Multispectral 3D Imaging of Pre-Cancer with PFC/LSS Angle-Resolved Technique

提案编号：1402926P.I.：Perelman，Lev T.标题：用PFC-LSS角度分辨技术进行癌前病变的多光谱3D成像意义：食道癌是目前美国增长最快的癌症。此外，食道癌的症状--包括吞咽困难、胸痛或窒息--通常直到疾病的晚期才会出现。食道癌几乎只发生在Barrett‘s食道患者中，Barrett’s食道是一种良性的食道反流并发症，影响了大约300万美国人。尽管被诊断为食道癌的患者预后不佳，但如果在早期发育不良阶段发现这种疾病，大多数食道癌是可以预防的。标准护理筛查异型增生使用视觉内窥镜和指定的活检模式。这一手术选择了一小部分受影响的组织进行病理检查，由于异型增生在视觉上无法区分，而且只影响一小部分食道，因此发现的概率很低。本课题组最近开发了一种新的检测食管异型增生的影像方法，在其第一次临床试验中，成功地发现了现有临床技术所遗漏的食管癌前隐匿性异型增生。在目前的形式下，这种方法缺乏深度信息，而深度信息是检测和评估异型增生和早期癌症的重要因素。因此，在这一应用中，我们建议将深度敏感性添加到我们的方法中，为癌前病变的高分辨率3D成像提供了一个全新的维度。我们相信，这种新的成像方法为早期发现各种器官的异型增生提供了巨大的希望。如果这种方法被常规使用，它将对公众具有相当大的意义和重要性，因为癌症前期将在更早的、目前看不见的阶段被诊断出来，那时它仍然是可以治疗的，生命将被挽救。技术描述：这个项目的目标是结合我们的论文邱某等人所描述的内窥镜兼容扫描光散射光谱(LSS)。自然医学，2010年，利用相函数校正(PFC)扩散法，开发了定量深度敏感成像方法，用于实时引导食道活检。内窥镜扫描LSS的策略是扫描整个食道，以获得关于上皮表面每2 mm位置的LSS信息。LSS将收集的光学数据与上皮细胞的基本光学参数相关联，其中包括例如上皮细胞核的大小分布和核密度，这是用于识别发育不良部位的重要组织学诊断标准。反过来，在我们的Vitkin等人中描述的PFC方法。自然界的普通人。2011年的论文修正了入口点附近的扩散理论，这是辐射传输中长期未解决的问题。结果表明，内窥镜扫描LSS和PFC的结合可以产生一种非常有前景的深度分辨多光谱三维成像方法，为早期癌症的多光谱高分辨率经皮成像提供了全新的维度。这种新的方法可以称为多光谱成像扫描PFC-LSS方法，就是在这种应用中提出的。我们将建立一个实验室的PFC-LSS成像装置来测试深度分辨诊断成像的思想，同时开发一种能够准确描述关于上皮组织的深度分辨成像和LSS信息的数学方法。在对可复制组织模体和新切除的食道组织进行实验室设置测试后，我们将修改我们现有的内窥镜扫描LSS临床仪器，以纳入PFC-LSS功能，以对可疑异常增生的上皮部位进行高分辨率3D成像。我们将测试新的内窥镜仪器在BIDMC介入内窥镜中心接受常规监视内窥镜检查的Barrett‘s食道患者中识别高度异型增生的性能。这项技术的准确性将使用临床接受的方法进行验证，即从可疑区域收集活检组织(在收集到光学PFC-LSS数据后立即)，并获得和比较这些活检组织的病理分析。我们认为，PFC-LSS成像为早期发现食道异型增生提供了极大的希望，因此可以避免不必要的活检，并将被遗漏的局灶性发育不良斑点进行活检。

Proposal Number: 1402926P.I.: Perelman, Lev T.Title: Multispectral 3D Imaging of Pre-Cancer with PFC-LSS Angle-Resolved TechniqueSignificance:Esophageal cancer is currently the fastest increasing cancer in the United States. Furthermore, the symptoms of esophageal cancer - including difficulty swallowing, chest pain, or choking - generally do not appear until advanced stages of the disease. Esophageal cancer develops almost exclusively in patients with Barrett's esophagus, an otherwise benign complication of esophageal reflux that affects approximately 3 million Americans. Although the prognosis of patients diagnosed with esophageal cancer is poor, most esophageal cancers can be prevented if the disease is detected at an early dysplastic stage. Standard-of-care screening for dysplasia uses visual endoscopy and a prescribed pattern of biopsy. This procedure, in which a tiny fraction of the affected tissue is selected for pathological examination, has a low probability of detection because dysplasia is visually indistinguishable and affects only small portion of the esophagus. Our group has recently developed a new imaging method for detection of esophageal dysplasia which in its first clinical tests successfully detected invisible precancerous dysplasia in esophagus missed by the available clinical techniques. In its current form this method lacks depth information, an important factor in detecting and evaluating dysplasia and early cancers. Thus, in this application, we propose to add depth sensitivity to our method, providing an entirely new dimension to high resolution 3D imaging of pre-cancer. We believe that this new imaging method offers great promise for the early detection of dysplasia in various organs. If this method were to be used routinely it would be of considerable significance and importance to the public, as the pre-cancer will be diagnosed at a much earlier, currently invisible, stage when it is still treatable, and lives will be saved.Technical Description:The goal of this project is to combine endoscopic compatible scanning light scattering spectroscopy (LSS) described in our paper Qiu et al. Nature Medicine 2010, with the phase function corrected (PFC) diffusion method to develop quantitative depth sensitive imaging method for guiding biopsy in real time in esophagus. The endoscopic scanning LSS strategy is to scan the entire esophagus to obtain LSS information about every 2 mm location of the epithelial surface. The LSS relates the collected optical data to the underlying optical parameters of the epithelial cells, which includes, for example, the size distribution of epithelial cell nuclei and nuclear density, the important histological diagnostic criteria used to identify the dysplastic sites. In turn, the PFC method described in our Vitkin et al. Nature Commun. 2011 paper fixes the diffusion theory near the point-of-entry, the longstanding unsolved problem in radiative transport. It appears that the combination of endoscopic scanning LSS and PFC can result in a very promising depth resolved multispectral 3D imaging approach which can provide entirely new dimension for the multispectral high resolution transcutaneous imaging of early cancer. This new method, which can be called the multispectral imaging scanning PFC-LSS method, is proposed in this application. We will build a laboratory PFC-LSS imaging setup to test the ideas of depth resolved diagnostic imaging and, at the same time, develop a mathematical approaches capable of accurate description of both the depth resolved imaging and LSS information about epithelial tissues. After testing the laboratory setup on reproducible tissue phantoms and on freshly resected esophageal tissue we will modifying our existing endoscopic scanning LSS clinical instrument to incorporate a PFC-LSS capability for high resolution 3D imaging of epithelial sites suspicious for dysplasia. We will test the performance of the new endoscopic instrument in identifying high grade dysplasia in patients with Barrett's esophagus undergoing routine surveillance endoscopy at the Interventional Endoscopy Center at BIDMC. The accuracy of the technique will be verified using clinically accepted methods of collecting biopsies from suspected areas (immediately after optical PFC-LSS data has been collected) and obtaining and comparing pathological analysis of these biopsies. We believe that PFC-LSS imaging offers great promise for the early detection of dysplasia in esophagus, and therefore unnecessary biopsies would be avoided and focal dysplastic spots would be biopsied that otherwise would be missed.