stents to ensure circulation through the stenosis, but now the stent can be placed in a dilated blood vessel without causing the usual endothelial damage. This will avoid restenosis, which is a very common complication of stent deployment in current practice, and avoid the need to replace the stent within 3 to 5 years.

[0123] Inhaled nitric oxide can be used to treat pulmonary hypertension and acute respiratory distress syndrome, especially in pediatric patients. The inhaled gas diffuses through the alveolar capillary membrane and causes vasodilation, resulting in a decrease in pulmonary vascular resistance and increased blood perfusion in the ventilated lung segments. This may improve the patient's blood oxygen level. The proposed invention can be used to dilate segments and branches of the pulmonary artery in a more targeted manner. The pulmonary artery and its branches can be accessed through the femoral vein via catheterization of the right heart. A balloon catheter can then be positioned in the target pulmonary artery branch. An optical fiber can be introduced into the inflated balloon in order to irradiate the arterial wall with a ring beam. The resulting vasodilation will propagate proximally and distally from the area contacted by the ring beam via nitrosation.

[0124] Another aspect of the present invention relates to a modified guidewire that can be used in arterial catheterization. Typically, the guidewire is fed through the blood vessel to reach the target location, and then the catheter is screwed into the guidewire to perform the intended process, for example, a thrombectomy procedure using a thrombectomy device (such as a stent retriever or an aspiration catheter). The process of the present invention includes removing the guidewire from the catheter and replacing the guidewire with an optical fiber that can emit a UV laser as an extended ring beam with sufficient intensity to dilate the blood vessel. An alternative to the steps of removing the guidewire and replacing the guidewire with an optical fiber is to set the optical fiber in the guidewire as a combined guidewire / optical fiber. A preferred embodiment of this aspect of the present invention includes a guidewire having a hollow core so that an axial cavity or lumen is formed through the entire length of the guidewire, and the axial cavity or lumen is configured in the form of a flexible metal tube structure. Contained in the guidewire is a silica optical fiber, the tip of which is preferably made of a UV transparent high refractive index material (such as diamond) and is designed to emit a ring beam. The flexible metal tube structure can be composed of a flexible metal alloy (such as nitinol). The optical fiber can be arranged to be unattached to the guidewire, or preferably attached relative to the inner wall of the hollow guidewire as desired. In this configuration ("locked position"), the guidewire and the optical fiber are integral to each other and work together as a single unit when placed within the blood vessel. In one embodiment, the optical fiber can be manually configured to a "locked position" whereby it is attached to the guidewire, and manually configured to an "unlocked position" to allow the guidewire and the optical fiber to be operated independently and separately from each other.

[0125] The distal segment of the integrated or combined guidewire and fiber optic embodiment is Fig. 8A The y-plane (sagittal) cross section is shown. Figure 8B , Figure 8C and Fig.8D Different fiber tip configurations are depicted, each having the effect of a negative axicon lens that projects a divergent laser beam onto the inner wall of the artery. A divergent laser beam is produced regardless of whether the output mode of the fiber is multimode or single mode (as adjusted by the fiber thickness). Fig. 8AShown is a combined hollow guidewire and optical fiber 800 according to an intended application, wherein the outer surface can be coated hydrophilically or hydrophobically. Optical fiber 802 is covered by a polymer coating 803 (cladding) ensuring total internal reflection, and the optical fiber is arranged in the hollow core 801 of a flexible metal guidewire. In one embodiment, the inner portion 804 of the guidewire includes a metal coil of the hollow core of the guidewire so that for a desired specific application, the main requirements of torsion, flexibility, formability, shape retention, and tactile feedback can be met. The distal end of optical fiber 805 (defined by the limits of its cladding 803) is substantially consistent with the end of a hemispherical guidewire cap 806. Cap 806 can be made of soft flexible material, intended to minimize the mechanical damage to the cavity (such as an artery) it is detecting, until the target position is reached.

[0126] In a preferred embodiment, the guidewire and optical fiber combination comprises a solid fused silica optical fiber having sufficient length to emit UV laser light from its distal end without being obstructed by the guidewire cap 806, while also not extending significantly beyond the guidewire cap 806, thereby protecting the blood vessels from the optical fiber tip during movement and placement at the target location. The apex of the outer tapered tip can be shielded from the guidewire until placed at the desired location. Any accumulation of particulates should be removed by flushing the catheter with saline.

