HK1202399B - Catheter system for vessel wall injection and perivascular renal denervation - Google Patents

Description

Catheter system for vessel wall injection and perivascular renal denervation

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. patent application No. 13/216,495, filed 24/2011, and U.S. patent application No. 13/294,439, filed 11/2011, each of which is incorporated herein by reference in its entirety.

Technical Field

The present application is in the field of devices for ablating muscle cells and nerve fibers for treating cardiac arrhythmias, hypertension, congestive heart failure and other disorders.

Background

Since the thirties of the twentieth century, it has been known that damage or ablation of sympathetic nerves in or near the outer layer of renal arteries can drastically reduce hypertension. Alcohol has been used in animal experiments as early as 1952. In particular, the application of alcohol to the exterior of the canine renal artery to produce denervation is described by RobertM. Berne in "Hemodynamics and Sodium evolution of degraded Kidney in and Unanesthed Dog" Am J Physiol, October1952171 (1) 148-158.

Currently, physicians commonly treat patients with Atrial Fibrillation (AF) using Radio Frequency (RF) catheter systems to ablate the conducting tissue in the left atrial wall of the heart around the ostium of the pulmonary vein. Similar techniques using radiofrequency energy have been successfully used inside the renal arteries to ablate sympathetic and other nerve fibers running in the outer wall of the renal artery in order to treat hypertension. In both cases, these are elaborate and expensive catheter systems that can induce heat, cryoablation, or other methods to damage peripheral tissue. Many of these systems also require significant capital expenditures for reusable equipment located outside the body, including RF generation systems and fluid handling systems for cryoablation catheters.

Because of anatomical similarities, for purposes of this disclosure, the term target wall refers herein to either the pulmonary vein wall near the pulmonary vein ostium for AF ablation applications, or the renal artery wall for hypertension or Congestive Heart Failure (CHF) applications.

In the case of atrial fibrillation ablation, ablation of tissue around multiple pulmonary veins can be technically challenging and very time consuming. This is especially true if an RF catheter is used that can ablate only one lesion at a time. There is also a failure rate for atrial fibrillation ablation using these types of catheters. Failure of current methods involves challenges in producing reproducible circumferential ablation of tissue around the ostium (perioral) of the pulmonary vein. There are also significant safety issues with current techniques that involve extremely long fluoroscopy and procedure times, which result in high levels of radiation exposure to the patient and operator, and can increase the risk of stroke in atrial fibrillation ablation.

Sympathetic denervation is also potentially dangerous for the treatment of hypertension or congestive heart failure using current techniques for RF ablation to produce sympathetic denervation from inside the renal arteries. The short-term complications and long-term sequelae of applying RF energy to the arterial wall from within the renal artery are not well-defined. Such energy applied within the renal artery and the attendant transmural renal artery injury can lead to late restenosis, thrombosis, renal artery spasm, embolism of debris within the renal parenchyma, or other problems within the renal artery. There may also be uneven or incomplete sympathetic nerve ablation, particularly if there is an anatomical abnormality, or atherosclerotic or fibrotic disease inside the renal arteries, so that there is uneven delivery of RF energy. This can result in treatment failure, or require additional and dangerous levels of RF energy to ablate nerves running along the adventitial plane of the renal artery.

The Ardian system for RF energy delivery also does not allow for effective circumferential ablation of renal sympathetic nerve fibers. If circumferential RF energy is applied to the annulus from within the renal artery (energy applied at the intimal surface to kill nerves in the adventitial outer layer), this can lead to an even higher risk of renal artery stenosis from thermal injury to the intima, media and adventitia circumference and transmural walls. Finally, an internal "burn" of the renal artery using RF ablation can be extremely painful. Thus, there are numerous and numerous limitations of current methods of using RF-based renal sympathetic denervation. Similar limitations apply to ultrasound or other energy delivery techniques.

Bullfrog described by Seward et al in U.S. patent nos. 6,547,803 and 7,666,163A micro-infusion catheter using an inflated elastomeric balloon to expand a single needle against the vessel wall may be used to inject a chemical ablative solution such as alcohol, but it would require multiple applications because it does not describe or anticipate circumferential delivery of ablative material around the entire circumference of the vessel. Most of the needle numbers shown by Seward are two, and BullfrogWould be difficult to miniaturize to fit through a small guide catheter to be used in the renal artery. If only one needle is used, the control and precise rotation of any device at the catheter tip is difficult at best, and can be dangerous if subsequent injections are not evenly spaced. This device also does not allow for precise, controlled and adjustable depth delivery of nerve ablation agents. This device may also have physical constraints as to the length of needle that can be used, limiting the ability to inject the agent to a sufficient depth into the diseased renal artery, particularly with thickened intima. BullfrogAnother limitation of (a) is that balloon inflation in renal arteries can induce stenosis due to balloon injury of the intima and media of the artery, as well as cause endothelial cell denudation.

Catheters for injecting drugs into the inner wall of blood vessels are described by Jacobson and Davis in U.S. patent No. 6,302,870. While Jacobson includes the concept of outwardly expanding needles, each of which has a handle to limit penetration of the needle into the vessel wall, his design relies on rotation of the tube with the needle at its distal end to allow it to attain an outwardly curved shape. The shaft design with a small disc attached a short distance proximal to the needle distal end is shown to have a fixed diameter that increases the overall device diameter to at least twice the shaft diameter so that if the shaft is large enough in diameter to stop the penetration of the needle, it significantly increases the diameter of the device. For renal denervation or atrial fibrillation applications, the length of catheter required would make such rotational control difficult. In addition, the penetration limiting handle is a fixed distance from the distal end of the needle. There is no means of adjustment of penetration depth, which may be important if it is desired to selectively target a particular layer in a blood vessel, or if it is desired to penetrate all the way through a volume of adventitia with a different wall thickness. Jacobson has not envisaged the use of injection catheters for denervation. Finally, in fig. 3 of Jacobson, when he shows the sheath over the expandable needle, there is no guide wire and the sheath has an open distal end, which makes advancement through the vascular system more difficult. Furthermore, if the needles are completely withdrawn from the interior of the sheath, they can become stuck within the sheath due to the handle and difficult to push out.

The prior art has not contemplated the use of anesthetics, such as lidocaine, which can reduce or eliminate any pain associated with denervation procedures if injected first or in or along with an ablative solution.

As early as 1980, alcohol has been shown to be effective in providing renal denervation in animal models, as disclosed by Kline et al in "Functional re-anervation and evaluation of persistence to NE after regional preservation in rates", American Physiological Society1980:0363-6110/80/0000-0000801.25, pages R353-R358. Although Kline restated in 1983 in the paper "Effect of fresh preservation on economic compression in rates with aerobic transformation" Hypertension,1983,5: 468-475: "applying 95% alcohol to blood vessels to destroy any remaining nerve fibers, using this technique for renal denervation, we have found that the renal NE concentration is more than 90% depleted (i.e. <10mg/g tissue) 4 days after the procedure, but Kline again discloses that the 95% alcohol solution applied during the procedure is effective in ablating nerves surrounding the renal arteries in rats. While drug delivery catheters, such as those designed by Jacobson to inject fluid into the arterial wall at multiple points, have existed since the nineties of the twentieth century and alcohol has been effective as a therapeutic element for renal denervation, there remains a need for intravascular injection systems specifically designed for perivascular circumferential ablation of sympathetic nerve fibers in the outer layer around the renal artery, with adjustable penetration depth to accommodate variability in renal artery wall thickness.

The prior art has not contemplated the use of anesthetics, such as lidocaine, which can reduce or eliminate any pain associated with denervation procedures if injected first or in or along with an ablative solution.

McGuckin, U.S. patent No. 7,087,040, describes a tumor tissue ablation catheter having three expandable tines for injecting fluid exiting a single needle. The teeth expand outward to penetrate tissue. The McGuckin device has an open distal end that does not provide protection from inadvertent needle sticks from tines. In addition, the McGuckin device relies on tines that are strong enough so that they can expand outward and penetrate tissue. To achieve such strength, the teeth will not be small enough to have negligible blood loss when retracted after fluid injection for renal denervation applications. There is also no operable penetration limiting mechanism that reliably sets the depth of penetration of the injection outlet from the tooth relative to the inner wall of the vessel, nor is there a preset adjustment for such depth. For applications in the treatment of liver tumors, a continuously adjustable tooth penetration depth is significant when multiple injections at several depths may be required; however, for renal denervation, it is critical to be able to tune precisely in depth so as not to infuse the ablative fluid too shallow and kill the media of the renal artery, or to infuse the ablative fluid too deep and miss nerves just outside or in the outer layers of the renal artery.

Finally, Fischell et al, in U.S. patent applications 13/092,363, describe expandable intravascular catheters having expandable needle injectors. In 13/092,363, Fischells discloses an intravascular catheter with a sheath that, unlike Jacobson, has a closed configuration that fully encloses a sharp needle to protect medical personnel from needle stick injuries and blood-borne pathogens. However, Fischell applications 13/092,363, 13/092,363 only show designs that operate into the wall of the left atrium surrounding the ostium of the pulmonary vein or into the wall of the aorta surrounding the ostium of the renal artery without access from inside the blood vessel.

Disclosure of Invention

The Intravascular Nerve Ablation System (INAS) of the present application enables the application of ablation fluids, using a single use catheter and without the need for additional fixation devices, with relatively short treatment times, creating circumferential lesions in the vessel wall or in the nerve tissue near the vessel wall. The primary focus of INAS use is in the treatment of cardiac arrhythmias, hypertension and congestive heart failure. Unlike Bullfrog or RF ablation devices that operate with one or at most two ablation points, the present invention is designed to provide perivascular fluid injection, allowing for more uniform circumferential damage to the nerves while minimizing damage to the intima and media layers of the vessel wall. The term circumferential delivery is defined herein as the simultaneous injection of a suitable ablative solution at least three points within the vessel wall, or the circumferential filling of a space outside the adventitia layer (outer wall) of a blood vessel. Unlike the Jacobson device of U.S. patent No. 6,302,870, which does describe circumferential delivery, the present invention does not rely on rotation of the tube to produce outward movement, nor does it have a fixed diameter shaft to limit penetration. Furthermore, while Jacobson shows the form in which his device is pulled back within a sheath-like tube, the tube has an open end, and Jacobson requires an increase in diameter to accommodate a manifold that allows fluid to flow in one lumen from the proximal end of the catheter to the outlet through multiple needles. The preferred embodiment of the present invention uses a manifold that fits within the lumen of the tube, thus greatly reducing the diameter of the catheter, which enhances delivery of the catheter to the desired site within the human body.

In particular, there is a definite need for a catheter system that is capable of highly efficient and reproducible perivascular ablation of nerves surrounding the renal artery ostium, or of nerves distal to the ostium in the renal artery wall, in order to compromise sympathetic nerve fibers that track from the perioral aortic wall into the renal artery, and thus improve control and treatment of hypertension, etc.

Such systems may also have significant advantages over other current techniques by allowing highly effective and reproducible perivascular circumferential ablation into the muscle fibers and conductance in the pulmonary vein wall near or at the pulmonary vein ostium within the left atrium of the heart. Such ablation may interrupt Atrial Fibrillation (AF) and other arrhythmias. Other potential applications of this approach may be evolved.

The present invention is a small (< 2mm diameter) catheter that includes multiple expandable syringes with sharp injection needles at their distal ends. The preferred embodiment also includes an expandable guide tube to guide the passage of the coaxial injection tube to facilitate penetration of the circumferentially arrayed sharp injection needles about the INAS body near its distal end. Ablative fluid may be injected through the distal ends of these needles, each of which has an injection outlet at or near its distal end. There is a penetration limiting member as part of the INAS such that the needle will only penetrate into the tissue of the target vessel wall to a preset distance. These may be a preset distance proximal to the distal end of each needle, similar to the handles of Jacobson et al, or a penetration limiting member may be built into the proximal section of the INAS. Limiting penetration is important for: reduce the likelihood of vessel wall perforation, optimize the depth of injection or adjust the depth into the perivascular volume just outside the vessel wall. In a preferred embodiment for PVRD (perivascular renal denervation), an expandable guide tube is first deployed against the renal artery inner wall and acts as a guide for a separate coaxial longitudinally movable injection tube with a sharpened injection needle with one or more injection outlet ports near the distal end.

Ideally, the injection needle should be small enough that there is no blood loss after withdrawal after full penetration through the renal artery wall. A significant advantage of embodiments of the present invention is that with such small (< 25 gauge) needles, the self-expanding structure can be quite fragile and unreliable for ensuring accurate penetration of the vessel wall. The present invention solves this problem in 2 ways. The use of a cord or wire attached at a fixed distance proximal to the distal end of the needle limits penetration and connects expandable injection needles to one another, helping to create uniform expansion of the injection needles to facilitate reliable penetration of the vessel wall. However, a preferred embodiment is the use of expandable guide tubes which open to the interior of the vessel and thus direct each injection needle directly to the point of penetration of the vessel wall. The guide tube may be constructed of a memory metal such as NITINOL or a plastic material such as polyamide or polyurethane. The guide tube should also be radiopaque or have radiopaque markers at the tip, such as tantalum, gold, or platinum bands. The ideal configuration for the guide tube is a pre-formed self-expanding plastic tube with a soft tip so as not to damage or accidentally penetrate into the vessel wall. The last 0.5-3mm of this plastic tube may be formed in a filled plastic with a radiopaque material such as barium or tungsten. It is also envisaged that two layers of plastic tubing, such as polyurethane on the outside and polyamide on the inside, may provide an even better structure. The hardness of the plastic used may also vary as follows: soft material at the tip, harder material in the bent and flared portion and softer material again in the section proximal to the expandable section. This last segment, which is softer, will facilitate the delivery of INAS around the almost right angle bend through the guide catheter into the renal artery.

To facilitate the guide tube's residence against the inner wall of the target vessel, it is contemplated that a distal portion of the injection tube, including the injection needle, will be formed with almost the same radius of curvature as the guide tube. In fact, the radius of curvature of the guiding tube will vary with the vessel diameter, being larger for smaller vessels which will constrain the tubes, not allowing them to open completely. Thus, ideally, the radius of curvature of the distal portion of each syringe containing the injection needle should be the same as the distal portion of the guide tube at its largest diameter.

The term expandable will be used throughout this specification to describe the outward movement of a portion of the present invention relative to the longitudinal axis of an INAS catheter. It involves outward movement of the guide tube, syringe and/or needle. This expansion may result from self-expansion of the self-expanding structure released from the constraining structure, or it may be expansion facilitated by distal or proximal movement of another mechanism within the INAS (e.g., a wire that pushes or pulls the expandable structure away from the longitudinal axis). Another term that may be used to describe this outward movement is that the terms may deviate. For example, the self-expanding structure deflects outwardly when released from its constraint, and the use of a wire that moves distally or proximally to cause outward movement of the deflectable members would be a structure that can be deflected by hand. It is also contemplated that the inflatable balloon may be used to deflect or expand the deflectable or expandable structure outwardly from the longitudinal axis of the INAS.

The preferred embodiment of the invention, which will function in vessels of different internal diameters, has both a guide tube and an injection needle at the distal end of the injection tube with a curved shape. Ideally, the expanded shape of the guide tubes would be such that they would reach an expanded diameter slightly larger than the largest vessel contemplated for use of the device if there were no internal vascular constraint. The guide tube shape should also have a distal end at 90 degrees plus or minus 30 degrees to the longitudinal axis of the INAS. For example, the INAS guide tube may have an unconstrained diameter of 9mm with the distal end bent back 100 degrees, i.e., 10 degrees further back than perpendicular to the longitudinal axis of the INAS. Thus, when constrained in an artery of 8mm or less, the angle over which the guide tube engages the interior of the vessel will be less than 100 degrees. For example, the distal tip of the guide tube may be approximately 90 degrees in a 7mm diameter vessel, 80 degrees in a 6mm vessel, and 70 degrees in a 5mm vessel. Even in 5mm vessels, the system will work due to the curved shape of the injection needle, which will curve back against the proximal end of the INAS and ensure proper penetration of the vessel wall. An important feature of the present invention is that the syringes curve back in the proximal direction as they extend from the distal end of the guide tube and penetrate through the vessel wall. It is typical for the injection outlet of each injection needle at the distal end of the injection tube to have a deployed position that is proximal to the distal end of the guide tube. For example, for an injection needle injection outlet at a distance of 2.5mm beyond the distal end of the guide tube, the injection outlet may be 1-2mm proximal of the distal end of the guide tube.

Because precise depth penetration is preferred, the conduits for either the INAS proximal or distal sections should have limited stretchability so that they do not elongate during deployment through the guide catheter into the renal artery. For example, stainless steel, L605 or NINTINOL may be the best material for the proximal section of the INAS. A metal reinforced tube with a reduced tendency to elongate may be optimal for the distal section of INAS where more flexibility is required to move around an almost right angle bend in the guide catheter from the aorta to the renal arteries.

The penetration limiting function of the INAS of the present invention as described herein uses one of the following techniques which will greatly reduce the diameter of the device and thus also improve its ability to be delivered into a human blood vessel, such as the renal artery, as compared to the Jacobson design of U.S. patent No. 6,302,870. These techniques include:

the use of a string or wire attached to multiple needles that can be folded during insertion to limit the diameter of the distal section of the INAS,

the use of one, two or more short NITINOL wires attached to the needle sidewall at its proximal end in the longitudinal direction. The wire is designed to have its distal end unattached and to have a memory state bent away from the needle so as to act as a penetration limiting member with respect to the needle. Such a wire will fold tightly against the needle, reducing the diameter of the distal section of the INAS,

the use of two bends in the needle, which form the penetration limiting member and which are also in the circumferential direction so as not to increase the diameter of the distal section of the INAS, and

the preferred embodiment includes the use of outwardly curved guide tubes through which the needle slides in the longitudinal direction. The restriction on penetration in this design is integrated into the proximal end of the INAS and does not require a diametric volume in the INAS distal section. This last embodiment has the additional advantage of allowing the depth of penetration to be adjusted. The adjustment may include markings that allow for precise depth adjustment.

