Label-free optical imaging for human mesoscale connectivity with a focus on deep brain stimulation targets

用于人体中尺度连接的无标记光学成像，重点关注深部脑刺激目标

• 批准号: 10586107
• 负责人: TANER AKKIN
• 金额: $ 49.71万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-07 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586107
• 关键词: 3-Dimensional; Algorithms; Anatomy; Animal Model; Architecture; Atlases; Axon; Birefringence; Brain; Brain Diseases; Brain Mapping; Brain imaging; Cells; Deep Brain Stimulation; Development; Diffusion Magnetic Resonance Imaging; Disease; Dissection; Electroencephalography; Electron Microscopy; Face; Fascicle; Fiber; Foundations; Functional Magnetic Resonance Imaging; Future; Generations; Goals; Histologic; Human; Image; Imaging technology; Injections; Internal Capsule; Label; Lasers; Lateral; Location; Macaca mulatta; Maps; Mental disorders; Methods; Microscopic; Motor; Motor Cortex; Neurons; Optical Coherence Tomography; Optics; Pathway interactions; Pattern; Performance; Phase; Population; Rattus; Resolution; Sampling; Structure; Structure of subthalamic nucleus; Synapses; System; Techniques; Technology; Thalamic structure; Tissues; Tracer; Visible Radiation; Visualization; Work; analytical tool; attenuation; brain circuitry; brain tissue; cingulate cortex; connectome; density; falls; gray matter; human imaging; image processing; imaging modality; improved; in vivo; meter; multiparametric imaging; nanoscale; nervous system disorder; neural tract; neuroimaging; neurosurgery; nonhuman primate; novel; optical imaging; polarized light; quantitative imaging; reconstruction; targeted treatment; tractography; white matter

PROJECT SUMMARY AND ABSTRACT Many neurological and psychiatric disorders are essentially connectionist disorders: certain sets of neurons have abnormally increased or decreased connectivity with other sets of neurons. Deep brain stimulation (DBS) therapies target small, unique populations of axons and/or cell bodies in order to treat brain disorders and normalize connectivity. Thus, mapping the wiring diagram of the brain is an important goal. Macroscale connectivity has been studied indirectly in humans using noninvasive neuroimaging. In order to develop a much higher resolution connectivity map of the brain, this project will develop depth-resolved polarized light imaging to visualize axons and fiber tracts. Since brain imaging and mapping at microscopic resolution is feasible with intrinsic optical contrasts (e.g. polarization-based) and depth-resolved block-face imaging is desired before histological processing, we have developed the serial optical coherence scanner (SOCS) for large-scale or whole brain imaging with microscopic resolution. SOCS combines a polarization-maintaining fiber based polarization-sensitive optical coherence tomography and a tissue slicer. This project will create a novel SOCS system that can image axonal tracts at the micron scale spatial resolution using unbiased optical contrasts (Aim 1). The approach will be evaluated, refined, and compared in the same brain tissue to neural tract-tracer labeling of tracts associated with DBS targets for brain disorders, in nonhuman animal models (Aim 2). The approach will then be applied to DBS targets in the human brain (Aim 3). The physical scales at which this project investigates the brain microstructure are unique (1-10 μm resolution across centimeters of tissue). This project will pave the way for the foundation of a future human connectome at the micron scale, which is the highest resolution achievable with current optical technology for imaging an entire human brain.

项目总结和摘要 许多神经和精神疾病本质上都是联结障碍： 与其他神经元的连接异常增加或减少。脑深部电刺激 (DBS)治疗针对小的、独特的轴突和/或细胞体群体 并使连通性正常化。因此，绘制大脑的线路图是一个重要的目标。宏观尺度 已经使用非侵入性神经成像在人类中间接地研究了连通性。为了开发 更高分辨率的大脑连接图，该项目将开发深度分辨偏振光 成像以可视化轴突和纤维束。由于大脑成像和映射在微观分辨率是 利用固有光学对比度（例如，基于偏振）和深度分辨块面成像是可行的， 在组织学处理之前，我们开发了串行光学相干扫描仪（SOCS）， 显微镜分辨率的大规模或全脑成像。SOCS结合了极化维持 基于光纤的偏振敏感光学相干断层扫描和组织切片机。该项目将创建一个 新型SOCS系统可以使用无偏光学以微米级空间分辨率对轴突束进行成像 对比（目标1）。该方法将在相同的脑组织中进行评估，改进和比较，以神经 在非人类动物模型中，与脑疾病DBS靶点相关的神经束示踪剂标记 (Aim 2）。然后将该方法应用于人脑中的DBS目标（目标3）。物理尺度在 该项目研究的大脑微观结构是独特的（1-10 μm的分辨率跨越厘米 组织）。该项目将为未来人类连接体在微米尺度上的基础铺平道路， 这是目前用于对整个人脑成像的光学技术所能达到的最高分辨率。