DEVICES AND METHODS FOR DILATING TUBULAR ANATOMICAL STRUCTURES - Patent application

Abstract

Described are methods and devices for dilating tubular anatomical structures. The devices and methods may be useful for extracting blood clots in mammalian arteries by concentrically irradiating the inner wall of the occluded artery using an ultraviolet (UV) laser beam delivered by an optical fiber. The dilation occurs as a result of the photophysical production and release of nitric oxide from cells lining the arterial wall when the UV laser light is projected as a ring beam onto the inner arterial wall.

Description

[Technical field]

[0001] 2. Background of the Invention The present invention relates to the dilation of tubular anatomical structures, such as tubes or tubules, arteries, bronchioles, ureters, vessels, etc., using ultraviolet (UV) laser light to photophysically stimulate the release of nitric oxide from smooth muscle cells lining the tubular anatomical structures, resulting in relaxation (radial expansion) of the structures. More particularly, the present invention relates to an optical fiber having a conical tip for directing an annular beam of UV light to the inner surface of the tubular anatomical structure. [Background technology]

[0002] Currently, four types of approaches are used to treat obstructive disorders. These are: (1) the use of high intensity pulsed lasers to disrupt thrombi or emboli, either by ablation or photoacoustic bombardment (direct ultrasound has also been used); (2) catheterization, angioplasty and stent placement to physically expand the lumen of blood vessels constricted by atheroma; (3) administration of thrombolytic or thrombectomy agents to chemically break down the clot, often followed by administration of platelet inhibitors (also called antiplatelet agents) to prevent rethrombosis; and (4) Thrombectomy, in which an obstructing thrombus is removed by mechanical extraction, thus restoring blood flow. Includes.

[0003] Each of these currently available methods is associated with potentially deleterious effects on the vessel wall: for example, endothelial damage is currently unavoidable during thrombectomy, providing poor efficacy or questionable quality of recovery in some circumstances.

[0004] Currently, two methods are used to remove vascular occlusions in a dedicated clinical setting: (1) aspiration, where negative pressure is applied proximal to the clot; and (2) extraction with a stent retriever, in which a mesh network of expanded wires is deployed within the clot, resulting in direct integration of the clot into the mesh as the retriever is retracted, thus removing the clot; is considered to be quite useful.

[0005] Either aspiration or stentriever techniques can damage the arterial endothelium and arterial wall layers in different but characteristic ways, suggesting future negative consequences in arterial structure and function. To date, the primary focus has been on rapid removal of the clot by these mechanical means, without any particular consideration of local or peripheral damage, especially to the normally antithrombotic endothelium. All improvements to these methods have been strictly limited to mechanical improvements in aspiration suction efficiency or stentriever integration with the clot in an effort to remove the entire clot with one application (pass) of the device. Despite the clear recent success of thrombectomy in removing arterial occlusions, these current procedures are not perfect. The arterial endothelium can be damaged by mechanical friction during clot extraction. Blood vessel rupture is a known risk of any of the currently used interventional procedures, such as aspiration catheters or stentrievers, and arterial wall perforation can occur during catheter insertion, especially when accessing the entry points to branch arteries. Furthermore, current patient recovery after thrombectomy procedures, especially behavioral, is not optimal. Approximately 50% of patients present with signs of residual damage, but this has only recently become an area of ​​concern, since the main focus of practitioners has been on specialized methods of clot extraction. In this context, recovery is compromised when extraction is inefficient (requiring up to five passes and therefore a much greater mechanical interaction with the vessel wall).

[0006] Methods have been proposed to address the problems of damage and risks resulting from known procedures. For example, U.S. Patent No. 6,539,944 describes the use of ultraviolet (UV) laser light with or without additional agents to break down occlusive thrombi in arteries. In other words, UV laser light itself is used to promote the breakup of thrombi using its photophysical generation of nitric oxide (NO·), a thrombin inhibitor, which destabilizes adjacent platelet aggregates into individual platelets when secreted from irradiated smooth muscle cells in the arterial wall. This patent is incorporated herein in its entirety by reference. Summary of the Invention [Problem to be solved by the invention]

[0007] What is needed in the art is an apparatus and method for expanding tubular anatomical structures, including smooth muscle cells, during the treatment of a patient, while reducing and minimizing damage to the anatomical structures and lowering the risk of resulting harm to the patient when undergoing a medical procedure. This can be accomplished with the expansion system according to the present invention. Preferably, the system according to the present invention can minimize contact between the mechanical device of the system and the anatomical structure to be expanded, thereby providing a minimal contact expansion system. For example, when prepared by such a system, where UV laser light and non-mechanical pressure directly induces expansion of an occluded artery, thrombectomy using an aspiration catheter, stentriever, or other mechanical thrombus extraction device can be achieved more easily with less endothelial damage. Preparing the artery in this manner for a later deployed thrombus removal device promotes reduced friction and chemical adhesion before, during, and after the retraction of the clot, and therefore less mechanical damage to the arterial wall. [Means for solving the problem]

[0008] BRIEF SUMMARY OF THE INVETION The present invention is particularly useful for dilating arteries using optical fibers capable of delivering UV light in the form of an annular laser beam to the arterial wall to reverse vasospasm associated with hemorrhagic stroke or to facilitate removal of blood clots (thrombi) from the vascular system. A method for dilating tubular anatomical structures using an optical fiber with a conical tip to generate an annular shape and deliver a laser beam to the inner wall of the tubular anatomical structure is also part of the present invention.

[0009] The devices and methods may be particularly applicable to the treatment of thrombi formed in stroke, myocardial infarction and other iso-occlusive disorders, particularly in the vasculature of the brain, in thrombectomy procedures performed on partially or completely occluded arteries. It may also be applicable to breaking up distal microvascular thrombi known to occur in hemorrhagic stroke as a manifestation of "early brain injury."

[0010] Thus, the present invention includes a fused silica optical fiber for carrying UV laser light, the optical fiber having a distal end configured as an inverted cone (i.e., a negative cone lens) or an inverted cone, both of which can emit the UV laser light as a cone beam, the emitted cone beam of UV laser light impinging on an inner wall of a tubular anatomical structure in a ring-shaped or annular configuration.

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

[0012] Preferably, the optical fiber of the present invention or a tip coupled thereto can have a diamond at its distal end to optimize the emission of the conical beam, for example, modifying the size, shape, emission angle, or intensity of the beam, and in some cases can be improved by the use of diamond or diamond-like materials such as zirconium oxide as the material for the tip. Alternatively, the tip can be constructed from a polymeric material that is transparent to ultraviolet light, for example a specialty plastic with a high refractive index.

[0013] A preferred embodiment of the optical fiber tip of the present invention has the shape of an inverted cone (e.g., a negative axicon) that can emit an annular beam into water at an emission angle β of up to 56° from the central longitudinal axis of the optical fiber. An inverted cone tip can emit light at an angle β of up to 71.5°. These angles are necessarily approximations because the natural angular spread of a laser beam can exceed the critical angle for total internal reflection, thereby reducing some portion of the beam power.

[0014] The greater the angle permitted by Snell's law, the thinner the projection of the ring beam on the illuminated surface with a corresponding increase in laser intensity. Preferably, the inverted cone tip is capable of emitting an annular "ring-like" beam into water with an emission angle β ranging from 20° to 56° from the central longitudinal axis of the optical fiber, with the outer cone terminating the emission angle range at 71.5°. This angle of emission allows the optical fiber or tip of the present invention to emit an annular beam of maximum allowable intensity onto the inner wall of a tubular anatomical structure.

[0015] The present invention further relates to a dilation system including a thrombectomy catheter modified as a system using an optical fiber to deliver UV laser light, the optical fiber having a distal end or including a tip at its distal end, the optical fiber or tip configured in a conical shape to emit the UV laser light as a beam with a conical trajectory. The dilation system including the optical fiber of the present invention may have the distal end or tip of the optical fiber configured as an inverted (inwardly projecting) cone or an outwardly projecting cone. The dilation system including the optical fiber of the present invention may be used in combination with an aspiration thrombectomy catheter or a stentriever. Preferably, the dilation system of the present invention minimizes physical contact with the dilated anatomical structure, but still allows the incidence of UV laser light on the structure. Since the incidence and resulting dilation can be sustained (>1 day), a preferred embodiment of the present invention is referred to as a "minimal contact sustained dilation system". Thus, a preferred embodiment of the system includes a "minimal contact sustained dilation system".

[0016] In use, the dilation system of the present invention may be utilized in a method for dilating a tubular anatomical structure within a patient's body. The method according to the present invention includes: - providing a catheter containing a UV-transparent balloon inflated with a UV-transparent gadolinium-based contrast agent into which an optical fiber for carrying UV laser light is inserted, the optical fiber having a distal end or tip having a conical configuration; - emitting UV laser light energy through a balloon (inflated with gadolinium contrast agent so as to be continuous with the inner wall of the tubular anatomical structure) as a circular beam of consistent intensity onto smooth muscle cells within the inner wall of the tubular anatomical structure, which induces nitrogen (NO2) absorption within the arterial smooth muscle cells. ーUV light stimulates the photophysical production and release of nitric oxide (NO·) from endothelial stores, thereby stimulating relaxation of smooth muscle cells and dilation of tubular anatomical structures. Dilation can also be achieved when the endothelium is disrupted, and NO· photophysically generated by exposure to UV light mimics in function the NO· normally generated by the endothelial enzyme oxynitrite synthase.

[0017] The method is: - positioning a UV fiber optic dilation system within an artery containing the clot to within about 1-10 vessel diameters of the clot; - inflating the UV-transparent balloon catheter with UV-transparent gadolinium contrast fluid to the inner wall of the artery sufficiently to stop blood flow but not to dilate the artery with mechanical pressure; - Nitrite (NO2) in smooth muscle cells - emitting bursts of UV light energy as a laser beam through the gadolinium-inflated balloon walls and onto smooth muscle cells within the wall of the artery to stimulate production of NO· from stores of NO·, thereby stimulating and allowing active dilation of the artery to be observed; - removing the clot mechanically (e.g., by thrombectomy), thereby restoring circulation (recirculation) to the trunk and its branches. The present invention may be adapted or applied in an endovascular thrombectomy procedure further comprising:

[0018] First, a UV-transparent balloon catheter is deployed within the tubular structure to center the conical tip of the inserted optical fiber to ensure uniform irradiation intensity around the circumference of the structure. The balloon can be inflated to the inner diameter of the tubular structure with a UV-transparent gadolinium contrast agent to ensure visibility in X-ray examination. UV irradiation is then administered through the balloon fluid into the wall.

