Patent Grant
10576099
The present technology is related to systems, devices, and methods for treating intracranial aneurysms.
An intracranial aneurysm is a portion of an intracranial blood vessel that bulges outward from the blood vessel's main channel. This condition often occurs at a portion of a blood vessel that is abnormally weak because of a congenital anomaly, trauma, high blood pressure, or for another reason. Once an intracranial aneurysm forms, there is a significant risk that the aneurysm will eventually rupture and cause a medical emergency with a high risk of mortality due to hemorrhaging. When an unruptured intracranial aneurysm is detected or when a patient survives an initial rupture of an intracranial aneurysm, vascular surgery is often indicated. One conventional type of vascular surgery for treating an intracranial aneurysm includes using a microcatheter to dispose a platinum coil within an interior volume of the aneurysm. Over time, the presence of the coil should induce formation of a thrombus. Ideally, the aneurysm's neck closes at the site of the thrombus and is replaced with new endothelial tissue. Blood then bypasses the aneurysm, thereby reducing the risk of aneurysm rupture (or re-rupture) and associated hemorrhaging. Unfortunately, long-term recanalization (i.e., restoration of blood flow to the interior volume of the aneurysm) after this type of vascular surgery occurs in a number of cases, especially for intracranial aneurysms with relatively wide necks and/or relatively large interior volumes.
Another conventional type of vascular surgery for treating an intracranial aneurysm includes deploying a flow diverter within the associated intracranial blood vessel. The flow diverter is often a mesh tube that causes blood to preferentially flow along a main channel of the blood vessel while blood within the aneurysm stagnates. The stagnant blood within the aneurysm should eventually form a thrombus that leads to closure of the aneurysm's neck and to growth of new endothelial tissue, as with the platinum coil treatment. One significant drawback of flow diverters is that it may take weeks or months to form aneurysmal thrombus and significantly longer for the aneurysm neck to be covered with endothelial cells for full effect. This delay may be unacceptable when risk of aneurysm rupture (or re-rupture) is high. Moreover, flow diverters typically require antiplatelet therapy to prevent a thrombus from forming within the main channel of the blood vessel at the site of the flow diverter. Antiplatelet therapy may be contraindicated shortly after an initial aneurysm rupture has occurred because risk of re-rupture at this time is high and antiplatelet therapy tends to exacerbate intracranial hemorrhaging if re-rupture occurs. For these and other reasons, there is a need for innovation in the treatment of intracranial aneurysms. Given the severity of this condition, innovation in this field has immediate life-saving potential.
Various examples of aspects of the subject technology are described as numbered clauses (1, 2, 3, etc.) for convenience. These are provided as examples and do not limit the subject technology. It is noted that any of the dependent clauses may be combined in any combination, and placed into a respective independent clause, e.g., Clause 1, Clause 13, or Clause 22.
1. A method for treating an aneurysm, the method comprising:
2. The method of Clause 1 wherein the aneurysm is an intracranial aneurysm.
3. The method of Clause 1 wherein:
4. The method of Clause 1 wherein delivering the biopolymer and the chemical crosslinking agent from the lumen into the internal volume includes delivering the biopolymer and the chemical crosslinking agent from the lumen into the internal volume as components of a single cohesive strand that at least partially agglomerates to form a mass occupying at least 75% of the internal volume, and wherein the internal volume is a total internal volume of the aneurysm.
5. The method of Clause 1, further comprising:
6. The method of Clause 5 wherein:
7. The method of Clause 1 wherein the biopolymer includes chitosan, a derivative of chitosan, an analog of chitosan, or a combination thereof.
8. The method of Clause 7 wherein the chemical crosslinking agent includes genipin, a derivative of genipin, an analog of genipin, or a combination thereof.
9. The method of Clause 8 wherein mixing the biopolymer and the chemical crosslinking agent includes mixing the biopolymer and the chemical crosslinking agent such that a weight ratio of the biopolymer to the chemical crosslinking agent is within a range from 10:1 to 100:1.
10. The method of Clause 1, further comprising reinforcing a neck of the aneurysm while the biopolymer and the chemical crosslinking agent are disposed within the internal volume and while the chemical crosslinking is ongoing.
