Radially compatible catheter for perivascular fluid injection

Abstract

An intravascular catheter for perivascular and / or periurethral tissue ablation includes multiple needles advanced through a supported guide tube that expands about a central axis to engage the interior surface of the wall of the renal artery or other vessel of the human body, allowing for the injection of an ablation fluid to ablate tissue and / or nerve fibers in the outer layer or deep in the outer layer of the vessel or in prostate tissue. Applications include renal denervation for the treatment of hypertension, atrial fibrillation, congestive heart failure, tissue ablation for COPD, BPH, prostate cancer, prevention of restenosis after balloon angioplasty or stent implantation, and other diseases.

Description

[Technical field]

[0001] Some aspects of the present disclosure are applicable to the field of devices for advancing needle-like structures for injection of fluid into mass tissue outside the inner wall of a target vessel in the human body. Applications include renal denervation for the treatment of hypertension, atrial fibrillation, congestive heart failure, tissue ablation for COPD, BPH, prostate cancer, prevention of restenosis after balloon angioplasty or stent implantation, and other diseases. [Background technology]

[0002] It has been known since the 1930s that injury or ablation of sympathetic nerves at or near the outer layer of the renal artery (renal denervation) can dramatically reduce hypertension. Since 1952, alcohol has been used for renal denervation based on tissue ablation in animal experiments. Specifically, Robert M. Beme in Non-Patent Document 1 describes painting alcohol to the outside of the renal artery in dogs to produce denervation.

[0003] Due to similarities in anatomy, for purposes of this disclosure, the term target vessel will refer herein to the renal artery for hypertension or congestive heart failure (CHF) applications, the urethra for BPH and prostate applications, and the bronchus of the lung for COPD applications.

[0004] Recent technologies for renal denervation include energy delivery devices that use radio frequency or ultrasound energy, such as Medtronic's Simplicity® RF ablation catheter, Recor's ultrasound ablation-based system, and Ablative Solutions' Peregrine® chemodenervation catheter.

[0005] There are some limitations to the Simplicity™ system for RF energy delivery, as it does not allow for efficient circumferential ablation of renal sympathetic nerve fibers. If circumferential RF energy is applied from the inside of the renal artery at the annular section (energy applied at the intimal surface to kill nerves in the outer adventitial layer), this may result in even higher risk of renal artery stenosis due to circumferential and transmural thermal damage to the intima, media, and adventitia. Finally, the "burning" of the inner wall of the renal artery with RF ablation can be extremely painful. Long-term RF ablation renal denervation procedures require sedation, sometimes requiring very large doses of morphine or other sedatives, and anesthesia close to general anesthesia to control the intense pain associated with repeated burning of the vessel wall. Thus, there are numerous and substantial limitations of the current approach using RF-based renal sympathetic denervation. Similar limitations apply to ultrasound or other energy delivery techniques.

[0006] The Bullfrog® microinjection catheter described by Seward et al. in U.S. Patent Nos. 5,399,623 and 5,433,366, which uses an inflatable elastic balloon to expand a single needle against the vessel wall, can be used for injection of chemical ablative solutions such as alcohol, but these patents do not describe or allow for circumferential delivery of the ablative agent around the entire circumference of the vessel, thus requiring multiple applications. The maximum number of needles shown by Seward is two, and the Bullfrog® two-needle version is difficult to miniaturize to fit through the small guide catheters used in the renal arteries. If only one needle is used, controlled and precise rotation of the device at the end of the catheter is difficult at best and can be dangerous if subsequent injections are not evenly spaced. This device does not allow for precise controlled and adjustable depth of delivery of the neuroablative agent. This device may also have physical constraints on the length of the needle that can be used, thus limiting the ability to inject the agent to the appropriate depth, particularly in diseased renal arteries with thickened intima. Another limitation of Bullfrog® is that balloon inflation in the renal artery may induce slow vascular stenosis due to balloon injury of the intima and media of the artery as well as cause denudation of endothelial cells.

[0007] In US Patent No. 5,399,363, Jacobson and Davis describe a catheter for injecting drugs into the inner wall of a blood vessel. Jacobson includes the concept of multiple outwardly expanding needles, each with a shank to limit needle penetration into the vessel wall, but Jacobson's design relies on the rotation of a tube with a needle at its distal end to cause the needle to curve outward. The illustrated shank design of a small disk attached a short distance proximal to the needle distal end has a fixed diameter that would increase the overall diameter of the device by at least twice the diameter of the shank, so that if the shank were large enough in diameter to stop needle penetration, it would add significantly to the diameter of the device. Using a shank with a larger diameter than the tube would increase the profile of the device and would also prevent the needle from being fully retracted back inside the tubular shaft from which it emerges, leaving the needle exposed and potentially causing an accidental needlestick injury. For either renal denervation or atrial fibrillation applications, the length of the catheter required makes such rotation difficult to control. Also, the stalk, which limits penetration, is a fixed distance from the distal end of the needle. There is no built-in adjustment for penetration depth, which may be important when trying to selectively target a particular layer in a vessel or when needing to penetrate all the way to the mass beyond the adventitia in vessels with different wall thicknesses. Jacobson does not envision the use of an infusion catheter for denervation. Finally, FIG. 3 of the Jacobson patent shows a sheath over an expandable needle without a guidewire, the sheath having an open distal end that makes advancement through the vascular system more difficult. Also, because of the stalk, the needle may get caught inside the sheath if it is fully retracted inside the sheath, making it difficult to push out.

[0008] As early as 1980, alcohol was shown to be effective in providing renal denervation in animal models such as those published by Kline et al. in Non-Patent Document 2. Kline states that "95% alcohol was applied to the vessel to destroy remaining nerve fibers. Using this technique for renal denervation, we found that it dramatically reduced renal norepinephrine concentrations by more than 50% (i.e., less than 10 mg / g tissue) two weeks after surgery." Again in 1983, Kline again published in Non-Patent Document 3 that a 95% alcohol solution applied during surgery was effective in ablating the nerves surrounding the renal artery in rats. Drug delivery catheters such as those described by Jacobson, designed to inject fluid into the arterial wall at multiple locations, have been around since the 1990s.

[0009] McGuckin in US Pat. No. 5,399,633 describes a tumor tissue ablation catheter with three expandable tines for injection of fluids exiting a single needle. The tines expand outward to penetrate tissue. McGuckin's device has an open distal end that offers no protection from inadvertent needle sticks by the sharp tines. McGuckin's device also relies on the sharp tines to be of sufficient strength to allow them to expand outward and penetrate tissue. To achieve such strength, the tines must be large in diameter, so severe extravascular bleeding can occur when the tines are retracted following fluid injection for renal denervation applications. There is no viable penetration limiting mechanism that reliably sets the depth of penetration of the distal opening from the tines against the inner wall of the vessel, nor is there any preset adjustment for such depth. For applications to treat liver tumors, a continuously adjustable depth of tine penetration may be reasonable, as multiple injections at several depths may be required. However, for renal denervation, the ability to precisely set the penetration depth so as not to inject the ablation fluid too shallowly and damage the media of the renal artery, or too deeply and miss the adventitia layer of the renal artery and the nerves surrounding the adventitia layer.

[0010] Although alcohol has historically been shown to be effective as a therapeutic agent for renal denervation and is FDA-approved for use in nerve ablation, there is a need for an intravascular injection system specifically designed for perivascular circumferential ablation of sympathetic nerve fibers with sufficient penetration depth in the outer layer around the renal artery to accommodate variations in vessel wall thickness and to accommodate the fact that many renal artery nerves are located some distance outside the adventitia of the artery.

[0011] No. 6,393,436 issued on June 16, 2015; U.S. Pat. No. 6,493,633 issued on November 10, 2015; U.S. Pat. No. 6,493,633 issued on February 9, 2016; U.S. Pat. No. 6,493,4 ... April 26, 2016; U.S. Pat. No. 6,593,533 issued on December 27, 2016; U.S. Pat. No. 6,593,633 issued on January 10, 2017; U.S. Pat. No. 6,593,433 issued on June 3, 2014; U.S. Pat. No. 6,593,633 issued on October 2, 2017, which are hereby incorporated by reference in their entireties. In U.S. Patent No. 5,393,636 issued on May 4, 2018, U.S. Patent No. 5,393,636 issued on November 6, 2018, U.S. Patent No. 5,393,636 issued on March 12, 2019, U.S. Patent No. 5,393,636 issued on July 16, 2019, U.S. Patent No. 5,393,636 issued on September 10, 2019, U.S. Patent No. 5,393,636 issued on November 26, 2019, and U.S. Patent No. 5,393,636 issued on March 3, 2020, Fischell et al. show several embodiments of a fluid delivery catheter for injection of fluid into the perivascular space of a vasculature of the human body. The mechanisms shown by Fischell et al. in U.S. Patent No. 6,399,433, issued on April 3, 2018, ... September 24, 2019, and U.S. Patent No. 6,399,433, issued on December 31, 2011, which are hereby incorporated by reference in their entireties, are used to advance electrodes with or without fluid injection capability into the inner wall of a target vessel and beyond for neural sensing, electrical stimulation, and energy-based tissue ablation.

