Endoluminal intravascular catheters, systems and related methods

Abstract

Endoluminal neurovascular microcatheters, systems and related methods for directly infusing a diminutive neurovascular vessel. A microcatheter comprises a longitudinally elongated catheter body of at least 135 cm extending from a proximal end portion to a free distal end of a distal end portion configured to directly infuse or aspirate a diminutive neurovascular vessel. The catheter body is longitudinally variably flexible, and comprises a tubular wall structure that defines a continuous, unobstructed inner lumen that is open at the free distal end. The distal end portion comprises a plurality of micropores, between proximal and distal radiopaque markers, that define a minimum cross-sectional dimension less than or equal to 0.01 inch and a cross-sectional area less than or equal to 0.05 mm2. At least the free distal end defines a maximum outer diameter of 1 mm or less, and a maximum inner diameter of the lumen 0.7 mm or less.

Description

Atty Ref . No.: 6473.001AWOENDOLUMINAL INTRAVASCULAR CATHETERS, SYSTEMS AND RELATED METHODSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application perfects and claims priority benefit of U.S. Provisional Patent Application No. 63 / 779,480, filed on March 28, 2025, entitled Catheter With Micropore Technology, and U.S. Provisional Patent Application No. 63 / 780,689, filed on March 31, 2025, entitled Catheter With Micropore Technology, the entirety of which are hereby expressly incorporated herein by reference.FIELD OF THE DISCLOSURE

[0002] The present disclosure relates generally to endoluminal intravascular microcatheters and related methods, developed for diagnostic and therapeutic indications. More particularly, the present disclosure related to endoluminal neurovascular microcatheters and related systems and methods that are configured to safely and effectively access the diminutive vessels of a brain or spine and directly infuse a target or treatment site with a liquid therapeutic agent or diagnostic material or sample the target site to treat or sample the target site or proximate area of interest.BACKGROUND

[0003] The neurovascular system of a human comprises, inter alia, a complex network of blood vessels, arteries of which, supply the brain and spinal cord with oxygen and nutrients. Conversely, venous portions of the neurovascular system serve to drain blood and waste products from, inter alia, the brain and spine. For example, the great vein of Galen drains the anterior and central regions of the brain, emptying into the dural sinuses and ultimately into the internal jugular veins, thereby preventing a build up of toxic metabolites and / or raise intracranial pressures in the blood vessels of the brain.

[0004] The blood supply to the brain is via two main pairs of arteries: the carotid arteries and the vertebral arteries. The carotid arteries are located in the front of the neck and mainly supply the front and middle parts of the brain, by dividing into anterior cerebral and middle cerebral arteries on each side. The front part of the brain, mainly the frontal lobe, is responsible for thinking, planning, decision-making, problem-solving, controlling behavior and emotions, and movement. It also plays a role in speech. The middle part of the brain, which includes parts of the parietal lobe and deeper structures, helps with processing touch,Atty Ref . No.: 6473.001AW0pain, temperature, and spatial awareness. It also plays a role in coordinating movement and integrating sensory information from different parts of the body.

[0005] The vascular system of the back of the brain includes the vertebral arteries, basilar artery, and other arteries that supply blood to the cerebellum, brainstem, and occipital lobes. Regarding vertebral arteries, two vertebral arteries branch from the subclavian arteries in the neck and run generally along with the spinal column into the skull. The basilar artery, essentially the main artery that supplies blood to the back of the brain (comprising the posterior cerebral circulation), originates where the vertebral arteries join near the brainstem, and effectively supplies blood to the brainstem, cerebellum, and occipital lobes. The Circle of Willis includes a loop of blood vessels near the bottom of the brain that connects major arteries, and provides a redundant function, ensuring that blood can flow to the affected part of the brain, should there be an ischemic issue with one of the main arteries.

[0006] The back of the brain is integral to proper physiological function, and controls many vital functions, including breathing, heart rate, swallowing, vision, movement, and balance. When the arteries supplying blood to the brain are blocked due to a thrombus (a blood clot) the brain cells in that area start to die within minutes, and is a medical emergency.

[0007] When a blood vessel of the brain and / or spine of a human become blocked or obstructed, such as from a blood clot or fatty plaque (atherosclerosis) for example, it is a condition referred to as a stroke. The effects of the stroke depend on which vessel (artery or vein) is blocked, and the part of the brain and / or spine that is affected. An ischemic stroke occurs when a vessel supplying blood to the brain (i.e., an artery of the neurovascular system of the brain) is obstructed, and is the most common type of stroke and requires fast treatment to reduce brain and / or spine damage. If an obstruction involves the venous system of the brain and / or spine, then blood builds up behind the obstruction, causing swelling, pressure, and sometimes bleeding in the brain and / or spine, which can lead to headaches, seizures, vision problems, weakness and in severe cases death.

[0008] Stroke treatment, such as for an ischemic stroke, focuses on restoring blood flow as quickly as possible. Doctors may administer a “clot-busting” thrombolytic liquid medication tissue plasminogen activator (tPA), like alteplase and tenecteplase, into the patient’s neurovascular system generally (e.g., intravenously), which works by traveling through the patient’s vascular system and eventually, and hopefully, to the clot, where the medication may act to dissolve the clot. Unfortunately, not enough medication often reaches the clot to effectively or fully dissolve or otherwise treat the clot, especially in diminutive vessels of theAtty Ref . No.: 6473.001AWObrain and / or spine (such as when insufficient blood flow is present due to the clot). And because thrombolytic medication has serious side effects, only a certain amount of the medication can be given to a patient. Such thrombolytic medication is thereby often ineffective in treating clots in the neurovascular system (e.g., in the diminutive vessels of the brain and / or spine), such as diminutive arteries.

[0009] In some cases, such as when thrombolytic medication is ineffective at removing a clot or when a large clot is involved, a procedure called mechanical thrombectomy is performed. In a thrombectomy a suction catheter, and potentially mechanical devices are inserted through a catheter lumen, configured to break up the clot is guided through the neurovascular system and to the clot to physically remove the clot. However, a thrombectomy is substantially more invasive and can carry more risks than dissolving or otherwise treating a clot via medication. Further, current thrombectomy catheters and mechanical devices are unable to reach some “deep” neurovascular vessels or target / treatment sites, such as due to their required rigidity (e.g., to provide suction) and / or large cross-sectional size and the diminutive size and delicate nature of such neurovascular vessels. Over 25% of all ischemic strokes are due to occlusion of distal arteries in the brain with diameters less than about 2 mm, and currently no mechanical devices exist for safe and targeted treatment.

[0010] It is noted that accessing diminutive vessels of the human neurovascular system may also be desired or necessary for the treatment or diagnosis of other conditions besides clots. For example, it may be desirable or advantageous to obtain blood, tissue or other samples directly from such diminutive vessels for the diagnosis of a particular anomaly, issue, disease, injury or condition. Furthermore, in conditions such as brain hemorrhage from rupture of a blood vessel or aneurysm, there is leakage of blood in the brain and around the blood vessels. One such type of bleeding is commonly referred to as subarachnoid hemorrhage and often involves a phenomenon called vasospasm wherein further constriction of the diminutive arteries occurs. Current treatment of this condition includes injection of liquid medicants using catheters distant from the target site resulting in only fractional amount of medicant reaching the target treatment site. As another example, it may be desirable or advantageous to directly access such diminutive vessels to treat a cancer, tumor other medical anomaly, issue, disease, injury or condition located within the diminutive vessel or near or about the diminutive vessel.

[0011] Accessing such diminutive vessels, for mechanical removal of a clot and / or for directly applying medication thereto for example, is difficult and dangerous as the diminutiveAtty Ref . No.: 6473.001AW0vessels are hard to reach given their location “deep” or distant along the neurovascular system, their diminutive size, and their delicate nature.

[0012] For example, the walls of vessels of the human neurovascular system (e.g., brain blood vessels, such as arteries of the brain and / or spine) are generally thinner than blood vessels of comparable diameter in other vascular systems (i.e., blood vessels of other parts of the human body). Neurovascular blood vessels have three layers like rest of the human vascular system, but the thickness and composition of the layers varies. The inner layer (the Tunica Intima) of neurovascular blood vessels is configured similarly to blood vessels of other parts of the human vascular system, except that they have fewer cells making up the inner layer. The middle layer (the Tunica Media) of neurovascular blood vessels is significantly thinner relative to the vessel size, and comprises lesser elastic fibers, than blood vessels of other parts of the human vascular system. The middle layer (the Tunica Adventitia) of neurovascular blood vessels is very thin and underdeveloped, and lacks an elastic layer, which renders them significantly more vulnerable to tearing or rupture compared to any other vessel of the human vascular system. It is also noted that neurovascular blood vessels are not surrounded by muscle or fat as with blood vessels of other parts of the human vascular system, but rather essentially float in fluid, which deprives them of any support structure making them fragile and high risk for rupture.

[0013] Accordingly, safely and effectively accessing and directly treating the diminutive vessels of the human neurovascular system is a challenge. Conventional approaches to treatment of these neurovascular diminutive vessels has been indirect and non-target to particularly effected portion of a vessel, and have thus proved ineffective to a degree.Current neurovascular treatment devices, systems and method have failed to address all considerations, such as reliable catheter trackability and deliverability to a target / treatment site within the diminutive vessels, proximal support and distal navigation of the catheter to such hard-to-reach diminutive neurovascular vessels, and flexibility in the performance of one of a plural of different treatment options at the diminutive neurovascular vessels.Neurovascular microcatheters that are capable of targeting infusion of medicants / agents to a particular portion of a neurovascular vessel (or a clot or anomaly thereof or proximate thereto) would be advantageous and desirable.

[0014] There thus remain gaps in catheter technology, which would benefit from new inventive approaches, which are effective in safely accessing diminutive vessels of the human neurovascular system, and performing effective treatment by directly delivering treatment toAtty Ref . No.: 6473.001AWOa targeted site at or within the diminutive neurovascular vessels, and which otherwise address the drawbacks of the current state of the art.SUMMARY

[0015] Aspects of the present invention provide endoluminal neurovascular microcatheters, systems and related methods for safely and effectively directly targeting, accessing and treating neurovascular diminutive vessels (or nearby anatomical areas) of a human brain or spine. The endoluminal neurovascular microcatheters may comprise a longitudinally elongated catheter body of at least 135 cm extending from a proximal end portion to a free distal end of a distal end portion configured to directly infuse and / or sample diminutive vessels of a brain or spine of a human patient. The catheter body may be longitudinally variably flexible, and comprise a tubular wall structure that defines a continuous, unobstructed inner lumen that is open at the free distal end. The distal end portion comprises a plurality of micropores, such as between proximal and distal radiopaque markers, that define a minimum cross-sectional dimension less than or equal to 0.01 inch and a cross-sectional area less than or equal to 0.05 mm2. At least the free distal end may define a maximum outer diameter of 1 mm or less, and a maximum inner diameter of the lumen 0.7 mm or less.

[0016] The endoluminal neurovascular microcatheters are particularly configured to safely and effectively directly access and treat neurovascular diminutive vessels (or nearby anatomical areas) of a human brain or spine via traditional access points of the human vascular system. The endoluminal neurovascular microcatheters have sufficient length to reach the neurovascular diminutive vessels which are located far along the human vascular system, and also the sufficient structural integrity in an axial / longitudinal direction for proximal / longitudinal translation, an angular or rotational direction for torsional control, and a lateral directional for bending to navigate the tortuous and branching nature of the vascular and neurovascular vessels and to reduce vessel injury (particularly the neurovascular diminutive vessels). The endoluminal neurovascular microcatheters comprise a tensile and torque strength, kink resistance, and softness that balances pushability / navigability and softness via longitudinally variably stiffness or flexural rigidities (i.e., flexural rigidity graduated zones and transition points) to facilitate the safe and accurate advancement of the microcatheters through and into the neurovascular diminutive vessels. The endoluminal neurovascular microcatheters comprise optimal pushability, stability, and support for reliable endoluminal delivery and use in neurovascular diminutive vessels. The lumen, including theAtty Ref . No.: 6473.001AWOportion extending to and open at the free distal end, is configured to accept a traditional steerable guidewire therethrough to aide in the translation of the microcatheters through the vascular and neurovascular vessels and placement / positioning of at least the distal end portion directly in the neurovascular diminutive vessels.

[0017] The open lumen of the free distal end and the plurality of micropores of the distal end portion of the endoluminal neurovascular microcatheters are configured for optimal direct targeted infusion of neurovascular diminutive vessels with a liquid therapeutic agent or diagnostic material, or for sampling of material by aspiration (e.g., blood or other biological material) from the neurovascular diminutive vessels. Specifically, the plurality of micropores and the open lumen at the free distal end are configured such that a substantially uniform and / or effective infusion of a liquid, such as a liquid therapeutic agent or diagnostic material, is formed or emitted from the infusion portion when a flow of the liquid is formed through the lumen from the proximal portion (e.g., via the hub) under pressure directly targeted in a neurovascular diminutive vessel, such as at / in a clot thereof. For example, the plurality of micropores and the open lumen at the free distal end are configured such that at least about 50 %, and more preferably at least about 70%, of the liquid introduced into the inner lumen is infused from the plurality of micropores, and less than about 50%, and more preferably less than about 30%, of the liquid is infused from the free distal end, via a weeping, leaking or “drip” non-jetting type flow directly in a neurovascular diminutive vessel (that contains a clot, for example). In this way, the distal end portion can be translated through a clot within a neurovascular diminutive vessel, for example, such that some of the plurality of micropores span across the clot with the free distal end positioned past the clot, for direct targeted infusion of the vessel (and potentially a clot) of a medicant or similar liquid therapeutic or diagnostic agent (e.g., a thrombolytic medicant).

[0018] A flow of a clot-dissolving liquid medicant or the like may be forced through the inner lumen via the proximal end portion of the microcatheter body (which can be positioned outside of the body / vascular system), which is predominantly (e.g., at least about 50%, or more preferably at least about 60%, or even more preferably at least about 70%) infused substantially uniformly through the plurality of micropores directly at and next to the clot on each side of the clot, which some additional liquid medicant infused past the clot via the free distal end. This direct, targeted infusion profile advantageously effectively acts on and treats, such as dissolves, a clot as the longitudinal sides of the clot are directly treated and the interior of the clot is directly treated (i.e., in direct contact with liquid medicant and with interaction throughout the length of the clot). Further, the additional liquid medicant infusedAtty Ref . No.: 6473.001AW0from the free distal end can act on the “front” side of a clot, such as being in forced against the “front” side of the clot via blood pressure acting on such side of the clot (depending on the direction of approach of the microcatheter and the direction of blood flow) to more aggressively treat such a front side (which may be a more dense or otherwise difficult portion of the clot to dissolve or treat). It is noted that the plurality of micropores may be configured such that a relatively higher flow rate and / or volume of the liquid medicant is infused from a particular longitudinal portion or grouping of the plurality of micropores (e.g., a medial portion or grouping of the plurality of micropores) to even more target the treatment of the clot. For example, a medial portion of the plurality of micropores may include a greater number of micropores or larger micropores such that the medial portion can be extended through a clot to directly more aggressively treat the interior of the clot along its longitudinal length with more medicant / agent (while the proximal and distal portions of the plurality of micropores directly treat the front and back sides of the clot with relatively less medicant / agent, for example). This would therefore potentially result in improved efficiency, efficacy and safety related to medicant use.

[0019] The open lumen at the distal free end is configured to allow the catheter to be utilized with a traditional steerable catheter guidewire, but yet prevent jetting there from during infusion of a liquid medicant / agent. Specifically, the cross-sectional size or diameter of the lumen is sized (and shaped) to allow a steerable catheter guidewire to freely pass therethrough such that the catheter can be translated freely over the guidewire. For example, the inner lumen of the size catheter defines a diameter equal to or greater than .008 inches, or equal to or greater than about .01 inches, or equal to or greater than about .014 inches, or equal to or greater than about .018 inches, or equal to or greater than about .02 inches.

[0020] Further, the cross-sectional size or diameter (and shape) of the lumen along at least a distal free end portion of the distal end portion of the catheter body extending to and defining the distal free end is sized to prevent a jet or distinct / defined strong stream of the liquid medicant / agent when the flow of the liquid medicant / agent is forced through the lumen from the hub or proximal end portion of the catheter body, but rather from a weeping, dripping or leaking infusion or flow of the liquid medicant / agent. It is noted that the viscosity and / or surface tension characteristics (and / or the flow rate and or pressure) of the particular liquid medicant / agent. Accordingly, the endoluminal neurovascular microcatheters disclosed herein are configured based on the surface tension, viscosity and other relevant intermolecular fluid properties (e.g., intermolecular force-dependent fluid properties) of typical liquid medicants / agents used in neurovascular diminutive vessels, such as but not limited to liquidAtty Ref . No.: 6473.001AWOthrombolytic and antithrombotic medicants or agents. For example, the endoluminal neurovascular microcatheters disclosed herein are configured based on the infusion of liquid medicants / agents with a viscosity less than about 7 cP (centipoise), or less than about 5 cP, or less than about 3 cP, or more specifically less than about 2 cP, or even more specifically about 0.25 cP to about 1.5 cP. As another example, the endoluminal neurovascular microcatheters disclosed herein are configured based on the infusion of liquid medicants / agents with a surface tension within the range of about 30 mN / m (or dynes / cm) to about 100 mN / m, or more preferably within the range of about 40 mN / m to about 90 mN / m, or more preferably within the range of about 50 mN / m to about 80 mN / m, or more preferably within the range of about 70 mN / m to about 80 mN / m.

