WO2023212373A2 - Dispositifs intravasculaires et méthodes d'administration de liquides et d'agents thérapeutiques à l'intérieur de parois de vaisseaux sanguins et de structures intravasculaires - Google Patents

Dispositifs intravasculaires et méthodes d'administration de liquides et d'agents thérapeutiques à l'intérieur de parois de vaisseaux sanguins et de structures intravasculaires Download PDF

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Publication number
WO2023212373A2
WO2023212373A2 PCT/US2023/020489 US2023020489W WO2023212373A2 WO 2023212373 A2 WO2023212373 A2 WO 2023212373A2 US 2023020489 W US2023020489 W US 2023020489W WO 2023212373 A2 WO2023212373 A2 WO 2023212373A2
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WO
WIPO (PCT)
Prior art keywords
needle
infusion
vessel
infusate
tissue
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PCT/US2023/020489
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English (en)
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WO2023212373A3 (fr
Inventor
Fletcher T. Wilson
Jeffrey M. Elkins
Kent D. Dell
Herbert Mendoza
Michi E. Garrison
Original Assignee
Intervene, Inc.
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Publication date
Priority claimed from US17/661,507 external-priority patent/US20220331555A1/en
Application filed by Intervene, Inc. filed Critical Intervene, Inc.
Publication of WO2023212373A2 publication Critical patent/WO2023212373A2/fr
Publication of WO2023212373A3 publication Critical patent/WO2023212373A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1002—Balloon catheters characterised by balloon shape
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/32—Surgical cutting instruments
    • A61B17/3203—Fluid jet cutting instruments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/34—Trocars; Puncturing needles
    • A61B17/3478—Endoscopic needles, e.g. for infusion
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0082—Catheter tip comprising a tool
    • A61M25/0084—Catheter tip comprising a tool being one or more injection needles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22051—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation
    • A61B2017/22065—Functions of balloons
    • A61B2017/22069—Immobilising; Stabilising
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22082—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22094—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for for crossing total occlusions, i.e. piercing
    • A61B2017/22095—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for for crossing total occlusions, i.e. piercing accessing a blood vessel true lumen from the sub-intimal space
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0082—Catheter tip comprising a tool
    • A61M25/0084—Catheter tip comprising a tool being one or more injection needles
    • A61M2025/0087—Multiple injection needles protruding laterally from the distal tip
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A61M2025/1052—Balloon catheters with special features or adapted for special applications for temporarily occluding a vessel for isolating a sector

Definitions

  • the present technology generally relates to intravascular catheter systems, and more particularly to intravascular catheter systems for delivery of therapeutic agents, diagnostic agents, and/or other substances into the tissue and wall layers of blood vessels and other body conduits.
  • Some vascular diseases and clinical conditions can benefit from the delivery of therapeutic drugs, or other agents, into and/or around a blood vessel wall or other body conduit.
  • local drug delivery catheters and implants have been used to deliver anti-restenosis drugs to an inner tissue surface of a blood vessel to prevent or reduce the severity of restenosis after a balloon angioplasty or stent procedure in the blood vessel.
  • Local drug delivery catheters include infusion catheters with or without side-holes, drug-coated balloon catheters, balloon catheters with porous walls or porous outer channels, or double balloon catheters with a porous shaft for drug delivery in between the two balloons.
  • the drug delivery catheters must be able to deliver adequate quantities of a drug to the vessel wall without either injuring the wall or compromising flow.
  • Other technologies include local injection catheters with needles that infuse drug into the adventitial space of a vessel wall.
  • An example of such a device is the Bullfrog Catheter (Mercator Medsystems. Emeryville, CA) that includes a single needle for drug delivery directed radially outward from the catheter through the vessel wall and into the perivascular space when the balloon is inflated.
  • Another example is the Peregrine System Infusion Catheter (Ablative Solutions, San Jose, CA) which is also designed for needle puncture and infusion into the perivascular space of a blood vessel.
  • the Peregrine System has three needles and relies on a pre-shaped spring structure of the needle elements to direct the needles completely through the vessel wall. These devices, as well as other perivalvular space drug delivery systems, puncture through all layers of the vessel wall and are thus limited to delivering drugs to the perivascular space at discreet sites.
  • Intravascular stents with drug-eluting capabilities including metallic stents with drug-impregnated coatings or drug-impregnated polymer stents, have also been developed for local drug delivery to reduce the restenosis or re-occlusion rate after implantation of the stent.
  • These devices are used when stent implantation is the primary therapy for treatment of vessel stenosis but suffer from late thrombosis due to delayed or impaired healing of the endothelium around the stent caused by the drug and/or the polymer coating. Additionally, these devices are limited to procedures that already involve stent implantation.
  • Figure 1 illustrates a system including an infusion device configured in accordance with some embodiments of the present technology'.
  • Figures 2A and 2B are an enlarged cross-sectional side view and an enlarged isometric view, respectively, of a distal portion of the infusion device of Figure 1 configured in accordance with some embodiments of the present technology.
  • Figure 2C is a cross-sectional view of the distal portion of the infusion device of Figure 2B in accordance with some embodiments of the present technology'.
  • Figures 3A-3E are side views of the distal portion of the infusion device of Figures 1 during various steps of an infusion procedure in accordance with some embodiments of the present technology.
  • Figures 4A and 4B are cross-sectional side views of a tissue manipulation component of an infusion device in accordance with some embodiments of the present technology.
  • Figures 5A and 5B are side views of a tapered sheath with side holes configured in accordance with some embodiments of the present technology.
  • Figures 6A and 6B are cross-sectional side and front views, respectively, of a distal end portion of an eccentric needle configured in accordance with some embodiments of the present technology.
  • Figure 7 is an enlarged side view of a distal end portion of an infusion device with an adjustable needle height configured in accordance with some embodiments of the present technology.
  • Figure 8 is a cross-sectional side view of an infusion device with a lumen for a visualization device configured in accordance with some embodiments of the present technology.
  • Figure 9 is a side view of a distal portion of an infusion device with a mechanical expansion element configured in accordance with some embodiments of the present technology.
  • Figure 10 is a side view of an infusion device with multiple infusion assemblies configured in accordance with some embodiments of the present technology.
  • Figures 11A-11C are partially cross-sectional side views of the distal portion of the infusion device of Figure 10 during various steps of a dual-site infusion procedure in accordance with some embodiments of the present technology.
  • Figures 12A-12C are side views of a distal portion of an infusion device during various steps of an infusion procedure in accordance with some embodiments of the present technology.
  • Figures 13A-13C are side views of a distal portion of an infusion device during various steps of an infusion accordance with further embodiments of the present technology.
  • Figures 14A-14C are isometric, side, and end views, respectively, of a distal end portion of an infusion device with an adjustable needle height configured in accordance with some embodiments of the present technology.
  • Figures 15A-15C are isometric, side, and end views, respectively, of a distal end portion of an infusion device with an adjustable needle height configured in accordance with embodiments some of the present technology.
  • Figures 16A-16C are side views of the distal portion of an infusion device of the ty pe illustrated in Figure 1 during various infusion procedures in accordance with various embodiments of the present technology.
  • Figures 17A and 17B are isometric and cross-sectional side views, respectively, of a distal end portion of an infusion device which can infuse in a forward direction configured in accordance with embodiments some of the present technology.
  • Figure 18 is a flow diagram of a process for delivering the infusate to treat a vessel obstruction in accordance with some embodiments of the present technology.
  • the present technology generally relates to medical systems, devices and methods for delivery of drugs, other therapeutic agents, diagnostic agents, and/or other fluids or substances (collectively referred to as “infusates”) into the tissue walls, intraluminal tissues, intraluminal spaces, layers of various body conduits, and/or a space adjacent to the body conduits (e.g., perivascular space).
  • Some embodiments of the present technology provide the delivery of the infusates into a space created between the outer and inner boundaries of a blood vessel wall (e.g., the medial layer of the vessel wall and/or to the adventitial layer of the vessel wall, sometimes also referred to as an intramural space) and/or into the perivascular space outside the vessel wall.
  • Some embodiments of the present technology provide the delivery' of the infusates into intravascular tissue or other anatomical structures (e.g., atherosclerotic plaque, fibrous tissue, thrombus, other stenotic tissue, and/or other structures/tissue within the vessel), between the intravascular tissue/ structure and the natural inner surface of the vessel wall, and/or between an intravascular implant (e.g., a stent, graft, or stent graft) and the inner surface of the vessel wall.
  • intravascular implant e.g., a stent, graft, or stent graft
  • Some embodiments of the present technology provide the delivery of the infusates into an intraluminal space to help break down an obstructive material in a vessel lumen, such as thrombus and/or other occlusive material.
  • the infusate can be delivered into an intraluminal space adjacent the obstructive material, into the obstructive material, and/or into a boundary layer between the obstructive material and a vessel wall.
  • a wall layer e.g., intramural space
  • the delivery of the infusates into a wall layer (e.g., intramural space) or other anatomical structure is expected to retain the infusates in tissue layers rather than being washed out if delivered superficially to the inner surface, into a wall layer (intramural) or other anatomical structure (e.g., an obstructive tissue such as a partial or total occlusion, thrombotic tissue, artificial vessel-shunts, and/or any other suitable structure).
  • the infusate delivery disclosed herein is more targeted to the vessel wall and/or other anatomical structure than current perivascular infusion devices.
  • intramural refers to a location within the layers of vessel wall tissue between the innermost and outermost surfaces of a vessel wall
  • intramural refers to a location within the layers of vessel wall tissue between the innermost and outermost surfaces of a vessel wall
  • the “intramural” systems, devices, and methods described herein can additionally, or alternatively, be used to deliver infusates to other in a similar manner and using similar mechanisms as described herein with respect to intramural fluid/agent delivery.
  • the intramural systems, devices, and methods described herein can additionally, or alternatively, be used to deliver infusates into the perivascular space just beyond the outer surface of the vessel wall, other intravascular tissue, anatomical structures, a space between intravascular tissue and the natural inner surface (also referred to as an inner layer) of the vessel wall, an intravascular implant and/or other internally positioned devices, and/or a space between an intravascular implant (or other device) and the inner surface of a vessel.
  • tissue can include muscle, epithelial, connective and nervous tissue. Further, when discussed with respect to the structures through which the devices herein penetrate and/or deliver infusates, “tissue” can also refer to atherosclerotic plaque, fibrous tissue, thrombus, other stenotic tissue, and/or other structures within or surrounding a vessel.
  • Infusate delivery systems include devices for accessing a layer of a vessel wall at one or more sites in a section of a blood vessel (e.g., an artery or vein wall) and a means for infusing infusates into the accessed vessel wall layer and/or the perivascular space.
  • the systems disclosed herein can also include variations in the number of puncture sites per device, controls of the perfusion parameters (e.g., flow rate or pressure), control of the thickness and length of the vessel layer accessed, and/or control of other functional parameters associated with hydrodissection, infusate delivery, and/or vessel layer access.
  • the systems include a means to provide intravascular imaging, such as an imaging catheter with an imaging element to provide an image of the treatment site.