[0012] Together, these two groups of patents form the "Fischell Patents" for reference throughout this specification and are hereby incorporated by reference in their entirety. In some embodiments described therein, the Fischell Patents use a needle guide element in the form of a guide tube to aid in the advancement and penetration of a needle / wire with a sharp distal end through the inner wall of a target vessel. Such a structure may be important to allow the use of small diameter needles / wires that do not cause blood loss when retracted following use in a blood vessel.

[0013] Throughout this specification, the terms ablation fluid, ablation solution, and / or ablation material are used interchangeably to include liquid or gaseous substances delivered to a tissue mass in the human body with the intent to damage, kill, or ablate nerves or tissue within the tissue mass.

[0014] Also, throughout this specification, the term inner wall or interior surface as applied to blood vessel, vessel wall, artery, or arterial wall means the inside surface of the vessel wall, the same inside being the vessel lumen. Also, the term infusion outlet is defined as the distal opening in the needle through which the infused fluid exits. With respect to the infusion needle, either infusion outlet or distal opening may be used interchangeably herein.

[0015] The term "deep" of a structure is defined as beyond the structure or outside the structure, such as "deep in the adventitia" referring to the mass of tissue outside the adventitia of an artery.

[0016] The term perivascular refers to the mass of tissue outside the inner wall of the target vessel. For arteries, this includes the tunica media, external elastic lamina, tunica adventitia, and periaventitial tissue. [Prior art documents] [Patent documents]

[0017] [Patent Document 1] U.S. Patent No. 6,547,803 [Patent Document 2] U.S. Pat. No. 7,666,163 [Patent Document 3] U.S. Patent No. 6,302,870 [Patent Document 4] U.S. Patent No. 7,087,040 [Patent Document 5] U.S. Patent No. 9,056,185 [Patent Document 6] U.S. Pat. No. 9,179,962 [Patent Document 7] U.S. Patent No. 9,254,360 [Patent Document 8] U.S. Patent No. 9,301,795 [Patent Document 9] U.S. Patent No. 9,320,850 [Patent Document 10] U.S. Pat. No. 9,526,827 [Patent Document 11] U.S. Pat. No. 9,539,047 [Patent Document 12] U.S. Pat. No. 9,554,849 [Patent Document 13] U.S. Pat. No. 9,795,441 [Patent Document 14] U.S. Patent No. 10,118,004 [Patent Document 15] U.S. Pat. No. 10,226,278 [Patent Document 16] U.S. Pat. No. 10,350,392 [Patent Document 17] U.S. Pat. No. 10,405,912 [Patent Document 18] U.S. Pat. No. 10,485,951 [Patent Document 19] U.S. Pat. No. 10,576,246 [Patent Document 20] U.S. Pat. No. 9,931,046 [Patent Document 21] U.S. Pat. No. 9,949,652 [Patent Document 22] U.S. Patent No. 10,022,059 [Patent Document 23] U.S. Patent No. 10,420,481 [Patent Document 24] U.S. Pat. No. 10,517,666 [Non-patent literature]

[0018] [Non-Patent Document 1] "Hemodynamics and Sodium Excretion of Denervated Kidney in Anesthetized and Unanesthetized Dog" Am J Physiol, October 1952 171 :(1) 148~158 [Non-Patent Document 2] "Functional re-interiorvation and development of supersensitivity to NE after renal denervation in rats", American Physiological Society 1980:0363-6110 / 80 / 0000-0000801.25, pp. R353-R358 [Non-Patent Document 3] “Effect of renal denervation on arterial pressure in rats with aortic nerve transaction” Hypertension, 1983, 5:468~475 Summary of the Invention [Means for solving the problem]

[0019] The use of guide tubes as needle guiding elements for catheters such as the Peri-vascular Tissue Ablation Catheter (PTAC) of U.S. Patent No. 6,233,636 has been disclosed in the "Fischell Patents," including U.S. Patent No. 6,233,636 issued on June 16, 2015, U.S. Patent No. 6,233,636 issued on November 10, 2015, U.S. Patent No. 6,233,636 issued on February 9, 2016, U.S. Patent No. 6,233,636 issued on April 5, 2016, U.S. Patent No. 6,233,636 issued on April 26, 2016, U.S. Patent No. 6,233,636 issued on December 27, 2016, U.S. Patent No. 6,233,636 issued on January 10, 2017, and U.S. Patent No. 6,233,636 issued on June 3, 2014, all of which are hereby incorporated by reference in their entireties. Such guide elements are essential for support of small diameter needles to access tissue masses deep within the interior wall of a target vessel.

[0020] Some aspects of the present disclosure include a Fluid Injection Catheter (FIC) that uses an injection tube with a distal needle that is advanced and retracted through a guide tube. The FIC includes several embodiments that improve upon the prior art.

[0021] Perivascular tissue ablation catheter PTAC100, as shown in Figure 3 of U.S. Patent Nos. 5,233, 5,393, 6,471, 6,514, 6,689, 7,713, 7,821, 7,936, 7,103, 7,112, and 5,223, Fischell et al., shows a distal subassembly that includes a central support with support ramps for guide tubes and outer tube extensions that are located outside of the central support for connecting the outer tube extensions to the proximal end of the distal taper section of the catheter. Some aspects of the present disclosure include improvements related to extending the outer tube extension distally over a substantial portion of the taper section of the catheter.

[0022] Some aspects of the present disclosure include a dual layer outer tube extension with a slit flap opening structure that forms a window in the outer layer of the outer tube extension, which increases reliability for extension and retraction of the guide tube.

[0023] Some aspects of the present disclosure include embodiments that may be of small enough diameter to be placed through a 6 French guide catheter, i.e., 6 French compatible. This is accomplished through specific design specifications that allow for a practical set of guide tubes and infusion tubes with a distal needle with adequate radiopacity, but with an overall diameter of less than 0.07 inches in diameter. These include the use of infusion tubes with an outer diameter of less than 0.01 inches and an inner diameter of less than 0.007 inches, with an internal radiopaque wire with a diameter of less than 0.0055 inches. Additional embodiments include modifications of the infusion tube with the distal needle to allow for a smaller diameter.

[0024] Some aspects of the present disclosure include embodiments having a welded bond on the proximal end of the radiopaque wire that is inserted into the lumen of the infusion tube to provide longitudinal stability to the radiopaque wire with respect to the distal needle.

[0025] Some aspects of the present disclosure include a double-layered outer tube catheter shaft to increase flexibility while maintaining pushability.

[0026] Some embodiments of the present disclosure include structures such as alignment holes to secure alignment between the two layers of the outer tube extension, and a pin and slot mechanism to align the central support piece with the outer tube extension through which the injection tube with the distal needle is advanced and retracted.

[0027] Some aspects of the present disclosure include a fluid injection catheter (FIC) with a dual layer outer tube extension, where the outer layer includes slotted flaps to improve reliability of advancing and retracting the guide tube.

[0028] Some embodiments of the present disclosure include an outer tube extension with a distal extension of more than 5 mm that secures the catheter to the distal taper section.

[0029] Some aspects of the present disclosure include a pin in the central support to align with a slot in the inner layer of the outer tube extension to radially and longitudinally align the central support with the opening in the outer tube extension. The slot also allows for fixing this alignment when the outer layer of the outer tube extension is contracted onto the inner layer.

[0030] Some aspects of the present disclosure include a proximal weld joint for the proximal end of the radiopaque wire positioned inside the infusion tube to prevent significant distal movement of the radiopaque wire relative to the infusion tube.

[0031] Some embodiments of the present disclosure include a section of a multi-lumen catheter that is attached inside the main infusion lumen of the FIC to prevent proximal movement of the radiopaque wire.

[0032] Some embodiments of the present disclosure include appropriate scaling of the inner tube, intermediate tube, outer tube, guide tube, and infusion tube, as well as appropriate scaling of associated radiopaque elements to make the FIC compatible with a 6 French guide catheter.