[0019] The method of the invention is preferably carried out by guiding UV light onto the vessel wall within about 1 to about 4 vessel diameters away from the clot. The method can be carried out using continuous UV light emission, or acousto-optically Q-switched (pulsed) UV light emission at high frequency (5-25 kHz) with pulse widths 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 picosecond pulse widths, e.g., pulsed at 100 MHz with pulse widths greater than 10 picoseconds, or as a square wave over at least 2-15 seconds. In a preferred embodiment, the UV light is emitted at a wavelength of about 180-400 nm, more preferably at a wavelength of about 300-400 nm. A preferred embodiment emits the UV light using a frequency-tripled Nd:YAG laser emitting light at 355 nm (e.g., near the absorption maximum of NO·-releasing substances such as S-nitrosothiols). A suitable incident intensity of UV light is from about 3 to about 20 watts per square centimeter.

[0020] It should be understood that in accordance with the methods described herein, the thrombectomy catheter used in the thrombectomy procedure can be an aspiration catheter or a catheter through which a stentriever is inserted.

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

[0022] One of the objectives of the present invention is to optimize the integrity of the artery during or after thrombectomy by reducing the frictional or chemical bond resistance to mechanical extraction of the occlusive clot. The device and method of the present invention comprises providing an appropriately intense UV laser irradiation of the arterial inner wall proximal to the clot when using an aspiration catheter or distal to the clot when using a stentriever when performing a clot extraction technique (although it may be advantageous to irradiate in both distal and proximal directions). UV laser irradiation with a ring-shaped beam whose axis is collinear with the artery induces a pronounced dilation of the arterial wall in a few seconds, and the dilation effect propagates in the proximal and distal directions to weaken or release the frictional and / or chemical bond of the clot to the wall.

[0023] Another object of the present invention is to provide an aspiration catheter or stentriever that further includes an optical fiber capable of carrying UV light to the distal or tip of the catheter, where the UV light can be emitted for a brief period of time, e.g., 2-15 seconds, upon saline flush or balloon catheter inflation to clear blood from the vessel wall (but not to mechanically dilate the artery) and thus be directed to the smooth muscle cells that comprise the vessel wall. One particular embodiment introduces a laser beam through an optical fiber deployed within the vessel that includes a protruding (external) conical tip that can, with one reflection and one refraction, in effect, act as a diverging lens for the beam (in effect, a negative axicon). This design creates a circumferential illumination pattern as an expanding conical ring, thereby creating an annular beam of laser light on the wall of the tubular anatomical structure to which the beam is directed. The protruding conical output tip is preferably fabricated using a UV-transparent material with a refractive index n greater than fused silica, such as diamond, zirconium oxide, or custom polymeric materials with n greater than 2 that can be optically bonded to silica. As the exit angle β increases, the beam intensity and efficiency of arterial dilation also increases with decreasing width of the beam projected along the arterial wall because the ring-shaped area that is irradiated also decreases. Any projected length along the arterial wall will lead to dilation if the intensity criteria is met, but a larger beam exit angle promotes a higher intensity and therefore a more efficient use of the beam.

[0024] The UV ring beam intensity around the artery circumference is intended to be constant to ensure reproducibility of the procedure. This is facilitated by centering the optical fiber by a UV-transparent balloon catheter. If the structure is an artery, the inflated balloon seals off blood flow but does not, itself, inflate 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 cone tip as well, although for diamond the maximum emission angle (e.g., about 56°) will be less than that from the external tip (e.g., 71.5°).The intent is to provide two different approaches to generating a beam in the shape of an expanding ring, the relative benefits of which are discussed above and may be evaluated for clinical use.

[0026] In another embodiment of the invention, an optical fiber for emitting UV laser light is provided within a guidewire used in an arterial catheter. Preferably, this embodiment has the guidewire formed as a hollow tube such that an axial cavity or lumen is formed throughout the length of the guidewire. An optical fiber with an external inverted or etched (diffractive optical element-DOE) conical tip according to the invention described herein can be disposed within the hollow guidewire cavity. The optical fiber can be attached within the guidewire cavity or can be detachable therefrom. In one embodiment, the optical fiber can be manually configured into a "locked position" whereby it is attached to the guidewire and can also be manually configured into an "unlocked position" whereby the guidewire and the optical fiber can operate independently and separately from each other. The combination of an optical fiber disposed within a guidewire can be advantageous by eliminating certain steps in the catheterization process. The combined guidewire and optical fiber can have a distal end configured to emit a conical beam of UV laser light.

[0027] In one embodiment, the distal end of the combined guidewire and optical fiber is configured as an external cone. In another embodiment, the distal end of the combined guidewire and optical fiber is configured as an inverted cone that can emit a conical beam of UV laser light. In yet another embodiment, the combined guidewire and optical fiber has a flat distal end with a concentric circular groove (DOE) etched on top of it that acts as a negative axicon lens.

[0028] The distal end of the combination 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 polymeric material (e.g., plastic).

[0029] One aspect of the invention relates to a method for reperfusing an arterial vessel distal to a thrombus, the method comprising: i) providing an optical fiber capable of carrying UV laser light; ii) extending an optical fiber through the thrombus; iii) emitting UV laser light from the optical fiber distal to the thrombus to dilate the arterial vessel distal to the thrombus; iv) removing the thrombus; , thereby permitting blood flow to and reperfusion of the dilated arterial microvessels.

[0030] In one embodiment, the method includes emitting UV laser light from the optical fiber proximal to the thrombus prior to extending the optical fiber through the thrombus. In another embodiment, after emitting UV laser light from the optical fiber distal to the thrombus, the optical fiber can be retracted to a position proximal to the thrombus and then UV laser light can be emitted proximal to the thrombus. In one embodiment, the method includes emitting UV laser light from the optical fiber proximal to the thrombus before and after extending the optical fiber through the thrombus. In one embodiment, the method includes a thrombus that is an occlusive thrombus.

[0031] The extension of the optical fiber through the thrombus may preferably be to a distance suitable for UV irradiation of the far distal field where reperfusion may be promoted by dilation. Any emission or pulse of UV laser light in the process described herein may be repeated to produce the desired effect of arterial dilation. The arterial vessel that is dilated and experiences reperfusion is preferably an arteriole. Nitric oxide, which is also produced by the interaction of the emitted UV laser light with smooth muscle cells, can disintegrate or break up (by thrombectomy) platelet clots formed in the artery or arteriole distal to the thrombus, because it inhibits thrombin, which is required for strong platelet-platelet binding via fibrinogen.

[0032] In the methods for reperfusion of an arterial vessel distal to a thrombus described herein, a fiber optic 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 invention, the step of removing the thrombus is preferably carried out using a thrombectomy device. The thrombectomy device used to remove the thrombus may be a stentriever or an aspiration catheter.

[0034] Another embodiment of the invention relates to a method for promoting reperfusion (i.e., restoring circulation) in small arterial branches distal to a thrombus that cannot be directly treated by thrombectomy, the method comprising: i) providing an optical fiber capable of carrying UV laser light; ii) extending an optical fiber through a thrombus occluding a major artery; iii) emitting UV laser light from the optical fiber distal to the thrombus to dilate small branch arteries distal to the thrombus; iv) removing the thrombus; , thereby allowing blood flow (i.e., recirculation) through major arterial trunks, such as arterioles (which cannot be directly treated by thrombectomy), and through dilated and thrombed distal small arteries and arterial branches to establish reperfusion.

[0035] In one embodiment, the method includes emitting UV laser light from the optical fiber proximal to the thrombus prior to extending the optical fiber through the thrombus. In another embodiment, after emitting UV laser light from the optical fiber distal to the thrombus, the optical fiber can be retracted to a position proximal to the thrombus and then UV laser light can be emitted proximal to the thrombus. In one embodiment, the method includes emitting UV laser light from the optical fiber proximal to the thrombus before and after extending the optical fiber through the thrombus. In one embodiment, the method includes a thrombus that is an occlusive thrombus.

[0036] Any of the UV laser light emissions or pulses in the processes described herein can be repeated to produce the desired effect of arterial dilation. The arterial vessels that are dilated and undergo reperfusion are preferably branch arteries or arterioles. UV laser light can also be emitted to destabilize (by thrombectomy) platelet clots that have formed in the artery or arteriole distal to the thrombus.

[0037] In the methods for reperfusing a small arterial branch distal to a thrombus described herein, a fiber optic can be provided in combination with a hollow guidewire as described above.

[0038] In a method for reperfusing a small arterial branch distal to a thrombus according to the present invention, the step of removing the thrombus from the main trunk is preferably performed using a thrombectomy device. The thrombectomy device used to remove the thrombus may be a stentriever or an aspiration catheter. [Brief description of the drawings]

