Patent Application
20220287733
The present technology relates to devices, systems, and methods for disrupting obstructions in body lumens. In particular, the present technology is directed to devices, systems, and methods for detecting and disrupting clot material in blood vessels.
Stroke is a serious medical condition that can cause permanent neurological damage, complications, and death. Ischemic stroke is the result of a thrombus or embolus obstructing blood flow in a cerebral blood vessel and thus to brain tissue, leading to dysfunction of the affected brain tissue. As approximately two million neurons die each minute following onset of a stroke, it is critical that the stroke be diagnosed and treated as quickly as possible to preserve function of the affected brain tissue.
A variety of approaches exist for treating patients experiencing an ischemic stroke. For example, a clinician may administer anticoagulants (e.g., warfarin) or thrombolytic agents (e.g., tissue plasminogen activator (tPA)), or may undertake intravascular interventions such as mechanical thrombectomy procedures. However, such approaches suffer from certain drawbacks. For example, there is a limited window in which thrombolytic agents can be administered following stroke onset. Further, thrombolytic agents such as tPA have limited efficacy in treating large vessel occlusions and may cause adverse events if improperly administered to a patient experiencing a hemorrhagic stroke. While mechanical thrombectomy procedures have a longer administration window and can be more effective than thrombolytic agents alone in some cases, such procedures require advanced imaging, specific equipment, and highly skilled and trained clinicians. Consequently, mechanical thrombectomy is not an accessible treatment option for many patients. Further, delays in time to treatment by mechanical thrombectomy as a result of time required to transport a patient to an appropriate facility and prepare the patient for the procedure can result in greater neurological damage, disability, and mortality. Accordingly, improved systems and methods for treating stroke are needed.
The present technology relates to systems and methods for disrupting obstructions such as clot material in body lumens. In particular embodiments, the present technology relates to systems and methods for noninvasively detecting and disrupting blood clots in cerebral blood vessels. The subject technology is illustrated, for example, according to various aspects described below, including with reference to
1. A method comprising:
2. The method of Clause 1, wherein the first data comprises three-dimensional coordinates.
3. The method of Clause 1 or Clause 2, wherein the second data comprises a three-dimensional position vector.
4. The method of any one of Clauses 1 to 3, wherein the reference marker is a first reference marker, the method further comprising positioning second and third reference markers proximate a head of the patient.
5. The method of any one of Clauses 1 to 4, wherein the reference marker is extracorporeally-positioned.
6. The method of any one of Clauses 1 to 5, wherein the reference marker is retroreflective.
7. The method of any one of Clauses 1 to 6, wherein the reference marker is radiopaque.
8. The method of any one of Clauses 1 to 7, wherein obtaining the first data comprises obtaining an image of the reference marker using an optical camera system.
9. The method of Clause 8, wherein the optical camera system comprises at least two cameras.
10. The method of any one of Clauses 1 to 9, wherein obtaining the first data comprises determining three-dimensional coordinates of the reference marker using a position sensing device.
11. The method of any one of Clauses 1 to 10, wherein obtaining the first data comprises obtaining an image of the reference marker using a medical imaging device.
12. The method of Clause 11, wherein the medical imaging device uses a modality comprising x-ray, fluoroscopy, magnetic resonance imaging, computed tomography, ultrasound, positron emission tomography, single photon emission coherence tomography, optical coherence tomography, magnetic particle imaging, or magnetic particle spectroscopy.
13. The method of Clause 11 or Clause 12, wherein obtaining the second data comprises obtaining an image of the patient and the clot using the medical imaging device.
14. The method of any one of Clauses 1 to 13, further comprising marking the clot with a marking agent.
15. The method of Clause 14, wherein the marking agent is a biomarker.
16. The method of Clause 15, wherein the biomarker is a peptide.
17. The method of Clause 16, wherein the peptide is a fibrin-binding peptide.
18. The method of Clause 14, wherein the marking agent is a nanoparticle.
19. The method of Clause 18, wherein the nanoparticle is an iron oxide nanoparticle.
20. The method of Clause 18, wherein the nanoparticle is a gold nanoparticle.
21. The method of Clause 14, wherein the marking agent is a contrast agent.
22. The method of Clause 21, wherein the contrast agent comprises microbubbles or a radiotracer.
23. The method of any one of Clauses 14 to 22, wherein marking the clot comprises intravenously administering the marking agent to the patient.
