HK40119968A - Devices and methods for expansion of tubular anatomy - Google Patents

Description

Devices and methods for the expansion of tubular anatomical structures

Background Technology

This invention relates to the expansion of tubular anatomical structures by using ultraviolet (UV) lasers to photophysically stimulate the release of nitric oxide from smooth muscle cells on the inner wall of tubular anatomical structures (such as tubes or tubules, arteries, bronchioles, ureters, blood vessels, etc.), resulting in structural relaxation (radial expansion). More specifically, this invention relates to an optical fiber having a tapered tip for guiding annular UV beams to the inner surface of tubular anatomical structures.

There are currently four types of methods used to treat occlusive disorders. These include:

(1) High-intensity pulsed lasers are used to destroy thrombi or emboli by ablation or photoacoustic shock (direct ultrasound is also used);

(2) Catheter insertion, angioplasty and stent placement to physically expand the vascular lumen that has constricted due to atherosclerosis;

(3) Thrombolytic or thrombectomizing agents are administered to chemically separate the thrombus, followed typically by the administration of platelet inhibitors (also known as antiplatelet agents) to prevent thrombus reformation; and

(4) Thrombectomy, in which occlusive thrombi are removed by mechanical aspiration to restore blood flow.

Each of these currently available methods is associated with potentially harmful effects on the vessel wall. For example, endothelial damage is currently unavoidable in thrombectomy, and in some cases, endothelial damage can lead to poor treatment outcomes or questionable recovery quality.

There are currently two methods considered sufficient for removing vascular blockages in specialized clinical settings:

(1) Aspiration, in which negative pressure is applied proximally to the clot, and

(2) Removal by stent extractor (stenttriever) in which a mesh extension filament network is deployed in the clot, so that the clot is directly integrated into the mesh when the extractor is removed, thus removing the clot.

Both aspiration and stent retrieval methods can damage the arterial endothelium and arterial wall in different but unique ways, foreshadowing future negative impacts on arterial structure and function. At this point, the primary focus has been on the rapid removal of clots via these mechanical means, with less consideration given to local or peripheral damage, particularly to the normally antithrombotic endothelium. All improvements to these methods have been strictly limited to mechanical improvements in aspiration efficiency or the integrability of the stent retrieval device with the clot in an attempt to remove the entire clot with a single application of the device. While thrombectomy has recently achieved significant success in removing arterial occlusions, current procedures are not perfect. During clot retrieval, the arterial endothelium can be damaged due to mechanical friction. Vessel rupture is a known risk of any interventional procedure currently in use, such as aspiration catheters or stent retrieval devices, and arterial wall perforation can occur during catheter insertion, especially when entering the branch artery inlet. Furthermore, patient recovery after current thrombectomy procedures is not optimal, particularly in terms of behavior. Approximately 50% of patients show signs of residual damage, but this has only recently become an area of concern because practitioners have primarily focused on the technical aspects of clot aspiration. In this context, recovery is compromised if aspiration is inefficient (requiring up to five attempts, thus involving more mechanical interaction with the vessel wall).

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

There is a need in the art for an apparatus and method for dilating tubular anatomical structures containing smooth muscle cells during a patient's treatment while simultaneously mitigating and minimizing damage to the anatomical structure and reducing the risk of subsequent harm to the patient during medical procedures. This can be accomplished by an dilation system according to the invention. Preferably, the system of the invention minimizes contact between the mechanical components of the system and the anatomical structure being dilated, thus providing a minimal-contact dilation system. For example, when preparing with such a system, thrombectomy using aspiration catheters, stent thrombectomy devices, or other mechanical thrombectomy devices can be performed more easily and with less endothelial damage, where UV laser, rather than mechanical pressure, directly induces dilation of the occluded artery. Preparing the artery in this way for subsequent deployment of thrombectomy devices helps reduce friction and chemical bonding, and therefore less mechanical damage to the arterial wall before, during, and after clot removal.

Summary of the Invention

This invention is particularly applicable to the dilation of arteries using optical fibers capable of delivering UV light in the form of a ring-shaped laser beam to the arterial wall to reverse vasospasm consistent with hemorrhagic stroke or to facilitate the removal of blood clots (thrombi) from the vascular system. A method for dilating tubular anatomical structures by using a tapered-tipped optical fiber to create a ring shape and deliver a laser beam to the inner wall of the tubular structure is also part of this invention.

This device and method are particularly suitable for thrombectomy procedures involving partially or completely occluded arteries, for the treatment of stroke, myocardial infarction, and other vascular occlusive disorders, especially thrombi that form within the vascular system of the brain. It can also be used to dissolve distal microvascular thrombi known as a manifestation of “early brain injury” in hemorrhagic stroke.

Therefore, the present invention includes a fused silica fiber for carrying a UV laser, wherein the fiber has a distal end configured as an inverted cone (i.e., a negative conical lens) or an everted cone, both of which are capable of emitting the UV laser as a conical beam. The emitted conical UV laser beam impacts the inner wall of a tubular anatomical structure in a ring or annular configuration.

The tapered distal end of the optical fiber can be configured as a tip that is separate from the optical fiber itself, i.e., not part of the optical fiber, but optically coupled and preferably physically coupled and connected to the distal end of the optical fiber, such that the tip is in optical communication with the optical fiber. Preferably, the tip is configured to have a distal end that is formed as an outwardly folded cone capable of emitting a UV laser as a tapered beam.

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

A preferred embodiment of the fiber tip of the present invention is in the shape of an inverted cone (e.g., a negative-axis pyramid), which is capable of emitting a ring-shaped beam into water from above the central longitudinal axis of the fiber at an emission angle β of up to 56°. An outwardly tapered tip can emit light at an angle β up to 71.5°. These angles are necessarily approximate values because the natural angular spread of the laser beam may exceed the critical angle for total internal reflection, thereby reducing some of the beam power.

The larger the angle allowed by Snell's law, the thinner the projection of the ring beam onto the irradiated surface, with a corresponding increase in laser intensity. Preferably, the inverted conical tip can emit a ring-shaped beam into water from the central longitudinal axis of the fiber at an emission angle β ranging from 20° to 56°; for the outer cone, the limit of the emission angle range is 71.5°. Utilizing this emission angle, the ring-shaped fiber or tip of the present invention can emit a ring-shaped beam of maximum permissible intensity onto the inner wall of a tubular anatomical structure.

The present invention further relates to an expansion system comprising a thrombectomy catheter modified to carry a UV laser using an optical fiber having a distal end or including a tip thereat, wherein the optical fiber or the tip is configured in a tapered shape to emit the UV laser as a beam with a tapered trajectory. An expansion system incorporating the optical fiber of the present invention may configure the distal end or tip of the optical fiber as an inverted (inwardly projecting) cone or an externally projecting cone. An expansion system incorporating the optical fiber of the present invention may be used in conjunction with an aspiration thrombectomy catheter or a stent thrombectomy device. Preferably, the expansion system of the present invention minimizes physical contact with the anatomical structure to be expanded, but still allows the UV laser to impact the structure. Because the impact and the resulting expansion can be continuous (>1 day), a preferred embodiment of the present invention is referred to as a “minimum contact continuous expansion system.” Therefore, a preferred embodiment of the system includes a “minimum contact continuous expansion system.”

In use, the expansion system of the present invention can be used in methods for expanding tubular anatomical structures within a patient's body. The method according to the present invention includes the following steps:

- Provides a catheter housing that accommodates a UV-transparent balloon expanded with a UV-transparent gadolinium-based contrast agent, within which an optical fiber for carrying a UV laser is inserted, wherein the optical fiber has a distal or tip with a tapered configuration; and

- UV laser energy is emitted as a ring beam of uniform intensity onto the smooth muscle cells within the tubular anatomy via a balloon (expanded with gadolinium contrast agent to be adjacent to the inner wall of the tubular anatomy). This stimulates the photophysical generation and release of nitric oxide (NO) from the nitrite ( _NO₂⁻ ) reserves in ^the arterial smooth muscle cells, thereby causing relaxation of the smooth muscle cells and dilation of the tubular anatomy. Dilation can be achieved even with endothelial disruption; the photophysical NO generated by UV light exposure functionally replicates the NO normally produced by the endothelial enzyme nitric oxide synthase.

This method can be adapted to or applied to endovascular thrombectomy procedures, and further includes the following steps:

- Position the UV fiber optic ablation system within approximately 1 to 10 vessel diameters of the clot within the artery containing the clot;

- The UV-transparent balloon catheter is extended to the inner wall of the artery using UV-transparent gadolinium contrast fluid. This is sufficient to stop blood flow but does not cause the artery to dilate due to mechanical pressure.

- A burst of UV light energy is emitted as a laser beam through the wall of the gadolinium-expanded balloon and onto the smooth muscle cells in the arterial wall to stimulate the production of NO from the nitrite ( _NO2- ⁾ reserves in the smooth muscle cells, thereby stimulating active dilation of the artery, which can be observed; and

- Mechanically remove the clot (e.g., through thrombectomy) to restore circulation to the trunk of the artery and its branches (recirculation).

First, a UV-transparent balloon catheter is deployed into the tubular structure to center the tapered tip of the inserted optical fiber, ensuring uniform irradiation intensity around the periphery of the structure. The balloon can then be expanded to the inner diameter of the tubular structure using a UV-transparent gadolinium contrast agent to ensure visibility during X-ray examination. UV irradiation is then conducted through the balloon fluid and into the wall of the balloon.