[0021] For example, in some embodiments, an endoluminal neurovascular microcatheter comprising a hub portion configured to remain outside of the patient, and a catheter body being longitudinally elongated and extending from a proximal end portion coupled to the hub portion to a free distal end at a distal end portion configured to access diminutive vessels of a brain or spine of a human patient is disclosed. The catheter body comprises a tubular wall structure that defines a continuous, unobstructed inner lumen that is open at the free distal end. The catheter body is longitudinally variably flexible such that the proximal end portion of the catheter body comprises a first flexural rigidity, a medial portion of the catheter body extending longitudinally between the proximal and distal end portions comprises a second flexural rigidity that is less than the first flexural rigidity, and the distal end portion of the catheter body comprises a third flexural rigidity that is less than the second flexural rigidity. The distal end portion of the catheter body comprises a proximal radiopaque marker, a distal radiopaque marker, and a plurality of micropores extending through the tubular wall structure from the inner lumen to an exterior of the tubular wall structure configured to infuse the diminutive vessels with a liquid therapeutic agent or diagnostic material. The plurality of micropores are positioned longitudinally between the proximal and distal radiopaque markers, and arranged in a longitudinally spaced successive pattern. Each micropore of the plurality of micropores defines a minimum cross-sectional dimension of less than or equal to 0.01 inch and a cross-sectional area less than or equal to 0.05 mm2. At least a free end portion of the distal end portion of the catheter body longitudinally extending to the free distal end defines a maximum outer diameter of less than or equal to 1 mm, and defines a maximum inner diameter of the lumen thereof of less than or equal to 0.7 mm.

[0022] In some embodiments, the inner lumen comprises a continuous defined inner diameter size from the proximal end portion to the free distal end. In some such embodiments, at leastAtty Ref . No.: 6473.001AWOthe free end portion of the distal end portion of the catheter body comprises a continuous defined exterior cross-sectional size along its longitudinal length. In some such embodiment, the free end portion of the distal end portion comprises a longitudinal length of at least 3 cm. In some other such embodiments, the distal end portion of the catheter body comprises a proximal portion extending longitudinally from the medial portion to the free end portion of the distal end portion, the proximal portion of the distal end portion defines a maximum inner diameter of the lumen thereof of less than or equal to 0.9 mm.

[0023] In some embodiments, the catheter body comprises a tapered maximum exterior cross-sectional diameter that decreases along its longitudinal length from the proximal end portion to the free distal end of the distal end portion. In some such embodiments, the maximum exterior cross-sectional diameter of the catheter body tapers from less than or equal from 1.4 mm at a proximal end of the proximal end portion to less than or equal to 1 mm at the free distal end of the distal end portion.

[0024] In some embodiments, the distal end portion of the catheter body comprises a tapered tip portion that extends from a distal end of an infusion portion of the distal end portion and defines the free distal end, the tapered tip portion comprises a tapered outer cross-sectional diameter such that the outer cross-sectional diameter at the free distal end is less than the outer cross-sectional diameter at the distal end of the infusion portion, and the plurality of micropores are disposed in the infusion portion. In some such embodiments, the outer cross-sectional diameter of the tapered tip portion continuously gradually tapers inwardly from the distal end of the infusion portion to the free distal end. In some other such embodiments, the tapered tip portion comprises a tapered inner diameter of the inner lumen such that the inner diameter at the free distal end is less than the inner diameter of the inner lumen at the distal end of the infusion portion. In some such embodiments, the inner cross-sectional diameter of the inner lumen of the tapered tip portion continuously gradually tapers inwardly from the distal end of the infusion portion to the free distal end. In some other such embodiments, the tapered tip portion comprises a longitudinal length with the range of about 0.5 cm to about 1.5 cm, and the defines a maximum inner diameter of the lumen at the free distal end of less than or equal to 0.6 mm. In some embodiments, the distal radiopaque marker is positioned between a longitudinally distal-most micropore of the plurality of micropores and the tapered tip portion. In some embodiments, the third flexural rigidity is within the range of about 0.4 gram-force per cm2(gf / cm2) to about 2 gf / cm2at the distal free end of the tapered tip portion of the distal end portion.Atty Ref . No.: 6473.001AWO

[0025] In some embodiments, the plurality of micropores define an infusion portion of the distal end portion of the catheter body. In some such embodiments, the infusion portion is longitudinally spaced from the free distal end, and the distal radiopaque marker is positioned at a distal end of the infusion portion. In some such embodiments, the proximal radiopaque marker is positioned at a proximal end of the infusion portion.

[0026] In some embodiments, the infusion portion comprises a longitudinal length of at least 3 cm. In some embodiments, the infusion portion comprises a longitudinal length of at least 5 cm. In some embodiments, the infusion portion comprises a longitudinal length of at least 10 cm. In some embodiments, the infusion portion comprises a longitudinal length within the range of 3 cm to 30 cm.

[0027] In some embodiments, a maximum outer diameter of the catheter body decreases along the longitudinal length such that the outer cross-sectional diameter at the free distal end is less than the outer cross-sectional diameter at the proximal end portion. In some such embodiments, a maximum outer cross-sectional diameter of the proximal end portion of the catheter body is greater than a maximum outer cross-sectional diameter of the medial portion of the catheter body, and a maximum outer cross-sectional diameter of the medial portion of the catheter body is greater than the maximum outer diameter of the distal end portion of the catheter body. In some embodiments, the proximal end portion of the catheter body comprises a first proximal portion that comprises a first maximum outer cross-sectional diameter, and a first distal portion that comprises a second maximum outer cross-sectional diameter that is less than the first maximum outer cross-sectional diameter, the medial portion of the catheter body comprises a second proximal portion that comprises a third maximum outer cross-sectional diameter that is less than the second maximum outer cross-sectional diameter, and a second distal portion that comprises a fourth maximum outer cross-sectional diameter that is less than the third maximum outer cross-sectional diameter, and the maximum outer diameter of the distal end portion of the catheter body is less than the fourth maximum outer cross-sectional diameter. In some such embodiments, the distal end portion comprises a third proximal portion that comprises a fifth maximum outer cross-sectional diameter that is less than the fourth maximum outer cross-sectional diameter, and a second distal portion that defines the free distal end and comprises a sixth maximum outer cross-sectional diameter that is less than the fifth maximum outer cross-sectional diameter.

[0028] In some embodiments, the maximum outer cross-sectional diameter of the catheter body continuously gradually tapers inwardly from a proximal end of the proximal end portionAtty Ref . No.: 6473.001AWOto the free distal end. In some embodiments, the maximum outer cross-sectional diameter of the proximal end portion of the catheter body is less than or equal to 1.5 mm. In some embodiments, the inner lumen comprises a continuous defined inner diameter size from the proximal end portion to the free distal end. In some such embodiments, a radial wall thickness of the catheter body decreases in thickness along the longitudinal length such that the outer cross-sectional diameter at the free distal end is less than the outer cross-sectional diameter at the proximal end portion.

[0029] In some embodiments, the plurality of micropores are positioned longitudinally between the first and second radiopaque markers. In some embodiments, the inner lumen defines a circular cross-sectional shape. In some embodiments, the catheter body defines an outer circular cross-sectional shape.

[0030] In some embodiments, the micropores are longitudinally spaced such that adjacent micropores of the plurality of micropores are longitudinally spaced apart at least 1 mm from each other. In some embodiments, the micropores are longitudinally spaced such that adjacent micropores of the plurality of micropores are longitudinally spaced apart at least 2 mm from each other. In some embodiments, the micropores of the plurality of micropores are evenly longitudinally spaced apart from each other.

[0031] In some embodiments, the micropores of the plurality of micropores are unevenly longitudinally spaced apart from each other such that a first longitudinal group of micropores of the plurality of micropores comprises a first longitudinal spacing, and a second longitudinal group of micropores of the plurality of micropores comprises a second longitudinal spacing that is less than the first longitudinal spacing. In some such embodiments, the second longitudinal group of micropores is longitudinally distal of the first longitudinal group of micropores. In some such embodiments, a third longitudinal group of micropores of the plurality of micropores comprises a third longitudinal spacing that is greater than the second longitudinal spacing, and the third longitudinal group of micropores is longitudinally distal of the second longitudinal group of micropores.

[0032] In some embodiments, the plurality of micropores are arranged in a longitudinally and circumferentially spaced successive pattern. In some such embodiments, adjacent micropores of the plurality of micropores are circumferentially spaced at least 30 degrees measured angularly between radii extending from a longitudinal axis defined by the catheter body. In some such embodiments, the adjacent micropores of the plurality of micropores are longitudinally spaced at least 1 mm from each other.Atty Ref . No.: 6473.001AWO

[0033] In some embodiments, the plurality of micropores are arranged in a spiral pattern about the catheter body. In some embodiments, the plurality of micropores are arranged in successive pairs of micropores that are successively circumferentially spaced at least 30 degrees measured angularly between radii extending from a longitudinal axis defined by the catheter body. In some embodiments, the micropores of the plurality of micropores define substantially the same cross-sectional area.

[0034] In some embodiments, the micropores of the plurality of micropores define differing cross-sectional areas. In some such embodiments, the cross-sectional areas of the plurality of micropores gradually increase in succession longitudinally distally. In some other such embodiments, the cross-sectional areas of the plurality of micropores increase longitudinally distally such that a first longitudinal group of micropores of the plurality of micropores comprises a first cross-sectional size, and a second longitudinal group of micropores of the plurality of micropores comprises a second cross-sectional size that is greater than the first cross-sectional size, the second longitudinal group of micropores being longitudinally distal to the first longitudinal group of micropores. In some such embodiments, a third longitudinal group of micropores of the plurality of micropores comprises a third cross-sectional size that is less than the second cross-sectional size, and the second longitudinal group of micropores is longitudinally distal to the third longitudinal group of micropores. In some embodiments, the cross-sectional areas of the plurality of micropores alternate successively longitudinally between a first second cross-sectional size and a second cross-sectional size that differs from the first cross-sectional size.

[0035] In some embodiments, the plurality of micropores each define a circular cross-sectional shape. In some embodiments, the plurality of micropores each define an oval cross-sectional shape. In some embodiments, the plurality of micropores each define a non-circular shape. In some such embodiments, the plurality of non-circular shaped micropores each define a maximum longitudinal size that is greater than a maximum lateral size.

[0036] In some embodiments, the plurality of micropores and the maximum inner diameter of the lumen of the free distal end are configured relative to each other such that the catheter body infuses at least 70% of the liquid therapeutic agent or diagnostic material introduced into the inner lumen into a diminutive vessel via the plurality of micropores, and less than or equal to 30% of the liquid therapeutic agent or diagnostic material introduced into the inner lumen into the diminutive vessel via the free distal end.Atty Ref . No.: 6473.001AWO

[0037] In some embodiments, the tubular wall structure is formed of at least one polymer layer or portion. In some such embodiments, the at least one polymer layer is formed of polyurethane, nylon, PEB A, a fluoropolymer or a combination thereof. In some other such embodiments, the wall structure further comprises reinforcement material or members coupled with the at least one polymer layer or portion. In some such embodiments, the reinforcement material or members comprise one or more helical wires that extend from the proximal end portion to the distal end portion. In some such embodiments, the one or more helical wires comprise a flat or round wire with a helical coil pitch within the range of about 0.008 inches and about 0.012 inches.

[0038] In some embodiments, the tubular wall structure comprises an inner liner that forms the inner lumen, and at least one outer layer that extends over the inner liner layer. In some such embodiments, the inner liner is formed of a fluoropolymer material. In some other such embodiments, the outer liner comprises an outer jacket layer. In some such embodiments, the outer jacket layer comprises at least one of a polymer material portion and / or at least one layer of helical fibers or strips. In some embodiments, the outer layer comprises a hydrophilic coating.

[0039] In some embodiments, the first flexural rigidity to lateral bending stiffness is within the range of about 30 gram-force per cm2(gf / cm2) to about 46 gf / cm2at a longitudinal midpoint of the proximal end portion. In some embodiments, the second flexural rigidity to lateral bending stiffness is within the range of about of 8 gf / cm2to about 25 gf / cm2at a longitudinal midpoint of the medial portion. In some embodiments, the third flexural rigidity to lateral bending stiffness is within the range of about 3.6 gf / cm2and about 16 gf / cm2at about longitudinal midpoint of the distal end portion. In some embodiments, the third flexural rigidity is within the range of about 2 gf / cm2and about 6.5 gf / cm2at the distal free end of the distal end portion.

[0040] In some embodiments, the inner lumen of the free end portion of the distal end portion of the catheter body defines a maximum inner diameter of less than or equal to 0.6 mm. In some such embodiments, at least a free end portion of the distal end portion of the catheter body defines a maximum outer diameter of less than or equal to 0.9 mm.

[0041] In some embodiments, the catheter body defines a longitudinal length extending from the proximal portion at the hub portion to the free distal end of at least 150 cm.

[0042] In some embodiments, the catheter body defines a longitudinal length extending from the proximal portion at the hub portion to the free distal end of at least 135 cm. In some suchAtty Ref . No.: 6473.001AWOembodiments, the longitudinal length of the catheter body is less than or equal to about 170 cm.

[0043] In another aspect, the present disclosure provides an endoluminal neurovascular microcatheter system comprising any one of the microcatheters as described herein above, and a steerable catheter guidewire defining a maximum outer diameter of less than or equal to 0.6 mm.

[0044] In some embodiments, the guidewire comprises a longitudinal length of at least 180 cm, and at least a distal end portion of the guidewire is curved, or is malleably shapable or plastically deformable into a curved shape.

[0045] In some embodiments, the catheter body defines a longitudinal length extending from the proximal portion at the hub portion to the free distal end of at least 135 cm. In some such embodiments, the longitudinal length of the catheter body is less than or equal to about 170 cm. In some embodiments, the catheter body defines a longitudinal length extending from the proximal portion at the hub portion to the free distal end of at least 150 cm.

[0046] In some embodiments, the at least a free end portion of the distal end portion of the catheter body defines a maximum outer diameter of less than or equal to 0.9 mm, the inner lumen of the free end portion of the distal end portion of the catheter body defines a maximum inner diameter of less than or equal to 0.6 mm, and the guidewire defines a maximum outer diameter of less than or equal to 0.5 mm.

[0047] In another aspect, the present disclosure provides a method of treating a brain or a spine of a human patient via a diminutive vessel thereof, comprising: obtaining any one of the microcatheters as described herein above; inserting a steerable catheter guidewire defining a maximum outer diameter of less than or equal to 0.6 mm into and through the inner lumen of the microcatheter; inserting the guidewire into a first vessel of a vascular system of human patient, and translating the guidewire through the vascular system to a diminutive neurovascular vessel of a brain or spine of the human patient; and translating the microcatheter over the guidewire and through the vascular system such that the distal end portion is positioned within a target site of the diminutive neurovascular vessel.

[0048] In some embodiments, the method further comprises infusing the target site of the diminutive vessel with a volume of a liquid therapeutic agent or diagnostic material via the plurality of micropores and the distal free end. In some such embodiments, at least 70% of the infused liquid therapeutic agent or diagnostic material is introduced into the target site of the diminutive neurovascular vessel via the plurality of micropores, and less than or equal toAtty Ref . No.: 6473.001AW030% of the infused liquid therapeutic agent or diagnostic material is introduced into the target site of the diminutive neurovascular vessel via the free distal end.

[0049] In some embodiments, the method further comprises aspirating the target site of the diminutive neurovascular vessel by allowing biological material from within or proximate to the target site to flow into the inner lumen via at least the plurality of micropores, and longitudinally proximally through the catheter body to the proximal end portion.

[0050] In some embodiments, translating the guidewire through the vascular system comprises performing a series of incremental translations of the guidewire through the vascular system, and translating the microcatheter over the guidewire and through the vascular system comprises performing a series of incremental translations of the microcatheter over the guidewire and through the vascular system, the incremental translations of the guidewire and the incremental translations of the microcatheter being performed in an alternating series.

[0051] In some embodiments, translating the microcatheter over the guidewire and through the vascular system such that the distal end portion is positioned within the target site of the diminutive neurovascular vessel comprises translating the distal end portion through at least 25 cm of the vascular system to reach the neurovascular system of the vascular system. In some embodiments, translating the microcatheter over the guidewire and through the vascular system such that the distal end portion is positioned within the target site of the diminutive neurovascular vessel comprises translating the distal end portion through at least 50 cm of the vascular system to reach the neurovascular system of the vascular system. In some embodiments, translating the microcatheter over the guidewire and through the vascular system such that the distal end portion is positioned within the target site of the diminutive neurovascular vessel comprises translating the distal end portion through at least 25 cm of the vascular system to reach the neurovascular system of the vascular system.

