CN118541195A - Devices and methods for dilation of tubular anatomical structures - Google Patents

Abstract

A method and apparatus for dilating a tubular anatomical structure is described. The apparatus and method can be used to extract blood clots in mammalian arteries by using an ultraviolet (UV) laser beam delivered by an optical fiber with an external or inverted tapered tip to concentrically irradiate the inner wall of an occluded artery. When the UV laser is projected onto the inner arterial wall as a ring beam, dilation is caused by the photophysical generation and release of nitric oxide from the cells lining the inner wall of the arterial wall. This "minimal contact continuous dilation system" prepares the artery for safer mechanical extraction by thrombectomy due to reduced friction and dissolution of chemical bonds.

Description

Device and method for expansion of tubular anatomical structures

Background

The present invention relates to the expansion of tubular anatomical structures using Ultraviolet (UV) lasers to photophysically stimulate nitric oxide release from smooth muscle cells of the inner wall of the tubular anatomical structure, such as a tube or tubule, artery, bronchiole, ureter, vessel, etc., resulting in relaxation (radial expansion) of the structure. More particularly, the present invention relates to an optical fiber having a tapered tip for directing an annular UV light beam to the inner surface of a tubular anatomical structure.

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

(1) A high intensity pulsed laser is used to destroy the thrombus or embolus by ablation or photoacoustic impingement (direct ultrasound is also used);

(2) Catheterization, angioplasty, and stenting to physically enlarge a lumen of a blood vessel that has contracted due to atherosclerosis;

(3) Thrombolytic or thrombolytic agents are administered to chemically isolate the thrombus, followed by the usual administration of platelet inhibitors (also known as antiplatelet agents) to prevent thrombosis; and

(4) Thrombectomy, in which the occlusive thrombus is removed by mechanical aspiration, thereby restoring blood flow.

Each of these methods currently available is associated with potentially detrimental effects on the vessel wall. For example, endothelial injury is currently unavoidable in thrombectomy and in some cases, may render the efficacy poor or quality of recovery questionable.

Two methods are now considered sufficient for removing vascular occlusions in a specialized clinical setting:

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

(2) Extraction by a stent retriever (stentriever)) wherein a mesh-like expanded wire network is deployed distal to the clot, resulting in the clot integrating directly into the mesh as the retriever is withdrawn, thus removing the clot.

Aspiration or stent-graft approaches may damage the arterial endothelium and arterial wall layers in different but unique ways, suggesting future negative effects on arterial structure and function. In this regard, the main concern has been to rapidly remove clots by these mechanical means, with less consideration being given to local or peripheral injury, especially to the endothelium, which is often antithrombotic. All improvements to these methods are strictly limited to mechanical improvements in aspiration efficiency, or the integration of stent retrievers with the clot, in order to attempt to remove the entire clot by one application (pass) of the device. While thrombectomy has recently achieved significant success in removing arterial occlusions, these current procedures are not perfect. During clot extraction, the arterial endothelial layer may be damaged by mechanical friction. Vascular rupture is a known risk of any interventional procedure currently in use, such as aspiration catheters or stent-grafts, and arterial wall perforation may occur during catheterization, particularly when accessing a branched arterial inlet. Furthermore, patients following thrombectomy recover quite poorly, especially in terms of behavior. About 60% of patients show signs of residual injury, but this has not become a field of concern until recently, as the major concern for practitioners has been the skill of clot extraction. In this context, recovery is compromised if the extraction is inefficient (up to five times are required and therefore there are more mechanical interactions with the vessel wall).

Methods have been proposed for solving the damage and risk problems caused by previously known procedures. 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 thrombus in an artery. In other words, the UV laser itself is used to promote the dissolution of the thrombus by means of its photophysical generation of thrombin inhibitors, namely Nitric Oxide (NO), a free radical that destabilizes neighboring platelet aggregates upon secretion from irradiated smooth muscle cells in the arterial wall. Which is incorporated by reference herein in its entirety.

There is a need in the art for a device and method for dilating a tubular anatomical structure containing smooth muscle cells during treatment of a patient while reducing and minimizing trauma to the anatomical structure and reducing the risk of subsequent injury to the patient upon receiving a medical procedure. This may be accomplished by the expansion system according to the invention. Preferably, the system of the present invention can minimize contact between the mechanical device of the system and the anatomy being dilated, thereby providing a minimally contact dilation system. For example, thrombectomy using aspiration catheters, stent-grafts or other mechanical thrombus extractors can be more easily accomplished and with less endothelial injury when prepared with such systems, where UV laser light, rather than mechanical pressure, directly causes dilation of the occluded artery. Preparing the artery for a subsequently deployed thrombectomy device in this manner helps to reduce friction and chemical bonding, and thus, less mechanical damage to the artery wall before, during, and after clot removal.

Disclosure of Invention

The invention is particularly useful for dilating an artery using an optical fiber capable of delivering UV light in the form of a ring laser beam to the wall of the artery to reverse vasospasm following hemorrhagic stroke or to facilitate removal of blood clots (thrombi) from the vasculature. A method of expanding a tubular anatomical structure using a tapered tipped optical fiber to create an annular shape and to deliver a laser beam to the inner wall of the tubular anatomical structure is also part of the present invention.

The devices and methods can be particularly useful in thrombectomy procedures performed on partially or fully occluded arteries for the treatment of stroke, myocardial infarction, and other vascular occlusive disorders, particularly thrombosis formed within the vasculature of the brain. It may also be suitable for dissolving distal microvascular thrombosis known to occur in hemorrhagic stroke as a manifestation of "early brain injury".

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

The tapered distal end of the optical fiber may be provided as a tip that is separate from, i.e. not part of, the optical fiber itself, but is optically coupled 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 formed as an everting cone capable of emitting UV laser light as a cone beam.

Preferably, the optical fiber of the present invention or the tip coupled thereto may include diamond at its distal end to optimize the emission of the cone beam, for example, the size, shape, emission angle or intensity of the beam may be modified and even improved by using diamond as the material of the tip or using diamond-like materials such as zirconia. Alternatively, the tip may be composed of an ultraviolet transparent high refractive index specialty plastic.

The preferred embodiment of the fiber tip of the present invention is in the shape of an inverted cone (e.g., a negative axicon) capable of emitting an annular beam of light into the water from an emission angle β of 56 ° above the central longitudinal axis of the fiber. The everting tapered tip may emit light at an angle beta of up to 71.5 deg.. These angles must be approximations because the natural angular spread of the laser beam may exceed the critical angle for total internal reflection, thereby reducing some portion of the beam power

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

The invention further relates to a dilation system comprising a thrombectomy catheter modified to a system employing an optical fiber to carry UV laser, the optical fiber having a distal end or comprising a tip at its distal end, wherein the optical fiber or the tip is configured in a tapered shape for emitting UV laser light as a tapered beam. The expansion system comprising the optical fiber of the present invention may configure the distal end or tip of the optical fiber as an inverted (inwardly protruding) taper or an externally protruding taper. An aspiration thrombectomy catheter or stent thrombolytic device may be used to employ the expansion system comprising the optical fiber of the present invention. Preferably, the dilation system of the present invention minimizes physical contact with the dilated anatomy, but still allows the UV laser to impinge on the structure. Since the impact and resulting expansion may be sustained, the preferred embodiment of the present invention is referred to as a "minimum contact sustained expansion system". Thus, a preferred embodiment of the system includes a "minimum contact sustained expansion system".

