Whole Brain Nanoscale Preservation/Imaging

全脑纳米级保存/成像

• 批准号: 9392273
• 负责人: Robert McIntyre
• 金额: $ 4.56万
• 依托单位: NECTOME, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9392273
• 关键词: Aldehydes; Animals; Architecture; Archives; Biological; Biological Preservation; Biology; Blood Vessels; Brain; Brain Diseases; Brain imaging; Brain region; Chemistry; Cryopreservation; Diffusion; Electron Microscopy; Failure; Formaldehyde; Foundations; Genetic; Genomics; Germany; Glutaral; Goals; Gold; Grant; Human; Image; Imaging Techniques; Institutes; Label; Laboratories; Light Microscope; Methods; Microscopy; Mind; Modeling; Molecular; Mus; Nature; Neurobiology; Neurosciences; Osmium; Osmium Tetroxide; Pattern; Perfusion; Pharmaceutical Preparations; Pharmacologic Substance; Plant Resins; Plastic Embedding; Preparation; Protocols documentation; Research Personnel; Resolution; Sampling; Services; Slice; Staining method; Stains; Structure; Techniques; Technology; Thick; Time; Vision; Work; base; brain tissue; connectome; design; genome analysis; interest; light microscopy; nanoscale; nervous system disorder; next generation; sample fixation; tool; wasting; whole genome

Abstract/Summary Nectome will create technologies to enable whole-brain nanoscale preservation and imaging, a vital step towards a deep understanding of the mind and of the brain's diseases. Current brain-processing technologies compromise between whole-brain applicability or nanoscale resolution; our technologies will achieve both si- multaneously. Similar to the way that next-generation genetic sequencing has helped to unlock the potential of genomics, these technologies will provide a foundation and set the path for the next generation of brain imag- ing. We will modify the two most promising nanoscale brain preparation techniques, expansion microscopy (1) and plastic embedding (2), to use vascular perfusion (3) instead of diffusion. This will enable them to overcome their current thickness limit of 150 microns in order to scale to whole brain samples. We will also integrate both methods with aldehyde-stabilized cryopreservation (ASC), a powerful brain-banking technique which can durably preserve the nanoscale structure of whole brains for centuries with no decay (4). Electron microscopy (EM) has been used for over 50 years to analyze brain tissue and is considered the “gold standard” for nanoscale brain imaging. Expansion microscopy (ExM) is a very recently developed brain imaging technique that physically expands brain tissue to 10–20 times its original size, enabling nanoscale resolution of brain tissue with normal light microscopes and with fluorescent labels to detect a diverse array of molecules normally invisible with electron microscopy. Whole-brain adaptations of EM and ExM will be of great interest to pharmaceutical companies wishing to evaluate the effects of drugs on brain ultrastructure and seeking to avoid wasting large amounts of brain tissue as is currently done in many studies. We also see immense application in the burgeoning field of Connectomics (the study of the brain's detailed pattern of connectivity), and in brain banks wishing to store important brain samples with unprecedented detail. We foresee commercial opportunity in offering brain preservation and processing both as a service for processing whole brains, and as a kit for researchers who wish to accomplish this nanoscale preservation and imaging in their own labs.

摘要/概要 Nectome将创造技术，使全脑纳米级保存和成像，这是至关重要的一步 深入了解大脑和大脑疾病当前的大脑处理技术 全脑适用性或纳米级分辨率之间的妥协;我们的技术将实现两个si- 穆尔西亚。类似于下一代基因测序有助于释放 基因组学，这些技术将提供一个基础，并为下一代的大脑图像设定道路， ing.我们将修改两个最有前途的纳米级大脑制备技术，扩大显微镜（1） 塑料包埋（2），以血管灌注（3）代替扩散。这将使他们能够克服 他们目前的厚度限制为150微米，以便扩展到整个大脑样本。我们还将整合两者 方法与稳定的冷冻保存（ASC），一个强大的脑银行技术，可以持久 将整个大脑的纳米级结构保存数百年而不腐烂（4）。 电子显微镜（EM）用于分析脑组织已有50多年的历史，被认为是“黄金”。 纳米级脑成像的标准。膨胀显微镜（ExM）是一种非常新开发的脑成像技术， 一种将脑组织物理膨胀到原来大小10-20倍的技术，能够实现纳米级分辨率 用普通的光学显微镜和荧光标记来检测不同的分子 通常用电子显微镜看不见。 EM和ExM的全脑适应性将引起制药公司的极大兴趣， 评估药物对大脑超微结构的影响，并寻求避免浪费大量的脑组织， 目前在许多研究中都是如此。我们也看到了巨大的应用在新兴领域的连接（ 研究大脑的详细连接模式），以及希望存储重要大脑样本的大脑银行 前所未有的细节。我们预见到提供大脑保存和处理的商业机会 既可以作为处理整个大脑的服务，也可以作为希望完成这种纳米级研究的研究人员的工具包， 在他们自己的实验室里保存和成像。