Apparatus and method for dilation of tubular anatomical structures

Abstract

To provide a method and apparatus for dilating a tubular anatomical structure.SOLUTION: An apparatus and method for dilating a tubular anatomical structure may be useful for extracting blood clots in a mammalian artery by concentrically illuminating the inner wall 102 of the occluded artery using an ultraviolet (UV) laser beam delivered by an optical fiber 101 having an external or inverted conical tip. Dilation results from the photophysical production and release of nitric oxide from the cells lining the arterial wall when UV laser light is projected as a ring beam onto the inner arterial wall. This "minimal contact persistent dilation system" prepares the artery for safer mechanical extraction by thrombectomy due to reduced friction and dissolution of chemical bonds.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] 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 onto the interior surface of the tubular anatomical structure. [Background technology]

[0002] Currently, four types of modalities 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 impact (direct ultrasound has also been used); (2) catheterization, angioplasty, and stent placement to physically widen the vessel lumen 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 the 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 injury is currently unavoidable during thrombectomy, providing poor efficacy or questionable quality of recovery in some circumstances.

[0004] Currently, there are two methods for removing vascular obstructions in dedicated clinical settings: (1) aspiration, in which negative pressure is applied proximal to the clot; and (2) extraction with a stent retriever (stentriever), in which a mesh network of expanded wires is deployed distal to the clot, resulting in direct integration of the clot into the mesh when the retriever is retracted, thus removing the clot; is considered to be quite useful.

[0005] Both aspiration and stentrieber techniques can damage the arterial endothelium and arterial wall layers in different but characteristic ways, suggesting future negative consequences for arterial structure and function. To date, the primary focus has been on rapid removal of clots by these mechanical means, without particular consideration of local or peripheral damage, especially to the normally thrombogenic endothelium. All improvements to these methods have been strictly limited to mechanical improvements in aspiration suction efficiency or stentrieber integration with the clot in an effort to remove the entire clot with a single 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 currently used interventional procedure, such as aspiration catheters or stentriebers, and arterial wall perforation can occur during catheter insertion, especially when accessing entry points to branch arteries. Furthermore, patient recovery after thrombectomy is quite poor, especially in terms of behavior. Approximately 60% of patients present with signs of residual damage, but this has only recently become an area of ​​concern, as 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 damage and risk issues arising from previously 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 dissolve occlusive thrombi within an artery. In other words, UV laser light itself is used to promote thrombus dissolution using the photophysical generation of nitric oxide (NO·), a free radical thrombin inhibitor that, when secreted from irradiated smooth muscle cells within the arterial wall, destabilizes adjacent platelet aggregates. This patent is incorporated herein by reference in its entirety. Summary of the Invention [Problem to be solved by the invention]

[0007] What is needed in the art is a device and method for dilating tubular anatomical structures containing smooth muscle cells during patient treatment 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 achieved with the dilatation system of the present invention. Preferably, the system of the present invention minimizes contact between the mechanical components of the system and the anatomical structure being dilated, thereby providing a minimal-contact dilatation system. For example, when prepared with such a system, in which UV laser light and non-mechanical pressure directly induce dilatation 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 subsequently deployed thrombectomy device promotes reduced friction and chemical adhesion before, during, and after clot retraction, thus resulting in less mechanical damage to the arterial wall. [Means for solving the problem]

[0008] Brief Summary of the Invention 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 the removal of blood clots (thrombi) from the vasculature. A method for dilating tubular anatomical structures using an optical fiber with a conical tip to create 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 the vasculature of stroke, myocardial infarction, and other iso-occlusive disorders, particularly the brain, in thrombectomy procedures performed on partially or completely occluded arteries. It may also be applicable to breaking up distal microvascular thrombi, which are known to occur in hemorrhagic stroke as a manifestation of "early brain injury."

[0010] Accordingly, 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 conical lens) or an inverted cone, both of which are capable of emitting the UV laser light as a conical beam, the emitted conical beam of UV laser light impinging on the 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 part of, the optical fiber itself, but is optically coupled, 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 that is capable of emitting UV laser light as a conical beam.

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

[0013] One 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 divergence 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 allowed by Snell's law, the thinner the projection of the ring beam on the illuminated surface, with a corresponding increase in laser intensity. Preferably, an inverted cone tip can emit an annular beam into water at an emission angle β of 20° to 56° from the central longitudinal axis of the optical fiber, with the outer cone limiting the emission angle range to 71.5°. This emission angle allows the optical fiber or tip of the present invention to emit an annular beam onto the inner wall of a tubular anatomical structure.

[0015] The present invention further relates to a dilation system including a modified thrombectomy catheter, which uses an optical fiber to deliver UV laser light. The optical fiber has a distal end or includes a tip at its distal end, and the optical fiber or tip is configured in a conical shape to emit the UV laser light as a conical beam. The optical fiber-containing dilation system 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 optical fiber-containing dilation system of the present invention may be used with an aspiration thrombectomy catheter or a stentriever. Preferably, the dilation system of the present invention minimizes physical contact with the dilated anatomical structure while still allowing the UV laser light to impinge on the structure. Because the impingement and resulting dilation can be persistent, a preferred embodiment of the present invention is referred to as a "minimal-contact persistent dilation system." Accordingly, a preferred embodiment of the system includes a "minimal-contact persistent dilation system."

