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

提案编号：1402926 P.I.：Perelman，Lev T.标题：PFC-LSS角分辨技术用于癌前病变的多光谱三维成像意义：食管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出现。食管癌几乎完全发生在巴雷特食管患者中，巴雷特食管是食管反流的一种良性并发症，影响约300万美国人。虽然被诊断患有食管癌的患者的预后很差，但如果在早期发育不良阶段检测到疾病，大多数食管癌是可以预防的。异型增生的标准护理筛查使用目视内窥镜和规定的活检模式。这种方法只选择一小部分受影响的组织进行病理学检查，检测的可能性很低，因为发育异常在视觉上无法区分，只影响食管的一小部分。我们的小组最近开发了一种新的成像方法来检测食管异型增生，在其第一次临床试验中成功地检测到了不可见的食管癌前异型增生错过了现有的临床技术。在目前的形式下，这种方法缺乏深度信息，这是检测和评估发育异常和早期癌症的重要因素。因此，在本申请中，我们建议为我们的方法增加深度灵敏度，为癌前病变的高分辨率3D成像提供全新的维度。我们相信，这种新的成像方法为各种器官的发育异常的早期检测提供了很大的希望。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，因为癌前病变将在一个更早的、目前不可见的阶段被诊断出来，那时它仍然是可治疗的，生命将被挽救。技术描述：本项目的目标是将联合收割机内窥镜兼容扫描光散射光谱（LSS）结合在我们的论文Qiu et al. Nature Medicine 2010中描述的，应用相函数校正（PFC）扩散方法，建立了食管深度敏感成像的定量方法，用于真实的实时引导食管活检。内窥镜扫描LSS策略是扫描整个食管以获得关于上皮表面的每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，所述基本光学参数包括例如上皮细胞核的尺寸分布和核密度，这是用于识别发育异常部位的重要组织学诊断标准。反过来，在我们的Vitkin et al. Nature Commun. 2011年的论文修正了进入点附近的扩散理论，这是辐射传输中长期未解决的问题。看来，内窥镜扫描LSS和PFC的组合可以导致一个非常有前途的深度分辨多光谱3D成像方法，它可以提供全新的维度的多光谱高分辨率经皮成像的早期癌症。这种新的方法，它可以被称为多光谱成像扫描PFC-LSS方法，在此应用中提出。我们将建立一个实验室PFC-LSS成像装置，以测试深度分辨诊断成像的想法，同时，开发一种数学方法，能够准确描述深度分辨成像和LSS信息的上皮组织。 在对可重复组织模型和新鲜切除的食管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，对可疑异型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识别在BIDMC的介入内窥镜中心接受常规监测内窥镜检查的Barrett食管患者的高度异型增生方面的性能。该技术的准确性将使用临床上接受的方法进行验证，这些方法包括从可疑区域收集活检（在收集光学PFC-LSS数据后立即），并获得和比较这些活检的病理分析。我们相信，PFC-LSS成像为食管异型增生的早期检测提供了很大的希望，因此可以避免不必要的活检，并且可以对否则会被遗漏的局灶性异型增生点进行活检。

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.