The method of the invention is preferably performed by directing UV light onto the vessel wall within approximately 1 to 4 vessel diameters away from the clot. This method can be performed using continuous UV light emission or UV light emission with acousto-optic Q-switching (pulsed) at a high frequency (5 to 25 kHz) (with a pulse width greater than 40 nanoseconds) to ensure transmission through the silica fiber due to minimized two-photon absorption, or as a quasi-continuous beam having a picosecond pulse width, for example, pulsed at 100 MHz with a pulse width >10 picoseconds, or as a square wave lasting at least 2 to 15 seconds. In a preferred embodiment, the UV light is emitted at a wavelength of approximately 180 to 400 nm, more preferably at a wavelength of approximately 300 to 400 nm. A preferred embodiment uses a frequency-triple-harmonic Nd:YAG laser emitting light at 355 nm to emit UV light (close to the maximum absorption value of NO-emitting substances, such as S-nitrosothiol). The preferred incident intensity of the UV light is between approximately 3 W/cm² and approximately 20 W/cm².

Based on the methods described herein, it will be understood that the thrombectomy catheter used in the thrombectomy procedure can be an aspiration catheter or a catheter through which a stent thrombectomy device is inserted.

The object of this invention is to provide a less invasive or damaging method for removing thrombi from arteries in mammals by non-mechanically opening a large-diameter path for use with invasive interventional devices and for the passage of the thrombus to be removed. This and other objects of the invention are provided by one or more embodiments described herein.

The object of this invention is to optimize arterial integrity during and after thrombectomy by reducing frictional or chemical bonding resistance to the mechanical removal of occluded clots. The apparatus and method of this invention include, during the performance of thrombectomy techniques, providing UV laser irradiation of appropriate intensity to the arterial wall proximal to the clot when using an aspiration catheter or distal to the clot when using a stent thrombectomy device (however, simultaneous distal and proximal irradiation may be advantageous). UV laser irradiation via a ring beam with its axis collinear with the artery causes significant dilation of the arterial wall within seconds, wherein the dilation effect propagates proximally and distally to weaken or release frictional and/or chemical bonding between the clot and the wall.

Another object of the present invention is to provide an aspiration catheter or stent thrombectomy device that further includes an optical fiber capable of transmitting UV light to the distal or tip of the catheter. The UV light can be emitted for a very short period, e.g., 2 to 15 seconds, during saline flushing or balloon catheter dilation to clear blood from the vessel wall (but without mechanically dilating the artery), and is thus guided to the smooth muscle cells constituting the vessel wall. One particular embodiment introduces a laser beam via an intravascularly deployed optical fiber comprising a protruding (external) tapered tip that can effectively serve as a diverging lens (in effect, a negative-axis pyramid) for the beam through a single reflection and a single refraction. This design will produce a circumferential irradiation pattern as an expanding conical ring, thereby generating a ring-shaped laser beam on the wall of the tubular anatomy to which the beam is directed. The protruding tapered output tip is preferably made of a UV-transparent material with a refractive index n higher than fused silica, such as diamond, zirconium oxide, or a custom polymer material with n>2 that can be optically coupled to silica. As the exit angle β increases, beam intensity and arterial dilation efficiency also increase, while the beam width projected along the arterial wall decreases because the irradiated annular region also shrinks. If the intensity criterion is met, any projection length along the arterial wall will cause dilation, but a larger beam exit angle favors greater intensity and therefore more efficient use of the beam.

The intensity of the UV ring beam around the circumference of the artery is intended to be constant to ensure the repeatability of the procedure. This is facilitated by centering the fiber optic cable using a UV-clear balloon catheter. If the structure is an artery, expanding the balloon will block blood flow but will not itself dilate the artery. The arterial wall is then irradiated through the balloon wall with minimal contact with the artery.

These same considerations also apply to the inverted conical tip, but in diamond, the maximum emission angle (e.g., about 56°) will be smaller than the maximum emission angle of the outer tip (e.g., 71.5°). The intention is to provide two different ways to produce beams in an extended ring shape, the relative benefits of which have been described above and can be evaluated for clinical application.

In another embodiment of the invention, an optical fiber for emitting a UV laser is disposed within a guidewire used in an arterial catheter. Preferably, this embodiment comprises a guidewire formed as a hollow tube, such that an axial cavity or inner cavity is formed along the entire length of the guidewire. An optical fiber having an external, inverted, or etched (diffractive optical element - DOE) tapered tip as described herein can be disposed within the cavity of the hollow guidewire. The optical fiber can be attached to or removed from the cavity of the guidewire. In one embodiment, the optical fiber can be manually configured to a “locked position” whereby it is attached to the guidewire, and manually configured to an “unlocked position”, thereby allowing the guidewire and the optical fiber to be operated independently and separately from each other. It can be advantageous to combine and arrange the optical fiber within the guidewire by eliminating certain steps of the catheter insertion process. The combined guidewire and optical fiber can have a distal end configured to emit a tapered UV laser beam.

In one embodiment, the distal end of the combined guidewire and fiber is configured as an external cone. In another embodiment, the distal end of the combined guidewire and fiber is configured as an inverted cone capable of emitting a tapered UV laser beam. In yet another embodiment, the combined guidewire and fiber includes a flat distal end on which concentric circular grooves (DOEs) are etched to serve as a negative-axis pyramidal lens.

The distal end of the combined guidewire and optical fiber may include a separate tip in optical communication with the optical fiber. This separate tip in optical communication with the optical fiber may be made of diamond, zirconium oxide, or a polymer material (e.g., plastic).

One aspect of the present invention relates to a method for reperfusion of an artery distal to a thrombus, wherein the method includes the following steps:

i) Provide optical fibers capable of carrying UV lasers;

ii) Extend the optical fiber through the thrombus;

iii) Firing a UV laser from an optical fiber distal to the thrombus to dilate the artery distal to the thrombus; and

iv) Remove the blood clot;

This allows blood to flow into the dilated arterial microvessels and be reperfused.

In one embodiment, the method includes the step of emitting a UV laser from the fiber proximal to the thrombus before extending the fiber through the thrombus. In another embodiment, after emitting a UV laser from the fiber distal to the thrombus, the fiber can be withdrawn to a location proximal to the thrombus, and then a UV laser can be emitted proximal to the thrombus. In one embodiment, the method may include emitting a UV laser from the fiber proximal to the thrombus before and after extending the fiber through the thrombus. In one embodiment, the method includes the thrombus as an occlusive thrombus.

The optical fiber can be extended through the thrombus, preferably to a distance suitable for the distal field of UV irradiation, in which reperfusion can be enhanced by dilation. Any emission or pulse of the UV laser described herein can be repeated to produce the desired arterial dilation effect. The arterial vessel dilated and undergoing reperfusion is preferably a microartery. Nitric oxide generated by the interaction of the emitted UV laser with smooth muscle cells can also dissociate (through dethrombosis) or break down platelet clots formed in arteries or microarteries distal to the thrombus, because nitric oxide inhibits thrombin, which is required for strong platelet binding via fibrinogen.

In the method described herein for reperfusion of arteries distal to thrombi, optical fibers can be provided in combination with hollow guidewires as described above.

In the method according to the invention for establishing recirculation or reperfusion in an occluded artery, a thrombectomy device is preferably used to remove the thrombus. The thrombectomy device for removing the thrombus can be a stent thrombectomy device or an aspiration catheter.

Another embodiment of the invention relates to a method for enhancing reperfusion (i.e., restoring circulation) in small arterial branches distal to a thrombus that cannot be directly treated by thrombectomy, wherein the method includes the following steps:

i) Provide optical fibers capable of carrying UV lasers;

ii) Allowing the optical fiber to extend through the thrombus that occludes the aortic trunk;

iii) Firing a UV laser from an optical fiber distal to the thrombus to dilate small branch arteries distal to the thrombus; and iv) Removing the thrombus.

This allows blood to flow through the aortic trunk (i.e., recirculation) and through distal arterioles and arteriole branches (such as microarteries, which cannot be directly treated by thrombectomy) formed by dilation and dethrombosis to establish reperfusion.

In one embodiment, the method includes the step of emitting a UV laser from the fiber proximal to the thrombus before extending the fiber through the thrombus. In another embodiment, after emitting a UV laser from the fiber distal to the thrombus, the fiber can be withdrawn to a location proximal to the thrombus, and then a UV laser can be emitted proximal to the thrombus. In one embodiment, the method may include emitting a UV laser from the fiber proximal to the thrombus before and after extending the fiber through the thrombus. In one embodiment, the method includes the thrombus as an occlusive thrombus.

Any emission or pulse of the UV laser described herein can be repeated to produce the desired arterial dilation effect. The arteries that dilate and undergo reperfusion are preferably branch arteries and arterioles. The UV laser can also be emitted to destabilize platelet clots formed in arteries or arterioles distal to the thrombus (through dethrombosis).

In the method described herein for reperfusion of small arterial branches distal to a thrombus, an optical fiber can be provided in combination with a hollow guidewire as described above.

In the method according to the invention for reperfusion of small arterial branches distal to a thrombus, a thrombectomy device is preferably used to perform the step of removing the thrombus from the aortic trunk. The thrombectomy device for removing the thrombus can be a stent thrombectomy device or an aspiration catheter.

Attached Figure Description

Figure 1A shows the upper half of the z-plane cross-section of a laser ring beam (generated by an optical fiber with an outer tapered tip having a conical half-angle α) with a Gaussian intensity distribution G _₀, which produces an extended Gaussian beam profile G _{_w} upon impact with the inner wall of an artery of radius R. Note that the beam has an extreme angular extension of 2θ_{_w}. The ring beam is cylindrically symmetric about the optical axis, with its central maximum emanating at an angle β. The intensity profile of G _₀ is drawn at 1/9 scale. The intensity of G_{_w} at point “p” is a function of r _{_w} = (z – z_{_o} )sinβ and also a function of (z ^² + R^² ) ^{^1/2} .