11. The method of Clause 10, further comprising:
12. The method of Clause 10, further comprising:
13. A method for treating an aneurysm, the method comprising:
14. The method of Clause 13 wherein the aneurysm is an intracranial aneurysm.
15. The method of Clause 13 wherein:
16. The method of Clause 13 wherein disposing the tissue scaffold material within the internal volume includes delivering the tissue scaffold material into the internal volume as a single cohesive strand that at least partially agglomerates to form a mass occupying at least 75% of the internal volume, and wherein the internal volume is a total internal volume of the aneurysm.
17. The method of Clause 13 wherein the tissue scaffold material includes a physical crosslinking agent.
18. The method of Clause 17 wherein:
19. The method of Clause 13 wherein the biopolymer includes chitosan, an analog of chitosan, or a combination thereof.
20. The method of Clause 19 wherein the chemical crosslinking agent includes genipin, a derivative of genipin, an analog of genipin, or a combination thereof.
21. The method of Clause 20 wherein a weight ratio of the biopolymer to the chemical crosslinking agent within the tissue scaffold material is within a range from 10:1 to 100:1.
22. A system for treating an aneurysm, the system comprising:
23. The system of Clause 22, wherein the biopolymer has a non-zero degree of chemical crosslinking within the first precursor material.
24. The system of Clause 22 wherein:
25. The system of Clause 24 wherein:
26. The system of Clause 22 wherein the biopolymer includes chitosan, a derivative of chitosan, an analog of chitosan, or a combination thereof.
27. The system of Clause 26 wherein the chemical crosslinking agent includes genipin, a derivative of genipin, an analog of genipin, or a combination thereof.
28. The system of Clause 22 wherein:
29. The system of Clause 28 wherein the contrast agent is selected to provide diminishing radiopacity.
30. The system of Clause 28 wherein the contrast agent includes iohexol, a derivative of iohexol, an analog of iohexol, or a combination thereof.
31. A method for at least partially filling a volume at a treatment location, the method comprising:
advancing a catheter toward the treatment location, wherein the catheter includes an elongate lumen and an exit port at a distal end portion of the lumen;
mixing a biopolymer and a chemical crosslinking agent to initiate chemical crosslinking of the biopolymer;
flowing the biopolymer and the chemical crosslinking agent toward the volume via the lumen while the chemical crosslinking is ongoing; and
delivering the biopolymer and the chemical crosslinking agent from the lumen into the volume via the exit port while the chemical crosslinking is ongoing.
32. The method of Clause 31, wherein advancing the catheter comprises advancing the catheter through a blood vessel.
33. The method of Clause 31, wherein the treatment location comprises an aneurysm and the volume comprises an internal volume of the aneurysm.
34. The method of Clause 31, wherein the treatment location comprises a vein and the volume comprises a lumen of the vein.
35. The method of Clause 34, wherein the vein is located in a leg.
36. The method of Clause 35, further comprising reducing leg vein varicosity by occluding the vein lumen via said delivering.
37. The method of Clause 31, wherein the treatment location comprises an artery that vascularizes a tumor and the volume comprises a lumen of the artery.
38. The method of Clause 31, wherein the treatment location comprises a vascular or cardiovascular implant and the volume comprises an endoleak.
39. The method of Clause 31 wherein:
40. The method of Clause 31 wherein delivering the biopolymer and the chemical crosslinking agent from the lumen into the volume includes delivering the biopolymer and the chemical crosslinking agent from the lumen into the volume as components of a single cohesive strand that at least partially agglomerates to form a mass occupying at least 75% of the volume, and wherein the volume is a total internal volume of an aneurysm.
41. The method of Clause 31, further comprising:
42. The method of Clause 41 wherein:
43. The method of Clause 31 wherein the biopolymer includes chitosan, a derivative of chitosan, an analog of chitosan, or a combination thereof.
44. The method of Clause 43 wherein the chemical crosslinking agent includes genipin, a derivative of genipin, an analog of genipin, or a combination thereof.
45. The method of Clause 44 wherein mixing the biopolymer and the chemical crosslinking agent includes mixing the biopolymer and the chemical crosslinking agent such that a weight ratio of the biopolymer to the chemical crosslinking agent is within a range from 10:1 to 100:1.
46. The method of Clause 31, wherein the treatment location comprises an aneurysm and the volume comprises an internal volume of the aneurysm, and further comprising reinforcing a neck of the aneurysm while the biopolymer and the chemical crosslinking agent are disposed within the internal volume and while the chemical crosslinking is ongoing.
