WO2003057060A1

WO2003057060A1 - Method for treatment of vascular occlusions with inhibition of platelet aggregation

Info

Publication number: WO2003057060A1
Application number: PCT/US2002/041671
Authority: WO
Inventors: Christopher Reiser
Original assignee: The Spectranetics Corporation
Priority date: 2001-12-28
Filing date: 2002-12-30
Publication date: 2003-07-17
Also published as: EP1458301A1

Abstract

This invention is primarily directed to a method for treating vascular occlusions with retardation reduction or prevention of platelet aggregation to deter the occurrence of thrombus. A catheter-based device generates energy, effective to destroy certain biologic tissue by reducing it to cellular size debris and retard or prevent the re-growth of certain platelet containing biological tissue by affecting its ability to aggregate. Pulsed laser light is guided through a catheter encased fiberoptic, the distal end of which is placed in substantial contact with an occlusion in the presence of a liquid medium which is substantially transparent to the laser light, to provide the energy for emulsifying the occlusion while treating platelets disposed upon the interior vascular wall to retard or prevent formation of thrombus. By pulsing the laser at an appropriate repetition rate, a pulsing radiation field can be established locally in the occlusion. The optical energy, impinging the occlusion, generates a rapid positive pressure spike through a liquid to vapor aqueous phase transition, and a subsequent rapid negative pressure spike is produced through a vapor to liquid aqueous phase transition to emulsify the biologic material to cellular size debris. By steady, slow movement of the distal end of the catheter encased fiber optic, so that it remains in substantial contact with the remaining biologic material to be removed a repetitive series of these laser energy produced spikes, emulsify and/or liquefy the biological matter forming the occlusion while treating the surrounding interior vascular tissue to retard or prevent subsequent thrombus growth. Preferably an excimer laser system is used. This method can be used in vivo for the treatment of, for example, thrombolytic vascular conditions to remove and retard recurrence of such conditions.

Description

METHOD FOR TREATMENT OF VASCULAR OCCLUSIONS WITH INHIBITION OF

PLATELET AGGREGATION

BACKGROUND OF THE INVENTION

FIELD OF THE INVENTION

[0001] The present invention relates to the treatment of blockages in tubular tissues and organs with concurrent reduction of platelet aggregation; and more specifically, relates to the removal of intravascular occlusions such as atherosclerosis or thrombus in a manner such as to retard or prevent recurrence of the thrombus at the removal site.

DISCUSSION OF RELATED ART

[0002] Angioplasty had its origin with balloon angioplasty. In balloon angioplasty, the cardiologist inserts a long, hollow, narrow tube (catheter), into an artery through an incision. Using X-ray technology, the doctor can monitor the exact place of the catheter inside an artery. The cardiologist advances the tube through the blood vessels to reach the blockage. A second, thinner catheter is then inserted into the first catheter. At the tip of the second catheter exists a small miniature, deflated balloon. Once in proper position, the miniature balloon is inflated, causing the narrowed area of the artery to become slightly wider. In some cases, a device known as a stent is inserted via another narrow catheter. A stent reduces the likelihood that the artery becomes narrowed again after the angioplasty procedure.

[0003] Laser angioplasty had its origin in the 1980s to overcome inherent problems with and limitations of balloon and stent angioplasty-restenosis. Laser irradiation was demonstrated to ablate atherosclerotic tissue, which allowed recanalization of lesions that could not be traversed by conventional balloon catheters. In order for laser angioplasty to be effective, however, without lateral tissue damage, a laser with the proper wavelength and energy was required. The object was to remove (or tunnel through) the obstruction to allow restoration of blood flow without damaging the blood cells or the blood vessel tissues. Damage to surrounding tissue from balloon or laser angioplasty may trigger clotting of the blood, which may result in the reoccurrence of the occlusion. Thermal damage caused by laser energy being absorbed by the tissues depends on the wavelength of the laser, duration of the beam, tissue color, consistency, and water content. [0004] There are generally three methods of laser angioplasty: thermal, photothermal, and photoablative. In thermal laser angioplasty, a laser is used to heat a biocompatible metal alloy tip attached to a fiberoptic waveguide. The surgeon guides the probe through the obstruction causing a small lumen for the blood to flow through. This method can cause extensive thermal damage of the tissues as well as carbonization and necrosis of the vessel walls. Photothermal laser angioplasty involves contact of a laser probe that rapidly heats the plaque (obstruction) to the point of vaporization by direct absorption of the light energy. This method is more productive and safer than the thermal method, but still can cause damage to vessel walls.

[0005] The third general method is photoablative laser angioplasty that involves the use of an ultraviolet laser. The excimer, excited dimer, laser uses either two noble gas atoms or a noble gas atom in conjunction with a halogen atom to lase at different wavelengths, mostly ultraviolet (UV). Excimer lasers ("cool" lasers) were, thus, found particularly useful because they generate nanosecond, high power, UV and UVB pulses that cause bonds to break and plaques to vaporize by acoustic shock waves and/or photoablative effect. Excimer laser angioplasty technology involves moving a fiberoptic catheter through the circulatory system to destroy and thus remove or tunnel through occlusions along the arterial wall.

[0006] The energy source of an excimer laser can be a beam of electrons at high energy or many electrons at high current discharge (10,000 A). XeCl is a common excimer laser that is used for angioplasty. In a typical XeCl laser, an electron collides with a Xe atom causing it to go to an unstable electronic configuration, which allows it to bind with a CI atom and produce XeCl*. Since there are no XeCl* molecules at a low energy state, population inversion takes place with the resulting emissions around 300 nm. [0007] With refinements in laser fiber optics for catheter born systems, the FDA approved an excimer laser procedure in 1992 for clinical use as a recanalization device in both coronary and peripheral arteries. However, the requirement to follow laser angioplasty with balloon angioplasty in the majority of cases and the uncertainty of the effect of laser tissue removal on restenosis, has affected the usage of this procedure. The restenosis resulting from laser angioplasty related to several effects including clotting of blood from treatment injury to surrounding tissue. For example, Petit et al. observed that laser angioplasty resulted in occurrence or reoccurrence of thrombus (blood clots) more than 11% of the time. (Pettit et al., "Thrombolysis by Excimer Laser Photoablation," Lasers in Life Sciences, vol. 5, No. 3, pp. 185-197, 1993). Thus, laser angioplasty was considered by some to be a higher risk procedure with respect to restenosis than balloon angioplasty alone.