[0039] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1A] Figure 1 shows the upper half of a z-plane cross section of a laser ring beam with Gaussian intensity distribution G0 (generated by an optical fiber with an external conical tip with a cone half angle α) as it impinges on the inner wall of an artery of radius R to produce an expanded Gaussian beam profile Gw. Note that the beam has a polar angular spread of 2θw. The ring beam is cylindrically symmetric about the optical axis with its central maximum emitted at angle β. The intensity profile of G0 is drawn to 1 / 9 scale. The intensity of Gw at point "p" is a function of rw=(z-zo)sinβ and (z2+R2)1 / 2. [Figure 1B] The ray tracing along the laser axis in a protruding (external or inverted) conical tip optical fiber is shown. The dotted line (OO*) traces the idealized ray path of the laser light in a silica optical fiber with a conical tip (total apex angle = 2α) at ​​the output end. The beam follows total internal reflection at point P as long as the angle of incidence θ1 is above the critical angle θcrit (64.653°) at the silica / water interface (and thus by inspection α<90°-θcrit), and then emerges from point Q in the water-based medium with θcrit=64.653°. The locus of points defined by O* when rotated around the optical axis results in a ring-shaped beam. N1 and N2 are normals to the top and bottom of the cone. From the figure, by inspection, α+θ1=90° and ω=180°-2θ1, so that δ=3θ1-180°=90°-3α. The locus of the ring beam is a conical surface defined by the angle β(α)=θ1-α-γ(α) and by inspection, γ(α) is expressed as sin-1{(n1 / n2)cos3α}. From Snell's law, β(α) can now be determined as a function of the half angle α of the optical fiber tip: [Figure 2A] 1 shows an external conical tip machined on a 36° full apex cone angle (2α) fused silica fiber according to one embodiment of the present invention. [Figure 2B]Figure 2A shows a UV laser ring beam generated in water by the external conical tip shown. Table 1 shows α, β(α) and the reflection and refraction angles for a pure silica optical fiber, and Table 2 shows β(α) when the tip is optically bonded to diamond. The range and value of β(α) (up to 71.5°) is significantly increased for diamond compared to silica itself (up to 48.4°). [Diagram 3] 1 shows the optical properties of an inverted cone tip optical fiber, showing the path of reflected and refracted laser light (entering from the right side) in a fused silica fiber with an inverted cone tip or a tip made from diamond, with the beam entering water (saline) on the inner artery wall. The maximum angle β (α) of emission from diamond into water is about 56°, which far exceeds that from silica alone (25.4°), see Table 3. [Figure 4A] The placement of the optical fiber tip and intravascular UV illumination in the basilar artery (BA) of one of three dogs is shown. The dilation produced by UV illumination is semi-localized, and for a basilar artery length of approximately 40 mm, the dilation can extend up to 60 mm further from the trajectory of the ring beam illumination of the adjacent (vertebral) artery. [Figure 4B] The placement of the optical fiber tip and intravascular UV illumination in the basilar artery (BA) of one of three dogs is shown. The dilation produced by UV illumination is semi-localized, and for a basilar artery length of approximately 40 mm, the dilation can extend up to 60 mm further from the trajectory of the ring beam illumination of the adjacent (vertebral) artery. [Figure 4C] The placement of the optical fiber tip and intravascular UV illumination in the basilar artery (BA) of one of three dogs is shown. The dilation produced by UV illumination is semi-localized, and for a basilar artery length of approximately 40 mm, the dilation can extend up to 60 mm further from the trajectory of the ring beam illumination of the adjacent (vertebral) artery. [Diagram 5]1 shows the initial deployment of a balloon catheter over a guidewire (dark grey) inserted near an arterial occlusion (thrombus) prior to UV laser facilitated thrombectomy. The balloon is partially inflated. Once the balloon is inflated or nearly inflated, the guidewire is effectively centered within the artery. At this point, the guidewire can be retracted to dilate any obstructing kinks (if present) to reduce resistance to further insertion of the guidewire and replaced with a UV emitting optical fiber to further trace an optimal route through the artery for the UV emitting optical fiber and then the thrombectomy device. [Figure 6]FIG. 5 shows the balloon catheter fully inflated on the centered guidewire, and the guidewire (white line) retracted and replaced by an optical fiber, which emits UV laser light from a conical tip synthesized to generate a ring beam (elliptical locus of hash marks) at a desired angle β in the vicinity of the occlusion (thrombus). The output end of the fiber can be placed as close to the thrombus as permitted by the balloon, but the UV ring beam irradiation elicits a sustained arterial dilation starting from less than 4 and up to 40 diameters away from the thrombus. At beam intensities of 3 to 20 watts / cm2, dilation occurs within seconds and extends into the thrombotic segment. The optical fiber is then retracted, and a thrombectomy device is then placed over the expanded balloon. In this configuration, with the occluded arterial segment expanded, an aspiration catheter is introduced to retract the thrombus, now with less frictional resistance. To deploy the stentriever, the guidewire must penetrate the thrombus, possibly near the edge, above which balloon deployment and other steps would occur as described. Here, expansion distal to the thrombus allows the stentriever to be deployed at a larger diameter, as long as the integrability of the stentriever is maintained, thereby ensuring maximum capture of the thrombus and complete extraction with less fragmentation. Similarly, in view of the possibility of fragmentation, the aspiration procedure may benefit from proximal as well as distal irradiation, since the force of aspiration is not uniformly distributed along the thrombus. [Figure 7] A pictorial overview of the application of ultraviolet laser-induced dilation to thrombectomy to minimize wall damage due to mechanical friction is provided. [Figure 8A] A combination hollow guidewire and optical fiber is depicted, where the optical fiber is disposed within the hollow guidewire. [Figure 8B] A combination hollow guidewire and optical fiber is depicted, where the optical fiber is disposed within the hollow guidewire and has an outer conical tip. [Figure 8C]A combination hollow guidewire and optical fiber is depicted, where the optical fiber disposed within the hollow guidewire has an inverted conical tip. [Figure 8D] A combination hollow guidewire and optical fiber is depicted, where the optical fiber disposed within the hollow guidewire has an etched tip (ie, a diffractive optical element-DOE) that functions as a negative axicon lens. [Figure 9A] FIG. 1 shows a front view of the distal end of an optical fiber that has been etched to have concentric rings of V-shaped grooves formed in the optical fiber to create a diffractive optical element (DOE) that functions as a negative axicon lens. [Figure 9B] 9B shows a cross-sectional perspective view of the optical fiber of FIG. 9A. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0040] Detailed Description of the Invention The present invention relates to devices and methods for dilatation of tubular anatomical structures, such as arteries, where dilatation is induced by directing a suitably intense ultraviolet (UV) laser beam onto the wall of the tubular anatomical structure that does not functionally damage the cells of the structure. The devices, systems or methods of the present invention may be useful within anatomical structures such as anatomical conduits, tubes or tubules, blood vessels such as arteries, bronchioles, ureters, vasculature or the like.

[0041] The preferred embodiment uses a fused silica optical fiber with an inverted conical tip. The tip preferably comprises a UV-transparent material with a large refractive index in optical contact with the fused silica optical fiber. UV-transparent very hard materials with high refractive index such as diamond (refractive index at 355 nm of 2.48) or zirconium oxide (refractive index at 355 nm of 2.3) or custom-designed high refractive index (n>2) polymeric materials are preferred for the tip. Such tips can provide the ability to generate UV ring beam exit angles (half cone angles) of up to 56° (when using an inverted conical tip) or 71.5° (when using an inverted conical tip), both fabricated from diamond.

[0042] A preferred embodiment of the present invention relates to an optical fiber, preferably with a diameter of 10-100 μm, more preferably 50-100 μm, for carrying UV laser light to a distal or tip end of the optical fiber and emitting a cone-shaped beam of UV laser light that impinges on the inner wall of a tubular anatomical structure in the form of an expanding annular ring or ring-shaped beam. The optical fiber is preferably a solid fused silica optical fiber. The solid optical fiber used in the preferred embodiment is not a hollow optical fiber, and the solid optical fiber does not have a hollow optical fiber as any part or extension thereof.

[0043] To achieve this ring-shaped beam formation, the distal end of the fused silica optical fiber can be formed with a conical shape, such as, for example, an external conical shape (projecting outward) or can be an inverted conical shape (projecting inward). As shown in FIG. 1A using a silica optical fiber with an external conical tip 101 positioned within a microcatheter 104, the upper half of the z-plane cross section of a laser ring beam is shown to have a Gaussian intensity distribution G0 produced by the optical fiber with an external conical tip with a cone half angle α. The distribution G0 corresponds to an expanded Gaussian beam profile G w The beam impinges on the inner wall 102 of the artery having a radius R to generate a beam 103. w Note that the ring beam has a polar angular spread of β. The ring beam is cylindrically symmetric about the optical axis and its central maximum is emitted at an angle β. w The intensity of r w =(zz o )sinβ and (z 2 +R 2 ) 1 / 2 As shown, optical fiber 101 is positioned proximal to thrombus 105 (T) for use.

[0044] FIG. 1B is a detailed view of the fused silica optical fiber with the external conical tip 101 shown in FIG. 1A, showing the laser axial ray tracing within the protruding (external) conical tip optical fiber. * ) traces the path of an idealized ray of laser light in a silica optical fiber with a conical tip (total apex angle = 2α) at ​​the output end. The beam has an angle of incidence θ1 that crosses the critical angle θ at the silica / water interface. crit (64.653°) (and therefore α<90°-θ crit ), undergoes total internal reflection at point P, then emerges from point Q in a water-based medium, and crit = 64.653°. When rotated around the optical axis, O * The locus of points defined by results in a beam in the shape of a ring. N1 and N2 are normals to the upper and lower surfaces of a cone. From the figure, and by inspection, α+θ1=90° and ω=180°-2θ1, so δ=3θ1-180°=90°-3α. The locus of the ring beam is a cone-shaped surface defined by the angle β(α)=θ1-α-γ(α) and by inspection. γ(α) is the sin -1 From Snell's law, β(α) can now be determined as a function of the half angle α of the fiber conical tip.

[0045] FIG. 2A is a photograph of an optical fiber 200 according to the present invention, showing an external conical tip 201 on a 36° full apex cone angle (2α) fused silica fiber according to one embodiment of the present invention.

[0046] Figure 2B shows a UV laser ring beam generated underwater in a glass container 205 by an optical fiber with an external conical tip as shown in Figure 2A. The ultraviolet laser beam is transformed into an expanding ring shape 210 as shown in Figure 2B as a diffusing ring on fluorescent paper, and the ring beam can then illuminate the inner circumference of the artery after blood displacement using saline injection or a UV transparent balloon filled with a UV transparent gadolinium based contrast medium.

[0047] Table 1 herein below provides the extent of the beam's path within the fused silica outer conical tip in terms of the fiber half-cone angle α, and the angles associated with one total internal reflection and one refraction that result in the beam leaving the tip at an angle β (α). The ring beam cross section (angle depth 2θ) along the artery wall w , see FIG. 1A) can vary from Gaussian to a super-Gaussian "top hat" profile, which is the typical output pattern for multimode optical fibers, implying essentially constant intensity across the ring width at its maximum expression. These intensity patterns are not essential to the production of broadening, but they do affect the average and peak power of the beam and its upper limit.