[0052] In some embodiments, the guidewire comprises a longitudinal length of at least 180 cm, and at least a distal end portion of the guidewire is curved, or is malleable or plastically deformable into a curved shape. In some embodiments, at least a free end portion of the distal end portion of the catheter body defines a maximum outer diameter of less than or equal to 0.9 mm, the inner lumen of the free end portion of the distal end portion of the catheter body defines a maximum inner diameter of less than or equal to 0.6 mm, and the guidewire defines a maximum outer diameter of less than or equal to 0.5 mm.Atty Ref . No.: 6473.001AWO

[0053] A further advantageous microcatheter embodiment of the present disclosure is directed to a dual-lumen microcatheter effective for achieving simultaneous or contemporaneous delivery of a stent or other mechanical device / apparatus, and direct targeted infusion of fluid treatment agents, into vessels, such as into diminutive neurovascular vessels of a brain or spine of a human patient.

[0054] In some aspects, the present disclosure provides a dual-lumen endoluminal neurovascular microcatheter, comprising: a hub portion configured to remain outside of the patient, and a catheter body being longitudinally elongated and extending longitudinally from a proximal end portion coupled to the hub portion to a free distal end at a distal end portion configured to access neurovascular vessels of a brain or spine of a human patient. The catheter body comprises: an inner tubular wall structure extending form the hub portion that defines a continuous, unobstructed inner lumen that is open at the free distal end; and an outer tubular wall structure extending from the hub portion that defines a continuous outer lumen that extends about the inner tubular wall structure and is closed at the free distal end. The catheter body is longitudinally variably flexible, and the proximal end portion of the catheter body comprises a first flexural rigidity, a medial portion of the catheter body extending longitudinally between the proximal and distal end portions comprises a second flexural rigidity that is less than the first flexural rigidity, and the distal end portion of the catheter body comprises a third flexural rigidity that is less than the second flexural rigidity. The distal end portion of the catheter body comprises a proximal radiopaque marker, a distal radiopaque marker, and a plurality of micropores extending through the outer tubular wall structure from the outer lumen to an exterior of the catheter body configured to infuse the neurovascular vessels with a liquid therapeutic agent or diagnostic material. The plurality of micropores are arranged in a longitudinally spaced successive pattern longitudinally between the proximal and distal radiopaque markers, and each micropores defines a minimum cross-sectional dimension of less than or equal to 0.01 inch and a cross-sectional area less than or equal to 0.05 mm2.

[0055] In some embodiments, the inner tubular wall structure defines a first radial wall thickness extending from the proximal end portion to the distal end portion, and the outer tubular wall structure defines a second radial wall thickness extending from the proximal end portion to the distal end portion that is less than the first radial wall thickness.

[0056] In some embodiments, the outer tubular wall structure is more flexible than the inner tubular wall structure along a longitudinal length of the catheter body. In some embodiments,Atty Ref . No.: 6473.001AWOthe inner tubular wall structure defines a structural integrity that is greater than a structural integrity of the inner tubular wall structure along a longitudinal length of the catheter body.

[0057] In some embodiments, the inner tubular wall structure is self-supporting such that it naturally maintains the inner lumen in a substantially fully full open arrangement, and wherein the outer tubular wall structure is not self-supporting such that it does not naturally maintain the outer lumen in a substantially fully full open arrangement.

[0058] In some embodiments, the catheter body further comprises a plurality of strut portions extending between and coupling portions of an outer side of the inner tubular wall structure and portions of an inner side of the outer tubular wall structure. In some such embodiments, the plurality of strut portions radially space portions of the outer tubular wall structure and the inner tubular wall structure.

[0059] In some embodiments, the distal end of the outer lumen is closed via an end structure that extends radially between the inner and outer tubular wall structures and seals off a distal portion of the outer lumen. In some such embodiments, the end structure is the distal radiopaque marker. In some other such embodiments, the end structure is a radially extending wall. In yet some other such embodiments, the distal end of the outer lumen is closed via the outer and inner tubular wall structures being sealed to each other. In some embodiments, the distal end of the outer lumen is longitudinally proximal of the free distal end of the catheter body.

[0060] In some such embodiments, the catheter body defines a longitudinal length within the range of about 25 cm to about 140 cm. In some such embodiments, at least a free end portion of the distal end portion of the catheter body longitudinally extending to the free distal end defines a maximum outer diameter of less than or equal to 1.5 mm. In some such embodiments, the proximal end portion of the catheter body defines a maximum outer cross-sectional diameter of less than or equal to 2 mm.

[0061] In some embodiments, the inner lumen defines a maximum inner diameter within the range of about 0.3 mm (or 0.4 mm) to about 0.7 mm. In some embodiments, the outer lumen defines a maximum radial thickness within the range of about 0.1 mm to about 0.4 mm. In some such embodiments, the inner lumen defines a maximum inner diameter of less than or equal to 0.7 mm at least at the free distal end.

[0062] In some embodiments, a portion of the catheter body comprising the proximal radiopaque marker, the distal radiopaque marker, and the plurality of micropores defines an infusion portion of the distal end portion of the catheter body, and wherein the infusionAtty Ref . No.: 6473.001AWOportion comprises a longitudinal length of at least 3 cm. In some such embodiments, the infusion portion comprises a longitudinal length of at least 5 cm. In some such embodiments, the infusion portion comprises a longitudinal length of at least 10 cm. In some embodiments, the infusion portion comprises a longitudinal length within the range of 3 cm to 30 cm.

[0063] In some embodiments, the micropores are longitudinally spaced such that adjacent micropores of the plurality of micropores are longitudinally spaced apart at least 1 mm from each other. In some embodiments, the plurality of micropores are arranged in a longitudinally and circumferentially spaced successive pattern.

[0064] These, and other objects, features and advantages of this invention will become apparent from the following detailed description of the various aspects of the invention taken in conjunction with the accompanying drawings.BRIEF DESCRIPTION OF DRAWINGS

[0065] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate embodiments of the invention and together with the detailed description herein, serve to explain the principles of the invention. The drawings are only for purposes of illustrating preferred embodiments and are not to be construed as limiting the disclosed inventions. It is emphasized that, in accordance with the standard practice in the industry, various features may or may not drawn to scale. The dimensions of features of a drawing may be arbitrarily increased or reduced for clarity of discussion, and therefore the scale of any figure should not limit the scope of the invention. However, many drawings and / or aspects thereof are drawn to scale, and may form part of the inventions. Therefore, the scale of any components or features illustrated in any figure is specifically disclosed, incorporated herein and part of this disclosure.

[0066] The foregoing and other objects, features and advantages of the invention are apparent from the following detailed description taken in conjunction with the accompanying drawings in which:

[0067] FIG. 1 is a side perspective view of an exemplary embodiment of an endoluminal neurovascular microcatheter configured for targeted infusion of diminutive vessels of a brain or spine of a human patient, in accordance with an aspect of the present invention;

[0068] FIG. 2 is a proximal perspective view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;Atty Ref . No.: 6473.001AWO

[0069] FIG. 3 is another proximal perspective view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0070] FIG. 4 is another proximal perspective view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0071] FIG. 5 is a distal perspective view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0072] FIG. 6 is a distal perspective view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0073] FIG. 7 is a distal perspective view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0074] FIG. 8 is a distal perspective view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0075] FIG. 9 is a first or left lateral side view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0076] FIG. 10 is a second or right lateral side view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0077] FIG. 11 is a top or bottom plan cross-sectional view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0078] FIG. 12 is a proximal end view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0079] FIG. 13 is a distal end view of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0080] FIG. 14 is a side cross-sectional view of a distal end portion of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0081] FIG. 15 is a distal perspective view of the distal end portion of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0082] FIG. 16 is a side cross-sectional view of a distal free end portion of the distal end portion of the exemplary endoluminal neurovascular microcatheter of FIG. 1;

[0083] FIG. 17 is a side cross-sectional view of a proximal portion of the distal end portion of the exemplary endoluminal neurovascular microcatheter of FIG. 1;Atty Ref . No.: 6473.001AWO

[0084] FIG. 18 is a distal perspective view of tapered tip distal end portion of another exemplary embodiment of an endoluminal neurovascular microcatheter configured for targeted infusion of diminutive vessels of a brain or spine of a human patient, in accordance with an aspect of the present invention;

[0085] FIG. 19 is a proximal perspective view of the exemplary endoluminal neurovascular microcatheter of FIG. 18;

[0086] FIG. 20 is a side view of the exemplary endoluminal neurovascular microcatheter of FIG. 18;

[0087] FIG. 21 is a side cross-sectional view of the exemplary endoluminal neurovascular microcatheter of FIG. 18;

[0088] FIG. 22 is a side perspective view of another exemplary embodiment of an endoluminal neurovascular microcatheter configured for targeted infusion of diminutive vessels of a brain or spine of a human patient, in accordance with an aspect of the present invention;

[0089] FIG. 23 is a distal perspective view of the exemplary endoluminal neurovascular microcatheter of FIG. 22;

[0090] FIG. 24 is a side view of a distal end portion of the exemplary endoluminal neurovascular microcatheter of FIG. 22;

[0091] FIG. 25 is a side cross-sectional view of a distal end portion of the exemplary endoluminal neurovascular microcatheter of FIG. 22;

[0092] FIG. 26 is a side perspective view of another exemplary embodiment of an endoluminal neurovascular microcatheter configured for targeted infusion of diminutive vessels of a brain or spine of a human patient, in accordance with an aspect of the present invention;

[0093] FIG. 27 is a side perspective view of another exemplary embodiment of an endoluminal neurovascular microcatheter configured for targeted infusion of diminutive vessels of a brain or spine of a human patient, in accordance with an aspect of the present invention;

[0094] FIG. 28 is a side cross-sectional view of a distal end portion of another exemplary embodiment of a dual-lumen endoluminal neurovascular microcatheter configured forAtty Ref . No.: 6473.001AW0targeted infusion of diminutive vessels of a brain or spine of a human patient, in accordance with an aspect of the present invention; and

[0095] FIG. 29 is a distal or proximal cross-sectional view of a distal end portion of the exemplary endoluminal neurovascular microcatheter of FIG. 22.DETAILED DESCRIPTION

[0096] In this detailed description and the following claims, the terms “distal” and “proximal” are also be used herein to describe a positional relationship of features. For example, “proximal” and “distal” can be utilized to describe a physical spacing or distance between features (e.g., “proximal” and “distal” features). As another example, “proximal” and variations thereof (e.g., proximate) can mean close or closer to a referenced feature, end or a user, and the “distal” and variations thereof can mean far or further away from a referenced feature, end or a user. The term “medial” is also used herein to refer a feature or portion being situated in about the middle or toward the middle of a respective component, portion, aspect, device, member, side, end, feature or any other referenced structure between respective “proximate” or “proximal” and “distal” component, portion, aspect, device, member, side, end, feature or any other referenced structure.

[0097] Similarly, positions or directions may be used herein with reference to anatomical structures or surfaces. For example, as the current endoluminal microcatheters and related systems and methods are described herein with reference to use with blood vessels (e.g., arteries and veins), such as neurovascular vessels, of a human. However, the endoluminal microcatheters and related systems and methods may equally or similarly be employed with other vessels or vessel-like passageways of the human body, or with vessels or other passageways of non-human mammals or animals, for example.

[0098] The terms “substantially”, “approximately”, “about”, “relatively” or other such similar terms that may be used throughout this disclosure, including the claims, are used to describe and account for small fluctuations, such as due to variations in processing. For example, they can refer to less than or equal to ± 10%, such as less than or equal to ± 5%, such as less than or equal to ± 2%, such as less than or equal to ± 1%, such as less than or equal to ± 0.5%, such as less than or equal to ± 0.2%, such as less than or equal to ± 0.1%, such as less than or equal to ± 0.05%.

[0099] Generally stated, disclosed herein are endoluminal neurovascular microcatheters, systems and related methods for safely and effectively directly targeting, accessing and treating diminutive vessels (or nearby anatomical areas), and specifically diminutiveAtty Ref . No.: 6473.001AWOneurovascular vessels of a human brain or spine. The endoluminal neurovascular microcatheters comprise a longitudinally elongated catheter body extending from a proximal end portion to a free distal end of a distal end portion configured to directly infuse and sample diminutive vessels of a brain or spine of a human patient (i.e., targeted infusion to a particular area of interest within a diminutive vessels, such as but not limited to a clot). The catheter body is longitudinally variably flexible / stiff, and is formed by a tubular wall structure that defines a continuous, unobstructed inner lumen that is open at the free distal end which defines a maximum outer diameter of 1 mm or less. The distal end portion also comprises a plurality of micropores between proximal and distal radiopaque markers for radioscopically locating the location of the plurality of micropores (i.e., under fluoroscopy). The micropores and the lumen are configured to provide a substantially targeted infusion in / at the particular area of interest in a diminutive vessel (e.g., neurovascular diminutive vessel). The micropores may thereby define a cross-sectional area less than or equal to 0.05 mm2, and the lumen at at least the distal free end may define maximum inner diameter of 0.7 mm or less. The micropores and the lumen are also configured to be compatible with catheter guidewires, so as to prevent protrusion / translation of the guidewire therethrough during use of the catheter and guidewire in a vascular system. The micropores may thereby define minimum cross-sectional dimension less than or equal to 0.01 inch.

[0100] The endoluminal neurovascular microcatheters are particularly configured to safely and effectively directly access and treat neurovascular diminutive vessels (or nearby anatomical areas) of a human brain or spine via traditional access points of the human vascular system. Traditional access points for endoluminal devices and procedure include the common femoral artery and the radial artery in the wrist, but also the brachial artery in the upper arm, the subclavian artery under the clavicle, and the carotid artery in the neck. The endoluminal neurovascular microcatheters have sufficient length to reach the neurovascular diminutive vessels which are located far along the human neurovascular system (from traditional endoluminal entry points), such as being at least 135 long in some embodiments. Also, the microcatheters have sufficient structural integrity in an axial / longitudinal direction for proximal / longitudinal translation, an angular or rotational direction for torsional control, and a lateral directional for bending to navigate the tortuous and branching nature of the vascular and neurovascular vessels and to reduce vessel injury (particularly the neurovascular diminutive vessels). The endoluminal neurovascular microcatheters comprise a tensile and torque strength, kink resistance, and softness that balances pushability / navigability and softness via longitudinally variably flexural rigidities (i.e., flexural rigidity or stiffnessAtty Ref . No.: 6473.001AWOgraduated zones and transition points) to facilitate the safe and accurate advancement of the microcatheters through and into the neurovascular diminutive vessels. The endoluminal neurovascular microcatheters comprise a pushability, stability, and support for reliable endoluminal delivery and use in diminutive (neurovascular) vessels. As noted above, lumen, including the portion extending to and open at the free distal end, is configured to accept a traditional guidewire therethrough to aide in the translation of the microcatheters through the vascular and neurovascular vessels and placement / positioning of at least the distal end portion directly in the neurovascular diminutive vessels.

[0101] The open lumen of the free distal end and the plurality of micropores of the distal end portion of the endoluminal neurovascular microcatheters are configured for optimal direct targeted infusion of neurovascular diminutive vessels with a liquid therapeutic agent or diagnostic material, or for sampling of material (e.g., blood or other biological material) from the neurovascular diminutive vessels. Specifically, the plurality of micropores and the open lumen at the free distal end are configured such that a substantially uniform and / or effective direct / targeted infusion of a liquid, such as a liquid therapeutic agent or diagnostic material, is formed or emitted from the infusion portion when a flow of the liquid is formed through the lumen from the proximal portion (e.g., via the hub) under pressure directly - thereby directly targeted to a particular portion of a vessel portion or anatomical area of interest, such as at / in a clot within a portion of a neurovascular vessel. For example, the plurality of micropores and the open lumen at the free distal end are configured such that about 70% of the liquid introduced into the inner lumen is infused from the plurality of micropores, and about 30% (or less) of the liquid is infused from the free distal end, via a weeping, leaking or “drip” nonjetted type “slow” flow directly in a neurovascular diminutive vessel (that contains a clot, for example). In this way, the distal end portion can be translated through a clot within a diminutive vessel, for example a neurovascular diminutive vessel, such that some of the plurality of micropores span longitudinally within / across the clot with the free distal end positioned past the clot, for direct directed infusion of the vessel and clot of a thrombolytic medicant or other liquid therapeutic or diagnostic agent. It is noted that conditions other than a clot may be similarly directly infused or targeted with a liquid therapeutic or diagnostic agent, whether such condition is within the area of interest or target site within the vessel or adjacent or proximate to the vessel.