[0008] The phenomenon of blood clotting is for the most part beneficial. Platelets (the body's natural blood-clotters) bind together (so called platelet aggregation) when the body has been cut. Also known as thrombocytes, platelets play a major role in blood coagulation, clotting and hemostasis (stoppage of bleeding). Platelets are the smallest blood components. Platelets detect and attach themselves to specific molecular markers that are typically produced when a blood vessel is damaged or ruptured and adhere to the vascular damage site. Through a complex mechanism, they express molecules on their surfaces that attract other blood cells, and that stimulates the production of fibrinogen and fibrin. Once the polymerization of fibrin begins, a gel is rapidly formed that entraps water and various blood cells. This clot may harden with time as it desiccates (dries), or may grow fibrous strands (scar) over the ensuing months. Without this important clotting function of the platelets, excessive and potentially life-threatening amounts of blood would be lost after simple cuts or scrapes.

[0009] There are, however, times when their formation is harmful. Under normal conditions, platelets don't attach to each other or to the walls of blood vessels unless the body has been injured. Although, there are times when blood clots are formed even when a person has not been wounded, heretofore angioplasty has increased the tendency of forming clots or platelet aggregation at the work site and in surrounding tissue. These blood clots, like all blood clots, can be dangerous if they are large enough to block a blood vessel (a thrombus). They also pose a threat if the clot or pieces of the clot break off, travel through the bloodstream and block a blood vessel in another part of the body (an embolism).

[0010] Thus, one drawback to angioplasty has been the platelet aggregation leading to the formation of clots from disturbed tissue at the worksite. Depending on the size and location of these blood clots, they could increase the person's risk of a heart attack or stroke. Therefore, antiplatelet drugs, which are a type of anticoagulant, have been prescribed for angioplasty patients to reduce the likelihood that the platelets will gather together (aggregate) and form potentially harmful blood clots. All patients, for example those with bleeding ulcers, cannot use antiplatelet medications. Additionally, these medications are not always effective.

[0011] Many researchers have theorized about the mechanism involved in the first steps of clotting which involves the ability of the platelets to find and adhere to a vascular site. Some researchers have hypothesized that exposure to UV light may deactivate the platelets. Others have reported the clotting of lased platelets. A number of researchers have shown that illumination of blood samples with continuous-wave UVB light from light bulbs can inactivate leukocytes (white blood cells) without affecting platelets. Pamphilon (Pamphilon DF, Potter M, Cutts M, et al. Platelet concentrates irradiated with ultraviolet light retain satisfactory in vitro storage characteristics and in vivo survival. Brit J Maematology 1990; 75:240-244) showed that UVB -irradiated platelets showed satisfactory function and storage capability after treatment with 3 mJ/mm² of UVB radiation. At higher doses of UVB treatment, other authors reported various kinds of damage to platelets. At doses above 20 mJ/mm², Grijzenhoult (Grijzenhout MA, Aarts-Riemens MI, Akkerman WN et al. Ultraviolet-B irradiation of platelets induces a dose-dependent increase in the expression of platelet activation markers with storage. Brit J Haematology 1993; 83:627- 632) found that platelets began to express activation markers during storage. This suggests that a dose range of 20-80 mJ/mm may actually cause an increase in platelet activity, instead of a stunning of platelet activity. Further, van Marwick Kooy (van Marwijk Kooy M, Akkerman JWN, van Asbeck 5, et al. UVB radiation exposes fibrinogen binding sites on platelets by activating protein kinase C via reactive oxygen species. Brit J Haematology 1993; 83:253-258) observed that over a dose range of 4-16 mJ/mm², platelets were stimulated to express fibrinogen binding sites by a nontraditional biochemical process. Further, Pfefer (Pfefer TJ, Choi B, Vargas G et al. "Pulsed laser-induced thermal damage in whole blood," J Biomechan Eng 2000; 122 196-202) warns that extending the dose rate into higher values causes thermal damage in blood that leads to a well-characterized immediate clotting response that would be very deleterious to a patient's condition. One thing that is clear however is that, heretofore, laser ablation of occlusion has resulted in increased incidences of clotting and requires anticoagulants and clot dissolving drugs. [0012] In fact, the negative side effects of excimer laser coronary angioplasty (ELCA) were studied by clinical researchers in the period 1988-1993. In particular, one group in Boston observed particularly poor clinical outcomes in arteries containing blood clot (thrombus). It was thought that thrombus, being an easily fractured substance, was incompletely ablated, causing rather large pieces of material to float downstream and form blood clots in the small downstream arteries. Various complications were reported in this patient group, related to the lack of blood flow through the arteries. Largely, based on this experience, it became generally accepted that the presence of thrombus in an artery excluded the use of excimer laser angioplasty in that artery.

[0013] U.S Patent 6,022,309 issued February 8, 2000 to Celliers et al, for Opto- acoustic thrombolysis applied laser angioplasty to vascular thrombus. This is an example of a catheter-based laser device for generating an ultrasound excitation of a liquid medium to fragment a thrombus. Pulsed laser light is guided through an optical fiber to provide the energy for producing the acoustic vibrations. The optical energy is deposited in a liquid medium to generate an acoustic impulse. Thus, the laser energy is used to generate the acoustic shock wave in the solution. This effect is described further in the specification as laser light absorbed by the fluid surrounding the catheter. Unlike laser angioplasty, the present invention does not rely on direct ablation of the occlusion, but instead uses a high frequency train of low energy laser pulses to generate ultrasonic excitations in the fluids in close proximity to the occlusion. By pulsing the laser at a repetition rate (which may vary from 10 Hz to 100 kHz) an ultrasonic radiation field is established locally in the medium. Thus, Celliers et al. teaches the use of an ultrasonic wave to dislodge the occlusion tearing it into fragments or pieces.

