Endovascular catheter system for targeted photothermal ablation of perivascular nerves

Abstract

An endovascular system for targeted photothermal ablation of perivascular nerves is disclosed. A catheter includes a fluid lumen communicating with outlet orifices, and an electromagnetic radiation emitter positioned within a support structure that apposes the array against a vessel wall. A proximal console independently controls irradiation and injection parameters. In use, a nanofluid comprising plasmonic nanoparticles, such as gold nanorods tuned for near-infrared absorption, is injected into or through the vascular wall and subsequently irradiated intraluminally; the nanofluid absorbs energy and converts it to heat to ablate adjacent nerve fibers while reducing non-target tissue heating.

Description

DESCRIPTIONTITLE OF THE INVENTION

[0001] Endovascular Catheter System for Targeted Photothermal Ablation of Perivascular NervesTECHNICAL FIELD

[0002] The present invention relates to minimally invasive vascular intervention. More specifically, it concerns endovascular systems, catheters, nanofluid compositions, and control consoles configured to inject an electromagnetic-absorptive agent into or through a vessel wall and to deliver intraluminal electromagnetic radiation to effect localized photothermal ablation of perivascular nerves, such as renal sympathetic nerves. The invention pertains to IPC classes including A61 B 18 / 20 (methods or apparatus for sterilising or disinfecting, particularly photodynamic therapy, photothermy, or photophoresis), A61 M 25 / 00 (catheters; needles), and A61 K 49 / 18 (preparations for testing in vivo, particularly X-ray contrast agents or suspensions thereof, e.g., for angiography).BACKGROUND OF THE INVENTION

[0003] Resistant hypertension remains a major unmet clinical need, affecting approximately 10-20% of hypertensive patients and contributing to cardiovascular morbidity and mortality worldwide. Endovascular renal denervation (RDN) has re- emerged as a promising therapy following clinical trials demonstrating blood pressure reductions in select patients; however, existing systems, such as those using radiofrequency (RF) ablation or ultrasound, frequently heat intervening fluids and adjacent tissues indiscriminately. This indiscriminate heating risks intimal damage, endothelial dysfunction, acute vessel injury, procedural pain, inconsistent efficacy due to variable energy penetration to the adventitial nerve plexus, and prolonged recovery times.

[0004] Conventional RF or ultrasound modalities deposit energy primarily at or near the intima / media layers of the vessel wall, and efficacy at the adventitial nerve plexus, where sympathetic nerves are predominantly located, can be inconsistent, particularly at lower energy settings employed to mitigate intimal injury. Prior art, such as microwave ablation systems, or intraluminal ultrasound within cooling balloons, aims to spare the arterial wall but still suffers from challenges in precise depth control and circumferential uniformity.

[0005] Nanoparticle-mediated approaches, including photothermal hydrogels or nano shells, have been explored for RDN or related vascular therapies, but these often rely on external delivery, percutaneous injection, or non-endovascular methods, limiting clinical translatability and increasing procedural complexity. There is a critical need for a device and method that localize energy deposition at the nerve target while sparing the intima and media, provide predictable depth and circumferential distribution of ablation, enable real-time operator control of injection and irradiation parameters, and integrate with standard endovascular workflows under fluoroscopic guidance.SUMMARY OF THE INVENTION

[0006] Disclosed herein is an endovascular catheter system that addresses the limitations of prior art by injecting an electromagnetic-absorptive nanofluid directly into or through the vessel wall and subsequently irradiating the region intraluminally. The nanofluid converts incident electromagnetic energy (e.g., near-infrared light) to localized heat, thereby ablating adjacent perivascular nerve fibres, such as renal sympathetic nerves, while substantially reducing non-target tissue heating in the intima, media, and lumen. This targeted photothermal ablation enhances procedural safety, efficacy, and consistency compared to indiscriminate energy delivery systems.

[0007] In one aspect, the system comprises a catheter including a circumferential hypotube array having a plurality of outlet orifices and a distal electromagnetic emitter (e.g., a near-infrared laser or LED) positioned coaxially within a support structure. The support structure imparts outward radial force to appose the hypotube array against the vessel wall and counteracts reaction forces during high-pressure injection, ensuring stable positioning and uniform nanofluid distribution. Optionally, each outlet orifice is encircled by a radiopaque marker band concentric with the orifice for fluoroscopic visualization)

[0008] A proximal console may independently control (i) irradiation parameters, such as wavelength, power, intensity, duration, and duty cycle, and (ii) injection parameters, such as pressure, volume, flow profile, and pulse timing. The console may incorporate an actuated syringe, peristaltic pump, or piezoelectric metering mechanism for precise nanofluid delivery, with optional integration of physiological feedback (e.g., temperature or impedance sensors) for closed-loop control.

[0009] In certain embodiments, the nanofluid comprises plasmonic nanoparticles, such as gold nanorods (GNRs) with aspect ratios tuned for peak near-infrared (NIR) absorption (e.g., longitudinal plasmon resonance at 808 nm), dispersed in a biocompatible carrier fluid. Exemplary emitter wavelengths lie between 750-1 100 nm, including clinically relevant bands such as 785 nm, 808 nm, 830 nm, 850 nm, 980 nm, and 1064 nm selected for optimal tissue penetration and nanoparticle absorption while minimizing haemoglobin and water interference.

[0010] Variants of the system include balloon-assisted expansion for enhanced apposition in tapered vessels, configurations for generating spiral or helical lesion patterns via rotational catheter manipulation, protocols for multiple passes with repositioning along the vessel, and software-controlled treatment routines stored on a non-transitory computer-readable medium. These features enable customized ablation zones tailored to vessel anatomy and patient-specific needs, such as renal artery diameters ranging from 3-7 mm.

[0011] The integration of Photothermal Therapy (PTT) into renal denervation represents a novel and promising approach to managing resistant hypertension. By utilizing the precise and controlled heating capabilities of nanoparticles activated by electromagnetic radiation (typically NIR light) this invention could offer a more effective and safer alternative to traditional nerve ablation methods. Advantages will include less unnecessary damage to surrounding tissue, less pain and trauma for patients, less procedural time and more efficient and effective treatment.