[0016] In use, the dilation system of the present invention may be employed in a method of dilating a tubular anatomical structure within a patient's body. The method according to the present invention comprises: - 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 with a conical configuration; - emitting UV laser light energy through a balloon (inflated with gadolinium contrast agent adjacent to the inner wall of the tubular anatomical structure) as a circular beam onto smooth muscle cells within the inner wall of the tubular anatomical structure; This is due to the release of nitrite (NO2 - ) stores, which causes relaxation of smooth muscle cells and dilation of tubular anatomical structures.

[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 sufficiently up to the medial wall of the artery to stop blood flow, but not to dilate the artery by mechanical pressure; - Nitrite (NO2) in smooth muscle cells - emitting bursts of UV light energy as a laser beam through the gadolinium-inflated balloon wall onto smooth muscle cells in the wall of the artery to stimulate production of NO· from stores of NO·, whereby active dilation of the artery can be stimulated and observed; - removing the clots; The device may be adapted or adapted for an intravascular thrombectomy procedure further comprising:

[0018] First, a UV-transmitting 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 periphery of the structure. The balloon is inflated to the inner diameter of the tubular structure with UV-transmitting gadolinium contrast agent to ensure visibility on x-ray examination. UV irradiation is then administered intramurally through the balloon fluid.

[0019] The method of the present invention is preferably carried out by directing UV light onto the vessel wall within about 1 to about 4 vessel diameters away from the clot. The method can be carried out by using continuous UV light emission or acousto-optically Q-switched (pulsed) UV light emission at high frequencies (5-25 kHz) with pulse widths greater than 50 nanoseconds, 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 for at least 2 to a maximum of 10 seconds. In a preferred embodiment, the UV light is emitted at a wavelength of about 180-400 nm, more preferably about 300-400 nm. One preferred embodiment uses a frequency-tripled Nd:YAG laser emitting light at 355 nm to emit the UV light. The preferred incident intensity of the UV light is about 3 to about 20 watts per square centimeter.

[0020] It is understood that, according to 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 disengage therethrough. This and other objects of the present invention are provided by one or more of the embodiments described herein.

[0022] The objective of the present invention is to optimize arterial integrity during and after thrombectomy by reducing the frictional or chemical adhesion resistance to mechanical extraction of the occlusive clot. The device and method of the present invention involve providing appropriately intense UV laser irradiation of the medial arterial wall proximal to the clot when using an aspiration catheter or distal to the clot when using a stentriever when performing a thrombus extraction procedure. UV laser irradiation with a ring-shaped beam whose axis is collinear with the artery induces a distinct dilation of the arterial wall within seconds, and the dilation effect propagates proximally and distally to weaken the frictional and / or chemical adhesion 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 delivering UV light to the distal or tip of the catheter. The UV light can be emitted for a short period of time, e.g., 2-10 seconds, during saline flushing or balloon catheter inflation to clear blood from the vessel wall (but not mechanically dilate the artery), and thus can 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, with one reflection and one refraction, can effectively act as a diverging lens for the beam. This design generates a peripheral illumination pattern as an expanding conical ring, thereby generating an annular beam of laser light on the wall of the tubular anatomical structure through 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 that of fused silica, such as diamond, zirconium oxide, or custom plastics with an 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 length 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 induce dilation if the intensity criterion is met, but a larger beam exit angle promotes greater intensity and therefore more efficient use of the beam.

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

[0025] These same considerations apply equally to inverted cone tips, except that for diamond, the maximum emission angle (e.g., about 56°) is less than that from an 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 can be evaluated for clinical use. [Brief explanation of the drawings]

[0026] 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 a 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 - z) sin β and (z² + R²)½. [Figure 1B]The figure shows ray tracing along the laser axis within a protruding (external or inverted) conical-tip optical fiber. The dotted line (OO*) traces the idealized ray path of laser light within a silica optical fiber with a conical tip (total apex angle = 2α) at ​​the output end. The beam undergoes total internal reflection at point P as long as the angle of incidence θ exceeds the critical angle θ (64.653°) at the silica / water interface (and thus by inspection α < 90° - θ), and then emerges from point Q into the water-based medium with θ = 64.653°. The locus of points defined by O* when rotated around the optical axis results in a ring-shaped beam. N and N are normals to the top and bottom of the cone. From the figure, by inspection, α + θ = 90° and ω = 180° - 2θ, and therefore δ = 3θ - 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. Table 1 shows the α, β(α) and reflection and refraction angles for a pure silica optical fiber, and Table 2 shows β(α) when the tip is optically coupled 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°). [Figure 3]Figure 3 shows the optical properties of an inverted cone-tip optical fiber, showing the path of reflected and refracted laser light (entering from the right) 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 irradiation within the basilar artery (BA) of one of three dogs is shown. The dilation produced by UV irradiation 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 irradiation of the adjacent (vertebral) artery. [Figure 4B] The placement of the optical fiber tip and intravascular UV irradiation within the basilar artery (BA) of one of three dogs is shown. The dilation produced by UV irradiation 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 irradiation of the adjacent (vertebral) artery. [Figure 4C] The placement of the optical fiber tip and intravascular UV irradiation within the basilar artery (BA) of one of three dogs is shown. The dilation produced by UV irradiation 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 irradiation of the adjacent (vertebral) artery. [Figure 5] Figure 1 shows the initial deployment of a balloon catheter over a guidewire (dark gray) inserted near an arterial occlusion (thrombus) prior to UV laser-assisted 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 expand any obstructing kinks (if present) to reduce resistance to further insertion of the guidewire and replaced with the UV-emitting optical fiber to further trace the optimal route through the artery for the UV-emitting optical fiber and then the thrombectomy device. [Figure 6]Figure 5 shows a balloon catheter fully inflated on a centered guidewire, with the guidewire (white line) retracted and replaced by an optical fiber. The optical fiber emits UV laser light from a conical tip designed to generate a ring beam (elliptical locus of hash marks) at a desired angle β near the occlusion (thrombus). The output end of the fiber can be positioned as close to the thrombus as permitted by the balloon, but the UV ring beam irradiation induces 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 a few seconds and extends into the thrombus segment. The balloon is then deflated and retracted, and a thrombectomy device is now placed on the optical fiber used as the guidewire (however, practitioners may prefer to replace the optical fiber with a standard guidewire and then retract the balloon). In this configuration, an aspiration catheter is introduced to retract the thrombus, but now with less frictional resistance because the occluded arterial segment is dilated. To deploy the stentriever, the guidewire must penetrate the thrombus, possibly near its edge, and balloon deployment and other steps above occur as described. Here, dilation distal to the thrombus allows the stentriever to be deployed at a larger diameter, thereby ensuring maximum capture and complete extraction of the thrombus while maintaining stentriever integrity. [Figure 7] 1 provides a schematic overview of the application of ultraviolet laser-induced dilation to thrombectomy to minimize wall damage due to mechanical friction. DETAILED DESCRIPTION OF THE INVENTION