In use, the expansion system of the invention may be used in a method for expanding a tubular anatomical structure in a patient. The method according to the invention comprises the following steps:

-providing a catheter housing containing a UV transparent balloon expanded with a UV transparent gadolinium-based contrast agent, in which a fiber for carrying a UV laser is inserted, wherein the fiber has a distal end or tip with a tapered configuration; and

UV laser energy is emitted as an annular beam onto smooth muscle cells in the inner wall of the tubular anatomy by the balloon (which expands by the gadolinium contrast agent so as to be adjacent to the inner wall of the tubular anatomy). This will stimulate photophysical production and release of Nitric Oxide (NO) from nitrite (NO ₂ ^-) reserves in the arterial smooth muscle cells, whereby the nitric oxide causes relaxation of the smooth muscle cells and expansion of the tubular anatomy.

The method may be adapted or applied to an intravascular thrombectomy procedure, further comprising the steps of:

-positioning the UV fiber optic dilation system within about 1 to 10 vessel diameters of a clot within an artery containing the clot;

expanding the UV transparent balloon catheter to the inner wall of the artery with a UV transparent gadolinium contrast fluid sufficient to prevent blood flow but not to dilate the artery due to mechanical pressure,

-Emitting a burst of UV light energy as a laser beam through the gadolinium-expanded balloon wall and onto smooth muscle cells in the arterial wall to stimulate the production of NO from nitrite (NO ₂ ^-) reserves in the smooth muscle cells, thereby stimulating and observable active dilation of the artery; and

-Removing the clot.

A UV transparent balloon catheter is first deployed into a tubular structure to center the tapered tip of the inserted optical fiber in order to ensure uniform irradiation intensity around the periphery of the structure. The balloon may be expanded to the inside diameter of the tubular structure with a UV transparent gadolinium contrast agent to ensure visibility in x-ray examination. The UV radiation is then conducted through the balloon fluid and into the wall.

The method of the present invention is preferably performed by directing UV light onto the vessel wall within about 1 and about 4 vessel diameters away from the clot. The method may be performed using continuous UV light emission or UV light emission with acousto-optic Q (pulsing) at high frequency (5 to 25 kHz), with pulse width greater than 50 nanoseconds, or as a quasi-continuous beam with picosecond pulse width, for example, pulsed at 100MHz and pulse width >10 picoseconds, or as a square wave lasting at least 2 to 10 seconds. In a preferred embodiment, the UV light is emitted at a wavelength of about 180 to 400nm, more preferably about 300 to 400 nm. One preferred embodiment uses a frequency tripled Nd: YAG laser that emits light at 355nm to emit UV light. The preferred incident intensity of UV light is between about 3 watts per square centimeter and about 20 watts per square centimeter.

According to the methods described herein, it will be appreciated that the thrombectomy catheter used in a thrombectomy procedure may be an aspiration catheter or a catheter through which a stent-graft is inserted.

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

The object of the present invention is to optimize arterial integrity during and after thrombectomy by reducing frictional or chemical bonding resistance to mechanical extraction of an occluding clot. The devices and methods of the present invention include providing UV laser radiation of appropriate intensity to the inner wall of the artery proximal to the clot when using an aspiration catheter or distal to the clot when using a stent thrombolytic device when performing a thrombus aspiration technique. UV laser irradiation by an annular beam having an axis collinear with the artery will cause significant distension of the arterial wall within seconds, wherein the distension effect will propagate proximally and distally to impair the friction and/or chemical bonding of the clot to the wall.

It is another object of the present invention to provide an aspiration catheter or stent embolectomy further comprising an optical fiber capable of delivering UV light to the distal end or tip of the catheter, wherein the UV light may be emitted for a short period of time, e.g., 2 to 10 seconds, during a saline flush or balloon catheter expansion to clear blood from the vessel wall (but not mechanically dilate the artery) and thus directed to smooth muscle cells that make up the vessel wall. One particular embodiment introduces the laser beam through an intravascularly deployed optical fiber that includes a protruding (external) tapered tip that can actually act as a diverging lens for the beam by primary reflection and primary refraction. This design will produce a circumferential irradiation pattern as an expanding conical ring, thereby producing a ring-shaped laser beam on the wall of the tubular anatomy at which the beam is directed. The protruding tapered output tip is preferably made using a UV transparent material with a refractive index n higher than fused silica, such as diamond, zirconia or custom plastic that can be optically coupled to n >2 of silica. As the exit angle β increases, the beam intensity and arterial dilation efficiency also increase, while the length of the beam projected along the arterial wall decreases, as the irradiated annular area also decreases. Any projected length along the artery wall will cause dilation if the intensity criteria are met, but a larger beam exit angle favors greater intensity and thus more efficient use of the beam.

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

These same considerations apply to an inverted cone tip, but in diamond the maximum emission angle (e.g., about 56 °) will be less than the maximum emission angle of the outer tip (e.g., 71.5 °). The intention is to provide two different ways to produce an expanded ring shaped beam of light, the relative benefits of which have been described above and which can evaluate clinical applications.

Drawings

Fig. 1A shows the upper half of the z-plane cross-section of a laser ring beam with gaussian intensity distribution G ₀ (produced by an optical fiber with an external conical tip with conical half angle a) that produces expanded gaussian beam profile G _w when impinging on the inner wall of an artery with radius R. It should be noted that the beam has a polar angle spread of 2θ _w. The ring beam is cylindrically symmetric about the optical axis, with its central maximum being emitted at an angle β. The intensity profile of G ₀ is plotted to a 1/9 scale. The G _w intensity at point "p" is a function of r _w＝(z–z_o) sin beta, as well as (z ²+R²)^1/2).

Fig. 1B shows laser axial ray tracing in a protruding (external or everted) tapered-tipped fiber. The dashed line (OO) traces the path of an ideal laser ray at the output end of a silica fiber with a tapered tip (total apex angle = 2 a). As long as the angle of incidence θ ₁ is greater than the critical angle at the silica/water interface θ _crit (64.653 °) (and therefore examined α <90 ° - θ _crit), the beam will follow total internal reflection at point P and then enter the aqueous medium from point Q, θ _crit = 64.653 °. When rotated around the optical axis, the locus of points defined by O will produce a ring shaped beam. N ₁ and N ₂ are normals to the top and bottom surfaces of the cone. According to this figure, it was checked that α+θ ₁ =90° and ω=180 ° -2θ ₁, so δ=3θ ₁ -180 ° =90 ° -3α. The ring beam trajectory is a conical surface defined by the angle β (α) =θ ₁ - α - γ (α), which is also examined. Gamma (alpha) is expressed as sin ^-1{(n₁/n₂) cos 3 alpha. According to snell's law, β (α) can now be determined from the half angle α of the tapered tip of the fiber.

FIG. 2A shows an external tapered tip machined on a 36 DEG full-apex taper angle (2α) fused silica fiber in accordance with an embodiment of the present invention.

Fig. 2B illustrates a UV laser ring beam generated in water by the external conical tip shown in fig. 2A. Table 1 shows the values of α, β (α) and the reflection and refraction angles for pure silica fibers, and table 2 shows β (α) when the tip is an optical coupling diamond. The range and value of β (α) for diamond (up to 71.5 °) is significantly increased compared to silica itself (up to 48.4 °).

Fig. 3 shows the optical properties of an inverted cone-tipped fiber, showing the path of reflected and refracted laser light (entering from the right) in a fused silica fiber with an inverted cone-tipped or tipped made of diamond, where the beam enters into the water (saline) and onto the internal arterial wall. The maximum emission angle β (α) of diamond into water is about 56 °, which far exceeds the maximum emission angle from silica alone (25.4 °); see table 3.