The adjustment of the depth of penetration by the mechanism in the proximal end of the INAS may be physician controlled or accessible only during device production. In the first case, the use of intravascular ultrasound or other imaging techniques can be used to identify the renal artery thickness at the desired site for PVRD. The clinician will then adjust the depth accordingly. It is also contemplated that INAS may be preset in the factory using a depth adjustment that would be inaccessible to the clinician and would provide different product codes if multiple depths were required. For example, three depths may be available, such as 2mm, 2.5mm, and 3 mm. Other advantages of factory adjustable depth are simplified calibration and quality generation, as variations in INAS with each production may require final factory adjustment of needle depth so as to provide a precise depth of penetration. It is also an advantage for factory filing to use one or more preset depths during trial and approval to limit potential errors in setting the wrong depth. Finally, it is contemplated that both internal adjustments regarding factory production and calibration and externally available adjustments with depth markings may be integrated into the INAS.

A syringe having a distal needle is in fluid communication with an injection lumen in the catheter body, which is in fluid communication with an injection port at the proximal end of the INAS. Such an injection port will typically include a standard connector, such as a luer connector for connection to a source of ablation fluid.

This injection system also contemplates the use of a very small gauge needle (less than 25 gauge) to penetrate the arterial wall, so that needle penetration may be safe even if a plane or volume of tissue is targeted, either at the adventitia layer of the aorta, pulmonary vein or renal artery, or deep (beyond) the adventitia layer of the aorta, pulmonary vein or renal artery. It is also contemplated that the distal needle may be a cutting or coring needle, and for cutting needles, the injection outlet port may be proximal to the cutting tip, cutting into the sidewall of the syringe or a small injection hole (bore) in the distal needle.

The expandable syringes may be self-expanding, constructed of resilient materials, memory metals such as NITINOL, or they may be constructed of metal or plastic and may be expanded by other mechanical methods. For example, an expandable leg with a distal injection needle may be secured to the exterior of an expandable balloon whose diameter may be controlled by the pressure used to inflate the balloon. Depending on the diameter of the vessel to be treated, there should be at least 2 syringes, while 3-8 tubes may be more suitable. For example, in a 5mm diameter renal artery, only 3 or 4 needles may be required, while in an 8mm diameter kidney, 6 needles may be required.

The entire INAS is designed to include a fixed distal wire, or be advanced over a wire in the following configuration: an on-wire configuration in which the guidewire lumen runs the entire length of the INAS, or a rapid exchange configuration in which the guidewire exits the catheter body at least 10cm distal of the INAS proximal end and runs outside of the catheter shaft for its proximal section. The form of the fixation wire is preferred as it will have the smallest distal diameter.

The INAS will also include a tubular thin-walled sheath that constrains the self-expanding syringe with the distal needle and/or guide tube prior to deployment and for removal from the body. The sheath also allows the distal end of the INAS to be inserted into the proximal end of a guiding catheter or introducer sheath. The sheath also acts to protect one or more operators from possible needle sticks and exposure to blood-borne pathogens at the end of the procedure when the INAS is removed from the patient.

It is also contemplated that the injection needles, guide tubes and injection tubes may be formed of or coated with or marked with a radiopaque material, such as gold or platinum, in order to make them clearly visible using fluoroscopy.

It is also contemplated that one or more of the injection needles may be electrically connected to the proximal end of the INAS so as to also serve as one or more diagnostic electrodes for assessing electrical activity in the vessel wall region.

It is also contemplated that 2 or more of the expandable legs may be attached to a power or RF source to deliver current or RF energy around the circumference of the target vessel to the oral wall to perform tissue and/or nerve ablation.

It is also contemplated that this device may be injected simultaneously or sequentially with one or more nerve ablative substances in order to optimize permanent sympathetic disruption (nerve disruption) in the renal artery segment. Contemplated neurotoxin agents that may be utilized include, but are not limited to, ethanol, phenol, glycerol, local anesthetics at relatively high concentrations (e.g., lidocaine, or other agents such as bupivacaine, cocaine, benzocaine, etc.), neurotoxic antiarrhythmics, botulinum toxins, digoxin or other cardiac glycosides, guanethidine, heated fluids including heated saline, hypertonic saline, hypotonic fluids, KCl, or heated nerve ablating substances such as those listed above.

It is also contemplated that the ablative substance may be a hypertonic fluid such as hypertonic saline (extra salt) or a hypotonic fluid such as distilled water. These will also cause permanent damage to the nerve and may be as good as or even better than alcohol or specific neurotoxins. These may also be injected hot or cold or at room temperature. The use of distilled water, hypotonic saline or hypertonic saline with injection volumes less than 1ml eliminates one step in the use of INAS, as small volumes of these fluids should be harmless to the kidneys, and therefore the need to completely flush the ablative fluid from INAS with saline is no longer required to prevent any of the ablative fluid from entering the renal arteries during catheter withdrawal. This means that if more toxic ablative fluid is used, there is only one fluid injection step per artery, rather than two steps.

The present invention also contemplates the use of an anesthetic, such as lidocaine, which can reduce or eliminate any pain associated with denervation procedures if injected first or in or along with the ablative solution.

It is also contemplated that imaging techniques such as multi-slice helical CT scanning, MRI, intravascular ultrasound, or optical coherence tomography may be utilized to obtain an exact measurement of the thickness and anatomy of the target vessel wall (e.g., renal artery) so that the exact and correct penetration depth for injecting the ablation agent can be known and set prior to advancing the injection needle or tube. Use of IVUS prior to use of INAS may be particularly useful in order to target the exact depth intended for injection. This exact depth can then be targeted using the adjustable penetration depth of the features in our preferred embodiment or embodiments. The selection of the penetration depth may be accomplished using the proximal section/handle, or by selecting a suitable product code for other designs, which may have two to five forms each with different penetration depth limits.

For use in the treatment of hypertension or CHF via renal sympathetic nerve ablation, a presently preferred guide tube embodiment of the INAS of the present invention will be used with the following steps:

1. the patient is sedated in a manner similar to interalcoholic ablation, such as general purpose (Versed) analgesics and narcotic analgesics.

2. The first renal artery is engaged with a guide catheter placed through the femoral or radial artery using standard arterial access.

3. After flushing all lumens of the INAS, including the injection lumen, with saline, the INAS distal end with the fixed distal wire is advanced into the guide catheter. The device is advanced through the guide catheter until the distal end of the guide catheter is at a desired location in the renal artery beyond the distal end of the guide catheter.

4. Pulling back the sheath allows the expandable guide tube to open until the distal end of the guide tube presses outward against the inner wall of the renal artery. This can be confirmed by visualization of the radiopaque tip of the guide tube.

5. Next, a radiopaque syringe/needle is advanced coaxially through the guide tube to penetrate through the Internal Elastic Lamina (IEL) into the vessel wall of the renal artery at a preset distance beyond the IEL (typically 0.5-4mm, but preferably about 2-3 mm). Ideally, a very small gauge injection needle may be advanced to a depth of-2-3 mm into the renal artery to deliver one or more nerve ablation agents at or deep within the adventitia plane in order to minimize intimal and media renal artery damage. The correct depth can be determined prior to INAS treatment using CT scanning, MRI, OCT, or intravascular ultrasound to measure renal artery wall thickness so that the correct starting depth setting for injection tube penetration is known prior to advancing the needle.

6. A suitable volume of nerve ablation fluid, such as ethanol (ethyl alcohol), distilled water, hypertonic saline, hypotonic saline, phenol, glycerol, lidocaine, bupivacaine, tetracaine, benzocaine, guanethidine, botulinum toxin, or other suitable neurotoxic fluid, is injected. This may include a combination of 2 or more nerve ablation fluids or local anesthetics together or in sequence (local anesthetic first reducing discomfort followed by delivery of ablation agent) and/or a high temperature fluid (or vapor), or an extremely cold (cryoablation) fluid into the vessel wall and/or into the volume just outside the vessel. Typically, injections will be 0.1-5 ml. This should create multiple ablation zones (one for each syringe/needle) that will intersect to form an ablation ring around the circumference of the target vessel. Contrast agents may be added to the injection during a test injection prior to the nerve ablation agent or during a treatment injection to allow x-ray visualization of the ablation zone.

7. Sufficient saline solution to completely flush the ablation agent out of the INAS injection lumen (dead lumen) is injected into the INAS. This prevents any of the ablative agent from accidentally entering the renal artery during needle retraction into the INAS. Such accidental discharge into the renal artery can cause damage to the kidney. This step can be avoided if distilled water, hypotonic or hypertonic saline is used as the ablative fluid.

8. The INAS syringe/needle is retracted inside the guide tube. The guide tube is then re-retracted and re-advanced into the sheath by advancing the sheath over the guide tube. This causes the guide tube to fold back under the sheath completely around the sharp needle. The entire INAS may then be pulled back into the guide catheter.

9. In some cases, the INAS may be rotated 20-90 degrees, or repositioned 0.2-5cm distal or proximal to the first injection site, and then repeated as needed to prepare a second ring or even more definitive ablating loops.

10. The same method as according to the previous steps can be repeated to ablate the tissue in the contralateral renal artery.

11. The INAS is completely removed from the guide catheter.

12. All remaining instruments are removed from the body.

13. A similar approach may be used for INAS, via trans-ventricular septal access into the left atrium to treat AF, via tissue ablation in the vessel wall of one or more pulmonary veins. When instructed, a suitable diagnostic electrophysiology catheter is advanced to confirm that ablation (in the case of atrial fibrillation) has been successful.

It is also contemplated that a syringe may be secured with needles to the outer surface of the expandable balloon on the INAS for delivering 2 or more needles into the vessel wall of the target vessel for injection of the ablative fluid.

While the primary embodiment of the present invention utilizes three or more needle injection sites to circumferentially apply alcohol or one or more other neurotoxic fluids to or deep within the renal artery wall for sympathetic nerve ablation, it is also contemplated that other modifications of this concept can be used to achieve the same result. In one case, it is contemplated that a circumferentially based fluid (ethanol or other ablative fluid, a combination of ablative fluids, or a heating fluid) may be applied to the "ring segment" of the renal artery in a circumferential manner by injecting the ablative fluid into the space between two inflatable balloons. Thus, after inflation of the proximal and distal occlusion balloons, an ablative fluid is injected into the space between the two inflated balloons and allowed to dwell for a short period of time, allowing the fluid, e.g., ethanol, to penetrate through the arterial wall and reach the adventitia layer, thus destroying and ablating sympathetic nerves running in this space. After the dwell period, the space may be flushed with saline and the balloon deflated.

Similarly, a single balloon with a small diameter near the middle of the balloon may function in the same manner, i.e., ethanol or other ablative fluid, or a combination of ablative fluids, or a heated fluid is injected into a "saddle-like" space in the central portion of the balloon that does not contact the arterial wall.

It is also contemplated that another embodiment may include a circumferential polymer, hydrogel or other carrier strip on the central portion of the inflatable balloon, wherein the carrier contains one or more neurotoxin agents such as alcohols, phenols, glycerol, lidocaine, bupivacaine, tetracaine, benzocaine, guanethidine, botulinum toxin, and the like. The balloon is inflatable at a relatively low pressure to oppose the intimal surface of the renal artery wall, and is inflated for a dwell time to allow circumferential penetration of the neurotoxin agent into the "loop segment" of the renal artery and to allow sympathetic nerve fiber ablation to operate near or in the adventitial plane.

It is also contemplated that the INAS catheter may be connected to a source of heated fluid or vapor to deliver a high temperature fluid to ablate or damage target tissue or nerves. The heating fluid may be saline, a hypertonic fluid, a hypotonic fluid alcohol, phenol, lidocaine, or some other fluid combination. Steam injection of saline, hypertonic saline, hypotonic saline, ethanol or distilled water or other fluid through the needle may also be performed in order to achieve thermal ablation of the target tissue or nerves at and around the needle injection site.

It is also contemplated that INAS may utilize a very small diameter needle syringe (e.g., 25-35 gauge) having a sharp needle at its distal end, such that one or more penetration limiting members or a combination of guide tubes and adjustable depth advancement of the syringe through the guide tube are used in order to set the penetration depth, advance the needle to or even through the adventitial plane of the renal artery or aortic wall, and allow the sympathetic-containing adventitial layer to be "soaked" with the neurotoxic fluid while causing minimal damage to the intimal and media vessel wall layers. These very fine needles can pass through the wall of the artery, still creating such small holes in the artery wall that blood leakage from the lumen to the outside of the vessel and media damage will be minimal and therefore safe. Thus, the present invention may have an injection into the wall of the renal artery, into the adventitia of the renal artery, or deep in the adventitial layer (periadventitial) of the renal artery, such that injection needle or outflow from the injection tube occurs via penetration all the way through the artery wall, to allow ablative fluid to flow around the artery and be "soaked" outside the artery with one or more neuroablative substances.

Another embodiment may include two or more holes on the outer surface of the central portion of the inflatable balloon, or small metal (very short) needles such as protrusions, in fluid communication with the injection lumen to allow injection into the wall of the renal artery and circumferential delivery of the neurotoxin agent(s). Other similar techniques may be envisioned in view of these teachings and the description of the embodiments to allow for other variations on this concept of a balloon expandable, circumferential ablation system for renal artery sympathetic nerve ablation.

As described in the methods above, the preferred embodiment of the present invention places a tool that limits penetration of the vessel wall at the proximal end of the INAS. In this embodiment, at least three guide tubes with expandable distal portions run along the distal portion of the length of the INAS. A guide tube control mechanism with an optional flush port is attached to the proximal end of the INAS and controls longitudinal movement of the guide tube.

One for each guide tube, with the syringe having a sharpened (coring or cutting needle) distal end with one or more injection outlet ports at or just proximal to the needle tip. The injection tube is coaxially located inside the guide tube. The distal end of the sharpened injection needle at the distal end of the injection tube is initially just "proximal" to the distal end of the guide tube. The proximal syringe control mechanism is attached to the proximal end of the syringe or, in a preferred embodiment, to the proximal end of a single syringe connected to multiple syringes by a connecting manifold. The syringe control mechanism, when advanced, advances the needle away from the distal end of the guide tube to a desired penetration depth. One example of how penetration is limited by the INAS proximal section is to have a syringe control mechanism at its distal end separate from the proximal end of the guide tube control mechanism, creating a needle advancement gap. The syringe control mechanism may have a means to adjust the needle advancement gap distance. Alternatively, the adjustment may be on the guide tube control mechanism or on a separate mechanism between the syringe handle and the guide tube handle. A fitting for injecting ablative fluid is attached near the proximal end of the INAS and is in fluid communication with the injection lumen of the injection tube.

The sheath is located outside the guide tube, which constrains it, in its initial configuration. The proximal end of the sheath is attached to a sheath handle that can be locked down to prevent longitudinal movement relative to the guide tube, or unlocked to allow the sheath to move in a proximal or distal direction to open and close the INAS.

The procedure for using the INAS proximal section is to flush each lumen in the INAS with saline. The distal end of the INAS is then advanced through the guide catheter into a blood vessel, such as a renal artery. The sheath control handle is then pulled back, holding the guide tube handle in place. This will allow the distal portion of the guide tube to expand outwardly against the wall of a vessel, such as a renal artery. Optionally, after the sheath is pulled back, the guide tubes can then be pushed forward gently using the guide tube handle to ensure their firm engagement against the vessel wall. The syringe handle is then advanced so as to push the distal end of the syringe with the sharpened injection needle away from the distal end of the guide tube, which contacts the interior of the vessel wall. The needle will penetrate into the tunica media of the vessel wall. Depending on the advancement gap, penetration of the needle into the vessel wall may be limited. Depending on the number and location of injection outlet ports, this may allow for selective injection through the injection outlet port of the needle into the media, adventitia, exterior of the adventitia (around the adventitia), or any combination of these. After the needle is properly placed within or through the vessel wall, a source of ablative fluid, such as ethanol, is attached to a fitting in the injection tube handle and fluid is injected through a lumen inside the injection tube and out through an injection outlet port into the tissue.

After the injection is complete, the syringe handle is pulled back to retract the needle into the distal portion of the guide tube. The sheath control handle is then advanced to collapse the guide tube and close the INAS. The sheath control handle is then locked down to prevent inadvertent opening of the INAS. The INAS is then pulled back onto the guide catheter and the same procedure can be repeated for the other renal arteries.

In a preferred embodiment, the proximal section of the INAS has a handle that includes a sheath control mechanism, a guide tube control mechanism, and a syringe control mechanism. This preferred embodiment has two moving sections. A first movement section attached to the sheath control mechanism moves the sheath relative to the guide tube and a second movement section moves the syringe relative to the guide tube. Each of these moving sections desirably also has a locking mechanism to prevent movement. Furthermore, it is envisaged that there will be an interlock between the two movement sections such that the needle cannot be advanced unless the guide tube is deployed and expanded outwardly, and a second interlock preventing the sheath from closing unless the needle has been retracted proximally into the guide tube. The lock/unlock mechanism may be a push button that is depressed to unlock and release to lock, or a rotating ring that is twisted in one direction to lock and twisted in the other direction to unlock.

The preferred embodiment will use the following push button switch mechanism. A button on a first moving section attached to a sheath control mechanism is depressed. This unlocks its movement relative to the guide tube control mechanism. This first movement section is pulled up proximally while the rest of the handle remains stationary. This will pull the sheath in a proximal direction relative to the guide tube, allowing the guide tube to expand outward against the interior of the renal artery. Releasing the button locks the sheath control mechanism to the guide tube control mechanism in the sheath open position, releasing the interlock that prevents advancement of the syringe control mechanism.

