Medical devices for delivering one or more agents and methods of use and manufacture

Abstract

Medical devices and methods for fluid delivery. In some uses, the devices are used in methods that include scoring a bodily lumen with expandable spines of an expandable scoring device. In some uses, the devices are used to deliver therapeutic agents through a plurality of needles and deliver anesthetic agents.

Description

MEDICAL DEVICES FOR DELIVERING ONE OR MORE AGENTS AND METHODS OF USE AND MANUFACTURECROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority from U.S. continuation-in-part (CIP) of U.S. App. 18 / 893,739, titled “MEDICAL DEVICES FOR DELIVERING ONE OR MORE AGENTS AND METHODS OF USE AND MANUFACTURE,” and filed September 23, 2024, which is incorporated by reference herein.

[0002] This application incorporates by reference herein for all purposes the entire disclosures of U.S Prov. App. 63 / 584,793 filed September 22, 2023, which is fully incorporated by reference herein for all purposes, continuation-in-part (CIP) of U.S. App. 18 / 435,287 filed February 7, 2024, which is a continuation of U.S. App. No. 18 / 345,746, filed June 30, 2023, now U.S. Patent No. 11,918,768, which is a continuation of U.S. App. No. 17 / 937,287, filed September 30, 2022, now U.S. Patent No. 11,759,550, which is a bypass continuation application of International App. No. PCT / US2022 / 027049, filed April 29, 2022, which claims priority to U.S. App. No. 63 / 182,701, filed April 30, 2021, U.S. App. No. 63 / 202,721, filed June 22, 2021, U.S. App. No. 63 / 202,933, filed June 30, 2021, U.S. App. No.63 / 203,472, filed July 23, 2021, and U.S. App. No. 63 / 240,812, filed September 3, 2021, the entire disclosures of which are incorporated by reference herein for all purposes.

[0003] This application is related to and incorporates by reference herein for all purposes the entireties of the following patent applications: WO / 2022 / 182598 and WO2024 / 177686.

[0004] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.FIELD

[0005] Intravascular (e.g., intimal, medial, adventitial, and / or perivascular) delivery of agents. In some embodiments, the methods can be used for the treatment of peripheral vascular disease, inclusive of both peripheral artery disease and peripheral venous disease. In other embodiments, the methods and devices may be adapted to ablate nerves disposed within and outside of the vessel wall to disrupt neural communication along the nerves, such as renal denervation (“RDN”) for the treatment of uncontrolled hypertension (HTN) and targeted lung denervation for the treatment of chronic obstructive pulmonary disease (COPD). All- 1 -SG Docket No.: 14764-703.601methods of use and applications of the devices, apparatuses, and systems incorporated by reference herein or expressly described herein are included in the “Field” section.BACKGROUND

[0006] Approaches are needed that facilitate desired and / or improved patient outcomes, examples of which are provided herein.SUMMARY OF THE DISCLOSURE

[0007] One aspect of the disclosure is a method of delivering an anesthetic agent in combination with a fluid agent with an intravascular delivery device, comprising: advancing an intravascular apparatus to a target location within a lumen, the apparatus including an inflatable balloon and an expandable infusion scaffold that includes a plurality of primary spines, the plurality of primary spines each including at least first and second radial openings through the primary spine; inflating the balloon to cause the plurality of primary spines to move toward a wall of the lumen; delivering an anesthetic agent with the intravascular apparatus to a wall of the lumen; deploying at least first and second needles from the at least first and second radial openings in the primary spines and into the lumen wall; and delivering a fluid agent from the at least first and second needles associated with each of the plurality of primary spines into the lumen wall.

[0008] One aspect of the disclosure is a method of scoring a lumen wall with a balloon-based intravascular fluid delivery device comprising: advancing an intravascular apparatus to a target location within a lumen, the apparatus including an inflatable balloon and an expandable infusion scaffold that includes a plurality of scoring spines, each of the plurality of scoring spines including a plurality of radial openings through the scoring spine; inflating the balloon to cause the plurality of scoring spines to expand and score the lumen wall; at a time subsequent to scoring the lumen wall, deploying at least first and second needles from radial openings in each of the plurality of scoring spines to penetrate the internal and / or external elastic lamina; and delivering a fluid agent from the at least first and second needles associated with each of the plurality of scoring spines into the lumen wall.

[0009] One aspect of the disclosure is a method of scoring a lumen wall with a balloon-based intravascular fluid delivery device comprising: delivering an inflatable balloon in an unexpanded state and an expandable infusion scaffold in an unexpanded state disposed about the balloon to a location within a vessel, the expandable infusion scaffold comprising a plurality of infusion spines extending along at least a portion of the inflatable balloon, the infusion spines each having a plurality of radial openings therein; expanding the balloon - 2 -SG Docket No.: 14764-703.601radially outward by delivering an inflation fluid to a volume within the balloon, wherein expanding the balloon expands the plurality of infusion spines radially outward and causes the plurality of infusion spines to move towards and into contact with an inner wall of the vessel; dilating the vessel wall as the balloon expands radially; scoring the vessel wall as the infusion spines press against the vessel wall; deploying a plurality of needles from the radial openings in each of the plurality of infusion spines and through the vessel wall; delivering a therapeutic agent through the plurality of needles and into the vessel wall; retracting the needles into the openings in each of the plurality of infusion spines; collapsing the balloonbased intravascular fluid delivery device; and removing the balloon-based intravascular fluid delivery device from the vessel.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] FIG. l is a side view of a distal region of an exemplary infusion device including an expandable scaffold in an expanded configuration.

[0011] FIG. 2A is a side view of a distal region of an exemplary infusion device including an expandable scaffold in an expanded configuration.

[0012] FIG. 2B is a side view of a distal region of an exemplary infusion device from FIG. 2A with needles deployed from elongate spines of the scaffold.

[0013] FIG. 3 A is an end view of a distal region of an exemplary infusion device with an inflatable member inflated.

[0014] FIG. 3B is an end view of a distal region of the exemplary infusion device in FIG. 3 A, shown with needles deployed.

[0015] FIG. 4A is an end view of a distal region of the exemplary infusion device from FIG.3 A, shown within an exemplary vessel.

[0016] FIG. 4B is an end view of a distal region of the exemplary infusion device in FIG. 3 A shown with needles deployed and within an exemplary vessel.

[0017] FIG. 5 is a distal region of an exemplary infusion device illustrating needles deployed from spines of an expandable scaffold.

[0018] FIGS. 6A-6D illustrate views of portions of an exemplary needle sub-assembly or rail track sub -assembly.

[0019] FIG. 6E illustrates an exemplary needle secured to a fluid delivery lumen.

[0020] FIG. 6F illustrates an exemplary rail.

[0021] FIG. 6G illustrates a portion of an exemplary infusion spine.

[0022] FIG. 7A illustrates a top view of an exemplary needle or rail track sub-assembly.- 3 -SG Docket No.: 14764-703.601

[0023] FIG. 7B illustrates a side view of the exemplary needle or rail track sub-assembly from FIG. 7A.

[0024] FIG. 8 is a side view of a plurality of exemplary needles deployed outward from an infusion spine.

[0025] FIG. 9 illustrates an exemplary cross section of an exemplary needle or rail track subassembly.

[0026] FIG. 10 illustrates an exemplary cross section of an exemplary needle or rail track sub-assembly.

[0027] FIG. 11 A illustrates a side view of an exemplary infusion device in a lower profile configuration.

[0028] FIG. 1 IB and 11C illustrate side and end views, respectively, of the exemplary infusion device from FIG. 11 A in an expanded configuration with needles deployed.

[0029] FIG. 12 illustrates a distal region of an exemplary infusion device in an expanded configuration, with regions that are more flexible than other sections of the spine.

[0030] FIG. 13 is a side view illustrating an exemplary infusion device, including a proximal region positioned to be disposed outside of a patient.

[0031] FIG. 14 is a side view illustrating an exemplary manner in which an inflatable member may be secured to a catheter shaft.

[0032] FIG. 15A is a representation of the renal artery and surrounding nerves.

[0033] FIGS. 15B and 15C illustrate, at different axial locations along a renal artery shown in FIG. 17, the renal nerve distribution stratified according to the total number and relative number of nerves.

[0034] FIG. 15CC is a close-up view of the section from FIG. 15C, including in better detail radial distances from the renal artery lumen.

[0035] FIG. 16 shows a portion of an ablation device adapted for renal denervation, including a first set of needles extending further radially than a second set of needles when in their relative deployed configurations.

[0036] FIG. 17 illustrates an exemplary total tissue ablation region, including a proximal ablation zone and a distal ablation zone, the proximal ablation zone extending further radially outward than the distal ablation zone. The tissue ablation region (as well as the ablation zones) extends at least partially circumferentially relative to the renal artery lumen.

[0037] FIG. 18 illustrates an exemplary needle comprising a visualization marker (e.g., marker band) on a non-deployable region or portion of the needle. The exemplary needle in FIG. 18 may be incorporated into any of the examples herein, including in any incorporated by reference herein. For example, the needle in FIG. 18 may be one needle of a plurality of- 4 -SG Docket No.: 14764-703.601needles within a spine, and any of the needles within any number of spines of the apparatus may include a visualization marker (which may be attached to or unitarily formed therewith, for example).

[0038] FIGS. 19A and 19B are exemplary fluoro images showing needles of the exemplary apparatus in an undeployed state and a deployed state, respectively, wherein the apparatus comprises one or more needles that comprise visualization markers (labeled as “marker bands”). Each axially moveable rail assembly may comprise more than one needle, and less than all of the needles may include a visualization marker (e.g., only distal needles of any or all of the rail assemblies may comprise a visualization marker, as is labeled in FIGS. 19A and 19B).

[0039] FIG. 20 illustrates an exemplary apparatus in an expanded configuration, the apparatus including one or more primary spines with needles deployed, and one or more secondary spines.

[0040] FIG. 21 illustrates an exemplary secondary or primary spine, with a discontinuity in the wall of the spine, wherein the discontinuity may facilitate delivery of a second agent out of the spine.

[0041] FIG. 22A illustrates an end view of exemplary device in a deployed configuration with needles deployed, wherein the device includes a plurality of primary spines and a plurality of secondary spines.

[0042] FIGS. 22B and 22BB illustrate an exemplary device with one or more primary spines and one or more secondary spines, wherein secondary spines are positioned in close proximity to the primary spines, adjacent to the primary spines (optionally, but not necessarily, contacting the primary spines).

