Optical Biopsy Using Optical Coherence Tomography

描述(申请人提供)：光学相干层析成像(OCT)是一种新兴的成像技术，它对组织形态进行高分辨率、横断面和三维(3D)原位和实时成像。光学相干显微镜(OCM)将OCT和共聚焦显微镜相结合，实现了细胞水平的分辨率和扩展的成像深度。假设OCT和OCM可以作为一种“光学活组织检查”，在不切除和处理标本的情况下显示活体内早期肿瘤的变化。如果成功，这些成像技术可以指导活检，以减少采样误差，提高灵敏度。该项目将技术开发、生物医学研究和临床研究垂直整合在一起，由麻省理工学院、贝丝以色列女执事医疗中心、波士顿VA医疗系统和哈佛医学院的研究人员共同努力。具体目标是：1.发展超高分辨率3D-OCT成像技术。3D-OCT将使新的可视化技术成为可能，例如生成任意横截面图像、类似于显微镜的投影视图、改进的形态定量测量以及用于可视化结构的组织的虚拟操作。我们建议开发临床内窥镜3D-OCT的新技术，以达到50万次/秒的轴向扫描速度和5？m的轴向图像分辨率，速度是标准OCT的100倍，分辨率是标准OCT的2-3倍。2.发展用于细胞水平成像的内窥镜光学相干显微镜(OCM)。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，有望提高癌症的早期诊断。光学相干显微镜(OCM)是OCT和共焦显微镜相结合的一种活体细胞成像技术。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.使用3D-OCT和OCM进行EX活体成像研究。体外成像是建立OCT和OCM诊断特征和组织病理学之间相关性的有效方法。我们将研究上、下消化道的病理，包括Barrett‘s食道、异型增生和腺癌，以及炎症性肠病中的异型增生和腺癌。我们还将调查乳腺癌。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，并评估在新病理学中的试点应用。4.上、下胃肠道的临床内窥镜影像。这一目标的假设是胃肠道的3D-OCT和OCM成像可以识别肿瘤性改变。我们将研究Barrett‘s食道、异型增生和上消化道腺癌，以及下消化道炎症性肠病中的结肠腺癌和异型增生。如果成功，这项拟议的研究将开发和展示新的成像技术，该技术将加强胃肠道内窥镜检查，并为改进对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.