Pressing a button on a second movement section attached to the syringe control mechanism unlocks movement of the syringe control mechanism relative to the guide tube control mechanism. The advancing injection tube control mechanism pushes the injection tube with the sharp needle out, through the distal end of the guide tube and into the vessel wall. The button is released, locking the syringe control mechanism to the guide tube control mechanism. In this configuration, the interlock will prevent the first displacement section from being able to advance the sheath relative to the guide tube upon needle deployment. After injection of the ablation material and flushing of the INAS with saline, the two steps were reversed. The button on the second movement section is now depressed and the syringe and needle are retracted proximally into the guide tube. The release button locks the syringe control mechanism relative to the guide tube control mechanism and releases an interlock that prevents the sheath from closing.

The button on the first displacement section can now be depressed and the sheath control mechanism advanced distally relative to the guide tube control mechanism, closing the INAS, and the guide tube is now retracted under the sheath.

In another embodiment, the second movement section is attached to the guide tube control mechanism and the syringe control mechanism is the third movement section. Here, the second movement section only unlocks the syringe control mechanism and the guide tube control mechanism, and the syringe control mechanism is a mechanism that is pushed distally to advance a syringe having a sharp injection needle.

While a push button is described above, a ring that rotates to lock and unlock the relative movement of the control mechanism is also contemplated.

The radiopacity of a particular portion of the catheter is critical to the use of INAS. Ideally, the fixation lead at the distal end of the INAS is radiopaque. This will also be at one or more of the following radiopaque markers: at the distal end of the sheath, on the proximal portion of the distal tip (obturator) of the INAS that is closed to the distal end of the sheath, at the end of each guide tube and the distal end or the entire length of each syringe/needle. A metal ring of tungsten, tantalum, gold or platinum may be used, or a radiopaque plastic formed from a dense material such as barium or tungsten fill may be used. The injection needle may have a needle or needle tip plated with a radiopaque metal, or if a coring needle, a sharp radiopaque plug in the distal end of the needle may be used. It is also contemplated that radiopaque wires may be placed inside the injection needle to enhance radiopacity. For example, platinum or gold wires having a smaller diameter than the needle lumens may be secured inside each needle lumen.

Thus, in deploying the INAS, the markings on the sheath and distal tip will separate to show the sheath's retraction. The marked ends of the guide tubes will then clearly show that they are separated and touching the inside of the vessel. When advanced, the syringe/needle is visible when extending beyond the distal end of the guide tube and clearly deep within the vessel lumen, which is visible with the contrast injection using the guide catheter. It is envisaged that fluoroscopy performed at 90 degrees to the INAS distal portion may unambiguously display the following markers from the centre to the outside:

radiopaque Ring marking the distal end of the sheath

Radiopaque markers outside the ring, at the end of the guide tube

A distal portion of the injection needle extending outwardly through the vessel wall, outside the radiopaque marker, beyond the distal tip of each guide tube.

While it is contemplated that there may be a number of from one to 8 syringes/needles within the 8 guide tubes, it is possible that 2,3 or 4 tubes are optimal for circumferential tissue ablation.

Another important feature of the INAS of the present invention is the design to reduce the internal volume of the INAS "dead space" to minimize the amount of saline required to flush the ablative fluid out of the catheter into the desired tissue volume. It is expected that less than 1ml of ablative fluid, such as ethanol, will be required to perform PVRD. The dead space should be less than 1ml, better still less than 0.5ml and ideally less than 0.2 ml. With certain design features, it is contemplated that the dead space can be reduced to less than 0.1 ml. Such features include the use of small diameter <0.5mm ID hypotubes for the inner tube for fluid injection of INAS, including volume occupying structures such as wires placed within the full length of the hypotube/inner tube to reduce the volume of the hypotube and hence the INAS dead space, and/or by having a small <0.5mm inner diameter and short <2cm length, designing a proximal injection port and or injection manifold with a small volume at the proximal end of the INAS. One technique contemplated to reduce the dead space inside the INAS injection lumen is to have wires inside one or more of the lumens to occupy volume.

While the guide tube embodiments will work well to allow the use of small diameter needles that minimize blood loss potential, other designs are contemplated, including:

a small diameter syringe/needle with a removable stylet that will provide enhanced radiopacity and/or structural strength to allow the forming tube/needle to be properly bent outward and penetrate the vessel wall.

Small diameter needle inserted into the distal end of a larger diameter pre-formed plastic or metal syringe

It is therefore an object of the INAS of the present invention to have a percutaneously delivered catheter that can be used to treat atrial fibrillation with one or more injections of ablative fluid into the vessel wall of the pulmonary vein near the ostium, or into the left atrial tissue surrounding one or more of the pulmonary veins.

It is another object of the INAS of the present invention to have a percutaneously delivered catheter that can be used to treat hypertension with one or more injections of ablative fluid into or deep within the vessel wall of the renal artery, or within the aortic wall surrounding the ostium of the renal artery.

It is another object of the INAS of the present invention to facilitate the injection of ablative fluid into or beyond the outer layers of the renal arteries to reduce or prevent damage to the inner layers, including the media of the renal arteries.

It is another object of the INAS of the present invention to have a design with a limited dead space of less than 0.2ml and ideally less than 0.1 ml.

It is another object of the present invention to have a two injection step method for renal denervation wherein the catheter is filled with saline prior to insertion into the body, followed by a first injection of an ablative fluid (e.g., ethanol) after needle deployment, followed by a second step of flushing all of the ablative fluid out of the catheter with saline or similar fluid that is not toxic to the kidneys. INAS was closed and the same two injection steps were used for the other renal arteries.

It is a further object of the present invention to utilize distilled water, hypertonic or hypotonic fluids as the ablation fluid of choice. This can reduce the injection of ablative fluid to one injection per renal artery (one step) and shorten the procedure.

It is a further object of the INAS of the present invention to have a percutaneously deliverable catheter that includes a plurality of circumferentially expandable injection tubes, each tube having a needle with an injection outlet at its distal end, allowing ablative fluid to be delivered into the targeted vessel wall or into a space beyond the vessel wall.

It is a further object of the present invention to have a flexible penetration limiting member or tool attached just proximal to the distal end of each injection needle, or a relatively blunt tipped guide tube, to limit the depth of the needle into or just through the vessel wall.

It is another object of the present invention to have a sheath that provides the open and closed positions of the INAS in combination with the distal tip. The closed position has the sheath and distal tip in such contact as to fully enclose the sharp needle, while the open position allows the needle to expand outwardly for injecting ablative fluid into or deep within the vessel wall.

It is a further object of the present invention to use heated or cooled ablative fluids, such as heated or cooled saline, as a source of tissue ablation, or to enhance the efficacy of already ablated fluids, such as ethanol.

It is a further object of the INAS of the present invention to have one or more of the injection needles act as diagnostic electrodes for measuring electrical activity within the target vessel wall.

It is a further object of the present invention to use a plurality of coaxially guided syringes that are slidably movable within a respective expandable guide tube to allow safe, controlled and adjustable depth passage of the syringe having a sharp needle at its distal end into and/or through the targeted vessel wall to allow controlled chemical ablation of nerves in the adventitia or periadventitial layer of an artery while minimizing intimal and media damage to the artery.

It is a further object of the present invention to provide for the injection of anesthetic prior to or during the injection of the ablative fluid in order to prevent or reduce any pain associated with denervation procedures.

It is a further object of the present invention to include one or more of the radiopaque markers described below to assist in locating, opening, closing and using the INAS. These include the following:

radiopaque Ring marking the distal end of the sheath

Radiopaque markers at the tip of the guide tube, metal strips or plastics with radiopaque fillers such as barium or tungsten

Radiopaque markers on the distal part of the injection needle

Radiopaque wires inside the lumen of the injection tube and/or needle

Outer layer of radiopaque marker or fixation wire

These and other objects and advantages of the present invention will become apparent to those skilled in the art upon a reading of the detailed description of the invention, including the drawings.

Drawings

Fig. 1 is a longitudinal cross-sectional view of a distal portion of a vascular nerve ablation system (INAS) of the present invention having a fixed lead at its distal end.

Fig. 2 is a schematic view of the distal portion of the INAS in its closed position when the INAS is configured for delivery into the body or covering the injection needle during removal from the body.

Fig. 3 is a schematic illustration of the distal portion of the INAS in its open position when the INAS is configured for delivery of an ablation solution into a target vessel wall.

Fig. 4 is a longitudinal cross-sectional view of the proximal end of the anchor wire embodiment of the INAS of fig. 1 to 3.

Fig. 5A is a schematic view of the distal portion of the closure INAS of fig. 2 as the INAS is first advanced out of the guide catheter into the renal artery.

Fig. 5B is a schematic view of the distal portion of the closed INAS when the sheath is pulled back to allow the expandable tube to open to the renal artery wall distal to the ostium.

Fig. 5C is a schematic view of the distal portion of the fully open INAS of fig. 3 with the needle fully embedded within the renal artery wall to allow infusion of the ablative substance into the vessel wall.

Fig. 5D is a schematic view of the distal portion of the INAS being closed when it is pulled back into the sheath to close the INAS, or for subsequent use in other renal arteries or for removal from the body.

Fig. 5E is a schematic view of the distal portion of the closed INAS of fig. 2 when the INAS has been closed by retraction of the distal portion of the INAS into the sheath, or for subsequent use in other renal arteries or for removal from the body.

Fig. 6 is a longitudinal cross-sectional view of an embodiment of an INAS delivered over a separate guidewire.

Fig. 7 is a longitudinal cross-sectional view of the proximal end of the inline embodiment of the INAS of fig. 6.

Fig. 8 is a longitudinal cross-sectional view of a syringe capable of delivering a heated ablative solution into the INAS of fig. 1-4.

Fig. 9 is a longitudinal cross-sectional view of the proximal section of the injection needle showing the longitudinal weld line penetrating the limiting member.

Fig. 10 is a longitudinal cross-sectional view of the proximal section of another embodiment of the present invention circumferentially delivering ablative fluid to the interior of a target vessel.

Fig. 11 is a longitudinal cross-section of another embodiment of the INAS of the present invention in its closed position, the INAS having four injection tubes slidable within four guide tubes. The syringes have a spike needle with an injection outlet port at the distal end of each syringe.

FIG. 12 is an enlargement of region S12 of FIG. 11 showing the distal portions of the syringe and guide tube.

Fig. 13 is a circumferential cross-section at S13-S13 of the INAS of fig. 11.

Fig. 14 is a longitudinal cross-section of the expanded distal portion of INAS.

Fig. 15 is an enlargement of the region S15 of fig. 14.

Fig. 16 is a longitudinal cross-section of the INAS proximal end of fig. 11-15.

Fig. 17 is an enlargement of the region S17 of fig. 16.

Fig. 18 is an enlargement of the region S18 of fig. 16.

Figure 19 is a longitudinal cross-section of an alternative embodiment of all but the distal portion of an INAS using multiple guide tubes.

Fig. 20 is a longitudinal cross-section of a central transition portion connecting the INAS proximal portion of fig. 19 with the INAS distal portion of fig. 11-14.

Fig. 21 is a circumferential cross-section at S21-S21 of the INAS central transition portion of fig. 20.

Fig. 22 is a circumferential cross-section at S22-S22 of the INAS central transition portion of fig. 20.

Fig. 23 is a circumferential cross-section at S23-S23 of the INAS central transition portion of fig. 20.

FIG. 24 is a longitudinal cross-section of the proximal end of an alternative embodiment of an INAS having a coring needle with a radiopaque wire within its lumen to provide visualization of the needle upon deployment.

FIG. 25A is a longitudinal cross-section showing an enlargement of the guide tube of the INAS of FIG. 24 and the distal portion of the coring needle.

Fig. 25B is an alternative embodiment of the distal section S25 of the INAS of fig. 24 having the same structure as fig. 25A with respect to the injection tube, but with a metal band as the radiopaque marker for the guide tube.

Fig. 26 is a schematic view of an embodiment of an INAS proximal portion having a locking mechanism activated by a depressible button.

FIG. 27 is a schematic view of a needle section of another embodiment of the INAS of the present invention having a core formed of three strands and a non-circular cross-section guide tube.

Fig. 28 is a central portion of the cross-section at S28-S28 of the INAS of fig. 27.

Fig. 29 is a schematic view of a distal portion of another embodiment of an INAS having a stranded core wire with a circular cross-section guide tube.

Fig. 30 is a schematic view of the interior portion of the INAS, which explicitly shows the proximal end of a radiopaque wire that runs the length of the syringe to provide radiopacity.

Fig. 31 is a cross-section at S31-S31 of fig. 30.

Fig. 32A is a schematic view of an embodiment of an INAS distal portion having a non-circular guide tube.

Figure 32B is a tip on a schematic showing the guide tube of figure 30A.

Fig. 33 is a schematic view of an alternative embodiment of an INAS handle that uses rotation of a member to lock and unlock motion between moving sections.

FIG. 34 is a schematic view of a guide tube and injection tube of another embodiment of the INAS of the present invention having three guide tubes separate from the main lead body.

Fig. 35 is a schematic view of another embodiment of an INAS of the present invention having a syringe with a distal needle having an injection outlet port.

Fig. 36A is a longitudinal cross-sectional view of another embodiment of the distal portion of the injection needle.

Fig. 36B is a longitudinal cross-sectional view of another embodiment of a distal portion of a plastic syringe having an injection needle inserted into a distal end thereof.

Fig. 36C is a longitudinal cross-sectional view of another embodiment of a distal portion of a metal syringe having an injection needle inserted into a distal end thereof.

Detailed Description

Fig. 1 is a longitudinal cross-sectional view of the distal portion of a vascular nerve ablation system (INAS)10 of the present invention, the distal portion of the INAS10 having a fixed lead 25 with a tip 28 at its distal end. Fig. 1 shows the INAS10 in its fully open position, the INAS10 having a self-expanding syringe 15, the self-expanding syringe 15 having a sharpened distal end to form an injection needle 19 that opens to its maximum diameter. The flexible wire tether 13 with the adhesive 14, which attaches the tether 13 to the injection tube 15, acts as a penetration limiting member to prevent the distal tip of the needle 19 from penetrating beyond the maximum distance L into the vessel wall. The syringe may be made of any elastomeric material, with the preferred material being NITINOL. If the tube is self-expanding to achieve the same purpose, a separate spring or inflatable balloon may be placed inside the syringe tube. The balloon can push the needle into the vessel wall with great force while increasing the system diameter.

Sheath 12 with radiopaque marker 27 is shown in fig. 1 in which it has been pulled back to allow full expansion of syringe 15. There are 4 syringes 15 in this embodiment of INAS10, although as few as2 and as many as 12 syringes 15 are contemplated. The distance L may be between 0.2 and 2mm, with about 1mm being most preferred.

The distal section 20 of the INAS10 includes a distal line 25, a tapered flexible tip 26, radiopaque markers 24, and a sheath engagement section 22, the sheath engagement section 22 ensuring that the distal portion of the INAS10 will be properly pulled back into the sheath 12 after the INAS10 is used to ablate tissue in a human blood vessel. The INAS10 is completely closed when the two radiopaque markers 27 and 24 are in close proximity to each other. This provides a visual indication during fluoroscopy.

The proximal end of the injection tube 15 is held by a manifold 17, which manifold 17 is attached to the outer tube 16 and to the interior of the distal end of the core wire 11. The proximal end of outer tube 16 is attached to hypotube 18, which hypotube 18 continues to the proximal end of INAS 10. The hypotube 18 is typically made of a metal, such as 316 stainless steel, and the outer tube 16 is made of plastic or metal reinforced plastic, such that it is flexible enough to allow the INAS to be easily advanced and retracted around bends in typical guide catheters, such as those used for angioplasty of the renal arteries or stents. The outer tube 16 is typically 5-30cm long, although it is also contemplated that the INAS10 could be designed without the hypotube 18 and with a plastic or metal reinforced plastic outer tube 16 running only to the proximal end.

The core wire 11 is attached to the inside of the hypotube 18 at a connection point 23. This attachment may be, for example, by adhesion, welding or brazing. Spot welding is the preferred method. In this way, the core wire 11 supporting the fixing wire 25 can be easily detached from the INAS 10. An injection lumen 21 inside the hypotube 18 is connected to the lumen of the outer tube 16, which lumen of the outer tube 16 is in fluid communication with the injection lumen 29 of each of the expandable tubes 15, allowing ablative material or solution to flow from the proximal end of the INAS10, through the hypotube 18, through the outer tube 16, through the expandable injection tube 16, and out the sharpened injection needle 19 into the vessel wall.

Fig. 2 is a schematic view of the distal portion of INAS10 'in its closed position when INAS10' is configured for delivery into the body or covering injection needle 19 during removal from the body. INAS10' includes a stationary wire 25 having a tip 28, a core wire 11, an outer tube 16, and a sheath 12. In this configuration, the two radiopaque markers 27 and 24 are adjacent to each other with the sheath 12 advanced to its fully distal position. Of great significance in this design is: in the closed position, the sharp needle 19 is fully encapsulated by the sheath 12, said sheath 12 closing on the proximal portion of the tapered tip 26.

Fig. 3 is a schematic view of the distal portion of the inventive Intravascular Nerve Ablation System (INAS)10 in its fully open position, the distal portion of the INAS10 having a fixed lead 25 with a tip 28 at the distal end of the fixed lead 25. Fig. 3 shows the INAS10 in its fully open position, the INAS10 having a self-expanding syringe 15, the self-expanding syringe 15 having a sharpened distal end to form an injection needle 19 that opens to its maximum diameter. The flexible wire tether 13 with the adhesive 14 attaching the tether 13 to the injection tube 15 acts as a penetration limiting member to prevent the distal tip of the needle 19 from penetrating beyond the maximum distance L shown in fig. 1 and 3 into the vessel wall.

