Visualizing Cortical Microstructures by Optical Coherence Tomography (OCT)

 描述(申请人提供)：显微结构和细胞类型分布的特定区域差异在人脑皮质区域中得到很好的确立；在不同的疾病条件下，例如皮质变薄，或者在更精细的分辨率水平上，特定的锥体或非锥体细胞群的变化，已经确定了特定的形态变化。然而，这些数据是基于相对较小的样本量，可以预期从高通量、高分辨率技术的发展中受益匪浅。目前，尽管目前正在进行大规模的研究，但“神经解剖学知识鸿沟”仍然是一个被广泛承认的问题。活体MRI图像的分辨率是有限的，但传统的组织学虽然提供细胞分辨率，但容易处理失真，而且众所周知，劳动密集型。光学相干成像(OCT)是一种很有前途的桥梁方法，它可以提供细胞水平的分辨率，并促进活体MRI图像的组织学水平的解释，从而将组织学的高分辨率能力与MRI优越的高通量、三维和纵向特征相结合。作为一个基本的先决条件，目前的提议旨在实现OCT图像的细胞级评估。实验设计的关键部分是：1)在OCT之前对小块组织(2x2x0.3 mm)进行成像；2)随后对组织块进行振动切片，获取与所成像的块表面相对应的切片，并通过传统组织学和免疫细胞化学对其进行处理，以寻找髓鞘、神经胶质或神经元的特异性标记；以及3)登记并比较两个数据集(即，OCT成像的相同的块表面，振动切片后成像，并进行组织学处理)。这是一个合作项目，它结合了OCT成像方面的专业知识(在马萨诸塞州总医院)和细胞类型和微观结构分析方面的专业知识(麻省理工学院和波士顿大学医学院)。成功将被定义为确定在OCT图像中忠实地捕捉到组织群体，包括识别故障点(如果有的话)。预计在最终的R01中，下一步是将相同的3步方案应用于病理皮质组织的标本，目的是建立一个形态变化的资源数据库，例如，可以用于更好地解释MRI图像(体外，但导致体内)，并与遗传或蛋白质组生物标记物进行预测性关联。

 DESCRIPTION (provided by applicant): Area-specific differences in microstructure and cell-type distribution are well-established across cortical regions in the human brain; and specific morphological changes have been identified in different disease conditions, such as cortical thinning or, at a finer level of resolution, changes in specific pyramidal or non-pyramidal cell populations. These data, however, are based on relatively small sample sizes and can be expected to benefit substantially from the development of high-throughput, high-resolution techniques. Currently, despite large scale initiatives now underway, the "neuroanatomical knowledge-gap" is still widely acknowledged to be a problem. In vivo MRI images are limited in resolution, but traditional histology, while offering cellular resolution, is prone to processing distortions and is notoriously labor-intensive. Optical coherence imaging (OCT) is a promising bridge approach that can provide cellular-level resolution and facilitate histology-level interpretation of in vivo MRI images, thus combining the high-resolution capacity of histology with the superior high-throughput, 3- dimensional, and longitudinal features of MRI. As an essential prerequisite, the current proposal aims to achieve a cellular-level evaluation of OCT images. Key parts of the experimental design are: 1) image small blocks of tissue (2x2x0.3mm) by OCT; 2) subsequently vibratome-section the tissue block, harvest the section corresponding to the imaged blockface, and process this by traditional histology and immunocytochemistry for markers specific to myelin, glia, or neurons; and 3) register and compare the two datasets (i.e., an identical blockface imaged by OCT, vibratome- sectioned post-imaging, and processed for histology). This is a collaborative project, which combines expertise in OCT imaging (at Massachusetts General Hospital) with expertise in cell type and microstructure analysis (MGH and Boston University School of Medicine). Success will be defined as determining that histological populations are faithfully captured in the OCT images, including identification of failure points, if any. Anticipated next steps, in an eventual R01, are to apply the same 3-step protocol to specimens of pathological cortical tissues, with the intention of establishing a resource database of morphological changes that could, for example, be used for finer interpretation of MRI images (ex vivo, but leading to in vivo) and predictive correlation with genetic or proteomic biomarkers.