Figure 1B illustrates axial ray tracing of a laser beam in an optical fiber with a protruding (outer or flared) tapered tip. The dashed line (OO*) traces the path of the ideal laser beam at the output end of a silica fiber with a tapered tip (total apex angle = 2α). As long as the incident angle _θ1 is greater than the critical angle _θcrit (64.653°) at the silica/water interface (and therefore α < 90° – _θcrit ), the beam will undergo total internal reflection at point P and then enter the water-based medium from point Q, where _θcrit = 64.653°. The trajectory of the point defined by O* produces a loop-shaped beam as the beam rotates about the optical axis. _N1 and _N2 are the normals to the top and bottom surfaces of the cone. According to the figure, α + _θ1 = 90° and ω = 180° - _2θ1 , therefore δ = _3θ1 - 180° = 90° - 3α. The ring beam trajectory is a conical surface defined by the angle β(α) = _θ₁ - α - γ(α), which was also determined by examination. γ(α) is expressed as ^sin⁻¹ {( _n₁ / _n₂ )cos 3α}. According to Snell's law, β(α) can now be determined based on the half-angle α at the tip of the fiber taper.

Figure 2A shows an external tapered tip machined on a fused silica fiber with a full apex tapered angle (2α) of 36° according to an embodiment of the present invention.

Figure 2B shows the UV laser ring beam generated in water by the external conical tip shown in Figure 2A. Table 1 shows the values of α and β(α) of pure silica fiber, as well as the reflection and refraction angles, and Table 2 shows β(α) when the tip is optically coupled diamond. The range and value of β(α) for diamond (up to 71.5°) are significantly increased compared to silica itself (up to 48.4°).

Figure 3 illustrates the optical properties of an inverted conical-tipped optical fiber, showing the path of reflected and refracted laser light (entering from the right) in a fused silica fiber with an inverted conical tip or a tip made of diamond, where the beam enters water (saline) and reaches the inner wall of the artery. The maximum emission angle β(α) of diamond entering water is approximately 56°, which is significantly greater than the maximum emission angle (25.4°) from silica alone; see Table 3.

Figures 4A, 4B, and 4C illustrate fiber tip placement and intravascular UV irradiation in the basilar artery (BA) of three dogs. The dilation induced by UV irradiation is semi-local; for a basilar artery with a length of ~40 mm, dilation can extend up to 60 mm from the trajectory of the ring beam irradiation of an adjacent (vertebral) artery.

Figure 5 illustrates 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. When the balloon is inflated or nearly inflated, the guidewire will be effectively centered in the artery. At this point, the guidewire can be withdrawn and replaced with a UV-emitting fiber to expand any obstructions (if present) to reduce resistance to further guidewire insertion, allowing for optimal tracking of the UV-emitting fiber and subsequent thrombectomy device through the artery.

Figure 6 shows the balloon catheter of Figure 5, fully inflated over a centrally located guidewire, which is then withdrawn and replaced by an optical fiber (white line) emitting a UV laser from its tapered tip. This laser is synthesized to produce a ring beam (elliptical oblique trajectory) at a desired angle β near the occlusion (thrombus). The output end of the fiber can be placed as close to the thrombus as the balloon allows, but the UV ring beam irradiation will cause sustained arterial dilation, starting from <4 diameters away from the thrombus and continuing up to 40 diameters. At beam intensities of 3 to 20 watts/ ^cm² , dilation will occur within seconds and extend into the thrombus segment. The fiber is then withdrawn, and the thrombectomy device is then mounted over the deflated balloon. In this configuration, an aspiration catheter is introduced to aspirate the thrombus, as the frictional resistance is now lower due to the dilation of the occluded arterial segment. To deploy the stent thrombectomy device, the guidewire must penetrate the thrombus (possibly near the edge) and the balloon deployed over it, followed by the other steps as described. Here, expansion distal to the thrombus will allow the stent thrombectomy device to be deployed with a larger diameter, thus ensuring maximum thrombus interception and complete retrieval with less fragmentation, provided the integrability of the stent thrombectomy device is preserved. Similarly, given the possibility of fragmentation, the aspiration procedure may benefit from both distal and proximal irradiation, since the suction force is not uniformly distributed along the thrombus.

Figure 7 provides an illustrated overview of applying ultraviolet laser-induced dilation in thrombectomy to minimize wall damage due to mechanical friction.

Figure 8A shows a combination of hollow guide wire and optical fiber, with the optical fiber arranged inside the hollow guide wire.

Figure 8B shows a combination of hollow guide wire and optical fiber, wherein the optical fiber arranged in the hollow guide wire has an external tapered tip.

Figure 8C shows a combination of a hollow guidewire and an optical fiber, wherein the optical fiber arranged within the hollow guidewire has an inverted conical tip.

Figure 8D shows a combination of a hollow guide wire and an optical fiber, wherein the optical fiber arranged within the hollow guide wire has an etched tip that serves as a negative-axis pyramidal lens (i.e., a diffractive optical element – DOE).

Figure 9A shows a front view of the distal end of the optical fiber, which is etched into concentric rings of V-shaped grooves formed in the fiber to produce a diffractive optical element (DOE) used as a negative-axis pyramidal lens.

Figure 9B shows a three-dimensional cross-sectional view of the optical fiber in Figure 9A.

Detailed Implementation

This invention relates to an apparatus and method for dilating tubular anatomical structures, such as arteries, wherein dilution is induced by directing an ultraviolet (UV) laser beam of appropriate intensity onto the wall of the tubular anatomical structure without causing functional damage to the cells of the structure. The apparatus, system, or method of this invention can be used for anatomical structures such as anatomical tubes, pipes, or tubules, blood vessels (such as arteries), bronchioles, ureters, and vasculature.

A preferred embodiment employs a fused silica fiber including an inverted conical tip. The tip preferably comprises a UV-transparent material with a high refractive index that is in optical contact with the fused silica fiber. For the tip, a UV-transparent and very rigid material with a high refractive index is preferred, such as diamond (refractive index 2.48 at 355 nm) or zirconium oxide (refractive index 2.3 at 355 nm), or a custom-designed high refractive index (n>2) polymer material. This tip can provide the ability to generate a UV ring beam exit angle (half-cone angle) of up to 56° (using an inverted conical tip) or 71.5° (using an outward-curved conical tip), both of which are made of diamond.

A preferred embodiment of the present invention relates to an optical fiber, preferably with a diameter of 10 to 100 μm, more preferably 50 to 100 μm, for transmitting UV laser light to the distal or tip end of the fiber and emitting a tapered UV laser beam that impacts the inner wall of a tubular anatomical structure in the form of an extended ring or annular beam. The optical fiber is preferably a solid fused silica optical fiber. In a preferred embodiment, the solid optical fiber used is not a hollow optical fiber, nor does the solid optical fiber include hollow optical fiber as any part or extension thereof.

To achieve this ring beam formation, the distal end of the fused silica fiber can be formed into a conical shape; for example, an externally conical shape (protruding outwards), or it can be an inverted conical shape (protruding inwards). As shown in Figure 1A using a silica fiber with an externally conical tip 101 positioned within a microcatheter 104, the upper half of the z-plane cross-section of the laser ring beam is shown as having a Gaussian intensity distribution G _₀ generated by the fiber with the externally conical tip, which is struck by the inner wall 102 of an artery with a radius R by the distribution G_₀ having a conical half-angle α, to produce an extended Gaussian beam profile G _{_w} 103. Note that the beam has an extreme angular extension of 2θ_{_w}. The ring beam is cylindrically symmetric about the optical axis, with its central maximum emitted at an angle β. The intensity of G _{_w} at point “P” is a function of r _{_w} = (z – z_{_o} )sinβ, and also a function of (z ^² + R ^²)^{^1/2}. As shown in the figure, fiber optic cable 101 is positioned proximal to thrombus 105(T) for use.

Figure 1B is a detailed view of the fused silica fiber with an external tapered tip 101 shown in Figure 1A, illustrating axial ray tracing of the laser in the fiber with the prominent (external) tapered tip. The dashed line (OO*) traces the path of the ideal laser beam at the output end of the silica fiber with the tapered tip (total apex angle = 2α). As long as the incident angle _θ1 is greater than the critical angle _θcrit (64.653°) at the silica/water interface (and therefore α < 90° – _θcrit ), the beam will follow total internal reflection at point P and then enter the water-based medium from point Q, _θcrit = 64.653°. The trajectory of the point defined by O* produces a loop-shaped beam when rotated about the optical axis. _N1 and _N2 are the normals to the top and bottom surfaces of the cone. According to the diagram, upon examination, α + _θ₁ = 90° and ω = 180° - _2θ₁ , therefore δ = _3θ₁ - 180° = 90° - 3α. The ring beam trajectory is a conical surface defined by the angle β(α) = _θ₁ - α - γ(α), which is also obtained through examination. γ(α) is expressed as ^sin⁻¹ {( _n₁ / _n₂ )cos 3α}. According to Snell's law, β(α) can now be determined based on the half-angle α at the tip of the fiber taper.