[0102] A flow of a clot-dissolving liquid medicant or other liquid therapeutic or diagnostic agent may be forced through the inner lumen via the proximal end portion of the microcatheter body (which can be positioned outside of the body / vascular system), which (e.g., at least aboutAtty Ref . No.: 6473.001AW070%) is predominantly infused substantially uniformly through the plurality of micropores directly at and next to the area of interest (e.g., a clot) on each side of the area of interest, with some additional liquid medicant infused past the area of interest via the free distal end. This direct, targeted infusion profile advantageously effectively acts on and treats the area of interest, such as acts to dissolve a clot, as the longitudinal sides of the area of interest are directly treated and the interior of the area of interest is directly treated. Further, the additional liquid medicant infused from the free distal end can act on the “front” side of the area of interest / clot, such as being in forced against the “front” side of the area of interest / clot via blood pressure acting on such side of the area of interest / clot (depending on the direction of approach of the microcatheter and the direction of blood flow) to more aggressively treat such a front side (which may be a more dense or otherwise difficult portion of the clot to dissolve or treat). It is noted that the plurality of micropores may be configured such that a relatively higher flow rate and / or volume of the liquid medicant is infused from a particular longitudinal portion or grouping of the plurality of micropores (e.g., a medial portion or grouping of the plurality of micropores) to even more target the treatment of the area of interest / clot. For example, a medial portion of the plurality of micropores may include a greater number of micropores or larger micropores such that the medial portion can be extended through an area of interest / clot to directly more aggressively treat the interior of the area of interest / clot along its longitudinal length with more medicant / agent (while the proximal and distal portions of the plurality of micropores directly treat the front and back sides of the clot with relatively less medicant / agent, for example).

[0103] The open lumen at the distal free end of the catheter is configured to allow the catheter to be utilized with a traditional steerable catheter guidewire, but yet prevent jetting therefrom during infusion of a liquid medicant / agent. Specifically, the cross-sectional size or diameter of the lumen is sized (and shaped) to allow a steerable catheter guidewire to freely pass therethrough such that the catheter can be translated freely over the guidewire. For example, the inner lumen is sized for use with commercially available catheters that define a diameter equal to or greater than .008 inches, or equal to or greater than about .01 inches, or equal to or greater than about .014 inches, or equal to or greater than about .018 inches, or equal to or greater than about .02 inches. Further, the cross-sectional size or diameter (and shape) of the lumen along at least a distal free end portion of the distal end portion of the catheter body extending to and defining the distal free end is sized to prevent a jet or distinct / defined strong stream of the liquid medicant / agent when the flow of the liquid medicant / agent is forcedAtty Ref . No.: 6473.001AWOthrough the lumen from the hub or proximal end portion of the catheter body, but rather from a weeping, dripping or leaking infusion or flow of the liquid medicant / agent as discussed above.

[0104] It is noted that the viscosity and / or surface tension characteristics (and / or the flow rate and or pressure) of the particular liquid medicant / agent. Accordingly, the endoluminal neurovascular microcatheters disclosed herein are configured based on the surface tension, viscosity and other relevant intermolecular fluid properties (e.g., intermolecular forcedependent fluid properties) of typical liquid medicants / agents used in neurovascular diminutive vessels, such as but not limited to liquid thrombolytic and antithrombotic medicants or agents. For example, the endoluminal neurovascular microcatheters disclosed herein are configured based on the infusion of liquid medicants / agents with a viscosity less than about 3 centipoise (cP), or more specifically less than about 2 cP, or even more specifically about 0.25 cP to about 1.5 cP. As another example, the endoluminal neurovascular microcatheters disclosed herein are configured based on the infusion of liquid medicants / agents with a surface tension within the range of about 30 mN / m (or dynes / cm) to about 100 mN / m, or more preferably within the range of about 40 mN / m to about 90 mN / m, or more preferably within the range of about 50 mN / m to about 80 mN / m, or more preferably within the range of about 70 mN / m to about 80 mN / m.

[0105] In some embodiments, the endoluminal neurovascular microcatheters may be a singlelumen catheter with the micropores arranged / spaced longitudinally between radiopaque markers, material or members. The micropores may be arranged in a repeating pattern, such as a pattern of four micropores spaced 90 degrees circumferential apart, and spaced a selected longitudinally distance apart in a lumen length direction for achieving or maintaining desirable structural characteristics and infusion profile. As another example, the micropores may be arranged in a general circumferentially spiral or serpentine pattern, a pitch of which is advantageously selected to maintain desired lumen performance characteristics and infusion profile. As yet another example, the micropores may be arranged in alternating micropore pairs, subsequent pairs being shifted circumferentially by 90 degrees from an adjacent pair along a lumen length.

[0106] In some embodiments, the free digital tip portion of the distal end portion of the catheter may be substantially cylindrical, such as defining a substantially constant maximum cross-sectional outer dimension or diameter and / or a substantially constant minimum cross-sectional inner dimension or diameter of the lumen thereof (i.e., a straight tipped catheter). In other embodiments, the free distal tip portion of the distal end portion of the catheter may beAtty Ref . No.: 6473.001AWOsubstantially tapered, such as defining a maximum cross-sectional outer dimension or diameter that tapers or narrows inwardly such that it becomes smaller as it extends toward the free distal end and / or a minimum cross-sectional inner dimension or diameter of the lumen thereof that tapers or narrows inwardly such that it becomes smaller as it extends toward the free distal end (i.e., a tapered tipped catheter).

[0107] In some embodiments, the proximal and distal radiopaque markers are provided adjacent to the proximal -most micropore and the distal -most micropore, respectively, so that the locations or longitudinal span of the micropores can be visualized via fluoroscopy for the targeted, direct infusion of liquid medicants / agents within / to a particular area of interest of / within a diminutive vessel (such as a neurovascular diminutive vessel) (or the or the aspiration or withdrawal of blood or other biological material from a targeted location / area of interest).

[0108] Referring now to FIGS. 1-17, an endoluminal intravascular catheter 100 according to the present disclosure is shown. The endoluminal intravascular microcatheter 100 is particularly configured as an endoluminal neurovascular microcatheter, although as one of ordinary skill in the art would appreciate the microcatheter 100 may be utilized and particularly effective in other vessels, pathways and other relatively narrow openings, cavities or areas.

[0109] As shown in FIGS. 1-17 the microcatheter 100 comprises a hub portion 104 configured to remain outside of a vessel (and patient), and a longitudinally elongate catheter body or body portion 102. With continued reference to FIGS. 1-17, the catheter body 102 extends longitudinally along its axis from a proximal end portion 112 coupled to the hub portion 104 to a free distal end 118 of a distal end portion 116. A medial portion 114 extends longitudinally between the proximal end portion 112 and the distal end portion 116. The distal end portion 116 is configured to access diminutive vessels, such as diminutive neurovascular of a brain or spine of a human patient. As discussed further below, the catheter body 102 comprises a tubular wall structure 106 that defines a continuous, unobstructed inner lumen 120 that is open at the free distal end 118. The distal end portion 116 of the catheter body 102 also comprises a proximal radiopaque marker 130, a distal radiopaque marker 132, and a plurality of micropores 122 extending through the tubular wall structure 106 from the inner lumen 120 to an exterior of the tubular wall structure 106 configured to infuse a diminutive vessel with a liquid therapeutic agent or diagnostic material (and / or aspirate the vessel, if desired).Atty Ref . No.: 6473.001AW0

[0110] As shown in FIGS.2-4, 11 and 12 the hub portion 104 includes an inner pathway or port 105 that is in fluid communication with the inner lumen 120 of the proximal end of the proximal end portion 112 of the catheter body 102. The inner pathway or port 105 of the hub portion 104 is configured to couple with infusion equipment, syringes, intravenous lines, stopcocks, caps or other fluid supply mechanism or devices to supply the fluid flow into and through the inner lumen 122, such as under pressure. The liquid may be a pure liquid, a liquid-solid suspension, gelatinous texture or the like that flows like a pure liquid. As noted above, the liquid may be a liquid medicant or other liquid therapeutic or diagnostic agent, such as but not limited to a liquid thrombolytic or an antithrombotic medicant or agent. As another example, the liquid may be a therapeutic or diagnostic liquid configured to pass through a vessel wall to an anatomical area of interest positioned exterior to a vessel. The pathway or port 105 may thus be configured to couple with infusion equipment to administer a fluid or medication into the inner lumen 122, and ultimately infuse the fluid or medication into a vessel (for treatment or diagnostic within or exterior to the vessel) via the distal end portion 114 of the microcatheter 100, as explained above and further below.[OHl] As also shown in FIGS. 1-13, the hub portion 104 may include a housing or mounting portion 107 configured to engagement of the hub portion 104, such as manual engagement by a user during use. For example, the housing or mounting portion 107 may provide surfaces, area or structure (e.g., wings) configured to be engaged by a user to translate the catheter body 102 longitudinally (distally and proximally) and / or rotate / torque the catheter 100 (and thus the catheter body 102) about the longitudinal axis to, ultimately, advance the catheter body 102 through a vascular system until the distal end portion 116 is positioned within an area of interest or treatment / target portion / zone within a diminutive vessel (e.g., extends through a clot within a diminutive neurovascular vessel). The housing or mounting portion 107 of the hub portion 104 may also provide surface area for the taping or other affixing of the hub portion 104 to a patient to prevent the microcatheter 100 from translating or becoming dislodged during use.

[0112] The catheter body 102 is substantially flexible and configured to laterally bend, flex and twist so as to extend intravascularly. Accordingly, although depicted as being straight or linear in the FIGS. 1-17, due to the flexural rigidity / flexibility of the catheter body 102, the axis of the catheter body 102 will be naturally or neutrally non-linear before use, and nonlinear during use as it extends circuitously intravascularly. Specifically, the flexibility / structural rigidity or integrity (flexural rigidity or flexibility) of the catheter body 102 is configured to provide enough stiffness or rigidity so as to be advanced / translatedAtty Ref . No.: 6473.001AW0through a vascular system longitudinally in a proximal-to-distal direction via force applied longitudinally / axially and / or torsionally / angularly (e.g., pushability) via the hub portion 104 or portions of the catheter body 102 extending outside of the body / vascular system.However, the flexural rigidity / flexibility of the catheter body 102 is also configured to provide substantial flexibility / bendability, softness and elasticity, without kinking, so as to curve and bend through the non-linear, tortious pathways and junctions / branching of vessels without piercing, breaking, ripping or otherwise damaging such vessels, such as neurovascular vessels which are particularly tortious and delicate.

[0113] The endoluminal intravascular microcatheters 100, and in particular the catheter body portion 102 thereof, have sufficient longitudinal length to reach diminutive vessels which are located far along the human vascular system from traditional endoluminal entry points, such as reaching diminutive neurovascular vessels via traditional endoluminal entry points. As shown in FIG. 9 in some such embodiments, the catheter body portion 102 defines a total / maximum longitudinal or axial total length LI from the hub portion 104 to the free distal end 118 of at least about 25 cm, or at least about 50cm, or at least about 75 cm, or at least about 100 cm, or at least about 125 cm, or at least about 135 cm, or at least about 150 cm, and less than about 170 cm. In some preferred embodiments, the catheter body portion 102 defines a total / maximum longitudinal or axial length LI of at least 135 cm. In some such embodiments, the total longitudinal / axial length LI of the catheter body portion 102 is within the range of 25 cm to about 170 cm, or about 75 cm to about 170 cm, or about 135 cm to about 170 cm.

[0114] The catheter body 102 is configured to balance such flexural rigidity requirements to safely reach and treat diminutive vessels located far (intravascularly) from traditional endoluminal entry points by being longitudinally variably flexible such that the proximal end portion 112 comprises a first flexural rigidity, the medial portion 114 comprises a second flexural rigidity that is less than the first flexural rigidity, and the distal end portion 116 comprises a third flexural rigidity that is less than the second flexural rigidity. In some such embodiments, the flexural rigidity / flexibility may be variable along the substantial entirety of the longitudinal length of the catheter body 102, such as gradually reducing or tapering over the longitudinal length of the catheter body 102 from the proximal end portion 112 at the hub portion 102 to the free distal end 118 (such as via gradual thinning of the wall thickness tubular wall structure 106). In some other embodiments, the flexural rigidity / flexibility may be variable along portions of the longitudinal length of the catheter body 102, such as gradually reducing or tapering over portions of longitudinal length of the catheter body 102Atty Ref . No.: 6473.001AWO(e.g., one or more portions of the proximal end portion 112, the medial portion 114 and / or the distal end portion 116). In some other embodiments, the flexural rigidity / flexibility may stepwise reduce or taper over the longitudinal length of the catheter body 102 from the proximal end portion 112 at the hub portion 102 to the free distal end 118, such as the proximal end portion 112 having one or more defined flexural rigidity for a longitudinal portion thereof, the medial portion 114 having one or more defined flexural rigidity for a longitudinal portion thereof and / or the distal end portion 116 having one or more defined flexural rigidity for a longitudinal portion thereof (such as via a stepwise thinning of the wall thickness tubular wall structure 106).

[0115] In some embodiments, the proximal portion 112 may comprise a flexural rigidity within the range of about 5e-06 Nm2to about 9e-06 Nm2, or within the range of about 6e-06 Nm2to about 8e-06 Nm2, the medial portion may comprise a flexural rigidity within the range of about 3e-06 Nm2to about 5e-06 Nm2, or within the range of about 3.5e-06 Nm2to about 4.5e-06 Nm2, and the distal portion may comprise a flexural rigidity within the range of about le-06 Nm2to about 3e-06 Nm2, or within the range of about 1.5e-06 Nm2to about 2.5e-06 Nm2. For example, in an exemplary embodiment, the proximal portion 112 (such as a longitudinal midpoint thereof) may comprise a flexural rigidity of less than or equal to about 7e-06 Nm2, the medial portion (such as a longitudinal midpoint thereof) may comprise a flexural rigidity of less than or equal to about 4e-06 Nm2, and the distal portion (such as a longitudinal midpoint thereof) may comprise a flexural rigidity of less than or equal to about 2e-06 Nm2. In some embodiments, the proximal portion 112 (such as a longitudinal midpoint thereof) may comprise a flexural rigidity of less than or equal to about 9e-06 Nm2, or less than or equal to about 8e-06 Nm2, or less than or equal to about 7e-06 Nm2. In some embodiments, the medial portion (such as a longitudinal midpoint thereof) may comprise a flexural rigidity of less than or equal to about 6e-06 Nm2, or less than or equal to about 5e-06 Nm2, or less than or equal to about 4e-06 Nm2. In some embodiments, the distal portion (such as a longitudinal midpoint thereof) may comprise a flexural rigidity of less than or equal to about 4e-06 Nm2, or less than or equal to about 3e-06 Nm2, or less than or equal to about 2e-06 Nm2.

[0116] In some embodiments, the first flexural rigidity or stiffness, as measured using a 3-point (lateral) bend stiffness test (measures flexibility, bending stiffness, and resistance to kinking by applying a perpendicular force to a supported sample (ASTM F2606 or ASTM D790-17)), of the proximal portion 112 at the longitudinal midpoint (and potentially along the entire longitudinal length) thereof comprises a bending stiffness within the range of aboutAtty Ref . No.: 6473.001AW030 gram-force. cm2(gf / cm2) to about 46 gf / cm2In some embodiments, the second flexural rigidity as measured using the 3 -point bend stiffness test at the longitudinal midpoint (and potentially along the entire longitudinal length) of the medial portion 114 comprises a bending stiffness within the range of about 8 gf / cm2to about 25 gf / cm2. In some embodiments, the third flexural rigidity as measured using a 3 -point bend stiffness test at the longitudinal midpoint (and potentially along the entire longitudinal length) of the distal portion 116 comprises a bending stiffness within the range of about 3.6 gf / cm2to about 16 gf / cm2. In some embodiments, the third flexural rigidity as measured using a 3-point bend stiffness test at the longitudinal midpoint of the distal portion 116 comprises a bending stiffness within the range of about 2 gf / cm2to about 6.5 gf / cm2. In some embodiments, the bending stiffness at the free distal end 118, as measured using the distal tip-flex test, comprises a bending stiffness within the range of about 0.4 gf / cm2to about 2 gf / cm2.

[0117] The minimum inner cross-sectional diameter / dimension of the inner lumen 120 has been discovered to be critical for both infusion of a liquid from the infusion portion 134 and the free distal end 118 during use (as opposed to a jetting or distinct stream emanating from the open lumen 120 at the free distal end as opposed to an infusion from the plurality of micropores 122 during use with a liquid (such as a liquid therapeutic agent or diagnostic material)), and to allow the microcatheter 100 to be utilized with a guidewire for the positioning of the microcatheter 100 intravascularly. As shown in FIGS. 16 and 17, the inner minimum cross-sectional diameter or dimension ID1 of the inner lumen 120 of the catheter body 102 may be a constant or continuous defined inner diameter / dimension from the proximal end portion 112 at the hub portion 104 to the free distal end 118 (i.e., the same or consistent inner cross-sectional diameter / dimension along the entirety of the longitudinal length of the inner lumen 120). In some such embodiments, to prevent jetting, the cross-sectional diameter or dimension ID1 of the inner lumen 120 of the catheter body 102 may be less than or equal to 0.7 mm, and in some relatively smaller embodiments the cross-sectional diameter / dimension of the inner lumen 120 may be less than or equal to 0.65 mm, and in some relatively smaller embodiments the cross-sectional diameter / dimension of the inner lumen 120 may be less than or equal to 0.6 mm. But to accept a traditional (steerable) catheter guidewire therethrough and allow the catheter body 106 to longitudinally slide over the guidewire, the cross-sectional diameter or dimension ID1 of the inner lumen 120 of the catheter body 102 may be equal to or greater than .008 inches, or equal to or greater than about .01 inches, or equal to or greater than about .014 inches, or equal to or greater thanAtty Ref . No.: 6473.001AW0about .018 inches, or equal to or greater than about .02 inches to accommodate such sized traditional (steerable) catheter guidewire.

