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.

这一阶段I SBIR开发了一个系统，可以轻柔，准确地插入大型光学神经科学问题 （例如，笑容镜头）改善衰老研究的结果。此外，该项目支持Qingguang 张。博士通过NIA研究和企业家发展浸入（REDI）计划 小型企业。他的项目的企业家开发活动将包括项目因素 在ISO-13485系统，验证和验证，专利开发，FDA-中达到设计冻结 监管互动和MedTech业务运营。张博士将与拥有的AMI导师互动 将他们的学术技能转换为一家小公司的商业和研发活动的经验。 公共卫生问题：衰老和神经退行性疾病与树突状丧失有关 复杂性，轴突的脱髓鞘以及降低神经元令人兴奋。光纤纤维等光学成像工具 光度法和可植入的笑容镜头耦合到头部安装显微镜，可用于图像 神经元的形态和活性超出了通过多光子显微镜访问的深度。然而， 其手术植入方法造成的组织损伤可能导致神经活动的类似变化 和形态学在衰老和认知下降中所见，使实验结果混淆。先前的研究 将针的振动插入到中枢神经系统中的周围组织和电极中 减少插入力和组织损伤。 需要一种工具来可靠地减少与植入大直径相关的组织损伤和应变 （>100μm）在光学神经科学中使用的成像镜片，以消除实验混杂并改善 与年龄相关的神经元形态和功能变化的研究。 价值主张：该项目开发了光学神经科学插入工具（ONIT）以改善插入 微笑镜头和其他光学神经科学系统的动力学。以后的工作将扩展到大量插入 设备，例如DBS问题，组织损伤较小，用于治疗人类神经退行性疾病。 目标1-优化，构建和测试轻量级系统系统。 （AMI：1-9个月）。 接受标准：构建计算机控制的超声执行器，能够1）抓握和 用真空压力释放光纤套管和笑镜头，2）以更少的速度推进植入物 比100µm/sec，3）减少纤维插管的穿刺力（直径200µm）> 60％> 60％ 啮齿动物脑组织模型和4）在插入过程中施加在执行器上的监测力。 AIM 2-证明对神经活动和组织学的体内测量的噪声的信号提高了信号 振荡插入大直径咧嘴插入后，神经元复杂性的标记六周 啮齿动物模型中的镜片。 （9-12月； AMI/PSU）。 接受标准：能够插入大直径的咧着嘴镜头而无需组织抽吸的能力， 植入物后，基线的衰减（> 50％）和诱发的GCAMP7F信号强度6WK。 神经变性的组织学指标降低（使用Sholl分析，神经元复杂性> 50％） 在500µm植入的咧着嘴镜头之内，疤痕形成（与对照GFAP+面积相比<50％） 振荡的插入。 商业化与营销：通过第三方分销商的早期销售将被重新投资以继续 向临床相关的系统开发，以插入类似的大型DBS电子，一个预计的市场 到2030年达到$ 4.3B。