Fig. 4A, 4B and 4C show fiber tip placement and intravascular UV irradiation in the Basal Artery (BA) of three dogs. The expansion caused by UV irradiation is semi-localized; for a basilar artery of length 40mm, the dilation can be extended from the locus of annular beam irradiation of the adjacent (spinal) artery up to 60mm.

Fig. 5 shows the initial deployment of a balloon catheter over a guidewire (dark grey) 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 effectively be centered in the artery. At this point, the guidewire may be withdrawn and replaced with a UV emitting fiber to expand the resistance to tortuosity (if present) to reduce the resistance to further insertion of the guidewire to further track the optimal path of the UV emitting fiber and subsequent thrombectomy device through the artery.

Fig. 6 shows the balloon catheter of fig. 5 fully inflated over the centered guidewire and the guidewire is withdrawn and replaced by an optical fiber (white line) that will emit UV laser light from the tapered tip that is synthesized to produce a ring beam (elliptical diagonal trajectory) at the desired angle β near the occlusion (thrombus). The output end of the fiber can be placed as close as the balloon allows to the thrombus, but UV ring beam irradiation will cause continuous arterial dilation starting from <4 diameters up to 40 diameters from the thrombus. At a beam intensity of 3 to 20 watts/cm ², the expansion will occur within a few seconds and extend into the thrombus segment. The balloon is then deflated and withdrawn, and the thrombectomy device is mounted on the optical fiber now being used as a guidewire (although practitioners may prefer to replace the optical fiber with a standard guidewire, and then withdraw the balloon). In the above configuration, a suction catheter will be introduced to withdraw the thrombus, with less frictional resistance now due to the distention of the occluded arterial segment. To deploy the stent embolectomy, the guidewire must penetrate the thrombus (possibly near the edge) and deploy a balloon thereon, and other steps are performed as described. Here, expansion distal to the thrombus will allow the stent retriever to be deployed at a larger diameter, ensuring maximum thrombus interception and complete extraction as long as the stent retriever's integrity is preserved.

Fig. 7 provides a pictorial overview of the application of ultraviolet laser-induced dilation to thrombectomy in order to minimize wall damage due to mechanical friction.

Detailed Description

The present invention relates to a device and method for the dilation of a tubular anatomical structure, such as an artery, wherein the dilation is caused by directing an Ultraviolet (UV) laser beam of suitable intensity onto the wall of the tubular anatomical structure, the directing onto the wall not causing functional damage to cells of the structure. The devices, systems or methods of the present invention may be used with anatomical structures such as anatomical tubes, tubes or tubules, blood vessels (such as arteries), bronchioles, ureters, vessels, and the like.

The preferred embodiment employs a fused silica fiber that includes an inverted tapered tip. The tip preferably comprises a UV transparent material having a high refractive index in optical contact with the fused silica fiber. For the tip, UV transparent and very hard materials with high refractive index are preferred, such as diamond (refractive index at 355nm of 2.48) or zirconia (refractive index at 355nm of 2.3), or custom designed high refractive index (n > 2) plastics. Such tips may provide the ability to create an exit angle (half cone angle) of the UV ring beam up to 56 ° (using an inverted cone tip) or 71.5 ° (using an everting cone tip), both tips being made of diamond.

One preferred embodiment of the present invention relates to an optical fiber, preferably having a core with a diameter of 10 to 100um, more preferably 50 to 100um, for transmitting UV laser light to the distal end or tip of the optical fiber, and emitting a cone-shaped UV laser beam, which impinges on the inner wall of the tubular anatomy in the form of an expanded annular ring or beam.

To achieve such annular beam formation, the distal end of the fused silica fiber may be formed in a tapered shape, such as an external tapered shape (outwardly convex), or may be an inverted tapered shape (inwardly convex). As shown in fig. 1A using a silica fiber with an external tapered tip 101 positioned within microcatheter 104, the upper half of the z-plane cross-section of the laser ring beam is shown as having a gaussian intensity profile G ₀ produced by the fiber with the external tapered tip, which is formed by a fiber with a conical half angle α. Distribution G ₀ impinges on the inner wall 102 of the artery having radius R to produce an expanded gaussian beam profile G _w 103. It should be noted that the beam has a polar angle spread of 2θ _w. The ring beam is cylindrically symmetric about the optical axis, with its central maximum being emitted at an angle β. The G _w intensity at point "P" is a function of r _w＝(z–z_o) sin β, as well as (z ²+R²)^1/2). As shown, the optical fiber 101 is positioned proximal to the thrombus 105 (T) for use.

FIG. 1B is a detailed view of the fused silica fiber with external tapered tip 101 shown in FIG. 1A, illustrating laser axial ray tracing in a protruding (external) tapered tip fiber. The dashed line (OO) traces the path of an ideal laser ray at the output end of a silica fiber with a tapered tip (total apex angle = 2 a). As long as the angle of incidence θ ₁ is greater than the critical angle at the silica/water interface θ _crit (64.653 °) (and therefore examined α <90 ° - θ _crit), the beam will follow total internal reflection at point P and then enter the aqueous medium from point Q, θ _crit = 64.653 °. When rotated around the optical axis, the locus of points defined by O will produce a ring shaped beam. N ₁ and N ₂ are normals to the top and bottom surfaces of the cone. According to this figure, it was checked that α+θ ₁ =90° and ω=180 ° -2θ ₁, so δ=3θ ₁ -180 ° =90 ° -3α. The ring beam trajectory is a conical surface defined by the angle β (α) =θ ₁ - α - γ (α), which is also examined. Gamma (alpha) is expressed as sin ^-1{(n₁/n₂) cos 3 alpha. According to snell's law, β (α) can now be determined from the half angle α of the tapered tip of the fiber.

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

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

Table 1 herein below provides the range of paths of the light beam in the fused silica external cone tip for fiber optic half cone angle α, as well as the angles associated with one total internal reflection and one refraction, resulting in the light beam exiting the tip at angle β (α). The ring beam cross-section along the arterial wall (angular width 2θ _w, see fig. 1A) can vary from a gaussian profile to a gaussian "top hat" profile, i.e., a typical output mode of multimode fiber, which, when expressed at maximum, means a substantially constant intensity across the ring width. These intensity patterns are not important for the generation of the dilation, but they do affect the average power and peak power of the beam and its upper limit.

An externally convex tapered tip according to an embodiment of the present invention is shown in fig. 1A, 1B and 2. A sharp external conical tip made of silicon dioxide (full apex angle <40 °, half cone angle <20 °; see fig. 1 and 2A) may break and/or become entangled due to intravascular obstructions, if any. The most passivated external silica tip (full apex angle about 50 °) is preferred (see table 2). Tips made of very hard materials such as diamond, zirconia or high refractive index (n > 2) plastics can avoid cracking, but may still become entangled depending on the complementary device array used. In practice, the optical fiber is introduced through a catheter, which provides protection.

Alternatively, the tapered tip may be inverted (inwardly protruding) at the distal end of the optical fiber, as shown in fig. 3. Preferably, the fused silica optical fiber 301 includes an inverted diamond cone tip 310 because such a design can avoid entrapment by intravascular obstructions and is less likely to be damaged during insertion or deployment. Such tips are capable of emitting an annular (ring-shaped) beam into water using an emission angle of up to 56 ° above the diamond tip (see table 3). The fused silica tapered tip may produce an emission angle between 20 ° and 24 ° relative to the central longitudinal axis of the optical fiber (see table 3). The efficiency of the beam intensity and expansion (and associated clot dissolution) process increases with increasing emission angle, so it is desirable to maximize this emission angle within the physical limits allowed by UV transparent high refractive index fiber optic tip materials (fused silica, diamond, zirconia, or custom plastics). The tip may be made of a UV transparent high refractive index (n > 2) material coupled with a conventional optical fiber, wherein the coupled tip and optical fiber are in optical communication with each other. The coupled tapered tip of the silica fiber may protrude outward from the distal end of the fiber and emit a ring-shaped beam at an angle of up to about 48 ° relative to the longitudinal axis of the fiber (table 1). If the tip is made of diamond (table 2), a wider emission angle range up to about 71.5 ° can be achieved.