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

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

Table 1 below provides the path range of the beam in the fused silica outer tapered tip of the fiber with a semi-conical angle α, and the angles associated with a first total internal reflection and a first refraction, resulting in the beam exiting the tip at an angle β(α). The annular beam cross-section along the arterial wall (angular width _2θw , see Figure 1A) can vary from a Gaussian profile to a super-Gaussian “high-cap” profile, i.e., the typical output mode of a multimode fiber, which at its maximum expression means a substantially constant intensity over the annular width. These intensity modes are not important for the generation of the expansion, but they do affect the average and peak power of the beam and their upper limits.

Figures 1A, 1B, and 2 illustrate an externally protruding tapered tip according to an embodiment of the invention. A sharp externally tapered tip made of silica (full apex angle <40°, half-taper angle <20°; see Figures 1 and 2A) may break and/or become entangled due to intravascular obstructions, if present. A maximally passivated external silica tip (full apex angle approximately 50°) is preferred (see Table 2). Tips made of very rigid materials (such as diamond, zirconium oxide, or high-refractive-index (n>2) polymers (e.g., plastics)) can avoid breakage, but entanglement is still possible, depending on the complementary device array used. In practice, optical fibers are introduced via catheters, which provide isolation and therefore protection.

Alternatively, the tapered tip can be inverted (protruding inward) at the distal end of the fiber, as shown in Figure 3. Preferably, the fused silica fiber 301 includes an inverted diamond tapered tip 310, as this design avoids entrapment by intravascular obstructions and is less likely to be damaged during insertion or deployment. This tip enables the emission of a ring-shaped beam into water at emission angles up to 56° above the diamond tip (see Table 3). The inverted fused silica tapered tip can produce emission angles between 20° and 24° relative to the central longitudinal axis of the fiber (see Table 3). The beam intensity and the efficiency of the expansion (and associated clot dissolution) process increase with the emission angle at which the ring beam of UV light is projected onto the inner wall of the tubular structure (i.e., the artery), thus maximizing this emission angle within the physical limits allowed by the UV-transparent high-refractive-index fiber tip material (fused silica, diamond, zirconia, or a custom polymer material). The tip can be made of a UV-transparent high-refractive-index (n>2) material coupled to a conventional fiber, wherein the coupled tip and fiber are optically connected to each other. The coupled tapered tip of a silica fiber can bulge outward from the distal end of the fiber and emit an unobstructed ring beam at an angle of up to approximately 48° relative to the longitudinal axis of the fiber (Table 1). If the tip is made of diamond (Table 2), a wider range of emission angles up to approximately 71.5° can be achieved.

Optical fibers, including those with tapered tips (convex outward (extraflexed) or inward (inverted)), can be used in the minimal-contact continuous dilation system of the present invention, for example, as part of a subsequently deployed arterial thrombectomy catheter system. The width of the annular or ring-shaped beam emitted by the optical fiber of the present invention depends on the fiber radius and angle α of the tapered fiber. This feature can be advantageous because the dilation effect in any tubular anatomy (including arteries) is driven by the beam intensity and can occur very rapidly (<1 second), depending on the concentration of photophysically generated nitric oxide (NO) in the cells lining the tubular anatomy (e.g., arterial wall). Irradiation at a given intensity will induce a corresponding dilation, which itself can propagate proximally and distally from the region of contact with the annular beam via a transnitroso reaction.

In a preferred embodiment, an optical fiber including an inverted conical tip or a blunt, everted conical tip can be used in conjunction with a balloon catheter including a UV-clear balloon for thrombectomy. Preferably, a guidewire introduced in the proximal segment of the occlusion can be centered through a UV-clear balloon catheter and expanded with a UV-clear gadolinium-based contrast agent, whereby the guidewire is replaced by an optical fiber.

Another preferred embodiment is the expansion system of the present invention, which includes an inverted conical tip or a blunt, everted conical tip that is combined with a balloon catheter and used sequentially with a stent retrieval device. In this embodiment, a guidewire is initially penetrated, wherein the guidewire must be centered in the expanded balloon catheter and then replaced by an optical fiber so that the UV ring beam appropriately impacts the inner wall with uniform circumferential intensity.

Another aspect of the present invention relates to a method for performing an intravascular thrombectomy procedure, wherein the method includes the following steps:

- Provides thrombectomy catheters compatible with UV-guided fiber optic cables;

- The UV transparent balloon catheter is extended to the inner wall of the artery using UV transparent contrast fluid, which is sufficient to stop blood flow but does not cause the artery to dilate due to mechanical pressure;

- Position the UV fiber optic thrombectomy catheter within one to four vessel diameters of the clot contained within the vessel;

- UV light energy is emitted as a ring beam onto the smooth muscle cells in the inner wall of the artery to induce the formation and release of nitric oxide (NO) and thereby dilate the artery, regardless of the integrity of the endothelium (a common source of NO) or the presence of blood; and

- Remove the clot.

The above procedure can be performed when preparing to use an aspiration catheter or stent thrombectomy device.

Figures 4A, 4B, and 4C illustrate the deployment of our fiber optic device to achieve intravascular 355 nm UV laser irradiation in the basilar artery (BA) 401, 402, and 403 at baselines in three dogs (the BA origin is indicated by * for each). The dilation caused by the subsequent UV irradiation is semi-local; for a basilar artery of ~40 mm in length, dilation can extend from the trajectory of the ring beam irradiation of the adjacent (vertebral) artery to 60 mm (Figures 4B and 4C). Figures 4B and 4C indicate that vertebral artery constriction prior to UV irradiation prevents the fiber tip from entering the basilar artery orifice. While for dog A, fiber tip 411 can be placed at 22% distal to the BA origin, which is optimal, for dogs B and C, fiber tips 421 and 431 can only be placed within 52% and 34% of the corresponding BA length proximal to their origin (*). For irradiation intensities of 12 to 20 W/ ^cm² , the average expansion reached 94% of the baseline after starting at 78%, and although it decreased linearly over a 40 mm range, expansion was still observed at the end of the BA.

Figure 5 illustrates the initial deployment of a balloon catheter 510 on a guidewire 520 inserted near the arterial occlusion (thrombus) 530 prior to UV laser-assisted thrombectomy. The balloon is partially inflated (shown here as not contacting the inner wall of the artery 540). When the balloon is inflated or nearly inflated, the guidewire will be effectively centered in the artery. At this point, the UV-emitting fiber can replace the guidewire and expand any obstructions (if present) to reduce resistance to the guidewire, and the guidewire can temporarily replace the UV fiber to further track the optimal route through the artery toward the thrombus, after which the UV fiber is reinserted, followed by the thrombectomy device.

Figure 6 illustrates the balloon catheter 510 of Figure 5, which is fully inflated over a guidewire to center it, and the guidewire has been replaced by an optical fiber 610 that emits UV laser light from a tapered tip capable of generating a ring beam 620 at the desired angle β. The output end of the fiber can be placed as close as possible to the thrombus 530 as the balloon allows, but UV ring beam irradiation will cause sustained expansion, starting from <4 diameters away from the thrombus and continuing up to 40 diameters. At beam intensities of 3 to 20 watts/ ^cm² , expansion will occur within seconds and extend into the thrombus segment. The fiber is then withdrawn, and a thrombectomy device (e.g., an aspiration catheter) is then mounted over the deflated balloon microcatheter, now with less frictional resistance due to the expansion of the occluded arterial segment. Alternatively, to deploy a stent thrombectomy device, the guidewire must penetrate the thrombus distally and a balloon must be deployed thereon, followed by the other steps as described above. Here, UV-induced expansion distal to the thrombus will allow the stent thrombectomy device to be deployed with a larger diameter, thereby ensuring that the thrombus can be intercepted and completely removed to the maximum extent possible, provided that the integrability of the stent thrombectomy device is preserved.

Figure 7 provides an illustrated overview of the steps employed in this invention to apply ultraviolet laser-induced dilation to thrombectomy in order to minimize wall damage due to mechanical friction. Figure 7 illustrates the steps of the method of the invention performed using the balloon catheter shown in Figures 5 and 6. In step A of Figure 7, a thrombus 701 is shown located in the middle cerebral artery 702 before the thrombectomy catheter of the invention is deployed. A microguidewire 720, typically used for balloon catheters, is inserted through the internal carotid artery 721 and positioned proximal to the thrombus 701 (step B). In step C, a UV-transparent balloon 730 is then inserted over the microguidewire 720, as in normal use of the device, and also positioned proximal to the thrombus 701. Step D shows the balloon catheter then being inflated 740 to contact the inner wall of the vessel (artery) 721, such that blood flow is significantly or completely blocked between the balloon and the vessel wall. The UV laser is deployed according to the method described herein, such that a ring-shaped beam is emitted to contact the inner wall of the blood vessel, and the vessel partially dilates 722 (propagating in both directions from the area contacted by the UV laser ring-shaped beam). The aspiration thrombectomy catheter 750 can be used in its conventional manner to aspirate the thrombus 701, which is shown in step F as being removed from the middle cerebral artery 702, using a stent thrombectomy device or an aspiration procedure as illustrated only by the example in step E. The dilation induced by UV laser irradiation facilitates the removal step.

Advantageously, the dilation method provides reduced mechanical friction, thereby minimizing damage to the arterial wall. Another advantage is that the platelet component of the clot will also dilate (see U.S. Patent 6,539,944), and the portion closest to the arterial wall will partially degrade into individual platelets (through dethrombosis), resulting in less adhesion to the wall and therefore less frictional resistance to the aspiration process. No emboli will be formed.