[0043] FIG. 22C illustrates an alternative to FIGS. 22B and 22BB, in which first and second secondary spines are in close proximity to a single primary spine, wherein the first and second secondary spines are on different sides of the primary spine adjacent to the primary spine (optionally, but not necessarily, contacting the primary spines).

[0044] FIG. 23 illustrates an exemplary scoring balloon catheter, which may integrate any of the features of any of the devices herein, and which may be used to perform any of the medical methods herein.

[0045] FIG. 24 is an exemplary embodiment that includes a customer coupler to custom syringe arrangement.

[0046] FIGS. 25A and 25B illustrate exemplary optional rapid exchange configurations.DETAILED DESCRIPTION- 5 -SG Docket No.: 14764-703.601

[0047] The disclosure herein has broad applicability in the intravascular delivery of one or more fluids to a subject. While some of the disclosure includes methods, devices and systems for the delivery of diagnostic and / or therapeutic agents for the purpose of denervating nerves surrounding renal arteries, these are merely exemplary and not limiting in any way. The devices and systems herein may be referred to as infusion devices and systems.

[0048] The disclosure related to scoring and scoring balloons described in PCT WO2022 / 232589, published November 3, 2022, is fully incorporated by reference herein.

[0049] Infusion devices herein may include a plurality of deployable needles, which are spaced axially (also referred to herein as longitudinally) and circumferentially apart around the infusion device, allowing more uniform circumferential coverage and a greater span of tissue along the length to be targeted with a fluid agent without having to move the infusion device within the vessel. It is of course understood that any of the treatments herein may include delivering a fluid agent, after which the infusion device may be moved to a different location within the vessel or to a different vessel before again delivering the same or a different fluid agent.

[0050] Additionally, infusion devices herein may be positioned against a vessel wall upon application of a radially outward force, which is generally described herein as a force applied by an inflatable member or balloon, although it is conceivable that non-inflatable members may alternatively be used. After the infusion device is apposed against the vessel wall, the needles can be deployed outward such that they pierce through the vessel wall and optionally into tissue surrounding the vessel. The desired therapeutic agent is delivered though the deployed needles, out of the needles, and into the target tissue and / or surrounding the vessel wall. In some methods, the volume and / or rate of infusion may be controlled based on one or more of a treatment zone, vessel inner diameter, and / or desired volume of agent infusion.

[0051] For renal or lung denervation, the ablative therapeutic fluids herein may be one or more agents adapted for chemical neurolysis, such as, and for example only, alcohol.

[0052] One aspect of the disclosure that follows describes non-limiting exemplary ablation devices (any of which may be referred to herein as infusion devices) that are adapted and configured to deliver one or more ablative therapeutic agents and provide one or more of the advantages set forth herein, such as efficiently delivering a desired volume or dose to a target region of tissue within and / or surrounding the vessel wall, and in some cases from 1 mm to 8 mm away from the renal artery lumen, depending on the axial location at which the ablative agent is being delivered.- 6 -SG Docket No.: 14764-703.601

[0053] In this disclosure, the phrase “primary spine” (or similar phrases) refers to infusion spines that include at least one radial opening from which a needle is deployed, even if the device does not include any secondary / spines.

[0054] FIG. 1 illustrates a distal region of an example of an infusion device and incorporates by reference the entire disclosure of FIG. 1 from U.S. Pat. No. 11,071,847. Infusion device 100 includes an expandable infusion scaffold 110 that includes at least first and second infusion spines 112a, 112b, and 112c (three shown in this example), which are shown in FIG. 1 in expanded configurations with the infusion needles deployed. Unless indicated herein to the contrary, the infusion spines herein may also be referred to as a plurality of infusion spines, or plurality of spines. Infusion spines are sized, positioned, and configured to be expandable by a generally radially outward force, which in this example is applied by an inflatable member 150. Any of the inflatable members herein may include one or more of a compliant material (e.g., polyurethane or silicone), a non-compliant material (e.g., polyester or nylon), or a semi-compliant material. As shown, the infusion spines 112a, 112b and 112c are circumferentially spaced about an outer surface of the inflatable member 150 with a long axis (LA) of the infusion device when the spines are expanded. The long axis in this embodiment is also a long axis of the inflatable member 150. In this example, the spines are parallel (or substantially parallel) with the long axis of the infusion device 100 and the inflatable member 150 when expanded, as shown. As used herein, the phrase substantially parallel in this context includes slight deviations from being parallel and includes spines that have configurations that still facilitate the efficient and effective delivery of therapeutic agent to the desired tissue. One of skill in the art will appreciate that substantially parallel as used in this context allows for some deviation from strictly parallel, such as at an angle of five or ten degrees relative to a long axis, for example.

[0055] In this example the inflatable member has a cylindrical configuration when expanded, as shown. The term cylindrical as used in this context includes configurations that approximate a cylinder even if not perfectly cylindrical, which may be the case if a plurality of infusion spines are attached or engaging an outer surface of the inflatable member and the balloon does not have a perfectly cylindrical configuration when expanded. Additionally, an inflatable member may still be considered to have a cylindrical configuration even if the inflatable member has at least one end region that is tapered or has any other configuration that is not orthogonal with the long axis, such as the tapered distal and proximal ends of the inflatable member that are shown in FIG. 1. Additionally, the balloon may optionally have an expanded configuration that is slightly tapered in the proximal to distal direction. Additionally, for example, an inflatable member with a general dumbbell configuration may - 7 -SG Docket No.: 14764-703.601be considered to have a cylindrical configuration. Additionally still, when the description herein describes inflatable members having cylindrical configurations when expanded, it refers to the configuration the inflatable member would take after being expanded outside of a patient. This is meant to clarify that when expanded or inflated within a vessel of the patient, there may be one or more anatomical restrictions that prevent the inflatable member from transitioning to the cylindrical configuration it would assume if expanded outside of a patient, such as the configuration of the vessel wall in which the infusion device is placed. In both scenarios, the inflatable member in these examples is considered to have a cylindrical configuration when expanded.

[0056] The infusion spines herein may be connected (directly or indirectly) to the inflatable member, such as by bonding, adhesion, or using any other suitable technique for securing the spines to an inflatable member. In any of the examples herein, the spines may alternatively not be connected to the inflatable member, but they are still adapted to be expanded by inflation of the inflation member due to their proximity to the inflatable member. For example, the expandable infusion scaffold may be delivered on or over a balloon-based catheter in a compressed low-profile delivery state, and then expanded by dilating the balloon-based catheter at the intended location within the vessel.

[0057] FIG. 1 shows an exemplary inflatable member 150 and an expandable infusion scaffold 110, both in an expanded state or configuration. For delivery, the expandable infusion scaffold is in a collapsed delivery configuration in which the infusion spines are closer to circumferentially adjacent spines than in the expanded state, such as shown in FIG. 11 A. It is understood that FIG. 11 A is meant to illustrate an infusion scaffold in a configuration in which it is not fully expanded (e.g., delivery configuration, or partially expanded). During delivery, the inflatable member is also in a lower profile unexpanded (and uninflated) collapsed delivery configuration. The internal volume of the inflatable member is also less in the delivery state than in the deployed state. Once the infusion device is delivered to the target location within a vessel, the inflatable member is inflated, which pressurizes the inflatable member. This expansion of the inflatable member causes the inflatable member to increase in a radial dimension and apply a force to the plurality of infusion spines that are disposed around the inflatable member. This causes the infusion spines to expand radially and which also causes the relative circumferential distance between the infusion spines to increase, an example of which is shown in FIG. 1 IB. The expandable infusion scaffold is thus expanded towards the vessel wall by inflating and expanding the inflatable member.

[0058] The inflatable member may have a variety of collapsed states or configurations. For example, the inflatable member may be folded in one or more locations to facilitate its - 8 -SG Docket No.: 14764-703.601collapse, while in other embodiments the inflatable member may not have a particular or well-defined collapsed state.

[0059] The inflatable members herein are sized and configured such that when expanded, the plurality of infusion spines will be moved radially outward and in contact or substantial contact with the vessel wall. It is understood that due to some variability in vessel wall size, some portion of any of the infusion spines may not make direct contact with vessel wall. The inflatable member may be sized such that it may have a deployed diameter that is larger than an intended vessel size to help ensure that the infusion spines are in contact or substantial contact with the vessel wall. Maintaining sufficient pressure in the inflatable member such that the infusion spines are in substantial contact with the vessel wall can help support the needles as they are deployed and pierce through the vessel wall, which is described in more detail below.

[0060] Any of the expandable scaffolds herein may have infusion spines that are optionally equidistantly spaced apart along their lengths, an example of which is shown in FIG. 1. For example, two infusion spines may be spaced apart 180 degrees around the inflatable member when the scaffold and infusion spines are expanded. Alternatively, three infusion spines may be spaced apart 120 degrees around the inflatable member when the scaffold and infusion spines are expanded. Alternatively, four infusion spines may be spaced apart 90 degrees around the inflatable member when the infusion spines are expanded, and so forth. In the collapsed delivery state, the infusion spines of the scaffold can also have the same general relative relationship even though they are closer together and not spaced as far apart.

[0061] While equal spacing between spines may in some applications provide more complete delivery of an agent to target tissue around or in the vessel wall, in alternative examples the infusion spines may not all be equidistantly spaced apart around the inflatable member.

[0062] FIG. 14 illustrates a distal portion of an exemplary infusion device, wherein the expandable scaffold is not shown for clarity. In this example, the infusion device includes an inflatable member 1650, which is shown inflated. A distal end of inflatable member 1650 is coupled to inner shaft or member 1670, and a proximal end of inflatable member 1650 is coupled to outer shaft 1672. The inner and outer shafts 1670 and 1672 define therebetween inflation fluid pathway 1674, which is in fluid communication with an interior volume of inflatable member 1650. The inner volume of inflatable member 1650 and fluid pathway 1674 are in fluid communication with a fluid inflation port, such as inflation port 1333 or inflation port 1433 shown in FIGS. 13 and 14, and which are described in more detail below. Alternatively, the inflatable members herein may be secured to the infusion device in a manner that may be the same or similar to known balloon angioplasty catheters, examples of- 9 -SG Docket No.: 14764-703.601which are described in U.S. 4,782,834 and U.S. 10,086,175, and which are incorporated by reference herein for all purposes. Any of the fluid deliver}' devices herein that include one or more spines may include features shown in and described relative to FIG. 14.

