Development of an Oscillated Insertion tool to Eliminate Surgically Induced Neurodegeneration for Optical Neuroimaging of Cognitive Aging and Dementia

开发振荡插入工具以消除手术引起的神经变性，用于认知衰老和痴呆的光学神经成像

• 批准号: 10792064
• 负责人: Kyle William Gheres
• 金额: $ 40.63万
• 依托单位: ACTUATED MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2024-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10792064
• 关键词: Academic skills; Acute; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease care; Alzheimer' s disease related dementia; Area; Award; Axon; Blood Vessels; Businesses; Cannulas; Central Nervous System; Certification; Chronic; Cicatrix; Cognitive aging; Computers; Coupled; Dementia; Demyelinations; Development; Device or Instrument Development; Devices; Diameter; Disease; Doctor of Philosophy; Electrodes; Emotional; Encapsulated; Family; Fiber; Fiber Optics; Financial Hardship; Freezing; Geometry; Glial Fibrillary Acidic Protein; Goals; Head; Histologic; Human; Image; Imaging Device; Immersion; Impaired cognition; Implant; Industrialization; Inflammation; Inflammatory; Investigation; Investments; Legal patent; Light; Marketing; Measures; Mechanics; Medical; Medical Device; Medical Research; Mentors; Methodology; Methods; Microscope; Monitor; Morphology; Motion; Motor; Needles; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Neurosciences; Noise; Operative Surgical Procedures; Optics; Patient-Focused Outcomes; Patients; Penetration; Perforation; Peripheral; Phase; Photometry; Postdoctoral Fellow; Pre-Clinical Model; Public Health; Puncture procedure; Quality of life; Research; Research Personnel; Resources; Rodent; Rodent Model; Sales; Signal Transduction; Silicon; Small Business Innovation Research Grant; Speed; Surface; System; Technology; Testing; Thinness; Tissue Model; Tissues; Translating; Ultrasonic Transducer; Ultrasonics; United States National Institutes of Health; Vacuum; Work; age related; aspirate; attenuation; brain tissue; care costs; clinical translation; clinically relevant; commercialization; comparison control; density; design; experience; grasp; imaging system; implantable device; implantation; improved; improved outcome; in vivo; innovation; lens; light weight; multiphoton microscopy; neural; neural implant; neuroimaging; neuronal excitability; operation; optical fiber; optical imaging; pre-clinical; preclinical study; pressure; programs; research and development; safety testing; tool; verification and validation

This Phase I SBIR develops a system for gentle and accurate insertion of large optical neuroscience probes (e.g., GRIN lenses) to improve outcomes in aging research. Additionally, the project supports Qingguang Zhang. Ph.D. through the NIA Research and Entrepreneurial Development Immersion (REDI) program at a small business. Entrepreneurial development activities for his project will include project factors such as reaching Design Freeze in an ISO-13485 system, Verification and Validation, Patent Development, FDA- Regulatory interactions and MedTech business operations. Dr. Zhang will interact with AMI mentors that have experience in translating their academic skillsets to commercial and R&D activities at a small company. Public Health Problem: Aging and neurodegenerative disorders are associated with loss of dendritic complexity, demyelination of axons and reduced neuronal excitability. Optical imaging tools such as fiber photometry, and implantable GRIN lenses coupled to head mounted microscopes, can be used to image neuron morphology and activity beyond the depths accessible through multiphoton microscopy. However, tissue damage caused by their surgical implantation methods can result in similar changes in neural activity and morphology as seen in aging and cognitive decline, confounding experimental results. Previous studies of oscillated insertion of needles into the peripheral tissue and electrodes in the central nervous system have reduced insertion force and tissue damage. A tool is needed to reliably reduce tissue damage and strain associated with implantation of large diameter (>100µm) imaging lenses used in optical neuroscience to eliminate the experimental confound and improve studies of age-related changes in neuron morphology and function. Value Proposition: This project develops the Optical Neuroscience Insertion Tool (ONIT) to improve insertion dynamics of GRIN lenses and other optical neuroscience systems. Later work will expand ONIT to insert large devices, like DBS probes, with less tissue damage, for treatment of neurodegenerative diseases in humans. Aim 1- Optimize, build, and test lightweight ONIT system. (AMI: Months 1-9). Acceptance Criteria: Construction of a computer controlled ultrasonic actuator capable of 1) grasping and releasing fiber optic cannula and GRIN lenses with vacuum pressure, 2) Advancing the implant at speeds less than 100µm/sec, 3) reducing the puncture force of fiber optic cannula (200µm diameter) >60% in an ex vivo rodent brain tissue model, and 4) monitoring force applied to actuator during insertion. Aim 2 - Demonstrate improved signal to noise of in vivo measures of neural activity and histological markers of neuron complexity for six weeks following oscillated insertion of large diameter GRIN lenses in a rodent model. (Months 9-12; AMI/ PSU). Acceptance Criteria: Ability to insert large diameter GRIN lenses without the need for tissue aspiration, reduced attenuation (>50%) of baseline and evoked GCaMP7f signal intensity 6wks following implant. Reduced histological indicators of neurodegeneration (>50% greater neuron complexity using Sholl analysis) and scar formation (<50% compared to control GFAP+ area) within 500µm of GRIN lenses implanted with oscillated insertion. Commercialization & Marketing: Early sales via third party distributors will be reinvested to continue development towards a clinically relevant system to insert similarly large DBS electrodes, a market expected to reach $4.3B by 2030.

第一阶段SBIR开发了一个系统，用于轻柔和准确地插入大型光学神经科学探针