"Multimodal Optical Imaging Endoscopy for Noninvasive ""Optical Biopsy"" in Tissues"

在加拿大，肺癌是癌症死亡的首要原因。据估计，2011年，肺癌占男性癌症死亡人数的11300人，占女性死亡人数的9300人。及早发现和治疗有可能大大改善这些统计数据。目前癌症诊断的金标准是组织活检，然后是组织病理学。在这一过程中，临床医生从可疑区域进行多个组织活检，并进行组织病理学检查。这一过程是侵入性的，而且耗时。光学活检术是一种利用光学成像技术研究活体亚细胞组织形态的新型工具。它可以提供与组织病理学相同的成像分辨率，但该过程是非侵入性的，并且是实时的。因此，“光学活检”可能会对癌症和其他疾病的诊断和治疗产生巨大的影响。 我们建议开发一种多模式光学成像内窥镜，用于非侵入性的肺“光学活检”。内窥镜将结合光学相干层析成像(OCT)和多光子显微镜(MPM)。OCT提供深度和宽度超过几毫米的分层组织结构的横断面解剖成像。它探测来自折射率不连续的背向散射光。MPM以亚细胞分辨率成像混浊组织中的细胞和细胞外基质。MPM提供有关胶原、弹性蛋白、NADH和黄素的生化特性的功能信息。当发展成单一内窥镜时，MPM/OCT可以提供多种对比度和多尺度视野。该提案将利用光纤、微型扫描仪和微型光学技术开发内窥镜MPM/OCT。该设计将针对同时进行大视场OCT和高分辨率MPM成像进行优化。内窥镜将能够通过OCT快速扫描大范围的组织区域以发现异常区域，并通过MPM对感兴趣的区域执行高分辨率放大成像以识别异常。该项目的发展将成为诊断和评估主要呼吸系统疾病治疗效果的重要工具。

Lung cancer is the foremost cause of cancer death in Canada. In 2011, lung cancer is estimated to account for 11,300 of cancer deaths in men and 9,300 in women. Early detection and treatment has the potential to greatly improve these statistics. The current gold standard of cancer diagnosis is tissue biopsy followed by histopathology. In this procedure, clinicians take multiple tissue biopsies from suspicious areas and perform histopathology examination. This procedure is invasive and time consuming. "Optical biopsy" is a new type of tool which uses optical imaging to examine subcellular tissue morphology in vivo. It can provide the same imaging resolution as histopathology but the procedure is noninvasive and in real-time. Therefore, "optical biopsy" can potentially have a huge impact on the diagnosis and treatment of cancer and other diseases. We propose to develop a multimodal optical imaging endoscopy for noninvasive "optical biopsy" of the lung. The endoscope will combined optical coherence tomography (OCT) and multiphoton microscopy (MPM). OCT provides cross-sectional anatomical imaging of layered tissue structures over a few millimeters deep and wide. It detects backscattered light from refractive index discontinuities. MPM images cells and extracellular matrix in turbid tissues with subcellular resolution. MPM provides functional information about biochemical specificity of collagen, elastin, NADH, and flavins. When developed into a single endoscope, MPM/OCT can provide multiple contrasts and multiscale field-of-views. The proposal will develop endoscopic MPM/OCT using optical fibers, miniature scanners, and micro-optics. The design will be optimized for simultaneous large field-of-view OCT and high resolution MPM imaging. The endoscope will be capable to quickly scan over a large tissue area to find abnormal regions with OCT, and perform a high-resolution zoom-in imaging on the regions of interest to identify the abnormalities with MPM. The development from this project will serve as an important tool for diagnosing and evaluating the effect of treatment of major respiratory diseases.