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

描述（由申请人提供）： 项目概要/摘要：用于胶质瘤成像的活体手持相干拉曼散射（CRS）显微镜胶质瘤的特征在于浸润性生长模式。然而，目前的临床影像学方式不能检测胶质瘤的浸润边缘。此外，神经胶质瘤浸润难以在实验系统中建模。一种能够直接原位成像肿瘤细胞扩散到正常脑中的成像方法将：（1）极大地有助于理解胶质瘤浸润，和（2）提高胶质瘤手术的准确性。在这里，我们提出了翻译相干拉曼散射（CRS）显微镜作为一种手段，成像人类胶质瘤。Sunney Xie教授的实验室开创了CRS显微镜，并将其应用于活细胞和组织的无标记化学成像。最近的CRS工作在受激拉曼散射（SRS）显微镜的发现和体内人体组织成像的演示中达到了高潮。SRS能够根据大分子成分（如脂质、蛋白质和DNA）的分布对生物样本进行高分辨率组织学成像。因为它依赖于内在的组织成分的对比度，SRS成像是自由的限制，染料-为基础的方法可视化组织架构。此外，SRS显微镜是独一无二的-适用于 体内原位成像，因为它可以基于激励信号的反向散射在真实的时间（成像速度高达每秒30帧）中执行。因此，SRS显微镜创造了研究患者中胶质瘤生物学的关键方面的可能性，例如在动物模型中难以重现的侵袭。此外，SRS显微镜可能最终成为一个有用的工具，用于提高手术的准确性，使检测残留的肿瘤细胞水平上的手术过程中。我们最近已经证明，传统的实验室-风格SRS显微镜可以准确地成像胶质母细胞瘤浸润在新鲜的，未经处理的人类手术标本离体和在体内的人类胶质母细胞瘤异种移植模型。现在，我们打算利用学术，临床和工业合作伙伴以及密歇根大学研究者援助计划的多学科团队的力量，实现这里提出的研究的长期目标：开发可在手术期间使用的手持式临床SRS系统，以更好地了解和治疗胶质瘤。本提案的目标是开发和确认SRS显微镜系统，以适合未来监管批准（IDE）的方式用于人体组织和动物模型。

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).