[0014] This fragmentation is one of the drawbacks in this method, as described above, as is amply shown in US patent 5,709,676 to Alt. Alt describes a two-step procedure. According to the specification, a method is provided for removing deposits of thrombus or plaque from the wall of a blood vessel of a patient by action of two individual procedures, after introduction of a catheter into a blood vessel from which such a deposit is to be removed. The first procedure is to deliver laser energy of predetermined wavelength range through an optical fiber in the catheter. The predetermined wavelength range is selected to generate a plasma-based ultrasonic shock wave in the vessel for application to the deposit to create, fissures, or cracks in the deposit. The second procedure is to deliver a preselected deposit-dissolving medication into the blood stream in the vicinity of the deposit through a channel or lumen in the catheter promptly after completion of the first procedure. The deposit-dissolving medication penetrates into openings created in the deposit by the shock wave to begin to break it up or dissolve it. Thereafter, the first and second procedures are repeated in the same sequence at least once, and preferably several times, to ultimately fragment the deposit so that the fragments may be removed through the channel in the catheter.

[0015] Thus, Alt describes how these fragments may be dissolved to keep them from becoming embolisms. Both, Alt and Celliers et al. disclose methods which produce macro sized fragments, which must be dissolved and eventually removed. Neither patent mentions post-procedure clotting from tissue damage.

[0016] It would therefore be advantageous to provide a method for laser treatment of occlusions of various types, including thrombus, which would reduce the biological obstruction to more or less cell sized debris, which could be absorbed by the body without lodging in the smaller capillaries, while treating surrounding tissue to retard, diminish or even prevent platelets aggregation.

SUMMARY OF THE INVENTION

[0017] Vascular occlusions can be treated with pulses of laser light which generate pressure spikes within the occlusion while minimizing the occurrence of post treatment embolism and retarding, diminishing or preventing the formation of post treatment retenosis. The medium within the working canal of the vessel, in contact with the occlusion is substantially transparent to the wavelength of the laser light used such that a substantial portion of the laser energy is absorbed by the occlusion. [0018] Pulsed laser light is transmitted through a catheter encased fiberoptic, the distal end of which is placed in substantial contact with an occlusion in the presence of a liquid medium which is substantially transparent to the laser light, to emulsify the occlusion to cellular sized debris while treating platelets disposed upon surrounding tissue to retard, minimize or prevent formation of thrombus. By pulsing the laser, a pulsed radiation field can be established locally within the occlusion to generate a rapid positive pressure spike through an aqueous, liquid to vapor, phase transition, and a subsequent rapid negative pressure spike through a vapor to liquid aqueous phase transition to reduce the biologic material to a cellular size debris. In addition, if an ultraviolet laser is used, the ultraviolet light breaks the occlusive tissue into subcellular debris by directly breaking the molecules of the tissue when those molecules absorb ultraviolet photons. This is the photo-ablative effect unique to ultraviolet laser angioplasty. By steady, slow movement of the distal end of the catheter, so that it remains in substantial contact with the remaining biologic material to be removed, a repetitive series of laser energy pulses emulsifies the entirety of the biologic matter forming the occlusion while treating the surrounding tissue to retard, inhibit or prevent platelet aggregation. Preferably an excimer laser system is used. This method can be used in vivo for the treatment of for example thrombolytic vascular conditions and to remove and retard recurrence of such conditions. [0019] In accordance with the inventive method, laser energy transmission is provided through a catheter encased fiberoptic to the distal end which is in substantial contact with a vascular occlusion, in the presence of a medium which is substantially transparent to the laser energy, to provide ablation of the occlusion to cellular sized debris with concurrent treatment to surrounding tissue to inhibit retard, minimize or even prevent platelet aggregation thus minimizing thrombosis. Dissolution of the occlusion is promoted by pulsed, laser energy produced, pressure spikes, which emulsify the occlusion. [0020] In one embodiment, a method for ablating a vascular obstruction comprises inserting a fiber optic into the vasculature to a point in substantial contact with an occlusion in the presence of a medium that is substantially transparent to the wavelength of the laser light, and delivering an amount of pulsed laser energy, through the fiber optic, to emulsify the occlusion to a non embolism sized debris while concurrently retarding, minimizing inhibiting or even preventing platelet aggregation on surrounding vascular tissue to minimize the occurrence of thrombus. Preferably, the laser light has (i) a pulse frequency within the range of 10 Hz to 200 Hz, (ii) a wavelength within the range of 200 nm to 2500 nm and (iii) an energy density within the range of 10 mJ/mm² to 100 mJ/mm².

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIG. 1 shows a longitudinal cross sectional view of an application of the optical fiber-based catheter used in an artery in accordance with the present invention. [0022] FIG. 2 shows a longitudinal cross sectional view of an application of the optical fiber-based catheter used in a vein in accordance with the present invention. [0023] FIG. 3 depicts an annular fiber arrangement of the distal tip of optical fiber- based catheter used in accordance with the present invention. [0024] FIG. 4 depicts a segmented fiber arrangement of the distal tip of the optical fiber-based catheter used in accordance with the present invention.

[0025] FIG. 5A shows the positioning of the distal tip of the catheter encased fiber optic in relation to the lesion to be treated by the method of the instant invention.

[0026] FIG. 5B shows the positioning of the distal tip of the catheter encased fiber optic in relation to the lesion during treatment by the method of the instant invention.

[0027] FIG. 5C shows the positioning of the distal tip of the catheter encased fiber optic in relation to the ablated lesion at the termination of treatment by the method of the instant invention.

[0028] FIG. 6 shows a graphic depiction of the positive and negative pressure spikes associated with the ablation of an occlusion in accordance with the process of the instant invention.

[0029] FIG. 7 shows a cross section of a vascular member treated in accordance with the process of the instant invention showing ablated material and the treated platelets.

[0030] FIG. 8 shows the distal tip of a fiber optic having non-parallel fibers.

