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

这一阶段的SBIR开发了一种用于温和而准确地插入大型光学神经科学探针的系统 (例如，GRIN镜片)，以改善衰老研究的结果。此外，该项目还支持青光 张某。通过NIA研究和创业发展沉浸(REDI)计划获得博士学位 小生意。他的项目的创业发展活动将包括以下项目因素 在ISO-13485系统中实现设计冻结，验证和确认，专利开发，食品和药物管理局- 监管互动和MedTech业务运营。张医生将与具有以下条件的AMI导师互动 在小公司将他们的学术技能转化为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细胞的丧失有关 复杂性、轴突脱髓鞘和神经元兴奋性降低。光纤等光学成像工具 光度学和与头戴式显微镜相连的植入式GRIN透镜可以用来成像 神经元的形态和活动超出了通过多光子显微镜可以接触到的深度。然而， 他们的手术植入方法造成的组织损伤可以导致类似的神经活动变化 以及衰老和认知衰退中的形态，这与实验结果相矛盾。以前的研究 将针摆动插入周围组织和中枢神经系统的电极 减少插入力和组织损伤。 需要一种工具来可靠地减少与大直径植入相关的组织损伤和应变 用于光学神经科学的(&gt；100微米)成像透镜消除实验困惑并改进 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)以改进插入 GRIN透镜和其他光学神经科学系统的动力学。以后的工作将扩展到插入大型 像DBS探头这样的设备，具有较少的组织损伤，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onit系统。(阿美：1-9个月)。 验收标准：建造计算机控制的超声波执行器，能够1)抓取和 用真空压力释放光纤插管和GRIN透镜，2)以较低的速度推进植入物 3)将直径为200微米的光纤插管的穿刺力在体外降低60% 啮齿类动物脑组织模型，以及4)在插入过程中对致动器施加的监控力。 目标2-证明改善了体内神经活动和组织学测量的信噪比 大直径GRIN摆动植入后6周神经元复杂性的标志物 啮齿动物模型中的镜片。(9-12个月；急性心肌梗塞/多发性硬化症)。 验收标准：能够在不需要组织抽吸的情况下插入大直径GRIN透镜， 植入后6周，基线和诱发GCaMP7f信号强度的衰减降低(&gt；50%)。 神经变性的组织学指标减少(使用Sholl分析，神经元复杂性增加50%) 和瘢痕形成(50%与对照GFAP+面积相比)在500微米内植入的GRIN晶状体 摆动插入。 商业化和营销：通过第三方分销商进行的早期销售将进行再投资，以继续 向临床相关系统发展，以插入类似大的DBS电极，预计市场将 到2030年达到43亿美元。

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.