Optical fibers comprising a tapered tip (outwardly convex (everting) or inwardly convex (inverting)) may be used in the minimally contact sustained expansion system of the invention, for example as part of a subsequently deployed atherectomy catheter system. The width of the annular or ring beam emitted by the optical fiber of the present invention depends on the artery diameter. This feature may be advantageous because the distending effect in any tubular anatomy (including arteries) is driven by the beam intensity and can occur very rapidly (< 1 second) depending on the photophysically generated Nitric Oxide (NO) concentration in the cells lined by the tubular anatomy (e.g., arterial wall). Irradiation at a given intensity will cause a corresponding expansion which itself may propagate proximally and distally from the region contacted by the annular beam via a trans-nitroso reaction.

In a preferred embodiment, an optical fiber comprising an inverted cone-shaped tip or a blunt everting cone-shaped tip may be used in combination with a balloon catheter comprising a UV transparent balloon to aspirate a thrombectomy catheter. Preferably, the guide wire introduced in the proximal segment of the occlusion may be centered by a UV transparent balloon catheter and expanded with a UV transparent gadolinium-based contrast agent, whereby the guide wire is replaced with an optical fiber.

Another preferred embodiment is the dilation system of the present invention that includes an inverted cone-shaped tip or a blunt everting cone-shaped tip in combination with a balloon catheter and used in sequence with a stent embolectomy. In this embodiment, the guidewire is initially penetrated, wherein the guidewire must be centered in the expanded balloon catheter and then replaced with an optical fiber in order for the UV ring beam to properly impinge on the inner wall with uniform circumferential intensity.

Another aspect of the invention relates to a method for performing an intravascular thrombectomy, wherein the method comprises the steps of:

providing a thrombectomy catheter compatible with a UV compatible optical fiber;

The UV transparent balloon catheter is expanded to the inner wall of the artery with a UV transparent contrast fluid, which is sufficient to stop blood flow but not to dilate the artery due to mechanical pressure,

Positioning a UV fiber optic thrombectomy catheter within one to four vessel diameters of a clot contained within a vessel;

Emitting UV light energy as a ring beam onto smooth muscle cells in the inner wall of the artery to cause the formation and release of Nitric Oxide (NO) and thereby dilate the artery, whether or not the endothelium (a common source of NO) is intact and whether or not blood is present; and

The clot is removed.

The procedure described above may be performed in preparation for use of the aspiration catheter or stent embolectomy.

Fig. 4A, 4B and 4C show the deployment of our fiber optic device to achieve intravascular 355nm UV laser irradiation in the Basal Arteries (BA) 401, 402 and 403, respectively, on the base lines of three dogs (BA origin is represented by x for each). The expansion caused by subsequent UV irradiation is semi-localized; for a basilar artery of length 40mm, the dilation can be extended from the locus of annular beam irradiation of the adjacent (spinal) artery to 60mm (fig. 4B and 4C). Fig. 4B and 4C indicate that spinal arterial constriction prevents the fiber tip from entering the basilar artery ostia prior to UV irradiation. While for dog a fiber tip 411 may be placed 22% distal to 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 respective BA length proximal to its origin. For irradiation intensities of 12 to 20 watts/cm ², the average expansion reached 94% of baseline after starting from 78%, and expansion was observed at the BA end, although linearly decreasing over the 40mm range.

Fig. 5 illustrates the initial deployment of a balloon catheter 510 over a guidewire 520 inserted near an arterial occlusion (thrombus) 530 prior to UV laser-assisted thrombectomy. The balloon is partially inflated (shown here as not contacting the inner wall of artery 540). When the balloon is inflated or nearly inflated, the guidewire will effectively be centered in the artery. At this point, the UV emitting fiber may replace the guidewire and expand the obstructive tortuosity (if present) to reduce resistance to the guidewire, and the guidewire may temporarily replace the UV fiber to further track the optimal path through the artery toward the thrombus, then reinsert the UV fiber, followed by the thrombectomy device.

Fig. 6 shows the balloon catheter 510 of fig. 5 fully inflated over the guidewire to center the guidewire and the guidewire has been replaced with an optical fiber 610 that will emit UV laser from a tapered tip capable of producing a ring beam 620 at the desired angle β. The output end of the fiber may be placed as close as the balloon allows to the thrombus 530, but UV ring beam irradiation will cause continued expansion, starting from <4 diameters up to 40 diameters from the thrombus. At a beam intensity of 3 to 20 watts/cm ², the expansion will occur within a few seconds and extend into the thrombus segment. The balloon is then deflated and withdrawn, and the thrombectomy device is mounted on the optical fiber now being used as a guidewire (or more likely, depending on the preference of the surgeon, replacing the optical fiber with the original guidewire). In the above configuration, a suction catheter will be introduced to withdraw the thrombus, with less frictional resistance now due to the distention of the occluded arterial segment. To deploy the stent embolectomy, the guidewire must penetrate the thrombus (possibly near the edge) and deploy a balloon thereon, and other steps are performed as described. Here, expansion distal to the thrombus will allow the stent retriever to be deployed at a larger diameter, ensuring maximum thrombus interception and complete extraction as long as the stent retriever's integrity is preserved.

Fig. 7 provides a diagrammatic overview of the steps taken by the present invention to apply ultraviolet laser induced dilation to a thrombectomy in order to minimize wall damage due to mechanical friction fig. 7 illustrates the steps of the method of the present invention performed using the balloon catheter shown in fig. 5 and 6. In step a of fig. 7, a thrombus 701 is shown as being located in a middle cerebral artery 702 prior to deployment of a thrombectomy catheter of the present invention. A microcatheter 720, typically used for balloon catheters, is fed 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 fed over the microcatheter 720, as in normal use of the device, and also positioned proximal to the thrombus 701. Step D illustrates then inflating 740 the balloon catheter to contact the inner wall of the vessel (artery) 721 such that blood flow is significantly or completely impeded between the balloon and the vessel wall. The UV laser is deployed according to the methods described herein such that the ring beam is emitted to contact the inner wall of the blood vessel and the blood vessel portion expands 722 (propagates in both directions from the region where the UV laser ring beam contacts). Using a stent embolectomy or an extraction procedure as shown by way of example only in step E, aspiration thrombectomy catheter 750 may be used in its conventional manner to extract a thrombus 701, which is shown removed from middle cerebral artery 702 in step F. The expansion caused by the UV laser contact may facilitate the removal step.

Advantageously, the dilation method may provide reduced mechanical friction, thereby minimizing damage to the arterial wall. Another advantage is that the platelet component of the clot will also expand (see us patent 6,539,944) and the portion closest to the arterial wall will be partially degraded into individual platelets (by antithrombotic) and thus less adherent to the wall and thus less frictional resistance to the extraction process. No emboli will be generated.

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

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

In the device or method of the present invention, the average incident intensity of the UV light is between about 3 watts per square centimeter and about 20 watts per square centimeter (W/cm ²).