  • the imaging catheter can be an intravascular ultrasound (“IVUS”) catheter that captures ultrasound images from within the vessel and/or any other suitable imaging device.
  • IVUS intravascular ultrasound
  • the devices disclosed herein can deliver the infusates into an intramural space within the layers of a blood vessel wall and/or perivascular space.
  • the intramural and/or perivascular delivery is expected to increase a drug retention period at the target site, reduce the distance from the target site to the endothelial layer (thereby reducing the distance an agent must travel, disperse, be directed, etc. once delivered), and provide the devices disclosed herein with a wide range of infusion pressure, flow rate, and volume when delivering infusates.
  • the infusate delivery system includes an infusion device that is able to selectively infuse into an intraluminal space (e g., adjacent an obstruction and/or stenosis), into an obstruction or partial obstruction, and/or into an intramural tissue layer). Additionally, or alternatively, the infusion device can access layers of variable thickness up to and beyond the thickness of the vessel wall. As a result, the infusion device can access spaces within the vessel wall and/or outside of the vessel. By delivering an infusate selectively into obstructive material located within an intraluminal space, an intramural space, and/or selectively into an extraluminal space, the infusion device is expected to provide multiple clinical benefits.
  • an intraluminal space e g., adjacent an obstruction and/or stenosis
  • the infusion device can access layers of variable thickness up to and beyond the thickness of the vessel wall.
  • the infusion device can access spaces within the vessel wall and/or outside of the vessel.
  • the infusion device can provide localized drug delivery into selective luminal target tissue at higher concentrations than systemic delivery, with a higher dwell period than typically provided by infusion catheters, because the agents are delivered into intraluminal tissue rather than into the blood flow, and/or deliver the drug closer to endothelial and/or or medial layers than existing local injection catheters which deliver fluid only to extraluminal tissue.
  • the term "obstruction" can refer to tissue or other material within a blood vessel that creates either a complete vessel occlusion or a partial vessel occlusion, such as a narrowing of the vessel (i.e., a stenosed vessel).
  • the infusion device is capable of delivering antiinflammatory agents into the vessel wall (e.g., into the wall of a blood vessel), into a residual thrombotic tissue, and/or into a boundary layer between thrombotic tissue and the vessel wall.
  • the infusion device can help counter the after-effects of a deep vein thrombosis (DVT) event, including venous wall thickening and scarring that can lead to impaired flow and/or failure of native venous valves.
  • DVD deep vein thrombosis
  • the infusion device is capable of infusing a thrombolytic agent and/or another enzymatic agent into an occlusive material and/or into a boundary layer between an intraluminal obstructive material and the vessel wall.
  • the infusion device can help facilitate a natural removal of blockage in the vessel (e.g., via gradual breakdown and removal through blood flow) and/or provide a pre-treatment for a subsequent thrombectomy procedure (e.g., by beginning to break up the obstructive material before a procedure to more fully remove it).
  • the present technology can be utilized to penetrate and/or manipulate tissue and advance along a planar region within the tissue for reasons other than agent infusion (e.g., separating tissue layers, creating pockets between tissue layers, and/or any other suitable purpose). Additionally, some embodiments of the present technology can have different configurations, components, or procedures than those described herein. Further, several of the features of the embodiments shown in Figures 1-15C can be combined with one another and/or omitted in some embodiments of the present technology. A person of ordinary skill in the art, therefore, will understand that the technology can have other embodiments with additional elements, or the technology can have other embodiments without several of the features shown and described below with reference to Figures 1-15C.
  • distal and proximal within this description, unless otherwise specified, the terms can reference a relative position of the portions of a catheter subsystem with reference to an operator and/or a location in the vasculature. Also, as used herein, the designations “rearward,” “forward,” “upward,” “downward,” etc., are not meant to limit the referenced component to use in a specific orientation. It will be appreciated that such designations refer to the orientation of the referenced component as illustrated in the Figures and that the systems of the present technology can be used in any orientation suitable to the user.
  • FIG. 1 illustrates a drug delivery system 100 (“system 100”) including an infusion device 101 (also referred to herein as “device 101”) configured in accordance with some embodiments of the present technology.
  • the device 101 includes a catheter shaft 120 (also referred to herein as a “catheter device”), a distal portion 110 at a distal end region of the catheter shaft 120 (or defined by the distal end region of the catheter shaft 120), and a handle 130 (also referred to as a “handle assembly”) at a proximal portion of the catheter shaft 120.
  • catheter shaft 120 also referred to herein as a “catheter device”
  • distal portion 110 at a distal end region of the catheter shaft 120 (or defined by the distal end region of the catheter shaft 120)
  • a handle 130 also referred to as a “handle assembly”
  • the device also includes a tissue manipulation device 140 (also referred to herein as a “needle” and/or a “tissue penetrating component”) that extends through a lumen of the catheter shaft 120.
  • the distal portion 110 includes a balloon 111 (also referred to as an “expandable component” or an “apposition member”), a housing 112 with transition surface and an offset surface (also referred to as a “support surface”), and at least one exit port (identified individually as a first exit port 113a and a second exit port 113b; referred to collectively as “exit ports 113”).
  • the tissue manipulation device 140 can extend through the first exit port 113a to puncture and/or otherwise manipulate adjacent tissue.
  • the housing 112 can be sufficiently rigid such that the distal portion 110 generally maintains its shape when pressed against tissue via expansion of the opposing balloon 111.
  • the handle 130 can include actuators (e.g., an actuating component 150, discussed in more detail below) and/or other mechanisms to control the components of the device 101 and/or to fluidly connect any of the components of the device 101 to external components.
  • Figures 2A-2C are various enlarged views of the distal portion 110 of the device 101 of Figure 1 in accordance with some embodiments of the present technology.
  • Figures 2A and 2B are an enlarged cross-sectional side and enlarged isometric view, respectively, of the distal portion 110 of the device 101
  • Figure 2C is an enlarged cross- sectional view of the distal portion 110 taken along the line 2C-2C illustrated in Figure 2B.
  • the distal portion 110 is constructed of a metal housing 112 (comprising a tube with a cut-away portion on the distal end) and an insert 116.
  • the metal tubular housing 112 provides the rigid structure to the distal portion 110.
  • a number of lumens extend from the handle 130 (Figure 1), through the catheter shaft 120 and terminate at various points along the distal portion.
  • a guidewire lumen 221 extends from terminates at the second exit port 113b at a distalmost end of the distal portion 110;
  • a needle lumen 222 terminates at the first exit port 113a proximal to the distalmost end; and one or more balloon inflation lumens (not shown in crosssection) terminate inside the balloon 111.
  • the guidewire lumen 221 allows a guidewire and/or an imaging device to move within the length of the device and through the distal portion 110 of the device.
  • a guidewire can extend through the handle 130, the catheter shaft 120 via guidewire lumen 221 and out of the second exit port 113b to guide the distal portion 110 into position adjacent a target site.
  • an imaging component sometimes referred to as a “visualization device”
  • an IVUS catheter can be advanced through the guidewire lumen 221 to a position within the distal portion 110 proximal to the distalmost end and/or out of the second exit port 113b.
  • the balloon lumens allow an inflation device (not shown) to be fluidly connected to the balloon 111 to inflate and/or deflate the balloon 111, as desired, during a procedure.
  • the inflation device can be carried by and/or fluidly coupled to the handle 130 ( Figure 1, discussed in more detail below).
  • the needle 140 is slidably positioned in the needle lumen 222 and can extend through the catheter shaft 120 and exit out of first exit port 113a.
  • the needle 140 can retract (e.g., in response to movement of the actuating component 150 on the handle 130 ( Figure 1)) into the needle lumen 222 while the distal portion 110 is positioned adjacent the target site (e.g., a predetermined point in a vessel wall), then advance out of the needle lumen 222 through the first exit port 113a.
  • the needle 140 can puncture and/or otherwise manipulate tissue at and/or around the target site.
  • the needle 140 can include a protective tube 242 and/or a plug 245, each of which are illustrated in Figure 2C.
  • the protective tube 242 also referred to herein as the “tube,” the “tapered tube,” a “sheath,” the “tapered sheath,” and/or a “protective cover” is positioned coaxially around the needle 140, while the plug 245 is positioned at least partially within an opening of the needle 140. Additional details on various embodiments of the tapered tube 242 are discussed below with respect to Figures 4A and 4B, while additional details on various embodiments of the plug 245 are discussed below with respect to Figures 6A and 6B.
  • the distal portion includes an offset surface 215 that extends from the first exit port 113a for a specific length.
  • the offset surface 215 is not a solid flat surface. Instead, in some embodiments (e.g., as illustrated), the offset surface is a plane defined by two rails 212a, 212b on either side of a trough 219 in the central portion of the distal portion 110.
  • the offset surface 215 defined by the two rails 212a, 212b is indicated by a dotted line in Figure 2C.
  • the first exit port 113a is positioned to sit partially above and partially below the offset surface (e.g., at least partially in plane with the offset surface 215).
  • the plane of the offset surface 215 is generally parallel to the longitudinal axis of the distal portion 110 and/or the needle lumen 222.
  • the distal portion 110 includes a transition portion 214 (also referred to as a "transition surface") from the outer surface (e g., from the housing 112) to the offset surface 215.
  • the transition portion 214 can be a ramp that is angled (e.g., sloping upward, at an obtuse angle relative to the offset surface 215, etc.) or perpendicular with respect to the offset surface 215.
  • the outer surface, the transition portion 214, and the offset surface 215 are configured to conform tissue (e.g., a vessel wall layer) in contact with the distal portion 110 to cover at least a portion of the first exit port 113a.
  • the balloon 111 is positioned on the opposite side of the distal portion 110 as the offset surface 215. Accordingly, as the balloon 111 inflates, the balloon 111 can push the outer surface, the transition portion 214, and the offset surface 215 against tissue at and/or adjacent the target site. As a result, the pressure from the balloon 111 can cause the tissue to conform against the distal portion 110.
  • the length of the offset surface 215 can determine the length of the vessel wall that can be accessed by the needle 140, and therefore the length of an intramural space that can created and/or dosed with an infusate therein. The length of the offset surface 215 can vary based on one or more intended uses for the device 101.
  • the length of the offset surface 215 can be between about 5 millimeters (mm) to about 50 mm, or from about 10 mm to about 30 mm. However, in various embodiments, the length of the offset surface 215 can be shorter than 5 mm, or longer than 50 mm.
  • the balloon 111 is replaced with another suitable expandable element, such as an expanding cage (e.g., Figure 9), shape memory material, and the like.
  • the distal portion 110 can also include a distal tapered tip 218 at the distalmost end of the device 101.
  • the distal tapered tip 218 provides an atraumatic leading edge to the device 101 while it is positioned at and/or adjacent the target site (e.g., within the vessel).
  • the distal tapered tip 218 is constructed from a softer material, such as an elastomer material.
  • the distal tapered tip 218 is impregnated and/or constructed from a material that is radiopaque such that the distal tapered tip 218 is clearly visible on fluoroscopy.
  • Figures 3A-3E are side views of the distal portion 110 of the infusion device 101 during various steps of an infusion procedure in accordance with some embodiments of the present technology.