[0063] Once the expandable inflation scaffold is expanded and in contact with (or at least substantially in contact with) or directly adjacent the vessel wall, each of a plurality of needles within a spine are deployed outward from a radial opening in the infusion spine, examples of which are shown in FIGS. 1 and 5. FIG. 1 illustrates a plurality of needles deployed from spines of the expandable infusion scaffold. In this merely illustrative example, there are three needles shown deployed from each of the infusion spines. In any of the embodiments herein, each infusion spine may be associated with from two to fifty needles, all of which can be deployed from a radial opening in the spine. As used in this context, the term “associated” refers to needles that are within any particular spine in a delivery state, and are deployable from that particular spine to pierce the vessel wall.

[0064] When this disclosure refers to an infusion spine, it is generally referring to one of the infusion spines of the expandable scaffold. Additionally, when a feature is described with respect to any particular or individual infusion spine, it is understood that all of the infusion spines of any particular scaffold may also have any or all of those features.

[0065] Sets of needles associated with any of the infusion spines herein are generally axially spaced apart, as shown in the examples of FIGS. 1, 2B and 5, for example. Spacing the needles axially apart can provide maximum coverage of the therapeutic agent along the length of the target tissue within and / or around the arterial wall (to target the nerves), which can increase the volume of tissue that may be targeted by using the infusion devices herein. Additionally, by having a plurality of infusion spines spaced around or about the device, with each infusion spine having a plurality of axially-spaced needles deployable therefrom, the infusion devices herein can ensure or increase the likelihood of delivering the ablative agent to as much target tissue within and / or around the vessel wall as possible without having to rotate or move the infusion device to provide the desired circumferential coverage of the infused agent. It is of course understood that the infusion devices herein may also be moved in between episodes of agent delivery into the vessel wall. In these instances, the needles may be retracted, and the infusion device can be moved to a different location within the vessel or to a different vessel. The inflatable member and the scaffold are generally collapsed (at least partially) before moving the infusion device to a new location. It is also understood that devices herein may include a single spine, for example in a helical configuration, wherein a plurality of needles are associated with the single spine.- 10 -SG Docket No.: 14764-703.601

[0066] In any the infusion devices herein, any two axially spaced needles associated with an infusion spine may be spaced from 1 mm to 40 mm apart, such as from 5 mm to 35 mm apart, such as from 10 mm to 30 mm apart, such as from 15mm to 20mm apart.

[0067] In some illustrative embodiments, any of the infusion devices herein may include from two to 50 needles total. For example, an infusion device with three spines, each associated with two needles, would have six needles total. Additionally, for example, an infusion device may include only one spine in a helical configuration that is associated with two needles (the proximal needle longer than the distal needle). Additionally still, for example, an infusion device may include only two spines, each associated with only two needles (the proximal needles longer than the distal needles), in which case the infusion device would include four needles total.

[0068] FIG. 1 illustrates an example in which infusion spines have the same lengths and have distal ends that extend as far distally as the other spine distal ends.

[0069] Needles in different spines may be axially aligned. For example, the exemplary needle placement in FIG. 1 shows three sets of needles that are axially aligned in three needle rows. A row as used in this context refers to two or more needles in different spines that are axially aligned.

[0070] In any of the infusion devices herein, the number of needles associated with each of the infusion spines may be the same. FIG. 1 shows an example of this, with three needles per spine. In alternatives, the number of needles in each of the infusion spines may not be the same. For example, one spine may be associated with two needles, while a second spine may be associated with three needles. Any of the infusion devices herein may have an expandable scaffold with a plurality of spines, optionally wherein none of the spines has the same number of needles as any other spine.

[0071] FIGS. 2A, 2B, 3A, 3B, 4A and 4B illustrate an exemplary infusion device 200 with an expandable infusion scaffold 210 that includes a plurality of infusion spines 212 (one labeled as 212a). Any suitable feature from FIG. 1 or described elsewhere herein may be incorporated into infusion device 200. Infusion device 200 also includes inflatable member 250 that when inflated and expanded causes the expandable infusion scaffold 210 to expand, described in more detail elsewhere herein. Each of the plurality of infusion spines includes a plurality of radial openings or windows 216 (shown in FIG. 2 A), through which the plurality of needles 214 (labeled as 214a, 214b and 214c for the different spines) extend when deployed. FIGS. 2A (side view), 3A (end view) and 4A (end view in an exemplary vessel 275) show the infusion device after the inflatable member 250 has been inflated but with the needles not yet deployed, while FIGS. 2B, 3B and 4B show exemplary needles 214 deployed- 11 -SG Docket No.: 14764-703.601through the openings in the infusion spines 212. FIG. 4B illustrates the needles 214 piercing into (which may be referred to as “through”) the vessel wall 275 and extending into the adventitia “A.” FIGS. 4 A and 4B illustrate intimal “I,” medial “M,” and adventitial “A” layers of the vessel. Any other disclosure herein from any other example may be incorporated into the examples in FIGS. 2A-4B. It is understood that FIG. 4B illustrates a use to target vessel wall tissue, while other embodiments herein are targeting tissue within and / or outside of the vessel wall to target, for example, renal nerves that may reside within and / or outside of the adventitial layer of the vessel wall.

[0072] Generally, the infusion spines herein include a lumen and a plurality of openings or windows therein, such as openings 216 in FIG. 2A. The needles herein are generally disposed within an infusion spine in a delivery state in which the needle tips are radially constrained by the spine, and are deployed from the infusion spine out of one of the needle openings in response to axial movement (proximal or distal) relative to the spine to pierce the vessel wall. The needles herein may be disposed within and deployed from the infusion spines in a variety of ways. Additionally, the needles herein may be in fluid communication with a fluid source in a variety of ways. The needles herein associated with an infusion spine may be deployable at the same time. The needles herein associated with an infusion spine may be deployable by moving them together as a unit, such as if they are coupled to a common axially movable member within the spine. The needles herein associated with an infusion spine may be separately deployable from within the spine.

[0073] Each of the plurality of needles associated with an infusion spine may be coupled to an axially moveable member that is disposed within the infusion spine, such that axial movement of the axially moveable member relative to the infusion spine causes the axial movement of the needle relative to the infusion spine. For example, the needles may each be coupled to separate axially movable members such that the needles within a spine may be axially moved independently from one another.

[0074] In some embodiments herein, the needles associated with an infusion spine are all adapted to move together in unison upon the axial movement of an axially movable member, which may be referred to in this context as a common axially moveable member.

[0075] In some embodiments the axially moveable member (which may be referred to as a rail or rail track) is a separate structure that does not specifically define a fluid lumen, although in these examples the axially moveable member may house therein one of more fluid lumens that are in fluid communication with one or more needles. Additionally, in these embodiments, one or more fluid lumens within the axially movable member may also be- 12 -SG Docket No.: 14764-703.601moved axially relative to the infusion spine in response to axial movement of the axially moveable member.

[0076] FIG. 5 illustrates a portion of an exemplary infusion device 500, which may incorporate any of the disclosure related to infusion device 100 shown in FIG. 1 or any other feature described herein. Infusion device 500 includes an expandable infusion scaffold 510, which includes a plurality of infusion spines 512a, 512b (a third infusion spine 512c is not visible in the side view of FIG. 5). The infusion spines 512a and 512b each include a plurality of openings 516 through which the needles are deployed. In this example, each of the spines is associated with three needles as shown, but more or fewer may be associated with each infusion spine as is described elsewhere herein.

[0077] FIGS. 6A-6F illustrate exemplary features of an exemplary needle subassembly 620 (any of which may be referred to herein as a rail track subassembly, and vice versa), with the infusion spine not shown for clarity. Rail track subassembly 620 is configured to both move the needles to deploy them from the infusion spine openings, as well as provide housing for one or more fluid lumens that are in fluid communication with one or more needles, and such fluid communication to the needles to deliver the agent into the vessel wall when the needles are deployed from the openings in the infusion spine. FIG. 6E illustrates an exemplary needle 614a coupled to fluid lumen 622 with an optional coupler 624. In other embodiments any of the needles herein may be directly connected to a fluid lumen. The needle 614a and fluid lumen 622, as shown in FIG. 6E, are then positioned within rail 623, which is shown alone in FIG. 6F. Rail 623 is an example of an axially movable member that is configured to be axially moved to cause the axial movement of a plurality of needles. Rail 623 is also sized and configured to house therein one or more fluid lumens, in this case fluid lumen 622” and fluid lumen 622”’, as shown in FIG. 6D. As shown in FIG. 6D, in this example each needle is in fluid communication with a distinct or individual fluid lumen, but they are coupled to rail 623 such that they move axially together in unison when rail 623 is moved. With respect to FIG. 6E, each needle is coupled to an individual fluid lumen as shown, then advanced through rail 623 and coupled thereto, as is shown in FIGS. 6A- 6D. FIG. 6D illustrates one example of a plurality of individual fluid lumens 622” and 622”’ housed or disposed within a lumen of rail 623. Rail 623, at least in this exemplary embodiment, can be moved axially to axially move all of the needles, as well as serve to house the individual fluid lumens therein.

[0078] The needle subassembly 623 shown in FIG. 6A can be then positioned in one of the infusion spines, such as by front loading or back loading. When the needle subassembly 620 is loaded into a infusion spine, the needles will deflect radially inward towards the openings 621 that are labeled in FIG. 6F, and the needle subassembly may be positioned in the infusion- 13 -SG Docket No.: 14764-703.601spine such that the needles and needle tips are just proximal to the infusion spine openings 616 (with the needle tips radially constrained by an inner surface of the spine), labeled in the exemplary spine 612 shown in FIG. 6G.

[0079] Any of the needles herein may be formed with a natural bias towards a deployed configuration in which the needles extend at least partially radially outward, such as is shown in FIGS. 6A, 6B, 6C, 6D and 6E. When the needles are collapsed radially down or inward for delivery, they may or may not have a perfectly linear configuration due to their naturally biased and curved deployed configuration. When collapsed for delivery, any of the needles may retain a slight curvature in their configuration, with their tips radially constrained by the inner surface of the spine.

[0080] The use of the term rail herein does not necessarily impart any structural limitations. The rails herein may be elongate members that are sized and adapted to be moveable within an infusion spine lumen to facilitate the movement of one or more needles. Any of the rails herein may be a tubular member or partial tubular member, such as rail 623 shown in FIGS. 6A-6F, or any other elongate member (with or without a lumen) that is sized and configured for axial movement within a spine.

[0081] As part of an exemplary manufacturing of a rail track assembly, the needle and corresponding fluid lumen may be front-loaded through the rail. A coupler (e.g., 624” or 624”’), if used, may be secured (e.g., bonded, welded, or otherwise secured thereto) to the needle and fluid lumen as shown in FIG. 6E. The rail openings 621 may be formed by removing sections of the material of rail 623, which may itself be an elongate tubular member, such as a stainless steel or nitinol tubular member.