[0118] The inner lumen 120 may define a circular cross-sectional shape (taken normal to the axis of the catheter body 102) along its longitudinal length, as illustrated. However, the inner lumen 120 may define other cross-sectional shapes in any portion(s) of the catheter body 102. Likewise, the catheter body 102 may define an outer / exterior circular cross-sectional shape (taken normal to the axis of the catheter body 102) along its longitudinal length, as illustrated. However, the catheter body 102 may define other outer / exterior cross-sectional shapes in any portion(s) of the catheter body 102.

[0119] As shown in FIGS 1-11 and 13-17, the maximum outer / exterior cross-sectional dimension or diameter of the catheter body 102 may be variable along the substantial entirety of the longitudinal length of the catheter body 102, such as gradually reducing or tapering over the longitudinal length of the catheter body 102 from the proximal end portion 112 at the hub portion 102 to the free distal end 118 (such as via gradual thinning / taper of the wall thickness tubular wall structure 106). In some other embodiments, the maximum outer / exterior cross-sectional dimension / diameter may be variable along portions of the longitudinal length of the catheter body 102, such as gradually reducing or tapering over portions of longitudinal length of the catheter body 102 (e.g., one or more portions of the proximal end portion 112, the medial portion 114 and / or the distal end portion 116). In some other embodiments, the maximum outer / exterior cross-sectional dimension / diameter may stepwise reduce or taper over the longitudinal length of the catheter body 102 from the proximal end portion 112 at the hub portion 102 to the free distal end 118, such as the proximal end portion 112 having one or more defined maximum outer / exterior cross-sectional dimension / diameter for a longitudinal portion thereof, the medial portion 114 having one or more defined maximum outer / exterior cross-sectional dimension / diameter for a longitudinal portion thereof and / or the distal end portion 116 having one or more defined maximum outer / exterior cross-sectional dimension / diameter for a longitudinal portion thereof (such as via a stepwise thinning / taper of the wall thickness tubular wall structure 106).

[0120] The maximum outer dimension / diameter of the catheter body 102 thereby decreases along the longitudinal length of the catheter body 102 such that the outer cross-sectional diameter at the free distal end 118 is less than the outer cross-sectional diameter at the proximal end portion 112, as shown. Accordingly, as shown in FIG. 10, the proximal end portion 112 of the catheter body 102 may define a second maximum outer cross-sectionalAtty Ref . No.: 6473.001AW0diameter 0D2 that is greater than a third maximum outer cross-sectional diameter OD3 defined by the medial portion 114 of the catheter body 102, and the third maximum outer cross-sectional diameter OD3 of the medial portion 114 of the catheter body 102 may be greater than a first maximum outer cross-sectional diameter OD1 defined by the distal end portion 116 of the catheter body 102. In some such embodiments, the proximal end portion 112 of the catheter body 102 may comprise a first proximal portion that defines the second maximum outer cross-sectional diameter OD2, and a first distal portion that defines a fourth maximum outer cross-sectional diameter OD4 that is less than the second maximum outer cross-sectional diameter OD2, and / or the medial portion 114 of the catheter body 102 comprises a second proximal portion that defines the third maximum outer cross-sectional diameter OD3 that is less than the fourth maximum outer cross-sectional diameter OD4, and a second distal portion that defines a fifth maximum outer cross-sectional diameter OD5 that is less than the third maximum outer cross-sectional diameter OD3, and with the first maximum outer cross-sectional diameter OD1 defined by the distal end portion 116 of the catheter body 102 being less than the fifth maximum outer cross-sectional diameter OD5. As also shown in FIG. 10, in some such embodiments, the distal end portion may comprise a third proximal portion that defines a sixth maximum outer cross-sectional diameter OD6 that is less than the fifth maximum outer cross-sectional diameter OD5, a medial portion that that defines a seventh maximum outer cross-sectional diameter OD7 that is less than the sixth maximum outer cross-sectional diameter OD6, and the free distal end portion extending from the medial portion to the free distal end 118 that defines the first maximum outer cross-sectional diameter OD1 at the distal free end 118 that is less than the seventh maximum outer cross-sectional diameter OD7. As noted above, the longitudinal taper of the maximum outer cross-sectional diameter / dimension may be formed via a decrease in wall thickness of the tubular wall structure 106 along the longitudinal length such that the inner lumen 120 cross-sectional dimension / diameter remains constant.

[0121] In some embodiments, a maximum outer cross-sectional diameter / dimension of the proximal end portion 112 of the catheter body 102 is less than or equal to 1.5 mm, or less than or equal to 1.4 mm, at the hub portion 102 or proximal end of the proximal end portion 112. In some embodiments, a maximum outer cross-sectional diameter of the distal end portion 116 of the catheter body 102 is less than or equal to 1 mm, or less than or equal to 0.9 mm, at the distal free end 118. In some embodiments, a proximal end of the distal end portion 116 may positioned at the proximal-most micropore 122, as described further below, and an outer cross-sectional dimension / diameter of less than or equal to 0.9 mm.Atty Ref . No.: 6473.001AWO

[0122] In some alternative embodiments (not shown), at least the free end portion of the distal end portion 116 of the catheter body 102 (longitudinally extending from the distal radiopaque marker 132 or the distal most micropore to the free distal end 118) comprises a continuous defined outer / exterior (maximum) cross-sectional dimension / diameter along its longitudinal length that does not vary or taper. In some such embodiments, the free end portion of the distal end portion 116 may comprise a longitudinal length of at least 3 cm.

[0123] As described above, the plurality of micropores 122 extending through the tubular wall structure 106 from the inner lumen 120 to an exterior of the tubular wall structure 106 are configured to infuse a vessel (or clot or other construct therein or proximate thereto) with a liquid therapeutic agent or diagnostic material. Accordingly, the distal portion 116 of the microcatheter 100 includes an infusion portion 134 that comprises the proximal and distal radiopaque markers 130, 132 and the plurality of micropores 122, as shown in FIGS. 11 and 14-17. The proximal and distal radiopaque markers 130, 132 may define the proximal and distal longitudinal extent or boundaries of the infusion portion 134. As shown, the infusion portion is longitudinally spaced from the free distal end 118 as the distal radiopaque marker 132 is longitudinally proximally spaced from the free distal end 118.

[0124] The infusion portion 134 is of a longitudinal length L2 sufficient to form an enveloping infusion profile that fully treats / targets an area of interest in (or proximate to) a vessel, as shown in FIG. 9 For example, in some embodiments, the infusion portion 134 comprises a longitudinal length of at least 3 cm, or at least 5 cm, or at least 10 cm. In some such embodiments, the infusion portion 134 comprises a longitudinal length within the range of about 3 cm to about 50 cm, or about 5 cm to about 50 cm, or about 3 cm to about 30 cm, or 5 cm to about 30 cm.

[0125] The proximal and distal radiopaque markers 130, 132 are comprised of a radiopaque material, and may fully or partially extend circumferentially about the inner lumen 120. As the plurality of micropores 122 are positioned longitudinally between the proximal and distal radiopaque markers 130, 132, the proximal and distal radiopaque markers 130, 132 can be used to radioscopically indicate the position / location of the plurality of micropores (i.e., under fluoroscopy) intravascularly, such as in relation to an area or location of interest / treatment within a vessel or proximate to a vessel. For example, for treatment of a clot within a diminutive neurovascular vessel, the catheter body 102 can be translated intravascularly, via traditional endoluminal entry points, such that the distal end portion is positioned within the diminutive neurovascular vessel with the clot, and the infusion portionAtty Ref . No.: 6473.001AWO134 extends through the clot. This relative position of the infusion portion 134 and the clot can be achieved by fluoroscopically positioning the distal end portion 116 through the vessel and the clot such that the distal radiopaque marker 132 is positioned past a distal side / end of the clot and the proximal radiopaque marker 130 is positioned past a proximal side / end of the clot (relative to the direction of travel of the distal end portion 116 through the vessel).

[0126] As shown in FIGS. 1-11 and 14-17, the micropores of the plurality of micropores 122 are spaced apart longitudinally from each other (i.e., adjacent micropores are longitudinally spaced apart). The plurality of micropores 122 are longitudinally spaced such that adjacent micropores are longitudinally spaced apart at least 1 mm from each other, or at least 2 mm, or at least 3 mm, or at least 4 mm from each other to ensure uniform infusion and sufficient structural integrity.

[0127] In some embodiments, the plurality of micropores 122 may be arranged in a longitudinally spaced successive pattern. For example, the plurality of micropores 122 may be evenly or uniformly longitudinally spaced apart from each other, as shown in FIGS. 1-11 and 14-17.

[0128] As another example, the plurality of micropores 122 may be spaced in accordance with an uneven / nonuniform but repeating pattern of spacing lengths, such as pairs of adjacent micropores being longitudinally spaced a first longitudinal length / di stance, but adjacent pair(s) being longitudinally spaced a second longitudinal length / di stance that differs from the first longitudinal length / di stance. As another example, groups of adjacent micropores of the plurality of micropores 122 may be longitudinally spaced apart at differing distances. In some such embodiments, the micropores of the plurality of micropores 122 may be unevenly longitudinally spaced apart from each other such that a first longitudinal group of micropores comprises a first longitudinal spacing, and a second longitudinal group of micropores comprises a second longitudinal spacing that is less than the first longitudinal spacing. In some such embodiments, the second longitudinal group of micropores may be longitudinally distal of the first longitudinal group of micropores. In some such embodiments, a third longitudinal group of micropores of the plurality of micropores 122 comprises a third longitudinal spacing that is greater than the second longitudinal spacing (and which may be the same as the first longitudinal spacing). The third longitudinal group of micropores may be longitudinally distal of the second longitudinal group of micropores such that the second longitudinal group of micropores is longitudinally between the first and second longitudinal groups of micropores.Atty Ref . No.: 6473.001AWO

[0129] In some embodiments, the plurality of micropores 122 may be arranged in a circumferential (or angular) spaced successive pattern. For example, longitudinally-adjacent micropores of the plurality of micropores 122 may be evenly or uniformly circumferentially spaced apart from each other, as shown in FIGS. 1-11 and 14-17. In some such embodiments, adjacent longitudinally-adjacent micropores may be circumferentially spaced apart by at least 15 degrees, or by at least 25 degrees, or by at least 40 degrees apart, or by at least 55 degrees apart (measured angularly between radii extending from a longitudinal axis defined by the catheter body 102 / lumen 120 to the center of the micropores 122). As another example, the plurality of micropores 122 may be spaced in accordance with an uneven / nonuniform but repeating pattern of circumferential spacing distances / degrees. As another example, pairs of adjacent micropores being circumferentially spaced a first circumferential spacing degree / di stance (or not circumferentially spaced), but adjacent pair(s) being circumferentially spaced a second circumferential spacing degree / di stance that differs from the circumferential spacing degree / di stance. As another example, groups of longitudinally adjacent micropores of the plurality of micropores 122 may be circumferentially spaced apart at differing degrees / di stances.

[0130] As shown in FIGS 1-11 and 14-17, the micropores of the plurality of micropores 122 of the exemplary illustrated microcatheter embodiment 100 are arranged in a longitudinally and circumferentially spaced successive pattern. For example, longitudinally-adjacent (or successive) micropores of the plurality of micropores 122 may be evenly / uniformly circumferentially spaced by at least 30 degrees, or by at least 45 degrees, or by at least about 60 degrees, or by at least about 75 degrees. As shown, the longitudinally-adjacent (or successive) micropores of the plurality of micropores 122 of the microcatheter 100 are evenly longitudinally spaced (at about 1 mm to about 3 mm from each other) and are evenly circumferentially / angularly spaced (at about 90 degrees from each other).

[0131] In some embodiments, the plurality of micropores 12 are arranged in a spiral pattern along and about the catheter body 106 / lumen 120 (or the longitudinal axis thereof). In some other embodiments, the plurality of micropores 122 are arranged in successive pairs of longitudinally spaced micropores that are successively circumferentially spaced apart by at least 30 degrees. In some alternative embodiments (not shown), longitudinally-adjacent (or successive) micropores of the plurality of micropores 122 may be unevenly / nonuniformly circumferentially / angularly spaced apart, or not circumferentially / angularly spaced apart.Atty Ref . No.: 6473.001AWO

[0132] The size of the plurality of micropores 122 has been discovered to be critical for balancing the infusion of a liquid from the infusion portion 134 during use rather than jetting or distinct streams emanating from the plurality of micropores 122 during use with a liquid (such as a liquid therapeutic agent or diagnostic material), and to allow the microcatheter 100 to be utilized with a guidewire for the positioning of the microcatheter 100 intravascularly while preventing the guidewire from extending through one of the plurality of micropores 122 during intravascular positioning and use. To achieve and balance both functions, each micropore may comprise / define a cross-sectional area less than or equal to 0.05 mm2and a minimum cross-sectional dimension (which may be a diameter) of less than about .01 inches. In some embodiments, each micropore may comprise / define a minimum cross-sectional dimension (taken normal to an axis of the micropore apertures) (such as the diameter thereof if circular in cross-section) of less than or equal to .008 inches, or less than or equal to .01 inches, or less than or equal to .014 inches, or less than or equal to .018 inches, or equal less than or equal to .02 inches to prevent such sized traditional (steerable) catheter guidewires from extending through a micropore.

[0133] In some embodiments with the microcatheter 100 specifically configured for aspiration of a diminutive vessel via the plurality of apertures 122 (rather than infusion via the plurality of micropores 122 and open inner lumen 120 at the free distal end 118), the cross-sectional dimensions of the plurality of micropores 122 may be relatively larger than being less than or equal to .01 inches or .02 inches. For example, in such microcatheters 100 configured for aspiration of a diminutive vessel, the plurality of micropores 122 may define a minimum cross-sectional dimension or diameter of at least about 1 mm, or at least about 2 mm, and / or may define a cross-sectional area of at least about 0.8 mm2, or at least about 3 2mm

[0134] In some embodiments, each of the plurality of micropores 122 may be of the same or substantially similar shape and size. For example, the micropores of the plurality of micropores 122 may define substantially the same cross-sectional area (and shape), as shown in FIGS. 1-11 and 14-17. However, in some other embodiments, the micropores of the plurality of micropores 122 may define differing cross-sectional areas. For example, the cross-sectional areas of the plurality of micropores 122 may alternate successively longitudinally between a first second cross-sectional size and a second cross-sectional size that differs from the first cross-sectional size. In some such embodiments, the cross-sectional areas of the plurality of micropores 122 may gradually increase in succession longitudinally distally. In some other such embodiments, the cross-sectional areas of the plurality ofAtty Ref . No.: 6473.001AWOmicropores 122 may increase longitudinally distally such that a first longitudinal group of micropores of the plurality of micropores 122 comprises a first cross-sectional size, and a second longitudinal group of micropores of the plurality of micropores 122 comprises a second cross-sectional size that is greater than the first cross-sectional size, the second longitudinal group of micropores being longitudinally distal to the first longitudinal group of micropores. In some such embodiments, a third longitudinal group of micropores of the plurality of micropores 122 may comprise a third cross-sectional size that is less than the second cross-sectional size, and the second longitudinal group of micropores may be longitudinally distal to the third longitudinal group of micropores.

[0135] As noted above, the micropores of the plurality of micropores 122 may define substantially the same cross-sectional shape, as shown in FIGS. 1-11 and 14-17. As shown, the plurality of micropores 122 may each define a circular cross-sectional shape. However, non-circular micropores may be advantageous for infusion and guidewire compatibility. For example, in some embodiments, the plurality of micropores 122 may each define an oval cross-sectional shape, such as with the longer diameter / dimension thereof oriented longitudinally. As another example, the plurality of micropores 122 may each define an irregular and / or non-circular cross-sectional shape, such as with a longer diameter / dimension thereof oriented longitudinally. In some embodiments, the plurality of non-circular shaped micropores each define a maximum longitudinal dimension / size that is greater than a maximum lateral / circumferential dimension / size.