Sheath 12 with radiopaque marker 27 is shown in fig. 3 in which it has been pulled back to allow full expansion of syringe 15. There are 4 syringes 15 in this embodiment of INAS. The distal section 20 of the INAS10 includes a fixed distal line 25, a tapered flexible tip 26, radiopaque markers 24, and a sheath engaging section 22, the sheath engaging section 22 ensuring that the distal portion will be properly pulled back into the sheath 12 after the INAS10 is used to ablate tissue in a human blood vessel. Also shown in FIG. 3 is outer tube 16 having an injection lumen 21 and a core wire 11.

Fig. 4 is a longitudinal cross-sectional view of the proximal end of the fixation wire embodiment of INAS10 of fig. 1-3. The hypotube 18 with injection lumen 21 also shown in fig. 1 has a luer fitting 35 with a lumen 36 attached to its proximal end, allowing a solution of a source of ablative substance to be injected through the lumen 36 of the luer fitting 35, into the injection lumen 21 of the hypotube 18, and then out of the injection needle 19 of fig. 1-3. The proximal end of sheath 12 is attached to the distal end of figure i-boster fitting 30, which figure i-boster fitting 30 has handle 36, inner hub 33, washer 39 and O-ring 43. When the handle 36 is tightened by screwing it down onto the inner hub 33, the O-ring will compress the seal of the figure-boster fitting 30 against the hypotube 18. Side tube 31 with luer fitting 32 having lumen 34 is designed to allow flushing of lumen 38 between sheath 12 and the interior of hypotube 18 with saline prior to insertion of INAS10 into the body. Prior to insertion into the body, the wye-boster fitting 30 is secured to the hypotube 18 with the sheath 12 in its distal-most position and the INAS10' closed as shown in fig. 2. When the distal end of INAS10' is properly positioned in one of the renal arteries, the wye-boster fitting is loosened and handle 36 is pulled in a proximal direction while luer fitting 35 remains in place. This will open the INAS10 and allow the syringe 15 of fig. 1 to expand outwardly in the blood vessel.

Fig. 5A is a schematic illustration of the distal portion of the closure INAS10 'of fig. 2 when INAS10' is first advanced out of the guide catheter 80 into the renal artery just distal of the aortic orifice. The INAS10' is advanced up to the marker band 24 distal of the distal end of the guide catheter 80. It is expected that an optimal distance of 5-15mm distal will work best, although shorter and longer distances are possible depending on the geometry of the renal artery and the penetration distance of the guide catheter 80 into the renal artery ostium.

Fig. 5B is a schematic view of the distal portion of INAS10 "closed when sheath 12 is pulled back to allow expandable tube 15 to open against the renal artery wall just distal of the ostium into the aorta. In this position, it is desirable that the angle A at which the distal end of the injection needle engages the interior of the vessel wall should be less than 80 degrees, and desirably between 40-60 degrees. If the angle is too large, the syringe can be snapped back instead of pushing the sharp needle into the vessel wall. If the angle is too small, the needle may not penetrate properly and may slide distally along the interior of the vessel wall. After sheath 12 is pulled back so that it no longer constrains expandable syringe 15, INAS10 "is then pushed in a distal direction, allowing syringe 15 to continue its outward expansion as injection needle 19 penetrates into the renal artery wall. When the cord 13 engages the renal artery wall, restricting penetration of the needle 19, penetration will stop. Alternatively, this "string" may be replaced by a nitinol wire structure that is resiliently attached to the injection tube 15 to provide a (stiffer) metal penetration limiting member.

Fig. 5C is a schematic view of the distal portion of the fully open INAS10 of fig. 3 with the needle 19 fully embedded within the wall of the renal artery to allow infusion of the ablative substance into the vessel wall. Although fig. 5C shows the cords 13 fully expanded, they are generally slightly smaller in diameter than their maximum diameter when they engage the wall of the renal artery to limit penetration of the needle 19. Preferably, the largest diameter of the INAS10 system selected for this procedure should be at least 2-4mm larger than the inner diameter of the renal artery. For example, if the renal artery diameter at the desired ablation site is 5mm in diameter, then INAS10 should be selected with a maximum diameter of 7-9 mm. In the configuration of fig. 5C, an ablative substance is injected through the needle 19 into the wall of the renal artery. The preferred ablative substance is ethyl alcohol (ethanol), which has historically been used to ablate tissue, preferably neural tissue in the cardiovascular system. Other agents such as phenol, glycerol, one or more local anesthetics such as lidocaine, guanethidine or other cytotoxic and/or neurotoxic agents are also contemplated as possible injectables (injectates).

Fig. 5D is a schematic view of the distal portion of INAS10 "closed when the distal portion of INAS10" is pulled back into sheath 12 to close INAS10", or for subsequent use in other renal arteries or for removal from the body. The shaded region shows an ablation zone 100 where tissue in the renal artery wall has been ablated. If the depth of penetration of the needle is set to a greater depth (e.g., 2.5-3 mm), the ablation zone may be deeper (primarily adventitia) and cause less damage to the intima and media layers of the renal artery wall than shown in fig. 5D.

Fig. 5E is a schematic illustration of the distal portion of the closed INAS10 'of fig. 2 when INAS10' has been closed by retraction of the distal portion of the INAS into sheath 12, or for subsequent use in other renal arteries or for removal from the body.

For this embodiment of INAS10, the method for hypertension would be the following steps:

1. the sterilized INAS10 was removed from its packaging to the sterile field, and the cavity 38 between the outer tube 12 and hypotube 18 was rinsed with saline.

2. Sheath 12 is advanced until INAS10' is in its closed position.

3. Lock the wye-boster fitting 30 down onto the hypotube 18 of figure 4.

4. Access to the aorta is via the femoral artery, typically with insertion of an introducer sheath.

5. The first targeted renal artery is engaged through the aorta using the guide catheter 80 of fig. 5A through 5E or a guide sheath having a sharpened distal end. This can be confirmed by injection with contrast media as required.

6. The distal end of INAS10 is placed within the proximal end of guide catheter 80 in its closed position of fig. 2. There is typically a wye-boster fitting attached to the distal end of the guide catheter 80 to restrict blood loss.

7. The closed INAS10 may be pushed through the open tuyeri-boster fitting into the guide catheter 80.

8. As shown in fig. 5A, the INAS10 is advanced through the guide catheter until the marker band 24 is distal of the distal end of the guide catheter within the renal artery.

9. Sheath 12 is pulled back in the proximal direction while luer fitting 35 and hypotube 18 proximal of INAS10 remain secured. This will allow the injection tube 15 to be directed against the wall of the renal artery as shown in fig. 5B.

10. Lock the wye-boster fitting 30 down onto the hypotube 18.

11. With the fig. iei-boster fitting at the proximal end of the guide catheter 80 released, the sheath 12 and hypotube 18 locked together are advanced, pushing the sharp needle 19 into or through the wall of the renal artery as the self-expanding injection tube 15 continues to expand outward. When penetration limiting member 13 engages the wall of the renal artery, thereby limiting the penetration of needle 19 to the desired depth, syringe 15 will stop penetrating.

12. A syringe or injection system providing the ablative fluid to be injected into the wall of the renal artery is attached to the luer fitting 35 of fig. 4.

13. An appropriate volume of ethanol (ethyl alcohol) or other suitable cytotoxic fluid, or a combination of nerve ablation fluids, or a heated fluid or vapor (e.g., a 90-95 degree heated saline solution) is injected from a syringe or injection system through the lumen 36 and out the needle 19 into the renal artery wall. A typical injection will be 0.3-5 ml. As shown by the ablation zones shown in fig. 5D and 5E, this should produce multiple intersecting ablation volumes (one for each needle) that should produce an annulus of ablated tissue around the circumference of the renal artery. The contrast agent and/or anesthetic agent, such as lidocaine, may be injected prior to or simultaneously with the ablative fluid. Saline may be used to flush nerve ablation fluid out of the inactive lumen prior to retraction of the syringe/needle.

14. Loosening the fig. y-boster fitting 30 and simultaneously holding the fig. y-boster fitting 30 and the sheath 12 stationary, pulls the luer 35 with the hypotube 18 in a proximal direction until the expandable tube 15 with the needle 19 is fully retracted within the distal end of the sheath 12 and the marker bands 27 and 25 abut one another. This is shown in fig. 5D and 5E.

15. In some cases, INAS10 may be advanced into the renal artery again, rotated between 20-90 degrees, and then the injection repeated to make even more volumetric ablations. It would be advantageous if the INAS10 had less than 4 syringes, and 4 syringes need not be shown herein.

16. The same method as according to steps 8-15 can be repeated to ablate the tissue around the other renal arteries during the same procedure.

17. The INAS10 in its closed position is removed from the guide catheter. In the closed position, the needle 19 is enclosed and cannot injure healthcare personnel or expose healthcare personnel to blood-borne pathogens.

18. All remaining instruments are removed from the body.

A similar method may be used with INAS10 to treat atrial fibrillation by inserting a guide catheter through the ventricular septum into the left atrium, where the wall of the target vessel is the wall of one of the pulmonary veins.

Fig. 6 is a longitudinal cross-sectional view of the distal portion of another embodiment of the vascular nerve ablation system (INAS)40 of the present invention, the INAS40 being delivered over a separate guidewire 60. Fig. 6 shows the INAS40 in its fully open position, the INAS40 having a self-expanding syringe 45, the self-expanding syringe 45 having a sharpened distal end to form a needle 49 that opens to its maximum diameter. The flexible cord 43 connects the syringe 45 and acts as a penetration limiting member to prevent the distal tip of the needle 49 from penetrating beyond the maximum distance D into the vessel wall. Unlike tether 13 of fig. 1, tether 43 enters a distance D from the distal end through a hole 57 in the sidewall of each syringe tube 45. A drop of adhesive (not shown) may be used to seal the hole and prevent the ablative substance or solution from leaking into the vessel wall during injection.

The sheath 42 is shown in the position in which it has been pulled back to allow full expansion of the syringe 45. There are 4 injection tubes 45 in this embodiment of the INAS40, although as few as2 and as many as 12 injection tubes 45 are contemplated. The distance D may be between 0.2 and 2mm, with about 0.5 to 1mm being most preferred.

The proximal end of the injection tube 45 is held by a manifold 47, which manifold 47 is attached to the interior of the distal ends of the outer tube 46 and the inner tube 48. An injection lumen 51 is located between inner tube 48 and outer tube 46 proximal to manifold 47. Ablation material injected through injection lumen 51 will flow into the proximal end of injection tube 45 and then exit injection needle 49, into one or more layers of the vessel and/or into the tissue volume just outside the vessel wall.

The distal section 50 of INAS40, which is coaxially attached to the distal section of inner tube 48, includes a tapered flexible tip 56, radiopaque markers 55, and a sheath engagement section 54, which sheath engagement section 54 ensures that the distal portion of INAS40 will be properly pulled back into sheath 42 after INAS40 is used to ablate tissue in the human vessel. The guidewire 60 may be advanced and retracted in a longitudinal direction inside the guidewire lumen 41, the guidewire lumen 41 being located inside the inner tube 48. INAS40 may be configured as an online or fast switching device. If on the wire, the guidewire lumen 41 inside the inner tube 48 runs all the way to the proximal end of the INAS40 as shown in FIG. 7. If a rapid exchange configuration is used, the wires would exit INAS40 and run outside of INAS40 for some portion of the length of INAS 40. If rapid exchange is used, a slot in sheath 42 is required to allow longitudinal movement of sheath 42 relative to the remainder of INAS 40. The proximal end of the rapid exchange configuration will be equal to the proximal end of the fixed wire INAS10 of fig. 4. For at least the most proximal 10cm, the guidewire generally runs outside the main body of INAS40, with the preferred embodiment having the guidewire exiting through the side wall of the outer tube 46 and the sheath 42 located 5-15cm from the distal end of INAS 40.

Fig. 7 is a longitudinal cross-sectional view of the proximal end 70 of the in-line embodiment of INAS40 of fig. 6. Inner tube 48 has luer fitting 78 attached to its proximal end. The guidewire 60 may be advanced through the guidewire lumen 41 inside the inner tube 48. The proximal end of outer tube 46 is attached to a hub 79, which hub 79 seals against inner tube 48, forming an injection lumen 51 between inner tube 48 and outer tube 46. A side tube 74 having a lumen 76 is connected into the hub 79 by a luer fitting 75, the luer fitting 75 being attached to the proximal end of the side tube 74. A syringe or other injection device may be attached to luer fitting 75 to inject the ablative substance or solution through lumen 76 into injection lumen 51, into injection tube 45 of fig. 6, and out the end of injection needle 49 into the vessel wall. The proximal end of the sheath 42 is connected to a hub 77, which hub 77 acts as a handle to slide the sheath 42 coaxially over the outer tube 46 to open and close the INAS40 of fig. 6. A side tube 72 having a lumen 73 is connected into the hub 77. Luer fitting 71 is attached to the proximal end of side tube 72 to allow flushing of lumen 62 between sheath 42 and outer tube 46 with saline solution prior to introduction of INAS40 into the human body. Although the hub 77 shown here is a plastic member, it is contemplated that a tuy-boster fitting, such as the tuy-boster fitting 30 of fig. 4, may be used herein, and may be advantageous because it allows the sheath 42 to be locked into position on the outer tube 46 during insertion and removal from the body, such that the distal end of the sheath 42 will remain in its distal-most position, protecting the injection needle 49 and protecting the health care provider from exposure to needle stick injuries.

Fig. 8 is a longitudinal cross-section of a single use syringe 90, the syringe 90 being for use in providing an ablative solution heated to a preset temperature for injection through the INAS10 of fig. 1-5C to ablate tissue in a human body. Syringe 90 includes a syringe 104 having a fluid storage volume 99 and a female luer fitting 93, the female luer fitting 93 typically being attached to a standard stopcock (not shown) that is connected to male luer fitting 35 at the proximal end of INAS10 of fig. 1-4. It is also contemplated that stopcock valve may be provided with or integrated into either injector 90 or INAS 10. The injector 104 is surrounded by a heating coil 94, the heating coil 94 being contained within a housing 95 filled with insulation 96. The power for the heating coil 94 comes from a battery 98 having a positive pole 91 and a negative pole 92 housed within a battery case 97. As shown in fig. 5C, the movable plug 101 with the handle 102 and distal sealing gasket 103 is used to inject the heated ablative fluid in the volume 99 through the luer fitting 93 into the INAS10 injection lumen 21 of fig. 4 where it then flows out through the injection needle 19 of fig. 1 and 3 and into the tissue. The injection lumen 90 may include a closed loop circuit with temperature display or one or more LEDs that let the user know when the ablative fluid in the injector 104 is at the desired temperature. The injection chamber 90 may be manufactured for a single preset temperature or may be adjusted to more than one temperature. While fig. 8 shows the injection plunger 101 being pushed by hand, it is also contemplated that a fluid pump or mechanical system to depress the plunger may be integrated into the injection lumen 90. The use of a heating fluid to ablate tissue may be effective by heating a normally benign substance such as saline to a point where heat causes tissue ablation, or heat may act to improve the ablation ability of fluids such as alcohol that typically ablate at room or body temperature.

Fig. 9 is a longitudinal cross-sectional view of the proximal section of injection needle 110, said injection needle 110 having a lumen 111 and a distal end 119, showing attached longitudinal memory wire penetration limiting members 114 and 116 having proximal portions 112 and 113, respectively. These proximal portions 112 and 113 are attached (glued, welded or brazed) to the exterior 115 of the needle such that when the needle 110 is released from inside the sheath 12 of fig. 1-4, the distal portions of the wires 114 and 116 will assume their memory state as shown in fig. 9, forming a means that will limit penetration of the needle tip 119 to about the preset distance L2. Because most arteries have a similar thickness, the distance L2 may be set to ensure that the ablative fluid injected through the needle lumen 111 will be present in the appropriate volume of tissue. The selection of a suitable volume may be set by different values of L2, such that the injection may be set in the media of the artery, the adventitia of the artery, or the exterior of the adventitia of the artery. Although two threads 114 and 116 are shown in fig. 9, one thread will also serve to limit penetration, or 3 or more threads may also be used. Ideally, one or more wires would be attached to the exterior of the needle 115 on the needle circumferential sidewall, rather than on the interior or exterior, where the wires 114 and 116 would increase the diameter of the closure INAS10 of fig. 1-4 before the sheath 12 is pulled back to deploy the needle.

It is also contemplated that injectors designed to deliver super-cooled ablative fluid into the INAS of fig. 1-4 are also suitable for the present application.

An important aspect of the present invention is the circumferential delivery of the ablation fluid relative to the vessel wall. Such delivery from one or more injection exit points must attack the nerve tissue circumferentially and at the correct depth to ensure efficacy, and ideally minimize damage to healthy and normal cellular structures of the intima and media layers. Circumferential delivery can be handled in three different ways as described above.

1. Injected into the vessel wall at three or more points around the circumference of the vessel.

2. Injection into the space outside the vessel wall-although this can be achieved with a single needle/exit point, this is best done with at least two exit points so that the needle can be kept small to allow the vessel wall to reseal upon needle retraction.

3. Injected into the interior to fill the annular gap and circumferentially deliver the ablative fluid to the inner surface of the vessel.

Fig. 10 is a schematic view of another embodiment of a proximal portion of an Intravascular Nerve Ablation System (INAS)200 of the present invention in its fully open position, the INAS200 having a fixed lead 225, the fixed lead 225 having a tip 228 at a distal end thereof. Fig. 10 shows the INAS200 in its fully open position, the INAS200 having a self-expanding syringe 215, the self-expanding syringe 215 having a sharpened distal end to form an injection needle 219 that opens to its maximum diameter. In this embodiment, the syringes 215 each have a double bend or bend 214, the double bend or bend 214 having a length L4 in the circumferential direction. The bend 214 acts as a penetration limiting member to prevent the distal tip of the needle 219 from penetrating beyond a maximum distance L3 into the vessel wall.