In the method according to the invention, UV light emission can last for a very short duration, such as 2 to 15 seconds, preferably about 5 seconds, or can be repeated, provided that blood in the light path is cleared by balloon contact or by saline injection in either case. The laser irradiation interval can be filled by a continuous-wave laser beam, or by a beam consisting of multiple consecutive MHz mode-locked pulses (approximately 10 picoseconds wide), referred to as a quasi-continuous beam, or by multiple consecutive 5 to 25 kHz pulses (up to 100 nanoseconds wide), referred to as an acousto-optic Q-switched beam. The UV light is preferably directed directly onto the vessel wall within approximately 20 vessel diameters of the thrombus. More preferably, when using a balloon, the UV light is directed directly onto the vessel wall within approximately 4 vessel diameters of the thrombus. In the preferred method, the vessel is an artery partially or completely occluded by the clot.

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

In the apparatus or method of the present invention, the average incident intensity of UV light is between about 3 watts per square centimeter and about 20 watts per square centimeter (W/ ^cm² ).

The apparatus and method of the present invention can be used in conjunction with the pre-administration of a pharmaceutically acceptable thrombolytic agent that facilitates the dissolution of (fibrinous) thrombi. Concerning is the release of clot fragments, which our platelet dethrombotic process avoids. The preferred thrombectomy procedure removes the clot without the fragmentation complications caused by the thrombolytic agent.

One particular embodiment introduces a laser beam via an intravascularly deployed optical fiber comprising a protruding (external) tapered tip that, through a single reflection and a single refraction, effectively acts as a beam-diverging lens (i.e., a negative-axis pyramidal lens). This design produces a circumferential irradiation pattern as an extended conical ring, thereby generating a ring-shaped laser beam on the wall of the tubular anatomical structure to which the beam is directed. The protruding tapered output tip is preferably made of a UV-transparent material with a refractive index higher than fused silica, such as diamond, zirconium oxide, or a custom polymer material (e.g., plastic) with n>2 that can be optically coupled to silica. As the beam exit angle increases within the limits defined 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 thus the irradiated area all decrease.

These same considerations also apply to the inverted conical tip, but the maximum emission angle will be smaller than that of the outer tip. The intention is to provide two different ways to generate an extended ring-shaped beam, the relative benefits of which have been described above and can be evaluated for clinical application.

Preferred fiber tips include an inverted tip configuration (Figure 3), which is less likely to be obstructed during use, although this possibility should be avoided through the deployment of the guiding conduit, as well as the possibility of arterial perforation.

Another embodiment is a fused silica fiber with an externally protruding tip (Figure 1B), which has a maximum unobstructed emission (semi-conical) angle of approximately 48.4° (see Table 2, but the limit is 50.3°). When the tip is sharp (full-apex conical angle less than 40°, see Figure 2A), the tip may break due to mechanical contact if a brittle material is used. This can be remedied by an externally conical tip made of a very hard material with a high refractive index, such as diamond. An outwardly flared diamond conical tip will allow a beam exit angle up to 71.5°. Of course, with increased bluntness (increased full-conical apex angle), the external tip (including the silica itself) will be more resistant to mechanical damage.

When UV light is absorbed by nitrite ( _NO₂⁻ ⁾ in the smooth muscle cells of the arterial wall, it photophysically releases nitric oxide (NO) at a concentration higher than that maintained by the endothelium during normal metabolism. This causes quasi-transient (tens of minutes to hours) and semi-local vasodilation of the blood vessels. The release of NO from the smooth muscle cells propagates proximally and distally over local distances of several centimeters from the site of UV light irradiation via a transnitrosotransferase reaction. UV lasers are used to induce vasodilation near the occlusion, thereby reducing friction (or chemical bonding) with the arterial wall when deploying thrombectomy devices to aspirate blood clots. Thus, vasodilation facilitates the separation of the clot from the vessel wall to which it adheres and facilitates easier and safer removal of the clot using conventional aspiration catheters or stent thrombectomy devices (by reducing the intensity and frequency of clot-vessel wall interactions). This invention can advantageously reduce the late pathological and behavioral consequences of structural and functional damage to the endothelial and intimal structures of occluded arteries undergoing thrombectomy.

The dilation of blood vessels increases their diameter, which can also facilitate the movement of catheters to the appropriate location, i.e., it can more easily pass through tortuous (severely tortuous) or narrowed blood vessels.

To achieve the objectives of the invention, a novel aspect relates to an advantageous configuration for the tip of an optical fiber from or through which UV irradiation is emitted. For example, it has been found that employing an externally tapered tip made of a very rigid but UV-transparent material (such as diamond) can more easily provide an external (semi-tapered) emission angle of up to 71.5° (relative to the fiber axis) and consequently a narrower projection of the ring beam of UV light onto the inner wall of the artery. The preferred angle is preferably determined in conjunction with other components of the system, such as a UV-transparent balloon expanded with a UV-transparent gadolinium-based contrast agent.

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

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

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

Another object of the present invention is to provide a UV-transparent balloon catheter that encapsulates a UV-compatible optical fiber, which is integrated with an aspiration thrombectomy catheter as part of a single dilation system. Preferably, the UV-compatible optical fiber integrated with the aspiration thrombectomy catheter or stent thrombectomy device has an everted tapered tip of diamond or zirconia (or a high-refractive-index polymer material) at its distal end.

In a preferred embodiment, a UV-transparent gadolinium-based contrast agent can be used to expand the balloon catheter; the balloon wall then diverts blood, providing an unobstructed path for the UV laser to travel to the arterial wall. According to the invention, the balloon is inflated for this purpose and also centers the tapered tip; it is not inflated to expand the inner diameter of the vessel wall. The gadolinium contrast agent is confined to the balloon and thus isolated from blood flow. In this embodiment, the balloon and contrast materials are sufficiently transparent to UV light to allow unobstructed passage of UV light through the encased catheter and balloon.

Another object of the present invention is a method for performing a thrombectomy procedure on a mammal in need, wherein the method comprises the following steps:

a) Provide an expansion system as described herein.

b) Position the UV fiber optic balloon catheter within one to four vessel diameters of the clot within the occluded vessel;

c) A square-wave pulse of continuous or high-repetition-rate UV laser energy is emitted as a beam within a specified average intensity range onto the smooth muscle cells lining the inner wall of a blood vessel to release NO from the cells and thereby induce vasodilation; and

d) Remove the optical fiber and introduce the thrombectomy device.

e) and then remove the clots by mechanical extraction.

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

UV light energy bursts, either continuously or in pulses, can be emitted at irradiation intervals of about 2 to 20 seconds, preferably at least about 5 to 15 seconds, and more preferably about 8 to 12 seconds. A 10-second burst may be the most preferred emission duration for the UV beam to dilate blood vessels to a sufficient diameter to reduce frictional interactions between the catheter and vascular tortuosity or stenosis, or to promote local separation of clots from the vessel wall.

In a preferred embodiment, the invention includes an expansion system comprising a suction catheter or stent thrombectomy device following a preparation period in which a ring beam of UV irradiation is supplied using a tapered-tipped optical fiber. The tapered tip of the optical fiber may bulge inward or outward from the distal end of the fiber, depending on the desired emission angle and the presence of obstructions along the desired path.

In use, an optical fiber with a tapered tip can emit a conical beam trajectory, which acts as a ring or annular beam irradiating the tubular anatomy around its inner circumference. Tubular anatomy structures that can be expanded with UV light are those lined with (smooth muscle) cells capable of storing nitric oxide (as nitrite) and releasing fully active nitric oxide (NO). This expansion can be advantageously used to dilate or expand arteries near the site of a thrombus to facilitate easier and safer thrombus removal by reducing mechanical friction and chemical bonding to the thrombus. The thrombus can be occlusive or non-occlusive. Vascular dilation at or near the site of a thrombus within the vessel can at least partially loosen the adhesion of the thrombus to the vessel wall or separate the thrombus from the vessel wall, thereby facilitating efficient removal of the thrombus using conventional aspiration or stent thrombectomy catheter techniques currently used in the medical field. Minimize peripheral damage to the occluded vessel before, during, and after aspiration.

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

Because the vasodilatory effect induced by UV radiation can propagate distally (and proximally), branch arteries can also be dilated by irradiating the main trunk at a distance of approximately 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 25, or 30 vessel diameters from the main trunk thrombus. This phenomenon can be particularly useful when the thrombectomy surgeon cannot access the thrombus-containing branch artery or arteriole practically but can access the main trunk proximally.

Preferably, the UV beam is directed onto the inner surface of a tubular anatomical structure, such as an artery, via a beam transmitted through an optical fiber placed inside the blood vessel by means of a catheter. Immediately after irradiation, but almost immediately thereafter and within seconds of irradiation with the laser beam, the blood vessel first dilates at the irradiated portion and then propagates continuously for several centimeters in both proximal and distal directions.

Under normal physiological conditions, dilation is mediated by nitric oxide (NO) produced by the endothelium. In contrast, UV laser-mediated photophysical production of NO is caused by the photolysis of nitrite ( _NO₂⁻ ) stored in undamaged smooth muscle cells in the arterial wall. Local NO concentrations up to 10 ^μM can be generated regardless of the severity of endothelial damage or even when the endothelium is absent (completely destroyed).

The photolysis of nitrite in smooth muscle cells produces NO and the S-nitrosation (RSH) of thiols, leading to the formation of S-nitrosothiols (RNSO), which causes local expansion via NO or its release from thionitrates (RSNO). These cause the denitrosation of other thiols, thus propagating the expansion radially, distally, and proximally by releasing more NO. This is a self-continuous chain process.

Photophysically generated nitric oxide can stimulate dilatational waves both proximally and distally. Therefore, at some point along the clot length, the frictional resistance to clot removal may be reduced. Consequently, the clot can be removed with less force, and thus the mechanical damage to the artery is less than currently observed, with fewer future complications at or distal to that site.