[0033] Some embodiments of the present disclosure include removing a portion of the radially outer portion of each section of two or more guide tubes to reduce the overall outer diameter of the portion of the FIC where the guide tubes are separated.

[0034] In some embodiments, a catheter for fluid delivery to tissue outside the inner wall of a target vessel of a human body is provided. The catheter may include a catheter body with at least two openings at a distal portion thereof and a central axis extending in a longitudinal direction. In some embodiments, the catheter body includes a fluid infusion lumen. In some embodiments, each of the at least two openings at the distal portion of the catheter body includes an opening cover including at least one slit. The catheter may include at least two needle guide elements adapted to advance distally and extend outwardly toward the inner wall of the target vessel through the opening covers of the at least two openings at the distal portion of the catheter body. The catheter may include at least two infusion needles adapted to be advanced outwardly through the at least two needle guide elements to penetrate the inner wall of the target vessel. In some embodiments, the at least two infusion needles have distal openings for fluid delivery to tissue outside the inner wall of the target vessel.

[0035] In some embodiments, the aperture cover comprises a hole. In some embodiments, the at least one slit comprises a proximal slit. In some embodiments, the at least one slit comprises a longitudinal slit. In some embodiments, the distal portion of the catheter body comprises two layers, including an inner layer and an outer layer. In some embodiments, the aperture cover is formed in the outer layer. In some embodiments, a portion of the catheter body further comprises three concentric tubular structures, including an outer tube, an intermediate tube, and an inner tube. In some embodiments, the intermediate tube is adapted to move longitudinally relative to the outer tube. In some embodiments, the inner tube is adapted to move longitudinally relative to the intermediate tube. In some embodiments, a proximal portion of at least one of the three concentric tubular structures is formed from a metal hypotube. In some embodiments, the catheter may include at least one radiopaque marker positioned on at least one of the following: the catheter body, the at least one needle guiding element, or at least one of the at least one infusion needle. In some embodiments, the slit in the aperture cover increases the reliability of the extension and retraction of the at least two needle guiding elements. In some embodiments, the slits in the aperture cover guide the at least two needle guide elements through the aperture cover. In some embodiments, the slits in the aperture cover protect the at least two needle guide elements from surface damage when the at least two needle guide elements are advanced and retracted from the catheter body. In some embodiments, the catheter can include a distal tapered section, and a distal portion of the catheter body is coupled to the distal tapered section over a length of at least 5 mm.

[0036] In some embodiments, a catheter for fluid delivery to tissue outside the inner wall of a target vessel of a human body is provided. The catheter may include a catheter body with at least two openings at a distal portion thereof and a central axis extending in a longitudinal direction. In some embodiments, the catheter body includes a fluid infusion lumen. The catheter may include at least two openings at a distal portion of the catheter body, each of the openings including an opening cover including a hole and a proximal slit. The catheter may include at least two infusion needles adapted to be advanced outwardly through holes in the opening covers of the at least two openings to penetrate the inner wall of the target vessel. In some embodiments, the at least two infusion needles have distal openings for fluid delivery to tissue outside the inner wall of the target vessel.

[0037] In some embodiments, the catheter can include at least two needle guiding elements adapted to advance distally and expand outwardly through the aperture covers of the at least two apertures, and the at least two infusion needles are adapted to be advanced outwardly through the at least two needle guiding elements. In some embodiments, the distal portion of the catheter body comprises two layers including an inner layer and an outer layer. In some embodiments, the aperture covers are formed in the outer layer and the at least two apertures are formed in the inner layer.

[0038] In some embodiments, a catheter for fluid delivery through to tissue outside the inner wall of a target vessel of a human body is provided. The catheter may include a catheter body with three openings at a distal portion thereof and a central axis extending in a longitudinal direction. In some embodiments, the catheter body includes a fluid infusion lumen. In some embodiments, each of the three openings at the distal portion of the catheter body includes an opening cover with a hole and a longitudinal slit. The catheter may include three needle guide elements adapted to advance distally and extend outwardly toward the inner wall of the target vessel through holes in the opening covers of the three openings at the distal portion of the catheter body. The catheter may include three infusion tubes with distal infusion needles adapted to be advanced outwardly through the three needle guide elements to penetrate the inner wall of the target vessel. In some embodiments, the three infusion tubes have distal openings for fluid delivery to tissue outside the inner wall of the target vessel.

[0039] In some embodiments, the longitudinal slit is proximal to the aperture. In some embodiments, the aperture cover protects the three needle guiding elements. In some embodiments, the distal portion of the catheter body is coupled to the distal taper section over a length of at least 5 mm.

[0040] In some embodiments, a catheter for fluid delivery to tissue outside an inner wall of a target vessel of a human body is provided. The catheter may include a catheter body including an outer tube extension having a proximal end, a central portion, and a distal portion. In some embodiments, the distal portion of the catheter body includes at least two openings. In some embodiments, the catheter body includes a central axis extending in a longitudinal direction, and the catheter body includes a fluid infusion lumen. The catheter may include at least two needle guiding elements adapted to advance distally and expand outwardly toward the inner wall of the target vessel through the at least two openings in the distal portion of the catheter body. The catheter may include at least two infusion needles adapted to be advanced outwardly through the at least two needle guiding elements to penetrate the inner wall of the target vessel. In some embodiments, the at least two infusion needles have distal openings for fluid delivery to tissue outside the inner wall of the target vessel. The catheter may include a distal tapered section having a proximal portion and a distal end. In some embodiments, the distal portion of the outer tube extension is fixedly attached to the outside of the proximal portion of the distal taper section over a length of at least 5 mm.

[0041] In some embodiments, at least two openings in the distal portion of the outer body include an opening cover that includes a hole and a proximal slit. In some embodiments, the outer tube extension includes an inner layer and an outer layer. In some embodiments, a distal portion of the outer layer of the outer tube extension is fixedly attached to the outside of the proximal portion of the distal taper section. In some embodiments, a portion of the catheter body further includes three concentric tubular structures including an outer tube, an intermediate tube, and an inner tube. In some embodiments, the intermediate tube is adapted to move longitudinally relative to the outer tube. In some embodiments, the inner tube is adapted to move longitudinally relative to the intermediate tube. In some embodiments, a proximal portion of at least one of the three tubes is formed from a metal hypotube. In some embodiments, a distal portion of the outer tube extension is fixedly attached to the outside of the proximal portion of the distal taper section over a length of at least 10 mm. In some embodiments, the catheter may include at least one radiopaque marker positioned on at least one of the following: the catheter body, the at least one needle guiding element, or the at least one infusion needle.

[0042] In some embodiments, a catheter for fluid delivery to tissue outside an inner wall of a target vessel of a human body is provided. The catheter may include a catheter body including an outer tube extension having a proximal end, a central portion, and a distal portion including three openings. In some embodiments, the catheter body includes a central axis extending in a longitudinal direction. In some embodiments, the catheter body includes a fluid infusion lumen. The catheter may include three guide tubes adapted to advance distally and extend outwardly through the three openings in the distal portion of the catheter body toward the inner wall of the target vessel. The catheter may include three infusion tubes with distal infusion needles adapted to be advanced outwardly through the three guide tubes to penetrate the inner wall of the target vessel. In some embodiments, the three infusion tubes with distal infusion needles have distal openings for fluid delivery to tissue outside the inner wall of the target vessel. The catheter can include a distal tapered section having a proximal portion and a distal end, the distal portion of the outer tube extension being joined to the proximal portion of the distal tapered section over a length of at least 5 mm.

[0043] In some embodiments, each of the at least three apertures in the distal portion of the catheter body comprises an aperture cover. In some embodiments, the aperture cover protects the three needle guiding elements. In some embodiments, the aperture cover guides the three needle guiding elements. In some embodiments, the outer tube extension comprises an inner layer and an outer layer. In some embodiments, the outer layer of the outer tube extension is fixedly attached to the outside of the proximal portion of the distal taper section. In some embodiments, the outer layer of the outer tube extension comprises an aperture cover spanning the three apertures. In some embodiments, a portion of the catheter body further comprises three concentric tubular structures including an outer tube, an intermediate tube, and an inner tube. In some embodiments, the outer tube is coupled to the outer tube extension. In some embodiments, the distal portion of the outer tube extension is coupled to the proximal portion of the distal taper section over a length of at least 10 mm.