DETAILED DESCRIPTION OF THE INVENTION

[0031] Preferably, the procedure used in accordance with the invention is similar to conventional balloon angioplasty. As will be detailed below, the vascular lesion, blockage or occlusion is crossed with a flexible guide wire. The laser catheter, which contains a central guide wire lumen, is introduced through a guide catheter, which allows introduction of solutions (medium) to the vessel being treated. The distal tip of the fiber catheter is placed in substantial contact with the proximal end of the occlusion to be removed. It will be guided through the process along the guide wire. A medium (solution), which is substantially transparent to the wavelength of the laser light, is introduced into the blood vessel so that the energy will pass through the medium and penetrate the occlusion to be removed. The laser is activated to perform precise, controlled occlusion removal (ablation) by sending bursts of ultraviolet laser light through the catheter and against the occlusion. The catheter is then slowly advanced through the blockage along the guide wire reopening the vessel while medium is delivered to the vessel-working channel. When the indicated occlusions are cleared, the catheter is withdrawn. [0032] A preferred system for the vascular ablation of a thrombus comprises a XeCl excimer laser delivering pulses of light at 308 nm, with a pulse width of at least 100 ns and a pulse repetition rate of between about 25 and 100 Hertz. The light from the laser is launched into pure synthetic silica fibers contained in an intravascular catheter. At the distal end of the catheter, the fluence is preferably in the range of from about 30 to 45 mJ/mm of fiber surface area.

[0033] In operation, the distal tip of the fiber catheter is advanced to the proximal end of the thrombus mass. In the presence of a catheter delivered gentle saline flush, the distal tip is advanced at a rate of from about 0.25 to about 0.75 mm per second while the laser is pulsing. The process is repeated until the distal catheter tip reaches the distal edge of the lesion being treated.

[0034] The pressure spike of the instant invention comprises an energy induced, expansion of the material of the occlusion to produce a rapid, positive pressure spike and subsequent rapid energy diffusion to surrounding tissue to produce a negative pressure spike. The presence of a medium transparent to the wavelength of the laser light allows substantial energy to impinge on the occlusion to cause emulsification and/or liquefaction of the occlusion resulting in harmless cell sized debris which is flushed from the site and reabsorbed by the body. The distal tip of the catheter progresses through the occlusion with each set of pulses to remove the blockage and, simultaneously, treating the surrounding vascular area to retard or prevent platelet aggregation. [0035] In FIG. 1 there is shown the laser angioplasty configuration according to the invention for an artery. A blood vessel 10 with vascular wall 12, a blocking thrombus lesion 14, and a stenotic plaque deposit 16 comprise the vessel to be treated. A laser 20 provides laser light into optical fiber 22, located within a laser catheter 24, which has been inserted into the blood vessel 10 through guide catheter 26. The exterior diameter of the laser catheter 24 is smaller than the interior diameter of guide catheter 26 to provide an irrigation lumen 28 through which solutions and medicaments can be introduced into vessel working channel 18. A retrograde flushing passage 32 is formed between the exterior of the guide catheter 26 and the vascular wall 12 to provide for exit of occlusion debris irrigated from the vessel-working channel 18. A guide wire 30 extends through laser catheter 24 in a centered guide wire lumen (not shown). The thrombus 14 is crossed with guide wire 30. The distal end of fiber 22 is placed in substantial contact with the proximal end of thrombus 14 within blood vessel 10. A solution or medium, which is substantially transparent to the laser light, so that the energy will pass through the medium and impinge on the thrombus 14, is introduced into the vessel-working channel 18 through irrigation lumen 28.

[0036] In operation, the guiding catheter 26 is introduced (left or right depending on the target coronary artery) using a standard flexible guide wire 30. The flexible guide wire 30 is then inserted across the thrombus 14. The position of the guide wire 30 is monitored within the vessel 10 under fluoroscopy. The guide wire 30 is inserted into the centered lumen in the laser catheter 24 by introducing the proximal end of the guide wire 30 into the distal tip of the laser catheter 24, and the laser catheter 24 is carefully advanced in small increments, to avoid kinking the guide wire 30. The guide wire 30 is maintained in its position in the patient's circulatory system while advancing the laser catheter 24. The laser catheter 24 is inserted into the guide catheter 26 and advanced to the guide catheter's 26 distal tip while maintaining the guide wire 30 position. The guide catheter's 26 position in the ostium of the vessel 10 is reconfirmed with contrast media injection and fluoroscopy prior to advancing the laser catheter 24 to the thrombus 14. The laser catheter 24 is advanced to the thrombus 14 while maintaining the guide wire's 30 position in the patient's circulatory system. Contrast medium solution is then injected through the irrigation lumen 28 to verify the positioning of the laser catheter 24 under fluoroscopy. Following confirmation of the laser catheter's 24 position in substantial contact with thrombus 14, all residual contrast media is flushed from the irrigation lumen 28 and arterial working channel 18 including the lasing site and vascular structures adjacent to the lasing site. A solution, which is transparent to the laser light wavelength, such as physiologic saline solution or lactated Ringer's solution, is then infused into the arterial working channel 18 including the lasing site and vascular structures adjacent to the lasing site through the irrigation lumen 28. The laser 20 is activated and the laser catheter 24 slowly advanced allowing the laser energy to remove the desired material. The lasing site is continually irrigated with solution through irrigation lumen 28, which flushes debris from the working channel 18, and exits through retrograde flushing passage 32. The laser catheter 24 is advanced at a rate commensurate with the laser energy and pulse repetition rate being used per pass. A rate of approximately 0.5 mm to approximately 1 mm per five-second lasing train at 25 pulses per second is exemplary. An advancement rate that is too rapid will fail to emulsify the thrombus completely and cause larger debris.

[0037] Turning to FIG. 2 there is shown the laser angioplasty configuration according to the invention for a vein. A vein 110 with vascular wall 112, an elongated blocking thrombus lesion 114, comprise the vessel to be treated. As shown in FIG. 1, a laser 20 provides laser light into optical fiber 22, located within the laser catheter 24 (shown in FIG. 2), which has been inserted into the blood vessel 110 through guide catheter 26. The exterior diameter of the laser catheter 24 is smaller than the interior diameter of guide catheter 26 to provide an irrigation lumen 28 through which solutions and medicaments can be introduced into vessel working channel 118. A guide wire 30 extends through laser catheter 24 in a centered guide wire lumen (not shown). The thrombus 114 is crossed with guide wire 30. The distal end of fiber 22 contained in laser catheter 24 is placed in substantial contact with the proximal end of thrombus 114 within vein 110. A solution, which is substantially transparent to the laser light so that the energy will pass through the medium and impinge on the thrombus 114, is introduced into the vessel-working channel 118 through an irrigation lumen 28. In this figure it is seen that distal end of fiber 22 contained in laser catheter 24 is slightly convex as is the thrombus 114. This configuration creates lased areas 134 filled with medium. Because the medium is substantially transparent to the laser light substantially all the energy will pass through the medium in areas and impinge on the thrombus 114, thus, the medium will not heat appreciably ahead of the thrombus 114. The operation in this procedure is substantially the same as for FIG. 1.