  • Figure 3A shows the distal portion 110 of the device 101 being positioned over a guidewire 317 within a vessel V (shown in cross section).
  • the vessel V is defined by a lumen L and a vessel wall W and includes a target site 306.
  • the infusion procedure can include positioning distal portion 110 of the device 101 adjacent to the target site 306.
  • the balloon I l l is inflated, as shown in Figure 3B.
  • the distal portion 110 has a sufficient rigidity to at least partially conform the vessel wall W to the distal portion 110 when the balloon 111 is inflated (e.g., rather than bending against the vessel wall W). Accordingly, the vessel wall W conforms to the outer surface, the transition portion 214, and the offset surface 215 of the distal portion 110.
  • Figure 3C illustrates the needle 140 advancing out of the first exit port 113a to puncture at least a layer of vessel wall W.
  • the height H of a tip 341 of the needle 140 above the offset surface 215 and/or a height of a distal opening of the needle 140 determines the thickness of the tissue layer that is accessed.
  • a fluid is infused through a lumen in the needle 140 at a controlled pressure as the needle 140 is advance. The fluid can assist the needle 140 in piercing, accessing, and/or manipulating the vessel wall W to access the tissue layer.
  • the fluid flow from the needle 140 can be directed at the adjacent intramural tissue in the vessel wall W.
  • the hydrostatic pressure generated by the fluid flow separates layers in the vessel wall W in a hydrodissection step and creates an intramural space 340 within the vessel wall W.
  • the needle 140 is advanced between the layers of the vessel wall W without hydrodissection.
  • the needle 140 can be advanced in a plane at least substantially parallel to the plane of the offset surface 215 and/or the central longitudinal axis of the distal portion 110. Accordingly, the needle 140 advances along a path at the same depth within the layers of the vessel wall W (e.g., resulting in a generally uniform thickness of the layer of the vessel wall W).
  • the needle 140 can advance as long as the full length of the offset surface 215 without repenetrating the vessel wall W (e.g., reentering the vessel V and/or fully penetrating the vessel wall W).
  • the offset surface 215 can help support the vessel wall W as the needle 140 advances.
  • FIGS 16A-16C are side views of adistal portion 1610 of an infusion device 1601 during various infusion procedures in accordance with further embodiments of the present technology.
  • the infusion device 1601 is generally similar to the infusion device 101 discussed above with reference to Figures 3A-3E.
  • the distal portion 1610 of the infusion device 1601 includes afirst exit port 1613a fluidly coupled to a needle lumen for receiving a needle 1640, and an expandable component 1611 (e.g., a balloon) at the distal end 1610.
  • an expandable component 1611 e.g., a balloon
  • the illustrated embodiments can be used to deliver an infusate that includes matrix metalloproteinases (MMPs).
  • MMPs matrix metalloproteinases
  • MMPs are capable of degrading extracellular matrix proteins to help break down obstructive materials (e.g., occlusions, such as thrombotic structures that occur naturally and/or after various intraluminal procedures).
  • obstructive materials e.g., occlusions, such as thrombotic structures that occur naturally and/or after various intraluminal procedures.
  • the MMPs include collagenase, which can break down collagenic structures such as those found in chronic arterial and venous occlusions.
  • the infusion device 1601 is configured to allow the needle 1640 to advance beyond the distalmost end of the distal portion 1610 to access an intraluminal infusion site (also referred to herein as an “intraluminal site”).
  • the infusion site may be adjacent an obstructive material (e.g., a thrombotic material) that is partially occluding (or fully occluding) the lumen of the vessel V, a space within the obstructive material and/or a space within a boundary layer between the obstructive material and the inner surface of the vessel wall W (e.g., into thrombotic tissue bonded to the vessel wall W).
  • an obstructive material e.g., a thrombotic material
  • the device 1601 can be positioned adjacent an obstruction Oi (e.g., a vessel occlusion such as thrombotic tissue) to target the needle 1640 toward and/or into the obstruction Oi without expanding the expandable component 1611.
  • an obstruction Oi e.g., a vessel occlusion such as thrombotic tissue
  • the infusion site can be adjacent the obstruction Oi since blood flow will not carry the infusate away.
  • the device 1601 has advanced the needle 1640 into a space within the total obstruction Oi to deliver the infusate into an infusion site within the obstruction Oi.
  • the expandable component 1611 can be partially or fully expanded when delivering the infusate to the obstruction Oi.
  • the device 1601 can be positioned adjacent a partial obstruction O2 (e.g., due to stenosis), and the expandable component 1611 can be expanded to facilitate targeting the obstruction O2.
  • the expandable component 1611 presses against the vessel wall W the expandable component 1611 and/or an offset surface 1615 at the distal end 1610 can cause the corresponding portion of the vessel V to at least partially straighten, including even before the offset surface 1615 is pressed into apposition with the opposite side of the vessel wall W.
  • the obstruction O2 can become more accessible to the needle 1640 traveling distal to the distal portion 1610 (e.g., by aligning an exit port 1613a and the obstruction O2 along a longitudinal axis).
  • the expandable component 1611 can help direct the needle 1640 forward into the partial obstruction O2 because the distal portion 1610 is parallel with the straightened vessel V, rather than at an angle to the vessel V.
  • the needle 1640 may advance distal to the distal portion 1610 into and/or through the vessel wall W and to the outside of the vessel V.
  • the device 1601 can advanced the needle 1640 into the partial obstruction O2 and/or into a boundary layer of the obstruction O2 with the vessel wall W.
  • the infusion site can be an intramural site (e.g., a space within the vessel wall W, such as any of the intramural spaces accessed by the device in Figures 3A-3E) and/or an extraluminal site external to the vessel V in which the device 1601 is positioned (sometimes referred to herein as a “working vessel”).
  • the infusion site can be in a second vessel adjacent the working vessel V.
  • the device 1601 can advance through a working vessel V that does not contain any obstructive material (or is otherwise more accessible to the device 1601), then advance the needle 1640 external to the working vessel V (e.g., into the second vessel).
  • the device 1601 can be positioned within the working vessel V, and the expandable component 1611 can be fully expanded to press the distal region 1610 into apposition with the vessel wall W.
  • the vessel wall W can be conformed to the transition surface 1614 enough to allow the needle 1640 to pierce entirely through the vessel wall W and into an extraluminal space (e.g., surrounding tissue, a neighboring vessel).
  • the needle height at the exit port 1613a can be adjusted. Accordingly, the needle height (in the direction away from the expandable component 1611) can be increased to enable the reach of the needle 1640 into extraluminal spaces.
  • a protective tube is positioned coaxially around the needle 140.
  • the purpose of the protective tube is to cover the point of the needle 140 after the needle 140 has punctured the vessel wall W to access the intramural wall layers.
  • the tube is expected to protect the accessed layer of the vessel wall W from the needle 140 and, thereby, reduce the likelihood that the point of the needle 140 will unintentionally puncture through the accessed wall layer and/or the vessel wall W as it is advanced forward within the layer of the vessel wall W.
  • Figures 4A and 4B are side cross-sectional views of the needle 140 and the tapered tube 242 penetrating into and advancing within a vessel wall 404 in accordance with some embodiments of the present technology.
  • the tube 242 has a tapered leading edge that defines an atraumatic surface that helps facilitate advancement of the tube 242 and the needle 140 through a puncture point in the vessel wall 404.
  • the needle 140 is advanced until it punctures the vessel wall 404.
  • the tube 242 can then be advanced to cover all, or a portion, of the needle 140.
  • the tube 242 advances a desired distance into the intramural layer. In some embodiments, the advancement is accomplished (e.g., driven, controlled, monitored, and the like) via actuators (e.g., knobs, levers, mechanical drivers, electrical drivers, and the like), on the handle 130 ( Figure 1).
  • actuators e.g., knobs, levers, mechanical drivers, electrical drivers, and the like
  • Figures 5 A and 5B are side views of a tapered tube 542 that includes one or more side holes 544 (three shown) configured in accordance with embodiments of the present technology.
  • the side holes 544 are positioned at a distal tip 546 of the tube 542.
  • the tube 542 is proximal to the needle 140 when the needle is first advanced to puncture the vessel wall.
  • the side holes 544 can be fully and/or partially flush with the exterior surface of the needle 140.
  • the needle 140 can be pulled back to expose the side holes 544, for example as illustrated in Figure 5B.
  • the side holes 544 allow delivery of a fluid 560 (e.g., the infusate and/or a diluted infusate) exiting the needle 140 in both a transverse and longitudinal direction from the tube 542. If the end of the needle 140 is blocked by its position in the tissue (e.g., by a thrombus, atherosclerotic plaque, and/or other structure within or surrounding a vessel), infusion would exit from the side holes only.
  • a fluid 560 e.g., the infusate and/or a diluted infusate
  • the flow pattern can be adjusted by adjusting the shape, size, and distribution of the side holes.
  • the tube 542 (or the distal tip 546 of the tube 542) is made from a compressible material and/or a shape memory material.
  • the tube 542 deforms (e.g., compresses) to close or narrow the opening at the distal tip 546.
  • the deformation further directs flow through the side holes 544 in a transverse direction.
  • the needle 140 has one or more side holes (not shown) that are blocked when the tube 542 is positioned over the needle 140.
  • the tube 542 can retract to expose the side hole(s) in the needle 140, allowing the needle 140 to direct the fluid 560 in both the longitudinal and transverse directions (i.e., distally from the device 101 ( Figure 2) and laterally from the needle 140).
  • FIGS 6A and 6B are cross-sectional side and end views, respectively, of a distal end portion of a needle 640 with a partially blocked distal opening 648 (also referred to as “the needle opening 648”) in accordance with embodiments of the present technology.
  • the distal opening 648 of the needle 640 is partially blocked by a plug 645 that, in various embodiments, can be a removable, adjustable, or permanent feature of the needle 640.
  • the plug 645 is made of the same material as the needle 140 (e.g., stainless steel) and is soldered, welded, or otherwise adhered to the inner lumen of the needle 640.
  • the plug 645 is positioned on a low er portion of the distal opening 648, thereby offsetting the distal opening 648 towards the distal-most tip of the needle 640. Said another way, the plug 645 biases the open space of the distal opening 648 at least partially above a central axis needle of the needle 640 (extending along the longitudinal axis of the needle 640). The offset allows the needle opening 648 to be enclosed within a vessel wall before the needle 640 is fully advanced into the vessel wall.
  • the lower portion e.g., corresponding to the space of the distal opening 648n blocked by the plug 645) can still be outside and/or engaging the vessel wall.
  • the plug 645 can contact the vessel wall while the open space of the needle opening 648 is fully within the vessel wall. Further, the plug 645 can create a fluid tight seal with the vessel wall, allowing a dissection fluid (e.g., saline) to flow out of the needle opening 648 to create the intramural space within a thinner layer of the vessel wall (e.g., less that the full thickness of the needle 640).
  • a dissection fluid e.g., saline
  • the offset of the needle opening 648 allows an infusate to be delivered to the vessel wall close to the inner endothelial layer of the blood vessel while still enclosed in an intramural space for retention.