The devices and methods of the present invention may be used in conjunction with the pre-administration of a pharmaceutically acceptable thrombolytic agent that aids in thrombolysis (of fibrin). There is concern about the emission of clot fragments, which our platelet antithrombotic process can avoid. The preferred thrombectomy procedure is to remove the thrombus without the complications of debris caused by the thrombolytic agent.

One particular embodiment introduces the laser beam through an intravascularly deployed optical fiber that includes a protruding (external) tapered tip that can actually act as a diverging lens for the beam by primary reflection and primary refraction. This design will produce a circumferential irradiation pattern as an expanding conical ring, thereby producing a ring-shaped laser beam on the wall of the tubular anatomy at which the beam is directed. The protruding tapered output tip is preferably made using a UV transparent material with a higher refractive index than fused silica, such as diamond, zirconia or custom plastic that can be optically coupled to n >2 of silica. When the beam exit angle increases within the limits specified by snell's law, the beam intensity on the wall and the efficiency of arterial dilation will increase, as 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 apply to an inverted cone tip, but the maximum emission angle will be less than the maximum emission angle of the outer tip. The intention is to provide two different ways to produce an expanded ring shaped beam, the relative benefits of which have been described above and which can evaluate clinical applications

The preferred fiber tip includes an inverted tip configuration (fig. 3) that is less likely to be obstructed during use, although its deployment through a guiding catheter should avoid this possibility as well as the possibility of arterial perforation.

Another embodiment is a fused silica fiber with an external raised tip (fig. 1B) having a maximum emission (semi-cone) angle of about 48.4 ° (see table 2). When the tip is sharp (full apex taper angle less than 40 °, see fig. 2A), if a brittle material is used, the tip may experience breakage due to mechanical contact. This situation can be remedied by an external conical tip made of a very hard material with a high refractive index, such as diamond. The everting diamond cone tip will allow an exit angle of up to 71.5 °. Of course, with increasing dullness (increasing full cone apex angle), the outer tip (including the silica itself) will be more resistant to mechanical damage.

The UV light, when absorbed by nitrite (NO ₂ ^-) in smooth muscle cells of the arterial wall, is capable of releasing Nitric Oxide (NO) at a concentration higher than that maintained by the endothelium during normal metabolism. This can cause quasi-temporary (tens of minutes to hours) and semi-local dilation of the vessel. The release of NO from smooth muscle cells propagates itself proximally and distally from the site irradiated with UV light by a trans-nitroso reaction for a local distance of up to a few centimeters. UV lasers are used to cause vasodilation near the occlusion, thereby reducing friction (or chemical bonding) with the arterial wall when the thrombectomy device is deployed to extract blood clots. Thus, dilation of the vessel may facilitate separation of the clot from the vessel wall to which it is adhered, and facilitate easier and safer removal of the clot (by reducing the strength and frequency of the interaction of the clot with the vessel wall) using conventional aspiration catheters or stent-grafts. The present invention may advantageously reduce the post-consequences of structural and functional damage to the endothelial and intimal structures of occluded arteries undergoing thrombectomy.

The dilation of the vessel increases the diameter of the vessel, which may also facilitate the catheter moving through the appropriate location, i.e., may more easily pass tortuous (severe bending) or stenosis of the vessel.

To achieve the object of the invention, a novel aspect relates to an advantageous configuration of a tip for an optical fiber from or through which UV radiation is emitted. For example, it has been found that using an outer conical tip composed of a very hard but UV transparent material such as diamond can more easily provide an outer (semi-conical) emission angle of up to 71.5 ° (relative to the fiber axis) and consequent narrower projection of the ring beam of UV light. The preferred angle is preferably determined in association with other components of the system, such as a UV transparent balloon extended 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 cone tip. The inverted cone tip is preferably composed of a UV transparent high refractive index material such as diamond, zirconia or custom 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 fiber.

It is another object of the present invention to provide an optical fiber capable of transmitting UV light surrounded by a catheter, wherein the optical fiber is comprised of an inverted cone-shaped tip, preferably comprised of a UV transparent material (such as diamond, zirconia or custom plastic) capable of emitting an annular beam for the cerebral artery. The narrow beam width will concentrate the energy absorbed by the cells of the blood vessel so that even with a relatively low power laser an effective amount of NO will be released for significant vasodilation to occur.

It is a further object of the present invention to provide a dilation system which in a final step may include an aspiration catheter or stent embolectomy, preceded by a balloon catheter surrounding a fused silica optical fiber capable of delivering UV light to the distal end of the catheter. Preferably, the expansion system comprises a fused silica optical fiber for UV irradiation, wherein there is a tapered tip at the distal end of the optical fiber. Preferably, the tapered tip is composed of a UV transparent material with a high refractive index, such as diamond, zirconia, or custom plastic. More preferably, the tapered tip is an everting tapered tip configuration. Alternatively, the fused silica fiber optic component of the dilation system of the present invention comprises a thrombectomy aspiration catheter or stent thrombolytic system comprising an optically contacted inverted cone tip composed of an ultraviolet transparent high refractive index material such as diamond, zirconia or custom plastic.

It is a further object of the present invention to provide a UV transparent balloon catheter that encloses a UV compatible optical fiber that is incorporated with an aspiration thrombectomy catheter as part of a single dilation system. Preferably, a UV compatible optical fiber coupled to an aspiration thrombectomy catheter or stent thrombolytic device will incorporate a diamond or zirconia (or high refractive index plastic) everting tapered tip at its distal end.

In a preferred embodiment, a UV transparent gadolinium-based contrast solution may be used to expand the balloon catheter; the balloon wall then displaces the blood, which provides an unobstructed path for the UV laser light to travel to the inner wall of the artery. According to the invention, the balloon is inflated for this purpose and also centers the conical tip; it is not inflated in order to expand the inner diameter of the vessel wall. Gadolinium contrast agent is localized to the balloon and is therefore isolated from the blood flow. In this embodiment, the balloon material and contrast material are sufficiently transparent to UV light to allow the UV light to pass unimpeded through the wrapped catheter and balloon.

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

a) Providing a dilation system as described herein

B) Positioning a UV fiber optic thrombectomy catheter within one to four vessel diameters of a clot within an occlusion vessel;

c) Square wave pulses of continuous or high repetition rate pulsed beam UV laser energy are emitted as a beam within a specified average intensity range onto smooth muscle cells lined by the inner wall of the blood vessel to release NO from the cells and thereby cause dilation of the blood vessel; and

D) The clot is removed by mechanical extraction.

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

UV light energy bursts in continuous or pulsed form may 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. The 10 second burst may be the most preferred duration of emission of the UV beam for dilating the vessel to a sufficient diameter to reduce frictional interactions of the catheter with the vessel tortuosity or stenosis, or to promote separation of the clot from the vessel wall.

In a preferred embodiment, the invention includes a dilation system comprising an aspiration catheter or stent embolectomy after a preparation period that employs a tapered tipped optical fiber to supply an annular beam of UV radiation. The tapered tip of the optical fiber may protrude inwardly or outwardly from the distal end of the optical fiber, depending on the desired launch angle and whether there is an obstruction along the desired path.

In use, an optical fiber comprising a tapered tip may emit a tapered beam trajectory that irradiates a tubular anatomical structure as an annular or ring beam around the inner circumference of the tubular structure. Tubular anatomical structures that can be expanded with UV light are those lined with (smooth muscle) cells capable of storing (as nitrite) and releasing Nitric Oxide (NO). Such expansion may be advantageously used to expand or dilate the artery at a location near the thrombus to facilitate easier and safer removal of the thrombus by reducing mechanical friction. The thrombus may be an occlusive thrombus or a non-occlusive thrombus. Vasodilation at or near the site of a thrombus within a vessel may loosen or separate the thrombus from the vessel wall, thereby facilitating effective removal of the thrombus by conventional aspiration or stent-graft catheter techniques currently used in the medical arts. Peripheral damage to the occluded vessel should be minimized before, during and after extraction.