[0048] An externally protruding conical tip according to an embodiment of the present invention is shown in Figures 1A, 1B and 2. A sharp external conical tip made of silica (full apex angle less than 40°, half cone angle less than 20°, see Figures 1 and 2A) may be subject to breakage and / or entanglement by intravascular obstacles (if present). A maximally blunt external silica tip (full apex angle of about 50°) is preferred (see Table 2). Breakage can be avoided by a tip made of a very hard material such as diamond, zirconium oxide or a high refractive index (n>2) polymeric material (e.g. plastic), but entanglement may still be possible depending on the array of complementary devices used. In practice, the optical fiber is introduced through a catheter that provides insulation and therefore protection.

[0049] Alternatively, the cone tip can be inverted (protruding inward) at the distal end of the optical fiber as shown in FIG. 3. Preferably, the fused silica optical fiber 301 has an inverted diamond cone tip 310, as this design can avoid being trapped by intravascular obstructions and is less likely to be damaged during insertion or deployment. Such a tip can emit an annular (ring-shaped) beam into water with an emission angle of up to 56° using a diamond tip (see Table 3). An inverted fused silica cone tip can produce an emission angle of 20° to 24° relative to the central longitudinal axis of the optical fiber (see Table 3). The beam intensity and efficiency of the expansion (and associated clot disintegration) process increases with the emission angle of the projection of the ring beam of UV light onto the inner wall of the tubular structure (i.e., artery), and it is therefore desirable to maximize this within the physical limits allowed by the UV-transparent high refractive index fiber tip material (fused silica, diamond, zirconium oxide, or custom polymeric material). The tip can be made of a high refractive index (n>2) material that is transparent to UV coupled to a conventional optical fiber, with the coupled tip and optical fiber in optical communication with each other. The coupled conical tip of a silica optical fiber can protrude (project) outward from the distal end of the optical fiber and can emit an unobstructed ring beam at angles of up to about 48° relative to the longitudinal axis of the optical fiber (Table 1). If the tip is constructed of diamond (Table 2), a much wider range of emission angles can be achieved, up to about 71.5°.

[0050] Optical fibers with outwardly protruding (inverted) or inwardly protruding (inverted)-conical tips can be utilized in the minimal contact persistent dilation system of the present invention, for example as part of a later 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 the angle α of the conical 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 sec) depending on the nitric oxide (NO·) concentration photophysically generated in the cells lining the tubular anatomical structure, such as the arterial wall. Irradiation at a given intensity induces a corresponding dilation, which can propagate itself proximally and distally from the area contacted by the annular beam via transnitrosation.

[0051] In a preferred embodiment, an optical fiber including an inverted cone tip or a blunt inverted cone tip may be used with a balloon catheter including a UV-transparent balloon in combination with an aspiration thrombectomy catheter. Preferably, a guidewire introduced into the segment proximal to the occlusion may be centered by the UV-transparent balloon catheter and inflated with a UV-transparent gadolinium-based contrast agent, whereupon the guidewire is replaced by the optical fiber.

[0052] Another preferred embodiment is a dilation system of the present invention including an inverted cone tip or a blunt inverted cone tip combined with a balloon catheter and used in turn with a stentriever. In this embodiment, a guidewire performs the initial penetration, which must be centered within the inflated balloon catheter, and then replaced by an optical fiber for the UV ring beam to properly impinge on the inner wall with uniform circumferential intensity.

[0053] Another aspect of the invention relates to a method of performing an endovascular thrombectomy procedure, the method comprising: - providing a thrombectomy catheter capable of accepting a UV-transmitting optical fiber; - inflating the UV-transparent balloon catheter with the UV-transparent contrast fluid sufficiently up to the inner wall of the artery to stop blood flow but to dilate the artery by mechanical pressure; - positioning a UV fiber optic thrombectomy catheter within 1-4 vessel diameters of a clot contained within a vessel; - emitting UV light energy as a ring beam onto smooth muscle cells in the inner wall of the artery to induce the formation and release of nitric oxide (NO·), thereby producing dilation of the artery, regardless of whether the endothelium (the normal source of NO·) is intact and whether blood is present; - removing the clots; Includes.

[0054] The above procedures may be performed in preparation for the use of an aspiration catheter or a stentriever.

[0055] Figures 4A, 4B, and 4C show the deployment of our fiber optic device to achieve intravascular 355 nm UV laser irradiation in the basilar artery (BA) 401, 402, and 403, respectively, at baseline in three dogs (BA origin is denoted by *, respectively). The dilation produced by the subsequent UV irradiation was semi-localized, and for a basilar artery length of approximately 40 mm, the dilation could extend up to 60 mm from the trajectory of the ring beam irradiation of the adjacent (vertebral) artery (Figures 4B and 4C). Figures 4B and 4C show that vertebral artery stenosis prevented the fiber tip's access to the ostium of the basilar artery before UV irradiation. For dog A, the fiber tip 411 could be placed 22% distal to the BA origin, which is optimal, whereas for dogs B and C, the fiber tips 421 and 431 could only be placed within 52% and 34% of the individual BA length proximal to its origin (*). 12~20 watts / cm 2 For an irradiation intensity of 100 nm, the mean dilation started at 78% and then progressed to 94% of baseline, decreasing linearly over a range of 40 mm, while dilation was still observed at the BA end point.

[0056] 5 shows the initial deployment of a balloon catheter 510 over a guidewire 520 inserted near an arterial occlusion (thrombus) prior to UV laser-assisted thrombectomy. The balloon is partially inflated (shown here as not touching the inner wall of the artery 540). Once the balloon is inflated or nearly inflated, the guidewire is effectively centered within the artery. At this point, the UV-emitting optical fiber may displace the guidewire and dilate any obstructing kinks (if present) to reduce resistance against the guidewire, and the guidewire may temporarily replace the UV fiber to further trace an optimal route through the artery toward the thrombus, before reinsertion of the UV fiber followed by a thrombectomy device.

[0057] Figure 6 shows the balloon catheter 510 of Figure 5 in an inflated state, fully inflated over the guidewire, thereby centering it, where the guidewire is replaced by an optical fiber 610, which emits UV laser light from a conical tip capable of generating a ring beam 620 at a desired angle β. The output end of the fiber can be placed as close to the thrombus 530 as permitted by the balloon, but the UV ring beam irradiation induces a sustained expansion starting at less than 4 and up to 40 diameters away from the thrombus. 3-20 watts / cm 2At a beam intensity of 100 nm, dilation occurs in a few seconds and extends into the thrombus segment. The optical fiber is then retracted and a thrombectomy device (e.g., an aspiration catheter) is then placed over the expanded balloon microcatheter with now less frictional resistance because the occluded arterial segment has been expanded. Alternatively, to deploy the stentriever, the guidewire would have to penetrate the thrombus through its distal end, and balloon deployment and other steps above would occur as described. Here, the UV-induced dilation distal to the thrombus allows the stentriever to be deployed at a larger diameter, as long as the integrability of the stentriever is maintained, thereby ensuring maximum capture and complete extraction of the thrombus.

[0058] FIG. 7 provides a schematic overview of the steps used in the application of the present invention to ultraviolet laser-induced dilatation thrombectomy to minimize wall damage due to mechanical friction. FIG. 7 shows the steps of the method of the present invention carried out using the balloon catheter shown in FIG. 5 and FIG. 6. In step A of FIG. 7, a thrombus 701 is shown as being located in the middle cerebral artery 702 prior to deployment of the thrombectomy catheter of the present invention. A microguidewire 720, typically used in balloon catheters, is fed through the internal carotid artery 721 and positioned proximal to the thrombus 701 (step B). Then, in step C, a UV-transparent balloon 730 is fed over the microguidewire 720 and positioned proximal to the thrombus 701, as in normal use of the device. Step D shows that the balloon catheter is then inflated 740 to contact the inner wall of the blood vessel (artery) 721 such that blood flow is significantly or completely impeded between the balloon and the vessel wall. UV laser light is deployed according to methods described herein such that the annular beam is emitted to contact the inner wall of the blood vessel, causing the blood vessel to partially dilate (propagating in both directions from the area contacted by the UV laser annular beam) 722. In an extraction procedure using a stentriever, or as shown by way of example only in step E, an aspiration thrombectomy catheter 750 may be used in its conventional manner to extract a thrombus 701, which is shown as being removed from the middle cerebral artery 702 in step F. The dilation produced by the UV laser irradiation may facilitate one or more of the removal steps.

[0059] Advantageously, the described method of expansion provides reduced mechanical friction, thereby minimizing damage to the arterial wall. Another advantage is that the platelet component of the clot also expands (see U.S. Pat. No. 6,539,944), and the portion closest to the arterial wall is partially degraded (by thrombus formation) into individual platelets, thus providing less adhesion to the wall and therefore less frictional resistance to the extraction process. No emboli are generated.

[0060] In the method according to the invention, the UV light emission can be continuous for a short duration of time, such as 2-15 seconds, preferably about 5 seconds, or in either case can be repeated as long as the light path is cleared from blood by balloon contact or saline injection. The laser irradiation interval can be filled by a beam that is itself composed of a plurality of successive MHz mode-locked pulses (about 10 picoseconds in width), referred to as a continuous wave laser beam or a quasi-continuous beam, or a plurality of successive 5-25 KHz pulses (up to 100 nanoseconds in width), referred to as an acousto-optic Q-switched beam. The UV light is preferably directed onto the vessel wall within about 20 vessel diameters of the thrombus. More preferably, the UV light is directed onto the vessel wall within about 4 vessel diameters of the thrombus when using a balloon. In one preferred method, the vessel is an artery partially or completely occluded by a clot.

[0061] The UV light is emitted at a wavelength of about 180-400 nm, preferably at a wavelength of about 300-400 nm. In a preferred embodiment, the UV light is emitted using a frequency tripled Nd:YAG laser emitting light at 355 nm (other Nd-containing crystals such as Alexandrite exist). NO· production is measured as maximal at 350 nm, but laser UV light is not currently available at 350 nm wavelengths and may use 355 nm wavelengths with a slight decrease in efficiency. Newly developed lasers at 349 nm and 360 nm exist, but are not yet reliable enough to be used clinically. Other UV-generating lasers that may be used with the present invention (but not to the point of ablation) include XeF lasers (351 nm) and continuous wave (CW) argon ion lasers (351, 364 nm). Any diode or dye laser may also be used, provided that output can be obtained within the UV range required for non-ablative vasodilatory effects. Diode lasers are currently unable to produce wavelengths within the optimum region. However, if the physical difficulties in fabrication were overcome, diode lasers could also be used, and would be much smaller than the lasers proposed above. In principle, any laser that emits UV radiation, either directly or as a result of frequency doubling or tripling, could be used.