[0136] As also discussed above, the plurality of micropores 122 and the open lumen 122 at the free distal end 118 are configured to form an effective targeted infusion that treats a particular area of interest within a vessel. Accordingly, in some embodiments, the plurality of micropores 122 and the maximum inner diameter ID1 of the lumen 120 at at least the free distal end 118 are configured relative to each other such that the catheter body 102 infuses at least 50% of a liquid therapeutic agent or diagnostic material introduced into the inner lumen 120 into a diminutive vessel via the plurality of micropores 122, and less than or equal to 50% of the liquid therapeutic agent or diagnostic material introduced into the inner lumen 120 into the diminutive vessel via the free distal end 188. More preferably, in some embodiments, the plurality of micropores 122 and the maximum inner diameter ID1 of the lumen 120 at at least the free distal end 118 are configured relative to each other such that the catheter body 102 infuses at least 60% of a liquid therapeutic agent or diagnostic material introduced into the inner lumen 120 into a diminutive vessel via the plurality of micropores 122, and less than or equal to 40% of the liquid therapeutic agent or diagnostic materialAtty Ref . No.: 6473.001AWOintroduced into the inner lumen 120 into the diminutive vessel via the free distal end 188. Even more preferably, in some embodiments, the plurality of micropores 122 and the maximum inner diameter ID1 of the lumen 120 at at least the free distal end 118 are configured relative to each other such that the catheter body 102 infuses at least 70% of a liquid therapeutic agent or diagnostic material introduced into the inner lumen 120 into a diminutive vessel via the plurality of micropores 122, and less than or equal to 30% of the liquid therapeutic agent or diagnostic material introduced into the inner lumen 120 into the diminutive vessel via the free distal end 188.

[0137] As shown and discussed above, the wall thickness of the tubular wall structure 106 of the catheter body 102 may thin or taper along its longitudinal length as it extends from the proximal end 102 toward or to the free distal end 118, which may thereby reduce or taper the inner lumen 120 and / or the outer / exterior size from the proximal end 102 to the free distal end 118. The tubular wall structure 106 may be formed of any biocompatible material, layers or construction that provides the needed structural integrity and dimensional requirements of the microcatheter 100 as discussed above.

[0138] The tubular wall structure 106 may form a generally soft, rounded tip at the free distal end 118 for smooth navigation, and a flexible body or shaft portion extending between the hub portion 104 and the free distal end 118 to maneuver through complex and often tortuous blood vessel curves, while maintaining a stable proximal shaft for device delivery to a target intravascular location. In some embodiments, the tubular wall structure 106 is formed of at least one polymer layer or portion. For example, the tubular wall structure 106 may comprise at least one layer formed of at polyurethane, nylon, polyether block amide (PEBA), a fluoropolymer (such as polyethylene, polytetrafluoroethylene (PTFE) and fluorinated ethylene propylene (FEB)), silicone or a combination thereof. In some embodiments, the tubular wall structure 106 may include two or more layers (e.g., radially arranged layers), support members or sleeves, reinforcement members or material or other construction or configurations.

[0139] In some embodiments, the outermost surface or sides of the tubular wall structure 106, and thereby the exterior surface of the microcatheter 100 itself, may include a hydrophilic coating. The hydrophilic coating may be configured to bind with water or bodily fluid (such as within a vessel) to create a smooth, slippery, low-friction biocompatible outer surface. In some embodiments, a hydrophilic coating may comprise a polyvinylpyrrolidoneAtty Ref . No.: 6473.001AW0(PVP) or a hydrogel. In some other embodiments, a hydrophilic coating may comprise polyurethane, pebax™, nylon, silicone or a combination thereof.

[0140] The microcatheter 100 may be utilized to treat a patient via directly accessing and treating (a therapeutic treatment, a treatment for diagnosis or sampling, or testing) a diminutive vessel of the patient (e.g., a diminutive neurovascular vessel). It is noted that the microcatheter 100 may be used to treat an issue with or within a particular treatment or treatment site or area of interest of the diminutive vessel itself, or adjacent or proximate to the target / treatment site or area of interest of the diminutive vessel. For example, the microcatheter 100 may be utilized to infuse a blockage or clot within a diminutive vessel, or aspirate or sample a target / treatment or area of interest of or within the diminutive vessel As another example, the microcatheter 100 may be utilized to infuse a the diminutive vessel with a material that passes through the vessel wall, to thereby treat a target / treatment or area of interest outside / exterior to the diminutive vessel (which may be adjacent or proximate to the diminutive vessel, such as a tumor, cancer or other issue located outside the vessel). As discussed above, the microcatheter 100 may be used to infuse any liquid medicant or other liquid therapeutic or diagnostic agent.

[0141] As discussed above, the microcatheter 100 may be utilized with a catheter guidewire, such as a steerable catheter guidewire defining a maximum outer diameter of less than or equal to 0.6 mm and greater than or equal to about .008 inches. One or more microcatheter 100 and one or more catheter guidewire may be combined and form a system or kit. The catheter guidewire may be a guidewire described herein or otherwise. For example, in some embodiments, the guidewire may comprises a longitudinal length of at least 180 cm, and / or at least a distal end portion of the guidewire may be curved or malleable / plastically deformable into a curved shape.

[0142] The catheter guidewire may be inserted into a first vessel of a vascular system (e.g., a neurovascular system) of human patient, and translated through the vascular system to a diminutive vessel of a brain or spine of the human patient (or other vessel). The catheter guidewire may first be inserted through the hub portion 104 via the opening 105 and the lumen 120 of the catheter body 102 before being inserted into the vascular system, or the lumen 120 of the catheter body 102 and the hub portion 104 may be translated over the guidewire after inserted into the vascular system.

[0143] The microcatheter 100 may be translated over a guidewire and through a vascular system such that the infusion portion 134 and the distal free end 118 the distal end portionAtty Ref . No.: 6473.001AW0116 is positioned within a target / treatment of a diminutive vessel of the vascular system, such as a diminutive vessel of a neurovascular system of a brain or spine of a huma patient. It is noted that the guidewire and the microcatheter 100 may be translated through a vascular system via incremental translations comprising a series of alternating incremental translations of the guidewire through the vascular system (and through the microcatheter 100) and incremental translations of the microcatheter 100 over the guidewire and through the vascular system, until the distal end portion 116 reaches an area of interest or target / treatment within a diminutive vessel of the vascular system.

[0144] With the distal end portion 116 positioned within an area of interest or target / treatment within a diminutive vessel of a vascular system, in some embodiments, the diminutive vessel may be infused with a volume of a liquid therapeutic agent or diagnostic material via the plurality of micropores 122 and the open lumen 120 of distal free end 188 of the distal end portion 116 of the microcatheter 100, such as via injecting or forming a flow through the microcatheter 100 via the opening 105 of the hub portion 104. As another example, with the distal end portion 116 positioned within an area of interest or target / treatment within a diminutive vessel of a vascular system, the area of interest / treatment site / target site may be aspirated by the microcatheter 100 by allowing (or sucking) a flow of biological material from within the area of interest / treatment into the inner lumen 120 via the plurality of micropores 120 and or the open lumen 120 at the free distal end 118 (and allowing or sucking the material to flow longitudinally proximally through the catheter body 102 to the hub portion 104).

[0145] FIGS. 18-21 illustrate another exemplary microcatheter 200 according to the present disclosure. The microcatheter 200 of FIGS. 18-21 is substantially similar to the microcatheter 100 of FIGS. 1-17 described above, and therefore like reference numerals preceded with “2” as opposed to “1” are used to indicate like components, aspects, features, functions or portions, and the description above directed thereto equally applies to microcatheter 200, and is not repeated for brevity and clarity purposes. As shown in FIGS. 18-21, the microcatheter 200 differs from the microcatheter 100 in the configuration of the distal end portion 216 extending to / from the free distal end 218.

[0146] As shown in FIGS. 18-21, the microcatheter 200 includes a tapered tip portion 250 that defines the free distal end 218. The tapered tip portion 250 extends from the infusion portion 234 or just distally past the infusion portion 234 at about where the free distal end 118 of the microcatheter 100 was located. For example, the tapered tip portion 250 may extend distallyAtty Ref . No.: 6473.001AWOfrom about the location of the distal radiopaque marker 232 or about 1 cm to about 10 cm distally past the distal radiopaque marker 232. The infusion portion 234 is a longitudinal portion of the distal end portion 216 that comprises the plurality of micropores 222, and the tapered tip portion 250 extends distally therefrom and is void of the plurality of micropores 222. The distal radiopaque marker 232 may thereby be positioned between a longitudinally distal-most micropore of the plurality of micropores 220 and the tapered tip portion 250.

[0147] In some embodiments, the microcatheter 200 may define a total longitudinal length L3 from the distal-most micropore 222 to the free distal end 218 of the tapered tip portion 250 of about 0.1 cm to about 5 cm, or about 0.2 cm to about 4 cm, or about 0.3 cm to about 3 cm, or 0.4 cm to about 4 cm, or about 0.5 cm to about 1.5 cm.

[0148] The tapered tip portion 250 defines a maximum outer / exterior cross-sectional dimension or diameter that reduces or tapers, such as gradually or continually, over the longitudinal length of the tapered tip portion 250 from a proximal end thereof to the free distal end 218, as shown in FIGS. 18-21. Accordingly, the maximum outer cross-sectional diameter / dimension OD1 at the free distal end 218 is less than the outer cross-sectional diameter / dimension OD7 at the proximal end of the tapered tip portion 215 (e.g., at a distal end of the infusion portion 234). In some embodiments, the degree or angle of taper of the maximum outer / exterior cross-sectional dimension or diameter of the tapered tip portion 250 is greater (i.e., more tapered or a sharper taper) than that of the proximal portion 212, the medial portion 214 and the rest of the distal portion 216 (such as the infusion portion 234). In some embodiments, the maximum outer cross-sectional diameter / dimension OD1 at the free distal end 218 is within the same dimensional ranges and dimensions disclosed with respect to the free distal end 118 of the microcatheter 100. In some such embodiments, the outer cross-sectional diameter / dimension OD7 at the proximal end of the tapered tip portion 250 is within the range of about 0.5 mm (about 0.018 inches) to about 1 mm (about 0.041 inches). In some such embodiments, the maximum outer cross-sectional diameter / dimension OD1 at the free distal end 218 of the tapered tip portion 250 is within the range of about 15% to about 60% less than the outer cross-sectional diameter / dimension OD7 at the proximal end of the tapered tip portion 250.

[0149] The tapered tip portion 250 also differs from the illustrated exemplary embodiment of the distal end portion 118 of microcrater 100 in that the minimum inner cross-sectional diameter / dimension of the inner lumen 220 extending through the tapered tip portion 250 to the free distal end 218 (and open at the free distal end 218) from the infusion portion 234 or a portion of the distal end portion 216 that extends distally from the infusion portion 234. TheAtty Ref . No.: 6473.001AWOminimum inner cross-sectional diameter / dimension of the inner lumen 220 of the tapered tip portion 250 may such as gradually or continually taper over the longitudinal length of the tapered tip portion 250 from a proximal end thereof to the free distal end 218, as shown in FIGS. 18-21. Accordingly, minimum inner cross-sectional diameter / dimension ID1 of the inner lumen 220 of the tapered tip portion 250 at the free distal end 218 is less than the minimum inner cross-sectional diameter / dimension ID3 at proximal end of the tapered tip portion 250 (e.g., proximate to a distal end of the infusion portion 234). In some such embodiments, the minimum inner cross-sectional diameter / dimension ID1 of the inner lumen 220 of the tapered tip portion 250 at the free distal end 218 is within the range of about 15% to about 60% less than the minimum inner cross-sectional diameter / dimension ID3 at proximal end of the tapered tip portion 250.

[0150] In some embodiments, the minimum inner cross-sectional diameter / dimension ID1 of the inner lumen 220 of the tapered tip portion 250 at the free distal end 218 is within the same dimensional ranges and dimensions disclosed with respect to the free distal end 118 of the microcatheter 100, such as being less than or equal to 0.6 mm for example. However, as discussed above, the inner diameter / dimension of the lumen 220 of the catheter body 202 but for the tapered tip portion 250 may be substantially constant and non-tapered, but the lumen 220 of the tapered tip portion 250 tapered inwardly from the minimum inner cross-sectional diameter / dimension ID3 at proximal end of the tapered tip portion 250 to the minimum inner cross-sectional diameter / dimension ID1 at the free distal end 218. In some embodiments, the minimum inner cross-sectional diameter / dimension ID3 at proximal end of the tapered tip portion 250 is within the range of about 0.3 mm (about 0.013 inches) to about 0.7 mm (about 0.03 inches). FIGS. 22-25 illustrate another exemplary microcatheter 300 according to the present disclosure. The microcatheter 300 of FIGS. 22-25 is substantially similar to the microcatheter 100 of FIGS. 1-17, and microcatheter 200 of FIGS. 18-21, described above, and therefore like reference numerals preceded with “3” as opposed to “1” or “2” are used to indicate like components, aspects, features, functions or portions, and the description above directed thereto equally applies to microcatheter 300, and is not repeated for brevity and clarity purposes. As shown in FIGS. 22-25, the microcatheter 300 differs from the microcatheter 100 and the microcatheter 200 in the configuration of the catheter body 302.

[0151] As shown, the catheter body 302 includes as at least one tubular inner liner layer 306 that forms or defines the inner lumen 320 (such as a polymer tubular inner liner, which may be formed of one or more fluoropolymer material such as a PTFE), and an outer or covering layer 360 extending over the at least a portion of the inner liner layer 306. The inner linerAtty Ref . No.: 6473.001AWOlayer 306 may be configured the same or substantially similarly as the tubular wall structure 106 and the tubular wall structure 206. In some embodiments, outer or covering layer 360 may extend over the exterior or outer surface / side of the inner liner layer 306 such that the outer or covering layer 360 is radially proud of the inner liner layer 306. In some embodiments, outer or covering layer 360 may extend over only an inner portion of the inner liner layer 306 such that the outer or covering layer 360 is partially or fully embedded within the inner liner layer 306.

[0152] The outer or covering layer 360 may comprise an outer layerjacket and / or reinforcement material or members configured to provide structural integrity to the inner liner layer 306, physical and / or chemical protection of the inner liner layer and / or flexibility and softness. For example, the outer or covering layer 360 may be configured to substantially provide the pushability, trackability and / or steerability of the catheter body 302.

[0153] The outer jacket or covering layer 360 may include one or more layers, members, strips, strands, fibers or a combination thereof that extend over the inner liner layer 306 circumferentially and longitudinally, as shown in FIGS. 22-25. For example, one or more portions of the outer jacket or covering layer 360 may spiral about the inner liner layer 306. In some embodiments, the outer jacket or covering layer 360 may comprise braided, woven interposed or cross-spiraled layers, portions or members. In some embodiments, the outer jacket or covering layer 360 may be formed of PEBA, polyurethane, polyethylene, vortec™, a metal material or a combination thereof extending over the inner liner layer 306. In some embodiments, the outer jacket or covering layer 360 comprises at least one reinforcement material or members, such as one or more helical wires that extend from the proximal end portion 312 to the distal end portion 316.

[0154] As shown best in FIGS. 24 and 25, the outer or covering layer 360 may not extend over the distal-most portion of the distal end portion 316 to the free distal end 318, such as but not limited to the tapered tip portion 350 (if included). In some other embodiments, the outer or covering layer 360 may extend fully from the hub portion 304 at the proximal end portion 312 to the free distal end 318 of the distal end portion 316. The distal-most end portion of the outer or covering layer 360 may taper inwardly toward / to inner liner layer 306 or the tapered tip portion 350 to form a necking 362. The necking 362 may be configured to provide a smooth transition between the outer or covering layer 360 and the underlying inner liner layer 306 or the tapered tip portion 350.Atty Ref . No.: 6473.001AW0

[0155] FIG. 26 illustrates another exemplary microcatheter 400 according to the present disclosure. The microcatheter 400 of FIG. 26 is substantially similar to the microcatheter 100 of FIGS. 1-17, the microcatheter 200 of FIGS. 18-21, and the microcatheter 300 of FIGS. 22-25, described above, and therefore like reference numerals preceded with “4” as opposed to “1”, “2” or “3” are used to indicate like components, aspects, features, functions or portions, and the description above directed thereto equally applies to microcatheter 400, and is not repeated for brevity and clarity purposes. As shown in FIG. 26, the microcatheter 400 differs from the microcatheter 100, the microcatheter 200 and the microcatheter 300 in the configuration of the catheter body 402.

[0156] As shown in FIG. 26, the catheter body 402 includes at least one coil or spiral member 465 that extends longitudinally and circumferentially about at least a portion of the tubular wall structure / inner liner layer 406 or the outer / covering layer 460. The coil or spiral member 465 may extend over the tubular wall structure / inner liner layer 406 or the outer / covering layer 460, or be embedded within the tubular wall structure / inner liner layer 406 or the outer / covering layer 460.

[0157] The coil or spiral member 465 may be configured to provide or enhance the pushability, trackability and / or steerability of the catheter body 402. In some embodiments, the coil or spiral member 465 comprises a coiled / spiral wire or like member, as shown. The pitch of the coils / spirals may be configured such that the coil or spiral member 465 extends between the plurality of micropores 422 (i.e., the plurality of micropores 422 are positioned within the spaces between the coils / pitch of the coil or spiral member 465) so that the coil or spiral member 465 does not block or interfere with the functioning of the plurality of micropores 422.

[0158] In some embodiments, the coil or spiral member 465 may be formed of a metal material, such as but not limited to stainless steel, tungsten or nitinol. However, other materials and construction of the coil or spiral member 465 may equally be employed..