[0012] For example, radiofrequency ablation can cause excessive heating, potentially damaging surrounding tissues. By delivering a mediating absorptive agent, such as gold nanoparticles, our system increases the specificity of PTT treatments, protecting untargeted tissue by lowering energy requirements, and may decrease the need for invasive electrode placement.

[0013] This summary is provided to introduce a variety of concepts in a simplified form that is disclosed further in the detailed description of the embodiments. This summary is not intended to identify key or essential inventive concepts of the claimed subject matter, nor is it intended for determining the scope of the claimed subject matter.

[0014] Briefly summarized, disclosed herein is a system consisting of an endovascular catheter device for ablating nerves in patients including: hypotube array comprising of fluid outlet orifices and circumferential radiopaque marker bands; one or more electromagnetic radiation emitters located coaxially inside the support structure; a plurality of retaining rings that secure the hypotube array to the support structure; at least one support structure configured to support the hypotube array; and a distal collar capable of allowing a guidewire to pass through.

[0015] In one embodiment, the device consists of a self-expanding or actuated hypotube array with incorporated fluid outlet ports or orifices located around a central axis to engage the interior surface of the wall of the renal artery or other vessel of a human body allowing the injection of a nano fluid for ablating tissue, such as nerve fibers.

[0016] The system also controls the depth of penetration of the nano fluid into and beyond the tissue of the vessel wall. The preferred embodiment of the catheter includes structures which provide radial and lateral support to the hypotube array so that they expand uniformly and maintain their position against the interior surface of the vessel wall as the fluid injection is carried out to deliver the nano fluid to the target area.In yet another embodiment, the system includes an intravascular catheter having an injection structure capable of delivering a nanofluid into / through the vessel wall at a range of pressures, volumes and durations of injection. The system also emits a targeted intravascular electromagnetic radiation source. A nanofluid, acting as an electromagnetic absorptive agent, is injected into the target area via the injection structure. Upon injection to the area of interest or target area the nanofluid is exposed to electromagnetic radiation delivered through the intravascular electromagnetic radiation source at the appropriate output parameters. The nanofluid absorbs the electromagnetic energy and converts it into heat, causing thermal ablation of vascular nerve fibers surrounding them.

[0017] The invention may also be expressed as a device for targeted photothermal ablation of perivascular nerves, the device comprising:

[0018] a nanofluid delivery structure comprising at least one fluid outlet that faces away from a central longitudinal axis of the device and is movable away from that axis; and an electromagnetic radiation emitter.

[0019] The invention may also be expressed as a device wherein a circumferentially- distributed array of the fluid outlets surrounds the central longitudinal axis.

[0020] The invention may also be expressed as a device wherein the delivery structure is radially movable or expandable away from the central longitudinal axis.

[0021] The invention may also be expressed as a device that further comprises a support disposed radially inboard of the at least one fluid outlet and configured to act radially outwardly on the delivery structure.

[0022] The invention may also be expressed as a device wherein the support is selfexpanding when released from a restraining sheath.

[0023] The invention may also be expressed as a device wherein the support is inflatable by fluid pressure.

[0024] The invention may also be expressed as a device wherein the delivery structure comprises a plurality of tubular conduits each having at least one of the fluid outlets penetrating a wall of the conduit.

[0025] The invention may also be expressed as a device wherein each conduit has outwardly convex curvature along its length.

[0026] The invention may also be expressed as a device wherein at least one of the fluid outlets is disposed at a radially outward apex of each conduit.

[0027] The invention may also be expressed as a device wherein each conduit is flexible whereby deflection of the conduits can move the fluid outlets away from the central longitudinal axis.

[0028] The invention may also be expressed as a device wherein more than one tubular conduit create a circumferential lumen array.

[0029] The invention may also be expressed as a device wherein the fluid outlet orifice is in communication with a needle-like lumen that extends radially outward into or through the vessel wall.The invention may also be expressed as a device wherein the electromagnetic radiation emitter comprises a near-infrared light-emitting diode (LED).

[0030] The invention may also be expressed as a device wherein the electromagnetic radiation emitter comprises an optical fiber coupled to a laser diode.

[0031] The invention may also be expressed as a device wherein the emitter operates at a wavelength between 750 and 1 100 nm.

[0032] The invention may also be expressed as a device wherein the console adjusts at least one of wavelength, power, intensity, duty cycle, and exposure duration being delivered by the electromagnetic radiation emitter.

[0033] The invention may also be expressed as a device wherein the console adjusts at least one of injection pressure, volume, flow rate, and pulse timing.

[0034] The invention may also be expressed as a device further comprising software stored on a non-transitory medium configured to execute a treatment routine coordinating injection and irradiation to form a circumferential or helical lesion pattern.The invention may also be expressed as a device wherein the support structure comprises one or more tubes, slotted tubes, braided sleeves, or elastic struts providing uniform expansion.

[0035] The invention may also be expressed as a device wherein each hypotube includes an orifice geometry, such as a circular, oval, tubular or conical orifice geometry to define a jet profile and penetration depth.

[0036] The invention may also be expressed as a device wherein the orifice location is protruding more radially than other portions of the lumen, such that the orifice location is more inclined to embed in the vessel wall

[0037] The invention may also be expressed as a device further comprising temperature or impedance sensing to provide feedback control of irradiation.

[0038] The invention may also be expressed as a device wherein the tubular conduits further comprise fluoroscopic marker bands aligned with respective outlet orifices to indicate injection sites.

[0039] The invention may also be expressed as a device wherein the console includes an actuated syringe or peristaltic pump to meter the nanofluid.

[0040] The invention may also be expressed as a device wherein the catheter is configured for renal artery treatment sites and sized for diameters between 1 and 8 mm.

[0041] The invention may also be expressed as a device wherein the emitter is arranged coaxially within the delivery system. a) The invention may also be expressed as a device wherein an emitter is positioned more radially extended than the central axis of the artery or system, encouraging contact with the artery wall and minimizing the path length of the irradiation through the blood stream.