  • the offset of the needle opening 648 can be advantageous if the vessel wall is very thin, (e.g., for a vein wall with less than 1 mm wall thickness) and a thin layer is required to stay within an intramural space in the vessel wall rather than exiting into the outer adventitial or penvascular space.
  • the device 101 includes features to adjust the needle height H.
  • Figure 7 is an enlarged side view of a distal portion 710 of an infusion device 701 that includes features to adjust the needle height in accordance with some embodiments of the present technology .
  • the distal portion 710 can include a height adjustment feature 725 in a distal portion of a needle lumen 722.
  • the needle 740 advances out of the first exit port 713a, the needle 740 is at least partially carried by the height adjustment feature 725, thereby setting the height of the needle 740 above the offset surface 215.
  • the height adjustment feature 725 can be raised or lowered, thereby raising or lowering the height of the needle 740.
  • the height adjustment feature 725 can be a rod with a ramp at the tip that is pushed or pulled to increase or decrease the height; a strip that bulges out to varying degrees when pushed; and/or an expandable structure (e.g., a balloon, an expandable cage, a shape memory device, and the like) that is expanded to varying degrees.
  • an expandable structure e.g., a balloon, an expandable cage, a shape memory device, and the like
  • Figures 14A-15C illustrate an embodiment of a distal portion 1410 of an infusion device 1401 with adjustable needle height above an offset surface 1415 configured in accordance with some embodiments of the present technology.
  • Figure 14A is an isometric view of the distal portion 1410 with a needle guide component 1402 (also referred to as ’‘the needle guide 1402” and a “guide component”) that terminates at the first exit port 1413a.
  • the needle 1440 (not shown in Figure 14A for clarity) can be positioned in a track 1405 (e.g., a groove or protrusion) of needle guide 1402. The track 1405 can then position the needle in a specific position with respect to the center of the needle guide 1402.
  • Rotating the needle guide 1402 also rotates the position of the track 1405, and therefore the position of the needle.
  • the height Hi ( Figure 14B) of the needle moves between a maximum height position (Hi) and a minimum height position (H2).
  • the needle guide 1402 is configured such that the height of the needle 1440 is at the highest position Hi.
  • the needle 1440 is then advanced during use of the device 1401 (e.g., during a procedure) at the highest position Hi.
  • Figures 15A-15C illustrate the distal portion 1410 with the needle guide 1402 configured to position the needle at the minimum height position.
  • the needle 1440 (not shown in Figure 15A) is advanced at the minimum height position H2 during use of the device 1401 (e.g., during a procedure).
  • the needle guide 1402 can be rotated to any angle between the top and bottom angles shown in Figures 14A-14B and 15A-15C, respectively, to set the needle height to any height between the maximum height position Hi and the minimum height position H2.
  • the needle guide 1402 extends from the first exit port 1413a along the shaft 1420 and is operably coupled to a needle height adjustor (not shown) at the handle 130 ( Figure 1). By rotating, or otherwise manipulating, the needle height actuator, the user can set the needle height at any position at and/or between the maximum height position Hi and the minimum height position H2.
  • the amount of offset of the track 1405 determines the distance between the maximum height position Hi and the minimum height position H2.
  • the maximum height position Hi and the minimum height position H2, respectively, are also at least partially determined by the dimensions of the needle guide 1402, the geometry of the first exit port 1413a, and the offset surface 1415 of distal portion 1410.
  • the track 1405 extends the entire length of needle guide 1402.
  • the track 1405 extends only in the distal portion of needle guide 1402.
  • the needle guide 1402 can be formed from a plug 1445 with the track 1405, inserted into the end of a tube 1430.
  • the tube 1430 can extend the length of the shaft 1420 and attach to the needle height actuator of the handle 130 ( Figure 1).
  • the needle can then be positioned within the tube 1430 and exit out of the first exit port 1413a on the track 1405 of the plug 1445.
  • the needle 1420 can then infuse the agent into the tissue.
  • the needle 1420 is configured to infuse the agent into the tissue at a height selected by the user.
  • the needle 1420 advances and retracts along the offset surface 1415 for any length up to the end of the offset surface 1415. In some embodiments, the needle 1420 can advance past the offset surface 1420 to a point distal to the distal portion 1410 of the infusion device 1401. For example, in various embodiments, the needle 1420 can advance 1 cm, 2 cm, or 3 cm past the distal portion 1410 of the infusion device 1401.
  • the infusion devices disclosed herein can include various additional (or alternative) features to adjust the height of the needle.
  • the tube 542 ( Figure 5A) can include an inner lumen that is partially offset from a central axis of the tube 542 (or eccentric to the outer surface of the tube 542).
  • the needle is at least partially earned by the inner lumen, such that rotating the tube 542 has the effect of lowering or raising the needle according to the offset of the inner lumen.
  • the handle 130 ( Figure 1) includes an actuator (e.g., a knob, lever, and the like) that controls the rotation of the tube 542.
  • device can include features that allow the device to bend slightly upwards and/or downwards at the distal portion and/or at the transition between the catheter shaft and the distal portion.
  • the slight bending can have the effect of varying the height of the needle as it exits the first exit port.
  • the bending motion is caused and/or controlled by wires or other pulling mechanisms attached to one side of the distal portion and running the length of catheter shaft to an actuator on the handle.
  • the pulling mechanisms are attached to the distal portion on the side corresponding to the desired bend direction (e.g., on the inside of the curve or bend).
  • the device can include multiple pulling mechanisms, allowing the distal portion to bend in multiple directions.
  • the device can include a first pulling mechanism on a first side (e.g., the bottom) of the distal portion and a second pulling mechanism on a second side (e.g., the top) of the distal portion, allowing the distal portion to bend in first and second directions.
  • a first pulling mechanism on a first side e.g., the bottom
  • a second pulling mechanism on a second side e.g., the top
  • the user e.g., a surgeon or other medical care provider
  • the user can predetermine a thickness of the intraluminal tissue, vessel wall layer, and/or perivascular space they would like to access and deliver an infusate into, adjust the height of the needle, then puncture the vessel wall.
  • the user can perform an infusion in one layer at a first depth (and therefore with a first layer thickness), retract the needle out of the wall, adjust the needle height, then re-puncture to perform an additional infusion at a second layer at a second depth.
  • the device can access the target site multiple times to perform the infusion at multiple layers with varying depths (e.g., the first and second layers from above).
  • intravascular imaging can help facilitate the infusion procedure.
  • the user can intravascularly image the target site in a vessel before inserting and/or positioning the device 101 ( Figure 1).
  • the user can then use the intravascular images (and any related information) to predetermine the thickness of the vessel wall layer they would like to access and infuse an agent into.
  • IVUS Intravascular ultrasound
  • Various examples of imaging components carried by interveinal catheters are described in U.S. Patent Application No. 17/355,456 filed June 23, 2021 and incorporated herein by reference.
  • FIG. 8 is a side cross-sectional view of an infusion device 801 configured in accordance with some embodiments of the present technology.
  • the device 801 includes a guidewire lumen 821 (also referred to as the “lumen” or an “auxiliary component lumen”) which is configured to also accommodate an imaging component 816 (e.g., an intravascular imaging catheter) and/or a guidewire 817 therein.
  • an imaging component 816 e.g., an intravascular imaging catheter
  • a guidewire 817 is advanced to a position adjacent the target site, and the distal portion 810 of the device 801 is first positioned at a target site in a blood vessel over the guidewire 817.
  • the imaging component 816 can be positioned coaxially around the guidewire 817 to capture images of the vessel.
  • the imaging component 816 can be moveably positioned within the lumen 821 to visualize the needle advancement and infusate delivery steps of the infusion procedure. For example, as the device 801 is moved into position within the vessel, the imaging component 816 can capture intravascular images of the vessel wall adjacent the distal portion 810. The images can allow the user to determine adjustments to the target site and reposition the guidewire 817 (and therefore the end position of the distal portion 810) accordingly, without needing to remove the imaging component 816 to do so.
  • the guidewire 817 is removed and replaced with the imaging component 816 (e.g., an imaging catheter IC (e.g., including an optional component-specific guidewire)).
  • the device 801 includes separate lumens for the imaging component 816 and the guidewire 817 (e. g. , adj acent to each other and/ or spaced apart from on another).
  • FIG 9 is a side view of an infusion device 901 with a mechanical expansion element 911 (“expansion element 91 1 ”) configured in accordance with some embodiments of the present technology.
  • the infusion device 901 can include features generally similar to those of the infusion devices described above with respect to Figures 1-8.
  • the device 901 can include a distal portion 910 with offset surface 915, a catheter shaft 920, and a handle 930.
  • the expansion element 911 can be carried by the distal portion 910 to enable apposition of the vessel wall against the offset surface 915.
  • the expansion element 911 is a braided structure that includes an expandable braid.
  • the expandable braid expands outwardly from the housing of the distal portion 910 when a proximal end of the mechanical expansion element 911 is pushed towards the distal end (e.g., via an actuator carried by the handle 930), thereby shortening the length and expanding the diameter of the expansion element 911.
  • the actuator includes a push-pull mechanism (e.g., inner and outer activation shafts) operably coupled to the expansion element 911 that, when moved in a distal direction relative toa proximal-most point of the handle 930, pushes the proximal end of the mechanical expansion element 911 toward the distal end of the mechanical expansion element 911 (e.g., to expand the diameter of the expansion element 911); and, when moved proximally, elongates the expansion element 911 (e.g., to contract the diameter of the expansion element 911); or vice versa.
  • the travel distance of the proximal end e.g., the relative movement between the proximal and distal ends
  • the travel distance of the proximal end can be measured and/or indicated on the handle 930 (e.g., an actuator can include indicative marks).
  • the expansion element 911 can have other structures and/or expansion mechanisms, such as a cut ni tinol tube structure with a cut pattern that expands outwards when shortened, various suitable shape memory devices, expandable cages, and the like.
  • the infusion device 1001 can include multiple tissue manipulation assemblies that are spaced apart from each other along the distal portion 1010 of the device 1001.
  • the multiple tissue manipulation and infusion assemblies (also referred to as “infusion assemblies” or “manipulation assemblies”) allow the device 1001 to manipulate and/or infuse an agent into tissue at more than one target location withing a section of vessel without moving the distal portion 1010.
  • the manipulation and/or agent infusion at multiple sites can be performed concurrently (e g., simultaneously or generally simultaneously) and/or successively without moving the distal portion 1010.
  • a single procedure can be more efficient than when perfonned by a device with a single infusion assembly by reducing the time to manipulate and/or infuse an agent in multiple locations and/or more effective by multiplying the infusion sites that can be accessed during one infusion session (e.g., which may have a limited time frame for completion).
  • the infusion assemblies are positioned on opposite sides of the distal portion 1010, allowing the device 1001 to manipulate and/or infuse an agent into both sides of a vessel wall without rotating the distal portion 1010.
  • FIGS 11A-11C are partially cross-sectional side views of the distal portion 1010 of the infusion device 1001 of Figure 10 during various steps of a dual-site infusion procedure in accordance with some embodiments of the present technology.