[0082] Each infusion spine in the exemplary infusion device shown in FIGS. 6A-6F is associated with at least three subcomponents or subassemblies - the infusion needle(s), the infusion lumen(s), and the rail track subassembly housing the respective infusion needle(s) and infusion lumen(s).

[0083] Any of the disclosure related to FIGS. 6A-6G may be incorporated by reference into any of the suitable disclosure herein related to devices and methods of use that includes scaffolds that comprise spines and radial openings.

[0084] In any of the examples herein, any of the fluid delivery lumens may have an outer diameter from .001 inches to .01 inches, for example. Fluid delivery lumens herein may also be referred to herein as fluid lumens.

[0085] In any of the examples herein, any of the axially moveable members (such as any of the rails) may have an outer diameter from .005 inches to .05 inches.- 14 -SG Docket No.: 14764-703.601

[0086] In any of the examples herein, any of the axially moveable members may have openings (e.g., openings 621) that are axially spaced from 5 mm to 80 mm apart, such as from 10 mm to 50 mm.

[0087] In any of the examples herein, any of the axially moveable members may have openings (e.g., openings 621) that have a length from 2mm to 20 mm.

[0088] In any of the examples herein, any of the spines may have an outer diameter from 0.01 inches to .08 inches.

[0089] In any of the examples herein, any of the spines may have openings (e.g., openings 216, 516) that are axially spaced apart from 5 mm to 80 mm.

[0090] In any of the examples herein, any of the spines may have radial openings (e.g., openings 216, 516) may have openings with a diameter or length dimension from .05 mm to 10 mm.

[0091] FIGS. 7A and 7B, in top and side views, respectively, illustrate an exemplary rail track subassembly 720 (spine not shown for clarity), with three exemplary needles in deployed configurations. Any of the features from assembly 620 of FIG. 6 A may be incorporated into assembly 720. Rail track subassembly 720 includes rail 723, which has openings 721 therethrough (only one of which is labeled in FIG. 7A), and in this example there are three openings 721 in rail 723. Needles 714a are coupled to individual and distinct fluid lumens 722, optionally via couplers 724 but alternatively directed connected thereto, which may be secured to rail 723 to secure the needle to the rail 723 and provide unitary axial movement of the needles 714 (which are individually labeled as 714a’, 714a”, and 714a’”).

[0092] FIGS. 7A and 7B also illustrate how fluid lumens may extend through the rail 723 lumen. For example, fluid delivery lumen 722’ is in fluid communication with needle 714a’ and extends through rail 723. Fluid delivery lumen 722’ extends adjacent to central needle 714a” and fluid delivery lumen 722”, as shown in the central regions of FIGS. 7A and 7B. In the proximal region shown in FIGS. 7A and 7B, all three fluid delivery lumens 722’, 722” and 722’” are adjacent to one another within the rail 723. Any of the fluid delivery lumens herein may include a bend or deviation in its path such that it can pass next to a different needle and its associated fluid delivery lumen, which is shown in FIGS. 7A and 7B. In this manner, the needles can extend in the same direction from the spine, which can be seen in the top view of FIG. 7 A. In the top view of FIG. 7 A, the needles are all extending upward, or out of the page.

[0093] Any of the disclosure related to FIGS. 7A and 7B may be incorporated by reference into any of the suitable disclosure herein related to devices and methods of use that includes scaffolds that comprise spines and radial openings.- 15 -SG Docket No.: 14764-703.601

[0094] In some embodiments, the axially movable member may also at least partially define a fluid lumen that is in fluid communication with one or more needles, such as in the example shown in FIG. 8. FIG. 8 illustrates an exemplary needle assembly 820 shown within an exemplary spine 812a, which includes top or radially outward openings 816. Needle assembly 820 is an axially movable member that in this embodiment also at least partially defines a fluid delivery lumen as shown that is in fluid communication with all of the needles 814a. Needles 814a are shown in their deployed configuration (tissue not shown for clarity) extending out of the spine openings 816. Any other feature from any other example herein may be incorporated into the features shown in FIG. 8, including use with any other inflatable member herein. Any of the disclosure related to FIG. 8 may be incorporated by reference into any of the suitable disclosure herein related to devices and methods of use that includes scaffolds that comprise spines and radial openings.

[0095] FIGS. 11 A-l 1C illustrate an exemplary embodiment of a device, wherein FIGS. 1 IB and 11C show side and end views, respectively, in a deployed configuration. An exemplary guidewire 1154 disposed within guidewire lumen 1155 is also shown, which may be used to deliver any of the infusion devices herein using known guidewire delivery techniques and methods.

[0096] Any of the disclosure related to FIGS. 11 A-l 1C may be incorporated by reference into any of the suitable disclosure herein related to devices and methods of use that includes scaffolds that comprise spines and radial openings.

[0097] Any of the lumens herein (e.g., infusion spine lumen, rail lumen, and / or fluid lumen) may have or benefit from having one or more regions with sufficient flexibility to allow for the infusion device to be delivered to the target location in the vasculature. For example, any of the lumens herein may incorporate a tubular member having a wall with one or more regions with one or more discontinuities, such as cuts, therein (e.g., a laser cut or other technique) that imparts some degree of flexibility along at least a portion of its length. Discontinuities such as cuts made in a wall of any tubular member herein may be in the form of, for example without limitation, including combinations thereof, and at least partial spiral pattern, and at least partial brick pattern, or any other pattern that increases the flexibility of the wall of the lumen. More than one pattern may be implemented in the wall of any lumen (spine lumen, rail lumen, fluid delivery lumen, etc.), and the shape or configuration of a cut pattern may change along the length of the lumen.

[0098] Any of the fluid lumens herein may optionally include a non-permeable membrane on one or both of an inside or the outside, such as an elastomeric membrane (e.g., urethane, silicone, or hydrogel), which can prevent fluid from leaking therethrough. For example, any- 16 -SG Docket No.: 14764-703.601lumens that may include or more discontinuities (e.g., cuts) therein (e.g., laser cut tubes) may include one or more membranes secured thereto to maintain integrity.

[0099] Any of the lumens herein may comprise, for example, any combination of nitinol, stainless steel, polymer tubing, polyimide, braided tubing, or other structural material. Any of the lumens herein may be constructed to provide the desired fluid integrity and / or flexibility when being delivered to the target delivery site.

[0100] In some examples, sections of infusion spine(s) in between needle regions may be more flexible to provide more flexibility at those locations, while the spine regions where the needles are deployed may have relatively higher stiffness to aid the needle piercing through tissue or calcifications. FIG. 12 illustrates an exemplary infusion device 1200, with inflatable member 1250 and scaffold 1210 in expanded configurations or states. Scaffold 1210 includes a plurality of spines 1212a and 1212b. Infusion spine region 1207 may be configured to be more flexible than distal region 1209 and proximal region 1211 that are axially adjacent to region 1207. Needles may be present in regions 1209 and 1211, for example. Each spine may have a plurality of regions 1207 that are more flexible that other sections of the spine, any of which may be axially spaced apart with less flexible spine regions in between, which is described in more details with respect to FIG. 13. Any of the disclosure related to FIG. 12 may be incorporated by reference into any of the suitable disclosure herein related to devices and methods of use that includes scaffolds that comprise spines and radial openings.

[0101] FIG. 13 illustrates an exemplary infusion device 1300 shown with expandable member 1350 in an expanded configuration and a plurality of needles 1314 (only one of which is labeled) deployed from openings in spines 1312 (only one spine is labeled, and there may be additional spines and associated needles). In this example, the spines include first regions 1312’ at and around the locations where needles extend through openings therefrom, and regions 1312” axially adjacent and optionally in between first regions 1312’. First regions 1312’ may be considered to include the spine openings from which the needles extend. First regions 1312’ may be less flexible than regions 1312”. This arrangement may provide sufficient stiffness to the spine region where the needle extends therefrom, helping the needle pierce through tissue (or calcifications), while regions 1312” can provide more flexibility for tracking and delivery. Any of the spines herein may include first and second regions with different stiffness as in the example of FIG. 13.

[0102] As is set forth herein, the scaffold may or may not be attached to the inflatable member. In examples in which the scaffold (including the spines) is attached to the inflatable member, the spines may be secured to the inflatable member along their entire length, or less than their entire length. In some devices, the individual spines may be attached to the- 17 -SG Docket No.: 14764-703.601inflatable balloon at a plurality of axially spaced sections or regions along its length, and not directly attached to the inflatable member at one or more axially-spaced sections or regions along its length. For example only, with respect to FIG. 13, the plurality of spines may be attached to the inflatable member 1350 in regions 1312’, but not attached directly to the inflatable member 1350 in regions 1312”. Not directly attaching the spines to the inflatable member in regions 1312” may allow for more movement and flexibility in the more flexible regions 1312”, which may provide more flexibility overall in the region of the scaffold, which can help when delivering the device. Any of the disclosure related to FIG. 13 may be incorporated by reference into any of the suitable disclosure herein related to devices and methods of use that include scaffolds that comprise spines and radial openings.

[0103] FIG. 13 also illustrates exemplary rail track or needle subassemblies 1320’ and 1320” within corresponding spines, which may include a plurality of needles and one or more fluid lumens, which are described in more detail herein (there may be as many subassemblies as there are spines).

[0104] FIG. 13 also illustrates an exemplary proximal region of infusion device 1300. The proximal region includes an adaptor 1339, which in this example is a three-port adaptor. Adaptor 1339 includes an inflation port 1333 configured to couple to a fluid delivery device (e.g., Inflation Device commonly used with dilatation catheters) to deliver an inflation fluid to inflate expandable member 1350. Adaptor 1339 also houses a guidewire lumen 1341 therein, which is sized and configured to receive guidewire 1337 therein, which may facilitate delivery of any of the infusion devices herein over a guidewire. Adaptor 1339 also includes an actuator coupling region 1335, which may be sized and configured to couple to an actuation member, an example of which is described in more detail with respect to FIG. 14.

[0105] Any other feature from any other infusion devices herein may be incorporated into the example in FIG. 13, and vice versa.

[0106] Any of the needles may be deployable using an external component (that remains outside the patient) that is operatively coupled to one or more needles of the infusion device. In some exemplary embodiments, all of the needles in the infusion device are deployable in unison, and may be operatively coupled to a common deployment actuator. It is understood that other mechanisms may be used to deploy the needles, either in unison or not in unison. For example, the external portion (which may be referred to herein as a proximal region of the infusion device) may have more than one actuator, each of which may control a subsection of the plurality of needles.