[0127] The distal end of the combined guidewire and optical fiber can include a separate tip in optical communication with the optical fiber. The separate tip in optical communication with the optical fiber can be diamond, zirconium oxide, or a polymer material (e.g., plastic). For example, a diamond tip can be optically coupled to a silica optical fiber 802 and configured in three ways to produce an expanded laser beam. Figure 8B An optical fiber with an external tapered tip 811 is shown. Light 807 is shown entering and leaving the optical fiber by a total internal reflection. The internal reflection angle α and the emission angle β are shown at their maximum values ​​(32.5° and 71.5°, respectively). In a preferred embodiment, the combined guidewire and optical fiber can be configured in a locked position so that the tip apex can protrude slightly to pass through hard obstacles (such as calcified atherosclerosis). In one embodiment, the distal end of the optical fiber can be configured as an external tapered tip capable of emitting UV light in a tapered beam as described above.

[0128] Figure 8C 802 has an inverted tapered tip 812 in optical contact with the optical fiber. In one embodiment, the distal end of the optical fiber can be configured as an inverted tapered tip capable of emitting UV light in a cone-shaped beam as described above.

[0129] Fig.8D A diffractive optical element (DOE) is shown formed on a flat etched tip 809 of a diamond segment optically coupled to a silica host fiber to provide a 3D image from an input TEM00 Laser beam 808 generates a UV laser ring beam 810 similar to the ring beam generated by a negative axicon lens. Any of several known methods can be used in the field of rapid imaging to convert TEM 00 The laser beam is converted to a Bessel intensity distribution (ring). The shaping pattern may include concentric tilted rings (each ring may be a cascade of thin flat rings of successive thicknesses) formed on the flat output end of the optical fiber, with a mechanical resolution of about 5 μm. In one embodiment, the ring beam may subtend a full cone angle of at least 90°. In a preferred embodiment, the ring beam may subtend a full cone emission angle of 120° or more to enhance the expansive UV ring beam intensity, thereby requiring less laser input power. The fiber diameter, mode (which may be multimode), and output ring thickness are not critical to producing an operationally effective ring beam output. In one embodiment, the distal end of the optical fiber may be configured as a flat distal end having concentric circular grooves etched into the flat distal end, wherein the flat distal end is a diffractive optical element (DOE) as described above.

[0130] Fig. 9A and 9B An embodiment of an etched end portion of an optical fiber according to the present invention is shown. Fig. 9A A front view of the distal end of an optical fiber 800 is shown, which is etched into concentric rings of V-grooves formed in the optical fiber to create a diffractive optical element (DOE). The central V-groove 902 forms an inverted cone in the center of the optical fiber. Each concentric V-groove outside the center has a peak 901a and a valley 901b.

[0131] Fig. 9B Further demonstrated Fig.8D Side view and Fig. 9A 800. The pattern of alternating peaks 901a and valleys 901b in the flat distal end of the optical fiber 800 can be further appreciated in this view. Preferably, each peak 901a has the same height as the other peaks 901a, and each valley 901b has the same depth as the other valleys 901b. Fig. 9B Solid fused silica optical fibers are also demonstrated.

[0132] Advantageously, the one-piece or combined guidewire and optical fiber embodiments can eliminate certain steps of conventional catheter insertion procedures. Wherein, conventional catheter insertion procedures require the following steps: (1) inserting the guidewire, (2) placing the catheter over the guidewire, and then (3) removing the guidewire from the positioned catheter, and (4) replacing the guidewire with the optical fiber to dilate the blood vessel, the combination of the optical fiber within the guidewire can eliminate steps (3) and (4) because there is no need to remove the guidewire from the catheter and replace it with the optical fiber. The time saved by eliminating steps (3) and (4) is beneficial to the user and patient undergoing the procedure.