  • the device 1001 includes various features generally similar to the features of the devices described above with respect to Figures 1-9, such as the distal portion 1010, a catheter shaft 1020, and a handle 1030.
  • the distal portion 1010 includes a balloon 1011 with a central lumen 1021. Not shown in the cross-sectional view of the distal portion 1010 are one or more lumens for balloon inflation (e.g., providing fluid communication with the handle 1030).
  • the balloon 1011 can be any other suitable expandable component (e.g., a shape memory device, expandable cage, and the like).
  • the distal portion 1010 includes rigid offset components 1005a and 1005b (referred to collectively as “the rigid components 1005”) attached to opposite sides of balloon 1011.
  • Each of the rigid components 1005 includes a lumen 1006 with a corresponding exit port 1007, an offset surface 1009, and a transition to the offset surface.
  • the rigid components 1005 can be glued or otherwise attached to balloon 1011 in a manner that does not compromise the integrity of the balloon 1011 when inflated (e.g., by weakening the balloon 1011).
  • Guide tubes 1040a and 1040b extend from the proximal end of the rigid components 1005 towards the handle 1030 ( Figure 10).
  • the guide tubes 1040a and 1040b extend continuously to the handle 1030 and include two lumens 1042a and 1042b (referred to collectively as “the shaft lumens 1042”) within in catheter shaft 1020.
  • Two needles 1015a, 1015b can then extend from the handle 1030, through the shaft lumens 1042 and into (or out of) the rigid components 1005.
  • Figure 11A illustrates the device 1001 being positioned in a vessel before the balloon 1011 is uninflated.
  • Figure 11B illustrates the device 1001 after the balloon 1011 is inflated, bringing the vessel wall W in apposition to the rigid components 1005.
  • Figure 11C illustrates the device 1001 as the needles 1015 simultaneously advance partially out of the exit ports 1007 and into the vessel wall W at two target sites.
  • the depth of the access is determined by the height of the needles 1015 as they exit the exit ports 1007, as well as the height and shape of the needle opening.
  • the device 1001 includes tubes to cover the needles 1015 after they access the vessel wall W, for example in a similar manner to the embodiments discussed above with respect to Figures 4A and 4B.
  • the device 1001 includes three (or any other suitable number) infusion assemblies to access the vessel wall at three (or more) target sites simultaneously with one device 1001 (or without rotating or otherwise moving the distal portion 1010).
  • the distal portion 1010 includes a mechanical expansion element (e.g., a braid, laser cut tube, shape memory device, and the like) in place of the balloon 1011 illustrated in Figures 10 and 11 A- l 1C.
  • the balloon is a non-compliant, or limited compliance, balloon and the needle height is determined by the inflated balloon diameter combined with the dimensions of the rigid offset components 1005.
  • the needle height can also increase accordingly.
  • the balloon is a compliant balloon and the needle height is determined by the amount of balloon inflation by the user. For example, in a case where the user wants to infuse into an intraluminal site (e.g., a thrombotic material and/or other obstructive material), the balloon can be inflated to a diameter that is smaller than the diameter of the vessel lumen.
  • an intraluminal site e.g., a thrombotic material and/or other obstructive material
  • the needle can then advance into the intraluminal site and not puncture the vessel wall W.
  • a similar type of advancement can be achieved by a device that includes a non-compliant balloon that is smaller than the vessel diameter.
  • the dimensions of the offset component 1005 can be configured such that the needle puncture height is more than one vessel wall thickness past the balloon surface. Accordingly, the needle then punctures entirely through the vessel wall to a location outside the vessel (e.g., in the perivascular space around the vessel).
  • Figures 17A and 17B are isometric and cross-sectional views of a distal portion 1710 of an infusion device 1701 (“device 1701”) including multiple tissue manipulation assemblies 1724 in accordance with some embodiments of the present technology. As illustrated in Figures 17A and 17B, the device 1701 is similar to device 1001 discussed above with reference to Figure 10.
  • the device 1701 includes a distal portion 1710 that includes multiple tissue manipulation and infusion assemblies 1724 (four shown, referred to individually as first-fourth infusion assemblies 1724a-d; also referred to collectively as “infusion assemblies,” “manipulation assemblies,” and/or “needle-guiding components”) attached to an expandable device 1711 (e.g., a balloon and/or another suitable expandable element) to guide multiple tissue manipulation devices 1740 (four shown, referred to individually as first-fourth needles 1740a-d; also sometimes referred to collectively herein as “needles”).
  • the tissue manipulation assemblies 1724 are spaced radially apart from each other along the distal portion 1710 of the device 1701.
  • the needles 1740 can extend distal to the distal portion 1710 of device 1701 in a direction generally parallel (or fully parallel) to a longitudinal axis of the catheter shaft 1720 of device 1701.
  • the device 1701 can manipulate and/or deliver an infusate into an infusion site (e g., into intraluminal tissue) distal to the distal end 1710.
  • the device 1701 includes multiple needles 1740 and corresponding needle-guiding components 1724, the device 1701 can deliver the infusion to multiple infusion sites at one time (or sequentially without relocating the distal portion 1710).
  • each of the needles 1740 extends through a corresponding lumen 1722 ( Figure 17B) in the catheter shaft 1720, a corresponding exit port 1713a, and a corresponding one of the infusion assemblies 1724.
  • each of the first-fourth needles 1740a-d can include a transition region 1744 between the corresponding exit ports 1713a and the first-fourth infusion assemblies 1724a-d.
  • the transition region 1744 is not parallel to the longitudinal axis of the catheter shaft 1720.
  • the infusion assemblies 1724 can then direct the needles 1740 along the longitudinal axis of the catheter shaft 1720 to help ensure the needles 1740 travel distally along the longitudinal axis.
  • the infusion device 1701 can target infusion sites by selectively expanding the expandable device 1711 and advancing the needles 1701 distally through the infusion assemblies 1724.
  • the expandable device 1711 is a balloon.
  • the balloon can be compliant, semi-compliant, or non-compliant.
  • the balloon compliance, the balloon size with respect to the vessel, and/or the balloon inflation strategy can all be selected and/or controlled to access specific, predetermined regions of an intraluminal site, an intramural site, and/or an extraluminal site.
  • the balloon can be inflated to target a boundary layer between an obstructive material and the vessel walls.
  • the balloon can be inflated to a diameter that presses the infusion assemblies 1724 into apposition with the vessel walls, allowing the needles 1740 to access extraluminal sites for infusion.
  • the infusion device 1701 also includes a central lumen 1721.
  • the central lumen can allow a guidewire, imaging device, and/or any other suitable tool to be advanced into the vessel.
  • the central lumen can allow a guidewire to be advanced to a position adjacent an infusion site to aid in positioning the infusion device 1701.
  • the guidewire can then be retracted and/or an imaging device (e.g., an IVUS catheter) can be advanced to image the infusion site before, during, and/or after the infusion.
  • an imaging device e.g., an IVUS catheter
  • another tissue manipulation tool e.g., a tissue removing tool
  • a tissue removing tool can be advanced through the central lumen 1721 to help remove an obstruction after the delivery of the infusate by the needles 1740.
  • Figures 12A-12C are partially cross-sectional side views of a distal portion 1210 of an infusion device 1201 during various steps of an infusion procedure in accordance with some embodiments of the present technology.
  • the infusion procedure can deliver an infusate into intravascular tissue or other intravascular structures, and/or between intravascular tissue and the inner wall of a vessel.
  • Figure 12A illustrates the distal portion 1210 of the device 1201 being positioned over a guidewire 1217 at a target site of a vessel V (shown in cross-section).
  • the vessel V is generally defined by a lumen L and a vessel wall W.
  • a layer of intraluminal tissue T within the vessel lumen L is a layer of intraluminal tissue T, such as atherosclerotic plaque or thrombus.
  • Figure 12C illustrates a penetrating member 1240 as it is advanced into a layer of the tissue T and/or between the wall W and the tissue T.
  • the penetrating member 1240 does not need to pierce the vessel wall W, an instead can extend into the tissue T (e.g., at a depth between the tissue T and the inner wall W).
  • the penetrating member 1240 has a blunt, rounded, or atraumatic end to facilitate passage of the penetrating member 1240 between the tissue T and the vessel wall W (and/or into the tissue T at a depth apart from the vessel wall W) without a risk of inadvertently perforating the vessel wall.
  • the device 1201 does not include a sheath that extends over the penetrating member 1240 during advancement and/or infusate delivery.
  • the penetrating member 1240 is a needle with a sharp distal tip (e.g., the needle 140 of Figure 1).
  • one or more fluids can be delivered through a lumen in the penetrating member 1240 at a controlled pressure or flow' rate.
  • the pressure generated by the fluid flow can separate the layer between the tissue T and the wall W.
  • an infusate can be delivered into the tissue T and/or between the tissue T and the vessel wall W.
  • the infusate is at least partially delivered through the penetrating member 1240 during the advancement step (e.g., in a diluted form in the dissection fluid).
  • Figures 12A-12C refer to intravascular tissue, the device 1201 can operate in a similar fashion with respect to other anatomical or prosthetic structures within the vessel lumen L.
  • Figures 13A-13C are partially cross-sectional side views of a distal portion 1310 of an infusion device 1301 during various steps of an infusion procedure in accordance with embodiments of the present technology.
  • Figure 13A illustrates the distal portion 1310 of the device 1301 being positioned over a guidewire 1317 at adjacent a target site of avessel V (shown in cross-section) that is at least partially defined by a lumen L and a vessel wall W.
  • An intravascular implant 1380 e.g., a stent, graft, or stent graft (also shown in cross section)
  • the balloon 1311 is inflated, as illustrated in Figure 13B.
  • Figure 13C illustrates a penetrating member 1340 advanced between the wall W and the implant 1380.
  • the penetrating member 1340 can have a blunt or rounded end to avoid unintentionally puncturing the vessel wall W and/or damaging the implant.
  • one or more fluids e.g., a dissecting fluid and/or an infusate
  • the hydrostatic pressure generated by the fluid can separate the implant 1380 and the wall W, forming a space therebetween, and the penetrating member 1340 can advance into the space.
  • the infusate can be delivered into the space.
  • the infusate is additionally (or alternatively) delivered through the penetrating member 1340 during the needle advancement step (e.g., in a diluted form in the dissection fluid).
  • the tissue in the vessel wall W can grow around and/or through the implant 1380 over time (not shown).
  • the penetrating member 1340 advances along a trajectory substantially parallel to the longitudinal axis of the distal portion 1310 through the tissue ingrowth and/or between the implant 1380 and the vessel wall W to deliver the infusate into the tissue.
  • the infusate can then disperse into the vessel V.
  • the tissue penetrating member 1340 can deliver the infusate into an implant (not shown) that includes a thickness (e.g., a foam) and/or a cavity (e.g., an expandable member).
  • the infusate can then dispel from the implant over time (e.g., through porous walls of the implant, through openings in the implant, through valves of the implant, and the like).
  • All embodiments of an infusion device described above include a proximal handle (e.g., the handle 130 of Figure 1) coupled to various components of the device.
  • the needle 140 of device 101 can be connected (e.g., via a coupler element (not shown) such as a needle shaft) to the actuating component 150.