[0027] 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, ducts, or tubules, blood vessels such as arteries, bronchioles, ureters, vasculature, or the like.

[0028] A preferred embodiment uses a fused silica optical fiber with an inverted conical tip. The tip preferably comprises a UV-transparent material with a high refractive index in optical contact with the fused silica optical fiber. UV-transparent, very hard materials with a 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-index (n>2) plastics, 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.

[0029] One preferred embodiment of the present invention relates to an optical fiber having a core preferably between 10 and 100 μm, more preferably between 50 and 100 μm in diameter, for carrying UV laser light to the distal or tip of the optical fiber and emitting a conical 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.

[0030] 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 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 the laser ring beam is shown to have a Gaussian intensity distribution G produced by the optical fiber with an external conical tip having a cone half angle α. The distribution G is expressed as the expanded Gaussian beam profile G w The beam impinges on the inner wall 102 of the artery with radius R to generate 103. w Note that the ring beam has a polar angular spread of . The ring beam is cylindrically symmetric about the optical axis, and its central maximum is emitted at an angle β. G at point "P" 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.

[0031] FIG. 1B is a detailed view of the fused silica optical fiber with 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 is incident at an angle of incidence θ1 and meets 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 into a water-based medium, and passes through θ crit = 64.653°. When rotated around the optical axis, O *The locus of points defined by results in a ring-shaped beam. N1 and N2 are normals to the top and bottom surfaces of the cone. From the diagram, and by inspection, α+θ1=90° and ω=180°-2θ1, so 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 the sum of 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.

[0032] 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.

[0033] Figure 2B shows a UV laser ring beam generated underwater in a glass container 205 by an optical fiber with an external conical tip 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 periphery of the artery after blood displacement using a UV transparent balloon filled with a UV transparent gadolinium-based contrast medium.

[0034] Table 1 herein below provides the extent of the beam's path within the fused silica external 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 (angular depth 2θ) along the artery wall w , see FIG. 1A) can vary from a 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. While these intensity patterns are not essential to the creation of broadening, they affect the average and peak power of the beam and its upper limit.

[0035] An externally protruding conical tip according to one embodiment of the present invention is shown in Figures 1A, 1B, and 2. A sharp external conical tip (less than 40° total apex angle, less than 20° semi-conical angle, see Figures 1 and 2A) made from silica may be subject to breakage and / or entanglement by intravascular obstructions (if present). A maximally blunt external silica tip (approximately 50° total apex angle) is preferred (see Table 2). Breakage can be avoided with a tip made from a very hard material such as diamond, zirconia, or high refractive index (n>2) 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, which provides protection.

[0036] Instead, the conical tip is inverted (projects inward) at the distal end of the optical fiber, as shown in FIG. 3. Preferably, the fused silica optical fiber 301 includes an inverted diamond conical tip 310 because this design can avoid being caught 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 the diamond tip (see Table 3). A fused silica conical 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 agglomerate disintegration) process increase with emission angle, and therefore it is desirable to maximize it within the physical limits allowed by the UV-transparent, high-index fiber tip material (fused silica, diamond, zirconia, or custom plastic). The tip can be fabricated from a UV-transparent, high-index (n>2) material that is 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 a ring beam at an angle of up to about 48° relative to the longitudinal axis of the optical fiber (Table 1). If the tip is constructed from diamond (Table 2), a much wider range of emission angles can be achieved, up to about 71.5°.

[0037] Optical fibers including a conical tip—either protruding outward (everting) or protruding inward (inverted)—can be used in the present minimal-contact sustained dilation system, for example, as part of a later-deployed arterial thrombectomy catheter system. The width of the annular or ring beam emitted by the present optical fiber depends on the artery diameter. This feature can be advantageous because the dilation effect within any tubular anatomical structure, including arteries, is driven by beam intensity and can occur very quickly (<1 second) depending on the concentration of nitric oxide (NO·) photophysically generated within cells lining the tubular anatomical structure, such as the arterial wall. Irradiation at a given intensity induces a corresponding dilation, which can propagate proximally and distally from the area contacted by the annular beam via transnitrosation.