[0107] Any of the needles herein may be referred to as microneedles, and may be comprised of nitinol, stainless steel, and / or a combination of nitinol, stainless steel, and other materials- 18 -SG Docket No.: 14764-703.601that adapt the needle to be able penetrate into the vessel wall. Any of the needles herein may range in length from 0.1 mm - 6 mm (e.g., 1 mm - 3 mm; 1 mm - 2 mm; 2 mm - 4 mm; 3 mm - 4 mm) and in size from 20 gauge to 38 gauge, for example. For clarity, the lengths and / or size of individual needles may vary relative to any adjacent needles, either in the same spine or different spines. Furthermore, the relative inner diameter, outer diameter, and wall thickness of the individual needles may be uniform relative to adjacent needles, or they may vary relative to any adjacent needles, either in the same spine or different spines. Additionally, any of the needles herein may have at least one of an inner diameter (“ID”) and an outer diameter (“OD”) that varies along the length of the needle.

[0108] Any of the expandable infusion scaffolds herein may be configured to be an integral part of the balloon system. Alternatively, any of the expandable scaffolds herein may be configured as an independent structure that works ‘in synergy’ with a balloon-based system but is not attached to the balloon system and is not integral to such. As is described elsewhere herein, and incorporated into these embodiments, the expandable scaffold may take the form of various potential configurations designed to enable infusion lumen structural support and communication with the microneedles while also facilitating circumferential and longitudinal infusion of the intended agent to the target site.

[0109] In any of the infusion devices herein, the expandable infusion scaffold may comprise one or more infusion lumens extending in a longitudinal (axial direction; proximal -distal) or non-longitudinal pattern along at least a portion of the length of the balloon that is either integral to, or to be used in synergy with the infusion scaffold. Longitudinal in this context refers generally to at least a portion of an infusion lumen that is parallel with a longitudinal axis of inflatable balloon. In some embodiments, the scaffold may comprise one or more infusion lumens extending in a non-longitudinal pattern along at least a portion of the length of the balloon that is either integral to, or to be used in synergy with the infusion scaffold. Any of the infusion lumens herein may have one or more portions that extend longitudinally and one or more portions that extend non-longitudinally. Examples of a non-longitudinal configuration or pattern in this context include a spiral or helical configuration or other non- longitudinal pattern. For the sake of illustration, the following describes infusion lumens that run or extend longitudinally (axially) along at least a portion of the length of the scaffold. “Longitudinally” (and derivative thereof) and “axially” (and derivatives thereof) are generally used synonymously herein. “Linear” may also be used with longitudinal and axial when made in reference to a linear longitudinal or linear axial configuration, such as if parallel to a longitudinal (or long) axis of the infusion device or an inflatable member.- 19 -SG Docket No.: 14764-703.601

[0110] In some exemplary embodiments herein (such as in FIGS. 6A-6F), the microneedles are secured (e.g., directly attached, or attached via one or more intermediate components) to a rail or other elongate member that is loaded into and disposed in the infusion spine. Exemplary benefits of this design include, but are not limited to, 1) protection of the balloon, guide catheter, delivery sheath, vessel wall, or any other structure in proximity to the microneedles by isolating the sharp needle points during delivery to the target site and / or removal from the target site; 2) the ability to use the scaffold to facilitate controlled expansion of the infusion scaffold; and / or 3) added structural support during deployment of the needles. Needles that are secured to tracks or other elongate members herein may also enable the depth of needle deployment to be controlled or adjusted. For example, any of the rails herein may be in operable communication with an external portion (e.g., as shown in FIG. 13), wherein one or more actuators (e.g., rotatable knobs, axially movable sliders) in the external portion may be adapted to be actuated to control the relative degree of motion of the rail track subassembly (e.g., axial translation), and thereby control the length of the needles that exit radially or somewhat radially outward from the infusion spine.

[0111] Any of the rails herein may also be referred to as a support shaft, any of which may be solid or have a lumen therein. The rails herein may be made of any number of potential materials such as nitinol or stainless steel onto which the needles can be bonded or attached (directly or indirectly), and which may optionally be slatted or laser cut along at least a portion thereof to provide enhanced trackability. Additionally, any of the rails herein may be comprised of more than one type of material along the length of the device. Any of the individual needles herein may include a first end that may be straight or linear and the other free end may be pre-formed (e.g., heat set) to take a perpendicular or near perpendicular configuration (e.g. 60- 120 degrees) to the surface of the vessel when the needle is in its deployed state. A straight or linear section of a needle may be individually secured (e.g., directly attached) to an axially moveable member such as a rail, allowing the free end to be free to deform and assume its deployed shape (e.g., pre-set shape) as it exits the infusion spine opening.

[0112] Axial spacing between needles may be optimized based on the desired anatomical coverage of the agent within and / or outside of the vessel wall, along with spacing to facilitate optimal delivery and trackability of the infusion device to the target site.

[0113] As described elsewhere herein, the individual rail remains inside the respective infusion spine, serving as a mechanism by which to advance and retract the microneedles. One or more openings (or windows) in the infusion spine provide guidance (or a pathway) for the microneedle(s) to exit the infusion spine and can also be adapted to function as added - 20 -SG Docket No.: 14764-703.601structural support as the needle penetrates into the vessel wall. Any of the infusion spines and / or rails herein may comprise or more structures or features configured to function as an additional intraluminal guide, alignment feature(s), and / or ramp as the needle advances out of the infusion spine opening, examples of which are described in WO2022 / 232589, published November 3, 2022, any of which may be incorporated into any of the devices herein.

[0114] In any of the examples herein, advancement and retracting of one or more rails or support shafts, to which one or more microneedles are secured (directly or indirectly), may be enabled through a mechanical turn dial (or any other rotatable handle actuator) or any other mechanical actuation mechanism with intuitive settings to guide the user during deployment and retraction of the microneedles.

[0115] In any of the examples herein, after the microneedles are deployed, infusion may be initiated using, for example only, a controlled mechanism of volume delivery based on the target length and desired volume of agent infused.

[0116] In any of the examples herein, the number of needles per infusion spine may be of any desired number, inclusive but not limited to the range of two to fifty microneedles per infusion spine. In some embodiments, the microneedles may be attached or otherwise secured by techniques such as welding, soldering, mechanical crimping, adhesive, or other techniques to a rail and / or fluid delivery lumen. The needles herein may be bonded directly to a fluid delivery lumen, or they be bonded to one or more intermediate elements such as a coupler. Further, as is described in more details elsewhere herein, the depth of needle deployment may be controlled or adjusted, for example, by utilizing one or more controls in an external portion of the device that may be adapted to control the relative degree of motion of the rail track or support shaft subassembly and thereby control the length of needle that exits radially or somewhat radially outward from the device.

[0117] In some examples herein, each needle associated with a spine is in fluid communication with an individual and separate fluid delivery lumen along at least a portion of the catheter length.

[0118] Any of the fluid delivery lumens herein may have one of a variety of cross-sectional shapes inclusive of, but not limited to, round and kidney shaped. This may be done to help reduce the overall profile of the needle assembly without compromising the volume of agent that can be infused through the lumen(s). FIGS. 9 and 10 are exemplary and non-limiting sectional views of fluid delivery lumens.

[0119] Any of the lumens herein may be comprised of one or more materials inclusive of, but not limited to, polyimide, polymer, nitinol, composite, and / or combination thereof. Any of the fluid delivery lumens and needles within a rail may be secured using a variety of potential- 21 -SG Docket No.: 14764-703.601techniques such as, without limitation, crimping, welding, soldering, potting, adhesive, or other techniques inclusive of a combination thereof. In any of these embodiments, any single needles may thus be in fluid communication with a unique or distinct fluid delivery lumen that is only in fluid communication with that particular needle and not any other needles. In alternatives, a plurality of needles may be in fluid communication with a first fluid delivery lumen, and a different needle may be in fluid communication with a second fluid delivery lumen.

[0120] In any of the embodiments herein wherein the expandable scaffold is attached to the inflatable member, the scaffold and / or individual spines may be bonded to the balloon or secured to the balloon with one or more additional thin-walled layers of material, for example a polymer jacket and adhesive.

[0121] As disclosed elsewhere herein, in any of the embodiments herein, the infusion scaffold may be independent from the expansion balloon (not integrated therewith), yet is adapted to function in synergy with the expansion balloon. In these embodiments, the scaffold may be deployed prior to inflation of the balloon. For example, upon retraction of an outer scaffold sheath, the scaffold may be adapted to be self-expanding, partially selfexpanding, or non-self-expanding. The expansion balloon may be then advanced within the scaffold and dilated to continue to or fully expand the infusion scaffold. The scaffold structure may be deployed passively by retracting an outer sheath (as would a self-expanding stent) or by a mechanical means activated in the handle of the device. The infusion scaffolds herein may be compatible with any off-the-shelf angioplasty balloon, and the balloon may optionally be drug-coated or uncoated. In some of these embodiments, the scaffold may be pre-loaded onto the expansion balloon (yet not attached thereto), with both delivered to the target site in unison, and the infusion scaffold may then be expanded as the dilatation balloon is expanded. The scaffolds herein may thus be at least partially deployed with an expansion balloon, but need not be bonded thereto.

[0122] In alternative examples, the scaffolds herein may be independent without the use of an expansion balloon. For example, the scaffold may be deployed into a target vessel and expanded radially. Radial expansion may be accomplished passively by retracting an outer sheath (as would a self-expanding stent that is commonly used in the field) and / or by a mechanical mechanism activated in the handle of the device. In an exemplary embodiment, the infusion scaffold is configured and adapted to be expanded using a mechanical mechanism or approach that compresses parts of the infusion scaffold longitudinally. The needles may then be advanced, as is described in more detail herein.- 22 -SG Docket No.: 14764-703.601

[0123] In some methods of use, the expandable scaffolds herein may be delivered about an inflatable member, either attached to the balloon or not. After the inflatable member and scaffold are delivered to the target location within a vessel, an inflation can be delivered to an inner volume within the inflatable balloon to cause its expansion. This balloon expansion applies a force to the expandable scaffold, causing the scaffold and spine to radially expand towards the vessel wall. The balloon can be expanded until the infusion device makes contact with the vessel wall. The needles may then be deployed from the spine opening and through the vessel wall, which is described in more detail elsewhere herein, and optionally by distally advancing one or more rails within the spines. The agent may then be delivered from a fluid source, through the one or more fluid delivery lumens, and out of the one or more needle ports and into the tissue within and / or surrounding the vessel wall optionally including the adventitia and surrounding tissue to ablate the renal nerves. The needles may be retracted by retracting one or more rails, and the scaffold and inflatable member may then be collapsed. The infusion device may then be recaptured (e.g., within a sheath or guide catheter) within a delivery sheath and removed from the patient or delivered to another location for a subsequent agent delivery process.