  • the actuating component is configured to advance and/or retract the needle 140 when the actuating component 150 is turned.
  • the actuating component 150 additionally (or alternatively) advances the tube 442.
  • the actuating component 150 includes one or more subcomponents coupled to different components of the device 101.
  • a first subcomponent can be coupled to the needle 140, while a second subcomponent is coupled to the tube 442.
  • the needle 140 and the tube 442 can be advanced separately as required to access the wall layer then deliver the infusate (e.g., to puncture the wall then deliver the infusate through the through side holes 444 of the tube 442).
  • the actuating component 150 allows a user to control the relative position of the needle 140 and/or the tube 442 with respect to the distal portion 110 (or each other). For example, the user may adjust the position of the needle 140 and/or the tube 442 based on the infusion procedural plan, the stage of the procedural, and/or intravascular or fluoroscopic images.
  • the actuating component 150 allows the needle 140 and/or the tube 442 to be advanced out of the first exit port 113a by a maximum distance equal to or less than the length of the rigid section of the distal portion 110.
  • the maximum distance can be between about 5 mm, about 30 mm, about 40 mm, or about 50 mm depending on the length of the distal portion 110.
  • the handle 130 can include a port 160 that is in fluid communication with the needle 140.
  • the port 160 can be connected to a valve 162 (e.g., a stopcock or other suitable mechanism), and the valve 162 can be connected to two or more fluid lines (two shown).
  • a first fluid line can connect to an inflation device 164 filled with saline fluid for the hydrodissection step of the procedure
  • a second fluid line can be connected to an infusion component 166 (e.g., a syringe or pump) with a drug or other therapeutic agent (referred to collectively as “the agent”).
  • the inflation device 164 and/or the infusion component 166 can include a syringe that can be manually controlled, an inflation device with a pressure gauge and a controller (or manual adjustment mechanism), and/or a pump with a controller.
  • the controller can control volumetric flow rate, flow pressure, total flow infused, and/or any combination therein.
  • a procedure utilizing the device 101 can begin with the needle accessing the vessel wall. Tn some embodiments, the needle’s access is at least partially facilitated through a hydrodissection that includes infusing pressurized saline (or other suitable fluid) using inflation device 164. Once the vessel wall layer is accessed and an intramural space is created, the valve 162 can be turned towards the line with the infusion component 166. In some embodiments, the infusate is then automatically delivered in a controllable matter, for example by a pump in the infusion component 166, into the intramural space. In some embodiments, the access is completed without a hydrodissection fluid, for example by directly advancing the needle 140 of the distal portion of the device and into a vessel wall layer.
  • the valve 162 is movable between a closed position and an open position with the infusion component 166.
  • the infusion component 1 6 includes an internal mechanism (e.g., a valve, switch, and the like) to regulate flow out of the infusion component 166.
  • the infusion component 166 is manually operated, allowing the infusate to be delivered at a manually controlled rate.
  • the infusion component 166 includes an indicator that allows the user access to real time feedback about infusion pressure (e.g., a pressure gauge), a location of the needle and/or the tube (e.g., a location indicator based on the presence or absence of a pressure spike), and/or other relevant information.
  • delivery of the infusate can be automated such that the device 101 maintains a constant pressure during infusate delivery.
  • the valve 162 can be turned towards the line with the saline (or other suitable fluid) after delivering the infusate to provide a bolus of liquid. This can help ensure the infusate has been fully flushed from the device and delivered at the target site.
  • the handle 130 can include a port 170 that is connected to one or more of the lumens of Figure 2, such as the guidewire lumen 221.
  • the port 170 can be connected to a hemostasis valve (not shown) to allow for safe and sanitary introduction of guidewires and/or other suitable devices (e.g., the imaging component) down the guidewire lumen 221.
  • the handle 130 also includes a balloon inflation port 180 that is fluidly connected to balloon 111 and allows connection of an inflation device (not shown) to inflate the balloon 111.
  • the guidewire lumen 221 exits the shaft 120 at a location distal to the handle 130. This can accommodate various lengths of imaging catheters for use with system 100.
  • some imaging catheters may not be long enough to extend from the distal end 110 of the shaft 120 through the handle 130, but may have a length suitable for extending from the distal end 110 of the shaft 120 to an exit at a port distal to handle 130.
  • This embodiment can also reduce the components extending through the handle 130, thereby allowing for a lower profile handle and/or additional versatility for the system 100.
  • the handle 130 has an actuator which can pull back the catheter shaft 120 and/or distal portion 110 while maintaining the position of the needle 140 in the vessel. During a procedure, this allows the distal portion 110 and the balloon 111 to be pulled away from the target site (at or near the puncture location or near the first exit port 113a) while the infusate is delivered. The removal of the distal portion 110 and the balloon 111 can allow a clearer visualization of the infusion, for example by an intravascular imaging catheter extending through the guidewire lumen 221 and/or by an external fluoroscopy component.
  • the devices and/or their components discussed above can vary in size depending on the size of the target vessel or body conduit, the size of the target site, and/or the desired maximum flow rate through the device.
  • the needle can have a size of between about 20 gauge and about 35 gauge.
  • the needle can be smaller at the distal portion to facilitate access to the vessel wall, then step up in size and/or be connected to a larger tube so that flow resistance through the length of the lumen within the needle is reduced.
  • the expansion element can expand to provide adequate vessel wall apposition in vessels and have a maximum inner diameter from about 6 mm up to about 22 mm.
  • the device is coupled to an energy source that can be used in conjunction with intramural agent delivery to increase diffusion and uptake of the agent into the target site.
  • energy sources include electric current, magnetic field, ultrasound, pulsed light, or temperature, each of which are expected to improve the efficiency of the infusate delivery and/or absorption by the tissue.
  • the energy source can be carried by and/or incorporated into the distal portion of the device.
  • an electrode can be attached to the distal portion of the device to generate an electric current, magnetic field, and/or an ultrasound pulse.
  • a separate tool catheter can be deployed in a central lumen of the device (e.g., wdthin the guidewire lumen 221 ( Figure 2)).
  • the device can be removed and replaced with an energy catheter which is activated after the agent is delivered during the infusion step.
  • various manual techniques such as squeezing or massaging the patient from the outside (e.g., along the leg) can be used in conjunction with the infusion, including in conjunction with real time imaging of the infusion.
  • the infusion delivery device is coupled with another therapeutic device.
  • the guidewire lumen 221 ( Figure 2) of the infusion delivery device can be configured to deliver a balloon dilatation catheter, a stent delivery device, a thrombectomy device, and/or any other relevant interventional treatment device to provide an interventional therapy in conjunction with the infusion.
  • the infusion delivery device can perform an infusion procedure, then be removed and replaced wi th atherapy catheter to perform an interventional therapy.
  • the therapy device can be used first, then the infusion delivery device can perform an infusion procedure.
  • the device is inserted over a guidewire and into a vessel via an access site remote from the treatment site using standard intravascular techniques and equipment.
  • the distal portion of the device is positioned at a target site within the vessel.
  • the guidewire is then removed from the guidewire lumen and replaced with an intravascular imaging component (e g., an IVUS catheter).
  • the balloon (or other expansion element) is then expanded such that the vessel w all is pressed against the transition portion and the offset surface of the distal portion 110.
  • the needle which is connected to a pressurized fluid source (e.g., saline), is then advanced from the first exit port and pierces the vessel wall, then pressurized fluid is used to further access an intramural space within the vessel wall. That is, once the distal opening of the needle is completely enclosed by the vessel wall, the fluid builds up pressure and creates an intramural space.
  • the pressure of the fluid may be between about 1 atmosphere (atm) and about 4 atm.
  • the needle continues to advance for a first distance after puncturing the vessel wall (e.g., between about 3 mm and about 6 mm), then the tapered tube is advanced to cover the tip of the needle.
  • the needle and the tube are then advanced together for a second distance (e.g., in a range between about 0.5 cm and about 3 cm) as the pressurized fluid from the needle creates an intramural space in between the vessel wall layers.
  • the imaging component can then be advanced through the guidewire lumen 221 (or another suitable lumen) and positioned such that the imaging component can provide images and/or measurements related to the puncturing and access into the intramural layers.
  • the imaging component can also provide images that help visualize the intramural space created therein.
  • the valve 162 can be actuated to deliver an infusate (e.g., a drug or other therapeutic agent) into the intramural space.
  • the infusate can be mixed with a contrasting agent so that infusion can be viewed more easily through fluoroscopy devices.
  • the infusate can additionally, or alternatively, be mixed with an echogenic agent (e.g., gas-filled microbubbles, such as air bubbles, or suspended particles) such that the infusion can be visualized in cross section using the imaging component.
  • an echogenic agent e.g., gas-filled microbubbles, such as air bubbles, or suspended particles
  • the user can control the flow rate and volume of the infusates delivered until an adequate area is treated and/or an adequate infusates volume is delivered and/or absorbed.
  • the user can use the imaging information to determine an optimal volume, pressure, and/or flow rate, or base the infusion on a pre-determined volume of an infusate.
  • the infusate can be delivered at a steady flow rate and/or a steady pressure until the desired distribution or volume of the infusate is delivered and/or absorbed.
  • the infusion pressure is generally equal to or less than the pressure that was used to access the tissue layer and create the intramural space. In some embodiments, the infusion pressure is higher (e.g., in a range between about 4 atm and about 10 atm) to increase the size of the intramural space and the drug dispersion area.
  • the infusion pressure can be set to achieve a specific circumferential distribution of an infusate, for example encompassing 90, 180, 270, or 360 degrees of vessel wall. In some embodiments, the infusion pressure can be set to achieve a specific longitudinal distribution of the infusate (e.g., about 1 cm, 3 cm, 5 cm, and/or another distance from the puncture site).
  • the infusate can be delivered in a pulsed manner, either pulsed pressure or pulsed flow until the desired distribution or volume of the infusate is delivered.
  • a pulsed flow can be paired with real time cross-sectional imaging at a pre-specified target distance from the puncture location (e.g., about 3 cm caudal or cranial to the puncture location), as a means to determine if the hydrodissection fluid or infusate mixture has reached the pre-specified target distance.
  • the analysis can include a real-time imaging interpretation of pulsed or dynamic movement within the appropriate intramural or extra vascular layers at the pre-specified target distance.
  • the infusion can occur while the balloon 111 is inflated.
  • the intramural space can be created while the balloon 111 is inflated, then the balloon 111 can be deflated while (or before) the infusate is being delivered so that the vessel V is not compressed during the delivery.
  • the distal portion 110 is pulled back during the infusion stage of the procedure.
  • the needle can deliver at least a portion of the infusate during the needle advancement step (e.g., an initial dose that can be absorbed while the intramural space is created).
  • the pressurized fluid used to access the vessel wall W and create the intramural space includes a diluted amount of the infusate.
  • the needle 140 is advanced to a desired length and the pressurized fluid is delivered until a desired distribution area on the vessel wall receives the infusate and/or a desired volume is delivered.
  • a predetermined distribution area e.g., corresponding to predetermined target treatment site
  • a thickened fibrotic vessel wall can require a higher infusion pressure than a normal vessel wall.