[0038] In a preferred embodiment, an optical fiber including an inverted conical tip or a blunt inverted conical 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.

[0039] Another preferred embodiment is a dilation system of the present invention that includes 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 to properly impinge the UV ring beam on the inner wall with uniform circumferential intensity.

[0040] 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-enabled optical fiber; inflating the UV-transparent balloon catheter with UV-transparent contrast fluid sufficiently up to the medial wall of the artery to stop blood flow but dilate the artery by mechanical pressure; positioning a UV fiber optic thrombectomy catheter within 1 to 4 vessel diameters of a clot contained within the vessel; emitting UV light energy as a ring beam onto smooth muscle cells within the medial 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.

[0041] The above procedure may be performed in preparation for the use of an aspiration catheter or stentriever.

[0042] Figures 4A, 4B, and 4C show the deployment of our fiber optic device to achieve intravascular 355 nm UV laser irradiation within the basilar arteries (BAs) 401, 402, and 403 at baseline in three dogs (the BA origins are marked with *, respectively). The dilation produced by 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 from accessing the ostium of the basilar artery before UV irradiation. In Dog A, the fiber tip 411 could be placed 22% distal to the BA origin, which is optimal, whereas in Dogs B and C, the fiber tips 421 and 431 could only be placed proximal to their origins (*) within 52% and 34% of the individual BA lengths. 12-20 watts / cm 2 For an irradiation intensity of 1000 nm, the mean dilation started at 78% and then progressed to 94% of baseline, decreasing linearly over a 40 mm range, although dilation was still observed at the BA end point.

[0043] 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 replace 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.

[0044] Figure 6 shows the balloon catheter 510 of Figure 5 in an inflated state, fully inflated over a guidewire, thereby centering it; the guidewire has been 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 allowed by the balloon, but the UV ring beam irradiation induces a sustained expansion away from the thrombus, starting at less than 4 and up to 40 diameters. 3-20 watts / cm 2At a beam intensity of 1000 Hz, dilation occurs in a few seconds and extends into the thrombus-affected segment. The balloon is then deflated and retracted, and the thrombectomy device is now placed on the optical fiber used as a guidewire (or perhaps the optical fiber is replaced by the initial guidewire, according to the surgeon's preference). With the above configuration, the occluded arterial segment is dilated, and now an aspiration catheter is introduced to retract the thrombus with less frictional resistance. To deploy the stentriever, the guidewire must penetrate the thrombus, possibly near its edge, above which balloon deployment and other steps occur as described. Here, dilation distal to the thrombus allows the stentriever to be deployed at a larger diameter, thereby ensuring maximum capture and complete extraction of the thrombus while maintaining the integrity of the stentriever.

[0045] FIG. 7 provides a schematic overview of the steps used in the present invention's application of ultraviolet laser-induced dilatation to thrombectomy to minimize wall damage due to mechanical friction. FIG. 7 illustrates the steps of the present method performed using the balloon catheter shown in FIGS. 5 and 6. In step A of FIG. 7, a thrombus 701 is shown positioned within 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 typical use of the device. Step D then illustrates the balloon catheter being inflated 740 to contact the inner wall of the blood vessel (artery) 721 such that blood flow is significantly or completely obstructed between the balloon and the vessel wall. UV laser light is deployed according to the 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 example only in step E, an aspiration thrombectomy catheter 750 may be used in its conventional manner to extract the thrombus 701, which is shown as being removed from the middle cerebral artery 702 in step F. The dilation produced by the UV laser contact may facilitate one or more removal steps.

[0046] 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.

[0047] In the method according to the present invention, UV light emission can be continuous for a short duration, such as 2 to 10 seconds, preferably about 5 seconds, or can be repeated as long as the light path is cleared of blood by balloon contact or saline injection. The laser irradiation interval can be filled with a beam itself composed of multiple consecutive MHz mode-locked pulses (approximately 10 picoseconds in width), referred to as a continuous-wave laser beam or quasi-continuous beam, or multiple consecutive 5 to 25 kHz pulses (maximum 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, when using a balloon, the UV light is directed onto the vessel wall within about 4 vessel diameters of the thrombus. In one preferred method, the vessel is an artery partially or completely occluded by a clot.

[0048] The UV light is emitted at a wavelength of approximately 180-400 nm, preferably approximately 300-400 nm. In one 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; however, laser UV light is not currently available at this wavelength; the 355 nm wavelength may be used with a slight decrease in efficiency. Newly developed lasers at 349 nm and 360 nm exist, but are not yet reliable enough for clinical use. Other UV-generating lasers that can be used with the present invention (but not to the point of ablation) include XeF lasers (351 nm) and continuous-wave (CW) argon-ion lasers (351, 364 nm). Any diode or dye laser can also be used, provided that it can provide output within the UV range required for non-ablative vasodilatory effects. Diode lasers are currently unable to produce wavelengths within the optimum range. 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.

[0049] In the device 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 )

[0050] The devices and methods of the present invention may be used in combination with prior administration of a pharmaceutically 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 that removes the clot without the complications of fragmentation by the thrombolytic agent.

[0051] One particular embodiment introduces a laser beam through an optical fiber deployed within a blood vessel that includes a protruding (external) conical tip that, with one reflection and one refraction, can effectively act as a diverging lens for the beam. This design generates a circumferential illumination pattern as an expanding conical ring, thereby generating an annular beam of laser light on the wall of the tubular anatomical structure through which the beam is directed. The protruding conical output tip is preferably fabricated using a UV-transmitting material with a refractive index greater than that of fused silica, such as diamond, zirconium oxide, or custom plastic 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 dilation increase because the distance to the wall, the width of the beam projected along the arterial wall, and therefore the irradiated area, all decrease.