The ultraviolet laser beam used to dilate arteries and thereby treat occluded vessels can be continuous or pulsed. Using pulsed lasers reduces heat buildup and consequent damage in the target and surrounding tissues. If 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 appropriate time-averaged intensity of irradiation to the target tissue, while avoiding individual pulses of too high an intensity that could cause severe and persistent damage to the target tissue or to the fiber, i.e., irreversible damage over a physiologically relevant timeframe (e.g., a period of hours to weeks).

The wavelength of the UV light is preferably in the range of 180 to 400 nm. More preferably, the UV light is in the range of 300 to 400 nm. Even more preferably, the UV light is about 340 to 370 nm, and most preferably about 350 to 360 nm. A third-harmonic Nd:YAG laser emitting 355 nm irradiation is particularly preferred.

Other UV lasers that can be used in this invention (while avoiding ablation) include XeF lasers (351 nm), CW argon ion lasers (351 nm, 364 nm), or CW krypton ion lasers (351 nm, 356 nm). Any diode laser or dye laser can also be used as long as non-ablative output can be obtained in the UV range required for the vasodilatory effect. In principle, any laser that directly emits UV radiation or emits UV radiation as a result of frequency harmonics or triharmonics can be used.

For 355 nm UV laser irradiation, dilation is stimulated over a wide dynamic range for an intensity of 7 (intensities from 3 to approximately 20 W/ ^cm² ), resulting in a Gaussian beam shape. However, the dilation effect is independent of the beam shape. At the upper limit, vacuoles form in smooth muscle cells, but function is not impaired. The dilation effect depends on the average intensity. For example, a 100 nanosecond pulse sequence at 7 Hz and a peak power of 5 kW can be used at 20 W/ ^cm² without causing functional impairment.

Blood can be cleared from the path of the laser beam, for example, by flushing the opening of the catheter through which the beam exits immediately before irradiating the blood vessel wall or thrombus.

Preferably, the intensity of UV irradiation is adjusted to provide the minimum dose required to achieve the desired degree of vasodilation within the desired time frame prior to thrombectomy. For example, using a frequency-triple-harmonic Nd-YAG laser, an incident intensity of approximately 5 watts/ ^cm² produces approximately 20% to 30% dilation in small arteries (this dilation can be reversed by NO inhibitor drugs). Higher intensities of 12 to 20 watts/ ^cm² (equivalent to an energy flux of up to 1 J/ ^cm² per pulse at a pulse frequency of 20 Hz) can produce a similar increase in the diameter of larger arteries (approximately 1.5 mm), but intensities exceeding 20 watts/ ^cm² may alter the vessel wall structure (forming small vacuoles in smooth muscle tissue), but no functional impairment has been observed.

The incident intensity can then be increased in increments (e.g., 2 watts/ ^cm² or greater) until appropriate vasodilation is observed within a reasonable timeframe (e.g., within 5 seconds). Irradiation periods can be continuous, i.e., continuing until the dilation effect stabilizes, or they can be intermittent, in which case the duration of one or more irradiation periods can be varied at a given incident intensity to obtain an appropriate response; the induced dilation will be preserved and amplified. An appropriate vasodilatory response (i.e., the degree of dilation and the kinetics of its onset and duration) can be determined by the user; however, many users generally consider a response in the range of 20% to 40% increase in vessel diameter within 5 to 10 seconds to be appropriate.

The method of this invention is applicable to the treatment of various diseases involving arterial occlusion. Examples of such diseases include stroke, myocardial infarction, and occlusion or spasm of any peripheral artery (large or small artery).

In the method of using an aspiration catheter according to the present invention, a balloon catheter can be introduced, and then the aspiration catheter is introduced just above the catheter and below the balloon portion. As the balloon inflates, a UV optical fiber can then be introduced into the balloon. When the UV-transparent balloon inflates beyond the diameter of the aspiration catheter in front of a bend or narrowing, the UV optical fiber is then centered in the artery, and non-flowing blood is displaced from the projected light path. The UV beam can then be flashed for a few seconds to achieve sufficient dilation to allow the passage of a thrombectomy catheter used in the subject dilation system. Here, the balloon does not push against the artery to dilate it, but merely facilitates the displacement of blood away from the artery, while the laser ring beam follows an optically free path to non-mechanically dilate the artery. Balloons are very common, but overinflation can damage tissue.

Once the UV light is emitted onto the wall of the blood vessel and absorbed, the vessel will dilate and spread dilation regardless of whether blood or blood flow subsequently occurs. This process can be used to more easily traverse tortuous or narrow sections on the way to the clot. Therefore, structural and endothelial damage is minimized from the entry point to the target location. Once the clot is reached, a final irradiation is performed, including optional saline flushing, and then the clot is removed using an aspiration catheter.

For use with a stent retrieval device, a guidewire is inserted into the clot and moved just one or a few centimeters past it. A balloon catheter is then inserted and expanded distal to the clot, and a UV fiber is used to irradiate the distal segment instead of the guidewire. The UV fiber is then withdrawn, and the stent retrieval device is inserted through the balloon catheter to replace the UV fiber at the clot location. The balloon catheter can be withdrawn just proximal to the clot, and the stent retrieval device mesh spontaneously or in a controlled manner expands during catheter withdrawal to a diameter suitable for uniform and symmetrical clot retrieval. This allows the stent retrieval device mesh to better capture the entire clot and ensure retrieval efficiency.

Another benefit is the ability to use UV irradiation in locations where the catheter is difficult to pass through towards the target clot site; this will facilitate safer clot removal. Catheters that appear too large for the artery at some unexpected point can still be used after UV dilation. If a catheter size misselection occurs in the initial step, UV dilation can be used to dilate the artery without replacing the current catheter.

The design using the externally protruding tapered tip of silica fiber (α = 18°, Figures 1A, 1B and 2A) was developed for intravascular deployment via microcatheters.

Table 1. Emission angle β(α) (in degrees) of 355 nm light emitted from a silica optical fiber ( _n1 = 1.475) with an external tapered tip into water ( _n2 = 1.333) or air ( _n2 = 1.00); α = half angle at the apex of the tapered tip; β(α) = π/2 - α - γ(α), δ = π/2 - 3α, and γ(α) = sin ^-1 {( _n1 / _n2 )cos 3α}.

Note that the limit of α is (90° - the critical angle between glass and water, 64.653°) = 25.347°.

To increase β (and thus reduce the area of the ring beam facing the arterial wall), a short (approximately 0.5 mm) everted tapered segment made of a UV-transparent material with a high refractive index must be optically bonded to a silica fiber. Diamond is the optimal choice, with a refractive index n_{_d} = 2.48.

Table 2 presents the same calculations as above for a beam of light incident on water from an external diamond tip.

Table 2. Emission angle β(α) (in degrees) of a 355nm laser emitted from an external diamond-tipped silica fiber ( _n1 = 2.48) into water ( _n2 = 1.333) (see Figure 3); β(α) = 90 - α - γ(α), δ = 90 - 3α, and γ(α) = sin ^{- 1} {( _n1 / _n2 )cos 3α, where α = half the angle at the apex of the conical tip.

Note that the critical incident angle for total internal reflection (diamond to water) is 32.51°.

Table 3 shows the path range of a 355 nm laser emitted into water (saline) towards the arterial wall from an inverted conical tip made of silica and diamond. The emission angle β is a function of the inverted cone half-angle α (described in Figure 3). Some practitioners may prefer the inverted conical tip design because the tip is much less likely to get stuck on obstacles (if any) than an external conical tip.

Table 3. Emission angle β, in degrees, calculated according to Snell's law as a function of the inverted cone half-angle α of the silica and diamond tips for a ring beam emitted toward the arterial wall into the water (Figure 3). α = 90° - _θ₁ , where _θ₁ = θ₀g _,d and g = glass (silica), d = diamond, _θ₂ = _θ₀water , and β = _θ₀water - _θ₀s,d .

This calculation complements those for the outer 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 a reduced distance from the outer conical tip (both are better than silica alone). However, β is very sensitive to α, meaning the input beam must be well collimated to minimize the polar angle spread _2θw (see Figure 1A), and the inner conical tip must be ground very precisely to ensure high surface quality and thus minimize beam scattering. Here, _θcrit = _θdiamond = 32.51° and β = 57.49°. If _θdiamond = 32.50°, then _θwater = 88.44°, α = 57.50° and β = 55.94° (Table 3).

As an alternative to the tapered-tip optical designs for generating ring beams presented to date, we propose a combination of diffractive optics and optical fibers. The diffractive optics involve etching a geometric pattern onto a flat-ended optical fiber using any of several methods (e.g., photolithography, electron beam evaporation), the tip of which can be molten silica itself or other optically coupled UV-transparent high-refractive-index (n>2) materials, such as zirconium oxide, diamond, or custom-designed polymer materials (e.g., plastics), to obtain the desired diffraction phase profile. The pattern on the fiber tip resembles a circularly symmetrical bas-relief structure, i.e., a series of concentric rings of variable depth and radius, as precise material removal is necessary to form the desired diffraction phase profile. The desired output is a very sharp ring Bessel beam with minimal sidebands. For beams exiting the tip at an angle β>40°, high-refractive-index materials, such as the latter three (as previously described), are likely used. To our knowledge, ring beams greater than β=15° have not yet been generated in any medium using this technique, but manufacturers of diffractive optics are willing to expand its capabilities. A flat-end diffraction pattern placed on a suitable high-refractive-index material, including end caps of molten silica optical fibers immersed in water, is likely the optimal form of the device.

