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: 10443418
• 负责人: TANER AKKIN
• 金额: $ 51.75万
• 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/10443418
• 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; Gold; Histologic; Human; Image; Imaging technology; Injections; Internal Capsule; Label; Lasers; Lateral; Location; Macaca mulatta; Maps; Mental disorders; Methods; Microscopic; Motor; 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; Work; analytical tool; attenuation; base; brain circuitry; brain tissue; connectome; density; gray matter; human imaging; image processing; imaging modality; improved; in vivo; 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.

项目摘要和摘要 许多神经和精神病障碍本质上是连接主义疾病：某些神经元集 与其他神经元的连通性绝对提高或降低。深脑刺激 （DBS）疗法靶向轴突和/或细胞体的独特群体，以治疗脑部疾病 并标准化连接性。那是一个重要的目标。宏观 连通性已在人类中使用非侵入性神经影像学间接研究。为了发展一个 大脑的分辨率连接图要高得多，该项目将发展深度分辨的偏振光 成像以可视化轴突和纤维区。由于微小分辨率的脑成像和映射为 可行的具有固有的光学对比度（例如基于极化）和深度分辨的块面成像是 在组织学处理之前，我们已经开发了串行光学连贯扫描仪（SOCS） 具有微观分辨率的大型或全脑成像。 SOCS结合了两极分化维护 基于纤维敏感的光学相干断层扫描和组织切片机。这个项目将创建一个 新型SOCS系统，可以使用无偏光图像微米尺度的空间分辨率对轴突图像成像 对比（目标1）。该方法将在同一脑组织中评估，完善和比较 在非人类动物模型中 （目标2）。然后，该方法将应用于人脑中的DBS靶标（AIM 3）。物理尺度 该项目研究了大脑微观结构是独特的（跨厘米的1-10μm分辨率 组织）。该项目将为以微米尺度的未来人类连接的基础铺平道路， 通过当前的光学技术来对整个人类大脑进行成像，这是可以实现的最高分辨率。