[0052] These same considerations apply to an inverted cone tip as well, but the maximum emission angle will be less than that from an 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 are discussed above and can be evaluated for clinical use.

[0053] 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.

[0054] Another embodiment is a fused silica optical fiber (FIG. 1B) with an externally protruding tip having a maximum emission (half-cone) angle of approximately 48.4° (see Table 2). 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 a brittle material is used. This situation can be corrected by an external cone tip fabricated from a very hard material with a high refractive index, such as diamond. An inverted diamond cone tip allows an exit angle of up to 71.5°. Naturally, with increasing bluntness (increasing full cone apex angle), the external tip (including the silica itself) becomes more resistant to mechanical damage.

[0055] UV light destroys nitrite (NO2) in the smooth muscle cells of the arterial wall. - When absorbed by UV light, smooth muscle cells can release nitric oxide (NO·) at concentrations exceeding 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 via transnitrosation along localized distances of up to several centimeters proximally and distally from the site of irradiation with UV light. UV lasers induce vasodilation in the vicinity of the occlusion, thereby reducing friction with (and chemical bonding to) the arterial wall when a thrombectomy device is deployed to extract the blood clot. Thus, vasodilation can facilitate the detachment of the clot from the vessel wall to which it adheres, facilitating easier and safer removal of the clot using a conventional aspiration catheter or stentreaver (by reducing the intensity and frequency of its interaction with the vessel wall). The present invention advantageously reduces the consequences of subsequent structural and functional damage to the endothelial and intimal structures of the occluded artery to which thrombectomy is applied.

[0056] Dilation 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 more easily pass through kinks (severe bends) or stenoses in the blood vessel.

[0057] 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 use 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 a concomitant narrower projection of the ring beam of UV light. 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).

[0058] 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-index material such as diamond, zirconium oxide, or custom plastic, capable of emitting a ring beam with an emission angle (from the diamond) of up to 56° relative to the longitudinal axis of the fiber.

[0059] Another object of the present invention is to provide an optical fiber capable of delivering UV light contained within a catheter, preferably with an inverted cone-shaped tip constructed from a UV-transmitting material such as diamond, zirconium oxide, or custom plastic that can emit a ring beam for cerebral arteries. The narrow beam width concentrates the amount of energy absorbed by vascular cells, so that an effective amount of NO· is released to cause large vasodilation, even when a lower-power laser is used.

[0060] It is yet another object of the present invention to provide a dilation system that may include an aspiration catheter or stentriever preceded by a balloon catheter that includes a fused silica optical fiber capable of delivering UV light to the distal end of the catheter. 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 from a UV-transparent material with a high refractive index, such as diamond, zirconium oxide, or custom plastic. More preferably, the conical tip is an inverted cone 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 cone tip constructed from a UV-transparent, high refractive index material, such as diamond, zirconium oxide, or custom plastic.

[0061] 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 the aspiration thrombectomy catheter or stentriever incorporates a diamond or zirconium oxide (or high refractive index plastic) inverted cone tip at its distal end.

[0062] In one preferred embodiment, the balloon catheter can be inflated using a UV-transparent gadolinium-based contrast fluid; the balloon wall then displaces blood, thereby providing a clear path for UV laser light to travel to the medial arterial wall. According to the present invention, the balloon is inflated for this purpose, further centering the conical tip, rather than expanding 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 unimpeded passage of UV light through the enclosing catheter and balloon.

[0063] A further object of the present invention is a method for 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 thrombectomy catheter within the occluded vessel within 1-4 vessel diameters of the clot; c) emitting square wave pulses of UV laser light energy in a continuous or high repetition rate pulsed 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 coagulum by mechanical extraction; Includes.

[0064] In one embodiment, the UV fiber optic extension system preferably features a fused silica fiber with a diamond conical tip capable of emitting a ring beam at an angle of up to 71.5° (at the outer tip) relative to the longitudinal axis of the fiber, an angle that would be smaller for other known high refractive index materials such as zirconia and custom plastics.

[0065] Bursts of UV light energy, in continuous or pulsed form, may be emitted over an irradiation 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 dilate the blood vessel to a sufficient diameter to reduce frictional interaction of the catheter with kinks or stenosis in the blood vessel or to promote detachment of the clot from the vessel wall.

[0066] In one preferred embodiment, the present invention comprises a dilation system including an aspiration catheter or stentriever followed by a priming period using an optical fiber with 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.

[0067] In use, an optical fiber including a conical tip can emit a conical beam trajectory that irradiates a tubular anatomical structure as an annular or ring-shaped beam around the inner periphery of the tubular structure. Tubular anatomical structures that can be dilated by UV light are covered by smooth muscle cells that can store and release nitric oxide (NO·) (as nitrite). This dilation can advantageously be used to dilate or expand an artery at a location near a thrombus to facilitate easier and safer removal of the thrombus by reducing mechanical friction. The thrombus can be an occlusive or non-occlusive thrombus. Vasodilation at or near the site of a thrombus within a blood vessel can loosen or detach the thrombus from the vessel wall, thereby facilitating efficient removal of the thrombus via 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.