[0159] FIG. 27 illustrates another exemplary microcatheter 500 according to the present disclosure. The microcatheter 500 of FIG. 27 is substantially similar to the microcatheter 100 of FIGS. 1-17, the microcatheter 200 of FIGS. 18-21, the microcatheter 300 of FIGS. 22-25 and the microcatheter 400 of FIG. 26 described above, and therefore like reference numerals preceded with “5” as opposed to “1”, “2”, “3” or “4” are used to indicate like components, aspects, features, functions or portions, and the description above directed thereto equally applies to microcatheter 500, and is not repeated for brevity and clarity purposes. As shownAtty Ref . No.: 6473.001AW0in FIG. 27, the microcatheter 500 differs from the microcatheter 100, the microcatheter 200, the microcatheter 300 and the microcatheter 400 in the configuration of the catheter body 502.

[0160] As shown in FIG. 27, the microcatheter 500 is substantially similar to the microcatheter 400 of FIG. 26, but differs in that the catheter body 502 includes a first coil or spiral member 565 and a second coil or spiral member 567. The first and second coil / spiral members 565, 567 are substantially similar to the coil or spiral member 465 of the microcatheter 400, but the first and second coil / spiral members 565, 567 are coiled / spiraled in opposing directions. As shown, the first coil / spiral member 565 extends circumferentially about the about at least a portion of the tubular wall structure / inner liner layer 506 or the outer / covering layer 560 a first angular direction as it extends longitudinally distally (e.g., clockwise), and the second coil / spiral member 567 extends circumferentially about the about at least a portion of the tubular wall structure / inner liner layer 506 or the outer / covering layer 560 a second angular direction as it extends longitudinally distally that is opposite than the first angular direction (e.g., counterclockwise). The first and second coil / spiral members 565, 567 thereby cross each other as extend they longitudinally and circumferentially, as shown in FIG. 27.

[0161] FIGS. 28 and 29 illustrate another exemplary microcatheter 600 according to the present disclosure. The microcatheter 600 of FIGS. 28 and 29 is substantially similar to the microcatheter 100 of FIGS. 1-17, the microcatheter 200 of FIGS. 18-21, the microcatheter 300 of FIGS. 22-25, the microcatheter 400 of FIG. 26 and the microcatheter 500 of FIG. 27 described above, and therefore like reference numerals preceded with “6” as opposed to “1”, “2”, “3”, “4” or “5” are used to indicate like components, aspects, features, functions or portions, and the description above directed thereto equally applies to microcatheter 600, and is not repeated for brevity and clarity purposes. As shown in FIGS. 28 and 29, the microcatheter 600 differs from the microcatheter 100, the microcatheter 200, the microcatheter 300, the microcatheter 400 and the microcatheter 500 in the configuration of the catheter body 602.

[0162] As shown in FIGS. 28 and 29, the catheter body 602 of the microcatheter 600 is configured as a dual-lumen endoluminal neurovascular microcatheter. As shown, the microcatheter 600 comprises an inner tubular wall structure 676 extending from the hub portion that defines a continuous, unobstructed inner lumen 672 that is open at the free distal end 618, and an outer tubular wall structure 678 extending from the hub portion that defines aAtty Ref . No.: 6473.001AW0continuous outer lumen 670 that extends about the inner tubular wall structure 676 and is closed at a distal end of the outer lumen 670.

[0163] The inner lumen 672 may be configured to provide a passageway for the delivery of stents other mechanical devices / apparatus into a vessel, and the outer lumen 670 may be configured to provide a passageway for a simultaneous (and / or subsequent and / or prior) direct targeted infusion of a fluid into the vessel. The inner lumen 672 may thereby define a maximum inner diameter ID4 within the range of about 0.3 mm to about 0.7 mm, and the outer lumen 670 may define a maximum radial thickness T4 within the range of about 0.1 mm to about 0.4 mm. Further, at least a free end portion of the distal end portion 616 of the catheter body 606 extending longitudinally to the free distal end 618 may define a maximum outer diameter of less than or equal to 1.5 mm, or less than or equal to 2 mm. Accordingly, the dual-lumen microcatheter 600 may define a slightly larger cross-sectional size as compared to single-lumen catheters disclosed herein due to the dual-lumen configuration.

[0164] As shown, in some embodiments, the inner tubular wall structure 676 defines a radial wall thickness T3 extending radially between the inner and outer lumens 672, 670 (and extending longitudinally from the proximal end portion 612 to the distal end portion 616), and the outer tubular wall structure 678 defines a radial wall thickness T2 extending radially between the outer lumen 670 and the exterior of the catheter body 602 (and extending longitudinally from the proximal end portion 612 to the distal end portion 616) that is less than the radial wall thickness T3 of the inner tubular wall structure 676.

[0165] In some embodiments, the outer tubular wall structure 678 is more flexible than the inner tubular wall structure 676 along a longitudinal length of the catheter body 602. For example, the inner tubular wall structure 676 may define a structural integrity that is greater than a structural integrity of the inner tubular wall structure 678 along a longitudinal length of the catheter body 602. In some embodiments, the inner tubular wall structure 676 is self-supporting such that it naturally maintains the inner lumen 670 in a substantially fully full open arrangement, and the outer tubular wall structure 678 is not self-supporting such that it does not naturally maintain the outer lumen 670 in a substantially fully full open arrangement (i.e., without a flow of fluid flowing therethrough, which may fully open the outer lumen 670).

[0166] As noted above, the inner tubular wall structure 678 and the outer tubular wall structure 678 may be coupled to, and extend from the hub portion 604 (not shown). The hub portion 604 may thus include an inner pathway or port that is in fluid communication with theAtty Ref . No.: 6473.001AWOinner lumen 672 (and not the outer lumen 670) at the proximal end of the proximal end portion 612 of the catheter body 602, and an outer pathway or port that is in fluid communication with the outer lumen 670 (and not the inner lumen 672) at the proximal end of the proximal end portion 612 of the catheter body 602.

[0167] Other than the hub portion 604, the microcatheter 600 may include one or additional members or portions that are coupled to the inner and outer tubular wall structures 676, 678 and maintain them in the radially spaced arrangement. For example, as shown in FIG. 28, the catheter body 602 may include one or more struts 674 extending between and coupling portions of an outer side of the inner tubular wall structure 676 and portions of an inner side of the outer tubular wall structure 678. If a plurality of struts 674 are provided, adjacent struts 674 may be circumferentially spaced / arranged.

[0168] As noted above, the outer lumen 670 of the microcatheter 600 is closed or sealed off at a distal end thereof, which allows for the buildup of fluid pressure therein for the infusion of a liquid via the plurality of micropores 622. The outer lumen 670 may be closed by any configuration or member. As shown in FIG. 28, in some embodiments, the microcatheter 600 may include an end structure that extends radially between the inner and outer tubular wall structures 676, 678 and seals off a distal end of the outer lumen. In some such embodiments, as shown in FIG. 28, the end structure may be the distal radiopaque marker 632. In some other embodiments, a radially extending wall or other member, portion or device may close or seal off a distal end of the outer lumen. As yet another example, the distal portion of the outer lumen 670 may be closed or sealed off via the outer and inner tubular wall structures 676, 678 being sealed to each other, such as being bonded to each other or adhered or bonded to each other.

[0169] As may be recognized by those of ordinary skill in the art based on the teachings herein, numerous changes and modifications may be made to the above-described and other embodiments of the present disclosure without departing from the scope of the disclosure. The components of the catheters, systems and methods as disclosed in the specification, including the accompanying abstract and drawings, may be replaced by alternative component s) or feature(s), such as those disclosed in another embodiment, which serve the same, equivalent or similar purpose as known by those skilled in the art to achieve the same, equivalent or similar results by such alternative component(s) or feature(s) to provide a similar function for the intended purpose. In addition, the catheters, systems and methods may include more or fewer components or features than the embodiments as described andAtty Ref . No.: 6473.001AWOillustrated herein. For example, the catheters may include metal distal tips or ends, or distal ends that are formed of a different material or configuration than the body portion of the catheters. As another example, the micropores may not be distinct, defined through holes in the tubular wall structure of the catheters, but rather may be a mesh, sponge or microporous material that includes a structure containing pores or smaller interior through holes (e.g., zeolites or metal-organic frameworks).

[0170] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Reference throughout this disclosure to “one embodiment” or “an embodiment” or “some embodiments” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the presently disclosed inventions, and may be utilized in other embodiments in addition to the particular embodiment s) being described. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” or “in some embodiments” in various places throughout this disclosure are not necessarily all referring to the same embodiment or a single embodiment. Furthermore, the particular features, structures, or characteristics disclosed with respect to one or mor embodiments may be combined in any suitable manner in one or more other embodiments.

[0171] As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprise” (and any form of comprise, such as “comprises” and “comprising”), “have” (and any form of have, such as “has”, and “having”), “include” (and any form of include, such as “includes” and “including”), and “contain” (and any form of contain, such as “contains” and “containing”) are open-ended linking verbs. As a result, a method or device that “comprises,” “has,” “includes,” or “contains” one or more steps or elements possesses those one or more steps or elements, but is not limited to possessing only those one or more steps or elements. Likewise, a step of a method or an element of a device that “comprises,” “has,” “includes,” or “contains” one or more features possesses those one or more features, but is not limited to possessing only those one or more features.Furthermore, a device or structure that is configured in a certain way is configured in at least that way, but may also be configured in ways that are not listed.

[0172] The invention has been described with reference to the preferred embodiments. It will be understood that the operational embodiments described herein are exemplary of a plurality of possible arrangements to provide the same general features, characteristics, and generalAtty Ref . No.: 6473.001AW0system operation. Modifications and alterations will occur to others upon a reading and understanding of the preceding detailed description. It is intended that the invention be construed as including all such modifications and alterations.

Claims

Atty Ref . No.: 6473.001AW0CLAIMS1. An endoluminal neurovascular microcatheter, comprising:a hub portion configured to remain outside of the patient; anda catheter body being longitudinally elongated and extending from a proximal end portion coupled to the hub portion to a free distal end at a distal end portion configured to access diminutive vessels of a brain or spine of a human patient, the catheter body comprising a tubular wall structure that defines a continuous, unobstructed inner lumen that is open at the free distal end,wherein the catheter body is longitudinally variably flexible, and wherein the proximal end portion of the catheter body comprises a first flexural rigidity, a medial portion of the catheter body extending longitudinally between the proximal and distal end portions comprises a second flexural rigidity that is less than the first flexural rigidity, and the distal end portion of the catheter body comprises a third flexural rigidity that is less than the second flexural rigidity,wherein the distal end portion of the catheter body comprises a proximal radiopaque marker, a distal radiopaque marker, and a plurality of micropores extending through the tubular wall structure from the inner lumen to an exterior of the tubular wall structure configured to infuse the diminutive vessels with a liquid therapeutic agent or diagnostic material,wherein the plurality of micropores are arranged in a longitudinally spaced successive pattern, and each micropores defines a minimum cross-sectional dimension of less than or equal to 0.01 inch and a cross-sectional area less than or equal to 0.05 mm2, and wherein at least a free end portion of the distal end portion of the catheter body longitudinally extending to the free distal end defines a maximum outer diameter of less than or equal to 1 mm, and defines a maximum inner diameter of the lumen thereof of less than or equal to 0.7 mm.

2. The microcatheter of claim 1, wherein the inner lumen comprises a continuous defined inner diameter size from the proximal end portion to the free distal end.

3. The microcatheter of claim 2, wherein at least the free end portion of the distal end portion of the catheter body comprises a continuous defined exterior cross-sectional size along its longitudinal length.Atty Ref . No.: 6473.001AW04. The microcatheter of claim 3, wherein the free end portion of the distal end portion comprises a longitudinal length of at least 3 cm.

5. The microcatheter of claim 2, wherein the distal end portion of the catheter body comprises a proximal portion extending longitudinally from the medial portion to the free end portion of the distal end portion, the proximal portion of the distal end portion defines a maximum outer diameter of less than or equal to 0.9 mm.

6. The microcatheter of claim 2, wherein the catheter body comprises a tapered maximum exterior cross-sectional diameter that decreases along its longitudinal length from the proximal end portion to the free distal end of the distal end portion.

7. The microcatheter of claim 6, wherein the maximum exterior cross-sectional diameter of the catheter body tapers from less than or equal from 1.4 mm at a proximal end of the proximal end portion to less than or equal to 1 mm at the free distal end of the distal end portion.

8. The microcatheter of claim 1, wherein the distal end portion of the catheter body comprises a tapered tip portion that extends from a distal end of an infusion portion of the distal end portion and defines the free distal end, wherein the tapered tip portion comprises a tapered outer cross-sectional diameter such that the outer cross-sectional diameter at the free distal end is less than the outer cross-sectional diameter at the distal end of the infusion portion, and wherein the infusion portion is a longitudinal portion of the distal end portion that comprises the plurality of micropores.

9. The microcatheter of claim 8, wherein the outer cross-sectional diameter of the tapered tip portion continuously gradually tapers inwardly from the distal end of the infusion portion to the free distal end.

10. The microcatheter of claim 8, wherein the tapered tip portion comprises a tapered inner cross-sectional diameter of the inner lumen such that the inner cross-sectional diameter of the lumen at the free distal end is less than the inner cross-sectional diameter of the inner lumen at the distal end of the infusion portion.Atty Ref . No.: 6473.001AW011. The microcatheter of claim 10, wherein the inner cross-sectional diameter of the inner lumen of the tapered tip portion continuously gradually tapers inwardly from the distal end of the infusion portion to the free distal end.

12. The microcatheter of claim 10, wherein the tapered tip portion comprises a longitudinal length with the range of about 0.5 cm to about 1.5 cm, and defines a maximum inner diameter of the lumen at the free distal end of less than or equal to 0.6 mm.

13. The microcatheter of claim 8, wherein the distal radiopaque marker is positioned between a longitudinally distal-most micropore of the plurality of micropores and the tapered tip portion.

14. The microcatheter of claim 1, wherein the plurality of micropores define an infusion portion of the distal end portion of the catheter body.

15. The microcatheter of claim 14, wherein the infusion portion is longitudinally spaced from the free distal end, and wherein the distal radiopaque marker is positioned at a distal end of the infusion portion.

16. The microcatheter of claim 15, wherein the proximal radiopaque marker is positioned at a proximal end of the infusion portion.

17. The microcatheter of claim 14, wherein the infusion portion comprises a longitudinal length of at least 3 cm.

18. The microcatheter of claim 14, wherein the infusion portion comprises a longitudinal length of at least 5 cm.

19. The microcatheter of claim 14, wherein the infusion portion comprises a longitudinal length of at least 10 cm.

20. The microcatheter of claim 14, wherein the infusion portion comprises a longitudinal length within the range of 3 cm to 30 cm.Atty Ref . No.: 6473.001AW021. The microcatheter of claim 1, wherein a maximum outer diameter of the catheter body decreases along the longitudinal length such that the outer cross-sectional diameter at the free distal end is less than the outer cross-sectional diameter at the proximal end portion.

22. The microcatheter of claim 21, wherein a maximum outer cross-sectional diameter of the proximal end portion of the catheter body is greater than a maximum outer cross-sectional diameter of the medial portion of the catheter body, and a maximum outer cross-sectional diameter of the medial portion of the catheter body is greater than the maximum outer diameter of the distal end portion of the catheter body.

23. The microcatheter of claim 22, wherein the proximal end portion of the catheter body comprises a first proximal portion that comprises a first maximum outer cross-sectional diameter, and a first distal portion that comprises a second maximum outer cross-sectional diameter that is less than the first maximum outer cross-sectional diameter, wherein the medial portion of the catheter body comprises a second proximal portion that comprises a third maximum outer cross-sectional diameter that is less than the second maximum outer cross-sectional diameter, and a second distal portion that comprises a fourth maximum outer cross-sectional diameter that is less than the third maximum outer cross-sectional diameter, and wherein the maximum outer diameter of the distal end portion of the catheter body is less than the fourth maximum outer cross-sectional diameter.

24. The microcatheter of claim 23, wherein the distal end portion comprises a third proximal portion that comprises a fifth maximum outer cross-sectional diameter that is less than the fourth maximum outer cross-sectional diameter, and a second distal portion that defines the free distal end and comprises a sixth maximum outer cross-sectional diameter that is less than the fifth maximum outer cross-sectional diameter, the25. The microcatheter of claim 22, wherein the maximum outer cross-sectional diameter of the catheter body continuously gradually tapers inwardly from a proximal end of the proximal end portion to the free distal end.

26. The microcatheter of claim 22, wherein the maximum outer cross-sectional diameter of the proximal end portion of the catheter body is less than or equal to 1.5 mm.Atty Ref . No.: 6473.001AWO27. The microcatheter of claim 22, wherein the inner lumen comprises a continuous defined inner diameter size from the proximal end portion to the free distal end.

28. The microcatheter of claim 27, wherein a radial wall thickness of the catheter body decreases in thickness along the longitudinal length such that the outer cross-sectional diameter at the free distal end is less than the outer cross-sectional diameter at the proximal end portion.

29. The microcatheter of claim 1, wherein the plurality of micropores are positioned longitudinally between the first and second radiopaque markers.

