EP-4734854-A2 - SYSTEMS AND METHODS FOR IMAGING AND MODULATING THE NERVOUS SYSTEM USING AN ULTRASOUND-BASED BRAIN-COMPUTER INTERFACE

Abstract

Devices, methods, and systems related to ultrasound imaging or modulating of the nervous system are described. The devices may comprise, for example, one or more ultrasound transducers, wherein an ultrasound transducer from the one or more ultrasound transducers can comprise an implantable ultrasound transducer, wherein the implantable ultrasound transducer can comprise a sonolucent window. The methods and systems may also comprise, for example, a method of imaging and/or modulating the nervous system of a subject using the one or more ultrasound transducers. The method of imaging and/or modulating the nervous system of the subject can be based on a closed-loop operation, wherein an iteration of the imaging and/or the modulating of the nervous system is based on a prior iteration. The closed-loop operation can comprise ultrasound imaging and ultrasound-based modulating or electrophysiological modulating. The methods can further comprise methods of analyzing ultrasound data, such as via an artificial neural network.

Inventors

• NORMAN, Sumner Lee
• AFLALO, Tyson Nikiyas Sunyata
• BIEDERMAN, WILLIAM
• PINTON, Gianmarco
• NASTASKIN, Claire
• FRICK, SEAN
• GUAN, CHARLES
• GRISILLO, Phil Joseph

Assignees

• Forest Neurotech, LLC

Dates

Publication Date

20260506

Application Date

20240629

Claims (20)

1. CLAIMS What is claimed is: 1. An implantable transducer comprising: a housing; a sonolucent window disposed, at least in part, at a first end of the housing; and an ultrasound array disposed within the housing proximate the first end, the ultrasound array configured to emit ultrasound waves to an outside environment via the sonolucent window.
2. 2. The implantable transducer of claim 1, further comprising one or more one circuit boards disposed within the housing, the one or more circuit boards comprising one or more electronic components disposed thereon, the one or more electronic components and configured to send one or more signals to the ultrasound array.
3. 3. The implantable transducer of claim 2, wherein the one or more electronic components disposed on the circuit board are configured to process data received from the ultrasound array, the data indicative of brain function in a subject.
4. 4. The implantable transducer of claim 2 or 3, wherein the data comprises image data indicative of anatomical features of a subject.
5. 5. The implantable transducer of any of claims 1-4, wherein the implantable transducer is configured to be disposed in a hole in a skull of a subject.
6. 6. The implantable transducer of any of claims 1-5, wherein the implantable transducer is positioned in contact with a soft tissue of a subject.
7. 7. The implantable transducer of claim 5 or 6, wherein the implantable transducer is configured to cause an increase in local body temperature of less than 2 o C.
8. 8. The implantable transducer of claim 5 or 6, wherein the implantable transducer is configured to limit absolute local brain temperature to less than 39 o C.
9. 9. The implantable transducer of claim 5 or 6, wherein the implantable transducer is positioned in contact with a dura mater of the subject.
10. 10. The implantable transducer of claim 5 or 6, wherein the implantable transducer is located outside a brain parenchyma of the subject.
11. 11. The implantable transducer of any of claims 1-10, wherein the housing comprises a lip disposed at a second end of the housing, the lip configured to be mounted to an outer surface of a skull of a subject.
12. 12. The implantable transducer of any of claims 1-11, wherein the implantable transducer comprises a cable configured to transmit power or data to or from the implantable transducer.
13. 13. The implantable transducer of claim 12, wherein the cable protrudes through the housing of the implantable transducer.
14. 14. The implantable transducer of any of claims 1-13, wherein the sonolucent window comprises a biocompatible polymer.
15. 15. The implantable transducer of claim 14, wherein the biocompatible polymer is polymethyl methacrylate (PMMA), or Poly(ether) ether ketone (PEEK), polychlorotrifluoroethylene (PCTFE), polytetrafluoroethylene (PTFE), ultra-high-molecular- weight polyethylene (UHMWPE), polyethylene terephthalate (PET), low density polyethylene (LDPE), polyether block amide (PEBAX), and/or high-density polyethylene (HDPE).
16. 16. The implantable transducer of any of claims 1-15, wherein the ultrasound array is fabricated on a complementary metal-oxide semiconductor (CMOS) application specific integrated circuit (ASIC).
17. 17. The implantable transducer of any of claims 1-16, wherein the ultrasound array comprises a capacitive micromachined ultrasonic transducer (CMUT), piezoelectric micromachined ultrasonic transducer (PMUT) array or a Lead Zirconate Titanate (PZT) array.
18. 18. The implantable transducer of any of claims 1-17, wherein the implantable transducer is configured to couple to one or more wires, the implantable transducer configured to send and further configured to receive data via the one or more wires.
19. 19. The implantable transducer of any of claims 1-18, wherein the implantable transducer is configured to receive a plurality of ultrasound waves.
20. 20. The implantable transducer of any of claims 1-19, wherein the ultrasound array comprises a plurality of transducer elements.

