In vivo Handheld Coherent Raman Scattering (CRS) Microscopy for Glioma Imaging

描述(由申请人提供)： 项目摘要/摘要：在体手持相干拉曼散射(CRS)显微技术用于脑胶质瘤成像胶质瘤以浸润性生长为特征。然而，目前的临床影像设备不能检测到胶质瘤的浸润性边缘。此外，胶质瘤的浸润性很难在实验系统中建模。一种能够直接显示肿瘤细胞向正常脑组织扩散的原位成像方法，将有助于了解胶质瘤的侵袭情况，提高脑胶质瘤手术的准确性。在这里，我们建议将相干拉曼散射(CRS)显微镜转换为成像人类胶质瘤的一种手段。Sunney Xie教授的实验室开创了CRS显微镜的先河，并将其应用于标记-活细胞和组织的免费化学成像。最近关于CRS的工作已经达到高潮，发现了受激拉曼散射(SRS)显微镜，并展示了活体人体组织成像。SRS可以基于大分子成分的分布，如脂类、蛋白质和DNA，对生物标本进行高分辨率的组织成像。因为它依靠固有的组织成分进行对比，所以SRS成像不受基于染料的组织结构可视化方法的限制。此外，SRS显微镜是唯一非常适合于 活体，原位成像，因为它可以基于激发信号的反向散射，实时地执行(成像速度高达每秒30帧)。因此，SRS显微镜为研究患者胶质瘤生物学的关键方面创造了可能性，例如侵袭性，这是很难在动物模型中再现的。此外，SRS显微镜最终可能成为提高手术准确性的有用工具，因为它能够在手术中在细胞水平上检测残留肿瘤。我们最近已经证明，传统的实验室-型SRS显微镜可以准确地显示新鲜的、未处理的人类手术标本中的胶质母细胞瘤在体外和体内的人脑胶质母细胞瘤异种移植模型中的浸润。现在，我们打算利用学术、临床和工业合作伙伴组成的多学科团队以及密歇根大学研究员援助计划，来实现这里提出的研究的长期目标：开发一种可在手术中使用的手持临床SRS系统，以更好地了解和治疗胶质瘤。这项提案的目标是开发和验证一种用于人类组织和动物模型的SRS显微镜系统，其方式适合于未来的监管批准(IDE)。

DESCRIPTION (provided by applicant): Project Summary/Abstract: In vivo Handheld Coherent Raman Scattering (CRS) Microscopy for Glioma Imaging Gliomas are characterized by an infiltrative pattern of growth. However, current clinical imaging modalities are not capable of detecting the infiltrating margins of gliom. In addition, glioma infiltration is difficult to model in experimental systems. An imaging method capable of directly imaging the spread of neoplastic cells into normal brain, in situ, would: (1) contribute greatly to the understanding of glioma infiltration, and (2) improve the accuracy of glioma surgery. Here we propose the translation of coherent Raman scattering (CRS) microscopy as a means of imaging human gliomas. The laboratory of Prof. Sunney Xie has pioneered CRS microscopy and applied it to the label----free, chemical imaging of living cells and tissues. Recent work on CRS has culminated in the discovery of stimulated Raman scattering (SRS) microscopy and demonstration of in vivo human tissue imaging. SRS enables high----resolution, histologic imaging of biological specimens based on the distribution of macromolecular components such as lipids, proteins, and DNA. Because it relies on intrinsic tissue components for contrast, SRS imaging is free of the limitations of dye----based methods for visualizing tissue architecture. In addition, SRS microscopy is uniquely well----suited for in vivo, in situ imaging because it can be performed, based on back----scattering of the excitation signal, in real----time (imaging speed up to 30 frames per sec). Consequently, SRS microscopy creates the possibility of studying key aspects of glioma biology in patients, such as invasion, that are difficult to recreate in animal models. Moreover, SRS microscopy may ultimately become a useful tool for improving surgical accuracy by enabling detection of residual tumor on a cellular level during surgery. We have recently demonstrated that a traditional laboratory----style SRS microscope can accurately image glioblastoma infiltration in fresh, unprocessed human surgical specimens ex vivo and in vivo in human glioblastoma xenograft models. Now we intend to draw on the strength of a multidisciplinary team of academic, clinical, and industrial partners, as well as the University of Michigan Investigator Assistance Program, to achieve the long----term goal of the research proposed here: the development of a handheld clinical SRS system that can be used during surgery to better understand and treat gliomas. The goal of this proposal is to develop and validate an SRS microscopy system for use in human tissues and animal models in a manner appropriate for future regulatory approval (IDE).