Both external and internal tapered tips can generate a ring beam within a range of angles to the arterial wall. For external tips, the practical upper limit is approximately 48° for silica and approximately 71.5° for diamond, but closer to the maximum angle will be preferred. For internal (inverted) diamond tapered tips, the range can go up to 56°, which is preferred. The direct benefit of emitting the beam at the maximum acute angle is a reduced ring beam width and therefore higher laser intensity. Since the expansion process depends entirely on the beam intensity (between 3 and 20 watts/ ^cm² ), lower power (and potentially more compact) lasers can be used more efficiently. The internal tapered tip is designed for safety, as we noted in previous work that external silica tips could be damaged. It is obviously beneficial to present a device that will not be damaged by attachment to any other device or tissue component during insertion, as jamming is avoided and the tip structure is preserved. However, these effects are unlikely to occur in very hard materials such as diamond.

Given the description provided herein, these and other embodiments and applications of the invention will become apparent to those skilled in the art. A common but difficult-to-treat aspect of hemorrhagic stroke is vasospasm (constriction) of the main cerebral arteries. Blood ejected from a ruptured aneurysm into (e.g., the subarachnoid space) migrates along the artery, and hemoglobin from dissolved red blood cells enters the arterial wall and removes nitric oxide, thus causing spasm. This condition is currently untreatable; systemic vasodilators can lower (and have already lowered) blood pressure to the level required for the onset of the disease. Another currently untreatable aspect is early brain injury mediated by platelet occlusion of microvessels in the brain (i.e., prior to vasospasm). Despite extensive animal studies, no drug has been found to dissolve platelet thrombi in humans. The UV laser approach aims to definitively treat these two extremely difficult conditions. We have shown that in dogs with hemorrhagic stroke, vasospasm is reversed within three days. We also showed that platelet clots can indeed be dissolved by UV laser-induced nitric oxide because it inhibits thrombin, an enzyme required to maintain fibrinogen/platelet GPIIb-IIIa crosslinking between platelets.

We propose that, in addition to arterial recirculation, proximal UV irradiation of the main trunk, precisely at the junction of the main trunk leading to the feeding artery and its distal branches and microvascular beds, will allow and enhance blood reperfusion to areas that cannot be directly treated by thrombectomy. This is due to the self-replication of nitric oxide over a distance and its associated vasodilation, thus increasing the likelihood of tissue survival. For example, this could be used for emergency treatment of patients with ruptured cerebral aneurysms using standard interventional devices such as coils and stents. After aneurysm fixation, the neurointerventional physician can continue to position the microcatheter used for coiling further distal to the aneurysm. The microcatheter can be replaced with a UV-cured transparent balloon catheter, and the microguidewire can be replaced with an optical fiber. Distal UV irradiation will dissolve platelet emboli occluding microvessels within the vascular area, thereby enhancing reperfusion and improving patient clinical outcomes. Cerebral vasospasm may cause vascular constriction three to twenty-one days after aneurysm treatment. Furthermore, using a UV-protected transparent balloon catheter and optical fiber, UV irradiation near the narrowed vessel will dilate the artery and restore it to its original (or larger) diameter, thereby restoring blood circulation.

Atherosclerotic vascular disease can lead to narrowing or stenosis (narrowing) of the arterial lumen due to plaque formation. Current methods require balloon angioplasty to widen the lumen, followed by stent placement to secure the ostium. Angioplasty and stent placement first require traversing a microguidewire through the stenosis to obtain distal access. When the stenosis is moderate to severe, it is difficult to safely traverse the stenosis without removing the atherosclerosis. During stent placement procedures for atherosclerotic disease, the guidewire and device can be facilitated through the plaque by dilating the artery with UV (given that existing scar tissue will allow for this dilation). If the plaque is calcified, it can be very hard and incompressible. Additionally, balloon dilation can cause adjacent non-atherosclerotic segments to expand and stretch, even to the point of structural distortion. A common response to this trauma is hypertrophy, i.e., an abnormal healing response known to eventually occlude the ostium formed by the stent. We propose that non-mechanical dilation of the artery (even diseased arteries) via the nitric oxide pathway will significantly facilitate the use of endovascular devices to access the atherosclerosis distally. The NO approach will also minimize the overemphasis on vascular tortuosity and healing response, thus preserving the desired lumen and its lifespan. Endothelial damage to adjacent non-atherosclerotic segments will also be reduced. For example, in patients with severe carotid atherosclerosis, a UV-guided transparent balloon catheter can be positioned proximal to the stenosis using a microguidewire. The guidewire can be replaced with an optical fiber. Subsequent UV irradiation will dilate the arterial wall and widen the stenotic gap. The microguidewire can then replace the optical fiber, and the guidewire can now be more easily traversed through the widened stenosis for distal access. The balloon catheter can then be removed, and the plaque can be treated using a guidewire delivery system. The same system is typically used to safely place stents to ensure circulation through the stenotic vessel, but now the stent can be placed in the dilated vessel without the usual endothelial damage. This will avoid restenosis, a very common complication of stent deployment in current practice, and avoid the need for stent replacement within 3 to 5 years.

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

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 a target location, and a catheter is then screwed onto the guidewire to perform the intended procedure, such as a thrombectomy procedure using a thrombectomy device (e.g., a stent thrombectomy device or aspiration catheter). The procedure of the invention involves removing the guidewire from the catheter and replacing it with an optical fiber capable of emitting an extended ring beam of UV laser with sufficient intensity to dilate the blood vessel. An alternative involving the steps of removing the guidewire and replacing it with an optical fiber is to incorporate the optical fiber within the guidewire as a combined guidewire/optical fiber. A preferred embodiment of this aspect of the invention includes a guidewire having a hollow core such that an axial cavity or lumen is formed along the entire length of the guidewire, the axial cavity or lumen being configured in the form of a flexible metal tube structure. Contained within the guidewire is a silica optical fiber, the tip of which, preferably made of a UV-transparent high-refractive-index material (such as diamond), is designed to emit a ring beam. The flexible metal tube structure can be constructed of a flexible metal alloy (e.g., nitinol). The optical fiber can be configured not to be attached to the guidewire, or preferably attached relative to the inner wall of the hollow guidewire as needed. In this configuration (“locked position”), the guidewire and the optical fiber are integral with each other and work together as a single unit when placed within the blood vessel. In one embodiment, the optical fiber can be manually configured to the “locked position”, whereby it is attached to the guidewire, and manually configured to the “unlocked position”, thereby allowing the guidewire and the optical fiber to operate independently and separately from each other.

The distal segment of the integrated or combined guidewire and fiber embodiment is shown in a y-plane (sagittal) cross-section in Figure 8A. Figures 8B, 8C, and 8D depict different fiber tip configurations, each acting as a negative-axis pyramidal lens that projects a diverging laser beam onto the inner wall of the artery. A diverging laser beam is generated regardless of whether the fiber's output mode is multimode or single-mode (e.g., adjusted by fiber thickness). Figure 8A shows a combined hollow guidewire and fiber 800 according to the intended application, where the outer surface can be coated hydrophilically or hydrophobically. Fiber 802 is covered by a polymer coating 803 (cladding) that ensures total internal reflection, and the fiber is arranged within the hollow core 801 of a flexible metal guidewire. In one embodiment, the internal portion 804 of the guidewire includes a metal coil enclosing the hollow core of the guidewire, thereby satisfying key requirements for torsionability, flexibility, formability, shape retention, and tactile feedback for the desired specific application. The distal end of the optical fiber 805 (defined by the boundary of its cladding 803) substantially coincides with the end of the hemispherical guidewire cap 806. The cap 806 may be made of a soft, flexible material designed to minimize mechanical damage to the cavity it is probing (such as an artery) until the target location is reached.

In a preferred embodiment, the combination of guidewire and optical fiber comprises a solid fused silica optical fiber of sufficient length to emit UV laser light from its distal end without obstruction by the guidewire cap 806, and without significantly extending beyond the guidewire cap 806, thereby protecting the blood vessel from the influence of the optical fiber tip during movement and placement in the target location. The apex of the outer tapered tip can be shielded by the guidewire until it is placed in the desired position. Any accumulation of particles should be removed by flushing the catheter with saline.

The distal end of the combined guidewire and optical fiber may include a separate tip in optical communication with the optical fiber. This separate tip in optical communication with the optical fiber may be diamond, zirconium oxide, or a polymer material (e.g., plastic). For example, a diamond tip may be optically coupled to a silica fiber 802 and configured in three ways to generate an extended laser beam. Figure 8B illustrates an optical fiber with an external tapered tip 811. Ray 807 is shown entering and exiting the fiber via a single total internal reflection. The internal reflection angle α and 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 may be configured in a locked position such that the tip apex can protrude slightly to pass through hard obstacles (such as calcified atherosclerosis). In one embodiment, the distal end of the optical fiber may be configured with an external tapered tip capable of emitting UV light in the form of a tapered beam as described above.

Figure 8C illustrates a combination of a hollow guide wire and an optical fiber, wherein the optical fiber 802 has an inverted tapered tip 812 in optical fiber optic contact. In one embodiment, the distal end of the optical fiber may be configured to emit UV light in the form of an inverted tapered beam as described above.