Description

SYSTEMS AND METHODS FOR IMAGING AND MODULATING THE NERVOUS SYSTEM USING AN ULTRASOUND-BASED BRAIN-COMPUTER INTERFACE CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the priority benefits of United States Provisional Patent Application Serial No. 63/511,617, filed June 30, 2023, and United States Provisional Patent Application Serial No. 63/598,886, filed November 14, 2023, the contents of which are incorporated herein by reference in their entirety. FIELD OF THE DISCLOSURE [0002] The present disclosure relates generally to systems and methods for imaging and modulating a physiology, e.g., a nervous system, of a subject, and more specifically to, systems and methods for using implantable ultrasound transducers to image and modulate the nervous system of a subject. BACKGROUND [0003] Debilitating brain disorders and diseases that are resistant to treatment or drugs are prevalent. Existing neurotechnology solutions fall short of tackling the complex and individualized nature of human brain dysfunction. Existing solutions can be highly invasive, limited in spatial or temporal resolution, limited in spatial or temporal scope, or can be physically cumbersome to the extent that orthologous measurements of the subject are not readily procured. Advanced monitoring and therapeutic tools are needed to address the limitations of currently available drugs and neurotechnologies. [0004] For instance, neuropsychiatric and cognitive disorders, including depression and neuropathic pain, share common traits. Such disorders occur within circuits and systems distributed spatially throughout the nervous system. As another example, brain states associated with disorders evolve slowly over time, ranging from hours to months. Furthermore, the brain states can vary between people, even across persons diagnosed with identical brain dysfunctions. The distributed and time-evolving nature of the disorders can benefit from a broadscale and long- term approach to imaging and modulating the nervous system, for example, for monitoring or treating pathological brain function. BRIEF SUMMARY [0005] The methods and systems discussed herein address a technological issue: the lack of suitable systems and methods for monitoring and manipulating neural activity at sufficiently broad temporal and spatial scales and resolutions for human subjects. Existing systems and methods struggle with addressing this issue, because of fundamental physical and neurophysiological constraints inherent to the technology. The methods and systems disclosed herein comprise an ultrasound-based technology that can monitor and manipulate neural activity in humans at mesoscale or macroscale coverage, including, but not limited to, whole-brain level scales. The methods and systems disclosed herein leverage ultrasound-based physics for achieving macroscale-level interfacing with the brain. The macroscale-level brain computer interface described herein can observe and modulate neural circuit dynamics at scales as broad as brain-wide levels. The methods and systems herein comprise ultrasound-based neurotechnology platforms, which can further comprise a digital diagnostic and therapeutic ecosystem that can support the ultrasound-based platform. The systems and methods disclosed herein can make use of mesoscopic or macroscopic access across brain areas, such as, but not limited to, whole brain access, to achieve improved treatments for brain dysfunctions. [0006] In addition to improving the sensitivity and resolutions over existing methods, functional ultrasound imaging, as described herein, can be packaged into an implantable form factor, unlike, for example, functional magnetic resonance imaging (fMRI). In doing so, the described ultrasound imaging systems can promote high-resolution neuroimaging while subjects are engaged in natural and clinically relevant behaviors. In addition to clinically relevant neuroimaging applications, the disclosed systems can also accomplish neurostimulation of dysfunctional brain circuits, while the subject is engaged in clinically relevant behaviors. The neurostimulation of the subject can be in a closed loop (as discussed further below), such that when a relevant neural activity pattern and/or clinically relevant behavior is observed, therapeutic stimulation of a relevant brain circuit can be achieved. The device packaging described for the systems disclosed herein can also be repurposed for more general applications outside of the interfacing with neural activity, such as for the monitoring and stimulation of non-brain physiological systems. [0007] The systems and methods disclosed herein are overall compact and minimally invasive. The systems and methods comprise at least one, but usually multiple, small ultrasound transducers herein referred to as “implantable transducers,” “implantable sensors,” or “pucks.” The puck is designed to fit in a craniotomy (e.g., a drill hole of diameter 30 mm or smaller) in the skull, wh