[0068] 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 vessel diameters of the thrombus. As used herein, the term "vessel diameter" refers to the outer diameter of the artery. Preferably, the vessel is irradiated within about 10 vessel diameters of the thrombus. More preferably, the vessel is irradiated about 1 to 4 vessel diameters away from the thrombus. The vessel can be irradiated proximal or distal to the thrombus.

[0069] Branch vessels can also 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 thrombus, because the UV-induced defect dilation effect can propagate distally (and proximally). This phenomenon can be particularly useful when the surgeon does not have feasible access to the branch vessel containing the thrombus, but has proximal access to the trunk vessel.

[0070] Preferably, the UV light beam is directed onto the interior 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 undergoes dilation at the initially irradiated portion and then self-propagates continuously over a distance of several centimeters in the proximal and distal directions.

[0071] 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), which is stored within 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).

[0072] 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 (RNSOs), and the release of NO· or its nitrates (RSNOs), which transnitrosate other thiols, thereby propagating the dilation radially, distally, and proximally with the release of more NO·. This is a self-perpetuating cascade process.

[0073] Photophysically generated nitric oxide can stimulate waves of expansion in both proximal and distal directions, thus reducing frictional resistance to clot removal over some percentage of the clot's length. Thus, clots can be extracted with less force and less trauma to the artery than currently observed, with fewer future complications at the site or distal to the site or proximal to the site.

[0074] The laser beam used to dilate arteries and thereby treat blocked blood vessels can be continuous or pulsed. The use of a pulsed laser reduces heat buildup and resulting damage to 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 consistent with delivering an adequate time-averaged intensity of irradiation to the target tissue while avoiding individual pulses of such intensity that sustained damage, i.e., irreversible damage, is produced in the target tissue within a physiologically relevant time frame (e.g., over a period of hours to weeks).

[0075] The UV light preferably has a wavelength in the range of 180-400 nm. 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.

[0076] Other UV lasers that can 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 can 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, can be used.

[0077] For 355 nm UV laser irradiation, the expansion ranges from 3 to approximately 20 W / cm in intensity, assuming a Gaussian beam shape. 2 The dilatation effect is dependent 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 / cm without inducing functional damage. 2 It can be used in.

[0078] 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 from which the beam departs just before illuminating the vessel wall or thrombus.

[0079] 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, approximately 5 watts / cm 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 Higher intensities (up to 1 J / cm at a pulse rate of 20 Hz) 2 / pulse) can produce a similar increase in diameter in larger arteries (approximately 1.5 mm diameter), but 2 Intensities exceeding 1000kJ / s may alter the vessel wall structure (small vacuoles are formed in the smooth muscle tissue), but no functional damage is observed.

[0080] 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. 2The irradiation may be increased in increments of 0.1 to 1.5 (increments of 0.1 to 1.5 or more). The period of irradiation may be continuous, i.e., sustained, until the dilatation effect plateaus, or may be intermittent; the duration of one or more 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 vasodilatory 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.

[0081] 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.

[0082] In the method of the present invention using an aspiration catheter, a balloon catheter can be introduced, followed by an aspiration catheter directly above the catheter and behind the balloon portion. A UV fiber can then be introduced into the balloon. When the UV-transmitting balloon is expanded to just exceed the diameter of the aspiration catheter before any tortuous bends or stenosis, the UV fiber is centered within the artery, and non-flowing blood is displaced from the projected light path. The UV beam can then be flashed for several seconds to achieve sufficient expansion to allow passage of the thrombectomy catheter used in the dilation system. Here, the balloon does not press against the artery to dilate it, but merely facilitates the means for displacing blood away from the artery, with the laser ring beam following an optically free path to the non-mechanical dilation of the artery. Balloons, although quite common, can be damaged if overinflated.

[0083] As UV light is emitted and absorbed on the vessel wall, the vessel dilates, propagating the dilation independently 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.

[0084] When used in combination with a stentriever, the guidewire is penetrated and moved several centimeters past the clot. A balloon catheter is then inserted to center the guidewire within the distal segment, expanded as described above, and flashed just enough to displace quiescent blood. The guidewire is retracted and replaced by a UV fiber, which illuminates the cleared arterial segment directly distal to the clot for 5–10 seconds. After expansion, the UV fiber is retracted and the stentriever replaces it through the balloon catheter. The stentriever is now centered, and the balloon catheter can be retracted. The stentriever expands to a diameter larger than the artery, allowing it to better capture the entire clot and ensure extraction efficiency.

[0085] Another benefit is the ability to use UV irradiation in locations that are difficult to traverse with a catheter toward the target clot location, which promotes safer clot extraction. A catheter that appears too large for the artery at some unpredictable 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.

[0086] A design using a silica optical fiber with an externally protruding conical tip (α=18°, Figures 1A, 1B, and 2A) was developed for intravascular deployment via a microcatheter.

[0087] [Table 1]

[0088] 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 from a UV-transparent material with a larger refractive index must be optically spliced ​​to the silica fiber. The optimal option is to use a β-beam with a refractive index of 0.5 mm. d = 2.48.

[0089] Table 2 presents the same calculations as above for a beam launched into water from an external diamond tip.

[0090] [Table 2]

[0091] Table 3 shows the extent of the path of 355 nm laser light emitted into water (saline) toward the arterial wall from inverted cone tips fabricated from silica and diamond. The emission angle β is a function of the inverted cone half angle α (depicted in Figure 3). The inverted cone tip design may be preferred by some practitioners because the chance of the tip becoming trapped in an obstruction, if present, is much lower than with an external cone tip.