[0042] The invention may also be expressed as a device wherein the catheter further comprises a lumen for power leads isolated from the fluid lumen.

[0043] The invention may also be expressed as a kit, comprising a catheter, at least one sterile vial containing the nanofluid and instructions for use specifying parameter ranges for vessels of differing diameters

[0044] The invention may also be expressed as a kit further comprising a sterile tubing set, filters, and a disposable syringe compatible with the console.

[0045] The invention may also be expressed in terms of a method of ablating perivascular nerves, comprising:

[0046] navigating a photothermal ablation device to a target vascular segment;

[0047] pressing a nanofluid delivery structure of the device radially outwardly against a vessel wall of the target vascular segment;

[0048] delivering a nanofluid comprising plasmonic nanoparticles from at least one fluid outlet of the delivery structure into or through the vessel wall to locations adjacent to perivascular nerve fibres; and

[0049] by emitting electromagnetic radiation intraluminally at a wavelength absorbed by the nanofluid, generating heat local to the delivered nanofluid to ablate the adjacent nerve fibres preferentially relative to non-target tissues.

[0050] The invention may also be expressed in terms of a method including delivering the nanofluid from a plurality of fluid outlets in a circumferentially-distributed array.

[0051] The invention may also be expressed in terms of a method including repositioning the or each fluid outlet to another location within the arterial system and delivering the nanofluid to that other location.

[0052] The invention may also be expressed in terms of a method including repositioning the or each fluid outlet by rotating the delivery structure within the vessel.

[0053] The invention may also be expressed in terms of a method, including repositioning the or each fluid outlet by moving the delivery structure along the vessel.

[0054] The invention may also be expressed in terms of a method wherein the nanofluid comprises gold nanorods with an aspect ratio selected to position the plasmon resonance at approximately 808 nm.

[0055] The invention may also be expressed in terms of a method wherein irradiation is delivered in a pulsed mode having a duty cycle between 1 % and 99%.

[0056] The invention may also be expressed in terms of a method wherein irradiation is delivered in a non-pulsed mode

[0057] The invention may also be expressed in terms of a method further comprising monitoring a temperature proxy and pausing irradiation upon exceeding a threshold.

[0058] The invention may also be expressed in terms of a method wherein injection pressure is between 0.1 and 50 bar and total injected volume per site is between 0.05 and 1 .0 mL.

[0059] The invention may also be expressed in terms of a method wherein lesion sets are formed in a spiral pattern by rotating and translating the catheter between injections.

[0060] The invention may also be expressed in terms of a method wherein the vessel is a renal artery and the ablation targets renal sympathetic nerves.

[0061] The invention may also be expressed in terms of a method further comprising repositioning the catheter after irradiation to treat additional sites.

[0062] The invention may also be expressed in terms of a method, wherein the emitter wavelength is selected from 785 nm, 808 nm, 830 nm, 850 nm, 940nm, 980 nm, 1064nm, and 1270nm.

[0063] The invention may also be expressed in terms of a method wherein the carrier viscosity is adjusted to confine the bolus within the adventitia during irradiation.

[0064] The invention may also be expressed in terms of a method wherein the carrier comprises saline, phosphate-buffered saline, hyaluronic acid, PEG-modified hydrogel, or combinations thereof.

[0065] The invention may also be expressed in terms of a nanofluid, wherein the gold nanorods include a surface coating selected from polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), silica, or combinations thereof.

[0066] The invention may also be expressed in terms of a nanofluid, wherein nanoparticle concentration is between 10A9 and 10A12 particles per mL.

[0067] The invention may also be expressed in terms of a nanofluid, wherein the extinction coefficient at the excitation wavelength is at least 10A8 MA-1 cmA-1 .

[0068] The invention may also be expressed in terms of a nanofluid, further comprising an imaging agent selected from iodinated contrast or microbubbles to assist placement.

[0069] The invention may also be expressed in terms of a nanofluid, wherein the zeta potential is adjusted to between -30 mV and +10 mV for tissue compatibility.

[0070] A nano fluid is passed through the fluid lumen from proximal end to distal end at a predetermined pressure and volume. Upon reaching the fluid outlet orifice the fluid exits with enough velocity and pressure to penetrate the vessel wall to a predetermined depth. A customisable volume of nano fluid is delivered to the target area. A targeted intravascular electromagnetic radiation source located on the distal end of the treatment device is activated. This in turn heats the nano particles within the treatment region., which in turn heats the fluid bolus injected into the target site containing the renal nerves. This localised increase in temperature causes ablation of the nerves.BRIEF DESCRIPTION OF THE DRAWINGS

[0072] FIG. 1 is a cross-sectional view of a distal treatment section of the device in situ within a renal artery, illustrating the catheter shaft, guidewire lumen, connector tube housing the electromagnetic emitter, and the circumferential hypotube array apposed to the vessel wall.

[0073] FIG. 2 is a system-level schematic view showing the catheter handle integrated with a proximal console, wherein the console includes an electromagnetic radiation controller (e.g., laser driver) and an injection parameter controller (e.g., pump interface). A cross sectional view of the treatment site, with radially expanded array of hypotubes is shown. A cross sectional view of the radially collapsed device, proximal to the treatment site is also shown.

[0074] FIG. 3 shows the access and navigation of the device to the treatment site in the renal artery.

[0075] FIG. 4 illustrates the device in its radially collapsed configuration at the treatment site. Proximal and distal collars are in close proximity.

[0076] FIG. 5 illustrates the device in its radially expanded configuration at the treatment site. Proximal and distal collars are extended axially from each other. The hypotube array is radially expanded such that the fluid outlet at the apex of each fluid conduit is in contact with the artery wall.

[0077] FIG. 6 illustrates the injection of a bolus of nanofluid, via the fluid orifice, into the artery wall.

[0078] FIG. 7 is a cross-sectional view of the bolus formation immediately following injection of the nanofluid.

[0079] FIG. 8 illustrates the activation of the electromagnetic radiation emitter.

[0080] FIG. 9 illustrates the proximal repositioning of the radially collapsed device in the artery following an initial round of treatment in the more distal locations.