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

Since the UV-induced vasodilatory effect may be propagated distally (as well as proximally), the branch vessels may also be dilated by irradiating the main vessel at a distance of about 3, 4, 5, 6, 7, 8,9, 10, 12, 14, 16, 18, 20, 25 or 30 vessel diameters from the thrombus. This phenomenon may be particularly useful in situations where the surgeon cannot access the branch vessel containing the thrombus, but may access the main vessel proximally.

Preferably, the UV light beam is directed onto the inner surface of a tubular anatomical structure, such as an artery, by a light beam transmitted via an optical fiber placed inside a blood vessel by means of a catheter. Immediately after irradiation but almost after that and not more than a few seconds after irradiation with the laser beam, the blood vessel expands first at the irradiated portion and then continuously self-propagates in the proximal and distal directions for a distance of a few centimeters.

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 photocleavage of nitrite (NO ₂ ^-) stored in intact smooth muscle cells in the arterial wall. Local NO concentrations of up to 10 μm can be produced regardless of the severity of the endothelial injury or even when the endothelium is missing (completely destroyed).

Nitrite photolysis in smooth muscle cells produces NO, S-nitrosation of thiols (RSH), leading to the formation of S-nitrosylthiols (RNSO) and to local expansion via NO or its release from the thionitrate (RSNO); these denitrify other thiols, thereby propagating the expansion radially, distally and proximally by releasing more NO. This is a self-continued chain process.

Photophysically generated nitric oxide may stimulate the distention waves proximally and distally. Thus, the frictional resistance to clot removal may be reduced at some portion of the clot length. Thus, the clot can be extracted with less force and thus less mechanical damage to the artery than is currently observed, with fewer future complications at that site or distal or even proximal thereto.

The laser beam used to dilate the artery and thereby treat the occluded vessel may be continuous or pulsed. The use of pulsed lasers reduces heat build-up and consequent damage in the target and surrounding tissue. If a non-ablative pulsed laser, such as a quasi-continuous or acousto-optic Q-switched laser, is used, the pulse rate may be any rate consistent with delivering an appropriate time-averaged intensity of radiation to the target tissue while avoiding individual pulses of too high an intensity to cause permanent damage in the target tissue, i.e., irreversible damage over a physiologically relevant time frame (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 370nm, and most preferably about 350 to 360nm. YAG lasers emitting 355nm radiation at a frequency tripled Nd-YAG are particularly preferred.

Other UV lasers that may be used in the present invention (while avoiding ablation) include XeF lasers (351 nm), CW argon ions (351 nm, 364 nm) or CW krypton ions (351 nm, 356 nm). Any diode laser or dye laser may be used as long as it is capable of achieving a non-ablative output in the UV range required for vasodilation effect. In principle, any laser that emits UV radiation directly or as a result of frequency doubling or frequency triplets may be used.

For 355nm UV laser irradiation, expansion is stimulated over a wide dynamic range for an intensity of 7 (intensity of 3 to about 20W/cm ²), thus assuming a Gaussian beam shape. However, the expansion effect is independent of the beam shape. At the upper limit, vacuoles are formed in smooth muscle cells, but the function is not impaired. The expansion effect depends on the average intensity. For example, a 100 nanosecond pulse sequence of 7Hz and a peak power of 5 kilowatts may be used at 20W/cm ² without causing a functional impairment.

Blood in the path of the laser beam may be purged, for example, by flushing a small amount of physiological saline solution through the catheter opening from which the beam exits immediately before irradiating the vessel wall or thrombus.

The intensity of the UV irradiation is preferably adjusted to provide the minimum dose required to achieve the desired degree of vasodilation within the desired time frame prior to thrombectomy. For example, using a frequency tripled Nd-YAG laser, an incident intensity of about 5 watts/cm ² will produce about 20% to 30% expansion in the arterioles (this expansion can be reversed by NO inhibitor drugs). Higher intensities of 12 to 20 watts/cm ² (equivalent to energy flux per pulse up to 1J/cm ² at a pulse frequency of 20 Hz) can produce a similar increase in the diameter of the larger artery (about 1.5mm diameter), but intensities exceeding 20 watts/cm ² may alter the vessel wall structure (small vacuoles formed in smooth muscle tissue) but no functional impairment is observed.

The incident intensity may then be increased in increments (e.g., 2 watts/cm ² or more increments) until appropriate dilation of the vessel is observed within a reasonable time (e.g., within 5 seconds). The irradiation period may be continuous, i.e. until the distension effect is stable, or may be intermittent, in which case the duration of one or more irradiation periods may also be varied at a given incident intensity in order to obtain an appropriate response; the already induced expansion will be preserved and amplified. The appropriate vasodilation response (i.e., the degree of dilation and its kinetics of onset and duration) may be determined by the user; however, many users generally consider a response in which the vessel diameter increases by a range of 20% to 40% in 5 to 10 seconds to be appropriate.

The methods of the invention are useful for treating a variety of disease conditions involving arterial occlusion. Examples of such conditions include stroke, myocardial infarction, and blockage or cramping of any peripheral artery (aorta or arteriole).

In the method of using an aspiration catheter of the present invention, a balloon catheter may be introduced and then the aspiration catheter is placed just above the catheter and behind the balloon portion. The UV fiber may then be introduced into the balloon. When the UV transparent balloon expands just beyond the diameter of the aspiration catheter in front of the tortuous curve or stenosis, the UV fiber is then centered in the artery and the non-flowing blood is displaced from the projected optical path. The UV beam may then flash for a few seconds to obtain an expansion sufficient to allow the thrombectomy catheter used in the subject dilation system to pass through. Here, the balloon does not push against the artery to dilate it, but is simply a means to promote blood displacement away from the artery, while the laser ring beam follows an optically free path to dilate the artery non-mechanically. Balloons are very common but may be damaged if inflated too much.

Once UV light is emitted onto the wall of the blood vessel and absorbed, the blood vessel will distend and propagate distension, whether or not blood or blood flow is subsequently present. This procedure can be used to more easily traverse tortuous bends or stenoses en route to the clot. Thus, structural and endothelial damage is minimized from the entry point to the target site. Once the clot is reached, a final irradiation, including an optional saline flush, is performed, and then the aspiration catheter aspirates the clot.

For use in conjunction with a stent thrombolytic device, the guidewire will penetrate the clot and move several centimeters past the clot. The balloon catheter is then inserted to center the guidewire in the distal section and expanded and flushed just enough to displace the static blood as described above. The guidewire is withdrawn and replaced with a UV fiber that irradiates the cleared arterial segment for 5 to 10 seconds just distal to the clot. After expansion, the UV fiber is withdrawn and a stent thrombolyser is passed through the balloon catheter instead of the fiber. The stent embolectomy is now centered and the balloon catheter can be withdrawn. Expanding the stent embolectomy to a diameter larger than the artery allows for better capture of the entire clot and ensures extraction efficiency.

Another benefit is the ability to use UV radiation at locations where the catheter is difficult to pass toward the target clot site; this will facilitate safer clot extraction. Catheters that at some unexpected point appear to be too large for the artery can still be used after UV expansion. If a catheter size selection error occurs initially, UV dilation can be used to dilate the artery without replacing the current catheter.