[0038] In FIG. 3 and FIG. 4 there is shown the distal tip of the laser catheter 124 with guide wire lumen 125 and having two fiber 122 configurations. In FIG. 3 the fibers 122 are arranged annularly. While the fibers 122 still exit the distal end of laser catheter 124 perpendicular to the long axis of laser catheter 124, so that the light is emitted straight out the end, the fibers 122 can be fired as individual rings. This can be accomplished one ring at a time or in gang. In FIG. 4 the fibers 122 are arranged in pie shaped segments. While the fibers 122 still exit the distal end of laser catheter 124, perpendicular (so the light is emitted straight out the end) to the long axis of laser catheter 124, they can be fired as individual segments. This can be accomplished one segment at a time or in gang. The concept is to give the operator greater flexibility in delivering energy to the occlusion. By firing alternative panels in FIG. 4, half the energy per pulse can be delivered. Likewise, the configuration shown in FIG. 3 can be fired in, for example, alternate rings to provide half the energy per pulse.

[0039] Turning to FIG. 5 A, FIG. 5B, and FIG. 5C there is shown the process of the ablation of the occlusion in detail. Specifically, FIG. 5A shows the positioning of the distal end of fiber 222 contained in laser catheter 224 in relation to the thrombus 214 prior to commencing treatment, FIG. 5B shows the positioning of the distal end of fiber 222 contained in laser catheter 224 in relation to the thrombus 214 during treatment, and FIG. 5C shows the positioning of the distal end of fiber 222 contained in laser catheter 224 in relation to the ablated thrombus 214 at the termination of treatment. [0040] In FIG. 5 A, the distal tip of fiber 222 on guide wire 230, which crosses thrombus 214, is positioned in work area 218 through guide catheter 226. The exterior diameter of the laser catheter 224 is smaller than the interior diameter of the guide catheter 226 to provide an irrigation lumen 228, through which solution and medicaments are introduced into vessel working channel 218 in preparation for commencing ablation of the thrombus. The distal tip of fiber 222 is in substantial contact with thrombus 214. [0041] As shown in FIG. 5B, as the procedure progresses, lased light emits from the distal end of fiber 222 to ablate a section 215 directly in front of the laser catheter 224. The section 215 has a depth of about 50 to 100 microns, which is the extent of the penetration of the laser light into the thrombus 214. During this pulse, the material in 215 is homogenized or emulsified and sub cellular (non-embolism producing) debris is carried through vessel working channel 218, exiting through retrograde flushing passage 232. Platelets 234, shown on either surface of the previously ablated thrombus material 214 are treated or stunned so that they form a layer of inactivated platelets on the surface of the lased thrombus 214. As the laser catheter 224 progresses through the previously cleared area, a new pulse is activated and a similar 50 to 100 micron section 215 is emulsified and similarly flushed leaving behind inactivated platelets on the recanilized inner vascular surfaces. Thus, the distal tip of the fiber 222 is in substantially continuous contact with the thrombus 214. As seen in FIG. 5C, as the procedure is completed, the remaining thrombus material 214 is completely covered with inactivated platelets 234, and all cellular sized debris is removed for re-absorption by the body and blood flow restored. [0042] In FIG. 6 there is shown a pictorial graph of the pressure spikes created in accordance with the inventive method. This figure is meant as a graphic, simplified picture of the pressure spikes during the inventive procedure. The following theory is presented for elucidation and is not meant to be limiting. It is theorized that there are two thermal effects during laser angioplasty. The first is associated with a photoacoustic phenomenon. If the high heat of the fiber tip is not controlled, a sudden, drastic rise in temperature in the medium layer in contact with the fiber tip creates a sudden high pressure, creating a pressure wave that radiates away from the fiber tip in all directions. This photoacoustic effect, noticed by researchers in Holland, Germany, and elsewhere, and described in Alt and Celliers et al., creates an audible sound. When blood or other radiation absorbing media are present in front of the lesion, the effect is severe. If the intensity of this ^■ photoacoustic pressure wave is sufficiently great, tissue several millimeters away from the fiber tip is disrupted, even though the light from the fiber may never reach that tissue. Tissue damage associated with this traumatic pressure wave is thought to be associated with some of the deleterious side effects of excimer laser angioplasty including embolisms. This damage to surrounding tissue is also thought to trigger platelet agglomeration and thus clotting. Thus it is important to control the temperature from the fiber tip. [0043] The second photothermal effect caused by laser light heating the thin tissue layer of the occlusion at the fiber tip involves intracellular water. When the fiber tip is abutted proximate the occlusion and the media surrounding the work site is substantially transparent to the laser light, the energy is absorbed by the tissue and the water in the tissue undergoes a very rapid phase transition from liquid to steam. The result is a controlled intercellular rupture, leaving behind subcellular debris, which can be flushed from the site and absorbed by the body. Thus, the likelihood of macro debris, which can cause an embolism, is dramatically reduced and the need for the procedure of Alt is obviated or at least minimized.