Sheath 212 with radiopaque marker 227 is shown in fig. 10 in which it has been retracted to allow full expansion of syringe 215. There are 3 syringes 215 in this embodiment of INAS. The distal section 220 of the INAS200 includes a fixed distal line 225, a tapered flexible tip 226, radiopaque markers 224, and a sheath engagement section 222, which sheath engagement section 222 ensures that the distal portion will be properly pulled back into the sheath 212 after the INAS200 is used to ablate tissue in a human blood vessel. Also shown in FIG. 10 is outer tube 216 having an injection lumen 221 and a core wire 211. The INAS200 of fig. 10 will be used in the same manner as INAS10 of fig. 1 to 5E, with the difference being the use of a bend (double bend) 214 as a penetration limiting member. In contrast to the penetration limiter of figures 1-5E, which is attached to a syringe, the bend 214 is integrated into the syringe 215. The added bend 214 should be a substance that provides a double bend in the shape of a memory metal (e.g., NITINOL) tubing used to form each of the syringes 215, the syringes 215 having sharp ends that form the injection needle 219. In this embodiment, the injection tube itself limits penetration into the wall of the target vessel. The process for forming and heat treating NITINOL pipes to set the memory is well known.

The use of INAS for ablating tissue in the human body has been discussed. It also has the advantage of being used for intravascular injection of any fluid or drug. The ability to limit the depth of penetration allows it to selectively inject any fluid into the media, adventitia, or exterior of the adventitia. It is also contemplated that the use of the dual-bend penetration limiting member concept of figure 10 may be applied to any application where it is desirable to inject fluid into human tissue at a preset distance.

The term circumferential delivery is defined herein as at least three points injected at the same time as spaced apart circumferentially within the vessel wall, or circumferential filling of the space outside the adventitia layer (outer wall) of the vessel.

Fig. 11 is a longitudinal cross-section of another embodiment of the INAS300 of the present invention in its closed position, the INAS300 having four injection tubes 316, the four injection tubes 316 being slidable within four guide tubes 315 having an expandable distal portion. The syringes 316 with sharp needles 319 have an injection outlet port 317 near the distal end of each syringe 316. A sheath 312 with a distal radiopaque marker band 327 encloses a guide tube 315 with a coaxial syringe 316. The syringe 316 has an injection lumen 321. The distal end of each of the injection tubes 329 is tapered to provide a surface that will be generally parallel to the vessel wall as the guide tubes 315 expand outward during deployment. A distal portion of guide tube 315 having a length L5 is set to an expanded memory shape and is constrained from expansion by sheath 312 as shown in FIG. 11. Four guide tubes 315 are not attached or connected to core wire 311 at distance L5. Proximal to distance L5, guide tube 315 is attached or connected to core wire 311, wherein the preferred embodiment is shown in fig. 13, wherein core wire 311 and four guide tubes 315 are embedded within plastic cylinder 305.

The INAS300 distal end has a tapered section 326 attached to a distal shapeable fixation wire 320, the fixation wire 320 having a wire wrap outer 325, a core wire 311, and a tip 328. The tapered section 326 includes radiopaque markers 324 and a proximal taper 323 to facilitate closure of the sheath 312 over the proximal section 323 after the INAS300 is deployed to inject ablative fluid into the vessel wall.

Fig. 12 is an enlargement of region S12 of INAS300 of fig. 11, showing guide tube 315 coaxially positioned within sheath 312. A distal portion of an injection tube 316 having a sharp needle 319, a lumen 321, and an injection outlet port 327 is positioned coaxially inside a distal portion of a guide tube 315 having a tapered distal end 329. All or a portion of the needle 319 or one or more entire syringes may be constructed of a radiopaque material such as tantalum, platinum, or gold. It is also contemplated that the tip of the needle may be coated or plated with a radiopaque material, such as gold, or a platinum insert placed within the distal tip of the syringe prior to sharpening the tip into the cutting needle. Also shown are the core wire 311 and the proximal section 323 of the tapered section 326. It is also contemplated that a distal portion including distal end 329 of guide tube 315 may also be made of, coated with, or plated with a radiopaque material, such as gold.

Fig. 13 is a circumferential cross-section at S13-S13 of the INAS300 of fig. 11, clearly showing four guide tubes 315 attached to the exterior of the core wire 31. An injection tube 316 having an injection lumen 321 is positioned coaxially inside the guide tube 315. The syringe 316 is free to slide in the longitudinal direction within the lumen of the guide tube 315. The injection tube 316 may also be formed from nitinol and pre-shaped to parallel the curved distal shape of the guide tube 315 to enhance coaxial movement of the injection tube 316 within the guide tube 315. Guide tube 315, syringe 316 and core wire 311 are coaxially located within sheath 312, which sheath 312 is free to slide over these portions. It is also shown how guide tube 315 and core wire 311 may be embedded in plastic 305 to better hold the parts together, or they may be attached by welding, brazing, or the use of an adhesive. The use of plastic 305 also allows for a cylindrical surface against which the proximal portion of sheath 312 can be sealed to allow flushing of the space between the interior of sheath 312 and the exterior of plastic 305 with saline before use of the device begins.

Fig. 14 is a longitudinal cross-section of the expanded distal portion of INAS300' in a fully open configuration, with injection tube 316 shown advanced beyond the distal end of guide tube 315. The distal end of the syringe 316 has a sharp needle 319, said sharp needle 319 having an injection outlet port 317.

In this configuration, sheath 312 has been pulled back to allow guide tube 315 to expand outwardly. Guide tube 315 is typically made of a memory metal such as NITINOL. The syringe 316 may be made of any metal, such as 316 surgical grade stainless steel, or may also be made of NITINOL or a radiopaque metal, such as tantalum or platinum. If the elements 315 and 316 are not made of radiopaque metal, it is contemplated that the distal portions of the one or more injection tubes 316 and the one or more guide tubes 315 will be coated with a radiopaque material, such as gold, typically at or near the distal end of the one or more tubes, or that a piece of radiopaque material may be used to form the sharp needle 319, or near the sharp needle 319 to be positioned at the distal end of the injection tube. Diameter L6 indicates a memory configuration for fully opened guide tube 315. For use in the renal arteries, L6 is typically 3-10mm, and if only one size is prepared, 8mm is the best configuration because few renal arteries are larger than 7mm in diameter. Also shown in fig. 14 is distal end 329 of guide tube 315, which is parallel to the longitudinal axis of INAS300' in a fully open configuration. The distal portion of the INAS300' has a tapered section 326 attached to a stationary lead 320, the stationary lead 320 having a tip 328, an outer layer 325, and a core wire 311.

FIG. 15 is an enlargement of region S15 of FIG. 14 in that it shows syringe 316 having lumen 321 and distal needle 319 fully advanced beyond distal end 329 of guide tube 315. Also shown in fig. 15 is an arterial wall having an Internal Elastic Lamina (IEL), a middle lamina, an External Elastic Lamina (EEL), and an external lamina. Fig. 14 shows injection outlet port 317 positioned in the epicardial heart.

An important feature of the INAS300 of the present invention is that the penetration depth with respect to injection through the injection outlet port can be adjusted such that any of the following can be achieved.

1. Injected into the mesomembrane.

2. Injected into the mesomembrane and the ectomembrane by placing one of the injection outflow holes in each.

3. Injected into the outer membrane as shown in figure 15,

4. injected into the outer membrane and a volume outside the outer membrane, and

5. only into the volume outside the outer membrane.

In particular, the distance L7 by which the tip of the needle 319 extends beyond the tip 329 of the guide tube 315 may be adjusted using an instrument in the proximal end of the INAS 300.

Fig. 16 is a longitudinal cross-section of the proximal end of the INAS300 of fig. 11-15. Three handles, a proximal injection handle 330, a central guide tube handle 340, and a distal sheath control handle 350 allow relative longitudinal movement of the sheath 312, guide tube 315, and injection tube 316. For the position shown in fig. 16 with the sheath control handle 350 in its proximal-most position, the proximal-most position will indicate that the sheath 312 has been fully retracted in the proximal direction, which will allow the guide tubes 315 to expand outwardly as shown in fig. 14. A gap having a distance L8 between the injection handle 330 and the guide tube handle 340 may be adjusted using a screw adjustment tab 334 having threads 335 that allow the screw adjustment tab 334 to move relative to the proximal portion 333 of the injection handle 330. The gap L8 as set will limit penetration of the needle 319 and injection outlet port 317 of the injection tube 316 into the wall of the target vessel. Desirably, a scale may be marked on the proximal portion 333 of the proximal injection handle 330 so that the medical practitioner can set the gap L8 and adjust the penetration distance accordingly. Luer fitting 338 with access tube 336 is a port for injecting ablative fluid into the handle central lumen 332, said handle central lumen 332 being in fluid communication with lumen 321 of injection tube 316.

Central guide tube handle 340 includes an outer portion 342, a sealing member 344, the sealing member 344 sealing the distal and outer portions 342 of core wire 311 and providing four holes through which four syringes 316 can be slid into the proximal end of guide tube 315. A luer fitting 348 with an access tube 346 provides access to the space between the syringe 316 and the guide tube 315 through a hole in the guide tube 347.

The distal sheath control handle 350 includes a distal portion 354, which distal portion 354 is attached to the exterior of the sheath 312 with a luer fitting 358 and side tubing 356, providing access to the lumen under the sheath 312 to allow the lumen to be flushed with saline before operation begins. The handle 350 also has a proximal portion 352 and a resilient washer 359, the resilient washer 359 is compressed by screwing the proximal portion 352 into the distal portion 354 to lock the position of the sheath 312 relative to the guide tube 315.

Fig. 17 is an enlargement of region S17 of fig. 16, showing injection handle 330 attached by proximal luer fitting 338 to side tube 336 having lumen 331. The proximal portion 333 seals against the exterior of the side tube 336 and also against the exterior of the four injection tubes 316. This seal may be by adhesive or by molding or forming a proximal tab on the tubes 336 and 316. Lumen 331 of side tube 336 is in fluid communication with central lumen 332 of proximal portion 333, which central lumen 332 is in fluid communication with lumen 321 of injection tube 316. Thus, ablation fluid injected through luer 338 will flow into lumen 321 of injection tube 316 and will emerge through injection outlet port 317 shown in fig. 15 in or near the target vessel wall. Threads 335 on both the proximal portion 333 of the injection handle 330 and the screw adjustment tab 334 allow for adjustment of the gap L8 of fig. 16. The gap L8 as set will limit penetration of the needle 319 and injection outlet port 317 of the injection tube 316 into the wall of the target vessel. Desirably, a scale may be marked on the proximal portion 333 of the injection handle 330 so that the medical practitioner can set the gap L8 and adjust the penetration distance accordingly.

Fig. 18 is an enlargement of region S18 of fig. 16, showing the central guide tube handle 340 and the sheath control handle 350.

Central guide tube handle 340 includes an outer portion 342, a sealing member 344, which sealing member 344 attaches guide tube 315 and a distal portion of core wire 311 to outer portion 342. The outer portion 342 seals against the plastic 305 in which the guide tube 315 and the core wire 311 are embedded. Proximal to the proximal end of the plastic 305, a luer fitting 348 (shown in fig. 15) with access tube 346 provides access to the space between the injection tube 316 and the guide tube 315 through a hole 347 in the guide tube 315.

The distal sheath control handle 350 includes a distal portion 354, which distal portion 354 is attached to the exterior of the sheath 312 with a luer fitting 358 (shown in fig. 15) and a side tube 356, providing access to the lumen between the sheath 312 and the plastic 305 to allow the lumen to be flushed with saline before operation begins. The handle 350 also has a proximal portion 352 and a resilient washer 359, the resilient washer 359 is compressed by screwing the proximal portion 352 into the distal portion 354 to lock the position of the sheath 312 on the plastic 305. In this locked position, in which the INAS300 is closed as shown in fig. 11, the INAS300 is advanced into the body until the distal end of the marker band 324 of fig. 11 is in the renal artery. The proximal portion 352 is then loosened so that the sheath control handle 350 may be pulled in the distal direction while the central guide tube handle 340 remains fixed. It is contemplated that when the proximal end of the sheath control handle proximal tab 352 contacts the distal end of the outer portion 342 of the guide tube handle 340 as shown in fig. 18, the sheath 312 will fully contract to allow the guide tube 315 to expand against the wall of the target vessel.

The full operation for renal denervation using INAS300 is as follows:

1. the sterilized INAS300 is removed from its packaging to the sterile field, the injection lumen 321 of the syringe is flushed with saline, and the space between the sheath 312 and plastic 305 and the syringe 316 and guide tube 315.

2. Access to the aorta is via the femoral artery, typically with insertion of an introducer sheath.

3. The first targeted renal artery is engaged through the aorta using the guide catheter 80 of fig. 5A through 5E or a guide sheath having a sharpened distal end. This can be confirmed by injection with contrast media as required.

4. The distal end of the INAS300 is placed within the proximal end of the guide catheter in its closed position of fig. 11. There is typically a wye-boster fitting attached to the distal end of the guide catheter 80 to restrict blood loss.

5. The closed INAS300 is then pushed through the open tuyeri-boster fitting into the guide catheter.

6. The INAS300 is advanced through the guide catheter until the marker band 324 is distal of the distal end of the guide catheter within the renal artery.

7. The sheath 312 is pulled back in the proximal direction while the guide tube handle 340 remains fixed. This will allow the injection tube 315 to be directed against the wall of the renal artery, as shown in fig. 15.

8. Locking sheath control handle 350 down onto plastic 305.

9. The figure-boster fitting at the proximal end of the guide catheter is locked down onto the sheath 312.

10. The guide tube handle 340 is advanced to ensure that the distal end 329 of the guide tube 315 is in good contact with the wall of the renal artery and flares outward to point more closely perpendicular to the long axis of the renal artery wall.

11. While holding the guide tube handle 340 stationary, the injection handle 330 is advanced until its distal end contacts the proximal end of the guide tube control handle 340. This will cause the needle 319 to be advanced through the distal end 329 of the guide tube 315 into the wall of the target vessel to a suitable penetration limited by the two handles 330 and 340 being contacted.

12. A syringe or injection system that provides the ablative fluid to be injected into the wall of the renal artery is attached to the luer fitting 338. An anesthetic such as lidocaine and/or contrast agent may optionally be injected prior to the ablation fluid to prevent or reduce pain associated with the procedure and/or to ensure that the needle is in place. It is also contemplated that anesthetic or contrast agents may be combined with the ablative fluid.

13. An appropriate volume of ablative fluid is injected from a syringe or injection system through lumen 321 of the injection tube and out of injection outlet port 317 into and/or outside the renal artery wall. Typical injections will be 1-10 ml. As shown by the ablation zones shown in fig. 5D and 5E, this should produce multiple intersecting ablation volumes (one for each needle) that should produce an annulus of ablated tissue around the circumference of the renal artery.

14. While holding the guide tube handle 340 stationary. Pulling the injection handle 330 in a proximal direction retracts the needle 319 into the guide tube 315.

15. Unlocking sheath control handle 350 from plastic 305 while retaining guide tube handle 340 stationary, advancing sheath control handle 350 in the distal direction until guide tube 315 is fully folded back into the distal end of sheath 312 and marker bands 327 and 324 abut one another, indicating that INAS300 is now in its closed position as shown in fig. 11.

16. The same method as according to steps 6-15 can be repeated to ablate the tissue around the other renal arteries during the same procedure.

17. The INAS300 is removed from the guide catheter in its closed position. In the closed position, the needle 319 is double enclosed within a guide tube 315, the guide tube 315 being inside the sheath 312, so that the sharp needle 319 cannot injure the healthcare worker, or expose the healthcare worker to blood-borne pathogens.

18. All remaining instruments are removed from the body.

A similar method may be used with INAS300 to treat atrial fibrillation by inserting a guide catheter through the ventricular septum into the left atrium, where the wall of the target vessel is the wall of one of the pulmonary veins.

Fig. 19 is a longitudinal cross-section of a proximal portion of an alternative embodiment of the INAS400, the INAS400 having a simplified design compared to the INAS300 proximal portion of fig. 16. INAS400 uses the same distal portion design as INAS300 of fig. 11-15. Three handles, a proximal injection handle 430, a central guide tube handle 440, and a distal sheath control handle 450 allow for relative longitudinal movement of sheath 312, middle tube 415, and inner tube 416 with respect to injection lumen 421. For the position shown in fig. 19, having sheath control handle 450 near its proximal-most position, the proximal-most position will indicate that sheath 312 has been fully retracted in the proximal direction. In this position, as with INAS300 of FIGS. 11-18, this will cause the distal portion of guide tube 315 to expand outwardly as shown in FIG. 14.

A gap having a distance L9 between injection handle 430 and guide tube handle 340 may be adjusted using a screw adjustment tab 434 having threads 435 that allow screw adjustment tab 434 to move relative to proximal portion 433 of injection handle 430. Proximal to the screw adjustment tab 434 is a penetration limiting member that will limit the penetration of the needle 319 and the distance L9 that the injection outlet port 317 of the syringe 316 enters into the wall of the target vessel. Desirably, a scale may be marked on the proximal portion 433 of the proximal injection handle 430 so that the medical practitioner can set the gap L9 and adjust the penetration distance accordingly. A central tube 416 having a lumen 421 is sealed into a proximal tab 433 of the distal injection handle 430. The luer fitting 438 with access tube 436 is a port for injecting ablative fluid into the handle lumen 432. The lumen 439 of the luer fitting 438 is in fluid communication with the lumen 437 proximate the tube 436, which lumen 437 is in fluid communication with the injection lumen 421 of the inner tube 416. The inner tube 416 is typically a metal hypotube, although plastic tubes or tubes with braided wire or helical reinforcement are also contemplated.

A central guide tube handle 440 attached to the middle tube 415 and controlling longitudinal movement of the middle tube 415 includes a proximal portion 444, the proximal portion 444 being screwable into the distal portion 442. When screwed into distal portion 442, proximal portion 444 will compress washer 445, allowing handle 440 to lock down onto middle tube 415. This is also required during preparation for use, as luer fitting 448 with side tube 446 can be used to flush the space between inner tube 416 and middle tube 415 with saline solution.