[0124] An additional optional aspect of this disclosure is related to methods of, and devices and systems adapted for, renal denervation. This aspect of the disclosure includes devices that are adapted to deliver an ablative fluid to nerves within and surrounding a renal artery to ablate the renal nerves and treat hypertension. FIG. 15A is a perspective view that represents an anatomical region that includes an abdominal artery, a renal artery branching therefrom towards a kidney (not shown), and renal nerves surrounding the renal artery. Renal denervation approaches have attempted to ablate the renal nerves surrounding the renal artery to treat hypertension using a device positioned within the renal artery. FIGS. 15B and 15C illustrate, at different axial locations as represented in FIG. 15 A, the renal nerve distribution stratified according to the total number and relative number of renal nerves. FIG. 15CC is an enlarged image of FIG. 15C, showing a thicker red circle 1710 which represents a previous assumption that the vast majority of renal nerves are located within 3 mm of the renal artery lumen (wherein the lumen is represented as the thinner red circle 1712). As can be seen in FIG. 15CC, there are many renal nerves beyond 3 mm from the vessel wall 1712. Distances zones can be more clearly seen in FIG. 15CC, including regions of 0-2 mm, 2-4 mm, 4-6 mm, and >6 mm from the lumen wall 1712. Additionally, comparing FIGS. 15B and 15C illustrates that at the axial location shown in FIG. 15C (which is a section at the proximal region in FIG. 15 A), there are more nerves further from the lumen wall 712 than at the more distal location shown in FIG. 15b.- 23 -SG Docket No.: 14764-703.601

[0125] FIG. 16 illustrates an exemplary ablation device that optionally incorporates any of the features from any of the infusion devices herein, alone or any combination thereof. Based on the anatomical learnings shown in FIGS. 15A-15CC, ablation device 1800 may be particularly suited to more effectively ablate renal nerves. Device or apparatus 1800 includes an inflatable balloon 1803, shown expanded in FIG. 16, and spines 1802 disposed about the balloon 1803, as shown. Spines 1802 may include any of the features of any of the spines herein. One difference between device 1800 and alternative infusion devices herein is that device 1800 shows a first set of needles 1804 (three are shown) that, when deployed, extend further radially outward than a second set of needles 1806 when deployed (as shown in FIG. 16). The first set of needles 1804 is axially spaced (proximally in this case) from the second set of needles 1806. This causes device 1800, when in use, to deploy needles at different depths along the length of the renal artery with a single device placement. This facilitates delivering targeted denervation tailored to changes in radial distribution and concentration of nerves along the length of the renal artery, as shown in FIGS. 15A-15CC.

[0126] Proximal needles 1804 may extend radially from the radial opening of the respective spine, when in their fully deployed configurations, a distance from 1.5 mm - 6 mm, as measured in the height dimension “H” shown in FIG. 16 (orthogonal to a long axis of the device), optionally from 2 mm to 4 mm.

[0127] Distal needles 1806 may extend radially from the radial opening of the respective spine, when in their fully deployed configurations, a distance from .5 mm - 4 mm, optionally from 1 mm to 3 mm.

[0128] Proximal needles 1804 are an example of a set of needles that are axially aligned (in the side view shown in FIG. 16) in a proximal row when deployed, and distal needles 1806 are an example of a set of distal needles that are axially aligned (in the side view shown in FIG. 16) in a distal row when deployed. An axial distance or spacing “AD” between needle rows (labeled in FIG. 16) may be from 5 mm to 20 mm.

[0129] A distal needle 1806 and a proximal needle 1804 that are associated with one of the plurality of spines may be coupled to a rail that is axially movable within and relative to the associated spine (discussed above), such that the two needles are adapted to be axially moved together relative to and within the associated spine upon axial movement of the rail. The rail assemblies may be adapted such that the distal and proximal needles are adapted to be pushed distally together relative to the associated spine to the deployed configurations upon distal movement of the rail, or they may be adapted to be pulled proximally together relative to the associated spine to the deployed configurations upon proximal movement of the rail.- 24 -SG Docket No.: 14764-703.601

[0130] The plurality of spines may be arranged about the outer surface of the balloon in any arrangement described herein, such as a helical arrangement or an axial (longitudinal) arrangement.

[0131] Spines 102 may be secured to the inflatable balloon along at least a portion of the lengths, in any of the manners described herein, or they may not be secured to balloon.

[0132] A length of balloon 1803 where it is configured to be apposed against a renal artery wall may be from 10 mm to 40 mm, such as 20 mm to 30 mm, such as 25 mm.

[0133] Device 1800 may include no more than two rows of axially spaced needles, as shown, and optionally includes only six needles (three relatively shorter distal needles and three relatively longer proximal needles).

[0134] FIG. 17 represents part of an exemplary method of using device 1800, which is shown in FIG. 16. After balloon 1803 expansion, causing the spines 1802 to be moved toward the wall of the renal artery, and deploying the two sets of needles 1804 and 1806, FIG. 17 also represents first generally circumferential ablation zone 1904 after an ablative agent is delivered from the first set of (relatively longer) needles 1804, and second generally circumferential ablation zone 1906 after an ablative agent is delivered from the second set of (relatively shorter) needles 1806. As shown, the ablation zones 1906 and 1904 can overlap to some extent and are not necessarily distinct zones or regions. The ablation zones 1906 and 1904 can together create a total renal denervation ablation zone or region. The longer needles 1804 deliver an ablative agent into tissue where many nerves are located, as shown in FIG. 15C and FIG. 15CC (e.g., up to 8 mm from the renal artery). The shorter distal needles 1806 deliver ablative agent at a different axial location to target shallower tissue where many nerves are located, as illustrated in FIG. 15B. Device 1800, by being adapted to deploy needles to different depths at different axial locations (optionally axially spaced from 5 mm to 15 mm apart) along the length of the renal artery, a single device placement facilitates targeted denervation specific to changes in radial distribution and concentration of nerves along the length of the renal artery. Device 1800, by targeting different tissue depths at different axial locations, device 1800 can more effectively ablate a greater number of renal nerves that extend along and outside of the renal arteries.

[0135] The methods of renal denervation herein may include using the devices herein to deliver one or more neurolytic agents to the renal nerves to thereby ablate the renal nerves. For example only, the methods of renal nerve ablation herein may include delivering ethanol, guanethidine, vincristine, or other neurolytic agent to the renal nerves using any of the devices or apparatuses herein. The entire disclosure of Seward, K. (2019). Adventitial Guanethidine (MMS-008) in Comparison to Ethanol and a Prior Formulation of Guanethidine - 25 -SG Docket No.: 14764-703.601(MMS-007) for Renal Denervation: Preclinical Norepinephrine and Histopathology Results. Journal of the American College of Cardiology, 74(13), Suppl B., is incorporated by reference herein in this regard. The entire disclosure of Stefanadis, C. (2013). Chemical Denervation of the Renal Artery with Vincristine for the Treatment of Resistant Arterial Hypertension: First-in-Man Application. Hellinic Journal of Cardiology, 54, 318-231 is also incorporated by reference herein in this regard.

[0136] This disclosure includes additional embodiments below, which are not necessarily limited to devices for use in renal nerve ablation. For example, one or more features in any of the examples below may have application with any of the devices and the methods of use described in WO 2021 / 133966 Al, WO 2022 / 182598 Al, and WO 2022 / 232589 Al, which are fully incorporated by reference herein for all purposes.

[0137] One aspect of the disclosure is related to radiopaque needle marker bands (more generally described and used herein as needle visualization markers) may be integrated with and incorporated into any and all of the devices, systems and / or apparatuses herein (and any of their methods of use), including those incorporated by reference herein. It is thus understood that the visualization markers may be incorporated into devices and apparatuses regardless of the medical procedures for which they are used (e.g., on the veinous side, on the arterial side, for DVT, for PAD, for RDN, used in different bodily lumens, etc.).

[0138] To assist with visualization of needle movement and / or deployment, radiopaque marker bands may optionally be affixed to a portion of the infusion needles. As the rail track / needle assembly is moved axially (e.g., distally advanced), the radiopaque visualization marker provides visual confirmation of the rail-track / needle assembly advancement and / or positional information. Any of the needles in any apparatuses herein may comprise a visualization marker (or a plurality of visualization markers), which may be coupled to the needle during assembly, or which may be unitarily formed with the needle.

[0139] FIG. 18 represents a single needle 2001 in an exemplary deployed configuration, including a proximal end and a distal port or opening. Any of the needles herein may incorporate any feature shown in or described with respect to FIG. 18. As shown, the visualization marker (labeled as “marker band”) may optionally be coupled to (or unitarily formed with) a portion of the needle that is just proximal to the heat-set curve of the needle, and therefore does not exit the infusion spine opening nor penetrate the vessel wall (or other tissue) as the needle is advanced. Merely exemplary and non-limiting dimensions are shown in the side view of FIG. 18, including the exemplary length of the exemplary visualization marker (e.g., 1 mm). The exemplary radial dimension of the deployable portion of the needle- 26 -SG Docket No.: 14764-703.601is shown as 1.5 mm, as is the exemplary length (e.g., 7 mm + / - .5 mm) of the needle portion that is proximal to the deployable portion (which includes the visualization marker).

[0140] As the needles (and / or rails) are moved axially (e.g., advanced or retracted), the radiopaque marker bands on or incorporated into the needles can be seen under fluoroscopy, as shown in the fluoroscopy images in FIGS. 19A and 19B.

[0141] In any of the examples and embodiments herein, including in any of those described in WO 2022 / 232589 Al (which is fully incorporated by reference herein for all purposes), the inflatable member (e.g., balloon) may include at least first and second different materials. For example only, the balloon may include an inner layer of a first material and an outer layer of a second material that is different than the first material, wherein the layers are directly or indirectly coupled. Without intending to be limiting, it may be beneficial to include an inner layer of a first material with certain properties and an outer layer of a second material with certain properties different than those of the first material. For example, and without limitation, in any of the embodiments herein, an inner layer may comprise or consist of nylon (which may be relatively more stable and / or stronger as an inflatable member) and an outer layer may comprise or consist of polyurethane (for example only), which may facilitate a relatively stronger adhesive or thermal bond to one or more sleeves (e.g., a polyurethane sleeve, a PEBAX® sleeve, other polymeric materials, etc.) that are around the individual spines and that are bonded to the inflatable member (in those embodiments herein that include one or more sleeve(s).