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

Table 1. Emission angle β (α) (in degrees) of 355nm light emitted from a silica fiber (n ₁ =1.475) with an external tapered tip into water (n ₂ =1.333) or air (n ₂ =1.00); α = half angle at the apex of the conical tip; β (α) =pi/2- α - γ (α), δ=pi/2-3α, and γ (α) =sin ^-1{(n₁/n₂) cos 3α.

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

In order to increase β (and thus reduce the area subtended by the ring beam on the arterial wall), a short (about 0.5 mm) everting cone segment made of a higher refractive index UV transparent material must be optically bonded to the silica fiber. The best choice is diamond, which has a refractive index of n _d = 2.48.

Table 2 presents the same calculations described above for a beam of light injected into water from an external diamond tip.

Table 2. Emission angle β (α) (in degrees) of 355nm laser light emitted from an external diamond-tipped silica fiber (n ₁ =2.48) into water (n ₂ =1.333) (see fig. 3); β (α) =90- α - γ (α), δ=90-3α, and γ (α) =sin ^-1{(n₁/n₂) cos 3α, where α=half angle at the apex of the tapered tip.

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

Table 3 shows the path range of 355nm laser light emitted from an inverted cone tip made of silica and diamond into water (saline) toward the artery wall. The emission angle β is a function of the back taper half angle α (depicted in fig. 3). Some practitioners may prefer an inverted cone tip design because the likelihood of the tip getting stuck by an obstruction (if any) is much less than an external cone tip.

Table 3. Emission angle beta in degrees calculated as a function of the inverted cone half angle alpha of the silica and diamond tip according to snell's law for a ring beam emitted into water towards the arterial wall (fig. 3). α=90° - θ ₁, where θ ₁＝θ_g,d and g=glass (silica), d=diamond, θ ₂＝θ _{Water and its preparation method} , and β=θ _{Water and its preparation method} -θ_s,d.

Silica fiber, n _Glass diamond tipped silica fiber, n _{Diamond diamond}

This calculation is complementary to those of the external diamond cone tip and shows that the emission angle β is even greater compared to the back taper tip and thus provides increased beam intensity at a reduced distance from the external cone tip (both being more preferred than silica alone). However, β is very sensitive to α, meaning that the input beam must be well collimated to minimize the polar angle spread 2θ _w (see fig. 1A), and the internal tapered tip must be very precisely lapped to ensure high surface quality and thus minimize beam scattering. Here, θ _crit＝θ _{Diamond diamond} =32.51° and β=57.49 °. If θ _{Diamond diamond} = 32.50 °, then θ _{Water and its preparation method} = 88.44 °, α= 57.50 ° and β= 55.94 ° (table 3).

As an alternative to the cone-tip optical designs shown so far for producing ring beams, we propose a combination of diffractive optics and optical fibers. Diffractive optics involve etching a geometric pattern on a flat-end optical fiber by any of several methods (e.g., photolithography, electron beam evaporation) whose tip may be fused silica itself or other optically coupled UV transparent high refractive index (n > 2) substance such as zirconia, diamond, or custom designed plastic to obtain the desired diffraction phase profile. The pattern on the fiber ends resembles a circularly symmetric bas-relief structure, i.e., a series of concentric annular structures of varying depth and radius, because the material must be precisely removed to form the desired diffraction phase profile. The desired output is a very sharp annular bessel beam with minimal sidebands. For light beams leaving the tip at an angle β >40 °, it is likely that high refractive index substances, such as the latter three substances (as described earlier), are used. To our knowledge, ring beams greater than β=15° have not been produced in any medium by this technique, but manufacturers of diffractive optical devices would like to expand their functional range. A flat end diffraction pattern placed on a suitable high refractive index material comprising an end cap of fused silica fiber immersed in water may be the best form of the device.

Either the outer or inner conical tip can produce a ring beam within a range of angles to the arterial wall, with an upper limit of 48 ° for the outer tip, and 71.5 ° for the diamond, but preferably the maximum angle will be used. For an internal diamond cone tip, this may range up to 56 °, which is preferred. A direct benefit of emitting the beam at a maximum acute angle is that the ring beam width is reduced and thus the laser intensity is higher. Since the expansion process is entirely dependent on the beam intensity (between 3 and 20 watts/cm ²), a lower power (and possibly more compact) laser may be used more efficiently. The design of the inner conical tip is for safety, since in previous work we noted that the silica outer tip may be damaged. The presence of a device that is not damaged by attachment to any other device or tissue element upon insertion is clearly beneficial because jamming is avoided and the tip structure is preserved. However, these effects are unlikely to occur in very hard materials such as diamond.

These and other embodiments and applications of the present invention will become apparent to those skilled in the art in view of the description provided herein. A common but intractable aspect of hemorrhagic stroke is vasospasm (constriction) of the main cerebral artery. Blood injected into, for example, the subarachnoid space from a ruptured aneurysm migrates along the artery, and hemoglobin from the lysed erythrocytes enters the arterial wall and scavenges nitric oxide, thus causing a spasm. Such conditions are currently not reliably treated; any systemic expansion drug will reduce blood pressure to the point of onset. Another currently untreatable aspect is early brain injury mediated by platelet-occluding microvessels in the brain (i.e., prior to vasospasm). Despite extensive animal studies, none of the drugs will solubilize human platelet thrombi. UV laser methods aim to specifically treat these two extremely difficult conditions. We have shown that in dogs with hemorrhagic stroke, vasospasm reverses within three days. We also show that the platelet clot is indeed soluble by UV laser induced nitric oxide, as it inhibits thrombin, an enzyme required to maintain inter-platelet fibrinogen/platelet GPIIb-IIIa cross-linking.

We propose that UV irradiation of the blood supply artery only proximal to the junction of the blood supply artery (FEEDER ARTERY) with the distal branch and its microvascular bed will enable reperfusion of blood, not just arterial recirculation, due to self-replication of nitric oxide at a distance and its associated vasodilation, thus increasing the likelihood of tissue survival. For example, patients with ruptured cerebral aneurysms will be treated urgently by standard care interventional devices such as coils and stents. After the aneurysm is fixed, the neuro-interventional physician can continue to position the microcatheter for coiling to the farther side of the aneurysm. Microcatheters may be replaced with UV transparent balloon catheters and microcatheters may be replaced with optical fibers. Distal UV irradiation will lyse the platelet embolic microvasculature in the vascular region, thereby enhancing reperfusion and improving the clinical outcome of the patient. Three to twenty days after the aneurysm treatment, cerebral vasospasm may cause vascular constriction. Again, using a UV transparent balloon catheter and optical fiber, UV irradiation proximal to the vascular constriction will dilate the artery and restore the artery to its original (or larger) diameter, thereby restoring blood circulation.