[0133] Since the steps eliminated in the above-mentioned surgery save time and are beneficial to reperfusion, the combined guidewire / optical fiber of the present invention can reduce the incidence (about 50%) and severity of behavioral abnormalities associated with post-thrombectomy thrombectomy. These are confirmed at all levels of TICI flow conditions, even at level 3, which indicates that the main occluded artery is completely recanalized. However, TICI does not measure the blood return in its branch arteries or their arterioles, which is responsible for delivering nutrients directly to the tissue. Reperfusion is separate from the anterior recirculation and is currently not observable by angiographic techniques. Reperfusion is defined as the restoration of normal flow in arterial side branches and microvessels that cannot be approached or cleared by thrombectomy. Despite the recanalization of the aorta, the relative lack of reperfusion can well explain the variability of behavioral recovery. This is believed to be due to a variety of mechanisms, including microthrombosis or the embedding of emboli released in situ or from the extracted occluded thrombus in distal vessels. The goal of reperfusion is to save intervertebral tissue, which is metabolically static but not dead (infarcted), mainly due to retrograde filling of collateral circulation. However, if the subject area is already infarcted, reperfusion may induce very severe hemorrhagic consequences due to vessel wall degradation. Therefore, UV laser-induced dilation should be used only if the penumbra tissue is judged to be salvageable and hemorrhage is unlikely.

[0134] One aspect of the present invention relates to a method for reperfusing an arterial blood vessel distal to a thrombus, wherein the method comprises the following steps: i) providing optical fiber capable of carrying UV laser light; and ii) extending an optical fiber through the thrombus; and iii) emitting UV laser light from an optical fiber distal to the thrombus to dilate the arterial blood vessel distal to the thrombus; and iv) Removal of blood clots; Recirculation and blood flow are thereby permitted to dilated arterial vessels, including vessels that are not normally treatable by thrombectomy, and to allow reperfusion of the arterial vessels.

[0135] The optical fiber can extend through the thrombus preferably to a distance suitable for the UV irradiation distal field, in which reperfusion can be enhanced by expansion. Any emission or pulse of the UV laser in the process described herein can be repeated to produce the desired arterial expansion effect. The arterial vessels that expand and undergo reperfusion as described herein are preferably small branch arteries and arterioles. UV lasers can also be emitted to dissolve, dissociate, or decompose platelet clots formed in arteries or arterioles distal to the thrombus.

[0136] In one embodiment of the present invention, the method for reperfusing an arterial blood vessel distal to a thrombus further comprises the following steps: emitting UV laser light from an optical fiber proximal to the thrombus (inside the balloon catheter) before extending the optical fiber through the thrombus. Preferably, the arterial blood vessel proximal to the thrombus is irradiated with UV light for a time sufficient to dissolve the bound platelet layer.

[0137] In one embodiment, the method may include emitting UV laser light from the optical fiber proximal to the thrombus after extending the optical fiber through the thrombus and withdrawing the optical fiber to the proximal side of the thrombus. In another embodiment, the method may include irradiating the proximal side of the thrombus with UV laser light from the optical fiber before and after extending the optical fiber through the thrombus.

[0138] In another embodiment, the artery distal to the thrombus is irradiated with at least one UV light burst or several UV irradiation intervals as the optical fiber is withdrawn from the distal side of the thrombus to the proximal side of the thrombus. The artery distal to the thrombus is preferably irradiated for a time sufficient to dissolve the bound platelet layer. In a preferred embodiment, the UV light energy burst in continuous or pulsed form may be emitted at an irradiation interval of about 2 to 20 seconds, preferably at least about 5 to 15 seconds, and more preferably about 8 to 12 seconds.

[0139] In another embodiment, the method may include the additional step of emitting a UV laser to dissolve or break up aggregated platelet clots formed in arteries or arterioles distal to the thrombus. In one embodiment, the method includes the thrombus as an occlusive thrombus.

[0140] In one embodiment of the present invention, a method for reperfusing an arterial vessel distal to a thrombus includes an optical fiber disposed within a guidewire as described above.

[0141] Because the transnitrosative chain process produces nitric oxide along the path of the optical fiber, which can travel into the branch arteries, the distal segment and its branches can dilate, thereby preparing the branch arteries and arterioles to receive blood (reperfusion) when recirculation is achieved by thrombectomy.