[0142] The agent delivery devices herein may optionally include one or more secondary spines, examples of which are described herein, including in WO 2022 / 182598, published September 1, 2022, and PCT / US2023 / 069886, filed July 10, 2023, which are fully incorporated by reference herein, and wherein portions of which are provided below with reference to FIGS. 20, 21, 22 A, 22B, 22BB and 22C herein.

[0143] Secondary spine lumens herein may optionally be able to be made smaller than primary spine lumens due to smaller sizes of optional secondary spines, which can be smaller since they do not need to accommodate needle assemblies therein. For example, FIGS. 22A, 22B, 22BB, and 22C provide examples of secondary spines that are smaller in diameter than the primary spines.

[0144] FIG. 20 also illustrates optional secondary openings 2008 in primary spine 2002, which may be any of the one or more secondary openings herein. When optional secondary openings 2008 are not included in spine 2002, apparatus 2000 is an example of an apparatus with at least one primary spine without any secondary openings, and with at least one secondary spine.- 27 -SG Docket No.: 14764-703.601

[0145] One aspect of the disclosure herein is a method of intravascular fluid delivery and treatment, comprising: advancing an intravascular apparatus to a target location within a vessel; inflating a balloon toward a cylindrical configuration to cause one or more primary spines of an expandable infusion scaffold to expand toward a vessel wall and be disposed about an outer cylindrical surface of the balloon when the balloon is inflated, wherein the one or more primary spines include a plurality of radial primary openings and optionally one or more secondary openings; moving a plurality of needles axially within the one or more primary spines and deploying the plurality of needles out of the radial primary openings such that tips of each of the plurality of needles pierce into the vessel wall; delivering a primary fluid agent out of the plurality of needles and into the vessel wall; and delivering a secondary fluid agent out of openings in at least one of the primary spine or a secondary spine. Delivering the secondary fluid agent may optionally include delivering the secondary agent through a primary spine lumen and out of one or more primary and / or secondary openings in the primary spine to expose the vessel wall to the secondary agent. Delivering the secondary fluid agent may optionally include delivering the secondary agent through a secondary spine lumen and out of one or more secondary openings in the secondary spine(s).

[0146] The delivering steps may comprise delivering the primary fluid agent deeper into the vessel wall than the secondary fluid agent, such as into the adventitia (and / or perivascular space) with the secondary fluid agent exposed to the surface of the vessel wall and optionally to the intima.

[0147] In some embodiments delivering the primary fluid agent can comprise delivering an anti-restenosis agent out of the plurality of needles and into the vessel wall.

[0148] In some embodiments, delivering the secondary fluid agent can comprise delivering an anti -recoil agent out of the one or more secondary openings to expose the vessel wall (for example, at least the intimal layer) to the anti-recoil agent.

[0149] In some embodiments, the primary fluid agent may be the same as the secondary fluid agent.

[0150] The secondary and primary agents may be delivered at the same time, or at different times. In some uses, there may be some overlap in their deliveries, even if the deliveries are initiated at different times. In some embodiments, the primary agent may comprise more than one agent (e.g., two or more different therapeutics), which may be delivered simultaneously (e.g., in combination) or separately at different times.

[0151] In some embodiments, delivering the secondary agent out of the one or more primary and / or secondary openings may be initiated before the plurality of needles are deployed from the radial primary openings. In some embodiments, delivering the secondary agent out of the - 28 -SG Docket No.: 14764-703.601one or more primary and / or secondary openings may be initiated at a time subsequent to when the plurality of needles are deployed from the radial primary openings.

[0152] In some embodiments, delivering the secondary agent out of the one or more primary and / or secondary openings is initiated at a time prior to delivering the primary fluid agent out of the plurality of needles.

[0153] In some embodiments, delivering the secondary agent out of the one or more primary and / or secondary openings occurs while the primary fluid agent is being delivered out of the plurality of needles.

[0154] In some embodiments, delivering the secondary agent out of the one or more primary and / or secondary openings is initiated at a time subsequent to delivering the primary fluid agent out of the plurality of needles.

[0155] In some embodiments, such as shown in FIG. 18 in WO 2022 / 182598 (incorporated by reference herein), delivering a secondary fluid agent through a primary spine lumen comprises delivering the secondary fluid agent between an inner surface of the primary spine and an outer surface of an axially moveable rail to which the plurality of needles is secured. The primary agent may be delivered through a lumen of the rail before it reaches the plurality of needles.

[0156] The primary and secondary fluid agents may optionally be disposed in first and second fluid sources outside of the patient when in use and in fluid communication with the primary and secondary openings. The devices herein may be placed into communication with one or more fluid agent sources prior to the procedure, and thus do not necessarily need to be in communication with the sources when packaged. This may allow one of several different agents and / or types of agents to be delivered with the fluid delivery devices herein.

[0157] The disclosure herein describes spines that may be optionally laser cut to impart flexibility along their lengths, which can increase flexibility for delivery. In some embodiments, the laser cuts in the spines may in fact constitute the one or more secondary openings in the spine, which allows the secondary agent to pass through the cut(s) and into the vessel wall. Laser cuts herein are examples of more generalized discontinuities in the wall of the spine, where the discontinuity is a secondary opening that facilitates weeping of the secondary agent therethrough.

[0158] Both primary and optional secondary spines may include one or more discontinuities (e.g., one or more cuts therein) therein that are secondary openings. FIG. 21 is a side view of spine 2104 (which could be a primary or secondary spine) illustrating a secondary opening 2106 in the form of a laser cut helical pattern that facilitates delivery of secondary agent 2110 out of the spine 2104. In embodiments in which the spine has a laser cut pattern, part of the - 29 -SG Docket No.: 14764-703.601spine may be covered by a membrane to maintain fluid integrity, and the uncovered portion may act as the secondary opening. In these embodiments, the laser cut pattern may facilitate weeping of the secondary agent out of the secondary opening. In embodiments that include a laser cut pattern, a single, uninterrupted cut around the spine (e.g., in a helical configuration) may define a single secondary opening.

[0159] The needles may be adapted to be in communication with a first agent source outside the patient, and secondary openings may be adapted to be in communication with a second agent source outside the patient. The first and second sources may be the same sources, or they may be different sources. The different sources may contain therein the same agent or different agents.

[0160] FIGS. 22 A, 22B and 22C illustrate end views of exemplary devices 2200 in expanded configurations with needles 2220 deployed from primary spines 2204. Any of the disclosure herein may optionally be incorporated into the devices 2200 in FIGS. 22A-22C (including methods of use thereof). The devices 2200 in FIGS. 22A-22C are similar to the device shown in FIG. 20, although the device in FIG. 20 includes a primary spine that also includes secondary openings, and the primary spines 2204 in FIGS. 22A-22C optionally do not include secondary openings (although they may be modified to include secondary openings).

[0161] In this example shown in FIG. 22A, secondary spines 2230 are equidistantly-spaced (or substantially equidistantly spaced) from the two circumferentially closest or nearest primary spines, as shown. Additionally, secondary spines 2230 optionally have smaller outer diameters than the primary spines, as shown. The secondary spines 2230 may be able to be smaller in the outermost dimension compared to the primary spines since they do not need to accommodate needles (and axially movable needle assemblies) therein. In some embodiments, the secondary spines may have an outer diameter (“OD”) that is not more than half the OD of the primary spines, for example, and optionally not more than 25% of the OD of the primary spines. The optionally smaller size of the secondary spines can help reduce the overall delivery profile of the device, compared to similar devices where the primary and secondary spines have the same OD. FIGS. 22A-22C also illustrate primary agent 2212 and secondary agent 2210 being delivered.

[0162] FIGS. 22B and 22BB illustrate a variation on the device from FIG. 22A. Any unlabeled features of the device in FIGS. 22B and 22BB may have the same reference numbers shown in FIG. 22A. The secondary spines 2230 in FIGS. 22B and 22BB (only 1 is labeled in FIG. 22BB) are positioned closer or nearer to the primary spines 2204 compared to their position in the device in FIG. 22 A. In this example, the secondary spines are adjacent and proximate the primary spines. In this context, the term “proximate” refers to being close - 30 -SG Docket No.: 14764-703.601to or near, and may optionally be in contact with, the primary spines. In this context, the secondary spines in FIGS. 22B and 22BB.

[0163] that are “proximate” the primary spines are not equidistantly spaced from the circumferentially closest or nearest two primary spines, as shown. Placing secondary spines proximate the primary spines as shown may further help reduce the delivery profile of the device by placing the secondary spines in close proximity to the primary spines. The secondary spines may optionally comprise a flexible polymeric material, which may further help minimize the profile and / or trackability of the device.

[0164] For example only, the proximate secondary spines may be circumferentially offset between 0 and 45 degrees from the circumferentially closest primary spine (the angle measured circumferentially in the end view), or between 0 and 40 degrees, or between 0 and 35 degrees, or between 0 and 30 degrees, or between 0 and 25 degrees, or between 0 and 20 degrees, or between 0 and 15 degrees, or between 0 and 10 degrees, or between 0 and 5 degrees. For example, in FIGS. 22B (and 22C) the proximate secondary spines are between 0 and 10 degrees from the circumferentially nearest primary spines, but this is understood to be exemplary and non-limiting.

[0165] FIG. 22C illustrates a variation on the device 2200 in FIGS. 22B and 22BB, in which the device includes first and second secondary spines that are proximate to each of the primary spines, as shown. Any unlabeled features of the device in FIG. 22C may have the same reference numbers shown in the devices in FIGS. 22A-22BB. Any of the disclosure from FIGS. 22A-22BB may be incorporated into the device in FIG. 22C. First and second secondary spines are proximate to and on opposite sides of each of a primary spine in this example, as shown. Having a plurality of secondary spines about each primary spine may help expose more of the vessel wall to the secondary fluid agent, without significantly increasing the delivery profile. In this example two of the secondary spines are the same angle from the circumferentially nearest primary spine, but in variations of FIG. 22C the two secondary spines may be at different angles from the nearest primary spine (e.g., one at 10 degree and the other at 20 degrees).

[0166] The end view of FIG. 22C illustrates an angle between a primary spine and a secondary spine. As shown, the angle is defined by two dashed lines, one extending from a device long axis through a longitudinal axis of a primary spine and the other extending from the device long axis through a longitudinal axis of a secondary spine.