[0044] As the process proceeds the steam from many cells forms a macroscopic bubble that has been expertly photographed by several researchers. This bubble then very quickly collapses, as a second phase transition of steam to water occurs when the steam gives up heat to surrounding tissue and media. The onset of the steam bubble occurs several microseconds after the laser pulse; the bubble grows in size for approximately 100 microseconds, and then collapses. By about 250 microseconds after the laser pulse, the bubble has imploded and disappeared, and in so doing, radiates another negative pressure wave from the vicinity of the catheter tip. This pressure spike and subsequent implosion are simplified and pictorially displayed in FIG. 6, which is not to scale. [0045] FIG. 7 shows a treated vessel 312 with inactivated platelets 334 covering substantially all the treated vascular tissue including ablated plaque as well as ablated thrombus. Thus, unexpectedly, when this process is carried out under certain conditions as herein described, relating to wave lengths, repetitiveness, and energy intensity, the platelets and the blood cells surrounding the work site are deactivated and, therefore, there ability to aggregate is retarded or even prevented. This is especially dramatic when the media, in front the fiber tip, is substantially transparent to the laser wavelength. Thus for example, if an XeCl excimer laser is used (308 nm), blood present between the fiber tip and the tissue to be ablated is not preferred because the red blood cells tend to absorb light at that wave length causing an acoustic shock wave.

[0046] Thus one skilled in the art, in accordance with the present invention, can readily determine the parameters for a particular laser to effect ablation of the occlusion as well as the retarding effect to the platelets. The energy delivered to the tissue to be ablated is that amount effective to cause photo ablative expansion and contraction while stunning platelets to retard their aggregation tendencies.

[0047] Apparently, when the transient steam bubble is formed by the phase transition to effect the positive pressure spike, successful ablation of tissue with the 308 nm excimer system occurs. It has been shown that no tissue removal occurs when no steam bubble is formed. This tends to verify the theory that the tissue is homogenized or emulsified by exploding the cells from the inside out. Further lasing platelets in the vicinity of the catheter tip while leaving them in place to passivate the lesion or artery wall is accomplished with laser energies sufficiently high to create the transient phase transition with each laser pulse. Fluences below this range will not produce the desired pressure spike. Fluence above this level can also be used, but probably with only marginally greater effect or with a somewhat larger radius of action. The preferred range of fluence is between 30 and 80 mJ/mm²

[0048] In FIG. 8, there is shown another distal tip of laser catheter 324 having an array of fibers 322 that do not exit the distal end of laser catheter 324 perpendicular to the long end axis of the laser catheter 324. A concentric guide wire lumen carries guide wire 330 through the center of laser catheter 324. In accordance with this embodiment, the laser light is irradiated at various angles from the centerline of laser catheter 324 to provide laser energy to an occlusion other than in a perpendicular line. In this manner, laser light can be irradiated to provide ablative effects in accordance with the invention to the tops or bottom surfaces of occlusions as the laser catheter 324 passes through the occlusion in a manner as shown in FIG. 5 A, FIG. 5B, and FIG. 5C.

[0049] Catheters, useful in practicing the present invention, can be of various types. For example, one embodiment can consist of a catheter having an outer diameter of 3.5 millimeters or less, preferably 2.5 millimeters or less. Disposed within the catheter is the optical fiber which can be a 50 to 400 micron diameter or smaller silica (fused quartz) fiber such as the model SG 800 fiber manufactured by Spectran, Inc. of Sturbridge, Mass. The catheter may be multi-lumen to provide flushing and suction ports. In one embodiment the catheter tip can be constructed of radio-opaque and heat resistant material. The radio- opaque tip can be used to locate the catheter under fluoroscopy. [0050] The invention can be used with various catheter devices, including devices which operate under fluoroscopic guidance as well as devices which incorporate imaging systems, such as echographic or photoacoustic imaging systems or optical viewing systems.

[0051] The laser catheters that are preferably used in accordance with the inventive method consist of optical fibers encased within a polyester shaft. There are two major portions of the laser catheter shaft, the proximal portion, which terminates at the laser connector, and the distal portion, which terminates at the tip having direct patient contact. The fibers terminate at the distal tip within a polished adhesive end and at the proximal end within the laser connector. A radiopaque marker is located on the distal end of the laser catheter to aid localization within the coronary vasculature in conjunction with fluoroscopy. The guidewire lumen begins at the distal tip and is concentric with the fiber array, and exits the laser catheter about 9 cm away from the distal tip, which has direct patient contact. A proximal marker may be located on the outer jacket of the laser catheter, 104 cm from the distal tip, to assist in the placement of the laser catheter within a femoral guiding catheter without the need for fluoroscopy.

[0052] Multifiber laser catheters transmit energy from the laser to the obstruction in the artery. The ultraviolet energy is delivered to the tip of the catheter to photo-ablate fibrous, calcific, and atheromatous lesions, thus recanalizing diseased vessels. Preferably, the laser catheters may have a proprietary lubricious coating to ease their trackability through coronary vessels.

[0053] Preferably Lesions treatable in accordance with the instant invention are traversable by a guidewire and composed of atherosclerotic plaque and/or calcified material. In accordance with a preferred embodiment. The lesions should be definable by angiography. According to a preferred aspect, the process of this invention accomplishes lysis of thrombus, atherosclerotic plaque or any other occluding material in the tubular tissue.

[0054] As an adjunct treatment, a working channel which surrounds or runs parallel to the optical fiber may be used to dispense small quantities of thrombolytic drugs to facilitate further lysis of any significantly sized debris (>5 micrometer diameter particles) left over from the instant process.

[0055] Applications envisioned for this invention include any method or procedure whereby localized ablations are to be produced in the body's tissues through laser energy. The invention can be used in (i) endovascular treatment of vascular occlusions that lead to ischemic stroke, (ii) endovascular treatment of cerebral vasospasm, (iii) endovascular treatment of cardiovascular occlusions (iv) endovascular treatment of stenoses of the carotid arteries, (v) endovascular treatment of stenoses of peripheral arteries, (vi) general restoration of patency in any of the body's luminal passageways wherein access can be facilitated via percutaneous insertion, and (vii) lithotriptic applications including therapeutic removal of gallstones, kidney stones or other calcified objects in the body. [0056] The pulsed laser energy source used by this invention can be based on a gaseous, liquid or solid state medium. Rare earth-doped solid state lasers, ruby lasers, alexandrite lasers, Nd: YAG lasers and Ho:YLF lasers are all examples of lasers that can be operated in a pulsed mode at high repetition rate and used in the present invention. Any of these solid state lasers may incorporate non-linear frequency-doubling or frequency- tripling crystals to produce harmonics of the fundamental lasing wavelength. A solid state laser producing a coherent beam of ultraviolet radiation may be employed directly with the invention or used in conjunction with a dye laser to produce an output beam which is tunable over a wide portion of the ultraviolet and visible spectrum. [0057] Tunability over a wide spectrum provides a broad range of flexibility for matching the laser wavelength to the absorption characteristics of the tissue located at the distal end of the catheter. The output beam is coupled by an optical fiber to the surgical site through, for example, a percutaneous catheter. In operation, a pulsed beam of light removes and/or emulsifies thrombus or atherosclerotic plaque with less damage to the underlying tissue and less chance of perforating the blood vessel wall than prior art devices.