[0092] [Table 3]

[0093] This calculation complements that performed on the external diamond conical tip and shows that the emission angle β is even larger compared to the inverted conical tip, thus providing increased beam intensity at reduced distances from the external conical tip (both far preferable to silica alone). However, β is surprisingly sensitive to α, which is due to the fact that the input beam experiences a polar angular spread 2θ wThis means that the beam 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. 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).

[0094] As an alternative to previously demonstrated 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, electron beam evaporation) 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 zirconia, diamond, or custom-designed plastics to obtain the desired diffraction phase profile. The pattern on the end of the fiber resembles a circularly symmetric bas-relief—a series of concentric ring structures variable in depth and radius—because material must be removed with high precision to generate the desired diffraction 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. Although ring beams with β greater than 15° have not yet been produced by this technique in any medium, to the inventors' knowledge, 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 an optimal form of device.

[0095] An external or internal conical tip can generate a ring beam at a range of angles relative to the arterial wall; for external tips, the upper limit is 48° for silica and 71.5° for diamond, with the maximum angle preferably being used. For internal diamond conical tips, the range can be up to 56°, which is preferred. A direct benefit of emitting the beam at the maximum acute angle is a reduced ring beam width and therefore greater laser intensity. The expansion process reduces the overall beam intensity (3-20 watts / cm). 2 ), lower power (and possibly more compact) lasers can be used more efficiently. The internal conical tip is designed for safety purposes, since in previous work the inventors recognized that silica external tips can be damaged. Presenting 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 less likely to occur with very hard materials such as diamond.

[0096] These and other embodiments and uses of the present invention will be apparent to those skilled in the art in light of the description provided herein. A common but 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 any prolonged vasodilatory medication reduces blood pressure to the point of pathology. Another currently untreatable aspect is early brain damage (i.e., preceding vasospasm) mediated by platelet-occluded microvessels in the brain. Despite numerous animal studies, no drugs exist that dissolve platelet clots in humans. UV laser therapy is specifically intended to treat these extremely difficult conditions. The inventors have demonstrated reversal of vasospasm within three days in dogs with hemorrhagic stroke. We 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.

[0097] We propose that UV irradiation of the feeding artery directly proximal to the distal branch and its connection with the microvascular bed allows arterial recirculation and blood reperfusion due to the autorenewal of nitric oxide over distance and its associated vasodilation, thereby improving the likelihood of tissue survival. For example, patients with ruptured cerebral aneurysms are urgently treated with standard of care interventional devices such as coils and stents. After the aneurysm is fixed, the neurointerventionalist can proceed to position the microcatheter used for coiling further 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 breaks down microvessels occluded by platelet emboli within the vascular territory, thereby improving reperfusion and clinical outcomes for patients. Cerebral vasospasm can produce vasoconstriction 3 to 21 days after aneurysm treatment. Again, by using a UV-transmitting balloon catheter and optical fiber, UV irradiation proximal to the vasoconstrictor dilates the artery, restoring it to its original (or larger) diameter, thereby restoring blood circulation.

[0098] Atherosclerotic vascular disease can cause stenosis or narrowing of the arterial lumen (stenosis) due to plaque formation. This procedure requires luminal dilation by balloon angioplasty followed by stent placement to secure the opening. Angioplasty and stent placement 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 stent placement procedure for atherosclerosis, passage of the guidewire and device through the plaque can be facilitated by UV-induced dilation of the artery. When calcified, the plaque can be very hard and incompressible. Furthermore, balloon inflation can 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 ultimately occlude the opening created by the stent. The inventors propose that non-mechanical dilation of arteries, even diseased ones, through nitric oxide pathways substantially facilitates distal access of atheromas with endovascular devices. NO pathways also minimize vascular strain and overexpression of the healing response, thus preserving the desired lumen and its useful lifespan. Endothelial damage within 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, widening 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 a stenosis, except now the stent can be placed in a dilated vessel without endothelial injury.This avoids restenosis, a very common complication of currently performed stent deployment, and the need for stent replacement within 3-5 years.

[0099] Inhaled nitric oxide can be used to treat pulmonary hypertension and acute respiratory distress syndrome, particularly in pediatric patients. The inhaled gas diffuses through the alveolar-capillary membrane, creating vasodilation, resulting in reduced pulmonary vascular resistance and increased blood perfusion in ventilated lung segments. This potentially improves blood oxygenation in patients. The proposed invention can potentially be used in a more targeted manner to vasodilate pulmonary artery segments and branches. The pulmonary arteries and their branches can be accessed through the femoral vein via right-heart catheterization. A balloon catheter can then be positioned within the targeted pulmonary artery branch. An optical fiber can be introduced within the inflated balloon to irradiate the arterial wall with a ring beam. The resulting vasodilation propagates itself proximally and distally from the area contacted by the ring beam via transnitrosation.

[0100] Inhaled nitric oxide can be used to treat pulmonary hypertension and acute respiratory distress syndrome, particularly in pediatric patients. The inhaled gas diffuses through the alveolar-capillary membrane, producing vasodilation, thereby resulting in reduced pulmonary vascular resistance and increased blood perfusion in ventilated lung segments, potentially improving blood oxygenation in patients. The proposed invention could potentially be used in a more targeted manner to vasodilate pulmonary artery segments and branches.