[0062] In the apparatus or method of the present invention, the average incident intensity of UV light is about 3 to about 20 watts per square centimeter (W / cm 2 ).

[0063] The device and method of the present invention may be used in combination with prior administration of a pharma- ceutical acceptable thrombolytic agent to assist in clot dissolution (of fibrin). A concern is the release of clot fragments, which is avoided by our process of platelet dethrombosis. The preferred process of thrombectomy is one to remove the clot without the complications of fragmentation by the thrombolytic agent.

[0064] One particular embodiment introduces the laser beam through an optical fiber deployed in the blood vessel that includes a protruding (external) conical tip that can effectively act as a diverging lens for the beam (effectively a negative axicon lens) with one reflection and one refraction. This design creates a circumferential illumination pattern as an expanding conical ring, thereby creating an annular beam of laser light on the wall of the tubular anatomical structure to which the beam is directed. The protruding conical output tip is preferably fabricated using a UV-transmitting material with a refractive index greater than fused silica, such as diamond, zirconium oxide, or custom polymeric materials (e.g., plastics) with n>2 that can be optically bonded to silica. As the beam exit angle increases, within the limits imposed by Snell's law, the beam intensity on the wall and the efficiency of arterial expansion increase because the distance to the wall, the width of the beam projected along the arterial wall, and therefore the irradiated area, all decrease.

[0065] These same considerations apply to the inverted cone tip as well, but the maximum emission angle will be less than that from the external tip. The intent is to provide two different approaches to generating a beam in the shape of an expanding ring, the relative benefits of which have been discussed above and can be evaluated for clinical use.

[0066] A preferred fiber optic tip includes an inverted tip configuration (FIG. 3), which is less likely to become obstructed during use, but its deployment through a guide catheter avoids this possibility as well as the possibility of arterial perforation.

[0067] Another embodiment is a fused silica optical fiber with an externally protruding tip that has a maximum emission (half-cone) angle of about 48.4° without obstruction (see Table 2, but 50.3° in the limit) (FIG. 1B). If the tip is sharp (full apex cone angle less than 40°, see FIG. 2A), it may be subject to breakage from mechanical contact if brittle materials are used. This situation can be remedied by an external cone tip made from a very hard material with a high refractive index, such as diamond. An inverted diamond cone tip allows a beam exit angle of up to 71.5°. Naturally, with increasing bluntness (increasing full cone apex angle), the external tip (including the silica itself) has a greater resistance to mechanical damage.

[0068] UV light destroys nitrite (NO2) in the smooth muscle cells of the arterial wall. - When absorbed by the endothelium, UV lasers can photophysically release nitric oxide (NO·) at concentrations that exceed those maintained by the endothelium during normal metabolism. This induces a quasi-transient (tens of minutes to hours) and semi-localized dilation of blood vessels. The release of NO· from smooth muscle cells self-propagates by transnitrosation along localized distances of up to several centimeters proximally and distally from the site of irradiation with UV light. UV lasers are used to induce vasodilation in the vicinity of the occlusion, thereby reducing friction with (and chemical adhesion to) the arterial wall when a thrombectomy device is deployed to extract the blood clot. Thus, vasodilation may facilitate detachment of the clot from the vessel wall to which it adheres, and easier and safer removal of the clot using a conventional aspiration catheter or stentriever (by reducing the strength and frequency of its interaction with the vessel wall). The present invention may advantageously reduce the late-stage pathological and behavioral consequences of structural and functional damage to the endothelial and intimal structures of the occluded artery to which the thrombectomy procedure is applied.

[0069] Dilatation of the blood vessel increases the diameter of the blood vessel, which can also facilitate movement of the catheter into position, i.e., it can pass through kinks (severe bends) or narrowings in the blood vessel more easily.

[0070] To achieve the objectives of the present invention, one novel aspect relates to an advantageous configuration for the tip of the optical fiber from or through which UV radiation is emitted. For example, it has been discovered that the utilization of an external conical tip comprising a very hard, but UV-transparent material, such as diamond, can more easily provide an external (semi-conical) angle of emission of up to 71.5° (relative to the fiber axis) and at the same time a narrower projection of the ring beam of UV light on the inner arterial wall. The preferred angle is best determined in relation to other components of the system (e.g., a UV-transparent balloon inflated with a UV-transparent gadolinium-based contrast agent).

[0071] In another embodiment of the invention, the distal end of the optical fiber is capped with an inverted conical tip, preferably constructed from a UV-transparent, high refractive index material such as diamond, zirconium oxide, or a custom polymeric material (e.g., plastic), capable of emitting a ring beam with an emission angle of up to 56° (from the diamond) relative to the longitudinal axis of the fiber.

[0072] Another object of the present invention is to provide an optical fiber capable of carrying UV light contained by a catheter, the optical fiber being comprised of an inverted cone tip preferably constructed of a UV transparent material high refractive index material such as diamond, zirconium oxide or a custom polymeric material (e.g., plastic) capable of emitting a ring beam for cerebral arteries. The narrow beam width concentrates the amount of energy absorbed by the cells of the blood vessels such that an effective amount of NO· is released for large vasodilation to occur even when a lower power laser is used.

[0073] Yet another object of the present invention is to provide a dilation system that may include in a final step an aspiration catheter or stentriever preceded by a balloon catheter that includes a fused silica optical fiber capable of carrying UV light to the distal end of the optical fiber. Preferably, the dilation system includes a fused silica optical fiber for UV irradiation with a conical tip at the distal end of the optical fiber. Preferably, the conical tip is constructed of a UV-transmitting material with a high refractive index, such as diamond, zirconium oxide, or custom polymeric material (e.g., plastic). More preferably, the conical tip is an inverted conical tip configuration. Alternatively, the fused silica optical fiber component of the dilation system of the present invention includes a thrombectomy aspiration catheter or stentriever system that includes an optically contacted inverted conical tip constructed of a UV-transmitting high refractive index material, such as diamond, zirconium oxide, or custom polymeric material (e.g., plastic).

[0074] It is yet another object of the present invention to provide a UV-transparent balloon catheter that encapsulates a UV-compatible optical fiber in combination with an aspiration thrombectomy catheter as part of an integrated dilatation system. Preferably, the UV-compatible optical fiber in combination with an aspiration thrombectomy catheter or stentriever incorporates an inverted cone tip of diamond or zirconium oxide (or high refractive index polymeric material) at its distal end.

[0075] In a preferred embodiment, the balloon catheter may be inflated using a UV-transparent gadolinium-based contrast fluid, and the balloon walls then displace blood, thereby providing a clear path for the UV laser light to travel to the medial arterial wall. In accordance with the present invention, the balloon is inflated for this purpose to further center the conical tip, but not to expand the inner diameter of the vessel wall. The gadolinium contrast agent is localized to the balloon and thus isolated from the blood flow. In this embodiment, the balloon material and contrast material are sufficiently transparent to UV light to allow unhindered passage of the UV light through the enclosing catheter and balloon.

[0076] A further object of the present invention is a method of performing a thrombectomy procedure in a mammal in need thereof, the method comprising: a) providing an expansion system as described herein; b) positioning a UV fiber optic balloon catheter within the occluded vessel to within 1-4 vessel diameters of the clot; c) emitting square wave pulses of continuous or high repetition rate pulsed beam UV laser light energy as a beam within a defined average intensity range onto smooth muscle cells lining the inner wall of the blood vessel to release NO· from the cells and thereby produce vasodilation; d) removing the optical fiber and introducing a thrombectomy device; e) then removing the coagulum by mechanical extraction; has.

[0077] In one embodiment, the UV fiber optic extension system preferably features a fused silica fiber with a diamond cone tip capable of emitting a ring beam at an angle of up to 71.5° (for the external tip) relative to the longitudinal axis of the fiber, the angle being smaller for other known high refractive index materials such as zirconium oxide and custom polymeric materials (e.g., plastics).

[0078] Bursts of UV light energy in continuous or pulsed form may be emitted over an exposure interval of about 2 to 20 seconds, preferably at least 5 to 15 seconds, and more preferably about 8 to 12 seconds. A 10 second burst may be the most preferred duration of emission of the UV light beam to expand the blood vessel to a sufficient diameter to alleviate frictional interaction of the catheter with a tortuosity or stenosis of the blood vessel or to promote partial detachment of the clot from the vessel wall.

[0079] In one preferred embodiment, the invention includes a dilation system that includes an aspiration catheter or stentriever followed by a priming period with an optical fiber having a conical tip that delivers a ring-shaped beam of UV radiation. The conical tip of the optical fiber can protrude inward or outward from the distal end of the optical fiber depending on the angle of desired emission and the presence or absence of obstructions along the desired path.

[0080] In use, the optical fiber including the conical tip may emit a cone beam trajectory that irradiates the tubular anatomical structure as an annular or ring shaped beam around the inner circumference of the tubular structure. The tubular anatomical structure that may be expanded by UV light is covered by (smooth muscle) cells that store nitric oxide (NO·) (as nitrite) and can release fully activated nitric oxide. This expansion may advantageously be used to dilate or expand the artery at a location proximate to the thrombus to facilitate easier and safer removal of the thrombus by reducing mechanical friction and chemical binding thereto. The thrombus may be an occlusive thrombus or a non-occlusive thrombus. Vasodilation at or near the site of the thrombus within the blood vessel may at least partially loosen the adhesion of the thrombus to the vessel wall or detach the thrombus from the vessel wall, thereby facilitating efficient removal of the thrombus by conventional aspiration or stentriever catheter techniques currently used in the medical field. Peripheral damage to the occluded vessel is minimized before, during and after extraction.

[0081] Dilation of the artery in the region of the thrombus can occur when irradiation with UV light occurs within about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 25, or 30 vascular diameters of the thrombus. As used herein, the term "vascular diameter" refers to the outer diameter of the artery. Preferably, the blood vessel is irradiated within about 10 vascular diameters of the thrombus. More preferably, the blood vessel is irradiated about 1-4 vascular diameters away from the thrombus. The blood vessel can be irradiated proximal or distal to the thrombus.