[0167] Any of the secondary spines herein may be coupled (directly or indirectly) to at least some portion of the balloon and / or at least some portion of primary spines that are in close proximity to the secondary spines.- 31 -SG Docket No.: 14764-703.601

[0168] An additional aspect of the disclosure is related to the delivery of an anesthetic agent (e.g., lidocaine) from one or more secondary spines, examples of which are shown in figures 20-22C (if the device includes one or more secondary spines). To reduce potential discomfort during needle deployment (for any of the applications of the devices herein), openings in any the secondary spines herein can be used to deliver an anesthetic agent (e.g. lidocaine) to numb the tissue ahead of deployment of the infusion needles.

[0169] This could be of benefit in a number of potential clinical applications inclusive, but not limited to, the treatment of peripheral artery disease (PAD), treatment of deep vein thrombosis (DVT)-related post-thrombotic syndrome (PTS), and renal denervation (RDN) for the treatment of hypertension, which are described herein, including references incorporated by reference herein.

[0170] Optionally, an anesthetic agent can be delivered prior to the deployment of the infusion needles, enabling the anesthetic to infuse from the intimal layer of the vessel into the deeper tissue to increase the numbing effect of the anesthetic agent prior to needle deployment. The time delay between infusion of the anesthetic agent and deployment of the infusion needles may range from a few seconds to several minutes.

[0171] The anesthetic agent can also, or alternatively, be delivered through secondary openings in primary spines (examples of which are described herein) ahead of deployment of the infusion needles.

[0172] Alternatively, the anesthetic agent can be delivered through both of openings in the secondary spine(s) and secondary openings in the primary spine(s). Optionally, delivery of the agent through the openings in the secondary spine(s) and secondary openings in the primary spine(s) can be accomplished with a one-time bolus or through a continuous drip.

[0173] Either concurrent with, or time-delayed from, delivery of the anesthetic agent through openings in the secondary spine(s) and / or secondary openings in the primary spine(s), the anesthetic agent can also be delivered through the infusion needles.

[0174] The anesthetic agent can be delivered as a single agent or mixed with another agent, done so in any combination of delivery channels. For example only, the anesthetic agent delivered through the primary and / or secondary spine(s) can be a single agent, whereas the anesthetic delivered through the infusion needles can be mixed with another agent. Agents that could be mixed with the anesthetic agent for delivery though the infusion needles are optionally diagnostics agent (e.g., contrast media for fluoroscopic visualization of flow) and / or a therapeutic agent (e.g., anti-restenosis agents for the treatment of PAD, antiinflammatory agents for the treatment of DVT, and neurolytic agents for the treatment of hypertension).- 32 -SG Docket No.: 14764-703.601

[0175] If the anesthetic agent is delivered as a single agent through infusion needles, a second agent can be delivered following infusion of the anesthetic. Alternatively, the anesthetic agent can be mixed with a diagnostic agent for initial visualization of flow through the infusion needles, followed by delivery of a therapeutic agent through the infusion needles.

[0176] An additional aspect of the disclosure is related to scoring members, and optionally used to reduce potential discomfort during balloon expansion. Any of the primary spines herein may optionally be used as scoring spines (or scoring members) to score the lumen when expanded, as described generally in PCT / US2022 / 027049 (published as WO / 2022 / 232589A1, which is fully incorporated by reference herein for all purposes, including those related to methods of scoring), and as shown generally in figure 23.

[0177] Scoring balloons have been used commercially in the treatment of PAD to facilitate lower pressure dilatation, thereby reducing the risk of uncontrolled dissection during vessel dilatation and reducing the risk of acute recoil. The primary spines herein may also be referred to as scoring spines when expanded in any method of use herein. The scoring spines herein offer the same benefits when applied to the treatment of PAD, with the added benefit of the scoring spines also serving as conduits for delivery of micro-needles for targeted delivery of a drug into the vessel wall as illustrated herein.

[0178] The scoring spines also enable lower pressure inflations when treating venous occlusions. Venous occlusions can be difficult to dilate due to the presence of tough fibrotic tissue, scarring, and webbing. Current practice is to use high pressure dilatation balloons to expand these difficult to dilate venous lesions, yet high pressure inflations can be very painful for the patient. Enabling lower pressure dilatation with the scoring balloons herein therefore offers a compelling opportunity to reduce the level of pain experienced by the patient and the level of resultant pain management needed during the procedure. For venous lesions that cannot be stented, dilatation with the scoring balloons herein can also reduce the risk of acute recoil and reocclusion. As with other clinical indications for the platform, the scoring spines also optionally serve as conduits for delivery of micro-needles for targeted delivery of a drug into the vessel wall, for example only, delivery of an anti-inflammatory agent to reduce the risk or severity of post-thrombotic syndrome (PTS) associated with deep vein thrombosis (DVT). Enabling lower pressure lesion dilatation and targeted drug delivery with the same catheter also reduces both procedural time and disposable costs associated with the procedure.

[0179] An additional aspect of the disclosure includes a handle that includes a custom coupler as shown in FIG. 24. The custom coupler as shown is a custom coupler that is adapted and sized to be coupled to a custom syringe, which prevents infusion of a non- - 33 -SG Docket No.: 14764-703.601indicated agent using an off the shelf syringe. Any of the proximal handles herein may include a custom coupler.

[0180] An additional aspect of the disclosure is related to optional rapid exchange guidewire configurations, exemplary details of which are shown in FIGS. 25A and 25B. The rapid exchange design may be integrated into any of the devices and systems herein.- 34 -SG Docket No.: 14764-703.601

Claims

CLAIMS1. A method of delivering an anesthetic agent in combination with a fluid agent with an intravascular delivery device comprising: advancing an intravascular apparatus to a target location within a lumen, the apparatus including an inflatable balloon and an expandable infusion scaffold that includes a plurality of primary spines, the plurality of primary spines each including at least first and second radial openings through the primary spine; inflating the balloon to cause the plurality of primary spines to move toward a wall of the lumen; delivering an anesthetic agent with the intravascular apparatus to a wall of the lumen; deploying at least first and second needles from the at least first and second radial openings in the primary spines and into the lumen wall; and delivering a fluid agent from the at least first and second needles associated with each of the plurality of primary spines into the lumen wall.

2. The method of Claim 1, wherein delivering the anesthetic agent comprising delivering the anesthetic agent from secondary openings in the plurality of primary spines.

3. The method of Claim 1, wherein delivering the anesthetic agent comprising delivering the anesthetic agent from the at least first and second needles associated with each of the plurality of primary spines.

4. The method of Claim 3, wherein delivering the anesthetic agent from the at least first and second needles occurs before delivering the fluid agent from the at least first and second needles.

5. The method of Claim 3, wherein delivering the anesthetic agent from the at least first and second needles comprises delivering the anesthetic agent mixed with a contrast agent from the at least first and second needles, and which occurs before delivering a therapeutic fluid agent from the at least first and second needles.- 35 -SG Docket No.: 14764-703.6016. The method of Claim 1, wherein the apparatus further comprises one or more secondary spines disposed about the balloon, and wherein delivering the anesthetic agent comprises delivering the anesthetic agent from openings in the one or more secondary spines.

7. The method of Claim 6, wherein delivering the anesthetic agent further comprises delivering the anesthetic agent from one or more primary spine secondary openings.

8. The method of Claim 1, wherein the method is a method of renal denervation (RDN) with the fluid agent, pulmonary artery denervation (PADN) treating PAD with the fluid agent, treating DVT with the fluid agent, or treating COPD with the fluid agent.

9. The method of Claim 1, wherein delivering the anesthetic agent occurs prior to deploying the at least first and second needles.

10. The method of Claim 1, wherein delivering the anesthetic agent occurs between 1 second to five minutes before deploying the at least first and second needles.

11. The method of Claim 1, wherein delivering the anesthetic agent comprising delivering the anesthetic agent as a single agent or mixed with a secondary agent.

12. The method of Claim 11, wherein the anesthetic agent is mixed with a diagnostic agent, such as a contrast media.

13. The method of Claim 11, wherein the anesthetic agent is mixed with a therapeutic agent.

14. The method of Claim 13, wherein the therapeutic agent comprises at least one of an anti-restenosis agent for the treatment of PAD, an anti-inflammatory agent for the treatment of DVT, or a neurolytic agent for the treatment of hypertension.

15. The method of Claim 11, wherein the anesthetic agent is mixed with a secondary agent and delivered from the at least first and second needles.- 36 -SG Docket No.: 14764-703.60116. A method of scoring a lumen wall with a balloon-based intravascular fluid delivery device comprising: advancing an intravascular apparatus to a target location within a lumen, the apparatus including an inflatable balloon and an expandable infusion scaffold that includes a plurality of scoring spines, each of the plurality of scoring spines including a plurality of radial openings through the scoring spine; inflating the balloon to cause the plurality of scoring spines to expand and score the lumen wall; at a time subsequent to scoring the lumen wall, deploying at least first and second needles from radial openings in each of the plurality of scoring spines to penetrate the internal and / or external elastic lamina; and delivering a fluid agent from the at least first and second needles associated with each of the plurality of scoring spines into the lumen wall.

17. The method of Claim 16, wherein the advancing step comprising advancing the balloon coupled to the expandable infusion scaffold.

18. The method of Claim 16, wherein the advancing step comprising advancing the expandable infusion scaffold uncoupled from the balloon and positioned about the balloon.

19. A method of scoring a lumen wall with a balloon-based intravascular fluid delivery device comprising: delivering an inflatable balloon in an unexpanded state and an expandable infusion scaffold in an unexpanded state disposed about the balloon to a location within a vessel, the expandable infusion scaffold comprising a plurality of infusion spines extending along at least a portion of the inflatable balloon, the infusion spines each having a plurality of radial openings therein;- 37 -SG Docket No.: 14764-703.601expanding the balloon radially outward by delivering an inflation fluid to a volume within the balloon, wherein expanding the balloon expands the plurality of infusion spines radially outward and causes the plurality of infusion spines to move towards and into contact with an inner wall of the vessel; dilating the vessel wall as the balloon expands radially; scoring the vessel wall as the infusion spines press against the vessel wall; deploying a plurality of needles from the radial openings in each of the plurality of infusion spines and through the vessel wall; delivering a therapeutic agent through the plurality of needles and into the vessel wall; retracting the needles into the openings in each of the plurality of infusion spines; collapsing the balloon-based intravascular fluid delivery device; and removing the balloon-based intravascular fluid delivery device from the vessel.- 38 -SG Docket No.: 14764-703.601

Images