  • the infusion pressure to achieve the predetermined distribution area can be as high as about 10 atm, as low as about 2 atm, and/or dynamically adjusted throughout the procedure (e.g., based on intravascular or fluoroscopic imaging and/or a position of the needle 140), until the predetermined distribution area is achieved.
  • the predetermined distribution area can be of a particular circumferential coverage around the vessel, (e.g., 90, 180, 270 or 360 degrees around the vessel).
  • the predetermined distribution area can be of a particular length along the vessel (e.g., about 1 centimeter (cm), about 3 cm, or about 5 cm in one or both directions from the target site).
  • the infusion pressure can be lowered to deliver a desired total volume of infusate without increasing the size of the distribution area further.
  • the device 101 can be configured to penetrate, advance, and deliver an infusate between specific and/or predetermined layers of the vessel wall (e.g., at a predetermined layer, at a predetermined depth, etc.).
  • the device 101 is configured to specifically access the medial layer of an artery or vein, the adventitial layer of an artery or vein, the perivascular space around the vessel, and/or any other suitable layer or depth.
  • the device 101 is configured to extend between intravascular tissue, such as between the thrombus or atherosclerotic plaque and the vessel wall, and/or into the intravascular tissue itself.
  • the device 101 can also be configured such that the needle height is dynamically adjustable.
  • the user can adjust the needle height to selectively access one or more layers of the vessel wall (e.g., the medial, adventitial, or perivascular layers of the vessel wall) during the procedure.
  • the needle height adjustment can additionally (or alternatively) be used to accommodate vessels with varying wall thicknesses (e.g., to adjust operation of the device 101 to a particular patient anatomy, to selectively access a desired layer in the vessel wall, and the like).
  • the user can use imaging information (e g., from an IVUS) of an initial infusion to adjust the needle height for a subsequent infusion.
  • the distal portion 110 is re-positioned adjacent the target site (e.g., re-advanced if it was pulled back in a previous step) and the balloon Il l is re-mflated to compress the intramural layer such that the infusate is further dispersed in the layer of the vessel wall, and/or outward from the layer into outer layers (e.g., the adventitial layers or perivascular space surrounding the vessel) to aid in infusate dispersion into the vessel wall layers.
  • outer layers e.g., the adventitial layers or perivascular space surrounding the vessel
  • the device 101 can be pulled back and a separate expandable catheter (e.g., a separate balloon catheter) can be advanced through the guidewire lumen 221 to the target site.
  • a separate expandable catheter e.g., a separate balloon catheter
  • the imaging component and/or the guidewire 317 are removed prior to introduction of a separate expandable catheter.
  • the separate expandable catheter size is selected to be larger than the vessel diameter, for example 110% or 120% of the vessel diameter, such that it will compress the vessel wall when expanded and further disperse the infusate in the wall layer, and/or outward from the layer into outer wall layers and/or perivascular space.
  • the separate expandable catheter does not have a rigid offset surface such that dispersion with the separate expandable catheter more uniformly compresses the vessel wall.
  • the separate expandable catheter can include an inflatable balloon that partially contorts to apply a generally even pressure across the vessel wall.
  • the separate expandable catheter can also have a desired therapeutic effect on the vessel, for example when the procedure is treating a narrowing vessel and/or an occlusion.
  • the infusion device can be re-used at multiple locations to deliver the infusate at multiple locations along a vessel, thereby treating more locations than can be accommodated by a single puncture and infusate location.
  • real-time imaging information gained during the previous puncture can help dictate where the next puncture and infusion should take place.
  • the device 101 is used to deliver an infusate to an intramural layer of a vessel wall. After the infusate delivery, the device 101 is pulled back, a separate stent delivery catheter is advanced through the guidewire lumen 221, and a stent is implanted at the target site.
  • the stent delivery procedure can be used, for example, when the target site has a narrowing vessel and/or stenosis compromising flow through the vessel.
  • the stent implantation is the primary therapy for the procedure, but the preliminary infusate delivery from the device 101 is expected to mitigate various undesired negative effects of the stent implantation (e.g., vessel irritation).
  • an implant e.g., the stent
  • the device 101 and/or components thereof are configured to be advanced between the implant and the vessel wall.
  • the device 101 can be advanced to the site of a stent implantation with the first exit port 113a positioned at a location adjacent to the proximal edge of the stent.
  • the needle 140 can then be advanced out of the first exit port 113a and between the stent and the vessel wall.
  • the needle 140 can advance into the restenotic tissue itself (e.g., advanced through tissue within the stent and/or or between the stent and the tissue rather than between the stent and the vessel wall).
  • the needle 140 is advanced along a substantially straight path generally parallel to the support surface and/or the longitudinal axis of the device 101.
  • the infusate can be delivered during needle advancement and/or after the needle has completed advancement a desired distance at the target site.
  • Types of drugs that can mitigate the effects of restenosis as the infusate in any of the examples above include anti-thrombotic, anti-proliferative, anti-inflammatory drugs, or some combination therein.
  • examples include paclitaxel, sirolimus, everolimus, heparin, dexamethasone, or the flavonoid family of drugs.
  • Drug mixtures may also be injected as the infusate. Additionally, drug-impregnated microspheres can be delivered by the device 101.
  • Microspheres for controlled release of drugs are typically made from bioabsorbable polymers such as the polylactic acid family of polymers (PLA, PDLA, PLLA) and range in size from about 10 microns (pm) to about 20 pm (e.g., about .0004 inches to about .0008 inches).
  • Drug- impregnated microspheres injected into an intramural space of a vessel wall can extend the therapeutic effect of an infusate for a desired period.
  • a drug- impregnated polymer can be directly injected into the intramural space to prolong the diffusion of an infusate at the target tissue area.
  • injectable polymers examples include polylactic acid polymers such as PLLA or PDLA diluted with a biocompatible solvent such as N-methyl-2- pyrrolidone (NMP). Dilutions can vary depending on the required viscosity for inj ection and the desired final material characteristics. For example, the dilution can be about 50:50 PDLA and NMP.
  • NMP N-methyl-2- pyrrolidone
  • infusate delivery can be used in conjunction with treatment of thrombosis in the vein to mitigate post-thrombotic syndrome.
  • DVT deep vein thrombosis
  • removal of thrombus either through natural causes or treatment can often lead to thrombotic obstruction, valvular incompetence, or a combination of, thereby causing an array of clinical symptoms such as leg pain, leg heaviness, vein dilation, edema, skin pigmentation, and/or venous ulcers (known collectively as post-thrombotic syndrome (PTS)).
  • PTS post-thrombotic syndrome
  • the infusate delivery device is used to deliver infusates that have the potential to reduce the incidence of PTS, such as anti-inflammatory drugs into an intramural layer of the vessel wall.
  • the infusate delivery device is used to deliver anti-inflammatory drugs into a space between residual thrombus and the vessel wall and/or into the thrombus itself. Examples include corticosteroids such as dexamethasone, antithrombotic infusates such as heparin, or some combination.
  • the infusate delivery can occur after a thrombectomy procedure has been performed and the occlusive clot has been removed. Alternately, an infusate delivery procedure can be performed on patients who have previously had a DVT, or who may or may not have been treated for the DVT but are nonetheless at risk for PTS.
  • infusate delivery can be used in conjunction with various other treatments of patients at risk for aortic aneurysm or dissection.
  • a breakdown in elastin and collagen can cause an aortic wall to weaken, leading to increased risk of aneurysm dissection or ulcers.
  • An intramural delivery of an infusate (e.g., anti-inflammatory agent such as doxycycline) to the weakened aortic wall can counteract the effects of degradation of elastin and collagen.
  • the device can be used to inject collagen or biocompatible or bioabsorbable polymers (such as the injectable polymers described above), or adhesives to strengthen the aortic wall.
  • infusate delivery is used for a treatment of thrombosis and/or another vessel obstruction to facilitate removal of obstructive material.
  • the infusate can be delivered into an intraluminal location (e.g., into an obstructive material, an intraluminal site, and/or into a boundary layer between obstructive material and vessel wall), an intramural location, and/or another suitable infusion site (e.g., to a location external to a delivery vessel, such as a second vessel adjacent a delivery vessel).
  • the infusate can be delivered at the distal portion 110 of the device 101 (e.g., as discussed above with respect to Figs.
  • the infusate can be selected from an agent know n to aid in breaking down the obstructive material, and/or the attachment of the obstructive material to the vessel wall.
  • the infusate may be selected from a class of proteolytic enzymes, matrix metalloproteinases (MMPs), which are capable of degrading extracellular matrix proteins.
  • MMPs matrix metalloproteinases
  • Specific examples of the agent include collagenase, which is a sub-type of MMPs which break down collagenic structures such as those found in chronic arterial and venous occlusions. These include MMP-1, -8, 13, and -18.
  • MMPs such as MMP-3 or MMP-7 are fibrinolytic and may be more useful in breaking down fibrin- containing structures found acute arterial and venous occlusions.
  • the infusate can be selected from a class of thrombolytic agents such as tPA, urokinase, and the like.
  • the infusion device 101 is used to deliver the agent into a vessel obstruction (e.g., into an intraluminal site such as a thrombotic occlusion) and/or the boundary layer between the obstruction and to facilitate removal of the obstructive material.
  • the infusion drug may be selected based on the nature of the obstructive material.
  • the infusate can be selected from a type of MMP such as collagenase or fibrinolytic agent.
  • the agent may be selected from a group of thrombolytic agents or other suitable agents to break down the obstructive material.
  • the infusate can include a saline solution. Additionally, or alternatively, the procedure can include a hydrodissection step wdth saline, followed by an infusion step with an agent that breaks down obstructive material.
  • FIG 18 is a flow diagram of a process 1800 for delivering the infusate to treat a vessel obstruction in accordance with some embodiments of the present technology.
  • the vessel obstruction can be thrombotic tissue, a hemostatic clot, and/or any other relevant vessel occlusion.
  • the process 1800 is discussed primarily herein with reference to the infusion device 1601 of Figures 16A-16C. However, it will be understood that the process 1800 can be completed by any of the devices discussed above with reference to Figures 1-17B.
  • the process 1800 begins at block 1802 by positioning an infusion device (e.g., the infusion device 1601 of Figure 16A) adjacent an infusion site.
  • the infusion site can be an intraluminal location (e.g., within the vessel obstruction, an intraluminal site at or adjacent the vessel obstruction, and/or into a boundary layer between the vessel obstruction and the vessel wall), an intramural location (e.g., a space created within a vessel wall), and/or external to a vessel (e.g., a second vessel adjacent the vessel the infusion device is positioned within).
  • positioning the infusion device includes advancing the distal portion of the infusion device to a position adjacent the infusion site.
  • the infusion device can be advanced such that the infusion site is distal to the distal portion but within reach of a needle (or other tissue manipulation device, referred to collectively herein as the needle) exiting the distal portion.
  • the infusion device can be advanced such that the infusion site is radially spaced apart from the distal portion.
  • the process 1800 includes targeting the infusion site.
