Integrated Optical Coherence Tomography and Microscopy for Molecular-Targeted Ima

用于分子靶向成像的集成光学相干断层扫描和显微镜

基本信息

批准号：
8110925
负责人：
Chao Zhou
金额：
$ 9万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-15 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8110925
关键词：
Animal Model Antibodies Award Binding Biodistribution Biological Breast Caliber Cancer Biology Cancer Detection Cardiovascular Diseases Cell Culture Techniques Cells Clinical Confocal Microscopy Contrast Media Data Set Detection Development Environment Epidermal Growth Factor Receptor Frequencies Funding Glutamate Carboxypeptidase II Goals Histology Histopathology Human Image Imagery Imaging Techniques Imaging technology Institutes International Investigation Israel Knowledge Lasers Lead Ligands Massachusetts Medical center Mentorship Methods Microscopy Molecular Molecular Target Morphology Nanotechnology Neurodegenerative Disorders Noise Optical Coherence Tomography Optics Pathologist Pathology Pennsylvania Performance Phase Physics Proteins Protocols documentation Qualifying Research Research Training Resolution Screening for cancer Sensitivity and Specificity Signal Transduction Solid Source Specimen Specimen Handling Speed Staging Structure System Techniques Technology Therapeutic Time Tissues Toxic effect Training Universities absorption authority base cancer cell cytotoxicity design experience imaging modality improved in vivo medical schools molecular imaging nanoparticle neoplastic novel optical imaging phase change pre-clinical research programs protein expression skill acquisition skills small molecule tool tumor tumor progression

项目摘要

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.

描述（由申请人提供）：光学相干断层扫描（OCT）是一种用于实时评估体内三维（3D）组织结构形态的强大工具，其分辨率接近标准组织病理学的分辨率。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，当前的 OCT 和 OCM 成像技术还无法利用分子靶向造影剂的进步，因为没有已知的方法可以使用 OCT 和 OCM 生成分子造影剂。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。该项目的目标是在候选人进行的初步研究的基础上，开发能够实现 3D-OCT 和 OCM 成像分子对比的技术。该候选人周超博士在宾夕法尼亚大学完成了严格的物理学培训，目前正在麻省理工学院 (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扎实的背景。 K99/R00 奖项将在以下人员的共同指导下提供额外的研究和临床培训：麻省理工学院 OCT 技术国际权威 James G. Fujimoto 博士； John V. Frangioni 博士，贝斯以色列女执事医疗中心 (BIDMC) 和哈佛医学院 (HMS) 分子成像领域的杰出领导者； James L. Connolly 博士是 BIDMC 和 HMS 的世界知名乳腺病理学家。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和 3D 结构成像来改变 OCT 领域； 2）为癌症标志物的高灵敏度和特异性检测开辟了道路，可以轻松地与光热治疗技术相结合； 3) 作为与蛋白质表达水平异常相关的其他病理学（例如神经退行性疾病和心血管疾病）的其他 OCT 和 OCM 研究的启动点。这些进步将使组织的结构和病理状态能够在多个尺度上以微米级空间分辨率在体内实时进行 3D 成像。周博士还将获得宝贵的培训和研究经验，使他有资格领导独立研究项目并竞争独立研究经费。公共健康相关性：该计划将开发和验证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，该系统能够在体内实时进行 3D 分子靶向成像，并使用微米级技术。尺度空间分辨率。我们假设 3D、多尺度、分子靶向 OCT 和 OCM 成像的结合将大大提高早期癌症检测的灵敏度和特异性。当候选人过渡到独立调查时，该 K99/R00 应用程序还将作为候选人的培训工具。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（4）

Ultrahigh-resolution optical coherence microscopy accurately classifies precancerous and cancerous human cervix free of labeling.

DOI：
10.7150/thno.24599
发表时间：
2018
期刊：
Theranostics
影响因子：
12.4
作者：
Zeng X;Zhang X;Li C;Wang X;Jerwick J;Xu T;Ning Y;Wang Y;Zhang L;Zhang Z;Ma Y;Zhou C
通讯作者：
Zhou C

Segmentation of Drosophila heart in optical coherence microscopy images using convolutional neural networks.