[0081] FIG. 10 illustrates repositioned device in its radially expanded configuration in advance of a subsequent round of treatment.

[0082] FIG. 1 1 illustrates the interruption and damage of the target renal nerve following completion of the therapy

[0083] FIG. 12 illustrates an individual orifice apposed to a vessel wall.

[0084] FIG. 13 illustrates a needle that brings the orifice into the artery wall prior to injection of nanofluids.

[0085] FIG. 14 illustrates a balloon assisted radial expansion of the hypotube array and a cooling fluid supply systemDETAILED DESCRIPTION OF THE INVENTION

[0086] Unless indicated otherwise, terms have their ordinary meanings as understood by persons of ordinary skill in the art. Singular forms include plural referents unless the context unequivocally dictates otherwise. All numeric ranges are inclusive of their endpoints unless stated otherwise. The invention is described with reference to specific embodiments but is not limited thereto.Exemplification

[0087] Referring to the drawings, FIG. 1 shows an example embodiment of the distal end of the system. It shows a section of the distal end of the system at the treatment site (17) within the blood vessel (2).

[0088] In FIG. 1 , within the blood vessel 2 of a patient, a catheter 1 has been positioned at the treatment site (17) and the outer delivery sheath (1 ) has been partially withdrawn proximally to allow for the radial expansion of the hypotube array (20) into its treatment configuration. Within the proximal end of the catheter, there is a guidewire lumen (7) extending from the proximal end of the device to the very distal end (16), anelectromagnetic radiation emitter (8) and power leads (9) leading from the proximal end of the system to electromagnetic radiation emitter (8).

[0089] FIG. 1 shows an example embodiment of the distal end of the system. It shows a magnified view of a section of the distal end of the system at the treatment site (17) within the blood vessel (2). A catheter (1 ) is advanced to the treatment site (17) within the blood vessel (2). Fluid travels along the fluid lumen (3) from the proximal end of the system towards the distal end of the system.

[0090] The fluid lumens (3) carry fluid to an array of hypotubes (20). Retaining rings (1 1 ) couple the 8 hypotubes in the hypotube array (20) to the support structure (6). The distal ends of the hypotubes terminate at, and are connected to distal collar (23). The distal collar (23) is connected to the proximal collar (24) with a connector tube (25). The array of hypotubes (20) are radially expanded to make contact with the blood vessel wall (22) at the treatment site (17).

[0091] A fluid outlet orifice (4) is located at the apex of each hypotube in the hypotube array (20). A radiopaque marker band (5) can surround each hypotube in the hypotube array (20). The radiopaque marker band (5) can have an orifice that is concentric with the fluid outlet orifice (4). The hypotube array (20) has a support structure (6) to help provide outward radial force. The catheter (1 ) contains a guidewire lumen (7) extending from the proximal end, terminating at a distal collar (23).

[0092] A guidewire (10) runs through the guidewire lumen (7), exiting at the distal collar (23). The connector tube (25) contains an electromagnetic radiation emitter (8) with power leads (9) supplying power to the electromagnetic radiation emitter (8).

[0093] The delivery catheter (1 ) initially houses the entire expandable hypotube array (20) in it is collapsed configuration during navigation to the treatment site and vessel. The outer delivery catheter (1 ) is then partially withdrawn proximally to allow the expandable hypotube array (20) to expand to its larger treatment configuration, with each hypotube in the hypotube array (20) moving radially outward to make contact with the vessel wall.

[0094] Still referring to FIG. 1 , the hypotubes of the hypotube array (20) can be supported with outward radial force by support structures (6). The support structures (6) can be coupled to the hypotubes of the hypotube array (20) by retraining rings (1 1 ). The support structures (6) can also provide support by opposing the injection forces at the fluid outlet orifices (4). The fluid outlet orifices 4 can be positioned within the hypotubes of the hypotube array (20). In various time intervals, additional nanofluids can be injected by the medical professional within the fluid outlet orifices (4). Radiopaque marker bands (5) can be configured at each of the hypotube of the hypotube array (20) and be adjacent or abutting the artery walls (2).

[0095] Further, the radiopaque marker bands (5) can have an orifice that is concentric with the fluid outlet orifices. The injected nanoliquids can be passed through the hypotubes in the hypotube array (20) at the distal end of the treatment area to eventually be injected into the patient through the fluid outlet orifice (4).

[0096] With respect to FIG. 1 , power leads (9) can also be configured within a separate lumen running parallel to the guidewire lumen (7). The power leads (9) can supply power to the electromagnetic radiation emitter (8).

[0097] The system can repeat as many iterations as needed for the prescribed treatment of the patient. Further, the electromagnetic radiation emitted and injection parameters can be updated and varied depending on the treatment needs of each patient.

[0098] FIG. 2 illustrates other aspects of the system. A view of the system is illustrated. The system is capable of delivering various treatment liquids and materials into the patient at various intervals. Another aspect that is shown in FIG. 2 is a console (12) that has an electromagnetic radiation controller (13) that controls variation of ene gy parameters such as power, duration, intensity and wave length.

[0099] The energy parameters can relate to the electromagnetic radiation emitter (8) positioned at the distal end of the device and treatment site (17). The console also has an injection parameter controller (14) that controls the variation of injection parameters. The injection parameter controller (14) can vary the pressure, volume and velocity of nanofluid delivery relating to the materials being injected into the patient in various treatment intervals.

[0100] Referring again to FIG. 2, a handle (18) is also shown. Further, the handle (18) is located at the proximal end of the catheter. The handle (18) can help control the location, orientation and 1 1 function of the distal end of the system, navigating it to the treatment zone (17) and allowing the user to withdraw the delivery catheter (1 ) enough for the support structure (6) to radially expand.

[0101] The handle (18) may also activate and control injection of nanofluids, and emission of electromagnetic radiation. The distal end of the system will include the hypotubes in the hyoptube array (20) positioned around the electromagnetic radiation emitter (8).