24. The method of any one of Clauses 1 to 23, wherein positioning the reference marker, obtaining first data, obtaining second data, determining a position of the clot relative to the coordinate system, delivering energy, and marking the clot occur within a vehicle.
25. The method of Clause 24, wherein the vehicle is an ambulance.
26. The method of any one of Clauses 1 to 25, further comprising administering a fibrinolytic agent to the patient.
27. The method of any one of Clauses 1 to 26, further comprising intravenously administering a cavitation-facilitating agent to the patient.
28. The method of any one of Clauses 1 to 27, wherein the energy delivery device is a high-intensity focused ultrasound device.
29. The method of any one of Clauses 1 to 28, further comprising modifying a position or an orientation of the patient based on the position of the clot relative to the coordinate system.
30. The method of any one of Clauses 1 to 29, further comprising modifying a position or an orientation of the energy delivery device based on the position of the clot relative to the coordinate system.
31. The method of any one of Clauses 1 to 30, further comprising modifying a parameter of the energy delivery device based on the position of the clot relative to the coordinate system.
32. The method of Clause 31, wherein the parameter comprises a frequency, an acoustic power, a pulse width, a pulse duration, a number of pulses, or a treatment duration.
33. A method comprising:
34. The method of Clause 33, wherein obtaining the data characterizing the position of the clot relative to the global coordinate system comprises obtaining data characterizing the position of the clot relative to the local coordinate system of the detection system and, based on the relationship between the local and global coordinate systems, determining the position of the clot relative to the global coordinate system.
35. The method of Clause 33 or Clause 34, wherein the relationship comprises a transformation matrix.
36. The method of any one of Clauses 33 to 35, wherein the data comprises three-dimensional coordinates.
37. The method of any one of Clauses 33 to 36, wherein the detection system comprises a medical imaging device.
38. The method of any one of Clauses 33 to 37, wherein the marking agent comprises a peptide, a nanoparticle, or a contrast agent.
39. The method of any one of Clauses 33 to 38, wherein the focused energy is high-intensity focused ultrasound energy.
40. The method of any one of Clauses 33 to 39, further comprising positioning a reference marker proximate the patient.
41. The method of Clause 40, further comprising obtaining data characterizing a position of the reference marker relative to the global coordinate system of the treatment environment with the detection system.
42. A non-transitory computer readable medium having stored thereon instructions executable by a computing device to cause the computing device to perform functions comprising:
43. The non-transitory computer-readable medium of Clause 42, wherein the first data comprises three-dimensional coordinates.
44. The non-transitory computer-readable medium of Clause 42 or Clause 43, wherein the second data comprises a three-dimensional position vector.
45. The non-transitory computer-readable medium of Clause 42 or Clause 43, wherein the second data comprises three-dimensional coordinates.
46. The non-transitory computer-readable medium of any one of Clauses 42 to 45, wherein causing the energy delivery device to deliver focused energy to the treatment location comprises modifying a position of the energy delivery device.
47. The non-transitory computer-readable medium of any one of Clauses 42 to 46, wherein causing the energy delivery device to deliver focused energy to the treatment location comprises modifying a parameter of the energy delivery device.
48. A method for treating a patient in a treatment environment, the patient having a blood clot, wherein the method comprises:
49. The method of Clause 48, wherein the reference marker is a first reference marker and the method further comprises:
50. The method of Clause 48 or Clause 49, further comprising determining whether the patient is suffering a hemorrhagic or ischemic stroke based on the imaging.
51. The method of any one of Clauses 48 to 50, further comprising delivering itPA to the clot prior to delivering the focused energy.
