Visualizing Cortical Microstructures by Optical Coherence Tomography (OCT)

通过光学相干断层扫描 (OCT) 可视化皮质微结构

• 批准号: 9045706
• 负责人: Kathleen Rockland
• 金额: $ 20.71万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9045706
• 关键词: 3-Dimensional; Alzheimer' s Disease; Anterior; Area; Autistic Disorder; Autopsy; Axon; Biological Markers; Boston; Brain; Cell physiology; Cells; Data; Data Set; Databases; Development; Disease; Epilepsy; Evaluation; Experimental Designs; Failure; Fiber; General Hospitals; Genetic; Glial Fibrillary Acidic Protein; Glutamates; Goals; Harvest; Health; Histologic; Histology; Human; Image; Imagery; Individual; Intention; Intervention; Knowledge; Label; Location; Longevity; Magnetic Resonance Imaging; Massachusetts; Mental Depression; Microscopy; Molecular Genetics; Myelin; Neuroanatomy; Neuroglia; Neurons; Optical Coherence Tomography; Optics; Parvalbumins; Population; Primates; Process; Proteomics; Protocols documentation; Pyramidal Cells; Resolution; Resources; Rodent; Route; Sample Size; Sampling; Specimen; Staging; Staining method; Stains; Techniques; Temporal Lobe; Thick; Tissue imaging; Tissues; Universities; Validation; area striata; base; brain tissue; cell type; cingulate cortex; density; design; falls; fiber cell; fluorescence imaging; gray matter; image processing; immunocytochemistry; in vivo; inhibitory neuron; medical schools; myelination; novel; success; tissue fixing

 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.

 描述（由申请方提供）：在人脑的皮质区域中，已经明确了微结构和细胞类型分布的区域特异性差异;并且在不同的疾病条件下已经确定了特定的形态学变化，例如皮质变薄，或者在更精细的分辨率水平上，特定锥体细胞群或非锥体细胞群的变化。然而，这些数据是基于相对较小的样本量，预计将大大受益于高通量，高分辨率技术的发展。目前，尽管正在进行大规模的举措，“神经解剖学知识差距”仍然被广泛认为是一个问题。体内MRI图像的分辨率有限，但传统的组织学虽然提供细胞分辨率，但易于处理失真，并且是众所周知的劳动密集型。光学相干成像（OCT）是一种很有前途的桥梁方法，可以提供细胞水平的分辨率，并促进体内MRI图像的组织学水平解释，从而将组织学的高分辨率能力与MRI的上级高通量、三维和纵向特征相结合。作为一个基本的先决条件，目前的建议旨在实现细胞级的OCT图像的评价。实验设计的关键部分是：1）通过OCT对小组织块（2x2x0.3mm）成像; 2）随后对组织块进行振动切片，收获对应于成像块面的切片，并通过传统的组织学和免疫细胞化学对其进行处理，以获得对髓鞘、神经胶质或神经元特异的标志物;以及3）配准并比较两个数据集（即，通过OCT成像的相同块面，成像后振动切片机切片，并进行组织学处理）。这是一个合作项目，它结合了OCT成像（在马萨诸塞州总医院）的专业知识和细胞类型和微观结构分析（MGH和波士顿大学医学院）的专业知识。成功将定义为确定OCT图像中如实捕获组织学群体，包括识别失效点（如有）。在最终的R 01中，预期的下一步是将相同的3步方案应用于病理皮质组织的标本，目的是建立形态学变化的资源数据库，例如，可以用于MRI图像的更精细解释（离体，但导致体内）和与遗传或蛋白质组学生物标志物的预测相关性。