[0044] In some embodiments, a catheter for fluid delivery to tissue outside an inner wall of a target vessel of a human body is provided. The catheter may include a catheter body with a central axis extending in a longitudinal direction. In some embodiments, the catheter body includes an outer tube with a distal end and an outer tube extension coupled to the distal end of the outer tube. In some embodiments, the outer tube extension includes at least two openings. In some embodiments, the catheter body includes a fluid infusion lumen. The catheter may include at least two needle guiding elements adapted to advance distally and expand outwardly toward the inner wall of the target vessel through the at least two openings in the outer tube extension. The catheter may include at least two infusion needles adapted to be advanced outwardly through the at least two needle guiding elements to penetrate the inner wall of the target vessel. In some embodiments, the at least two infusion needles have distal openings for fluid delivery to tissue outside the inner wall of the target vessel. In some embodiments, the outer tube extension of the catheter body is formed of two layers including an outer layer and an inner layer.

[0045] In some embodiments, the catheter may include at least two aperture covers comprising holes and proximal slits. In some embodiments, the aperture covers are formed as part of the outer layer of the outer tube extension. In some embodiments, the catheter may include a tapered section comprising a distal end and a proximal section. In some embodiments, the outer tube extension further comprises a distal portion positioned distal to the at least two apertures. In some embodiments, the distal portion of the outer tube extension is fixedly attached to the proximal section of the tapered section over a longitudinal length of at least 5 mm. In some embodiments, the distal portion of the outer tube extension is fixedly attached to the proximal section of the tapered section over a longitudinal length of at least 10 mm. In some embodiments, the length of the distal portion of the outer tube extension substantially improves the strength of the attachment of the tapered section to the outer tube extension. In some embodiments, the distal portion of the outer tube extension is fixedly attached outside the proximal section of the tapered section. In some embodiments, the outer layer of the outer tube extension forms a flap spanning the at least two apertures. In some embodiments, the outer layer of the outer tube extension covers the at least two openings. In some embodiments, the outer layer of the outer tube extension comprises a hole that provides support for extension and retraction of the at least two needle guide elements. In some embodiments, the outer layer of the outer tube extension comprises a hole and a longitudinal slit, the longitudinal slit guiding the needle guide elements of the at least two needle guide elements toward the hole. In some embodiments, the outer layer of the outer tube extension protects the at least two needle guide elements from surface damage. In some embodiments, a portion of the catheter body further comprises three concentric tubular structures including an outer tube, an intermediate tube, and an inner tube. In some embodiments, the intermediate tube is adapted to move longitudinally relative to the outer tube. In some embodiments, the inner tube is adapted to move longitudinally relative to the intermediate tube. In some embodiments, a proximal portion of at least one of the three concentric tubular structures is formed from a metal hypotube. In some embodiments, the at least two infusion needles are non-coring needles.In some embodiments, the catheter may include at least one radiopaque marker positioned on at least one of the following: the catheter body, the at least one needle guiding element, or the at least one infusion needle.

[0046] These and other features and advantages will become apparent to those of ordinary skill in the art from a reading of the detailed description, including the associated drawings and claims. [Brief description of the drawings]

[0047] [Figure 1] 1 is a longitudinal cross-sectional view of a distal portion of a PTAC in its open position as configured for delivery of fluid to a tissue mass outside an inner wall of a target vessel. [Diagram 2] FIG. 13 is a longitudinal cross-sectional view of a distal portion of the FIC showing the dual layer outer tube and outer tube extension. [Diagram 3] FIG. 1 is a schematic diagram of the distal portion of the FIC. [Figure 4] FIG. 13 is a longitudinal cross-sectional view of an embodiment of the distal end of a FIC. [Diagram 5] FIG. 13 is a schematic diagram of the central support and its relationship to the guide tube and core guide wire. [Figure 6A] FIG. 13 is a schematic diagram showing the inner layer of an embodiment of the outer tube extension. [Figure 6B] FIG. 6B is a schematic diagram showing the alignment of the inner layer of FIG. 6A with the pin of the central support. [Figure 7] FIG. 13 is a schematic diagram showing the distal end of the inner tube and the proximal end of the infusion tube welded together, with the proximal end of the radiopaque wire running inside the infusion tube. [Figure 8] FIG. 8 is a schematic diagram showing an enlargement from the region of FIG. 7 showing the proximal end of the infusion tube with a welded radiopaque wire. [Figure 9]FIG. 1 is a schematic diagram of a portion of an embodiment of a FIC showing the distal end of the inner tube and the proximal portion of the infusion tube with a welded radiopaque wire, with a length of dual lumen catheter attached inside the lumen of the inner tube to prevent distal movement of the radiopaque wire. [Figure 10] FIG. 10 is a schematic diagram of a length of the dual lumen catheter of FIG. [Figure 11] FIG. 13 is a schematic diagram of an alternative embodiment of a guide tube of the FIC with a reduced exterior to reduce the overall FIC diameter. [Figure 12] 9 is a longitudinal cross-sectional view showing an alternative configuration to welding the three radiopaque wires shown in FIG. 8 as a method for preventing distal migration of the wires. FIG. [Figure 13] FIG. 13 is a longitudinal cross-sectional view of an embodiment of an infusion tube with an inner wire, the proximal end of which is circumferentially welded to the proximal end of the infusion tube. [Figure 14] FIG. 14 is a radial end view of the proximal end of the injection tube of FIG. 13. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0048] FIG. 1 is a longitudinal cross-sectional view of the distal portion of a perivascular tissue ablation catheter PTAC 100. Certain embodiments and features of PTAC are disclosed and illustrated in FIG. 3 of U.S. Patent Nos. 5,333, 5,493, 5,596, 6,741, 6,833, 6,971, 7,133, 7,113, 7,116, 7,117, 7,221, 7,222, 7,223, 7,225, 7,226, 7,227 ...

[0049] A fixed guidewire 110 with a corewire 111 and an outer layer 113 extends distally from the distal end of the tapered section 106. It should be noted that only a portion of the length of the guidewire 110 is shown in FIG.

[0050] 1 shows a dual layer guide tube 115 in a fully advanced position with a radiopaque marker 122 positioned through an opening 131 in the outer tube extension 104. The inner surface of the outer tube extension 104 forms part of a tubular shaft 120, which may be made from a hard material such as metal or high durometer plastic so that the guide tube 115 is relatively rigid as it is advanced and retracted. The outer tube extension 104 is a single layer with an opening 131.

[0051] The embodiment of the PTAC 100 includes an inner tube 105 , an intermediate tube 103 , and a metal hypotube connected to the proximal end of the outer tube 102 .

[0052] The central support 121 supports the guide tube 115 when it is pushed distally. The central support 121 also provides radial support for the advanced guide tube 115, preventing it from moving back away from the inner wall of the target vessel when the injection tube 116 with the sharp needle 119 is advanced through the guide tube 115, through the inner / internal wall of the target vessel, to a desired position 2-5 mm beyond the inner wall of the target vessel. In exceptional cases, the injection needle 119 at the distal end of the injection tube 116 can be advanced to a depth of 8 mm beyond the inner wall of the target vessel. Additional lateral support for the guide tube 115 is provided by the sides of the opening 131, which in combination with the central support 121 can provide radial and circumferential / lateral support both during the advancement of the guide tube 115 and, as a backup, during the delivery of the injection needle 119 through the inner wall of the target vessel. The support 121 may comprise a deflection surface, such as a curved or linear bevel, that may correspond to the radius of curvature of the distal surface of the guide tube 115 in curved embodiments.

[0053] An inner tube 105 with fluid injection lumens 133 connects to three injection tubes 116 through a manifold 125 such that the lumens of the injection tubes 116 are in fluid communication with the fluid injection lumens 133. The inner tube 105 and manifold 125 can slide along the longitudinal axis of the PTAC 100 inside an intermediate tube 103 which is shown to be of uniform diameter along its length, including the coaxial outer portion of the manifold 125.

[0054] FIG 2 is a longitudinal cross-sectional view of a distal portion of a fluid injection catheter (FIC) 200. The proximal end of FIG 2 shows a dual layer outer tube 202 with an outer layer 202A and an inner layer 202B, and an intermediate tube 203. The outer tube 202 is attached to a dual layer outer tube extension 204 with an outer layer 204A and an inner layer 204B, which are further attached to a tapered section 206. A fixed guidewire 210 with a corewire 211 extends distally from the distal end of the tapered section 206. It should be noted that only a portion of the length of the guidewire 210 is shown in FIG 2.