47. The method of Clause 46, further comprising:
48. The method of Clause 47, further comprising:
Many aspects of the present technology can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Instead, emphasis is placed on illustrating clearly the principles of the present technology. For ease of reference, throughout this disclosure identical reference numbers may be used to identify identical, similar, or analogous components or features of more than one embodiment of the present technology.
Systems, devices, and methods in accordance with embodiments of the present technology can at least partially address one or more problems associated with conventional technologies whether or not such problems are stated herein. Methods for treating intracranial aneurysms in accordance with at least some embodiments of the present technology include introducing an injectable scaffold material into the internal volume of an intracranial aneurysm (aneurysm internal volume). In animal studies, such methods have been found to provide (a) complete or nearly complete volumetric filling of the aneurysm internal volume, and (b) complete or nearly complete coverage of the aneurysm neck with new endothelial tissue. These features, among others, are expected to result in a lower recanalization rate than that of platinum coil treatments and faster aneurysm occlusion than that of flow diverters. Furthermore, the injectable scaffold material is expected to be bioabsorbed and thereby reduced in volume over time. Thus, unlike platinum coils, the injectable scaffold is expected to have little or no long-term mass effect. Furthermore, the injectable scaffold material can be configured to have diminishing radiopacity; therefore, when so configured it will not interfere future CT and MM imaging and procedures. Embodiments of the present technology can have these and/or other features and advantages relative to conventional counterparts whether or not such features and advantages are described herein.
Specific details of systems, devices, and methods for treating intracranial aneurysms in accordance with embodiments of the present technology are described herein with reference to
The system 100 can further include an injection syringe 116 and a first catheter 118 configured to deliver and receive, respectively, a mixture of the first and second precursor materials 103, 105 from the injection syringe 116. The injection syringe 116 can include a barrel 120, an exit port 122 at one end of the barrel 120, and a plunger 124 slidably received within the barrel 120 via an opposite end of the barrel 120. The first catheter 118 can include an elongate shaft 126 defining an elongate lumen (not shown), an exit port 128 at a distal end portion of the lumen, and a coupler 130 at a proximal end portion of the lumen. The coupler 130 can be configured to form a secure fluidic connection between the lumen and the exit port 122 of the injection syringe 116. The first catheter 118 can be configured to receive a mixture of the first and second precursor materials 103, 105 from the injection syringe 116 via the coupler 130 and to convey the mixture toward and into the internal volume of an intracranial aneurysm (or other treatment location such as any of those described herein) via the lumen and via the exit port 128. The system 100 can further include a second catheter 132 including an elongate sheath 134 and a wire 136 slidably disposed within the sheath 134. At a distal end portion of the wire 136, the second catheter 132 can include an atraumatic hook 138. The first and second catheters 118, 132 can be steerable or non-steerable and can be configured for deployment by guide wire, by guide sheath, or in another suitable manner. Furthermore, the first and second catheters 118, 132 can be of suitable sizes to both be located within an intracranial blood vessel at the same time. In at least some cases, the first catheter 118 is at most 3 French and/or the second catheter 132 is at most 3 French.
The system 100 can also include a tubular stent such as a flow diverter 140 carried by the second catheter 132 proximal to the hook 138. The flow diverter 140 can have an expanded state (as shown) and a low-profile state (e.g., a collapsed state) in which the flow diverter 140 is sufficiently compact to move longitudinally within the sheath 134. In at least some cases, the flow diverter 140 includes filaments that shift relative to one another as the flow diverter 140 moves between its expanded and low-profile states. The flow diverter 140, for example, can be a braided tube.
With reference now to
With reference to
The first and second precursor materials 103, 105 (
Mixing the biopolymer of the first precursor material 103 and the chemical crosslinking agent of the second precursor material 105 can initiate chemical crosslinking of the biopolymer. After the first and second precursor materials 103, 105 are mixed, chemical crosslinking of the biopolymer occurs for enough time to allow the resulting tissue scaffold material 310 to be delivered to the aneurysm 302 before becoming too viscous to move through the lumen of the first catheter 118. In addition, the period of time during which chemical crosslinking of the biopolymer occurs can be short enough to reach a target deployed viscosity within a reasonable time (e.g., in the range of 10-60 minutes; or at most 40 minutes, 30 minutes, 20 minutes, or 10 minutes) after delivery. The target deployed viscosity can be high enough to cause an agglomeration of the tissue scaffold material 310 to remain within the internal volume of the aneurysm 302 without reinforcing the neck 304.
