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

项目摘要和摘要 许多神经和精神障碍本质上是连接性障碍：某些神经元组 与其他神经元的连接性异常增加或减少。脑深部刺激 (DBS)疗法的目标是小而独特的轴突和/或细胞体，以治疗大脑疾病 并使连接正常化。因此，绘制大脑的接线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技术间接研究了人类的连接性。为了开发一种 更高分辨率的大脑连接图，这个项目将开发深度分辨偏振光 成像以显示轴突和纤维束。由于显微分辨率的脑成像和映射是 使用固有光学对比度(例如，基于偏振的)和深度分辨块面成像是可行的 在组织学处理之前，我们已经开发了系列光学相干扫描仪(SoCS)用于 具有显微分辨率的大规模或全脑成像。SoC结合了偏振维持 基于光纤的偏振敏感光学相干层析成像和组织切片器。该项目将创建一个 一种新型的SOCS系统，可以使用无偏光学技术在微米级空间分辨率下对轴突进行成像 对比(目标1)。该方法将在相同的脑组织和神经组织中进行评估、改进和比较。 在非人类动物模型中与DBS治疗脑疾病靶点相关的束的示踪剂标记 (目标2)。然后，该方法将应用于人脑中的DBS靶标(目标3)。物理规模在 本项目研究的大脑微结构是独一无二的(1-10μm分辨率跨厘米 组织)。该项目将为未来微米级的人类连接体铺平道路， 这是目前光学技术为整个人脑成像所能达到的最高分辨率。

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.