A distal sheath control handle 450 attached to the sheath 312 and controlling longitudinal movement of the sheath 312 includes a proximal portion 454, the proximal portion 454 being screwable into the distal portion 452. When screwed into the distal portion 452, the proximal portion 454 will compress the washer 455, allowing the handle 450 to lock down onto the sheath 312. This is also required during preparation for use, as luer fitting 458 with side tube 456 can be used to flush the space between middle tube 415 and sheath 312 with saline solution.

Fig. 20 is a longitudinal cross-section of a central transition portion 460 connecting a proximal portion of the INAS400 of fig. 19 with a distal portion of the INAS300 of fig. 11-15. The proximal end of the central transition portion 460 includes the same three concentric tubes located at the distal end of the handle portion of the INAS400 shown in fig. 19. Specifically, the proximal end of transition portion 460 includes an inner tube 416 having an injection lumen 421, a middle tube 415, and a sheath 312. At the distal end of the inner tube 416, a manifold 410 is inserted that seals the inner tube 416 to the four injection tubes 316 such that the lumens 421 of the inner tube 416 are in fluid communication with the lumens 321 of the four injection tubes 316. Furthermore, the longitudinal movement of the inner tube 416 will thus be translated into longitudinal movement of the four injection tubes 316.

The middle tube 415 is sealed inside the plastic member 405, said plastic member 405 also being sealed to the guide tube 315 and the core wire 311. The longitudinal movement of the middle tube 415 will be translated into longitudinal movement of the four guide tubes 315. The sheath 312 is the same sheath as the distal portion of the INAS300 of fig. 11-15.

FIG. 21 is a circumferential cross-section at S21-S21 of the central transition section 460 of FIG. 20. Viewed in the distal direction, three concentric tubes are visible in cross section: sheath 312, middle tube 415, and inner tube 416. The proximal end of the manifold 410 and the proximal ends of the four injection tubes 316 are visible inside the inner tube. It is also expressly seen that manifold 410 seals four injection tubes 316 into inner tube 416, and that lumen 321 of injection tubes 316 opens into lumen 421 of inner tube 416.

FIG. 22 is a circumferential cross-section at S22-S22 of the central transition section 460 of FIG. 20. Viewed in the distal direction, sheath 312 and central tube 415 are visible in cross section. The middle tube 415 is sealed into the distal portion of the plastic member 405. Also visible are the proximal ends of the four guide tubes 315 and core wire 411. It is also shown how four injection tubes 316 enter the proximal end of guide tube 315.

FIG. 23 is a circumferential cross-section at S23-S23 of the central transition section 460 of FIG. 20. This cross-section is equal to the circumferential cross-section shown in fig. 13, showing the sheath 312 and the plastic member 405 (305 in fig. 13), the plastic member 405 sealing the four guide tubes 315 and the core wire 311 and attaching the four guide tubes 315 and the core wire 311 together. The injection tubes 316 are concentrically located inside the four guide tubes 315. Fig. 20-23 show explicitly how the simplified proximal end of fig. 19 is connected to the distal portion of the INAS300 of fig. 11-15.

Fig. 24 is a longitudinal cross-section of the proximal end of an alternative embodiment of an INAS500, the INAS500 having a syringe 516, the syringe 516 having a coring needle 519, the coring needle 519 having a radiopaque wire 518 within its lumen to provide visualization of the needle upon deployment. The radiopaque wires 518 generally extend beyond the proximal end of the injection tube 515 where they will attach to the structure of the INAS 500. While the preferred configuration has the radiopaque wire 518 simply within the lumen of the injection tube 516, it is also contemplated that the radiopaque wire may be fixedly attached to the inside of the injection tube using an adhesive or brazing. If such attachment is used, the radiopaque wire may be shorter than the syringe 516 and disposed in the distal-most portion.

In this embodiment, the injection outlet port 517 is at the distal end of the coring needle 519. In this configuration, sheath 512 has been pulled back to allow guide tube 515 to expand outward. The guide tube 515 in this embodiment is made of one or two plastic layers that are pre-formed in an expanded curved shape. The injection tube 516 may be made of any metal, such as 316 surgical grade stainless steel, NITINOL, or a radiopaque metal such as tantalum or platinum. In this embodiment, the distal portion of each guide tube 516 has a radiopaque section 522 that is integrally formed with the guide tube and is typically constructed of radiopaque plastic, such as barium or tungsten filled polyurethane. Also shown in fig. 24 is the distal end 529 of guide tube 515, which guide tube 515 is parallel to the longitudinal axis of INAS500 at diameter L10 in its fully open configuration. For use in the renal arteries, L10 is typically 3-10mm, and if only one size is prepared, 8mm is the best configuration because few renal arteries are larger than 7mm in diameter.

It is important that the distal end 529 of the guide tube be in as close contact as possible to address the internal flattening of the renal artery, as if the angle is too sharp, the needle 519 may not properly pierce the arterial wall. This is also true when plastic is used for guide tube 515, although formed in a curved shape, the shape may become slightly straightened when pulled back within the sheath for an extended period of time. To this end, it is contemplated that the INAS500 will be packaged in its open configuration so as to reduce the time that the guide tube is in a straight shape within the sheath.

It is also contemplated that the starting shape of guide tube 516 will have a tip 529, with the tip 529 actually being shaped in a fully open position to bend further back than the 90 degrees shown in fig. 14 and 24. For example, if the starting angle is 135 degrees at 8mm diameter, which is the position of the fully open INAS500 when formed, the angle may be 120 degrees at 7mm diameter, 105 degrees at 6mm, 90 degrees at 5mm, 75 degrees at 4mm and 60 degrees at 3 mm. Thus, for a blood vessel between 3-7mm in diameter, the needle 519 will engage the wall of the blood vessel between 60-120 degrees. Thus, in this example, fig. 24 would be the shape of INAS500 within a 5mm diameter vessel.

The distal portion of the INAS500 has a tapered section 526, the tapered section 526 is attached to a fixed lead 520 having a tip 528, the fixed lead 520 has an outer layer 525 and a core wire 511. The distal end of sheath 512 is also shown with distal radiopaque markers 513. An enlarged view of section S26 is shown in fig. 26.

FIG. 25A is an enlargement of region S25 of FIG. 24, as it shows syringe 516 with lumen 521 and distal needle 519 fully advanced beyond distal end 529 of guide tube 515. The radiopaque wire 518 is shown explicitly within the lumen 521 of the injection tube 516. The syringe 516 will generally be smaller than a 25 gauge needle and desirably less than 0.015 "in diameter, with the lumen 521 being at least 0.008" in diameter. Thus, the radiopaque wire 518 must be sufficiently smaller than the diameter of the lumen 521 so as not to obstruct injection, but still large enough in diameter to be visible under fluoroscopy. Thus, an ideal diameter of 0.002"-0.006" should work, with a diameter of 0.004"-0.005" being ideal. The preferred outer and inner diameters for syringe 516 would be 0.012"-0.014" with lumen 521 between 0.008 "and 0.010".

Further, a guide tube 515 is shown having an inner elastic layer 527, an outer elastic layer 531 and radiopaque markers 522. Radiopaque markers 522 are shown molded here on inner plastic layer 527 distal to the tip of outer plastic layer 531. The radiopaque markers 522 should be at least 0.5mm long, with 1-2mm being preferred. For example, the inner plastic layer 527 may be teflon or polyimide, while the outer layer 531 may be a softer plastic such as polyurethane or tecothane. Ideally, distal end 529 of guide tube 515 will be soft enough to reduce the risk of penetration of the vessel wall when it is contacted during deployment. It is also contemplated that a metal band comprised of gold, platinum, or tantalum may also be used to mark the distal end of guide tube 515. It is also contemplated that the outer layer 531 and radiopaque marker 522 may be identical such that the entire guide tube 516 will be visible under fluoroscopy.

The use of radiopaque wire 518 also reduces dead space within injection tube 516, as it is important to minimize the amount of volume within the entire INAS500, with a desirable volume of less than 0.2 ml. This would facilitate a reduced time injection method for PVRD that would begin with flushing the INAS500 with saline.

One technique contemplated to reduce the dead space in any of the INAS injection lumens is to have a wire inside the lumen, such as wire 518 inside lumen 521, to occupy volume. Similarly, a wire may be inserted into the lumen 421 of the inner tube 416 of fig. 20 to occupy the volume in the lumen 421.

Once in the position where the needle passes through the renal artery wall, the appropriate amount of ablative fluid will be infused. Sufficient saline will then be injected to flush all of the ablative fluid completely out of the INAS 500. INAS500 will be closed and the second renal artery treated in the same manner. INAS500 will then be removed from the body. The radius of curvature R1 of the distal portion of syringe 516 should be approximately the same as the radius of curvature R2 of guide tube 515. This will prevent the guide tube 515 from moving proximally (backing up) when the needle 519 pierces the vessel wall. Thus, R1 and R2 should be within 2mm of each other. It is also contemplated that if the radii of curvature are significantly different, the radius of curvature R1 should be less than R2.

In fact, the radius of curvature of the distal portion of each guide tube 515 will vary with the vessel diameter, and for smaller vessels, larger, will constrain the tubes 515, not allowing them to open completely. Therefore, ideally, the radius of curvature of the distal portion of each injection tube 516 including the injection needle 519 should be the same as the radius of curvature of the distal portion of the guide tube 515 when the guide tube 515 is expanded to its maximum diameter.

Needle 519 extends a distance L11 beyond distal end 529 of guide tube 515. The distance is typically 2-4mm, with preferred distances being 2.5, 3.0 and 3.5mm, assuming the INAS500 distance L11 is preset in the factory.

Fig. 25B is an alternative embodiment of the distal section S25 of the INAS500 of fig. 24. Fig. 25B has the same structure as fig. 25A with respect to a syringe 516, the syringe 516 having an injection needle 519, the injection needle 519 having an injection outlet 517 and a radiopaque thread 518. The difference from fig. 25A is the radiopaque marker tool used to guide tube 515. In fig. 25B, guide tube 515 also has an inner layer 527 and an outer layer 531 having a distal end 529. A metallic radiopaque marker band 505 is attached to the exterior of guide tube 515 proximate distal end 529. The combination of metal strip 505 showing the distal end of guide tube 515 and radiopaque wire 518 showing the extension of injection tube 516 with injection needle 519 provides a good combination for visualizing the critical parts of INAS500 to ensure that injection outlet 517 is properly positioned before injecting the ablative fluid.

Fig. 26 is a schematic view of an embodiment of the proximal section 540 (or handle) of the INAS500, the INAS500 having a locking mechanism activated by depressible buttons 532 and 542. Specifically, when depressed, button 532 unlocks the movement of sheath control cylinder 535 relative to guide tube control cylinder 533. Sheath control cylinder 535 is attached to sheath 512 by transition section 538. Guide tube control cylinder 533 is attached to middle tube 505 of fig. 28, which middle tube 505 in turn is connected to guide tube 515 of fig. 24, 25 and 28. Sheath control cylinder 535 includes a notch 531 for limiting the pull back of sheath 512 in the proximal distance.

When depressed, the button 542 unlocks the movement of the needle control cylinder 545 relative to the guide tube control cylinder 533.

The handle 540 has two irrigation ports. A port 534 with a luer fitting is generally shown along with a cap 536. Port 534 is used to flush space 507 between sheath 512 and central tube 505, and the space between sheath 512 and guide tube 515, shown in fig. 28, with saline. An injection port 544, typically having a luer fitting, is shown along with a cap 546. Port 544 is used to flush the space 508 between middle tube 505 and inner tube 506 with saline. Port 554, typically having a luer fitting, is shown along with cover 556. Port 554 allows for the injection of ablative fluid into lumen 521 of fig. 28, which lumen 521 is in fluid communication with the lumen of injection tube 516.

The handle 540 also includes a gap adjustment cylinder 548 that, when rotated in one direction, reduces the distance the injection needle 519 extends beyond the end of the guide tube 515. Rotation of cylinder 548 in the other direction will increase the distance that injection needle 519 extends beyond tip 529 of guide tube 515. It is contemplated that the gap adjustment cylinder may be accessible to a user of the INAS500, with markings on the handle 540 indicating the distance to be reached. In a preferred embodiment, the gap adjustment cylinder 548 is only accessible during assembly and testing of the INAS500 to ensure that the properly calibrated distance L11 of fig. 25 is preset in the factory during manufacture and testing of each INAS 500. This ability to correct the distance L11 is critical for good yield in the manufacturing process. In other words, the distance L11 can be tuned exactly using the gap adjustment cylinder 548 even with a few millimeters variation in the relative lengths of the components of the INAS500, such as the inner tube 506 and the middle tube 505. In this preferred embodiment, INAS500 will be labeled according to a preset distance L11 shown in fig. 25. For example, INAS500 may be configured to have three different distances L11 of 2.5mm, 3mm, and 3.5 mm. It is also contemplated that a set screw or other mechanism, not shown, can be included to lock the gap adjustment cylinder 548 at the desired distance setting after calibration. Although a gap adjustment cylinder 548 is shown here, it is contemplated that other mechanisms, such as a sliding cylinder, may be used to adjust the distance L11.

The function of handle 540 to operate INAS500 for PVRD would include the following steps:

1. all of the internal volume of INAS500 is flushed with saline through ports 534, 544 and 554.

2. The INAS500 is inserted through a previously placed guide catheter that positions the distal portion of the INAS500 at a desired location in one of the renal arteries of the patient.

3. Depressing the button 532, and while holding the needle control cylinder 545, the needle control cylinder 545 locks to the guide tube control cylinder 533, pulling the sheath control cylinder 535 in the proximal direction until the notch 531 engages the port 544, limiting the pull back of the sheath 512.

4. The button 532 is released, which button 532 relocks the relative movement of the sheath control cylinder 535 with respect to the guide tube control cylinder 533.

5. Depressing button 542, the button 542 releases the relative movement of the needle control cylinder 545 with respect to the guide tube control cylinder 533 and, while holding sheath control cylinder 535, the sheath control cylinder 535 now locks to the guide tube control cylinder 533, advances the needle control cylinder 545 with distal end 549 until the penetration limiting member stops moving and presets the depth L11 of the needle 519 with respect to the distal end 529 of the guide tube 515. This can be done in two ways: 1) pushing the distal end 549 of the needle control cylinder 545 forward until it engages the guide tube flush port 544, or 2) as shown in fig. 26, the inner gap 547 is closed against the proximal end of the gap adjustment cylinder 548, which is inside the needle control cylinder 545.

6. The button 542 is released, and the button 542 relocks the movement of the needle control cylinder 545 on the guide tube control cylinder 533.

7. In this position, a syringe or manifold with a syringe (not shown) may be attached to port 554 and the desired volume of ablative fluid injected. For example, 0.2ml of ethanol may be injected. If verification of the position of the INAS500 needle 519 is required, angiography can be performed to look down the length of the renal artery so that the radiopaque rings 513 and 524 on the distal and tapered distal ends 520 of the sheath 512 are concentrically visible, outside of the radiopaque markers on the guide tube 522, and extending into the wall of the renal artery and into the perivascular space, with the distal portion of the injection tube 516 having an internal radiopaque wire 518. This may be done with or without injection of contrast media into the renal artery.

8. A syringe with saline solution is next attached to port 554, replacing the ablation fluid syringe. Ideally, slightly more saline is injected than the total volume of the inactive cavity to ensure that no ablative fluid remains in the INAS 500. For example, if the dead space in INAS500 is 0.1ml, 0.12-0.15ml saline would be a good amount to ensure that ablation fluid is all delivered to the appropriate tissue perivascular volume.

9. Depressing the button 542 while holding the sheath control cylinder 535, the needle control cylinder 545 is pulled back in the proximal direction until the injection needle 519 is fully retracted inside the guide tube 515. It is contemplated that there will be a ratchet mechanism or stop that will allow the needle 519 to fully retract when the needle control cylinder 545 reaches the correct position.

10. The button 542 is released, locking the movement of the guide tube control cylinder 533 by the needle control cylinder 545.

11. Depressing the button 532 releases the relative movement of the sheath control cylinder 535 with respect to the guide tube control cylinder 533, which guide tube control cylinder 533 is now locked to the needle control cylinder 545.

12. The sheath control cylinder 535 is advanced in the distal direction while the needle control cylinder 545 remains stationary. This will close INAS500, folding guide tube 515 back into sheath 512.

13. The INAS500 is pulled back into the guide catheter.

14. The guide catheter is moved to the other renal artery.

15. Steps 3 to 13 are repeated for the other renal arteries.

16. INAS500 is removed from the body.

While buttons 532 and 542 release the movement of the control cylinder when depressed and lock the control cylinder when released as described above, it is also contemplated that they interlock as follows:

1. the first interlock allows the needle control cylinder 545 to unlock only when the sheath control cylinder 535 is in its distal most position, where the sheath 512 is pulled back and the guide tube 515 is fully deployed.

2. The second interlock allows the sheath control cylinder 535 to unlock only when the injection needle control cylinder 545 is in its distal-most position, where the needle 519 is retracted into the guide tube 515.

The combination of buttons 532 and 542 with the control mechanism described above should make the use of INAS500 simple and foolproof. Button 532 is substantially pressed and sheath 512 is pulled back, releasing guide tube 515 to expand outwardly, followed by button 542 being pressed and advancing needle 519 forward to penetrate the wall of the renal artery. The injection is performed and then the reverse is done, button 542 is depressed and needle 519 retracted, then button 532 is depressed and sheath 512 is pushed forward, folding guide tube 515 and closing INAS 500.