52. The method of any one of Clauses 48 to 51, wherein the marking agent is a thrombus-binding peptide or nano-particles.
53. The method of any one of Clauses 48 to 52, wherein the focused energy is high-intensity focused ultrasound (HIFU).
54. The method of any one of Clauses 48 to 53, wherein the time to perform the method is about 1 to 2 hours.
55. The method of any one of Clauses 48 to 54, wherein the clot is a cerebral blood clot and the reference marker is positioned on the patient's head.
56. The method of any one of Clauses 48 to 55, wherein the marked clot and the reference marker are imaged with a CT scanner or an ultrasound scanner.
Many aspects of the present disclosure 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 disclosure.
The system 100 of the present technology is shown in
The detection system 102 and/or energy delivery device 106 may have a fixed position within the treatment environment, or may be movable within the treatment environment. In some embodiments, the detection system 102 and the energy delivery device 106 are integrated into a single device, and in some embodiments the detection system 102 and energy delivery device 106 are distinct components that are movable relative to one another.
In some embodiments, for example as shown in
The detection system 102 may be configured to determine the position of clot material within the treatment environment, such as the three-dimensional coordinates of the clot material. In some embodiments, the detection system 102 comprises a first data collector 103 configured to obtain data characterizing the position of the clot (“clot position data”). The first data collector 103 can include any suitable device or collection of devices configured to obtain the clot position data. In some embodiments, the first data collector 103 is a medical imaging device comprising a modality such as, but not limited to, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, x-ray, fluoroscopy, angiography, positron emission tomography (PET), single photon emission coherence tomography (SPECT), optical coherence tomography (OCT), or magnetic particle imaging (MPI). Additionally or alternatively, the first data collector 103 may include a non-imaging measurement modality including, but not limited to, metal detection, electromagnetic sensing, inductive proximity sensing, capacitive proximity sensing, eddy current sensing, hall effect sensing, or magnetic particle spectroscopy.
According to some embodiments, the system 100 includes a marking agent configured to be delivered to the affected blood vessel proximate the clot material to facilitate identification and/or visualization of the clot material by the first data collector 103. The marking agent can be a nanoparticle (e.g., a gold nanoparticle, an iron oxide nanoparticle, etc.), a biomarker (e.g., a fibrin-binding peptide, etc.), a contrast agent (e.g., microbubbles, radiotracers, etc.), or others. In some embodiments, properties of the marking agent are based, at least in part, on the first data collector 103 modality. For example, the marking agent can be a gold nanoparticle when the first data collector 103 modality is CT, an iron oxide nanoparticle when the first data collector 103 modality is MPI, a radiotracer when the first data collector 103 modality is PET, etc. According to some embodiments, the marking agent is configured to be administered intravenously to the patient.
In some embodiments, the detection system 102 comprises a second data collector 104 configured to obtain data characterizing the position of a reference marker 112 within the treatment environment (“reference position data”). The second data collector 104 can include any suitable device or collection of devices configured to obtain the reference position data. The second data collector 104 may comprise a modality such as, but not limited to, optical imaging, optical proximity sensing, time of flight sensing, medical imaging, or a non-imaging measurement modality as described elsewhere herein. Properties of the reference marker 112 may be based, at least in part, on the second data collector 104 modality. For example, the reference marker 112 may be retroreflective for use with an optical imaging system or radiopaque for use with an a radiographic (e.g., x-ray, CT) imaging system.