  • Targeting the infusion site can include orienting the infusion device, imaging the infusion site, and/or manipulating the vessel to allow the needle to advance out of an exit port and into the infusion site.
  • targeting the infusion site includes expanding an expandable component at the distal portion of the infusion device (e.g., the balloon 1611 of Figure 16B) to press partially against the vessel wall.
  • the vessel can be at least partially straightened by the expansion of the expandable component.
  • the infusion device can allow the needle to advance longitudinally (parallel to the vessel lumen) into an infusion site without unintentionally piercing the vessel walls.
  • straightening the vessel can help facilitate access to an infusion site distal to the infusion device (e.g., a full and/or partial occlusion) unintentionally piercing the vessel walls.
  • targeting the infusion site includes rotating the infusion device within the vessel (e.g., to target tissue on other radial walls within the vessel).
  • targeting the infusion site includes adjusting a height of the needle above the offset surface at the distal portion of the infusion device (e.g., thereby adjusting a distance between the needle and a central longitudinal axis of the catheter shaft of the infusion device).
  • the exit port for the needle can include a rotatable guide component (e.g., the needle guide 1402 of Figure 14A) to adjust the height of the needle above the offset surface, thereby allowing the radial position of the needle to be adjusted to accurately target the infusion site.
  • the process 1800 includes advancing the needle into the infusion site.
  • the infusion site can an intraluminal location, such as longitudinally adjacent an obstructive material (e.g., thrombotic tissue or another occlusion), a space within the obstructive material, and/or a space within boundary layer between the obstructive material and the vessel wall.
  • advancing the needle includes penetrating intraluminal tissue.
  • the infusion site can be at an intramural space (e.g., within the vessel wall, within a pocket created in the vessel wall, and the like).
  • advancing the needle includes hydrodissecting the vessel wall to create an intramural space within the wall.
  • the infusion site can be external to the vessel (e.g., into an occlusion in an adjacent vessel). Accordingly, in such embodiments, advancing the needle includes penetrating vessel wall to access the external infusion site (e.g., as discussed above with respect to Figure 16C).
  • the process 1800 includes hydrodissecting the obstructive material to help access the infusion site and/or to aid in breaking down the obstructive material.
  • the process 1800 can partially dissect the boundary layer between the obstructive material and the vessel wall to both access a space between the two and to help aid in separative the obstructive material (e.g., thrombotic tissue) from the vessel wall.
  • the obstructive material e.g., thrombotic tissue
  • the process 1800 includes delivering the infusate to the infusion site.
  • the infusate is delivered at a relatively low pressure to avoid dissecting any adjacent tissue.
  • the infusate is delivered at a pressure sufficient to at least partially dissect adjacent tissue (e.g., tissue in the boundary layer) and/or help ensure the infusate contacts and acts on the obstructive material.
  • the drugs in the infusate can act on surrounding tissue.
  • the infusate includes an MMP (e.g., collagenase and/or a fibrinolytic agent)
  • the MMP can begin breaking down the tissue in the obstructive material.
  • the process 1800 energizes the infusate and/or the tissue in and around the infusion site before, during, or after delivery to catalyze the action of a drug in the infusate.
  • the process 1800 can include directing ultrasound energy to the infusion site.
  • the infusion device can include a transmitter directed distal to the distal portion to direct ultrasound energy to the infusion site.
  • the ultrasound energy can be directed to the infusion site through an external source (e.g., a transmitter external to the patient’s body).
  • additional (or alternative) sources of energy e.g., heat and/or light
  • the infusate is delivered in the form of an agent compounded in a slow-release vehicle (e.g., polymer nano-particles or beads, foam from materials such as PVA, PLLA, liposomes, hydrogels, and the like).
  • a slow-release vehicle e.g., polymer nano-particles or beads, foam from materials such as PVA, PLLA, liposomes, hydrogels, and the like.
  • the slow release can extend the action of the agent over a longer period of time.
  • the process 1800 after delivering the infusate at block 1808, the process 1800 returns to block 1802 or block 1804 to position the infusion device adjacent a second infusion site and/or to target a second infusion site.
  • the process 1800 can deliver infusate to multiple infusion locations to improve the amount of the obstructive material that is removed.
  • the process 1800 can execute blocks 1802-1808 multiple times to deliver infusate to multiple radial locations of the boundary layer and/or multiple locations in the obstructive material.
  • the process 1800 accesses and delivers infusate to multiple infusion locations at a single time.
  • the process 1800 includes removing at least a portion of the obstructive material.
  • removing a portion of the obstructive material includes hydrodissecting a portion of the obstructive material (e.g., the portion acted on by the infusate) and allowing blood flow to carry away any removed portions. For example, when the infusate was delivered to a boundary layer, the infusate can break down the tissue at the boundary layer, then a hydrodissection process can further excise remaining tissue from the vessel wall.
  • removing a portion of the obstructive material includes capturing the removed portions (e.g., through a fluid removal lumen).
  • the process 1800 can be a stand-alone procedure to enhance the natural removal of obstructive material in a vessel of a patient.
  • the removal at block 1810 e.g., the hydrodissection
  • the process 1800 can be executed by the infusion device.
  • the process 1800 can be a partially adjunct procedure to a removal of an obstructive material.
  • the removal process at block 1810 can be completed by a separate device, such as a mechanical and/or aspiration thrombectomy device.
  • the removal process 1800 can occur during the same procedure.
  • an infusion device e.g., the device 101 of Figure 1
  • a separate device can complete the removal step at block 1810.
  • the process 1800 includes a dwell period between the infusion step and the removal step.
  • the infusate can be left to act on the obstructive material for about 30-60 minutes.
  • the infusion step can be completed in a first procedure; then the removal step can be completed in a second procedure one or more days later.
  • the infusate is provided a relatively large amount of time to act on (e.g., break down) the obstructive material.
  • a method of delivering a therapeutic agent to an infusion site comprising: positioning a distal portion of catheter shaft of an infusion device within a vein of a patient proximate to an infusion site; advancing a needle of the infusion device through an exit port of the needle lumen to the infusion site; and delivering, through the needle, an infusate to the infusion site to break down tissue at or adjacent the infusion site, wherein the infusate comprises a matrix metalloproteinase.
  • tissue is an intraluminal tissue that is at least partially occluding the vein beyond a distal end of the catheter, and wherein the method further comprises removing at least a portion of the intraluminal tissue after delivering the infusate to the infusion site.
  • the infusion site is a boundary layer between a thrombotic material and a vessel wall, and wherein advancing the needle toward the infusion site includes penetrating the boundary layer to access a space between the thrombotic material and the vessel wall.
  • tissue is an intraluminal tissue that is at least partially occluding the vein
  • infusion site is a space within the intraluminal tissue
  • advancing the needle to the infusion site includes advancing the needle into the intraluminal tissue.
  • targeting the infusion site includes at least partially expanding an expandable component on the distal end of the catheter shaft, wherein expanding the expandable component at least partially straightens a portion of the vein.
  • the exit port includes a rotatable guide component to adjust a distance between the needle and a central longitudinal axis of the catheter shaft before advancing the needle out of the exit port, and wherein targeting the infusion site includes adjusting the distance between needle and the central longitudinal axis of the catheter shaft.
  • the infusion site is external to the vein of the patient; the method further comprises pressing an engagement surface of a housing at the distal end of the catheter shaft against a vessel wall to conform the vessel wall to the engagement surface; and advancing the needle to the infusion site includes penetrating through the vessel wall conformed to the engagement surface to access the infusion site.
  • An infusion device comprising a handle assembly; a catheter shaft having a proximal portion coupled to the handle assembly and a distal portion, wherein the catheter shaft includes: a lumen extending from the proximal portion to the distal portion; a housing at the distal portion having an exit port in communication with the lumen, a transition surface adjacent the exit port and an offset surface distal to the exit port; and an expandable component at the distal end portion and positioned to press against a tissue wall to at least partially straiten a section of a vessel to orient the exit port toward an infusion site distal to the distal portion of the catheter shaft; and a needle positioned within the lumen and slidably movable along a path parallel to a longitudinal axis of the catheter shaft to access the infusion site after the expandable component expands, wherein the needle includes a fluid lumen to deliver a drug to break dow n thrombotic tissue at the infusion site.
  • An infusion device comprising: a handle assembly; a catheter shaft having a proximal end portion coupled to the handle assembly and a distal end portion, wherein the catheter shaft includes: one or more needle lumens extending from the proximal end portion to corresponding exit ports adjacent the distal end portion; a central shaft at the distal end portion, the housing including an expandable component circumferentially surrounding a central shaft and one or more needle guide components carried by the expandable component and individually corresponding to each of the one or more needle lumens; one or more needles each slidably extending through an individual one of the one or more needle lumens and into one of the one or more needle guide components, wherein each of the one or more needles includes a fluid lumen positioned to supply an infusate to an infusion site distal to the distal end portion when the catheter shaft is positioned with a vessel of a patient.
  • a method of operating the catheter device of claim 16 comprising any of the step of examples 1-15.
  • a method of operating the catheter device of claim 18 comprising any of the step of examples 1-9 and 11-13.
  • An infusion device for delivering an infusate to an infusion site as disclosed herein.
  • delivering the drug comprises delivering a matrix metalloproteinase to an infusion site within and/or adjacent an obstructive material.
  • a method of intravascularly delivering a therapeutic agent to a patient diagnosed with vessel obstruction comprising: positioning a distal portion of a catheter device at a target site within a vessel of the patient; accessing a boundary layer between the obstruction and the vessel wall; and delivering a drug to break down the attachment of the obstruction to the vessel wall.
  • a method of intravascularly delivering a pressurized fluid to a patient diagnosed with vessel obstruction comprising: positioning a distal portion of a catheter device at a target site within a vessel of the patient; accessing a boundary layer between the obstruction and the vessel wall; and delivering a pressurized fluid to aid in separation of the obstructive material from the vessel wall.

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Abstract

Sont divulgués ici des dispositifs intravasculaires et des méthodes d'administration intramurale de liquides de dissection et de solutions intraveineuses. Selon certains modes de réalisation, les systèmes comprennent un ensemble de perfusion qui peut accéder à une position dans un vaisseau adjacent à un site de perfusion et faire avancer un composant de manipulation de tissu à l'intérieur du site de perfusion pour administrer une solution intraveineuse thérapeutique. Le site de perfusion peut être un espace intraluminal, tel qu'à l'intérieur d'un matériau obstructif, adjacent au matériau obstructif et/ou à l'intérieur d'une couche limite entre le matériau obstructif et une paroi de vaisseau. L'ensemble de perfusion peut en outre administrer une solution intraveineuse qui comprend un médicament thérapeutique ou un autre agent à l'intérieur du site de perfusion.
PCT/US2023/020489 2022-04-29 2023-04-28 Dispositifs intravasculaires et méthodes d'administration de liquides et d'agents thérapeutiques à l'intérieur de parois de vaisseaux sanguins et de structures intravasculaires WO2023212373A2 (fr)

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US4794931A (en) * 1986-02-28 1989-01-03 Cardiovascular Imaging Systems, Inc. Catheter apparatus, system and method for intravascular two-dimensional ultrasonography
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