In at least some cases, the biopolymer has a non-zero degree of chemical crosslinking within the first precursor material 103 before mixing with the chemical crosslinking agent. This can be useful, for example, to customize the curing window for the tissue scaffold material 310 so that it corresponds well with an expected amount of time needed to deliver the material to the aneurysm 302. The degree of chemical crosslinking of the biopolymer within the first precursor material 103 before mixing with the chemical crosslinking agent, the ratio of the biopolymer to the chemical crosslinking agent, and/or one or more other variables can be selected to cause the tissue scaffold material 310 to have a viscosity suitable for delivery to the aneurysm 302 via the lumen of the first catheter 118 for a suitable period of time (e.g., a period within a range from 10 minutes to 40 minutes) after mixing of the first and second precursor materials 103, 105. In at least some cases, the first and second precursor materials 103, 105 are mixed in proportions that cause a weight ratio of the biopolymer to the chemical crosslinking agent in the resulting tissue scaffold material 310 to be within a range from 10:1 to 100:1, such as from 10:1 to 30:1, or from 15:1 to 50:1, or from 15:1 to 25:1. In a particular example, the first and second precursor materials 103, 105 are mixed in proportions that cause a weight ratio of the biopolymer to the chemical crosslinking agent in the resulting tissue scaffold material 310 to be 30:1.
Use of a biopolymer instead of an artificial polymer in the first precursor material 103 may be advantageous because biopolymers tend to be more readily bioabsorbed than artificial polymers and/or for other reasons. Furthermore, use of a chemical crosslinking agent instead of a physical crosslinking agent (i.e., a crosslinking agent that forms noncovalent crosslinks between chains of the biopolymer) in the second precursor material 105 may be advantageous because chemically crosslinked polymers tend to be more cohesive than physically crosslinked polymers and/or for other reasons. In the context of forming a tissue scaffold within an aneurysm, high cohesiveness of the tissue scaffold material 310 may be more important than it is in other contexts to secure the cured tissue scaffold material 310 within the aneurysm 302. For example, high cohesiveness of the tissue scaffold material 310 may reduce or eliminate the possibility of a piece of the tissue scaffold material 310 breaking free and entering a patient's intracerebral blood stream during delivery.
The first and second precursor materials 103, 105 may include other components and/or the system 100 may include other precursor materials intended for mixing with the first and second precursor materials 103, 105. For example, the first, second, and/or another precursor material may include a physical crosslinking agent. The presence of a physical crosslinking agent may be useful to form physical crosslinks that complement chemical crosslinks from the chemical crosslinking agent. The combination of chemical and physical crosslinks may enhance the cohesiveness of the tissue scaffold material 310. Suitable physical crosslinking agents for use with chitosan-based biopolymers include glycerophosphate, mannitol, glucose, and derivatives and analogs thereof. In these and other cases, the tissue scaffold material 310 may include multiple chemical crosslinking agents and/or multiple physical crosslinking agents.
A contrast agent is another component that may be added to the precursor materials. The presence of a contrast agent within the tissue scaffold material 310 can be useful to visualize delivery of the tissue scaffold material 310 using fluoroscopy. One problem with using conventional platinum coils in intracranial aneurysms is that the persistent radiopacity of the coils tends to interfere with visualizing other aspects of the treatment in follow-up imaging. For example, the presence of platinum coils within an aneurysm may make it difficult or impossible to detect by fluoroscopy the presence of blood-carried contrast agent that would otherwise indicate recanalization. In at least some embodiments of the present technology, a contrast agent within the tissue scaffold material 310 is selected to provide radiopacity that diminishes over time. For example, the contrast agent may initially be radiopaque to facilitate delivery of the tissue scaffold material 310 and then become less radiopaque to facilitate follow-up imaging. In a particular example, the first, second, and/or another precursor material includes iohexol or a derivative or analog thereof as a suitable contrast agent.
With reference again to
With reference to
With reference to
After the flow diverter 140 has been stowed within the sheath 134, the method 200 can include removing the second catheter 132 (block 218). As shown in
The following examples are provided to illustrate certain particular embodiments of the disclosure. It should be understood that additional embodiments not limited to the particular features described are consistent with the following examples.
A tissue scaffold material was prepared as a solution of 3.8% chitosan, 2.9% glycerophosphate, and 0.1% genipin (all percentages weight/volume). The ratio of genipin to chitosan in the resulting tissue scaffold material was 38:1.