[0102] The fluid outlet orifices (4) and radiopaque markers (5) will also be on the exterior of the hypotubes of the hypotube array (20) that abut the blood vessel wall (22) of the patient. The nano fluids can travel through the fluid lumens (3), through the hypotubes of the hypotube array (20) to the fluid outlet orifices (4) that may be positioned concentrically within the radiopaque marker band (5). The support structure (6) will provide the support for the hypotube array (20) and an outward radial force. In addition, the retaining rings (1 1 ) can couple the support structure (6) with the fluid lumen (3). As such, the nano-liquids can can be delivered to the target site through the injection orifice when sufficient injection parameters are used.

[0103] In FIG. 2 the variance of the injection parameters, such as volume, pressure, velocity by the injection parameter controller (14) can affect the level of injection and type of injection which the patient will receive and therefore the spread and volume of the bolus in the injected areas of nanofluids (15). This variable parameter helps the user to ensure adequate delivery of nanofluids (15) sufficient to allow ablation of nerves.

[0104] FIG. 3 shows the access and navigation of the device (1 ) to the treatment site (17) in the renal artery (32). Figure 3 shows a section of aorta (31 ) with a flexible access sheath (30) positioned within the aorta and curving into the renal artery (32) at a renal branch that supplies blood to the kidneys (33). The device (1 ) is situated, broadly coaxially, within the access sheath (30) and a guidewire (10) is situated, broadly co-axially within the device (1 ). Figure 3 shows endovascular access for the device to the right renal artery (32) and for clarity omits a similar access to the left renal artery (33) which can be achieved by withdrawing the device (1 ), guidewire (10) and access sheath (30) from theright renal artery, and then repositioning in left renal artery to ensure nerve ablation in renal nerves (35) to the left and right kidneys.

[0105] FIG. 4 illustrates the device (1 ) in its radially collapsed configuration at the treatment site (17) within a blood vessel (2). Proximal collar (24) and distal collar (23) are in close proximity and the hypotube array (20) is constrained radially within the catheter (1 ). Renal nerves (35) are shown outside the vessel wall (22) within the perivascular space.

[0106] FIG. 5 illustrates the device (1 ) in its radially expanded configuration at the treatment site (17). Proximal collar (24) and distal collar (23) are extended axially from each other. The hypotube array (20) is radially expanded such that the fluid outlet (4) at the apex of each fluid conduit (20) is in contact with the artery wall (22).

[0107] FIG. 6 illustrates the injection of a bolus of nanofluid (36), via the fluid orifice (4) in the fluid conduit (20), into the artery wall (22) and perivascular space surrounding the renal nerves (35).

[0108] FIG. 7 is a cross-sectional view of the bolus (36) formation immediately following injection of the nanofluid. The bolus (36) has been injected from the fluid outlet (4) situated in the most radially distant faces of the fluid conduits (20) into the artery wall (22) and perivascular space surrounding the renal nerves (35). The bolus (36) surrounds the perivascular nerves (35) to be ablated.

[0109] FIG. 8 illustrates the activation of the electromagnetic radiation emitter (8). Electromagnetic radiation (40) (represented by arrows) travels radially from the electromagnetic radiation emitter (8) towards the bolus (36). The nanofluid bolus (36) converts incident electromagnetic energy (e.g., near-infrared light) to localized heat, thereby ablating adjacent perivascular nerve fibres (35), such as renal sympathetic nerves, while substantially reducing non-target tissue heating in the intima, media, and lumen.

[0110] FIG. 9 illustrates the proximal repositioning of the radially collapsed device (1 ) in the blood vessel (2) following an initial round of treatment in the more distal locations. Whereas in previous figures the treatment zone was more distal (to the left of the images),figure 9 represents a subsequent treatment in a more proximal treatment zone (to the right of the images). The proximal collar (24) and distal collar (23) have been pulled axially together to collapse the hypotube array (20) and support structure (6).

[0111] FIG. 10 illustrates repositioned device (1 ) in its radially expanded configuration in advance of a subsequent round of treatment. The connector tube (25) which is connected to the distal collar (24) but can travel telescopically within the proximal collar (23) has been extended distally from the proximal collar (24) and the hypotube array (20) and support structure (6) is radially expanded once more in advance of injection of nanofluid bolus (36) and activation of electromagnetic radiation (40) from the electromagnetic radiation emitter (8).

[0112] FIG. 11 illustrates the interruption and damage of the target renal nerve (35) following completion of the therapy. Damaged sections (37) of renal nerve are represented by dotted lines that correspond with previous treatment sites (17) where boluses (36) and electromagnetic radiation was positioned.

[0113] FIG. 12 illustrates an individual orifice (4) apposed to a vessel wall (22). A radiopaque marker band (5) surrounds the fluid conduit (20) and protrudes with a diameter greater than that of the fluid conduit, and embedding itself deeper into the flexible vessel wall (22). The fluid orifice (4) is located at the apex of the fluid conduit (20). An arrow emerging from the orifice (4) represents the direction of travel of the nanofluid injection traveling radially outwards.

[0114] FIG. 13 illustrates needles (50) that brings the orifices (4) into the artery wall (22) prior to injection of nanofluid bolus (36). The needles can extend telescopically within the hypotube array (20).

[0115] FIG. 14 illustrates a balloon (60) assisted radial expansion of the hypotube array (20) and a cooling fluid supply system (62). The hypotube array (20) can be mounted on, or in contact with, the balloon (60) such that the expansion of the balloon (60) encourages the hypotube array (20) into a radially expanded position. A cooling fluid (61 ) positioned within the balloon (60) helps to minimise unwanted thermal heating of the intima. A cooling fluid supply system (62) extending to an external reservoir maintains a supply of fluid below body temperature.