30. The microcatheter of claim 1, wherein the inner lumen defines a circular cross-sectional shape.

31. The microcatheter of claim 1, wherein the catheter body defines an outer circular cross-sectional shape.

32. The microcatheter of claim 1, wherein the micropores are longitudinally spaced such that adjacent micropores of the plurality of micropores are longitudinally spaced apart at least 1 mm from each other.

33. The microcatheter of claim 1, wherein the micropores are longitudinally spaced such that adjacent micropores of the plurality of micropores are longitudinally spaced apart at least 2 mm from each other.

34. The microcatheter of claim 1, wherein the micropores of the plurality of micropores are evenly longitudinally spaced apart from each other.

35. The microcatheter of claim 1, wherein the micropores of the plurality of micropores are unevenly longitudinally spaced apart from each other such that a first longitudinal group of micropores of the plurality of micropores comprises a first longitudinal spacing, and a second longitudinal group of micropores of the plurality of micropores comprises a second longitudinal spacing that is less than the first longitudinal spacing.Atty Ref . No.: 6473.001AWO36. The microcatheter of claim 35, wherein the second longitudinal group of micropores is longitudinally distal of the first longitudinal group of micropores.

37. The microcatheter of claim 36, wherein a third longitudinal group of micropores of the plurality of micropores comprises a third longitudinal spacing that is greater than the second longitudinal spacing, and wherein the third longitudinal group of micropores is longitudinally distal of the second longitudinal group of micropores.

38. The microcatheter of claim 1, wherein the plurality of micropores are arranged in a longitudinally and circumferentially spaced successive pattern.

39. The microcatheter of claim 38, wherein adjacent micropores of the plurality of micropores are circumferentially spaced at least 30 degrees measured angularly between radii extending from a longitudinal axis defined by the catheter body.

40. The microcatheter of claim 39, wherein the adjacent micropores of the plurality of micropores are longitudinally spaced at least 1 mm from each other.

41. The microcatheter of claim 1, wherein the plurality of micropores are arranged in a spiral pattern about the catheter body.

42. The microcatheter of claim 1, wherein the plurality of micropores are arranged in successive pairs of micropores that are successively circumferentially spaced at least 30 degrees measured angularly between radii extending from a longitudinal axis defined by the catheter body.

43. The microcatheter of claim 1, wherein the micropores of the plurality of micropores define substantially the same cross-sectional area.

44. The microcatheter of claim 1, wherein the micropores of the plurality of micropores define differing cross-sectional areas.Atty Ref . No.: 6473.001AWO45. The microcatheter of claim 44, wherein the cross-sectional areas of the plurality of micropores gradually increase in succession longitudinally distally.

46. The microcatheter of claim 44, wherein the cross-sectional areas of the plurality of micropores increase longitudinally distally such that a first longitudinal group of micropores of the plurality of micropores comprises a first cross-sectional size, and a second longitudinal group of micropores of the plurality of micropores comprises a second cross-sectional size that is greater than the first cross-sectional size, the second longitudinal group of micropores being longitudinally distal to the first longitudinal group of micropores.

47. The microcatheter of claim 46, wherein a third longitudinal group of micropores of the plurality of micropores comprises a third cross-sectional size that is less than the second cross-sectional size, and wherein the third longitudinal group of micropores is longitudinally distal to the second longitudinal group of micropores.

48. The microcatheter of claim 44, wherein the cross-sectional areas of the plurality of micropores alternate successively longitudinally between a first second cross-sectional size and a second cross-sectional size that differs from the first cross-sectional size.

49. The microcatheter of claim 1, wherein the plurality of micropores each define a circular cross-sectional shape.

50. The microcatheter of claim 1, wherein the plurality of micropores each define an oval cross-sectional shape.

51. The microcatheter of claim 1, wherein the plurality of micropores each define a noncircular shape.

52. The microcatheter of claim 51, wherein the plurality of non-circular shaped micropores each define a maximum longitudinal size that is greater than a maximum lateral size.

53. The microcatheter of claim 1, wherein the plurality of micropores and the maximum inner diameter of the lumen of the free distal end are configured relative to each other suchAtty Ref . No.: 6473.001AWOthat the catheter body infuses at least 70% of the liquid therapeutic agent or diagnostic material introduced into the inner lumen into a diminutive vessel via the plurality of micropores, and less than or equal to 30% of the liquid therapeutic agent or diagnostic material introduced into the inner lumen into the diminutive vessel via the free distal end.

54. The microcatheter of claim 1, wherein the tubular wall structure is formed of at least one polymer layer or portion.

55. The microcatheter of claim 54, wherein the at least one polymer layer is formed of polyurethane, nylon, PEB A, a fluoropolymer or a combination thereof.

56. The microcatheter of claim 54, wherein the wall structure further comprises reinforcement material or members coupled with the at least one polymer layer or portion.

57. The microcatheter of claim 56, wherein the reinforcement material or members comprise one or more helical wires that extend from the proximal end portion to the distal end portion.

58. The microcatheter of claim 57, wherein the one or more helical wires comprise a wire with a helical coil pitch within the range of about 0.008 inches and about 0.012 inches.

59. The microcatheter of claim 1, wherein the tubular wall structure comprises an inner liner that forms the inner lumen, and at least one outer layer that extends over the inner liner layer.

60. The microcatheter of claim 59, wherein the inner liner is formed of a fluoropolymer material.

61. The microcatheter of claim 59, wherein the outer liner comprises an outer jacket layer.

62. The microcatheter of claim 61, wherein the outer jacket layer comprises at least one layer of helical fibers or strips.Atty Ref . No.: 6473.001AW063. The microcatheter of claim 59, wherein the outer layer comprises a hydrophilic coating.

64. The microcatheter of claim 1, wherein the first flexural rigidity at a longitudinal midpoint of the proximal end portion comprises at least one of:a flexural rigidity within the range of about 5e-06 Nm2to about 9e-06 Nm2; and a bending stiffness within the range of about 30 gf / cm2to about 46 gf / cm265. The microcatheter of claim 1, wherein the second flexural rigidity at a longitudinal midpoint of the medial portion comprises at least one of:a flexural rigidity within the range of about 3e-06 Nm2to about 5e-06 Nm2; and a bending stiffness within the range of about 8 gf / cm2to about 25 gf / cm2.

66. The microcatheter of claim 1, wherein the third flexural rigidity at a longitudinal midpoint of the distal end portion comprises at least one of:a flexural rigidity within the range of about le-06 Nm2to about 3e-06 Nm2; and a bending stiffness within the range of about 3.6 gf / cm2and about 16 gf / cm2.

67. The microcatheter of claim 1, wherein the third flexural rigidity at the distal free end of the distal end portion comprises a flexural rigidity within the range of about 2 gf / cm2and about 6.5 gf / cm2.

68. The microcatheter of claim 1, wherein the inner lumen of the free end portion of the distal end portion of the catheter body defines a maximum inner diameter of less than or equal to 0.6 mm.

69. The microcatheter of claim 68, wherein at least a free end portion of the distal end portion of the catheter body defines a maximum outer diameter of less than or equal to 0.9 mm.Atty Ref . No.: 6473.001AW070. The microcatheter of any one of claims 1-69, wherein the catheter body defines a longitudinal length extending from the proximal portion at the hub portion to the free distal end of at least 135 cm.

71. The microcatheter of claim 68, wherein the longitudinal length of the catheter body is less than or equal 170 cm.

72. The microcatheter of any one of claims 1-69, wherein the catheter body defines a longitudinal length extending from the proximal portion at the hub portion to the free distal end of at least 150 cm.

73. An endoluminal neurovascular microcatheter system, comprising:a microcatheter according to any one of claims 1-69; anda steerable catheter guidewire defining a maximum outer diameter of less than or equal to 0.6 mm.

74. The system of claim 73, wherein the guidewire comprises a longitudinal length of at least 180 cm, and wherein at least a distal end portion of the guidewire is curved, or is malleably shapable or plastically deformable into a curved shape.

75. The system of claim 73, wherein the catheter body defines a longitudinal length extending from the proximal portion at the hub portion to the free distal end of at least 135 cm.

76. The system of claim 75, wherein the longitudinal length of the catheter body is less than or equal to 170 cm.

77. The system of claim 73, wherein the catheter body defines a longitudinal length extending from the proximal portion at the hub portion to the free distal end of at least 150 cm.

78. The system of claim 73, wherein at least a free end portion of the distal end portion of the catheter body defines a maximum outer diameter of less than or equal to 0.9 mm, wherein the inner lumen of the free end portion of the distal end portion of the catheter bodyAtty Ref . No.: 6473.001AW0defines a maximum inner diameter of less than or equal to 0.6 mm, and wherein the guidewire defines a maximum outer diameter of less than or equal to 0.5 mm.

79. A method of treating a brain or a spine of a human patient via a diminutive vessel thereof, comprising;obtaining a microcatheter according to any one of claims 1-67;inserting a steerable catheter guidewire defining a maximum outer diameter of less than or equal to 0.6 mm into and through the inner lumen of the microcatheter;inserting the guidewire into a first vessel of a vascular system of human patient, and translating the guidewire through the vascular system to a diminutive neurovascular vessel of a brain or spine of the human patient; andtranslating the microcatheter over the guidewire and through the vascular system such that the distal end portion is positioned within a target site of the diminutive neurovascular vessel.

80. The method of claim 79, further comprising infusing the target site of the diminutive neurovascular vessel with a volume of a liquid therapeutic agent or diagnostic material via the plurality of micropores and the distal free end.

81. The method of claim 80, wherein at least 70% of the infused liquid therapeutic agent or diagnostic material is introduced into the target site of the diminutive neurovascular vessel via the plurality of micropores, and less than or equal to 30% of the infused liquid therapeutic agent or diagnostic material is introduced into the target site of the diminutive neurovascular vessel via the free distal end.

82. The method of claim 79, further comprising aspirating the target site of the diminutive neurovascular vessel by allowing biological material from within the diminutive neurovascular vessel at or proximate to the target site to flow into the inner lumen via at least the plurality of micropores, and longitudinally proximally through the catheter body to the proximal end portion.

83. The method of claim 79, wherein translating the guidewire through the vascular system comprises performing a series of incremental translations of the guidewire through the vascular system, wherein translating the microcatheter over the guidewire and throughAtty Ref . No.: 6473.001AW0the vascular system comprises performing a series of incremental translations of the microcatheter over the guidewire and through the vascular system, and wherein the incremental translations of the guidewire and the incremental translations of the microcatheter are performed in an alternating series.

84. The method of claim 79, wherein translating the microcatheter over the guidewire and through the vascular system such that the distal end portion is positioned within the target site of the diminutive neurovascular vessel comprises translating the distal end portion through at least 25 cm of the vascular system.

85. The method of claim 79, wherein translating the microcatheter over the guidewire and through the vascular system such that the distal end portion is positioned within the target site of the diminutive neurovascular vessel comprises translating the distal end portion through at least 50 cm of the vascular system.

86. The method of claim 79, wherein translating the microcatheter over the guidewire and through the vascular system such that the distal end portion is positioned within the target site of the diminutive neurovascular vessel comprises translating the distal end portion through at least 125 cm of the vascular system.

87. The method of claim 79, wherein the guidewire comprises a longitudinal length of at least 180 cm, and wherein at least a distal end portion of the guidewire is curved, or is malleably shapable or plastically deformable into a curved shape.

88. The method of claim 79, wherein at least a free end portion of the distal end portion of the catheter body defines a maximum outer diameter of less than or equal to 0.9 mm, wherein the inner lumen of the free end portion of the distal end portion of the catheter body defines a maximum inner diameter of less than or equal to 0.6 mm, and wherein the guidewire defines a maximum outer diameter of less than or equal to 0.5 mm.

89. A dual-lumen endoluminal neurovascular microcatheter, comprising:a hub portion configured to remain outside of the patient; anda catheter body being longitudinally elongated and extending longitudinally from a proximal end portion coupled to the hub portion to a free distal end at a distal end portionAtty Ref . No.: 6473.001AWOconfigured to access neurovascular vessels of a brain or spine of a human patient, the catheter body comprising:an inner tubular wall structure extending from the hub portion that defines a continuous, unobstructed inner lumen that is open at the free distal end; andan outer tubular wall structure extending from the hub portion that defines a continuous outer lumen that extends about the inner tubular wall structure and is closed at a distal end;wherein the catheter body is longitudinally variably flexible, and wherein the proximal end portion of the catheter body comprises a first flexural rigidity, a medial portion of the catheter body extending longitudinally between the proximal and distal end portions comprises a second flexural rigidity that is less than the first flexural rigidity, and the distal end portion of the catheter body comprises a third flexural rigidity that is less than the second flexural rigidity;wherein the distal end portion of the catheter body comprises a proximal radiopaque marker, a distal radiopaque marker, and a plurality of micropores extending through the outer tubular wall structure from the outer lumen to an exterior of the catheter body configured to infuse the neurovascular vessels with a liquid therapeutic agent or diagnostic material, andwherein the plurality of micropores are arranged in a longitudinally spaced successive pattern longitudinally between the proximal and distal radiopaque markers, and each micropores defines a minimum cross-sectional dimension of less than or equal to 0.01 inch and a cross-sectional area less than or equal to 0.05 mm2.

90. The dual-lumen microcatheter of claim 89, wherein the inner tubular wall structure defines a first radial wall thickness extending from the proximal end portion to the distal end portion, and wherein the outer tubular wall structure defines a second radial wall thickness extending from the proximal end portion to the distal end portion that is less than the first radial wall thickness.

91. The dual-lumen microcatheter of claim 89, wherein the outer tubular wall structure is more flexible than the inner tubular wall structure along a longitudinal length of the catheter body.Atty Ref . No.: 6473.001AW092. The dual-lumen microcatheter of claim 89, wherein the inner tubular wall structure defines a structural integrity that is greater than a structural integrity of the inner tubular wall structure along a longitudinal length of the catheter body.

93. The dual-lumen microcatheter of claim 89, wherein the inner tubular wall structure is self-supporting such that it naturally maintains the inner lumen in a substantially fully full open arrangement, and wherein the outer tubular wall structure is not self-supporting such that it does not naturally maintain the outer lumen in a substantially fully full open arrangement.

94. The dual-lumen microcatheter of claim 89, wherein the catheter body further comprises a plurality of strut portions extending between and coupling portions of an outer side of the inner tubular wall structure and portions of an inner side of the outer tubular wall structure.

95. The dual-lumen microcatheter of claim 94, wherein the plurality of strut portions radially space portions of the outer tubular wall structure and the inner tubular wall structure.

96. The dual-lumen microcatheter of claim 89, wherein the distal end of the outer lumen is closed via an end structure that extends radially between the inner and outer tubular wall structures and seals off a distal portion of the outer lumen.

97. The dual-lumen microcatheter of claim 96, wherein the end structure is the distal radiopaque marker.

98. The dual-lumen microcatheter of claim 96, wherein the end structure is a radially extending wall.

99. The dual-lumen microcatheter of claim 96, wherein the distal end of the outer lumen is closed via the outer and inner tubular wall structures being sealed to each other.

100. The dual-lumen microcatheter of claim 89, wherein the distal end of the outer lumen is longitudinally proximal of the free distal end of the catheter body.Atty Ref . No.: 6473.001AW0101. The dual-lumen microcatheter of claim 89, wherein the catheter body defines a longitudinal length within the range of about 25 cm to about 140 cm.

102. The dual-lumen microcatheter of claim 101, wherein at least a free end portion of the distal end portion of the catheter body longitudinally extending to the free distal end defines a maximum outer diameter of less than or equal to 1.5 mm.

103. The dual-lumen microcatheter of claim 102, wherein the proximal end portion of the catheter body defines a maximum outer cross-sectional diameter of less than or equal to 2 mm.

104. The dual-lumen microcatheter of claim 89, wherein the inner lumen defines a maximum inner diameter within the range of about 0.3 mm to about 0.7 mm.

105. The dual-lumen microcatheter of claim 89, wherein the outer lumen defines a maximum radial thickness within the range of about 0.1 mm to about 0.4 mm.

106. The dual-lumen microcatheter of claim 105, wherein the inner lumen defines a maximum inner diameter of less than or equal to 0.7 mm at least at the free distal end.

107. The dual-lumen microcatheter of claim 89, wherein a portion of the catheter body comprising the proximal radiopaque marker, the distal radiopaque marker, and the plurality of micropores defines an infusion portion of the distal end portion of the catheter body, and wherein the infusion portion comprises a longitudinal length of at least 3 cm.

108. The dual-lumen microcatheter of claim 107, wherein the infusion portion comprises a longitudinal length of at least 5 cm.

109. The dual-lumen microcatheter of claim 107, wherein the infusion portion comprises a longitudinal length of at least 10 cm.

110. The dual-lumen microcatheter of claim 107, wherein the infusion portion comprises a longitudinal length within the range of 3 cm to 30 cm.Atty Ref . No.: 6473.001AW0111. The dual-lumen microcatheter of claim 89, wherein the micropores are longitudinally spaced such that adjacent micropores of the plurality of micropores are longitudinally spaced apart at least 1 mm from each other.

112. The dual-lumen microcatheter of claim 89, wherein the plurality of micropores are arranged in a longitudinally and circumferentially spaced successive pattern.

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