[0082] Also, branch arterial vessels can be dilated by irradiating the trunk 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 trunk thrombus, because the UV-induced vasodilatory effect can propagate distally (as well as proximally). This phenomenon can be particularly useful in cases where the thrombectomy surgeon does not have viable access to the branch artery or arteriole that contains the thrombus, but does have proximal access to the trunk artery.

[0083] Preferably, the UV light beam is directed onto the inner surface of a tubular anatomical structure such as an artery by a beam delivered through an optical fiber placed inside the vessel using a catheter. Almost immediately after irradiation, but not more than a few seconds after irradiation by the laser beam, the vessel expands in the initially irradiated area and then self-propagates continuously over a distance of several centimeters in the proximal and distal directions.

[0084] Under normal physiological conditions, dilation is mediated by nitric oxide (NO·) produced by the endothelium. In contrast, UV laser-mediated photophysical generation of NO· results in the release of nitrite (NO2) stored in intact smooth muscle cells within the arterial wall. - Local NO concentrations of up to 10 μM can be generated regardless of the severity of endothelial damage or even when the endothelium is absent (completely destroyed).

[0085] Photolysis of nitrite in smooth muscle cells leads to local dilation via S-nitrosation of thiols (RSH) resulting in the formation of NO·, S-nitrosothiols (RNSO) and the release of NO· or its nitrates (RSNOs), which can transnitrosate other thiols, thereby propagating the dilation radially, distally and proximally with more release of NO·. This is a self-perpetuating cascade process.

[0086] Photophysically generated nitric oxide can stimulate waves of expansion in both the proximal and distal directions, thus reducing frictional resistance to clot removal over some percentage of the length of the clot, and thus allowing the clot to be extracted with less force and less trauma to the artery compared to what is currently observed, with fewer future complications at the site or distal to the site or proximal to the site.

[0087] The ultraviolet laser beam used to dilate arteries and thereby treat blocked blood vessels can be continuous or pulsed. The use of a pulsed laser can reduce heat buildup and resulting damage in the target and surrounding tissue. When a non-ablative pulsed laser, such as a quasi-continuous or acousto-optic Q-switched laser, is used, the pulse rate can be any rate that is consistent with the delivery of an adequate time-averaged intensity of irradiation to the target tissue while avoiding individual pulses of high intensity that would result in permanent damage, i.e., irreparable damage in a physiologically relevant time frame (e.g., over a period of hours to weeks), severely in the target tissue or to the optical fiber.

[0088] The UV light is preferably in the range of 180-400 nm in wavelength. More preferably, the UV light is in the range of 300-400 nm. Even more preferably, the UV light is about 340-370 nm, and most preferably, it is about 350-360 nm. A frequency tripled Nd:YAG laser emitting radiation at 355 nm is particularly preferred.

[0089] Other UV lasers that may be used with the present invention (while avoiding ablation) include XeF lasers (351 nm), CW argon ion (351, 364 nm) or CW krypton ion (351, 356 nm). Any diode or dry laser may also be used, provided that a non-ablative output can be obtained in the UV range required for the vasodilatory effect. In principle, any laser that emits UV radiation, either directly or as a result of frequency doubling or tripling, may be used.

[0090] For 355 nm UV laser irradiation, the expansion ranges from 3 to about 20 W / cm in intensity by assuming a Gaussian beam shape. 2 The stimulation can be performed over a wide dynamic range of 7 at intensities of 10 W / cm2. However, the dilatation effect is independent of the beam shape. At the upper limit, vacuoles form in the smooth muscle cells, but their function is not impaired. The dilatation effect depends on the average intensity. For example, a 7 Hz train of 100 nanosecond pulses with a peak power of 5 kilowatts can be delivered at 20 W / cm2 without inducing functional damage. 2 It can be used in.

[0091] Blood can be cleared from the path of the laser beam, for example, by flowing a small amount of saline solution through an opening in the catheter where the beam leaves just before illuminating the vessel wall or thrombus.

[0092] The intensity of the UV illumination 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, by using a frequency tripled Nd-YAG laser, a dose of approximately 5 watts / cm can be achieved. 2 An incident intensity of 12-20 watts / cm produces approximately 20-30% dilation in small arteries (this dilation can be restored by NO inhibitors). 2 Greater intensity (up to 1J / cm at 20Hz pulse rate) 2 / pulse) can produce a similar increase in diameter in larger arteries (approximately 1.5 mm diameter), but 2 Intensities exceeding this can alter the vascular wall structure (small vacuoles are formed in the smooth muscle tissue), but no functional damage is observed.

[0093] The incident power is then incremented (e.g., 2 Watts / cm) until adequate dilation of the blood vessel is observed within a reasonable time, such as within 5 seconds. 2 The intensity of the irradiation may be increased by an increment of 0.1 to 1.5 times the intensity of the vasodilator (increments of 0.1 to 1.5 times or more). The period of irradiation may be continuous, i.e., sustained, until the point at which the dilatation effect plateaus, or may be intermittent, and the duration of the period or periods of irradiation may also be varied at a given incident intensity to obtain an appropriate response, whereby the dilatation already induced is maintained and amplified. An appropriate vasodilator response, i.e., the degree of dilatation and its kinetics of onset and duration, may be determined by the user, but a response in the range of a 20-40% increase in vessel diameter in 5-10 seconds is generally considered adequate by many users.

[0094] The method of the present invention is suitable for treating a variety of disease states involving vascular occlusion. Examples of such conditions include stroke, myocardial infarction and occlusion or spasm of any peripheral blood vessel, large or small.

[0095] In the method of the present invention using an aspiration catheter, a balloon catheter can be introduced and then the aspiration catheter can be introduced directly above the catheter below the balloon portion. When the balloon is expanded, the UV fiber can be introduced into the balloon. When the UV transparent balloon is expanded to exceed the diameter of the aspiration catheter before the tortuous bend or stenosis, the UV fiber is centered in the artery and the non-flowing blood is displaced from the projected light path. The UV beam can then be flashed for several seconds to obtain sufficient expansion to allow the passage of the thrombectomy catheter used in the dilation system. Here, the balloon is not pressing against the artery in a crimped state to expand it, and only facilitates the means to displace blood away from the artery with the laser ring beam following an optically free path to non-mechanically dilate the artery. The balloon is very common, but can damage tissue if over-inflated.

[0096] When UV light is emitted and absorbed on the walls of the blood vessels, the vessels dilate and propagate the dilation independent of the subsequent presence of blood or blood flow. This process can be used to more easily traverse tortuous bends or stenoses on the way to the clot. Thus, structural and endothelial damage is minimized from the entry point to the target location. Once the clot is reached, a final irradiation, including an optional saline flush, is performed and then an aspiration catheter extracts the clot.

[0097] When used in combination with a stentriever, the guidewire is moved through the clot just one or more centimeters. A balloon catheter is then inserted and expanded just distal to the clot, and the guidewire is replaced by a UV fiber to irradiate the distal segment. The UV fiber is then retracted and the stentriever replaces it through the balloon catheter at the location of the clot. The balloon catheter can be retracted just proximal to the clot, and the stentriever mesh spontaneously expands upon catheter retraction or in a controlled manner to a diameter suitable for extracting the clot uniformly and symmetrically, thus better capturing the entire clot and ensuring extraction efficiency.

[0098] Another benefit is the ability to use UV irradiation in locations that are difficult to traverse with the catheter toward the target clot location, which facilitates safer clot extraction. A catheter that appears too large for the artery at some unanticipated point can still be used after UV dilation. If an error in catheter size selection occurs initially, UV dilation can be used to dilate the artery without the need to replace the current catheter.

[0099] A design of an externally protruding conical tip (α=18°, FIGS. 1A, 1B, and 2A) using a silica optical fiber was developed for intravascular deployment via a microcatheter.

[0100] [Table 1]

[0101] To increase β (and therefore reduce the area subtended on the arterial wall by the ring beam), a short (approximately 0.5 mm) inverted cone segment made of a UV-transparent material with a high refractive index must be optically spliced ​​into the silica fiber. The optimal option is a 100 nm diameter fiber with a diameter of 100 nm. d= 2.48.

[0102] Table 2 shows the same calculations as above for the beam leaving an external diamond tip in water.

[0103] [Table 2]

[0104] Table 3 shows the extent of the path of 355 nm laser light emitted into water (saline) from an inverted cone tip made from silica and diamond towards the artery wall. The emission angle β is a function of the inverted cone half angle α (depicted in FIG. 3). The inverted cone tip design may be preferred by some physicians because the likelihood of the tip getting caught in an obstruction, if any, is much less than with an external cone tip.

[0105] [Table 3]

[0106] This calculation complements those performed on the external diamond conical tip and shows that the emission angle β is much larger compared to the inverted conical tip, thus providing increased beam intensity at reduced distances from the external conical tip (both far more favorable than silica alone). However, β is surprisingly sensitive to α, which is the angle at which the input beam expands with increasing polar angle 2θ w This means that the cone tip must be well collimated to minimize θ (see FIG. 1A) and the inner conical tip must be very precisely polished to ensure high surface quality and thereby minimize beam scattering. Here, θ crit =θ diamond = 32.51° and β = 57.49°. diamond If θ = 32.50°, water = 88.44°, α = 57.50°, and β = 55.94° (Table 3).

[0107] As an alternative to the previously shown conical tip optical designs for generating ring beams, we propose the combination of diffractive optics with optical fibers. Diffractive optics involves etching a geometric pattern by any of several methods (e.g., lithography, e-beam deposition) on a flat-end optical fiber, the tip of which can be fused silica itself or other optically coupled UV-transparent high-index (n>2) materials such as zirconium oxide, diamond or custom-designed polymeric materials (e.g., plastics) to obtain the desired diffractive phase profile. The pattern on the end of the fiber resembles a circularly symmetric bas-relief - a series of concentric annular structures that are variable in depth and radius - because material must be removed with high precision to generate the desired diffractive phase profile. The desired output is a very sharp ring-shaped Bessel beam with minimal sidebands. For beams emerging from the tip at angles β>40°, high-index materials such as the latter three (already illustrated) are likely to be used. Ring beams with β=15° or greater in any medium have not yet been produced by this technique to our knowledge, but manufacturers of diffractive optical devices may extend the range of their capabilities. A flat-end diffractive pattern disposed on a suitable high-index material, including the end cap of a fused silica optical fiber immersed in water, may be the optimal form of device.