[0116] System Overview. The treatment system comprises a flexible endovascular catheter assembly and an optional proximal control console. The catheter includes: (i) a guidewire lumen (e.g., 0.035-inch diameter) extending from a proximal handle to and through a distal collar for over-the-wire navigation; (ii) a dedicated fluid lumen (e.g., 0.016-inch inner diameter, polyether block amide material) in fluid communication with a circumferential array of hypotubes (e.g., 8-16 hypotubes, nitinol or stainless steel, 0.5-1 .0 mm outer diameter); and (iii) an expandable support structure (e.g., self-expanding nitinol struts, braided polyethylene terephthalate sleeve, or baloon) that deploys radially outward, for example upon sheath retraction, to appose the hypotube array against the vessel wall with, for example, 0.5-2.0 N force per cm2, countering injection recoil. One or more electromagnetic emitters (e.g., a 200-600 pm core silica optical fiber coupled to a, for example, 1 -5 W NIR laser diode, or an array of surface-mount LEDs) are arranged within the central lumen of the support structure, for example coaxially, or adjacent to the hypotubes to irradiate the injected nanofluid regions with minimal blood path length (e.g., <2 mm). The system is sterilized (e.g., ethylene oxide) and compatible with, for example, 5-24Fr introducer sheaths typically used for femoral access and 4-7Fr sheaths typically used for radial endovascular access. The guidewire may have an atraumatic tip with a radiopaque marker.

[0117] Catheter Assembly. The circumferential hypotube array is formed by laser-cut or etched hypotubes arranged in a 360° configuration, for example spaced 1 -2mm mm apart circumferentially for uniform coverage. Each hypotube is curved along its length with radially outward convex curvature and features at least one outlet orifice, for example 1 - 3 outlet orifices (e.g., 50-200 pm diameter) at or near the radially outward apex for nanofluid ejection. Each orifice is optionally encircled by a radiopaque marker band (e.g., 0.1 -0.2 mm thick platinum-iridium, with a central aperture aligned to the orifice) to enable precise fluoroscopic targeting and confirmation of injection sites. The marker band may protrude 0.05-0.1 mm radially to enhance mechanical engagement with the intima during high-pressure injection, reducing slippage. The support structure ensures uniform expansion (e.g., from 2 mm collapsed to 4-8 mm expanded diameter) and positional stability, with an optional torqueable shaft for rotational alignment in branched vessels.

[0118] Injection Structure. The outlet orifices may be needle ports (e.g., integrated 22-30 gauge retractable nitinol needles for transmural penetration up to 1 -2 mm) or needle-less ports relying on fluid jet dynamics. Port geometries — such as circular (for broad dispersion), oval (for directional jets), conical seats (for focused penetration), or nipplering configurations (for controlled droplet formation) — define the jet profile, penetration depth (e.g., 0.5-3 mm into media / adventitia), and backpressure resistance. Injection parameters may be optimized via computational fluid dynamics modelling: pressures of, for example, 1 -50 bar are anticipated to achieve intramural or transmural delivery with minimal intimal tears , volumes of 0.05-1.0 mL per site, and pulsed profiles (e.g., 10-100 ms pulses at 1 -5 Hz) to allow tissue relaxation and reduce vessel distension. The array can be self-expanding (via superelastic nitinol at body temperature) or actively expanded (e.g., via integrated low-pressure balloon at 2-4 atm or hydraulic actuation).

[0119] Electromagnetic Emitter. The emitter may deliver pulsed or continuous-wave energy at wavelengths (such as 750-1 100 nm) preferentially absorbed by the plasmonic nanofluid (extinction coefficient >10A8 M-1cm-1) while exhibiting high transmission through blood (optical depth <1 cm) and arterial tissue. Suitable emitters may include: (i) multimode optical fibers (e.g., 400 pm core, numerical aperture 0.22) coupled to external diode lasers (e.g., 808 nm, 1 -10 W output); (ii) distal-mounted LED arrays (e.g., 850 nm, 500 mW per chip); or (iii) hybrid systems with diffusers for 360° illumination. Power (0.5- 5 W), duty cycle (10-90%), and exposure duration (10-120 s) can be controlled to achieve localized hyperthermia (55-80°C) at the nanofluid bolus, with <5°C rise in the intima anticipated. Beam divergence, prisms and emitter positioning can minimize off-target exposure, as validated by Monte Carlo simulations of light propagation.

[0120] Console and Control. The proximal console is a rack-mountable or cart-based unit with a touchscreen interface, microprocessor (e.g., ARM-based), and non-transitory memory (e.g., SSD) for logging parameters. It includes: (i) an electromagnetic radiation controller with wavelength tunability (via grating or multiple sources), power modulation (e.g., via pulse-width modulation), and safety interlocks (e.g., automatic shutdown if temperature exceeds 85°C); and (ii) an injection parameter controller interfacing with a metered delivery system (e.g., stepper-motor actuated syringe for 1 -50 mL volumes, or peristaltic pump at 0.1 -10 mL / min). Coordination software may execute predefined routines (e.g., inject-irradiate cycles for helical patterns) or allow manual overrides. The handle incorporates ergonomic controls (e.g., thumbwheels for expansion, buttons forinjection start / stop) and ports for sensor feedback (e.g., thermocouples or optical fibers for distributed temperature sensing).

[0121] Nanofluid Composition. The nanofluid consists of a biocompatible carrier (e.g., 0.9% saline, phosphate-buffered saline at pH 7.4, hyaluronic acid gel at 1 -5 mg / mL for viscosity control, or PEG-modified hydrogel for sustained release) suspending plasmonic nanoparticles. Preferred nanoparticles are gold nanorods (GNRs) synthesized via seed- mediated growth, with lengths 20-100 nm, diameters 5-20 nm, and aspect ratios 2-5 to tune longitudinal surface plasmon resonance (LSPR) to NIR bands (e.g., 808 nm peak). Other nanoparticle material options include palladium. Surface functionalization may include coatings such as polyethylene glycol (PEG, 5-10 kDa for stealth properties), polyvinylpyrrolidone (PVP) for stabilization, or silica shells for biocompatibility, achieving zeta potentials of -30 to +10 mV. Concentrations range from 10A9 to 10A12 particles / mL, with optical density 0.1 -2.0 at the excitation wavelength. Optional additives include imaging agents (e.g., iodinated contrast at 100-300 mgl / mL) for real-time visualization or microbubbles for acoustic enhancement. The nanofluid is, for example, sterile, pyrogen- free, and stable for 6-12 months at 4°C, with viscosity 1 -10 cP to facilitate jet injection while confining boluses to the adventitia (diffusion coefficient <10A-6 cm2 / s).