A flow loop with a model aneurysm (10 mm pouch diameter; 4 mm neck diameter) was used for bench testing the tissue scaffold material (Example 1). The distal end of a MARKSMAN® (ID 0.027″) microcatheter was located within the model aneurysm and secured by deploying a PIPELINE FLEX™ Embolization Device (Medtronic) (“P-Flex device”) across the neck of the model aneurysm. The tissue scaffold material was injected into the model aneurysm via the microcatheter within 10 minutes of mixing the chitosan, glycerophosphate, and genipin solutions. The resulting mass of tissue scaffold material was found to be stable within the model aneurysm for 2 hours under simulated pulsatile blood flow of 600 mL per minute.
Two model aneurysms (distal and proximal) were created in the carotid artery of each of two canine subjects. The model aneurysms had pouch diameters of approximately 10 mm and neck diameters of approximately 4 mm. Tissue scaffold material (Example 1) was injected into the distal and proximal model aneurysms of the first subject and into the distal model aneurysm of the second subject via the microcatheter (Example 2). P-Flex devices were deployed across the neck of the proximal model aneurysm of the first subject and across the necks of the distal and proximal model aneurysms of the second subject. After 9 days, the subject animals were euthanized and the model aneurysms were biopsied. The biopsies showed that the model aneurysms having the tissue scaffold material and a P-Flex device contained well-developed aneurismal thrombi encompassing all or nearly all of the model aneurysms' internal volumes. The model aneurysm having the tissue scaffold material and not having a P-Flex device included an aneurismal thrombus encompassing most of the model aneurysm's internal volume, but with some vacant areas at the perimeter of the internal volume near the model aneurysm's neck. The model aneurysm having a P-Flex device and not having the tissue scaffold material did not contain an aneurismal thrombus. No inflammation was observed in the parent vessels.
Two model aneurysms (distal and proximal) were created in the carotid artery of each of two canine subjects. The model aneurysms had pouch diameters of approximately 10 mm and neck diameters of approximately 4 mm. Tissue scaffold material (Example 1) was injected into the distal model aneurysm of the first subject and into the distal and proximal model aneurysms of the second subject via the microcatheter (Example 2). Platinum coils were introduced into the proximal model aneurysm of the first subject. A P-Flex device and a SOLITAIRE® Stent were deployed, respectively, across the necks of the distal and proximal model aneurysms of the first subject. After 90 days, the subject animals were euthanized and the model aneurysms were biopsied. The biopsies showed that the model aneurysms having the tissue scaffold material and not having a P-Flex device or a SOLITAIRE® stent as well as the model aneurysm having the tissue scaffold material and the P-Flex device showed complete endothelial coverage at the aneurismal neck.
This disclosure is not intended to be exhaustive or to limit the present technology to the precise forms disclosed herein. Although specific embodiments are disclosed herein for illustrative purposes, various equivalent modifications are possible without deviating from the present technology, as those of ordinary skill in the relevant art will recognize. In some cases, well-known structures and functions have not been shown and/or described in detail to avoid unnecessarily obscuring the description of the embodiments of the present technology. Although steps of methods may be presented herein in a particular order, in alternative embodiments the steps may have another suitable order. Similarly, certain aspects of the present technology disclosed in the context of particular embodiments can be combined or eliminated in other embodiments. Furthermore, while advantages associated with certain embodiments may have been disclosed in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages or other advantages disclosed herein to fall within the scope of the present technology.
Throughout this disclosure, the singular terms “a,” “an,” and “the” include plural referents unless the context clearly indicates otherwise. Similarly, unless the word “or” is expressly limited to mean only a single item exclusive from the other items in reference to a list of two or more items, then the use of “or” in such a list is to be interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of the items in the list. Additionally, the terms “comprising” and the like may be used herein to mean including at least the recited feature(s) such that any greater number of the same feature(s) and/or one or more additional types of features are not precluded. Directional terms, such as “upper,” “lower,” “front,” “back,” “vertical,” and “horizontal,” may be used herein to express and clarify the relationship between various elements. It should be understood that such terms do not denote absolute orientation. Reference herein to “one embodiment,” “an embodiment,” or similar formulations means that a particular feature, structure, operation, or characteristic described in connection with the embodiment can be included in at least one embodiment of the present technology. Thus, the appearances of such phrases or formulations herein are not necessarily all referring to the same embodiment. Furthermore, various particular features, structures, operations, or characteristics may be combined in any suitable manner in one or more embodiments of the present technology.
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