[0055] 2 also shows, in longitudinal cross section, the inner layer 265A, the outer layer 215A, and the dual layer guide tube 255A with the radiopaque marker 222A in its fully advanced position disposed through the opening 231A in the outer tube extension 204. The inner surface of the inner layer 204B of the outer tube extension 204 forms part of the tubular shaft 220 through which the guide tube 255A is advanced and retracted, which may be made of a hard material such as metal or high durometer plastic so as to be relatively rigid as the guide tube 255A is advanced and retracted. The outer layer 204A includes a flap 241A with a slit 242A just proximal to the hole 291A near the distal end of the outer tube extension 204. The flap 241A may cover the opening 231A in the outer tube extension 204. The flap 241A may include a slit 242A. The flap 241A may include a hole 291A. The hole 291A can be larger than the slit 242A. The hole 291A may be distal to the slit 242A. The slit 242A may be proximal to the hole 291A. The flap 241A may be a layer of material. The flap 241A may be a membrane. The flap 241A may be softer than other layers of the outer tube extension 204. The flap 241A may be malleable. The flap 241A may be flexible. The flap 241A may include a preformed hole 291A. The flap 241A may include a hole 291A that is formed or enlarged by the penetration of the guide tube 255A. The flap 241A may include a preformed slit 242A. The flap 241A may include a slit 242A that is formed or expanded by the penetration of the guide tube 255A. The hole 291A may be a preferred exit from the outer tube extension 204 for the corresponding guide tube 255A. In some uses, the guide tube 255A may be misaligned and may penetrate the slit 242A. The guide tube 255A may be pushed by the narrower slit 242A toward the wider hole 291A based in part on the shape of the slit 242A and hole 291A and / or the material of the flap 241A. The slit 242A may guide the corresponding guide tube 255A toward the hole 291A in the flap 241A.

[0056] In some embodiments, the flap 241A includes at least one slit. The flap 241A may include a proximal slit. The flap 241A may include a distal slit. The flap 241A may include a longitudinal slit. The flap 241A may include a circumferential slit. The flap 241A may include a single slit. The flap 241A may include a slit with a hole. The flap 241A may include a slit without a hole. The flap 241A may include a slit in the longitudinal direction. The flap 241A may include a slit in the radial direction. The flap 241A may include a slit in any direction. The flap 241A may include a curved slit. The flap 241A may include an X-shaped slit. The flap 241A may include a +-shaped slit. The flap 241A may include intersecting slits. The flap 241A may include spaced slits. In some embodiments, the flap 241A comprises a hole 291A. At least one slit may extend from the hole 291A. The at least one slit may intersect the hole 291A. The at least one slit may be continuous with the hole 291A. The at least one slit may be discontinuous with the hole 291A. The at least one slit may be separated from the hole 291A by a portion of the flap 241A. Although a hole with a proximal slit is shown here, it is also contemplated that the aperture cover may include a single slit with or without any of the following: a longitudinal slit, a radial slit, a slit in any direction, a curved slit, an X-shaped slit, or a +-shaped slit. The guide tube 255A extends through the flap 241A. The guide tube 255A may extend through both the hole 291A and the slit 242A.

[0057] The intermediate tube 203 is attached to the outer layers 215A, 215B, and 215C (not shown) of the guide tubes 255A, 255B, and 255C (not shown). A third guide tube 255C is shown in FIG. 3. In some embodiments, the intermediate tube 203 is attached at its proximal end to the distal end of a metal hypotube. Together, the metal hypotube connected to the intermediate tube 203 is used to simultaneously advance and retract the guide tubes 255A, 255B, and 255C. The injection tubes 216A, 216B, and 216C have sharp non-coring needles 219A, 219B, and 219C, respectively, at their distal ends. Infusion tubes 216A, 216B, and 216C (216C is shown in FIG. 3) can be coaxially advanced and retracted through guide tubes 255A, 255B, and 255C, which act as needle guide elements. Radiopaque wires 217A, 217B, and 217C are located within the lumens of injection tubes 216A, 216B, and 216C, respectively. Wires 216B and 216C are not shown in FIG. 2, but are shown in FIGS. 6 and 7.

[0058] In some embodiments, the FIC 200 has a distal end of a metal hypotube that is connected to a proximal end of the outer tube 202. Together, the metal hypotube and the outer tube 202 form the exterior of most of the proximal length of the FIC 200.

[0059] 2, the beveled surface 271A of the central support 221 supports the guide tube 255A as it is pushed outward distally against the inner wall of the target vessel. The central support 221 also provides radial support for the fully advanced guide tube 255A preventing the guide tube 255A from backing away from the inner wall of the target vessel when the injection tube 216A with the sharp needle 219A is advanced through the guide tube 255A, through the medial / inner wall of the target vessel, and to a desired location 2-12 mm beyond the inner wall of the target vessel.

[0060] The central stay 221 may have a distal extension 263 that is welded to the proximal end of the core wire 211 to secure the core wire 211 to the proximal portion of the FIC 200.

[0061] Additional lateral support for guide tube 255A is provided by the sides of aperture 231A, which in combination with central support 221 can provide radial and circumferential / lateral support both during advancement of guide tube 255A and, as a backup, during delivery of sharp injection needle 219A through the inner wall of the target vessel. Bevel 271A of central support 221 can be formed as a curved bevel, a linear bevel, or a combination of curved and linear bevels, and in curved embodiments can correspond to or be similar to the radius of curvature of the distal surface of guide tube 255A.

[0062] Although this description focuses on guide tube 255A and injection tube 216A, this description is applicable to two or more guide tube / injection tube combinations used in FIC 200 shown in Figures 2, 3, and 5.

[0063] It should be noted that the embodiment of the FIC 200 of Figure 2 has several significant improvements over the embodiment of the PTAC 100 of Figure 1. These improvements include the following: 1. Needles 219A and 219B with outlets 245A and 245B, respectively, are non-coring needles. In some embodiments, the needles can prevent clogging of the needles by tissue. 2. The distal section 235 of the outer layer 204A of the outer tube extension has a length L2 that is significantly longer than the relatively short distal section 135 of the outer tube extension 104 of FIG. 1. This will significantly improve the strength of the attachment of the tapered distal section 206 to the distal end of the FIC 200 compared to the tapered distal section 106 to the distal end of the PTAC 100 of FIG. 1. The outer layer 204A can be attached to the outer surface of the tapered distal section 206. The outer layer 204A can be attached to the outside of the tapered section 206 over a length of at least 2 mm. In some embodiments, the outer layer 204A can extend over 20 mm or more. The outer layer 204A and the tapered section 206 can form a more robust bond. The outer layer 204A and the tapered section 206 can be more firmly bonded. The outer layer 204A and the tapered section 206 can comprise different materials. In some embodiments, the outer layer 204A can be more flexible than the tapered section 206. A longer attachment length can strengthen the connection between the dissimilar materials of the outer layer 204A and the tapered section 206. 3. The flap 241A with slit 242A in the outer layer 204A of the outer tube extension 204 is not present in the PTAC 100 of FIG. 1. The flap 241A with slit increases the reliability of advancing and retracting the guide tube 255A through the opening 231A in the outer tube extension 204. The flaps 241A, 241B, and 241C may include holes and proximal slits. The flaps 241A, 241B, and 241C can protect the guide tubes 255A, 255B, and 255C with the relatively soft outer layers 215A, 215B, and 215C (not shown) from damage when the guide tube is advanced and retracted through the openings 231A, 231B, and 231C, respectively. The flaps 241A, 241B, and 241C can also protect the FIC 200 from tissue intrusion into the catheter body. The guide tubes 255A, 255B, and 255C can be guided towards holes in the flaps 241A, 241B, and 241C to provide a reliable means for ensuring accurate deployment of the guide tubes 255A, 255B, and 255C against the vessel wall. The flaps 241A, 241B, and 241C can provide lateral support to the guide tubes 255A, 255B, and 255C. The flaps 241A, 241B, and 241C can provide circumferential alignment of the guide tubes 255A, 255B, and 255C during deployment. 4. In an embodiment, the inner layer 204B is made of laser cut polyimide with three racetrack shaped openings 231A, 231B, and 231C cut at 120° intervals in the same plane. The outer layer 204A can be made of softer Pebax® with flaps 241A, 241B, and 241C formed from sections of the outer layer 204A that span the openings 231A, 231B, and 231C. This allows the guide tubes 255A, 255B, and 255C to slide against the softer Pebax® of the outer layer 204A rather than against the rigid edges of the polyimide inner layer 204B, allowing the guide tubes 255A, 255B, and 255C to be easily retracted / retracted through the openings 231A, 231B, and 231C, respectively. 5. The outer tube extension 204 may include two layers, an inner layer and an outer layer. The flaps 241A, 241B, and 241C may be formed on the outer layer. The outer layer may be attached to the tapered distal section over at least 5 mm. The distal portion of the outer layer of the outer tube extension may be fixedly attached to the outside of the proximal portion of the distal tapered section. The proximal catheter body may include three concentric tubular structures, an outer tube, a middle tube, and an inner tube. The outer tube extension may be attached to the distal end of the outer tube. The concentric tubular structures may allow movement for deployment of the guide tubes 255A, 255B, and 255C and the infusion tubes 216A, 216B, and 216C. In some embodiments, the column strength of the outer body extension 204 of the FIC 200 is an important attribute of the catheter design, and the outer body extension 204 must be stiff enough so that when the guide tubes 255A, 255B, and 255C (not shown) are deployed, there is no stretching or contraction of the outer body extension 204 that may change the deployed and / or retracted positions of the guide tubes 255A, 255B, and 255C and / or the injection tubes 216A, 216B, and 216C (not shown). In some embodiments, a material for the outer body extension with a smaller coefficient of friction is also desirable. 6. In some embodiments, the outer tube 202 is formed of two layers, an outer layer 202A and an inner layer 202B, because the outer tube 202 must be flexible so that it can be navigated into the renal arteries without kinking or otherwise compromising the functionality of the FIC 200. 7. In some embodiments, the outer tube 202 is constructed as a co-extrusion with the inner layer 202B being a relatively harder plastic with a durometer of 60 or greater. In some embodiments, the preferred material is 72D Pebax® which not only provides greater column strength but also has a slightly lower coefficient of friction at the interface with the outer surface of the guide tubes 255A, 255B, and 255C as they slide within the lumen of the inner layer 202B. 8. The outer layer 202A of the outer body extension 204 can be a softer, more pliable material with a durometer of 40 or greater. In some embodiments, the preferred material is 55D Pebax®, which allows for better flexibility (without kinking) for navigation into the renal arteries.