[0058] Various other pulsed lasers can be substituted for the disclosed laser sources. Similarly, various dye materials and configurations can be used in the dye laser. Configurations other than a free-flowing dye, such as dye-impregnated plastic films or cuvette-encased dyes, can be substituted in the dye laser. The dye laser can also store a plurality of different dyes and substitute one for another automatically in response to user- initiated control signals or conditions encountered during use (e.g. when switching from a blood-filled field to a saline field or in response to calcific deposits). Suitable dyes for use in the dye laser components of the invention include, for example, P-terphenyl (peak wavelength 339); BiBuQ (peak wavelength: 385); DPS (peak wavelength: 405); and Coumarin 2 (peak wavelength: 448). In yet another embodiment, the pulsed light source may be an optical parametric oscillator (OPO) pumped by a frequency-doubled or frequency-tripled solid-state laser. OPO systems allow for a wide range of wavelength tunability in a compact system comprised entirely of solid state optical elements. The laser wavelength in OPO systems may also be varied automatically in response to user-initiated control signals or conditions encountered during use. ,

[0059] Another implication of the technique is that other forms of energy delivered to the treatment site may create identical effects. The energy must be delivered to a small volume of tissue, typically on the order of a cubic millimeter or less, in a very short period of time, typically less than a microsecond. The energy will be rapidly turned into heat in the tissue, regardless of the form of energy arriving at the tissue. Thus, different laser wavelengths could be used to deposit the required energy in the tissue, or pulsed incoherent light, or even pulsed electrical or radio frequency energy.

[0060] Our current explanation for dissolution of thrombus with excimer laser catheters invokes the transient pressure waves created by the laser light pulse. These pressure waves are sufficiently intense to fracture the brittle fibrin strands that comprise the structural elements of a fresh thrombus. When the fibrin strands are broken into pieces about the same size as the red blood cells, the resulting emulsified mass can freely flow downstream without clogging even the smallest arteries.

[0061] This technique may also be applicable to the liquefaction or modification of other brittle tissue structures, such as calcified lesions, cartilage, bones, calculi, biliary stones,, etc. In fact, laser lithotripsy practices a similar technique, by applying a large pulse of energy to the external surface of kidney stones. The resulting surface explosion and pressure wave are meant to fracture the stone into small pieces more easily passed through the urinary tract.

[0062] Changes and modifications in the specifically described embodiments can be carried out without departing from the scope of the invention, which is intended to be limited by the scope of the appended claims.

[0063] _ It should be understood that the above description is intended to be illustrative and not limiting. Many embodiments will be apparent to those of skill in the art upon reading the above description. Therefore, the scope of the invention should be determined, not with reference to the above description, but instead with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. The disclosures of all patents, articles and references, including patent applications and publications, if any, are incorporated herein by reference in their entirety and for all purposes.

Claims

WHAT IS CLAIMED IS:

1. A method of treating occlusions, the method comprising: pulsing laser light through a catheter encased fiber optic to provide energy for ablating an occlusion while substantially preventing the formation of certain platelet containing biological tissue, the catheter encased fiber optic having a distal end that is in substantial contact with the occlusion.

2. The method of claim 1 wherein the ablation of the occlusion is to non- embolism sized debris.

3. The method of claim 2 wherein the non-embolism sized debris is cellular sized debris.

4. The method of claim 2 wherein the non-embolism sized debris is sub- cellular sized debris.

5. The method of claim 1 wherein the ablation of the occlusion is in the presence of a medium that is substantially transparent to the wavelength of the laser light.

6. The method of claim 5 wherein the ablation of the occlusion is in the presence of a saline containing solution.

7. The method of claim 1 wherein the occlusion is a vascular occlusion.

8. The method of claim 1 wherein the catheter encased fiber optic is advancing.

9. The method of claim 8 wherein the catheter encased fiber optic is advancing at a rate of at least about 0.5 mm per five-second lasing burst and at most about 1 mm per five-second lasing burst.

10. The method of claim 1 wherein the formation of certain platelet containing biological tissue is substantially prevented by affecting the platelets ability to aggregate.

11. The method of claim 1 wherein the ablation of the occlusion is promoted by pulsed, pressure spikes corresponding to the pulsed laser light.

12. The method of claim 11 , wherein the pulsed, pressure spikes are produced by aqueous phase transition.

13. The method of claim 11 wherein the pressure spikes comprise at least one positive pressure spike and at least one negative pressure spike.

14. The method of claim 13 wherein the at least one positive pressure spike is produced by an aqueous phase transition from liquid to vapor.

15. The method of claim 13 wherein the at least one negative pressure spike is produced by an aqueous phase transitions from vapor to liquid.

16. The method of claim 1 wherein the laser light has (i) a pulse frequency within a range of about 10 Hz to about 200 Hz, (ii) a wavelength within a range of about 200 nm to about 2500 nm and (iii) an energy density within a range of about 10 mJ/mm² to about 100 mJ/mm².

17. The method of claim 16, wherein the pulse frequency range comprises from about 10 Hz to about 100 Hz.

18. The method of claim 16, wherein the laser light has a pulse duration of less than about 200 microseconds.

19. The method of claim 1 wherein the reduction of the occlusion is promoted through a set of positive and negative pressure spikes occurring over a time frame of about 250 microseconds.

20. The method of claim 1, wherein the occlusion is selected from a group consisting of atherosclerotic plaque and thrombus.

