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

提案号：1402926pi。题目：使用PFC-LSS角度分辨技术的癌前多光谱3D成像意义：食管癌是目前美国增长最快的癌症。此外，食管癌的症状——包括吞咽困难、胸痛或窒息——通常要到疾病的晚期才会出现。食管癌几乎只发生在巴雷特食管患者中，这是一种良性的食管反流并发症，影响了大约300万美国人。虽然食管癌患者的预后很差，但如果在早期发育不良阶段就发现，大多数食管癌是可以预防的。标准的不典型增生筛查使用视觉内窥镜检查和规定的活检模式。这种方法是选择一小部分受影响的组织进行病理检查，由于不典型增生在视觉上难以区分，并且只影响一小部分食道，因此发现的可能性很低。我们小组最近开发了一种新的食道不典型增生的影像学检测方法，在第一次临床试验中成功地检测出了现有临床技术无法检测到的食管癌前不典型增生。目前这种方法缺乏深度信息，而深度信息是检测和评估不典型增生和早期癌症的重要因素。因此，在这个应用中，我们建议在我们的方法中增加深度灵敏度，为癌症前的高分辨率3D成像提供一个全新的维度。我们相信这种新的成像方法为早期发现各种器官的发育不良提供了很大的希望。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，因为癌症前期将在一个更早的、目前看不见的、仍可治疗的阶段被诊断出来，生命将得到拯救。技术描述：本项目的目标是结合我们Qiu et al.论文中描述的内镜兼容扫描光散射光谱（LSS）。Nature Medicine 2010，采用相位函数校正（PFC）扩散法开发定量深度敏感成像方法，实时指导食管活检。内镜扫描LSS策略是扫描整个食管，以获得上皮表面每2mm位置的LSS信息。LSS将收集到的光学数据与上皮细胞的基本光学参数联系起来，其中包括，例如，上皮细胞核的大小分布和核密度，用于识别发育不良部位的重要组织学诊断标准。反过来，我们的Vitkin等人描述的PFC方法。Nature common . 2011的论文将辐射输运中长期未解决的问题——扩散理论修复在接近入口点的地方。因此，内镜扫描LSS与PFC相结合是一种非常有前途的深度分辨多光谱三维成像方法，可为早期癌症的多光谱高分辨经皮成像提供全新的维度。本文提出了一种新的多光谱成像扫描PFC-LSS方法。我们将建立一个实验室PFC-LSS成像装置来测试深度分辨诊断成像的想法，同时，开发一种能够准确描述上皮组织深度分辨成像和LSS信息的数学方法。在对可复制组织幻影和新切除的食管组织进行实验室设置测试后，我们将修改现有的内窥镜扫描LSS临床仪器，以合并PFC-LSS功能，用于对可疑的非典型增生上皮部位进行高分辨率3D成像。我们将在BIDMC介入内窥镜中心测试这种新型内窥镜仪器在识别巴雷特食管高度发育不良患者中的性能，这些患者正在接受常规监测内窥镜检查。该技术的准确性将通过临床接受的方法来验证，即从可疑区域收集活检组织（在收集光学PFC-LSS数据后立即收集），并获得和比较这些活检组织的病理分析。我们认为PFC-LSS成像为食管发育不良的早期发现提供了很大的希望，因此可以避免不必要的活检，并对局灶性发育不良点进行活检，否则可能会错过。

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.