[0064] 3 is a schematic diagram of the distal portion of a FIC 200 with three concentric tubes, including an inner tube 205, an intermediate tube 203, and a double layer outer tube 202 with an inner layer 202B and an outer layer 202A. The outer layer 202A is attached at its distal end to the outer layer 204A of an outer tube extension 204 with a distal portion 235.

[0065] Distal portion 235 of outer layer 204A of outer tube extension 204 is attached over the proximal section of tapered distal section 206 with core wire 211. Outer layer 204A of outer tube extension 204 has proximal slits 242A, 242C, and 242B positioned over openings 231A, 231B, and 231C of FIG. 2, and opening covers in the form of flaps 241A, 241B, and 241C with holes 291A, 291C, and 291B.

[0066] The three guide tubes 255A, 255B, and 255C with outer layers 215A, 215B, and 215C and radiopaque markers 222A, 222B, and 222C are shown in a fully deployed position where they have been advanced through holes 291A, 291B. In some embodiments, the radiopaque band 222B is located between the outer layer 215B and the inner layer 215A of the guide tube 255B. It is also contemplated that the radiopaque markers 222A, 222B, and 222C may be attached to the outside of the outer layers 215A, 215B, and 215C.

[0067] The slits 242A, 242B, and 242C in the flaps 241A, 241B, and 241C protect the plastic guide tube outer layers 215A, 215B, and 215C from surface damage when the guide tubes 255A, 255B, and 255C are advanced and retracted into the body of the FIC 200. The flaps 241A, 241B, and 241C protect the plastic guide tube outer layers 215A, 215B, and 215C from damage when the catheter is advanced through the blood vessel. The flaps 241A, 241B, and 241C prevent the ingress of material into the catheter body through the opening 231A in the outer tube extension. Flaps 241A, 241B, and 241C form a membrane across openings 231A, 231B, and 231C through which guide tubes 255A, 255B, and 255C extend. A distal portion of intermediate tube 203 is attached to a proximal portion of guide tube outer layers 215A, 215B, and 215C such that as intermediate tube 203 is advanced and retracted longitudinally, guide tubes 255A, 255B, and 255C can be advanced and retracted simultaneously.

[0068] Infusion tubes 216A, 216B, and 216C with distal non-coring needles 219A, 219B, and 219C are designed to be coaxially located within guide tubes 255A, 255B, and 255C and extend outward from the distal ends of guide tubes 255A, 255B, and 255C. Lumen 275 of inner tube 205 is attached and sealed to the outside of injection tubes 216A, 216B, and 216C. Lumen 275 is in fluid communication with the lumens of injection tubes 216A, 216B, and 216C with distal openings 245A, 245B, and 245C. In some embodiments, inner tube 205 is attached at its proximal end to a metal hypotube.

[0069] 3 are two of the six layer locking holes 247AP and 247AD in the inner layer 204B of the outer tube extension 204 that, when heated and reflowed over the inner layer 204B, cause the outer layer 204A of the outer tube extension 204 to melt material into the holes 247AP and 247AD. This locks the two layers together to prevent movement of the inner layer 204B relative to the outer layer 204A. The other four holes 247BP, 247BD, 247CP, and 247CD may have a similar configuration.

[0070] It is also contemplated that the control handle may be used not only to move the guide tubes 255A, 255B, and 255C relative to the outer tube extension 204, but also to move the injection tubes 216A, 216B, and 216C with their sharp needles 219A, 219B, and 219C relative to the guide tubes 255A, 255B, and 255C.

[0071] 4 is a longitudinal cross-sectional view of an embodiment of a distal end of a FIC 200 with a tapered section 206 and a fixed guidewire 280. The fixed guidewire 280 with a distal end 266 includes an outer layer 265 and a corewire 211 with a tapered central portion 251 and a distal portion 261. The proximal portion of the corewire 211 is attached to the distal extension 263 of the central support, such as by adhesive, brazing, or welding. The distal portion 235 of the outer layer 204A of the outer tube extension of FIG. 2 and FIG. 3 is attached to the outside of the tapered section 206 over a length of at least 5 mm, and preferably 1 cm or more, which in combination with the corewire 211 being welded to the distal extension 263 of the central support provides a dual mechanism for strong fixation of the tapered section 206 and guidewire 280 to the central support 221 of FIG. 2 and thus to the proximal portion of the FIC 200. The distal portion 235 of the outer layer 204A of the outer tube extension in Figures 2 and 3 is attached to the outside of the tapered section 206 over a length of 5mm, 6mm, 7mm, 8mm, 9mm, 10mm / 1cm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm, 18mm, 19mm, 20mm, between 5mm and 10mm, or any range between two of the above values.

[0072] 5 is a schematic diagram of the central support 221 of the FIC 200 and its relationship to the guide tubes 255A, 255B, and 255C with outer layers 215A, 215B, and 215C, and the proximal tapered section 251 of the core wire 211. Also shown in FIG. 5 are the radiopaque band 222B of the guide wire 255B, and the distal non-coring needle 219B and the infusion tube 216B with opening 245B. The distal extension 263 of the central support 221 is shaped to allow for insertion of the core wire 211 into the distal extension 263 and subsequent attachment, such as by adhesive, brazing, soldering, or welding. The pin 298 of the central support 221 fits into a slot in the embodiment of the inner layer 404B of the outer tube extension 404 shown in FIGS. 6A and 6B.

[0073] FIG. 6A is a schematic diagram showing the inner layer 404B of an embodiment of the outer tube extension 404 with one of the three openings 431A shown in the embodiment. The slot 402 allows the pin 298 of the center support 221 of FIG. 5 to create the proper alignment between the center support 221 and the inner layer 404B during assembly. This alignment is shown in the schematic diagram in FIG. 6B, where the pin 298 of the center support 221 is fully engaged in the slot 402. The slot 402 also allows a location to help maintain alignment of the outer layer 404A of the outer tube extension 404 as it is heat-flowed and shrunk over the inner layer 404B, such that plastic melts into the slot 402 and prevents movement of one layer relative to the other. This may also eliminate the need for holes 247P and 247D in FIG. 3. Also shown is the beveled surface 271A of the center support 221 which provides support to the guide tube 255A of Figures 2, 3 and 5 as it is advanced outwardly.

