Optical Biopsy Using Optical Coherence Tomography

描述（由申请人提供）：这是麻省理工学院和VA波士顿医疗保健系统的研究人员之间的多学科合作，整合了成像技术研究、临床成像研究、医疗设备开发和动物成像研究。食管癌是一种致命的恶性肿瘤，5年生存率为16%。巴雷特食管（BE）和发育不良是食管腺癌（EAC）的先兆。射频消融术（RFA）作为一种有效的治疗发育不良BE的标准治疗方法，大大减少了恶性肿瘤的进展。然而，RFA平均需要30次治疗，BE的长期复发率为25%。光学相干断层扫描（OCT）可以进行高分辨率的组织形态原位和实时三维成像。假设是：1。内镜下OCT可以识别与RFA治疗反应相关的特征。影像引导消融治疗可用于治疗计划和实时消融监测；图像引导可以减少采样误差，增加对不典型增生和早期癌的切除活检诊断。目的1：内镜下OCT标记RFA治疗反应。我们将对接受RFA治疗的BE发育不良患者进行一项前瞻性、纵向研究，以确定与RFA治疗反应相关的结构特征。内镜下OCT将进行体积标记，包括be上皮厚度，鳞状下肠化生，以及由于消融不足而残留的腺体结构。我们将评估这些特征与RFA治疗疗效/持久性的相关性，包括治疗总次数和治疗后BE的复发。目的2：图像引导食管消融设备和技术。OCT可以实时成像食管结构和消融深度。我们建议开发一种oct引导的多区域RFA消融探头和oct引导的激光消融球囊并进行比较。研究将在猪食管上进行，通过OCT成像和组织学验证来建立剂量参数。然后将使用体内猪模型来评估简化消融方案和执行可控深度和面积消融的能力。目的3：超高分辨率内镜OCT检测不典型增生和早期癌。检测不典型增生和早期癌仍然具有挑战性，标准诊断程序依赖于四象限活检取样。我们建议发展超高速扫描源OCT和探针技术用于非典型增生和早期癌的检测。验证研究将在上消化道发育不良患者和下消化道内镜粘膜切除术（EMR）患者中进行，以评估与标准组织学相比OCT成像的敏感性和特异性。这项工作将开发新的成像方法，可以对RFA患者进行风险分层，使未来的图像引导临床消融设备成为可能，并提高对不典型增生和早期癌症诊断的敏感性。

DESCRIPTION (provided by applicant): This is a multidisciplinary collaboration between investigators at the Massachusetts Institute of Technology and the VA Boston Healthcare System integrating imaging technology research, clinical imaging studies, medical device development and animal imaging studies. Esophageal cancer is a lethal malignancy, with a five-year survival rate of 16%. Barrett's esophagus (BE) and dysplasia are precursors to esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) is becoming the standard of care as an effective treatment for dysplastic BE, greatly reducing progression to malignancy. However, RFA requires an average of >3 treatment sessions, and long term recurrence rates for BE are >25%. Optical coherence tomography (OCT) can perform high resolution, three-dimensional imaging of tissue morphology in situ and in real-time. The hypotheses are: 1. Endoscopic OCT can identify features associated with RFA treatment response, 2. Image guided ablation therapy can be developed for treatment planning and real time ablation monitoring, and 3. Image guidance can reduce sampling errors and increase yields for excisional biopsy diagnosis of dysplasia and early carcinoma. Aim 1: Endoscopic OCT markers for RFA treatment response. We will conduct a prospective, longitudinal study on patients with dysplastic BE being treated with RFA to identify structural features associated with RFA treatment response. Endoscopic OCT will be performed to volumetrically map markers including BE epithelium thickness, subsquamous intestinal metaplasia, and residual glandular structure due to insufficient ablation. We will evaluate the correlation of these features to RFA treatment efficacy/durability, including the total number of treatment sessions and recurrence of BE post treatment. Aim 2: Image guided esophageal ablation devices and techniques. OCT enables real time imaging of esophageal structure and ablation depth. We propose to develop and compare an OCT-guided multi-zone RFA ablation probe and OCT-guided laser ablation balloon. Studies will be performed on swine esophagus ex vivo to establish dosing parameters using OCT imaging and histological validation. An in vivo swine model will then be used to evaluate the ability to simpliy ablation protocols and to perform controlled depth and area ablations. Aim 3: Ultrahigh resolution endoscopic OCT for detecting dysplasia and early carcinoma. Detecting dysplasia and early carcinoma remains challenging and the standard diagnostic procedure relies on four quadrant biopsy sampling. We propose to develop ultrahigh speed swept source OCT and probe technologies for dysplasia and early carcinoma detection. Validation studies will be performed in patients with upper GI dysplasia and patients with lower GI endoscopic mucosal resection (EMR) to assess sensitivity and specificity of OCT imaging compared with standard histology. The proposed work will develop new imaging methods that could risk stratify RFA patients, enable future image guided clinical ablation devices, and increase sensitivity for dysplasia and early carcinoma diagnosis.