[0108] An external or internal conical tip may generate a ring beam at a range of angles relative to the arterial wall; for an external tip, the practical upper limit is about 48° for silica and 71.5° for diamond, although preferably a near maximum angle is used. For an internal (inverted) diamond conical tip, the range may be up to 56°, which is preferred. An immediate benefit of emitting the beam at the maximum acute angle is a reduced ring beam width and thus greater laser intensity. The expansion process reduces the overall beam intensity (3-20 Watts / cm2). 2), lower power (and perhaps more compact) lasers can be used more efficiently. The internal conical tip is designed for safety purposes, since in previous work the inventors have recognized that the silica external tip can be damaged. Presentation of a device that is not damaged upon insertion by attachment to any other device or tissue component is clearly beneficial, since capture is avoided and the tip structure is preserved. However, these effects are unlikely to occur with very hard materials such as diamond.

[0109] These and other embodiments and applications of the present invention will become apparent to those skilled in the art in light of the description provided herein. A common, yet intractable, aspect of hemorrhagic stroke is vasospasm (stenosis) of the middle cerebral artery. As blood released into the subarachnoid space from (for example) a ruptured aortic aneurysm travels along the artery, hemoglobin from lysed red blood cells enters the arterial wall and scavenges nitric oxide, thereby inducing spasm. This condition cannot currently be reliably treated, and prodromal drugs can (and do) lower blood pressure to the point of pathology. Another aspect that is currently untreatable is early brain damage (i.e., preceding vasospasm) mediated by platelet-occluded microvessels in the brain. Despite many animal studies, no drug exists that breaks down platelet clots in humans. The UV laser method is clearly intended to treat the therapy of these extremely difficult conditions. The inventors have shown reversal of vasospasm in three days in dogs that have suffered hemorrhagic stroke. The inventors have also shown that platelet clots can indeed be broken down by UV laser-induced nitric oxide because it inhibits thrombin, the enzyme required to maintain interplatelet fibrinogen / platelet GPIIb-IIIa cross-links.

[0110] The inventors propose that UV irradiation of the main trunk directed to the feeding artery just proximal to its connection between the distal branch and its microvascular bed will allow and promote reperfusion of blood into areas that cannot be directly treated by thrombectomy, in addition to arterial recirculation, due to the autoreplication of nitric oxide over distance and its associated vasodilation, thereby improving the likelihood of tissue survival. For example, a patient with a ruptured cerebral aneurysm is treated urgently with standard care interventional devices such as coils and stents. After the aneurysm is fixed, the neurointerventionalist may proceed to position a microcatheter used for coiling distal to the aneurysm. The microcatheter can be replaced by a UV-transparent balloon catheter, and the microguidewire can be replaced by an optical fiber. Distal UV irradiation dissolves microvessels occluded by platelet emboli within the vascular region, thereby improving reperfusion and improving the patient's clinical outcome. Cerebral vasospasm may produce vasoconstriction 3-21 days after aneurysm treatment. Again, by using a UV-transparent balloon catheter and optical fiber, UV irradiation proximal to the vasoconstriction causes the artery to expand and restore its original (or larger) diameter, thereby restoring blood circulation.

[0111] Atherosclerotic vascular disease can result in stenosis or narrowing of the arterial lumen (stenosis) due to the formation of plaque. The method calls for widening the lumen by balloon angioplasty, followed by stenting to fix the opening. Angioplasty and stenting first require a microguidewire to pass through the stenosis to gain distal access. When the stenosis is moderate to severe, it is difficult to safely pass a guidewire through the stenosis without dislodging the atheroma. During a stenting procedure for atherosclerosis, passage of the guidewire and device through the plaque can be facilitated by dilating the artery with UV (if existing scar tissue allows such dilation). Plaque, when calcified, can be very hard and incompressible. Balloon expansion can also cause adjacent non-atheromatous segments to expand and stretch to the point of further structural distortion. A common response to such trauma is hypertrophy, an abnormal healing response known to eventually occlude the opening created by the stent. The inventors propose that non-mechanical dilation of the artery, even diseased ones, by nitric oxide passages will substantially facilitate distal access of the atheroma with an intravascular device. The NO passages also minimize vascular distortion and overexpression of the healing response, thus preserving the desired lumen and its useful life. Endothelial damage in adjacent non-atheromatous segments is also reduced. For example, in patients with severe carotid atherosclerosis, a UV-transmitting balloon catheter can be positioned proximal to the stenosis with the assistance of a microguidewire. The guidewire can be replaced by an optical fiber. Subsequent UV irradiation dilates the arterial wall and widens the stenotic gap. The optical fiber can then be replaced by a microguidewire, which can now be more easily navigated through the widened stenosis to gain distal access. The balloon catheter can then be removed and a device delivery system can be passed over the guidewire for treatment of the plaque.The same system can generally be used to safely place a stent to ensure circulation through the stenosis, except now the stent can be placed in a dilated vessel without the usual endothelial injury, avoiding restenosis, a very common complication of currently performed stent deployment, and the need for stent replacement within 3-5 years.

[0112] Inhaled nitric oxide can be used to treat pulmonary hypertension and acute respiratory distress syndrome, especially in pediatric patients. Inhaled gas diffuses through the alveolar-capillary membrane and generates vasodilation, which results in reduced pulmonary vascular resistance and increased blood perfusion in the ventilated lung segment. This potentially improves blood oxygenation in the patient. The proposed invention can potentially be used in a more targeted manner to vasodilate segments and branches of the pulmonary artery. The pulmonary artery and its branches can be accessed through the femoral vein via right heart catheterization. A balloon catheter can then be positioned in the targeted pulmonary artery branch. An optical fiber can be introduced into the inflated balloon to irradiate the arterial wall with the ring beam. The resulting vasodilation propagates itself proximally and distally from the area contacted by the annular beam via transnitrosation.

[0113] Another aspect of the invention relates to a modified guidewire that can be used in arterial catheterization. Typically, a guidewire is fed through a blood vessel to reach a target location, followed by threading a catheter over the guidewire to perform the intended process, such as a thrombectomy procedure using a thrombectomy device such as a stentriever or aspiration catheter. The process of the invention includes removing the guidewire from the catheter and replacing it with an optical fiber capable of emitting UV laser light as an expanding ring beam with sufficient intensity to dilate the blood vessel. An alternative to the step involving removing the guidewire and replacing it with an optical fiber is to provide an optical fiber within the guidewire as a combined guidewire / optical fiber. A preferred embodiment of this aspect of the invention has a guidewire with a hollow core such that an axial cavity or lumen is formed throughout the length of the guidewire and is configured in the form of a flexible metal tube structure. Housed within the guidewire is a silica optical fiber, the tip of which is designed to emit a ring-shaped beam, preferably manufactured from a UV-transparent high refractive index material such as diamond. The flexible metal tube structure may be constructed from a flexible metal alloy such as Nitinol. The optical fiber may be provided unattached to the guidewire or, preferably, is optionally attached in relation to the inner wall of the hollow guidewire. In this configuration (the "locked position"), the guidewire and optical fiber are integral with one another and work together as a single unit when placed in a blood vessel. In one embodiment, the optical fiber may be manually configured into the "locked position" whereby it is attached to the guidewire and may also be manually configured into the "unlocked position" whereby the guidewire and optical fiber can operate independently and separately from one another.

[0114] In y-plane (sagittal) cross section in Figure 8A, the distal segment of an integrated or combined guidewire and optical fiber embodiment is shown. Figures 8B, 8C, and 8D depict different optical fiber tip configurations, each of which has the effect of a negative axicon lens, which projects a diverging laser beam onto the inner arterial wall. A diverging laser beam results, independent of whether the optical fiber output pattern is multimode or single mode, depending on the fiber thickness conditioning. Figure 8A shows a combined hollow guidewire and optical fiber 800, whose outer surface can be coated in a hydrophilic or hydrophobic manner according to the intended application. The optical fiber 802 is covered by a polymer coating 803 (cladding), which ensures total internal reflection, and is disposed within the hollow core 801 of a flexible metal guidewire. In one embodiment, the inner portion 804 of the guidewire comprises a metallic coil that encapsulates a hollow core of the guidewire such that the key requirements of torqueability, flexibility, moldability, shape retention, and tactile feedback can be met for the particular application desired. The distal end of the optical fiber 805 (defined by the limits of its cladding 803) coincides with the end of an essentially hemispherical guidewire cap 806. The cap 806 can be fabricated from a soft, pliable material intended to minimize mechanical trauma to the cavity being probed (such as an artery) until the target location is reached.

[0115] In a preferred embodiment, the guidewire and optical fiber combination comprises a solid fused silica optical fiber of sufficient length to emit UV laser light from its distal end without being impeded by the guidewire cap 806, without extending significantly beyond the guidewire cap 806 so that the blood vessel is protected from the optical fiber tip during movement and placement at the target location. The apex of the outer cone tip can be shielded by the guidewire until the time of placement at the desired location. Any particulate buildup could be removed by flushing the catheter with saline.

[0116] 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 polymeric material (e.g., plastic). For example, the diamond tip can be optically coupled to a silica fiber 802 and can be configured in three ways to generate an expanding beam of laser light. FIG. 8B shows an optical fiber with an external conical tip 811. A ray of light 807 is shown entering and leaving the fiber by one 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 such that the apex of the tip can protrude slightly to penetrate hard obstacles such as calcified atheroma. In one embodiment, the distal end of the optical fiber can be configured as an external conical tip that can emit UV light in a conical beam as described above.

[0117] 8C depicts a combination hollow guidewire and optical fiber, where the optical fiber 802 has an inverted conical tip 812 in optical contact with the fiber. In one embodiment, the distal end of the optical fiber can be configured as an inverted conical tip that can emit UV light in a conical beam as described above.