Figure 8D illustrates a diffractive optical element (DOE) formed on a flat etched tip 809 of a diamond segment optically coupled to a silica master fiber to generate a UV laser ring beam 810 from an input TEM ₀₀ laser beam 808, similar to a ring beam generated by a negative-axis pyramidal lens. Any of several known methods can be used in this rapid development field to convert the TEM ₀₀ laser beam into a Bessel intensity distribution (ring). The patterning can include concentric tilted rings (each ring can be a cascade of thin, flat rings of successive thicknesses) formed on the flat output end of the fiber, with a mechanical resolution of approximately 5 μm. In one embodiment, the ring beam can be oriented at a full conical angle of at least 90°. In a preferred embodiment, the ring beam can be oriented at a full conical emission angle of 120° or greater to enhance the intensity of the dilatant UV ring beam, thus requiring less laser input power. The fiber diameter, mode (which can be multimode), and output ring thickness are not critical for generating an operationally efficient ring beam output. In one embodiment, the far end of the optical fiber can be configured as a flat far end having concentric circular grooves etched into it, wherein the flat far end is a diffractive optical element (DOE) as described above.

Figures 9A and 9B illustrate embodiments of the etched end of an optical fiber according to the present invention. Figure 9A shows a front view of the distal end of an optical fiber 800, which is etched into concentric rings of V-shaped grooves formed in the fiber to produce a diffractive optical element (DOE). The central V-shaped groove 902 forms an inverted cone at the center of the fiber. Each concentric V-shaped groove outside the center has a peak 901a and a valley 901b.

Figure 9B further illustrates the concentric ring V-groove pattern shown in the side view of Figure 8D and the front view of Figure 9A. This view further clarifies the pattern of alternating peaks 901a and valleys 901b in the flat distal end of the fiber 800. Preferably, each peak 901a has the same height as the other peaks 901a, and each valley 901b has the same depth as the other valleys 901b. Figure 9B also shows a solid fused silica fiber.

Advantageously, an integrated or combined guidewire and fiber optic embodiment can eliminate certain steps in conventional catheter insertion procedures. Conventional catheter insertion procedures require the following steps: (1) inserting a guidewire, (2) placing a catheter on the guidewire, then (3) removing the guidewire from the positioned catheter, and (4) replacing the guidewire with a fiber optic cable to dilate the blood vessel. The fiber optic cable integrated within the guidewire eliminates steps (3) and (4) because it eliminates the need to remove the guidewire from the catheter and replace it with the fiber optic cable. The time saved by eliminating steps (3) and (4) is beneficial to both the user and the patient undergoing the procedure.

Because the steps eliminated in the aforementioned procedures save time and facilitate reperfusion, the combined guidewire/fiber of the present invention can reduce the incidence (approximately 50%) and severity of behavioral abnormalities associated with thrombectomy. These were confirmed in all levels of TICI flow status, even at grade 3, indicating complete recanalization of the main occluded artery. However, TICI does not measure blood return in its branch arteries or microvessels responsible for delivering nutrients directly to the tissue. Reperfusion is separate from pre-recirculation and is currently not observable by angiography. Reperfusion is defined as the restoration of normal flow in collateral branches and microvessels of arteries that cannot be accessed or cleared by thrombectomy. The relative lack of reperfusion despite aortic recanalization can well explain the variability in behavioral recovery. This is thought to be due to a variety of mechanisms, including microthrombus formation or the embedding of emboli in situ or from the removed occluded thrombus in distal vessels. The goal of reperfusion is to rescue intervertebral tissue, which is metabolically quiescent but not dead (infarcted), primarily due to retrograde filling of collateral circulation. However, if the main area is already infarcted, reperfusion can induce very serious hemorrhage due to vessel wall degradation. Therefore, UV laser-induced dilation should only be used when the penumbra tissue is deemed salvageable and the likelihood of hemorrhage is low.

One aspect of the present invention relates to a method for reperfusion of an artery distal to a thrombus, wherein the method includes the following steps:

i) Provide optical fibers capable of carrying UV lasers; and

ii) extending the optical fiber through the thrombus; and

iii) Firing a UV laser from an optical fiber distal to the thrombus to dilate the artery distal to the thrombus; and

iv) Remove the blood clot;

This allows for the recirculation and blood flow to dilated arteries (including those that are not normally treatable by thrombectomy) and allows for arterial reperfusion.

The optical fiber can be extended through the thrombus, preferably to a distance suitable for a distal field of UV irradiation, in which reperfusion can be enhanced by dilation. Any emission or pulse of the UV laser described herein can be repeated to produce the desired arterial dilation effect. The arteries dilated and undergoing reperfusion as described herein are preferably small branch arteries and arterioles. The UV laser can also be emitted to dissolve, dissociate, or break down platelet clots formed in arteries or arterioles distal to the thrombus.

In one embodiment of the invention, the method for reperfusion of an artery distal to the thrombus further includes the step of emitting a UV laser from an optical fiber (inside the balloon catheter) proximal to the thrombus before extending the optical fiber through the thrombus. Preferably, the proximal artery is irradiated with UV light for a duration sufficient to dissolve the bound platelet layer.

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

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

In another embodiment, the method may include the additional step of emitting a UV laser to dissolve or break down aggregated platelet clots formed in an artery or arteriole distal to the thrombus. In one embodiment, the method includes the thrombus as an occlusive thrombus.

In one embodiment of the invention, a method for reperfusion of an artery distal to a thrombus includes an optical fiber disposed within a guidewire as described above.

Because the chain process of transnitrosation produces nitric oxide along the path of the optical fiber, which can travel into the branch arteries, the distal segments and their branches can dilate, thus preparing the branch arteries and arterioles to receive blood (reperfusion) when recirculation is achieved through thrombectomy.

In another embodiment of the invention, the method for reperfusion of an artery distal to a thrombus includes the step of removing the thrombus using a thrombectomy device. The thrombectomy device for removing the thrombus may be a stent thrombectomy device. In the case of deploying a stent thrombectomy device, UV laser-induced dilation provides increased space for deployment, which can enhance clot integration while causing less damage to the dilated arterial wall. Alternatively, in another embodiment of the invention, the thrombectomy device may be an aspiration catheter. In the case of deploying an aspiration catheter, UV laser-induced dilation can provide reduced friction at both ends of the clot, which should reduce the currently required linear pressure at the distal end and thus inhibit fragmentation. All these procedural aspects are designed to remove the clot with minimal passes and also ensure enhanced distal reperfusion.

The foregoing disclosures and examples generally describe the invention and are provided for illustrative purposes, and are not intended to limit the scope of the invention. The invention described herein can be practiced without the presence of any one or more elements or limitations not specifically disclosed herein. Therefore, for example, in each instance herein, any one of the terms “comprising,” “essentially consisting of,” and “consisting of” can be replaced by any of the other two terms. These terms and phrases are used descriptively and not restrictively, and are not intended to be used without any equivalents of the features or portions thereof shown and described, but various modifications are recognized as possible within the scope claimed by the invention. Therefore, it should be understood that although the invention has been specifically disclosed by way of preferred embodiments and optional features, modifications and variations of the concepts disclosed herein can be adopted by those skilled in the art, and such modifications and variations are considered to be within the scope of the invention as defined by the claims.

Claims (17)

1. A combined guide wire and optical fiber capable of carrying UV laser, wherein the guide wire is formed as a hollow tube, and an optical fiber for carrying UV laser from a UV laser source is arranged within the hollow tube. 2. The combined guide wire and optical fiber capable of carrying UV laser as described in claim 1, wherein the hollow guide wire and the optical fiber capable of carrying UV laser are attached to each other. 3. The combined guide wire and optical fiber capable of carrying UV laser as claimed in claim 1, wherein the optical fiber capable of carrying UV laser has a distal end configured to emit a tapered UV laser beam. 4. The combined guidewire and optical fiber capable of carrying UV laser as claimed in claim 1, wherein the optical fiber capable of carrying UV laser has a distal end configured as an outer cone to emit a tapered UV laser beam. 5. The combined guide wire and optical fiber capable of carrying UV laser as claimed in claim 1, wherein the optical fiber capable of carrying UV laser has a distal end configured as an inverted cone to emit a tapered UV laser beam. 6. The combined guidewire and optical fiber capable of carrying UV lasers as claimed in claim 1, wherein the optical fiber capable of carrying UV lasers has a flat distal end, the flat distal end including concentric circular grooves etched into the flat distal end. 7. The combined guide wire and optical fiber capable of carrying UV laser as claimed in claim 3, wherein the distal end of the optical fiber capable of carrying UV laser is configured as a separate tip in optical communication with the optical fiber. 8. The combined guide wire and optical fiber capable of carrying UV laser as claimed in claim 7, wherein the individual tip in optical communication with the optical fiber comprises diamond. 9. The combined guidewire and optical fiber capable of carrying UV laser as claimed in claim 7, wherein the individual tip in optical communication with the optical fiber comprises zirconium oxide. 10. A method for reperfusion of an artery distal to a thrombus, the method comprising the steps of: - Extend an optical fiber capable of carrying a UV laser through the thrombus; - A UV laser is emitted from the optical fiber distal to the thrombus to dilate the artery distal to the thrombus; - Remove the blood clot; This allows blood to flow into these dilated arteries and be reperfused. 11. The method of claim 10, further comprising the following steps: - Before extending the optical fiber through the thrombus, a UV laser is emitted from the optical fiber proximal to the thrombus. 12. The method of claim 10, further comprising the following steps: - After emitting a UV laser from the fiber distal to the thrombus to dilate these arteries distal to the thrombus, the fiber is pulled out to a position proximal to the thrombus and emitted a UV laser from the fiber proximal to the thrombus. 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 stent thrombectomy device. 16. The method of claim 10, wherein the arterial vessels include microarteries. 17. The method of claim 10, wherein the thrombus is an occlusive thrombus.