[0074] 7 is a schematic diagram showing the proximal end of the inner distal portion of FIC 200 with infusion tubes 216A, 216B, and 216C with radiopaque wires 217A, 217B, and 217C in relationship to inner tube 205 and with outer layers 215A, 215B, and 215C and guide tubes 255A, 255B, and 255C with inner layers 265A, 265B, and 265C of FIC 200. Guide tube 255B is mostly hidden in this view. The proximal ends of radiopaque wires 217A, 217B, and 217C are welded together at weld joint 277.

[0075] The distal portion of lumen 275 of inner tube 205 is sealed to the outside of infusion tubes 216A, 216B, and 216C so that fluid injected into the proximal end of inner tube 205 flows into lumens 286A, 286B, and 286C, FIG. 8, of infusion tubes 216A, 216B, and 216C.

[0076] 8 is a schematic diagram showing an enlargement from region 8 of FIG. 7 of the inside of inner tube 205 showing the proximal ends of infusion tubes 216A, 216B, and 216C with radiopaque wires 217A, 217B, and 217C inserted into lumens 286A, 286B, and 286C and extending proximally from the proximal ends of infusion tubes 216A, 216B, and 216C. Also shown is welded joint 277, which may prevent significant distal movement of radiopaque wires 217A, 217B, and 217C relative to infusion tubes 216A, 216B, and 216C. The radiopaque wires may be formed from a radiopaque metal or alloy, such as tantalum, platinum, or gold. Also shown in Figure 8 is the space 289 between the contact points of the injection tubes 216A, 216C and inner tube 205 of Figure 7, and similar spaces between each pair of injection tubes 216A / 216B and 216B / 216C. In some embodiments, these spaces can be used for fluid flow, and there are openings on the outside of the injection tubes distal to the proximal ends of the injection tubes 216A, 216B, and 216C to increase flow into the injection tubes 216A, 216B, and 216C.

[0077] 9 is a schematic diagram of a portion of an embodiment of FIC 300 showing the proximal portions of injection tubes 316A, 316B, and 316C with welded wires 317A, 317B, and 317C and welds 377. In this embodiment, a length of dual lumen tube 390 is inserted into lumen 375 of inner tube 305. Length 390 is attached inside lumen 375 to prevent proximal movement of welded wires 317A, 317B, and 317C that could cause wires 317A, 317B, and 317C to exit the lumens of injection tubes 316A, 316B, and 316C. While FIG. 9 shows a relatively short section of dual lumen tube 390, it is contemplated that the length of dual lumen tube 390 can be as short as 0.5 cm and as long as 20 cm. The length of the dual lumen tube 390 can be 0.5 cm, 1 cm, 1.5 cm, 2 cm, 2.5 cm, 3 cm, 3.5 cm, 4 cm, 4.5 cm, 5 cm, 5.5 cm, 6 cm, 6.5 cm, 7 cm, 7.5 cm, 8 cm, 8.5 cm, 9 cm, 9.5 cm, 10 cm, 10.5 cm, 11 cm, 11.5 cm, 12 cm, 12.5 cm, 13 cm, 13.5 cm, 14 cm, 14.5 cm, 15 cm, 15.5 cm, 16 cm, 16.5 cm, 17 cm, 17.5 cm, 18 cm, 18.5 cm, 19 cm, 19.5 cm, 20 cm, between 1 cm and 5 cm, or any range between two of the above values. It is contemplated that any suitable shaped body that is attached inside lumen 275 just proximal to weld 377 and allows fluid flow around it will also provide a mechanism to prevent proximal movement of wires 317A, 317B, and 317C relative to injection tubes 316A, 316B, and 316C.

[0078] Figure 10 is an enlarged schematic view of the length 390 of the dual lumen catheter of Figure 9 along with the upper and lower lumens 394, 396 of tube 392. The division 398 between the upper and lower lumens 394, 396 can engage welds 377 when wires 317A, 317B, and 317C are moved proximally out of the lumens of infusion tubes 316A, 316B, and 316C.

[0079] 11 is a schematic diagram of an alternative embodiment of guide tubes 455A, 455B, and 455C of FIC 400. This embodiment may have a smaller potential maximum diameter than FIC 200, allowing it to be suitable for threading a 6 French guide catheter without reducing the primary diameter of the guide and infusion tubes.

[0080] The proximal sections of length L3 of the guide tubes 455A, 455B, and 455C of this embodiment of the FIC 400 are heat sealed together to reduce the diameter compared to the more distal portions of the guide tubes 455A, 455B, and 455C where the guide tubes 455A, 455B, and 455C are separated. It is when the guide tubes 455A, 455B, and 455C are separated that the diameter increases and affects the minimum achievable diameter for the FIC 400. To reduce this diameter, the embodiment shown in FIG. 11 removes material from the radially outermost portions of the guide tubes labeled 456A, 456B, and 456C. The guide tube 456B is hidden in FIG. 11. This material removal may be for a portion of the distal guide tube. In some embodiments, this material removal can be for all of the guide tube lengths distal to length L3. This creates a significant reduction in the overall diameter of the FIC400, allowing it to be compatible with 6 French guide catheters with minimal changes to the overall design.

[0081] In another embodiment, the area from which material is removed is: 1. may extend all the way to the proximal ends of guide tubes 455A, 455B, and 455C; 2. may extend all the way to the distal ends of the guide tubes 455A, 455B, and 455C; 3. The guide tubes 455A, 455B, and 455C may extend all the way from their proximal ends to their distal ends.

[0082] It is also contemplated that in some embodiments, the guide tubes 455A, 455B, and 455C may no longer be actual tubes since much of the material has been removed, but rather be U-shaped passages to act as needle guide elements, which still provide centering of the FIC 200 inside the target vessel, still guide the infusion tube outward, and still support the needles 219A, 219B, and 219C of FIG. 2 as they penetrate the inner wall of the target vessel.

[0083] In some U-shaped passage embodiments, only a short distal portion of guide tubes 455A, 455B, and 455C will have a circular cross section, in which embodiment, the short portion may include a radiopaque marker band as shown in elements 222A and 222B of FIG.

[0084] In some embodiments, one or more of the plastic layers of guide tubes 455A, 455B, and 455C can be made radiopaque using a process such as tungsten filling or by embedding radiopaque markers between the plastic layers.

[0085] 12 is a longitudinal cross-sectional view showing an alternative configuration to welding together three wires 217A, 217B, and 217C as shown in FIG. 8. Shown here is the proximal end of an infusion tube 416 with an inner wire 417. In this embodiment, the wire 417 is spot welded to the proximal end of the infusion tube 416 at weld 415. This embodiment has the advantage of preventing both proximal and distal movement of the wire 417 relative to the infusion tube 416. This embodiment allows fluid to flow into the lumen 475 of the infusion tube 416 when infused.

[0086] 13 shows a longitudinal cross-section of an embodiment of an infusion tube 516 with an internal wire 517. In this embodiment, the proximal end of the wire 517 is circumferentially welded to the proximal end of the infusion tube 516 at weld 515. This, by itself, prevents fluid flow into the lumen of the infusion tube 516, so a notch or slot 520 is cut into the outside of the proximal end of the infusion tube 516 with the circumferentially welded wire 517. After welding, or a weld that does not wrap around the entire circumference of the infusion tube 516, the slot 520 is formed to allow fluid flow into the lumen 575 of the infusion tube 516.

[0087] Figure 14 is a radial end view at 14-14 of the proximal end of the injection tube 516 of Figure 13. It shows the injection tube 516 with cut away surface 520, lumen 575, wire 517, and weld 515 attaching the proximal end of injection tube 516 to the proximal portion of wire 517.

[0088] 13 and 14 show the cutout at the proximal end of the injection tube 516, in some embodiments the cutout is distal to the proximal end of the injection tube 516, with fluid flow occurring in the space between the three injection tubes, such as the space 289 between injection tube 216A, injection tube 216C and inner tube 205 in FIG. 8.

[0089] In some embodiments, a preferred material for infusion tubes 416 and 417 is a shape memory metal such as Nitinol. Wires 417 and 517 may be formed from the same material as infusion tubes 416 and 516, or may be formed from a radiopaque material, which may include materials such as gold, platinum, and tantalum. Wires 417 and 517 may also be plated or coated with a radiopaque material.

[0090] Although the embodiments shown in Figures 2-11 show the use of three guide and infusion tubes, embodiments may be configured with only one guide and infusion tube, or as many as six guide and infusion tubes, in some embodiments, two or three guide and infusion tubes may be provided for use in a blood vessel of the human body.

[0091] Naturally, various other modifications, adaptations, and alternative designs are possible in light of the above teachings, and therefore, it is to be understood that, within the scope of the appended claims, the present invention may be practiced other than as expressly described herein.