In some embodiments, the reference marker 112 is positioned extracorporeally. For example, the reference marker 112 can be positioned proximate the head of the patient. In some embodiments, for example as shown in
According to some embodiments, the system 100 further comprises a computing device 110. The computing device 110 can be communicatively coupled to the detection system 102 and/or the energy delivery device 106. For example, the computing device 110 can be communicatively coupled to the first data collector 103 and/or the second data collector 104. Additionally or alternatively, the first data collector 103, the second data collector 104, and/or the energy delivery device 106 can each comprise a collection of devices in which one or more of the devices is a computing device. A computing device in accordance with the present technology can be any suitable combination of software and hardware. For example, the computing device can include a special purpose computer or data processor that is specifically programmed, configured, or constructed to perform one or more of the computer-executable instructions explained in detail herein. Additionally or alternatively, the computing device can include a distributed computing environment in which tasks or modules are performed by remote processing devices, which are linked through a communication network (e.g., a wireless communication network, a wired communication network, a cellular communication network, the Internet, a short-range radio network (e.g., via Bluetooth)). In a distributed computing environment, program modules may be located in both local and remote memory storage devices.
Computer-implemented instructions, data structures, and other data under aspects of the technology may be stored or distributed on computer-readable storage media, including magnetically or optically readable computer disks, as microcode on semiconductor memory, nanotechnology memory, organic or optical memory, or other portable and/or non-transitory data storage media. In some embodiments, aspects of the technology may be distributed over the Internet or over other networks (e.g. a Bluetooth network) on a propagated signal on a propagation medium (e.g., an electromagnetic wave(s), a sound wave) over a period of time, or may be provided on any analog or digital network (packet switched, circuit switched, or other scheme).
The system 100 can also include one or more input devices (e.g., touch screen, keyboard, mouse, microphone, camera, etc.) and/or one or more output devices (e.g., display, speaker, etc.) coupled to the computing device. In operation, a user can provide instructions to the computing device and receive output from the computing device via the input and output devices.
The energy delivery device 106 of the present technology can be configured to deliver energy to the clot and thereby disrupt the clot and restore blood flow in the previously obstructed blood vessel. In some embodiments, the energy delivery device 106 is a high-intensity focused ultrasound (HIFU) device configured to deliver focused ultrasound energy to the clot material. The energy delivery device 106 may be positioned extracorporeally. The energy delivery device 106 can be configured to receive data characterizing the position of the clot in the treatment environment from the detection system 102 and/or the computing device 110. Based on the data, a position, an orientation, and/or a parameter of the energy delivery device 106 can be modified to direct the energy to the clot material.
The method can continue with delivering focused energy from the extracorporeally-positioned energy delivery device 104 to the location, thereby disrupting the clot. In some embodiments, the reference marker is a first reference marker 112a and the method further comprises positioning a second reference marker 112b on the patient. In such embodiments, the method may proceed with imaging the marked clot and the first and second reference markers 112a, 112b to obtain position information characterizing the positions of the marked clot, the first reference marker 112a, and the second reference marker 112b relative to one another. The method can further include triangulating the location of the clot using the position information.
In any of the embodiments disclosed herein, the time to perform the method is about 1 to 2 hours, which is significantly faster than the current standard of care for stroke patients.
As described herein, the reference marker 404 may comprise properties based, at least in part, on the modality of the second data collector 406. For example, a reference marker 404 configured for use with a second data collector 406 comprising optical cameras may be retroreflective or may actively emit light (e.g., infrared light). The reference marker 404 may be configured to be removably adhered or coupled to the patient's head, as shown in
According to some embodiments, for example as shown in
As described elsewhere herein, the first data collector 402 may comprise any suitable device or collection of devices configured to obtain data characterizing a position of a clot in a blood vessel of a patient. For example, the first data collector 402 may be a CT scanner. In some embodiments, the detection system 400 may further comprise a marking agent configured to facilitate detecting the clot and obtaining data characterizing the position of the clot material by the first data collector 402.