Atherosclerotic vascular disease may result in narrowing or narrowing (narrowing) of the arterial lumen due to plaque formation. Current methods require that the lumen be enlarged by balloon angioplasty followed by stent placement to fix the opening. Angioplasty and stent placement first require passing a microcatheter through the stenosis to obtain a distal passageway. When the stenosis is moderate to severe, it is difficult to safely pass the guidewire through the stenosis without removing the atherosclerosis. During stent implantation procedures for atherosclerotic disease, the guidewire and device may be advanced through plaque by dilating the artery with UV. If the plaque calcifies, it may be very hard and incompressible. In addition, balloon dilation may cause adjacent non-atherosclerotic segments to expand and stretch even to the point of structural distortion. A common response to such wounds is hypertrophy, i.e., an abnormal healing response that is known to eventually block the opening formed by the scaffold. We propose that non-mechanical expansion of arteries (even diseased arteries) via the nitric oxide pathway will significantly facilitate distal access to atherosclerosis with intravascular devices. The NO pathway will also minimize vessel tortuosity and over-manifestation of the healing response and thus preserve the desired lumen and its useful life. Endothelial damage to adjacent non-atherosclerotic segments will also be reduced. For example, for patients with severe carotid atherosclerosis, a UV transparent balloon catheter may be positioned proximal to the stenosis with a microcatheter. The guide wire may be replaced with an optical fiber. Subsequent UV irradiation will expand the arterial wall and widen the narrow gap. The optical fiber can then be replaced with a micro-guidewire, and the guidewire can now more easily pass through the widened stenosis for distal access. The balloon catheter may then be removed and the plaque is treated by a guidewire delivery device delivery system. The same system can generally be used to safely place the stent to ensure circulation through the stenosis, but now the stent can be placed in the dilated vessel without causing endothelial damage. This will avoid restenosis, which is a very common complication of stent deployment in current practice, and avoid the need to replace the stent within 3 to 5 years.

Inhaled nitric oxide may be used to treat pulmonary arterial hypertension and acute respiratory distress syndrome, especially in pediatric patients. The inhaled gas diffuses through the alveolar-capillary membrane and causes vasodilation, resulting in reduced pulmonary vascular resistance and increased blood perfusion in the ventilated lung segment. This may improve the blood oxygen level of the patient. The proposed invention can be used in a more targeted way for dilating segments and branches of the pulmonary artery. The pulmonary artery and its branches can be accessed through the femoral vein via catheterization of the right heart. The balloon catheter may then be positioned in the targeted pulmonary artery branch. An optical fiber may 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 region of contact of the annular beam via nitrosation.

Inhaled nitric oxide may be used to treat pulmonary arterial hypertension and acute respiratory distress syndrome, especially in pediatric patients. The inhaled gas diffuses through the alveolar-capillary membrane and causes vasodilation, resulting in reduced pulmonary vascular resistance and increased blood perfusion in the ventilated lung segment. This may improve the blood oxygen level of the patient. The proposed invention can be used in a more targeted way for dilating segments and branches of the pulmonary artery.

The pulmonary artery and its branches can be accessed through the femoral vein via catheterization of the right heart. The balloon catheter may then be positioned in the targeted pulmonary artery branch. An optical fiber may 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 region of contact of the annular beam via nitrosation.

The foregoing disclosure 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 may be practiced without any one or more of the elements, limitations or limitations not specifically disclosed herein. Thus, for example, in each instance herein, any of the terms "comprising," "consisting essentially of … …," and "consisting of … …" can be replaced with any of the other two terms. These terms and phrases are to be regarded as illustrative rather than restrictive terms, and are not intended to use such terms and phrases that do not include any equivalents of the features shown and described, or portions thereof, but rather recognize that various modifications are possible within the scope of the invention as claimed. Therefore, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the claims.

Claims (27)

1. A fused silica optical fiber for carrying UV laser light, wherein the optical fiber has a distal end, wherein the distal end is configured as an inverted cone, and the inverted cone is capable of emitting the UV laser light as a cone-shaped beam. 2. The optical fiber of claim 1, wherein the emitted tapered UV laser beam impinges on the inner wall of the tubular anatomical structure in an annular or ring-like configuration. 3. The optical fiber of claim 1, wherein the distal end of the optical fiber comprises a tip coupled to the distal end of the optical fiber and in optical communication therewith, wherein the tip is configured as an inverted cone capable of emitting the UV laser as a cone-shaped beam. 4. The optical fiber of claim 3, wherein the tip coupled to the distal end of the optical fiber is diamond. 5. The optical fiber of claim 1, wherein the optical fiber is capable of emitting an annular beam into water at an emission angle β of about 14° up to 56° from a central longitudinal axis of the optical fiber. 6. A dilation system for dilating a tubular anatomical structure using UV laser, the dilation system comprising an optical fiber and a UV laser light source, the optical fiber having a distal end that is conical in shape and capable of emitting the UV laser as a conical beam. 7. The dilation system of claim 6, wherein the dilation system comprises a balloon catheter. 8. The dilation system of claim 7, wherein the optical fiber is centered within the balloon catheter. 9. The expansion system of claim 6, wherein the optical fiber has a distal end configured as an inverted cone. 10. The expansion system of claim 6, wherein the optical fiber has a distal end configured as an external convex cone capable of emitting an annular light beam into the water at an emission angle β of up to 71.5° from a central longitudinal axis of the optical fiber. 11. The expansion system of claim 6, wherein the optical fiber includes a tip coupled to and in optical communication with the optical fiber, wherein the tip is configured in a tapered shape. 12. The expansion system of claim 6, wherein the expansion system comprises a thrombectomy device. 13. A method for dilating a tubular anatomical structure in a patient, the method comprising: - providing a dilation system comprising a catheter housing, an optical fiber for carrying UV laser light from a UV laser light source, wherein the optical fiber has a distal end having a tapered configuration; - UV laser energy is emitted from the distal end of the optical fiber as a ring beam onto the smooth muscle cells of the inner wall of the tubular anatomical structure to stimulate the production and release of nitric oxide ( ^NO ) from nitrite ( _NO2- ) stores in these smooth muscle cells, whereby the nitric oxide causes relaxation of the smooth muscle and dilation of the tubular anatomical structure. 14. The method of claim 13, wherein the anatomical structure within the patient is selected from the group consisting of an anatomical tube, an anatomical tube or tubule, a blood vessel, a bronchiole, a ureter, and a vessel. 15. The method for dilating a tubular anatomical structure in a patient according to claim 13, wherein the method is applied to an intravascular thrombectomy procedure using a thrombectomy device, wherein the method further comprises the steps of: positioning the UV optical fiber within approximately 1 to 10 vessel diameters of a clot within an artery and centered within the diameter of the artery; emitting bursts of UV light energy as a laser beam onto smooth muscle cells on the inner wall of the artery to stimulate the production of NO from nitrite (NO ₂ ⁻ ) stores in the smooth muscle cells, thereby producing dilation of the artery; and The clot is removed. 16. The method of claim 13, wherein a balloon catheter is used to center the optical fiber. 17. The method of claim 13, wherein the balloon catheter is transparent to UV light. 18. The method of claim 13, wherein the UV light is directed onto the arterial wall within about 1 to about 4 vessel diameters from the clot. 19. The method of claim 13, wherein the UV light is pulsed at a high frequency of 5 to 25 kHz with a pulse width greater than 50 nanoseconds, or as a quasi-continuous 100 MHz beam with a pulse width of about 10 picoseconds, or as a continuous square wave lasting at least 2 seconds and up to 10 seconds. 20. The method of claim 13, wherein the UV light is emitted at a wavelength of about 180 to 400 nm. 21. The method of claim 13, wherein the UV light is emitted at a wavelength of about 300 to 400 nm. 22. The method of claim 13, wherein the UV light is emitted using a frequency tripled Nd:YAG laser emitting light at 355 nm. 23. The method of claim 13, wherein the incident intensity of the UV light is between about 3 W/cm2 and about 20 W/cm2. 24. The method of claim 15, wherein the thrombectomy device is an aspiration catheter. 25. The method of claim 15, wherein the thrombectomy device is a stent retriever. 26. The method of claim 13, wherein the tapered tip is configured as an inverted cone. 27. The method of claim 13, wherein the tapered tip is configured as an everted cone or an external convex cone.