[0092] It is contemplated that various combinations or subcombinations of the specific features and aspects of the embodiments disclosed above may be made and still be within the scope of one or more of the embodiments. Moreover, any specific feature, aspect, method, property, characteristic, quality, attribute, or element disclosed herein in connection with an embodiment can be used in all other embodiments described herein. Thus, it should be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for each other to form various aspects of the disclosed embodiments. Thus, it is understood that the scope of the present embodiments disclosed herein should not be limited by the specific disclosed embodiments disclosed above. Moreover, the embodiments are susceptible to various modifications and alternative forms, specific examples of which are shown in the drawings and described in detail herein. However, it should be understood that the embodiments are not limited to the specific forms or methods disclosed, but on the contrary, the embodiments cover the various embodiments described and all modifications, equivalents, and alternatives within the spirit and scope of the appended claims. Any method disclosed herein need not be performed in the order suggested. The methods disclosed herein include specific actions taken by the practitioner, but may also include any third-party instructions for those actions, either express or implied. Ranges disclosed herein encompass any and all overlaps, subranges, and combinations thereof. Terms such as "up to," "at least," "greater than," "less than," and "between" include the number being suggested. Numbers preceded by terms such as "approximately," "about," and "substantially," as used herein, include the number being suggested (e.g., about 10%=10%) and also represent a magnitude close to the stated magnitude that still performs the desired function and still achieves the desired result.For example, the terms "approximately," "about," and "substantially" can refer to dimensions that are within less than 10%, within less than 5%, within less than 1%, within less than 0.1%, and within less than 0.01% of the stated dimension. [Explanation of symbols]

[0093] 100 Perivascular Tissue Ablation Catheter, PTAC 102 Outer tube 103 Intermediate tube 104 Outer tube extension 105 Inner tube 106 Tapered Distal Section 110 Guidewire 111 Core Wire 113 Outer layer 115 Guide tube 116 Injection tube 119 needles 120 Tubular shaft 121 Center Support 122 Radiopaque Markers 125 Manifold 131 Aperture 133 Fluid injection lumen 135 Distal Segment 200 Fluid Injection Catheter, FIC 202 Outer tube 202A outer layer 202B Inner layer 203 Intermediate Tube 204 Outer pipe extension, outer body extension 204A outer layer 204B Inner layer 205 Inner tube 206 Tapered Distal Section 210 Guide Wire 211 Core Wire 215A, 215B, 215C outer layer 216A, 216B, 216C injection tube 217A, 217B, 217C Radiopaque Wire 219A, 219B, 219C Non-coring needles, needles 220 Tubular shaft 221 Center Support 222A, 222B, 222C Radiopaque markers, radiopaque bands 231A, 231B, 231C opening 235 Distal section, distal part 241A, 241B, 241C Flaps 242A, 242B, 242C Slit 245A, 245B, 245C Outlet, Distal Opening 247D, 247P, 247AD, 247AP, 247BP, 247BD, 247CP, 247CD layer locking hole 251 central portion, proximal tapered region 255A, 255B, 255C guide tubes 261 Distal part 263 Distal extension 265 Outer layer 265A, 265B, 265C inner layer 266 Distal End 271A Slope 275 Lumen 277 Welded joints 280 Fixed Guide Wire 286A, 286B, 286C lumen 289 Space 291A, 291B holes 298 Pin 300 FIC 305 Inner tube 316A, 316B, 316C injection tube 317A, 317B, 317C Wire 375 Lumen 377 Welding 390 A length of double lumen tubing 392 tube 394 Upper Lumen 396 Inferior lumen 398 Division 400 FIC 402 Slots 404 Outer tube extension 404A outer layer 404B inner layer 415 Welding 416 Injection tube 417 Internal Wire 455A, 455B, 455C guide tube 456A, 456B, 456C Guide tube 475 Lumen 515 Welding 516 Injection tube 517 Internal Wire 520 Notches, slots, cut-out surfaces 575 Lumen L1 Length of distal segment 135 L2 Length of distal segment 235

Claims

1. 1. A catheter for fluid delivery to tissue external to an inner wall of a target vessel in a human body, comprising: a catheter body having at least two openings in a distal portion of the catheter body, a longitudinally extending central axis, and a fluid infusion lumen; each of the at least two openings in the distal portion of the catheter body includes an opening cover including at least one slit; A catheter body; at least two needle guide elements adapted to advance distally and extend outwardly through the opening covers of the at least two openings in the distal portion of the catheter body toward the interior wall of the target vessel; at least two infusion needles adapted to be advanced outwardly through the at least two needle guide elements to penetrate the interior wall of the target vessel, the at least two infusion needles having distal openings for fluid delivery to the tissue outside the interior wall of the target vessel; A catheter comprising:

2. The catheter of claim 1 , wherein the aperture cover comprises a hole.

3. The catheter of claim 1 , wherein the at least one slit comprises a proximal slit.

4. The catheter of claim 1 , wherein the at least one slit comprises a longitudinal slit.

5. The catheter of claim 1 , wherein the distal portion of the catheter body comprises two layers, including an inner layer and an outer layer.

6. The catheter of claim 5 , wherein the aperture cover is formed on the outer layer.

7. The catheter of claim 1 , wherein a portion of the catheter body further comprises three concentric tubular structures including an outer tube, an intermediate tube, and an inner tube.

8. The catheter of claim 7 , wherein the intermediate tube is adapted to move longitudinally relative to the outer tube.

9. The catheter of claim 7 , wherein the inner tube is adapted to move longitudinally relative to the intermediate tube.

10. The catheter of claim 7 , wherein a proximal portion of at least one of the three concentric tubular structures is formed from a metal hypotube.

11. below, a. the catheter body; b. at least one needle guide element; or c. at least one injection needle; The catheter of claim 1 , further comprising at least one radiopaque marker positioned on at least one of the

12. The catheter of claim 1 , wherein the slits in the aperture cover increase reliability of extension and retraction of the at least two needle guide elements.

13. The catheter of claim 1 , wherein the slits in the opening cover guide the at least two needle guide elements through the opening cover.

14. The catheter of claim 1 , wherein the slits in the aperture cover protect the at least two needle guide elements from surface damage when the at least two needle guide elements are advanced and retracted from the catheter body.

15. The catheter of claim 1 , wherein the catheter further comprises a distal tapered section, the distal portion of the catheter body being joined to the distal tapered section over a length of at least 5 mm.

16. 1. A catheter for fluid delivery to tissue external to an inner wall of a target vessel in a human body, comprising: a catheter body having at least two openings in a distal portion of the catheter body, a longitudinally extending central axis, and a fluid infusion lumen; at least two openings in the distal portion of the catheter body, each opening comprising an opening cover comprising a hole and a proximal slit; at least two infusion needles adapted to be advanced outwardly through the holes in the opening covers of the at least two openings to penetrate the interior wall of the target vessel, the at least two infusion needles having distal openings for fluid delivery to the tissue outside the interior wall of the target vessel; A catheter comprising:

17. 17. The catheter of claim 16, further comprising at least two needle guiding elements adapted to advance distally and expand outwardly through the opening covers of the at least two openings, the at least two infusion needles adapted to be advanced outwardly through the at least two needle guiding elements.

18. 17. The catheter of claim 16, wherein the distal portion of the catheter body comprises two layers, including an inner layer and an outer layer.

19. 20. The catheter of claim 18, wherein the aperture cover is formed in the outer layer and the at least two apertures are formed in the inner layer.

20. 1. A catheter for fluid delivery through an inner wall of a target vessel in a human body to tissue external to the vessel, comprising: a catheter body having three openings in a distal portion thereof, a central axis extending in a longitudinal direction, a fluid injection lumen, each of the three openings in the distal portion of the catheter body having an opening cover including a hole and a longitudinal slit; three needle guide elements adapted to advance distally and extend outwardly through the holes in the opening covers of the three openings in the distal portion of the catheter body toward the interior wall of the target vessel; three injection tubes with distal injection needles adapted to be advanced outwardly through the three needle guide elements to penetrate the interior wall of the target vessel, the three injection tubes having distal openings for fluid delivery to the tissue outside the interior wall of the target vessel; A catheter comprising:

21. The catheter of claim 20, wherein the longitudinal slit is proximal to the hole.

22. The catheter of claim 20 , wherein the aperture cover protects the three needle guide elements.

23. 21. The catheter of claim 20, wherein the distal portion of the catheter body is joined to a distal tapered section over a length of at least 5 mm.

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