Integrated Optical Coherence Tomography and Microscopy for Molecular-Targeted Ima

描述（由申请人提供）：光学相干断层扫描（OCT）是一种用于在体内实时评估三维（3D）组织结构形态的强大工具，分辨率接近标准组织病理学。光学相干显微镜（OCM）将OCT与共焦显微镜相结合，以实现细胞特征的高横向分辨率和3D可视化。然而，目前的OCT和OCM成像技术还不能利用分子靶向造影剂的进步，因为没有已知的方法来使用OCT和OCM产生分子造影剂。我们的假设是，3D、多尺度OCT和OCM与分子靶向造影剂相结合，将提高早期癌症检测的灵敏度和特异性。该计划的目标是开发能够实现3D-OCT和OCM成像的分子对比度的技术，建立在候选人进行的初步研究基础上。 候选人Chao Zhou博士在宾夕法尼亚大学完成了严格的物理学培训，目前正在马萨诸塞州理工学院（MIT）继续进行博士后研究。他在生物医学光学成像技术和临床前研究方面拥有坚实的背景。K99/R 00奖将提供额外的研究和临床培训的共同指导下，从博士詹姆斯G。麻省理工学院OCT技术的国际权威Fujimoto博士、贝斯以色列女执事医学中心（BIDMC）和哈佛医学院（HMS）分子成像领域的杰出领导者John V. Frangioni博士以及James L.康诺利是BIDMC和HMS的世界著名乳腺病理学家。麻省理工学院和HMS提供的独特环境将鼓励成功的研究，这将垂直整合OCT和OCM的技术开发，并利用分子靶向造影剂和纳米技术的最新进展。该项目的成功完成将：1）通过实现分子敏感对比度和3D结构成像来改变OCT领域; 2）为高灵敏度和特异性检测癌症标志物开辟道路，这些标志物可以很容易地与光热治疗技术相结合;和3）作为与异常蛋白质表达水平相关的其它病理的附加OCT和OCM研究的起点，例如神经变性和心血管疾病。 这些进展将使组织的结构和病理状态能够在体内以真实的时间进行3D成像，并具有多尺度的微米级空间分辨率。周博士还将获得宝贵的培训和研究经验，使他有资格领导一个独立的研究项目，并争取独立的研究资金。 公共卫生相关性：该计划将开发和验证一种集成的超高速光学相干断层扫描（OCT）和光学相干显微镜（OCM）系统，该系统能够在3D，活体，实时和微米级空间分辨率下进行分子靶向成像。我们假设3D、多尺度和分子靶向OCT和OCM成像的组合将大大提高早期癌症检测的灵敏度和特异性。该K99/R 00应用程序也将作为候选人的培训工具，因为他过渡到独立调查。

DESCRIPTION (provided by applicant): Optical coherence tomography (OCT) is a powerful tool for assessing three-dimensional (3D) tissue architectural morphology in vivo and in real-time, with a resolution approaching that of standard histopathology. Optical coherence microscopy (OCM) combines OCT with confocal microscopy in order to achieve high transverse resolution and 3D visualization of cellular features. However, current OCT and OCM imaging technologies have not been able to leverage the advances in molecular-targeted contrast agents because there is no known method to generate molecular contrast using OCT and OCM. Our hypothesis is that 3D, multi-scale OCT and OCM, in combination with molecular-targeted contrast agents, will improve the sensitivity and specificity of early cancer detection. The goal of this program is to develop the technology that will enable molecular contrast for 3D-OCT and OCM imaging, building upon preliminary studies conducted by the candidate. The candidate, Dr. Chao Zhou, completed rigorous training in physics from the University of Pennsylvania and is continuing his postdoctoral research at the Massachusetts Institute of Technology (MIT). He has a solid background in biomedical optical imaging techniques and in pre-clinical research. The K99/R00 award would provide additional research and clinical training under co-mentorship from: Dr. James G. Fujimoto, an international authority on OCT technologies at MIT; Dr. John V. Frangioni, a distinguished leader in molecular imaging at Beth Israel Deaconess Medical Center (BIDMC) and the Harvard Medical School (HMS); and Dr. James L. Connolly, a world renowned breast pathologist at BIDMC and HMS. The unique environments provided by MIT and HMS will encourage successful research, which will vertically integrate technical development in OCT and OCM, and leverage recent advances in molecular-targeted contrast agents and nanotechnology. The successful completion of this program will: 1) transform the OCT field by enabling molecularly sensitive contrast and 3D structural imaging; 2) open the way for the highly sensitive and specific detection of cancer markers that can be readily combined with photothermal therapeutic techniques; and 3) serve as a launching point for additional OCT and OCM studies of other pathologies associated with abnormal protein expression levels, such as neurodegenerative and cardiovascular diseases. These advances will enable both the structure and pathological states of tissue to be imaged in 3D, in vivo, in real time, and with micron-level spatial resolutions at multiple scales. Dr. Zhou will also obtain valuable training and research experience so that he will be qualified to lead an independent research program and to compete for independent research funding. PUBLIC HEALTH RELEVANCE: This program will develop and validate an integrated, ultrahigh-speed optical coherence tomography (OCT) and optical coherence microscopy (OCM) system that enables molecularly targeted imaging in 3D, in vivo, in real-time, and with micron-scale spatial resolution. We hypothesize that the combination of 3D, multiple-scale, and molecular-targeted OCT and OCM imaging will greatly enhance the sensitivity and specificity for early cancer detection. This K99/R00 application will also serve as a training vehicle for the candidate, as he transitions to independent investigation.