Figure 27 is a schematic view of a needle section of another embodiment of an INAS550 of the present invention, the INAS550 having a core 561 formed from three strands 561A, 561B and 561C, and a non-circular cross-section guide tube 565 with a radiopaque distal section 572 and a distal end 579. INAS550 is somewhat similar to INAS500 of fig. 24. It has a sheath 512 with a distal radiopaque marker 513, a syringe 566 with a distal injection needle 569 and an injection outlet port 567. The tapered distal section 580 has a tapered section 576, a radiopaque marker 574, and a proximal section 573. Of importance in this embodiment is the backward curved shape of the syringe 566 with the injection needle 569. Specifically, the radius of curvature of the injection tube 566 should match or be slightly smaller (more curved) than the radius of curvature of the guide tube 565 and guide tube distal radiopaque section 572. This will prevent straightening of the guide tube 565 including the distal radiopaque section 572 as the needle 569 penetrates the wall of the target vessel. Fig. 27 shows the fully deployed shape of INAS550 with the center of injection outlet port 567 being proximal to the center of distal end 579 of guide tube 565 by distance L12, said guide tube 565 having a radiopaque section 572. L12 should be 0.5mm to 5 mm.

Fig. 28 is a central portion of the cross-section at S28-S28 of the INAS550 of fig. 27 having a sheath 512. It shows a non-circular cross-section guide tube 565 surrounding an injection tube 566. At positions S28-S28, a middle tube 564 is fixedly attached to the exterior of three guide tubes 565 and three wires 561A, 561B, and 561C, said middle tube 564 being connected to the guide tube control cylinder 533 of fig. 26, said three wires being twisted together to become a core wire 561 as shown in fig. 27. This can be accomplished by injecting plastic or adhesive to form the connection medium 555 within the cavity of the middle tube 564.

Fig. 29 is a schematic view of a distal portion of another embodiment of an INAS600, the INAS600 having a stranded core 611, the stranded core 611 having a circular cross-section guide tube 615, the circular cross-section guide tube 615 having a distal radiopaque section 622.

INAS600 is somewhat similar to INAS500 of fig. 24, except for stranded core wire 611 and three injection needles instead of 4. It has a sheath 612 with distal radiopaque markers 613, an injection tube 616 with a distal injection needle 619 and an injection outlet port 617. It also has a radiopaque wire 618 inside the syringe 616 to aid visualization during fluoroscopy. The tapered distal section 620 has a tapered section 626, a radiopaque marker 624, and a proximal section 623. Similar to the INAS550 of fig. 27 and 28, this embodiment has a rearward (proximal) curved shape of the injection tube 616, the injection tube 616 having an injection needle 619. Specifically, the radius of curvature of the injection tube 616 should match or be slightly smaller (more curved) than the radius of curvature of the guide tube 615 and the guide tube distal radiopaque section 622. This will prevent straightening of the guide tube 615, including the distal radiopaque section 622, as the needle 569 penetrates the wall of the target vessel.

For better visualization, in fig. 29, the proximal portions of the sheath 612 and the central tube 614 are shown as transparent, so that the internal structure of the INAS600 is apparent. Specifically, three circular cross-section guide tubes 615 are connected to middle tube 614 using techniques similar to INAS550 of fig. 28. Also shown is a wire 611A, which 611A is one of three wires that are twisted together to form a core wire 611, also shown in FIGS. 27 and 28. A manifold (not shown) similar to manifold 410 of fig. 20 is used to attach the interior of an inner tube 606 to the three injection tubes 616, the inner tube 606 being connected to the needle control cylinder 545 of fig. 26. The three injection tubes 616 are shown as they enter the proximal ends 605 of the three guide tubes 615.

Fig. 30 is a schematic view of the interior portion of the INAS600, the INAS600 specifically showing the proximal end of a radiopaque wire 618, the radiopaque wire 618 running the length of the injection tube 616 to provide radiopacity. These radiopaque lines 618 are similar to the radiopaque lines 518 of fig. 24 and 25. Clearly visible in this inner portion with sheath 612 and central tube 614 removed is transparent inner tube 606, 3 guide tubes 615, three injection tubes 616, 611A and 611B, said 611A and 611B being two of the constituent wires of core wire 611 of fig. 29. The manifold 610 is shown inside the inner tube 606 in fig. 30. The distal portion of manifold 610 is shown with the proximal portion being transparent. Although not shown, the proximal transparent portion of manifold 610 extends all the way to the proximal end of injection tube 616, similar to manifold 410 of fig. 20. Finally, the radiopaque wire 618 exiting the proximal end of the syringe tube 616 is folded back and travels back in the distal longitudinal direction in the space alongside the syringe tube 616.

As shown in fig. 31, which is a cross-section at S31-S31 of fig. 30, the manifold 610 is a molded or injected plastic or adhesive that seals the interior of the inner tube 606 with the three injection tubes 616 and the three radiopaque wires 618. In the complete catheter 600, not only the inner portion.

Fig. 32A is a schematic view of an embodiment of the distal portion of an INAS700 having a non-circular guide tube 715. Also shown is a core wire 711 and is tapered, having an elliptical or oval cross-section. Tapered distal section 720 has a tapered section 726, radiopaque markers 724, and a proximal section 723. The distal end of the sheath 712 is just visible. Guide tube 715 in this embodiment may be constructed of NITINOL or a formed plastic such as polyamide. The advantages of the non-circular cross-section of guide tube 715 are: better support for the syringe (not shown) is provided when the syringe is pushed distally to engage the inner wall of the target vessel.

Fig. 32B is a tip on the schematic of the INAS700 of fig. 32A, looking in a proximal direction, just proximal to the proximal end of the tapered distal section 720. Here, it can be seen that instead of the guide tubes 715 being oriented to expand outward in a purely radial direction, the guide tubes 715 are rotated 90 degrees to a radial direction to allow the non-circular cross-section to have a decreasing effect on the catheter diameter. The distal ends of core wire 711 and sheath 712 are visible in cross section.

Fig. 33 is a schematic view of an embodiment of the proximal section/handle 640 of the INAS600 having a locking mechanism activated by rotation of the sheath control lock 632 and the needle control lock 642. Specifically, counterclockwise rotation of the sheath control lock 632 forms the position shown in fig. 33 until the sheath flush tube 636 with luer port 634 is lined up with longitudinal slot 631, unlocking the movement of the sheath control cylinder 635, which sheath control cylinder 635 is attached to sheath 612 by tapered section 638. The sheath control cylinder 635 and tapered section 638 may now be pulled in a proximal direction relative to the guide tube control cylinder 633 to collapse the sheath relative to the guide tube as seen in the configuration of fig. 29. Once the sheath control cylinder 635 is pulled back all the way in the proximal direction, the sheath irrigation tube 632 is now lined up with circumferential slots 633 that extend in a clockwise direction within the sheath control lock 632. In this position, the sheath control lock may also be rotated in a counter-clockwise direction such that the sheath flush tube 636 is located within the circumferential slot 633 and longitudinal movement of the sheath control cylinder 635 is prevented. It is contemplated that a spring may be embedded in this mechanism such that sheath control lock 632 automatically springs up to a locked position once sheath flush 636 lines up with slot 633.

Once the sheath 612 has been retracted in the proximal direction as described above, the handle is ready to advance distally the injection tube 616 of fig. 29 with injection needle 619 to penetrate the vessel wall of the target vessel, said injection tube 616. Circumferential slots 643 and 648 are connected by longitudinal slot 641. Detents 647 attached to the exterior of needle control cylinder 645 track within three slots 643, 641, and 648 to lock and unlock the relative movement of guide tube control cylinder 633 with respect to needle control cylinder 645. To enable syringe 616 of fig. 29 to be advanced, needle lock cylinder 642 is rotated in a clockwise direction to align pins 647 with longitudinal slots 641. The needle control cylinder 645 is now movable in the distal direction, causing the syringe 616 to advance distally. When the pin 647 now reaches a position aligned with the circumferential slot 648, the pin 647 no longer moves in the distal direction and the penetration of the needle 619 is thus limited. In this configuration, additional clockwise rotation of needle lock cylinder 642 moves pin 647 into circumferential slot 648, which now locks longitudinal movement of needle control cylinder 645. A syringe may now be attached to the luer fitting 654 and appropriate ablative fluid injected into the perivascular space as needed. Additional injections of saline or other inert fluid will now be completed to flush the inner inactive lumen of the INAS600 and ensure that all of the ablative fluid is fully delivered to the desired site. Retraction of sheath 612 and reversal of distal movement of syringe 616 can now be accomplished by retroaction of the components of handle 640.

It is also contemplated that proximal section 640 may be constructed such that rotation in the opposite direction of any of the above-described steps will work. Combinations of rotational movement (such as described with respect to proximal section/handle 640 of fig. 33) and push button locking/unlocking mechanisms (such as shown with proximal section/handle 540) are expressly contemplated herein.

Fig. 34 is a schematic view of a guide tube 815 and an injection tube 816 of another embodiment of an INAS800 of the present invention, the INAS800 having three guide tubes 815, the three guide tubes 815 being separate from a primary lead body 813. Each guide tube 815 has two lumens, one for passage of the syringe 816 and the other for passage of a wire 818, the wire 818 providing a shape memory that encourages the guide tube 815 to open against the interior of the vessel wall of the target vessel. The wire 818 may also provide additional radiopacity for visualizing the guide tube 815. The guide tube 815 and guide tube body 813 in the INAS800 are made of a plastic material that is soft enough to allow the wire 818 to urge the guide tube 815 into the shape shown. It is also contemplated that the guide tube 815 itself will comprise a radiopaque material such as tungsten or barium. The wire 818 may be made of a shape memory alloy, such as NITNOL, or a preformed resilient material, such as spring steel. Also shown is the proximal end of the inner tubing 806, which inner tubing 806 is attached to a syringe 816 having a distal end with a sharpened injection needle 819 having an injection outlet 817.

FIG. 35 is a schematic view of another embodiment of an INAS900 of the present invention, the INAS900 having a syringe 916, the syringe 916 having a distal needle 919, the distal needle 919 having an injection outlet port 917. The INAS900 also has three guide tubes 915, the guide tubes 915 including flat wires 918 within the guide tubes 915. The flat wire 918 provides shape memory and optionally radiopacity for visualization of the guide tube 915. The flat wire 918 is typically made of a memory metal such as NITINOL or an elastic material such as spring steel. The guide tube 915 is typically made of a plastic material that is soft enough to allow the wire 818 to urge the guide tube 815 into the shape shown. Also shown are sheath 912 and core wire 911, which sheath 912 and core wire 911 are similar in function to those shown in many of the earlier embodiments of INAS. It is also contemplated that the guide tube 915 itself will comprise a radiopaque material such as tungsten or barium.

While each of the INAS embodiments shown herein have closed and open positions with a fully enclosed injection needle, it is envisioned that the system will function with an outer sheath that is open at its distal end as shown in the McGuckin device of U.S. patent No. 7,087,040. In such embodiments, needle stick injuries may be prevented by withdrawing the injection needles in a proximal direction a distance sufficient to hide them. Interlocks in the proximal section and/or the handle may lock the movement of the needles to prevent their inadvertent movement in the distal direction. This concept will work with the INAS design of fig. 1-10, as well as those embodiments having a guide tube as shown in fig. 11-35, wherein the needle will be retracted proximally within the guide tube, and the guide tube is then retracted within the sheath.

Fig. 36A is a longitudinal cross-sectional view of another embodiment of the distal portion of the injection tube 956 of the INAS950, with a distal injection needle 959. The other structure of INAS950 is similar to INAS10 of fig. 1. The injection needle 959 has an injection outlet 957. A stylet 958 is shown inside the lumen of the syringe 956. The stylet 958 has two potential uses, 1) it can stiffen the syringe 956 until it will maintain its proper curved shape and better penetrate the inner wall of the target vessel, and 2) it can provide additional radiopacity for visualization under fluoroscopy. It is also contemplated that the needle 959 can have a non-sharp tip and the stylet 958 can extend beyond the injection outlet 957 and be sharpened to provide a tool to penetrate the inner wall of the target vessel. The stylet 958 will be fully withdrawn or pulled back so as not to impede flow when the needle is properly positioned. A cord such as cord 13 of INAS10 of fig. 1 may provide a means of limiting penetration depth in this design.

Fig. 36B is a longitudinal cross-sectional view of another embodiment of the distal portion of the plastic proximal tube 965 of the INAS950, the INAS950 having a syringe 966, the syringe 966 having a distal injection needle 969 inserted into the distal end of the syringe 965. Radiopacity is provided by radiopaque marker bands 962 on the syringe 965 and radiopaque wires 968 inside the syringe 966. Injection needle 969 has an injection outlet 957. The injection tube 965 is made of a preformed plastic such as polyurethane or formamide, or a combination of two or more layers of plastic. The distal end 961 of syringe 965 provides a means for limiting penetration of needle 969. It is also contemplated that the injection tube 966 may be made of a radiopaque metal such as tantalum or L605 cobalt chromium, or the injection tube 966 may be plated or coated with a radiopaque metal such as gold. In these cases, the radiopaque wire 968 would not be needed.

FIG. 36C is a longitudinal cross-sectional view of another embodiment of the distal portion of a metal proximal tube 975, the metal proximal tube 975 having a syringe 976, the syringe 976 having a distal injection needle 979 inserted into the distal end of the syringe 975. Radiopacity is provided by radiopaque marker bands 972 on the syringe 975 and radiopaque wires 978 inside the syringe 976. The injection needle 979 has an injection outlet 977. Injection tube 975 is made of a preformed metal, such as NITINOL. The distal end 971 of the syringe 975 provides a means of limiting penetration of the needle 979.

While the present description has focused on the use of INAS for use in tissue ablation, it is also expressly contemplated that the devices and methods of fig. 1-33 may be applied to the use of the devices to inject any fluid for any purpose, including local drug delivery to a designated portion of a blood vessel or within a volume of tissue just outside of a blood vessel.

Many other modifications, adaptations, and alternative designs are certainly possible in light of the above teachings. It is, therefore, to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein.

Claims (72)

1. An intravascular nerve ablation system for delivering an ablative fluid to a volume of tissue within or adjacent a vessel wall of a target vessel, the intravascular nerve ablation system comprising:

a catheter body having a proximal end, a distal end, a central axis extending in a longitudinal direction, and a fluid injection lumen;

at least first and second guide tubes positioned distal of the distal end of the catheter body, each guide tube having a distal end, a lumen, and a distal portion that is expandable outwardly between a first position aligned with the central axis and a second position inclined away from the central axis so as to expand outwardly against a vessel wall of the target vessel, wherein the first and second guide tubes are configured to expand by self-expanding outward movement of the guide tubes from a self-expanding structure released from a constraining structure, or by distal or proximal movement-facilitated expansion of a mechanism within the intravascular nerve ablation system;

at least first and second injection tubes, each injection tube having an injection lumen providing a path for delivering the ablative fluid, the first and second injection tubes coaxially positioned within the lumens of the first and second guide tubes, respectively, each injection tube having a sharpened injection needle with an injection outlet at a distal end thereof, the first and second injection tubes adapted to slide distally and proximally within the lumens of the first and second guide tubes, respectively; and

a penetration depth limiting mechanism for limiting a penetration depth of the injection needle into a vessel wall of the target vessel.

2. The system of claim 1, further comprising a sheath fixedly attached to a sheath control mechanism positioned near a proximal end of the catheter body, the sheath positioned coaxially outside of the catheter body, the sheath having a closed position that allows the first and second guide tubes to expand outwardly against an interior of a vessel wall of the target vessel and an open position that completely encapsulates the first and second guide tubes, the first and second injection tubes, and the injection needle.

3. The system of claim 2, wherein distal portions of the first and second guide tubes are self-expanding, and expansion of the first and second guide tubes is caused by proximal movement of the sheath releasing the first and second guide tubes to move outwardly from a central axis of the catheter body.

4. The system of claim 2, further comprising an syringe control mechanism adapted to control distal and proximal movement of the first and second syringes as they slide within the lumens of the first and second guide tubes, respectively.

5. The system of claim 4, further comprising a label to indicate an order of use of the sheath control mechanism and the syringe control mechanism, the label selected from at least one of the following group of types: roman numerals letters, numbers, letters, arrows, and directional indicators.

6. The system of claim 1, wherein the system is configured to deliver the ablative fluid in a ring pattern.

7. The system of claim 1, further comprising a port for injecting the ablative fluid, the port being in fluid communication with a fluid injection lumen of the catheter body.

8. The system of claim 1, wherein the injection needle has a diameter of less than 25 gauge.

9. The system of claim 1, further comprising at least one radiopaque marker.

10. The system of claim 9, comprising a radiopaque marker on the sheath.

11. The system of claim 9, comprising a radiopaque marker on at least one of the guide tubes.

12. The system of claim 1, wherein the penetration depth limiting mechanism limits penetration of the injection outlets to a location near a vessel wall of the target vessel selected from one of the following group of locations: the media, adventitia, an adventitial exterior, both the media and the adventitia, or both the adventitia and the adventitial exterior of the target vessel.

13. An intravascular nerve ablation system for delivering an ablative fluid to a volume of tissue within or adjacent a vessel wall of a target vessel, the intravascular nerve ablation system comprising:

a catheter body having a proximal end, a central axis extending in a longitudinal direction, and a fluid injection lumen;

an external source of ablative fluid in fluid communication with the fluid injection lumen;

a first guide tube and a second guide tube, the first guide tube having a proximal end, a distal end, and a lumen, the first guide tube having a distal portion adapted to expand outwardly against a vessel wall of the target vessel, wherein the first guide tube and the second guide tube are configured to expand by self-expanding outward movement of the guide tubes from a self-expanding structure released from a constraining structure, or by distal or proximal movement-facilitated expansion of a mechanism within the intravascular nerve ablation system;

a first injection tube having an injection lumen in fluid communication with the fluid injection lumen of the catheter body, a portion of the first injection tube positioned coaxially inside the first guide tube, the first injection tube having a sharpened injection needle with an injection outlet at a distal end thereof, the injection lumen of the first injection tube in fluid communication with the fluid injection lumen of the catheter body, the first injection tube adapted to slide within the lumen of the first guide tube in proximal and distal directions;

a syringe control mechanism adapted to control proximal and distal movement of the first syringe relative to the first guide tube;

a port for injecting the ablative fluid positioned near a proximal end of the catheter body, the port in fluid communication with a fluid injection lumen of the catheter body;

and a penetration depth limiting mechanism for limiting a penetration depth of the injection outlet of the injection needle into a blood vessel wall of the target blood vessel.