As shown in
In some embodiments, for example as shown in
As noted above, a system for detecting and disrupting a clot in a blood vessel of a patient of the present technology may comprise a treatment environment including a detection system and an energy delivery device. In some embodiments, the treatment environment is mobile (e.g., a vehicle) such that the process 600 can be performed at a point of care remote from a hospital or clinic, thus minimizing adverse events associated with delays in treatment and the associated complications and adverse outcomes. As shown in
The process can proceed at block 606 with obtaining reference data (e.g., 3D coordinates) characterizing a position of each reference marker relative to a coordinate system of the treatment environment. In some embodiments, the reference data is obtained using the detection system. As previously described, the detection system can comprise a second data collector configured to obtain the reference data. Alternatively or additionally, the reference data may be obtained by a first data collector of the detection system. In some embodiments, the obtained reference data directly characterizes a position of each reference marker relative to a coordinate system of the treatment environment. In some embodiments, obtaining the reference data comprises obtaining local reference data characterizing a position of each reference marker relative to a local coordinate system of the second data collector. The local reference data may be converted to the reference data (e.g., by applying a transformation matrix obtained via calibration of the second data collector or first data collector).
In some embodiments, the process 600 includes block 608 in which the blood clot is marked with a marking agent. The marking agent may be administered intravenously to the patient upstream of the clot such that the marking agent travels downstream through the patient's vasculature until it reaches the clot and is positioned proximate the clot. As previously described, the marking agent can comprise a nanoparticle, a biomarker, a contrast agent, or another suitable material for facilitating detection of the clot.
The process 600 may proceed at block 610 with obtaining clot data characterizing a position of the clot in the coordinate system of the treatment environment. In some embodiments, the clot data is obtained using the detection system. As described elsewhere herein, the detection system can comprise a first data collector configured to obtain the clot data. Obtaining the clot data may comprise obtaining 3D coordinates of the clot and/or the reference markers to determine a position vector defining the distance between the position of the clot and the positions of the reference markers. The reference data (e.g., the 3D coordinates of each of the reference markers relative to the coordinate system of the treatment environment) and the position vector can be used to determine 3D coordinates of the clot relative to the coordinate system of the treatment environment (e.g., the clot data). In some embodiments, obtaining the clot data comprises obtaining local clot data characterizing the position of the clot relative to a local coordinate system of the first data collector and converting the local clot data into clot data (e.g., data characterizing the position of the clot relative to the coordinate system of the treatment environment) based on a relationship between the coordinate systems determined by calibration.
In some embodiments, focused energy is delivered to the clot to fragment the clot at block 612. The clot data obtained in block 610 can be received by an energy delivery device and a position, orientation, and/or parameter of the energy delivery device can be modified such that a position of a focal point of the focused energy is the same as the position of the clot within the treatment environment. Additionally or alternatively, a position and/or orientation of the patient can be modified to align the focal point with the clot. As described elsewhere herein, in some embodiments the energy delivery device is configured to deliver HIFU energy to the clot. The focused energy can induce fragmentation of the clot in order to clear the obstructing clot and restore blood flow to the affected blood vessel. In some embodiments, a thrombolytic agent (e.g., tPA, itPA) can be administered to the patient before, during, and/or after the delivery of energy to the clot. As previously described, a cavitation-facilitating agent may be administered to the patient before or during the delivery of energy to the clot to facilitate disruption of the clot.
Although many of the embodiments are described above with respect to systems, devices, and methods for detecting and disrupting obstructions such as clot material in cerebral blood vessels, the technology is applicable to other applications and/or other approaches, such as peripheral thrombolysis, thermal ablation, or targeted drug delivery. Moreover, other embodiments in addition to those described herein are within the scope of the technology. Additionally, several other embodiments of the technology can have different configurations, components, or procedures than those described herein. A person of ordinary skill in the art, therefore, will accordingly understand that the technology can have other embodiments with additional elements, or the technology can have other embodiments without several of the features shown and described above with reference to
As used herein, the terms “generally,” “substantially,” “about,” and similar terms are used as terms of approximation and not as terms of degree, and are intended to account for the inherent variations in measured or calculated values that would be recognized by those of ordinary skill in the art.
The descriptions of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Where the context permits, singular or plural terms may also include the plural or singular term, respectively. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. For example, while steps are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may also be combined to provide further embodiments.
Moreover, 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 term “comprising” is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and/or additional types of other features are not precluded. It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Further, while advantages associated with certain embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.