[0122] Methods of Use. A method for ablating perivascular nerves includes: (i) accessing the vasculature (e.g., femoral artery) and navigating the sheathed catheter over a guidewire to the target segment (e.g., main renal artery, 2-4 cm from ostium) under fluoroscopy; (ii) expanding the support structure to appose the hypotube array, for example by retracting the sheath; (iii) injecting the nanofluid (e.g., 0.1 -0.5 mL total, distributed across 8-12 sites) to form discrete adventitial boluses; (iv) activating the emitter for irradiation (e.g., 808 nm, 2 W, 30-60 s per site) to induce photothermal ablation (nerve fiber necrosis via protein denaturation at >60°C); and (v) monitoring via integrated sensors (e.g., impedance drop indicating lesion formation) and repositioning the catheter (e.g., 5-10 mm proximal / distal with 30-90° rotation) for multi-site treatment. Postprocedure, the catheter is withdrawn, and patients are monitored for 24-48 hours. The method targets renal sympathetic nerves to reduce norepinephrine spillover by >50%, as evidenced by preclinical models.

[0123] Kits. A kit includes: a catheter based injection system; one or more sterile catheters (which may be sized for vessels of 3-7 mm internal diameter); console disposables (e.g.,Luer-lock syringes, IV tubing sets with inline filters <0.2 pm, waste bags); an irradiation emitter that is advanced axially to the distal end of the catheter system; 1 -5 vials of nanofluid (e.g., 10 mL each, with lot-specific certificates); and instructions for use (IFU) specifying parameter ranges (e.g., injection pressure 5-20 bar for 4-5 mm arteries; irradiation 1 -3 W for 45 s). Optional components include calibration phantoms, software USB drives with treatment protocols, and accessories for vessel sizing (e.g., compliant balloons). The kit may be packaged in a sterile tray for single-use procedures.

[0124] Safety and Performance Considerations. By localizing heat generation within injected nanofluid boluses at the adventitia (e.g., <2 mm from nerves), the system is in principle capable of reductions in intimal thermal exposure by 70-90% compared to RF / ultrasound systems, as can be shown in finite element thermal models. Radiopaque markers can enable <1 mm targeting accuracy; programmable jet control minimizes variability (coefficient of variation may be <15% in bolus volume); and feedback mechanisms (e.g., algorithm pausing irradiation on >10°C / min rise or impedance anomalies) enhance safety. Biocompatibility testing per ISO 10993 is expected to show low thrombogenicity and inflammation. Potential risks (e.g., nanoparticle extravasation) are mitigated by dose limits (<5 mg Au total) and rapid clearance (half-life <24 hours via renal / hepatic routes). Clinical translation involves IDE studies demonstrating >80% nerve ablation efficacy with <5% major adverse events.EXAMPLES I EXPERIMENTAL DATA

[0125] Ex Vivo Heating with Nanorod-Laden Tissue. Porcine renal artery segments (n=10, 4-6 mm diameter) will be infused with GNR nanofluid (10A1 1 particles / mL, aspect ratio 3.5:1 , LSPR 808 nm) via simulated intramural injection. Under 808 nm irradiation (2 W, 60 s via 400 pm fiber), treated samples will exhibit temperature rises of 25-40°C (peak 65-75°C at bolus site), 5-12°C greater than saline-infused controls (AT 13-28°C), as measured by infrared thermography and fiber-optic probes. It is anticipated that histology (H&E staining) will confirm adventitial nerve ablation (axonal swelling, myelin loss) with intact intima.

[0126] Diffusion-Dependent Penetration. In gelatin artery phantoms (mimicking 10% attenuation at 808 nm), nanofluid boluses (0.2 mL, 5 bar injection) showed initial confinement to 1 -2 mm depth, with diffusion extending to 3-4 mm over 60 s (tracked viadark-field microscopy). Prolonged pre-irradiation soaking (30-120 s) increased heating extent by 20-50%, correlating with deeper nanofluid distribution and broader lesion widths (2-5 mm circumferential).

[0127] Optical Transmission Along Intraluminal Paths. Blood mimics (hemoglobin 15 g / dL) and artery phantoms (intralipid 1 % for scattering) exhibited 70-90% transmission at 808 nm over 1-2 cm paths, versus <50% at 600 nm (hemoglobin peak). System geometry (coaxial emitter, apposed array) minimized blood layer to <1 mm, achieving >60% energy delivery to boluses, as quantified by power meters and Monte Carlo ray-tracing.

[0128] Heating-Rate Comparison. Under identical irradiation (808 nm, 1.5 W, 30 s), tissues with aspect-ratio-tuned GNRs (4:1 , 10A10 / mL) heated at 1.2°C / s, versus 0.6°C / s for spherical AuNPs (50 nm) and 0.8°C / s for untuned GNRs (2:1 aspect). Higher concentrations (10A11 / mL) accelerated rates to 1 ,8°C / s, with plasmonic efficiency >80% conversion, validated by spectrophotometry and calorimetry. These data support tunable formulations for vessel-specific dosing.

Claims

CLAIMS1. A device for targeted photothermal ablation of perivascular nerves, the device comprising: a nanofluid delivery structure comprising at least one fluid outlet that faces away from a central longitudinal axis of the device and is movable away from that axis; and an electromagnetic radiation emitter.

2. The device of claim 1 , wherein a circumferentially-distributed array of the fluid outlets surrounds the central longitudinal axis3. The device of any preceding claim wherein the delivery structure is radially movable or expandable away from the central longitudinal axis.

4. The device of claim 3, wherein the device further comprises a support disposed radially inboard of the at least one fluid outlet and configured to act radially outwardly on the delivery structure.

5. The device of claim 4, wherein the support is self-expanding when released from a restraining sheath.

6. The device of claim 4, wherein the support is inflatable by fluid pressure.

7. The device of any preceding claim, wherein the delivery structure comprises a plurality of tubular conduits each having at least one of the fluid outlets penetrating a wall of the conduit.

8. The device of claim 7, wherein each conduit has outwardly convex curvature along its length.

9. The device of claim 8, wherein at least one of the fluid outlets is disposed at a radially outward apex of each conduit.