14. The system of claim 13, further comprising a sheath having a sheath control mechanism at a proximal end thereof, the sheath positioned coaxially outside the catheter body, the sheath having a closed position and an open position, the open position allowing the first guide tube and the first injection tube to expand outwardly to facilitate delivery of the ablative fluid to a vessel wall of the target vessel, the sheath control mechanism adapted to control longitudinal movement of the sheath between its closed and open positions.

15. The system of claim 14, wherein the closed position of the sheath facilitates complete encapsulation of the first guide tube and injection outlet at the distal end of the injection needle, the closed position providing complete protection from inadvertent release of fluid from a lumen of the intravascular nerve ablation system during insertion and removal from the target vessel, the closed position also preventing accidental needle stick injury to a patient or healthcare worker using the intravascular nerve ablation system.

16. The system of claim 15, further comprising a tapered distal portion that, in combination with the sheath, completely encapsulates the injection needle when the sheath is in its closed position.

17. The system of claim 14, further comprising a radiopaque marker near a distal end of the sheath.

18. The system of claim 14, further comprising a locking mechanism that, when engaged, prevents longitudinal movement of the sheath.

19. The system of claim 13, wherein the system is configured to deliver the ablative fluid in a helical pattern.

20. The system of claim 13, further comprising a component that prevents movement of the first injection tube relative to the first guide tube.

21. The system of claim 20, further comprising a handle positioned near a proximal end of the catheter body, the handle being a component configured to prevent movement of the first syringe with respect to the handle.

22. The system of claim 13, wherein the system is configured to deliver the ablative fluid into a specific tissue volume selected from at least one of: a media of a wall of the target vessel, an adventitia of a wall of the target vessel, a volume outside of the adventitia of a wall of the target vessel, the media and adventitia of a wall of the target vessel, and a volume outside of the adventitia and adventitia of the target vessel.

23. The system of claim 13, wherein the system is configured to deliver the ablative fluid at three or more injection exit points.

24. The system of claim 13, wherein the catheter body comprises a fixed wire attached to a distal end thereof.

25. The system of claim 13, configured for coaxial advancement over a separate guidewire.

26. The system of claim 13, wherein a distal portion of the first syringe is self-expanding.

27. The system of claim 26, wherein the self-expanding distal portion of the first injection tube is formed of NITINOL.

28. The system of claim 13, wherein the ablative fluid comprises at least one of the ablative fluids selected from the group consisting of: ethanol, phenol, glycerol, lidocaine, bupivacaine, tetracaine, benzocaine, guanethidine, botulinum toxin, distilled water, hypotonic saline solution, and hypertonic saline solution.

29. The system of claim 13, wherein the ablative fluid is a heated fluid composition.

30. The system of claim 13, wherein the ablative fluid is a cooled fluid composition.

31. The system of claim 13, wherein the ablative fluid is in the form of a vapor injected through a fluid injection lumen of the catheter body.

32. The system of claim 13, the syringe control mechanism and the penetration depth limiting mechanism positioned on a proximal handle.

33. A percutaneously delivered intravascular nerve ablation system for perivascular fluid delivery, the percutaneously delivered intravascular nerve ablation system comprising:

a fluid delivery catheter having a proximal control portion, a central catheter body, a distal fluid delivery portion;

the distal fluid delivery portion comprises 2 or more injection needles, each injection needle having a lumen, the injection needle having an injection outlet near a distal end thereof, the injection needle further adapted to move radially outward to penetrate a wall of a target vessel to set the injection outlet at a preset depth relative to an inner wall of the target vessel;

the distal fluid delivery portion comprises 2 or more expandable guide tubes comprising at least a first guide tube and a second guide tube, each guide tube having a distal end and a lumen, each guide tube having a distal portion adapted to expand outwardly against a vessel wall of the target vessel, wherein the first guide tube and the second guide tube are configured to expand by outward movement of the guide tubes from self-expansion of a self-expanding structure released from a constraining structure, or expansion facilitated by distal or proximal movement of a mechanism within the intravascular nerve ablation system;

the proximal control portion comprises a proximal port for injecting fluid and a control mechanism adapted to cause outward radial movement of the injection needle;

said central catheter body including an injection lumen providing fluid communication between said proximal port for injecting fluid and the lumen of said injection needle, said central catheter body further including means allowing said control mechanism to cause outward radial movement of said injection needle,

the fluid delivery catheter further comprises an internal fluid volume comprising an internal fluid volume of the catheter from a proximal end of a proximal port of the proximal control portion to an injection outlet near a distal end of the injection needle, the internal fluid volume being less than 0.5 ml.

34. The system of claim 33, wherein the internal fluid volume of the fluid delivery conduit is less than 0.2 ml.

35. The system of claim 33, wherein the internal fluid volume of the fluid delivery conduit is less than 0.1 ml.

36. The system of claim 33, wherein at least one of the cavities of the injection needle comprises a volume-occupying structure.

37. The system of claim 36, wherein the volume occupying structure comprises a wire configured to reduce the internal fluid volume.

38. The system of claim 37, wherein the wire is formed of a radiopaque material to enhance visualization of the injection needle under fluoroscopy.

39. A percutaneously delivered intravascular nerve ablation system for perivascular fluid delivery, the percutaneously delivered intravascular nerve ablation system comprising:

a fluid delivery catheter having a proximal control portion, a central catheter body, a distal fluid delivery portion;

the distal fluid delivery portion comprises 2 or more injection needles, each injection needle having a lumen, the injection needle having an injection outlet near a distal end thereof, the injection needle further adapted to move radially outward to penetrate a wall of a target vessel to set the injection outlet at a preset depth relative to the wall of the target vessel;

the distal fluid delivery portion comprises 2 or more expandable guide tubes comprising at least a first guide tube and a second guide tube, each guide tube having a distal end and a lumen, each guide tube having a distal portion adapted to expand outwardly against a vessel wall of the target vessel, wherein the first guide tube and the second guide tube are configured to expand by outward movement of the guide tubes from self-expansion of a self-expanding structure released from a constraining structure, or expansion facilitated by distal or proximal movement of a mechanism within the intravascular nerve ablation system;

the proximal control portion comprises a proximal port for injecting fluid and a control mechanism adapted to cause outward radial movement of the injection needle;

said central catheter body including an injection lumen providing fluid communication between said proximal port for injecting fluid and the lumen of said injection needle, said central catheter body further including means allowing said control mechanism to cause outward radial movement of said injection needle,

the injection needle further comprises a structure designed to provide enhanced visibility of the injection needle under fluoroscopy.

40. The system of claim 39, wherein at least a portion of at least one of the structures designed to provide enhanced visibility comprises a radiopaque material.

41. The system of claim 40, wherein the radiopaque material comprises at least one of tantalum, platinum, and gold.

42. The system of claim 40, wherein at least one of the lumens of the injection needle comprises a radiopaque wire.

43. The system of claim 40, wherein at least a portion of the injection needle comprises at least one of a radiopaque band, a ring, a filler, an insert, a plug, and a coating.

44. A percutaneously delivered intravascular nerve ablation system for perivascular fluid delivery, the percutaneously delivered intravascular nerve ablation system comprising:

a fluid delivery catheter having a proximal control portion, a central catheter body, a distal fluid delivery portion;

the distal fluid delivery portion comprises 2 or more expandable guide tubes, the 2 or more expandable guide tubes comprising at least a first guide tube and a second guide tube, each guide tube having a distal end and a lumen, each guide tube having a distal portion adapted to expand outwardly against a vessel wall of a target vessel, wherein the first and second guide tubes are configured to expand by self-expanding outward movement of the guide tubes from a self-expanding structure released from a constraining structure, or by distal or proximal movement-facilitated expansion of a mechanism within the intravascular nerve ablation system;

the distal fluid delivery portion further comprises 2 or more injection needles, each injection needle adapted to move distally and proximally within the lumen of the guide tube, each injection needle having an injection lumen and an injection exit near a distal end of the injection needle, the injection needles further adapted to move distally outward a preset distance beyond the distal end of the guide tube to penetrate a wall of a target vessel to set the injection exit at a preset depth relative to the wall of the target vessel;

the proximal control portion comprising a proximal port for injecting fluid and a control mechanism adapted to cause distal and proximal movement of the injection needle, the control mechanism further adapted to limit penetration of the injection outlet to a preset depth relative to the wall of the target vessel, the proximal control portion further comprising an internal mechanism to set the injection needle a preset distance beyond the distal end of the guide tube;

the central catheter body includes an injection lumen providing fluid communication between the proximal port for injecting fluid and the lumen of the injection needle, the central catheter body further including means allowing the control mechanism to cause distal and proximal movement of the injection needle.

45. The system of claim 44, wherein the internal mechanism that sets the preset distance is accessible to a user of the system.

46. The system of claim 44, wherein the internal mechanism that sets the preset distance is used to correct the preset distance during manufacturing, the internal mechanism being hidden from a user of the system.

47. A percutaneously delivered intravascular nerve ablation system for perivascular fluid delivery, the percutaneously delivered intravascular nerve ablation system comprising:

a fluid delivery catheter having a proximal control portion, a central catheter body, and a distal fluid delivery portion;

the distal fluid delivery portion having a movable component comprising an outer sheath;

the distal fluid delivery portion comprises 2 or more expandable guide tubes comprising at least a first guide tube and a second guide tube, each guide tube having a distal end and a lumen, each guide tube having a distal portion adapted to expand outwardly against a vessel wall of a target vessel, wherein the first and second guide tubes are configured to expand by self-expanding outward movement of the guide tubes from a self-expanding structure released from a constraining structure, or by expansion facilitated by distal or proximal movement of a mechanism within the intravascular nerve ablation system;

the distal fluid delivery portion further comprises 2 or more injection tubes having distal injection needles, the injection tubes and injection needles having injection lumens, each injection tube adapted to move distally and proximally within the lumen of the guide tube, each injection needle having an injection outlet near its distal end, each injection needle further adapted to move distally outward a preset distance beyond the distal end of the guide tube to penetrate the wall of a target vessel and set the injection outlet at a preset depth relative to the wall of the target vessel, the distal fluid delivery portion further comprising an outer sheath having a closed position and an open position, the open position positioning the distal end of the sheath a distance proximal of the distal position of the sheath in the closed position;

the proximal control portion comprising a proximal port for injecting fluid, an injection needle control mechanism adapted to cause distal and proximal movement of an injection tube having a distal injection needle relative to the guide tube, and a sheath control mechanism adapted to cause distal and proximal movement of the outer sheath between its closed position and its open position, the proximal control portion further adapted to limit penetration of the injection outlet to a preset depth relative to the wall of the target vessel, the proximal control portion further comprising a mechanism to adjust the preset distance, the proximal control portion having at least one locking mechanism to prevent movement of at least one of the movable components of the distal fluid delivery portion;

the central catheter body includes an inner tube coaxially located within a sheath, the inner tube having an injection lumen providing fluid communication between the proximal port for injecting fluid and a lumen of the injection tube in fluid communication with the lumen of the injection needle, the inner tube further providing a means for an injection needle control mechanism to cause distal and proximal movement of the injection tube with the distal injection needle relative to the guide tube.

48. The system of claim 47, wherein the proximal control portion comprises a locking mechanism configured to prevent distal and proximal movement of the sheath relative to the guide tube.

49. The system of claim 47, wherein the proximal control portion comprises a locking mechanism configured to prevent distal and proximal movement of the syringe relative to the guide tube.

50. The system of claim 47, wherein the proximal control portion comprises an interlock mechanism configured to prevent movement of another of the movable components of the distal fluid delivery portion if at least one of the movable components of the distal fluid delivery portion is in an undesired state.

51. The system of claim 50, wherein the proximal control portion comprises an interlock mechanism configured to prevent the outer sheath from moving to its closed position unless the injection needle is fully within the lumen of the guide tube.

52. The system of claim 50, wherein the proximal control portion comprises an interlock mechanism configured to prevent distal and proximal movement of the syringe unless the outer sheath is in its open position.

53. A percutaneously delivered intravascular nerve ablation system for perivascular delivery of a fluid, the percutaneously delivered intravascular nerve ablation system comprising:

a fluid delivery catheter having a longitudinal axis, a proximal control portion, a central catheter body, a distal fluid delivery portion, and a reservoir for injection fluid;

the distal fluid delivery portion having a movable component comprising 2 or more expandable guide tubes, the 2 or more expandable guide tubes comprising at least a first guide tube and a second guide tube, each guide tube having a lumen and a distal end having a center, each guide tube having a distal portion adapted to expand outwardly against a vessel wall of a target vessel, wherein the first guide tube and the second guide tube are configured to expand by outward movement of the guide tubes from self-expanding structures released from constraining structures or expansion facilitated by distal or proximal movement of a mechanism within the intravascular nerve ablation system;

the movable part further comprising 2 or more injection tubes with distal injection needles, the injection tubes and injection needles having injection cavities, each injection tube being adapted to be moved distally and proximally within the cavity of the guide tube, each injection needle having an injection outlet near its distal end, the injection needles further being adapted to be moved radially outwardly to a fully deployed position to penetrate the wall of a target blood vessel to set the injection outlets at a preset depth relative to the inner wall of the target blood vessel, the injection tubes with distal injection needles having a curved shape that, when the injection needles are in the fully deployed position, causes at least one injection outlet of the injection needles to be bent back in a proximal longitudinal direction relative to the center of the distal end of the guide tube;

the proximal control portion comprises a proximal port for injecting fluid and a control mechanism adapted to cause outward radial movement of the injection needle;

the central catheter body includes a fluid injection lumen providing fluid communication between the proximal port for injecting fluid and the lumen of the injection tube, the central catheter body further including means allowing the control mechanism to cause outward radial movement of the injection needles.

54. The system of claim 53, wherein a distal portion of the guide tube has a guide tube radius of curvature and a distal portion of the syringe comprising an injection needle has a needle radius of curvature, the guide tube radius of curvature and the needle radius of curvature being substantially the same when the guide tube is fully expanded.

55. An intravascular nerve ablation system for delivering a prescribed fluid into or out of a vessel wall of a human target vessel, the intravascular nerve ablation system comprising:

a catheter body having a central axis extending in a longitudinal direction, the catheter body having a fluid injection lumen in fluid communication with three or more sharp injection needles,

three or more guide tubes comprising at least a first, second and third guide tube, each guide tube having a proximal end, a distal end and a lumen, each guide tube having a distal portion adapted to expand outwardly against a vessel wall of the target vessel, wherein the first and second guide tubes are configured to expand by self-expanding outward movement of the guide tube from a self-expanding structure released from a constraining structure or by distal or proximal movement-facilitated expansion of a mechanism within the intravascular nerve ablation system;

the catheter body further comprising a distal tip and an outer sheath having a first closed position in which the sheath and the distal tip together enclose the sharp injection needle, the sheath having a second open position that allows the sharp injection needle to expand outwardly into a vessel wall of a target vessel;

an external fluid source in fluid communication with the fluid injection lumen and an injection outlet positioned near a distal end of the needle, the needle adapted to provide circumferential delivery of ablative fluid from the fluid injection lumen at a specified injection depth.

56. The system of claim 55, wherein the system is configured to deliver the ablative fluid into a specific tissue volume selected from the group consisting of:

the media of the wall of the target vessel,

the adventitia of the wall of the target vessel,

a volume outside the adventitia of the wall of the target vessel,

the media and adventitia of the wall of the target vessel, and

the adventitia and a volume outside the adventitia of the target vessel.

57. The system of claim 55, wherein the system is configured to deliver at three or more points.

58. The system of claim 55, further comprising a distal balloon to prevent the ablative fluid from flowing downstream in the target vessel.

59. The system of claim 55, wherein the catheter body comprises a fixed wire attached to a distal end thereof.

60. The system of claim 55, configured to be advanced coaxially over a separate guidewire.

61. A system according to claim 55, wherein the injection outlet is provided by at least one injection tube having a sharpened injection needle at its distal end, the injection outlet being near the distal end of the sharpened injection needle.

62. The system of claim 55, further comprising a distal self-expanding portion.

63. The system of claim 62, wherein the distal self-expanding portion comprises the injection outlet.

64. A system according to claim 63, wherein said distal self-expanding portion comprises at least one guide tube and said injection outlet is provided by at least one injection tube having a sharpened injection needle at its distal end adapted to be advanced and retracted through said at least one guide tube.

65. The system of claim 63, further comprising a sheath that allows the distal self-expanding portion to expand outward when the sheath is retracted to its proximal-most open position.

66. The system of claim 62, wherein the distal self-expanding portion is formed of NITINOL.

67. The system of claim 55, wherein the outer sheath includes a radiopaque marker near its distal end.

68. The system of claim 55, wherein the distal tip comprises a radiopaque marker.

69. The system of claim 55, wherein the fluid comprises at least one of the fluids selected from the group consisting of: chemotherapeutic agents, alcohols, ethanol, phenol, glycerol, lidocaine, bupivacaine, tetracaine, benzocaine, distilled water, hypertonic saline, hypotonic saline, guanethidine, and botulinum toxin.

70. The system of claim 55, wherein the ablative fluid is a heated fluid composition.

71. The system of claim 55, wherein the ablative fluid is a cooled fluid composition.

72. The system of claim 55, wherein the ablative fluid is in the form of a vapor injected through a fluid injection lumen of the catheter body.