[0142] In another embodiment of the present invention, a method for reperfusing an arterial vessel distal to a thrombus includes the step of removing the thrombus using a thrombectomy device. The thrombectomy device for removing the thrombus can be a stent retriever. In the case of deploying the stent retriever, the UV laser-induced expansion provides an increased space for deployment, which can enhance the conformability of the clot with less damage to the expanded arterial wall. Alternatively, in another embodiment of the present invention, the thrombectomy device can be an aspiration catheter. In the case of deploying the aspiration catheter, the UV laser-induced expansion can provide friction reduction at both ends of the clot, which should reduce the linear pressure currently required at the distal end and thereby inhibit fragmentation. All of these procedural aspects are intended to extract the clot with a minimum number of passes and also ensure enhanced distal reperfusion.

[0143] The above disclosures and examples generally describe the present invention and are provided for illustrative purposes and are not intended to limit the scope of the present invention. The present invention described herein can be practiced in the absence of any one or more elements, one or more restrictions not specifically disclosed herein. Therefore, for example, in each example herein, any one of the terms "comprising", "consisting essentially of" and "consisting of" can be replaced by any one of the other two terms. These terms and phrases are used as descriptive rather than restrictive terms, and are not intended to use such terms and phrases that do not include any equivalents of these features or parts thereof shown and described, but it is recognized that various modifications within the scope of the present invention are possible. Therefore, it should be understood that, although the present invention has been specifically disclosed by preferred embodiments and optional features, modifications and changes of the concepts disclosed herein may be adopted by those skilled in the art, and these modifications and changes are considered to be within the scope of the present invention defined by the claims.

Claims

1. A combined guide wire and optical fiber capable of carrying UV laser, wherein: The guide wire is formed as a hollow tube, and an optical fiber for carrying UV laser light from a UV laser source is arranged inside the hollow tube.

2. The combined guide wire and optical fiber capable of carrying UV laser according to claim 1, wherein: The hollow guidewire and the optical fiber capable of carrying the UV laser are attached to each other.

3. The combined guide wire and optical fiber capable of carrying UV laser according to claim 1, wherein: An optical fiber capable of carrying a UV laser has a distal end configured to emit a cone-shaped UV laser beam.

4. The combined guide wire and optical fiber capable of carrying UV laser according to claim 1, wherein: An optical fiber capable of carrying a UV laser has a distal end configured as an outer cone to emit a cone-shaped UV laser beam.

5. The combined guide wire and optical fiber capable of carrying UV laser according to claim 1, wherein: The optical fiber capable of carrying UV laser light has a distal end configured as an inverted cone to emit a cone-shaped UV laser beam.

6. The combined guide wire and optical fiber capable of carrying UV laser according to claim 1, wherein: An optical fiber capable of carrying UV laser light has a flat distal end including concentric circular grooves etched into the flat distal end.

7. The combined guide wire and optical fiber capable of carrying UV laser according to claim 3, wherein: The distal end of the optical fiber capable of carrying the UV laser light is provided as a separate tip in optical communication with the optical fiber.

8. The combined guide wire and optical fiber capable of carrying UV laser according to claim 7, wherein: The separate tip in optical communication with the optical fiber includes diamond.

9. The combined guide wire and optical fiber capable of carrying UV laser according to claim 7, wherein: The separate tip in optical communication with the optical fiber includes zirconium oxide.

10. A method for reperfusing an arterial vessel distal to a thrombus, the method comprising the following steps: - extending an optical fiber capable of carrying UV laser light through the thrombus; - emitting UV laser from the optical fiber distal to the thrombus to dilate the arterial blood vessel distal to the thrombus; - Remove the thrombus; This allows blood to flow to and reperfuse these dilated arterial vessels.

11. The method of claim 10, further comprising the steps of: - emitting UV laser light from the optical fiber proximal to the thrombus before extending the optical fiber through the thrombus.

12. The method of claim 10, further comprising the steps of: - After emitting UV laser from the optical fiber distal to the thrombus to dilate the arterial vessels distal to the thrombus, the optical fiber is withdrawn to a position proximal to the thrombus and UV laser is emitted from the optical fiber proximal to the thrombus.

13. The method of claim 10, wherein: The procedure of removing the thrombus is performed using a thrombectomy catheter.

14. The method of claim 14, wherein: The thrombectomy catheter is an aspiration catheter.

15. The method of claim 14, wherein: The thrombectomy catheter is a stent retriever.

16. The method of claim 10, wherein: These arterial vessels include arterioles.

17. The method of claim 10, wherein: The thrombus is an occlusive thrombus.

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