10. The device of claim 7, wherein each conduit is flexible whereby deflection of the conduits can move the fluid outlets away from the central longitudinal axis.1 1 .The device of any preceding claim, wherein more than one tubular conduit create a circumferential lumen array.

12. The device of any preceding claim, wherein the fluid outlet orifice is in communication with a needle-like lumen that extends radially outward into or through the vessel wall.

13. The device of any preceding system claim, wherein the electromagnetic radiation emitter comprises a near-infrared light-emitting diode (LED).

14. The device of any preceding system claim, wherein the electromagnetic radiation emitter comprises an optical fiber coupled to a laser diode.

15. The device of any preceding system claim, wherein the emitter operates at a wavelength between 750 and 1 100 nm.

16. The device of any preceding system claim, wherein the console adjusts at least one of wavelength, power, intensity, duty cycle, and exposure duration being delivered by the electromagnetic radiation emitter.

17. The device of any preceding system claim, wherein the console adjusts at least one of injection pressure, volume, flow rate, and pulse timing.

18. The device of any preceding system claim, further comprising software stored on a non-transitory medium configured to execute a treatment routine coordinating injection and irradiation to form a circumferential or helical lesion pattern.

19. The device of any preceding system claim, wherein the support structure comprises one or more tubes, slotted tubes, braided sleeves, or elastic struts providing uniform expansion.

20. The device of any preceding system claim, wherein each hypotube includes an orifice geometry, such as a circular, oval, tubular or conical orifice geometry to define a jet profile and penetration depth.21 .The device of any preceding system claim, wherein the orifice location is protruding more radially than other portions of the lumen, such that the orifice location is more inclined to embed in the vessel wall22. The device of any preceding system claim, further comprising temperature or impedance sensing to provide feedback control of irradiation.

23. The device of any preceding system claim, wherein the tubular conduits further comprise fluoroscopic marker bands aligned with respective outlet orifices to indicate injection sites.

24. The device of any preceding system claim, wherein the console includes an actuated syringe or peristaltic pump to meter the nanofluid.

25. The device of any preceding system claim, wherein the catheter is configured for renal artery treatment sites and sized for diameters between 1 and 8 mm.

26. The device of any preceding system claim, wherein the emitter is arranged coaxially within the delivery system.

27. The device of any preceding system claim, wherein an emitter is positioned more radially extended than the central axis of the artery or system, encouraging contact with the artery wall and minimizing the path length of the irradiation through the blood stream.

28. The device of any preceding system claim, wherein the catheter further comprises a lumen for power leads isolated from the fluid lumen.

29. A kit, comprising the system of claim 1 and at least one sterile vial containing a nanofluid comprising plasmonic nanoparticles, and instructions for use specifying parameter ranges for vessels of differing diameters.

30. The kit of claim 29, further comprising a sterile tubing set, filters, and a disposable syringe compatible with the console.31 .A method of ablating perivascular nerves, comprising: navigating a photothermal ablation device to a target vascular segment; pressing a nanofluid delivery structure of the device radially outwardly against a vessel wall of the target vascular segment; delivering a nanofluid comprising plasmonic nanoparticles from at least one fluid outlet of the delivery structure into or through the vessel wall to locations adjacent to perivascular nerve fibres; and by emitting electromagnetic radiation intraluminally at a wavelength absorbed by the nanofluid, generating heat local to the delivered nanofluid to ablate the adjacent nerve fibres preferentially relative to non-target tissues.

32. The method of claim 31 , including delivering the nanofluid from a plurality of fluid outlets in a circumferentially-distributed array.

33. The method of any preceding method claim, including repositioning the or each fluid outlet to another location within the arterial system and delivering the nanofluid to that other location.

34. The method of any preceding method claim, including repositioning the or each fluid outlet by rotating the delivery structure within the vessel.

35. The method of any preceding method claim, including repositioning the or each fluid outlet by moving the delivery structure along the vessel.

36. The method of any preceding method claim, wherein the nanofluid comprises gold nanorods with an aspect ratio selected to position the plasmon resonance at approximately 808 nm.

37. The method of any preceding method claim, wherein irradiation is delivered in a pulsed mode having a duty cycle between 1 % and 99%.

38. The method of any preceding method claim, wherein irradiation is delivered in a non-pulsed mode39. The method of any preceding method claim, further comprising monitoring a temperature proxy and pausing irradiation upon exceeding a threshold.

40. The method of any preceding method claim, wherein injection pressure is between 0.1 and 50 bar and total injected volume per site is between 0.05 and 1 .0 mL.41 . The method of any preceding method claim, wherein lesion sets are formed in a spiral pattern by rotating and translating the catheter between injections.

42. The method of any preceding method claim, wherein the vessel is a renal artery and the ablation targets renal sympathetic nerves.

43. The method of any preceding method claim, further comprising repositioning the catheter after irradiation to treat additional sites.

44. The method of any preceding method claim, wherein the emitter wavelength is selected from 785 nm, 808 nm, 830 nm, 850 nm, 940nm, 980 nm, 1064nm, and 1270nm.

45. The method of any preceding method claim, wherein the carrier viscosity is adjusted to confine the bolus within the adventitia during irradiation.

46. The nanofluid of claim 31 , wherein the carrier comprises saline, phosphate- buffered saline, hyaluronic acid, PEG-modified hydrogel, or combinations thereof.

47. The nanofluid of claim 31 , wherein the gold nanorods include a surface coating selected from polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), silica, or combinations thereof.

48. The nanofluid of any preceding composition claim, wherein nanoparticle concentration is between 10A9 and 10A12 particles per mL.

49. The nanofluid of any preceding composition claim, wherein the extinction coefficient at the excitation wavelength is at least 10A8 MA-1 cmA-1 .

50. The nanofluid of any preceding composition claim, further comprising an imaging agent selected from iodinated contrast or microbubbles to assist placement.

51. The nanofluid of any preceding composition claim, wherein the zeta potential is adjusted to between -30 mV and +10 mV for tissue compatibility.

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