Optical Biopsy Using Optical Coherence Tomography

描述（由申请人提供）：光学相干断层扫描（OCT）是一种新兴的成像技术，可以对原位和实时的组织形态进行高分辨率、横断面和三维（3D）成像。光学相干显微镜（OCM）将OCT与共聚焦显微镜相结合，以扩展成像深度实现细胞水平的分辨率。假设OCT和OCM可以作为一种“光学活检”，在不切除和处理标本的情况下，可视化体内早期肿瘤变化。如果成功，这些成像技术可以指导活检，减少采样误差，提高灵敏度。该项目垂直整合了技术开发、生物医学研究和临床研究，由麻省理工学院、贝斯以色列女执事医疗中心、波士顿VA医疗保健系统和哈佛医学院的研究人员共同努力。具体目标是：1。开发超高分辨率3D-OCT成像技术。3D-OCT将实现新的可视化技术，如任意横截面图像的生成、类似于显微镜的投影视图、改进的形态学定量测量和用于可视化组织结构的虚拟操作。我们建议开发临床内窥镜3D-OCT新技术，实现50万轴向扫描/秒的成像速度，轴向图像分辨率<5¿m，速度比标准oct快100倍，分辨率精细2-3倍。发展内窥镜光学相干显微镜（OCM）用于细胞水平成像。开发细胞分辨率内窥镜技术是生物医学成像领域的一个长期挑战，有望改善癌症的早期诊断。光学相干显微镜（OCM）是一种将OCT与共聚焦显微镜相结合的体内细胞成像技术。我们建议开发新的OCM技术来实现细胞水平的内窥镜成像。3. 3D-OCT和OCM的离体成像研究。离体成像是建立OCT和OCM诊断特征与组织病理学之间相关性的有力方法。我们将研究上、下Gl道病变，包括Barrett食管、不典型增生和腺癌，以及炎症性肠病中的不典型增生和腺癌。我们还将研究乳腺恶性肿瘤。这些研究将建立与组织学的对应关系，开发新的可视化方法，验证计算机辅助组织分类技术，并评估在新病理中的试点应用。4. 上、下胃肠道的临床内镜成像。本目的假设是胃肠道的3D-OCT和OCM成像可以识别肿瘤变化。我们将研究Barrett食管、上消化道发育不良和腺癌，以及下消化道炎症性肠病中结肠发育不良和腺癌。如果成功，该研究将开发和展示新的成像技术，这将增强胃肠道内窥镜检查，并为改进各种肿瘤的检测打开大门。

DESCRIPTION (provided by applicant): Optical coherence tomography (OCT) is an emerging imaging technology which performs high resolution, cross-sectional and three-dimensional (3D) imaging of tissue morphology in situ and in real time. Optical coherence microscopy (OCM) combines OCT with confocal microscopy to achieve cellular level resolution with an extended imaging depth. The hypothesis is that OCT and OCM can function as a type of "optical biopsy" to visualize early neoplastic changes in vivo without excision and processing of specimens. If successful, these imaging technologies could guide biopsy to reduce sampling error and improve sensitivity. This program vertically integrates technology development, biomedical research and clinical studies in a collaborative effort between investigators at the Massachusetts Institute of Technology, Beth Israel Deaconess Medical Center, Boston VA Healthcare System, and Harvard Medical School. The specific aims are: 1. Develop Ultrahigh Resolution 3D-OCT Imaging Technology. 3D-OCT will enable new visualization techniques such as generation of arbitrary cross-sectional images, projection views similar to microscopy, improved quantitative measurements of morphology and virtual manipulation of tissue for visualizing structure. We propose to develop new technology for clinical endoscopic 3D-OCT to achieve imaging speeds of 500,000 axial scans / second with <5 ¿m axial image resolution, factors of ~100x faster speed and ~2-3x finer resolution than standard OCT. 2. Develop Endoscopic Optical Coherence Microscopy (OCM) for Cellular Level Imaging. Developing techniques for cellular resolution endoscopy is a longstanding challenge in biomedical imaging and promises to improve early diagnosis of cancer. Optical coherence microscopy (OCM) is an in vivo cellular imaging technique which combines OCT with confocal microscopy. We propose to develop new OCM technology to enable cellular level endoscopic imaging. 3. Ex Vivo Imaging Studies Using 3D-OCT and OCM. Ex vivo imaging is a powerful methodology to establish correlations between OCT and OCM diagnostic features and histopathology. We will investigate upper and lower Gl tract pathologies including Barrett's esophagus, dysplasia, and adenocarcinoma, as well as dysplasia and adenocarcinoma in inflammatory bowel disease. We will also investigate breast malignancies. These studies will establish correspondence with histology, develop new visualization methods, validate computer assisted tissue classification techniques, and assess pilot applications in new pathologies. 4. Clinical Endoscopic Imaging of the Upper and Lower Gastrointestinal Tract. The hypothesis of this aim is that 3D-OCT and OCM imaging in the gastrointestinal tract can identify neoplastic changes. We will investigate Barrett's esophagus, dysplasia, and adenocarcinoma in the upper GI tract and dysplasia and adenocarcinoma of the colon in inflammatory bowel diseases in the lower GI tract. If successful, the proposed research will develop and demonstrate new imaging technology which will augment gastrointestinal endoscopy and open the door for improved detection of a wide range of neoplasias.