[0101] The pulmonary artery and its branches can be accessed through the femoral vein via right heart catheterization. A balloon catheter can then be positioned within the target pulmonary artery branch. An optical fiber can be introduced within the inflated balloon to irradiate the arterial wall with a ring beam. The resulting vasodilation propagates itself proximally and distally from the area contacted by the ring beam via transnitrosation.

[0102] The foregoing disclosure and examples generally describe the present invention and are provided for illustrative purposes only and are not intended to limit the scope of the present invention. The invention described herein may be practiced in the absence of any element or elements, or limitation, not specifically disclosed herein. Thus, for example, in each instance herein, any of the terms "comprising," "consisting essentially of," and "consisting of" may be replaced by either of the other two terms. Terms and expressions are used as terms of description, not limitation, and the use of such terms and expressions is not intended to exclude any equivalents of the features shown and described, recognizing that various modifications are possible within the scope of the invention as claimed. Thus, while the present invention has been specifically disclosed by preferred embodiments and optional features, it will be understood that those skilled in the art may employ modifications and variations of the concepts disclosed herein, and that such modifications and variations are deemed to be within the scope of the invention as defined by the claims.

Claims

1. 1. A fused silica optical fiber for carrying UV laser light, the optical fiber having a distal end configured as an inverted cone capable of emitting the UV laser light as a conical beam.

2. The optical fiber of claim 1 , wherein the emitted conical beam of UV laser light impinges on an inner wall of a tubular anatomical structure in a ring-shaped or annular configuration.

3. 10. The optical fiber of claim 1, wherein the distal end of the optical fiber includes a tip coupled to and in optical communication with the distal end of the optical fiber, the tip configured as an inverted cone capable of emitting the UV laser light as a conical beam.

4. The optical fiber of claim 3 , wherein the tip coupled to the distal end of the optical fiber is diamond.

5. 10. The optical fiber of claim 1, capable of emitting an annular beam into water at an emission angle β of about 14° up to 56° from a central longitudinal axis of the optical fiber.

6. An expansion system for expanding a tubular anatomical structure using UV laser light, comprising an optical fiber and a UV laser light source, the optical fiber being conical in shape and having a distal end capable of emitting the UV laser light as a conical beam.

7. The dilation system of claim 6 , comprising a balloon catheter.

8. The dilation system of claim 7 , wherein the optical fiber is centered within the balloon catheter.

9. The expansion system of claim 6 , wherein the optical fiber has a distal end configured as an inverted cone.

10. 7. The extension system of claim 6, wherein the optical fiber has a distal end configured as an externally protruding cone, the distal end capable of emitting an annular beam into water at an emission angle β of up to 71.5° from a central longitudinal axis of the optical fiber.

11. The expansion system of claim 6 , wherein the optical fiber includes a tip coupled to and in optical communication with the optical fiber, the tip configured as a conical shape.

12. The expansion system of claim 6 including a thrombectomy device.

13. 1. A method of dilating a tubular anatomical structure within a patient's body, comprising: providing an extension system including a catheter housing, an optical fiber for carrying UV laser light from a UV laser light source, said optical fiber having a distal end with a conical configuration; - Nitrite (NO) in smooth muscle cells ２ － and emitting UV laser light energy from the distal end of the optical fiber as a circular beam onto the smooth muscle cells of the inner wall of the tubular anatomical structure to stimulate the production and release of nitric oxide (NO.) from stores of NO., whereby the nitric oxide release causes relaxation of smooth muscle and dilation of the tubular anatomical structure. A method comprising:

14. 14. The method of claim 13, wherein the anatomical structure within the patient's body is selected from an anatomical conduit, an anatomical tube or tubule, a blood vessel, a bronchiole, a ureter, and a vasculature.

15. In an intravascular thrombectomy procedure using a thrombectomy device, positioning the UV optical fiber within about 1-10 vessel diameters of a clot in an artery and centered within the diameter of the artery; Nitrite (NO) in smooth muscle cells ２ － emitting bursts of UV light energy as a laser beam onto the smooth muscle cells on the inner wall of the artery to stimulate production of NO from stores of NO, thereby causing dilation of the artery; removing the clot; 14. The method of expanding a tubular anatomical structure within a patient's body of claim 13, further comprising:

16. The method of claim 13 , wherein the optical fiber is centered using a balloon catheter.

17. 14. The method of claim 13, wherein the balloon catheter is transparent to UV light.

18. 14. The method of claim 13, wherein the UV light is directed onto the arterial wall within about 1 to about 4 vessel diameters of the clot.

19. 14. The method of claim 13, wherein the UV light is pulsed at a high frequency of 5-25 kHz with a pulse width of greater than 50 nanoseconds, or as a quasi-continuous 100 MHz beam with a pulse width of about 10 picoseconds, or as a continuous square wave for at least 2 seconds and up to 10 seconds.

20. The method of claim 13, wherein the UV light is emitted at a wavelength of about 180 to 400 nm.

21. The method of claim 13, wherein the UV light is emitted at a wavelength of about 300-400 nm.

22. 14. The method of claim 13, wherein the UV light is emitted using a frequency-tripled Nd:YAG laser emitting light at 355 nm.

23. 14. The method of claim 13, wherein the incident UV light intensity is from about 3 to about 20 watts per square centimeter.

24. The method of claim 15 , wherein the thrombus removal device is an aspiration catheter.

25. The method of claim 15, wherein the thrombectomy device is a stentriever.

26. The method of claim 13 , wherein the conical tip is configured as an inverted cone.

27. The method of claim 13 , wherein the conical tip is configured as an inverted or externally protruding cone.

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