21. A method of treating a vascular obstruction, the method comprising: inserting a fiber optic into the vasculature to a point in substantial contact with the obstruction; and delivering an amount of pulsed laser energy through the fiber optic to reduce the obstruction to a non embolism sized debris while concurrently affecting platelet aggregation on surrounding vascular tissue.

22. The method of claim 21 further comprising advancing the fiber optic to stay in substantial contact with the obstruction.

23. The method of claim 22 wherein the fiber optic is advancing at a rate of at least about 0.5 mm per five-second lasing burst and at most about 1 mm per five-second lasing burst.

24. The method of claim 21 wherein the non-embolism sized debris is cellular sized debris.

25. The method of claim 21 wherein the non-embolism sized debris is sub- cellular sized debris.

26. The method of claim 21 wherein the ablation of the obstruction is in the presence of a medium that is substantially transparent to the wavelength of the laser light.

27. The method of claim 26 wherein the medium is a saline containing solution.

28. The method of claim 21 wherein the platelet aggregation on surrounding vascular tissue is affected by substantially preventing the platelets ability to aggregate.

29. The method of claim 21 wherein the ablation of the occlusion is promoted by pulsed pressure spikes corresponding to the pulsed laser light.

30. The method of claim 29 wherein the pulsed pressure spikes are produced by an aqueous phase transition.

31. The method of claim 29 wherein the pressure spikes comprise at least one positive pressure spike and at least one negative pressure spike.

32. The method of claim 31 wherein the at least one positive pressure spike is produced by an aqueous phase transition from liquid to vapor and the at least one negative pressure spike is produced by an aqueous phase transition from vapor to liquid.

33. The method of claim 21 wherein the laser light has (i) a pulse frequency within a range of about 10 Hz to about 200 Hz, (ii) a wavelength within a range of about 200 nm to about 2500 nm and (iii) an energy density within a range of about 10 mJ/mm to about 100 mJ/mm .

34. The method of claim 33 wherein the pulse frequency range comprises from about 10 Hz to about 100 Hz.

35. The method of claim 33 wherein the laser light has pulse duration of at most about 200 nanoseconds.

36. The method of claim 33 wherein the reduction of the obstruction is promoted through a set of positive and negative pressure spikes occurring over a time frame of about 250 microseconds.

37. The method of claim 21, wherein the obstruction is selected from a group consisting of atherosclerotic plaque and thrombus.

38. A method comprising: providing a source of laser light at a desired wavelength; inserting a fiber optic into vasculature to a point in substantial contact with an occlusion in the presence of a medium that is substantially transparent to the wavelength of the laser light, the fiber optic having a proximal end and a distal end; and delivering an amount of energy to the occlusion by coupling the laser light into the proximal end of the fiber optic so that the laser light emerges from the distal end of the fiber optic, wherein the amount of energy delivered to the occlusion is sufficient to effect reduction of the occlusion to cellular sized debris while affecting platelet aggregation on surrounding vascular tissue.

39. The method of claim 38 wherein affecting platelet aggregation corresponds to inhibiting, retarding, diminishing, minimizing or preventing platelet aggregation on surrounding tissue.

40. The method of claim 39 wherein the laser light has (i) a pulse frequency within a range of about 10 Hz to about 200 Hz, (ii) a wavelength within a range of about 200 nm to about 2500 nm and (iii) an energy density within a range of about 10 mJ/mm to about 100 mJ/mm².

41. The method of claim 40 where the pulse frequency range comprises from about 10 Hz to about 100 Hz.

42. The method of claim 40 wherein said laser light has pulse duration of less than about 200 nanoseconds.

43. The method of claim 40 wherein the reduction of the occlusion while simultaneously affecting platelet aggregation is promoted through a set of positive and negative pressure spikes occurring over a time frame of about 250 microseconds.

44. The method of claim 38 wherein the reduction of the occlusion while simultaneously affecting platelet aggregation is promoted by aqueous phase transition from liquid to vapor and from vapor to liquid.

45. The method of claim 38 wherein the occlusion is selected from a^group consisting of atherosclerotic plaque and thrombus.

46. The method of claim 38 wherein the medium is saline containing solution.

47. The method of claim 38 wherein the ablation of the occlusion is promoted by pulsed pressure spikes corresponding to the pulsed laser light.

48. The method of claim 38 further comprising advancing the fiber optic to stay in substantial contact with the occlusion.

49. The method of claim 48 wherein the fiber optic is advancing at a rate of at least about 0.5 mm per five-second lasing burst and at most about 1 mm per five-second lasing burst.

50. A method comprising: providing a fiber optic having a proximal end and a distal end; inserting a fiber optic into vasculature in the presence of biological saline solution so that the distal end of the fiber optic is in substantial contact with an occlusion; coupling laser light into the proximal end of the fiber optic, the laser light that emerges from the distal end of the fiber optic delivering an amount of energy to the occlusion that is sufficient to effect reduction of the occlusion to cellular sized debris while affecting platelet aggregation on surrounding vascular tissue, wherein affecting platelet aggregation corresponds to inhibiting, retarding, diminishing, minimizing or preventing platelet aggregation on surrounding tissue and wherein the reduction of the occlusion is promoted by pulsed pressure spikes comprised of a set of positive and negative pressure spikes occurring over a time frame of about 250 microseconds and resulting from the laser light having (i) a pulse frequency within a range of about 10 Hz to about 200 Hz, (ii) a wavelength within a range of about 200 nm to about 2500 nm, (iii) an energy density within a range of about 10 mJ/mm² to about 100 ml/mm², and (iv) a pulse duration of less than about 200 nanoseconds; and advancing the fiber optic at a rate of at least about 0.5 mm per five-second lasing burst and at most about 1 mm per five-second lasing burst so that the distal end of the fiber optic stays in substantial contact with the occlusion.

51. The method of claim 50, wherein the pulse frequency range comprises from about 10 Hz to about 100 Hz.

52. The method of claim 50 wherein the pressure spikes are promoted by a first aqueous phase transition from liquid to vapor and a second aqueous phase transition from vapor to liquid.

53. The method of claim 50, wherein the occlusion is selected from a group consisting of atherosclerotic plaque and thrombus.