[0118] Figure 8D shows an input TEM similar to that produced by a negative axicon lens. 00 Shown is a diffractive optical element (DOE) formed on a flat etched tip 809 of a diamond segment optically coupled to a silica main fiber to generate a UV laser ring beam 810 from a laser beam 808. TEM 00Any of several known methods can be used in this rapidly changing field to convert a laser beam into a Bessel intensity profile (ring shape). The molded pattern can include concentric beveled rings formed on the flat output end of the optical fiber with a mechanical resolution of about 5 μm (each of which can be a cascade of thin flat rings of successive thickness). In one embodiment, the ring beam can subtend a full cone angle of at least 90°. In a preferred embodiment, the ring beam can subtend a full cone emission angle of 120° or more to improve the extended ultraviolet ring beam intensity, thus requiring less laser input power. The fiber diameter, mode (which can be multimode), and thickness of the output ring are not critical to produce an operationally effective ring beam output. In one embodiment, the distal end of the optical fiber can be configured as a flat distal end with concentric circular grooves etched into the flat distal end, the flat distal end being a diffractive optical element (DOE) as described above.

[0119] Figures 9A and 9B show one embodiment of an etched end of an optical fiber in accordance with the present invention. Figure 9A shows a front view of the distal end of an optical fiber 800 that has been etched to have concentric rings of V-shaped grooves formed in the optical fiber to create a diffractive optical element (DOE). A central V-shaped groove 902 forms an inverted cone at the center of the optical fiber. Each of the central outer concentric V-shaped grooves has a peak 901a and a trough 901b.

[0120] Figure 9B further illustrates the concentric ring V-shaped groove pattern shown in the side view of Figure 8D and in the front view of Figure 9A. The pattern of alternating peaks 901a and troughs 901b in the flat distal end of optical fiber 800 can be further appreciated in this light. Preferably, each peak 901a is the same height as the other peaks 901a and each trough 901b is the same depth as the other troughs 901b. Figure 9B also illustrates a solid fused silica optical fiber.

[0121] Advantageously, the integrated or combined guidewire and optical fiber embodiments may eliminate certain steps of a conventional catheterization procedure. While a conventional catheterization procedure requires the steps of (1) inserting a guidewire, (2) placing a catheter over the guidewire, then (3) removing the guidewire from the positioned catheter, and (4) replacing the guidewire with an optical fiber to dilate the lumen, the optical fiber in the combined guidewire may eliminate steps (3) and (4) because it does not require the guidewire to be removed from the catheter and replaced by the optical fiber. The time saved by eliminating steps (3) and (4) may be advantageous to the user and the patient undergoing the procedure.

[0122] Due to the time saved by the elimination of the above-mentioned procedural steps to promote reperfusion, the combination guidewire / optical fiber of the present invention may reduce the incidence (about 50%) and severity of behavioral abnormalities associated with the outcome of thrombectomy. These have been demonstrated in all grades of TICI flow status, even at level 3, which indicates complete recanalization of the main occluded artery. However, TICI does not measure blood reflow in its branch arteries or its arterioles, which are responsible for the direct supply of nutrients to the tissue. Reperfusion is distinct from preceding recirculation and is not currently observable by angiographic techniques. Reperfusion is defined as the resumption of normal flow in arterial side branches and microvessels that cannot be accessed or cleared by thrombectomy. The relative lack of reperfusion despite recanalization of tumor arteries may well explain the variability in functional recovery. This is hypothesized to be due to several mechanisms, including the formation and entrapment of microthrombi in distal vessels in situ or from emboli released from extracted occlusive thrombi. The goal of reperfusion is to salvage the surrounding tissue, which is metabolically quiet but not dead (infarcted), mainly due to retrograde filling from the collateral circulation. However, if the zone of interest is already infarcted, reperfusion can induce the very serious consequence of hemorrhage, because the vessel walls are degraded. Therefore, UV laser-induced dilation should only be used when the surrounding tissue is deemed salvageable and the likelihood of hemorrhage is deemed low.

[0123] One aspect of the invention relates to a method of reperfusing an arterial blood vessel distal to a thrombus, the method comprising: i) providing an optical fiber capable of carrying UV laser light; ii) extending an optical fiber through the thrombus; iii) emitting UV laser light from the optical fiber distal to the thrombus to dilate the arterial vessel distal to the thrombus; iv) removing the thrombus; having This allows for recirculation and blood flow and reperfusion to and from dilated arterial vessels, including vessels that would normally be unrecoverable by thrombectomy.

[0124] The extension of the optical fiber through the thrombus may preferably be for a distance suitable for UV irradiation far distal field where reperfusion may be promoted by dilation. Any emission or pulse of UV laser light in the processes described herein may be repeated to produce the desired effect of arterial dilation. The arterial vessels that are dilated and experience reperfusion as described herein are preferably arterioles as well as small branch arteries. UV laser light may also be emitted to break up, detach, or disintegrate platelet clots formed within the artery or arteriole distal to the thrombus.

[0125] In one embodiment of the present invention, the method of reperfusing an arterial vessel distal to a thrombus further comprises emitting UV laser light from an optical fiber proximal to the thrombus (inside the balloon catheter) prior to extending the optical fiber through the thrombus. The arterial vessel proximal to the thrombus is preferably illuminated with UV light for a time sufficient to break down the associated platelet layer.

[0126] In one embodiment, the method can include emitting UV laser light from the optical fiber proximal to the thrombus after extending the optical fiber through the thrombus and retracting the optical fiber proximal to the thrombus. In another embodiment, the method can include irradiating the thrombus proximal with UV laser light from the optical fiber before and after extending the optical fiber through the thrombus.

[0127] In another embodiment, the arterial vessel distal to the thrombus is illuminated with at least one burst of UV light or several intervals of UV irradiation as the optical fiber retracts from the distal side of the thrombus to the proximal side of the thrombus. The arterial vessel distal to the thrombus is preferably illuminated for a time sufficient to break down the associated platelet layer. In a preferred embodiment, the bursts of UV light energy in continuous or pulsed form can be delivered over an irradiation interval of about 2-20 seconds, preferably at least about 5-15 seconds, and more preferably about 8-12 seconds.

[0128] In another embodiment, the method can include the further step of emitting UV laser light to break up or disintegrate aggregated platelet clots formed in an artery or arteriole distal to the thrombus. In one embodiment, the method includes a thrombus that is an occlusive thrombus.

[0129] In one embodiment of the present invention, a method for reperfusing an arterial vessel distal to a thrombus includes an optical fiber provided within a guidewire, as described above.

[0130] As the transnitrosation chain process produces nitric oxide all along the path of the optical fiber that may travel into the branch arteries, the distal segments and their tributaries dilate, thereby preparing the branch arteries and arterioles to receive (reperfuse) blood when recirculation is achieved by thrombectomy.

[0131] In another embodiment of the invention, a method of reperfusing an arterial vessel distal to a thrombus includes removing the thrombus using a thrombectomy device. The thrombectomy device used to remove the thrombus can be a stentriever. In the case of stentriever deployment, UV laser induced dilation can provide increased space for deployment, thereby improving clot integrability with less damage to the dilated arterial wall. Alternatively, in another embodiment of the invention, the thrombectomy device can be an aspiration catheter. In the case of aspiration catheter deployment, UV laser induced dilation can provide reduced friction at both ends of the clot and reduce the line pressure currently required at the distal end, thus inhibiting fragmentation. All these procedural aspects are intended to ensure extraction of the clot with a minimum number of passes and also improved distal reperfusion.

[0132] The above disclosure 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 may be practiced in the absence of any element or elements, or any limitation not specifically disclosed herein. Thus, for example, in each instance herein, any of the terms "comprise", "consist essentially of" and "consist of" may be replaced by either of the other two terms. Terms and expressions are used as terms of description, not of limitation, and the use of such terms and expressions is not intended to exclude any equivalents of the features shown and described, and it should be recognized that various modifications are possible within the scope of the invention as claimed. Thus, while the present invention is specifically disclosed by preferred embodiments and optional features, it should be understood that those skilled in the art may employ modifications and variations of the concepts disclosed herein, and such modifications and variations are deemed to be within the scope of the invention as defined by the claims.

Claims

1. A combination guidewire and optical fiber capable of carrying UV laser light, wherein the guidewire is formed as a hollow tube and the optical fiber is disposed within the hollow tube for carrying UV laser light from a UV laser light source.

2. 10. The combined guidewire and optical fiber capable of delivering UV laser light of claim 1, wherein the hollow guidewire and optical fiber capable of delivering UV laser light are attached to one another.

3. 2. The combined guidewire and optical fiber capable of delivering UV laser light as described in claim 1, wherein the optical fiber capable of delivering UV laser light has a distal end configured to emit a conical beam of UV laser light.

4. 2. The combined guidewire and optical fiber capable of delivering UV laser light as described in claim 1, wherein the optical fiber capable of delivering UV laser light has a distal end configured as an external cone for emitting a conical beam of UV laser light.

5. 2. The combined guidewire and optical fiber capable of delivering UV laser light as described in claim 1, wherein the optical fiber capable of delivering UV laser light has a distal end configured as an inverted cone to emit a conical beam of UV laser light.

6. 2. The combined guidewire and optical fiber capable of delivering UV laser light as described in claim 1, wherein the optical fiber capable of delivering UV laser light has a flat distal end, the flat distal end having a concentric circular groove etched therein.

7. 4. The combined guidewire and optical fiber capable of delivering UV laser light of claim 3, wherein the distal end of the optical fiber capable of delivering UV laser light is provided as a separate tip in optical communication with the optical fiber.

8. 8. The combination guidewire and optical fiber capable of delivering UV laser light as recited in claim 7, wherein the separate tip in optical communication with the optical fiber comprises diamond.

9. 8. The combination guidewire and optical fiber capable of delivering UV laser light as recited in claim 7, wherein the separate tip in optical communication with the optical fiber comprises zirconium oxide.

10. 1. A method of reperfusing an arterial vessel distal to a thrombus, comprising: - extending an optical fiber capable of carrying UV laser light through said thrombus; - emitting UV laser light from said optical fiber distal to said thrombus to dilate an arterial vessel distal to said thrombus; - removing said thrombus; thereby permitting blood flow and reperfusion to the dilated arterial vessel.

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

12. - emitting UV laser light from the optical fiber distal to the thrombus to dilate the arterial vessel distal to the thrombus, and then retracting the optical fiber to a position proximal to the thrombus and emitting UV laser light from the optical fiber proximal to the thrombus. The method of claim 10 further comprising:

13. The method of claim 10 , wherein the step 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 stentriever.

16. The method of claim 10 , wherein the arterial vessel comprises an arteriole.

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

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