Optical Spectroscopy in the Management of Colorectal Neoplasia

 描述（由申请人提供）： 该提案的中心目标是证明与目前的标准实践相比，光谱学在结直肠癌（CRC）筛查、管理和预防方面的益处。两个互补的应用将使用相同的平台进行测试：使用弹性散射光谱（ESS）来可靠地区分肿瘤性和非肿瘤性息肉，并使用ESS，低相干增强后向散射光谱（LEBS）和分波光谱（PWS）来感测致癌作用的场效应（FEC）。具体目标是：1.使用ESS进行息肉实时组织学评估的前瞻性临床研究。我们将使用ASGE-PIVI指南作为性能基准，前瞻性地测试和验证我们为ESS息肉分类设计的算法。2.场效应临床研究及联合应用研究。我们将同时收集算法训练和验证数据，用于在常规结肠镜检查过程中使用ESS感测FEC。对于相同的患者和相同的手术，我们将研究ESS作为CRC风险评估工具及其与息肉切除术发现肿瘤性息肉的效率和成功率的改善的关系（如果有的话）。此外，我们将使用LEBS获得的光学测量值和PWS分析的直肠刷检来交叉验证ESS获得的FEC传感结果。仪器：实施系统增强和工具设计，以实现临床友好性。我们会建立标准化和校正程序，使仪器能适应临床环境的变化，并开发新一代的临床硬件和软件界面。这将确保在不同的运营商和站点之间获得可比较的结果。ESS和LEBS将根据需要集成到一个混合动力系统箱中。用于引导息肉切除术和FEC传感的内窥镜介导工具将被设计为低成本和一次性的。方法学：本研究的候选受试者将从现有患者库中抽取，这些患者由其医生安排进行常规或监测结肠镜检查，或作为既往临床评价或既存疾病的结果。在获得签署的知情同意书后，所有患者将接受标准治疗。与正常检查和活检程序的主要偏差是在每次活检前进行光学测量和周围结肠粘膜测量，并在结肠镜检查期间采集直肠样本进行刷检细胞学检查。当需要活检时，在标准物理活检之前，将使用ESS光学活检钳对完全相同的组织进行光学活检。根据护理标准，活检将被送去进行组织病理学检查，并由三名对光谱结果不知情的独立病理学家进行审查。还将使用ESS沿沿着几个结肠段测量正常结肠粘膜。此外，将使用LEBS获得直肠粘膜的光学测量值，以及将使用PWS分析的直肠刷拭物。来自息肉的ESS光谱将与来自病理学家的大多数诊断相关。根据手术期间的发现，将正常结肠组织的ESS、LEBS和PWS测量值分配为属于肿瘤或非肿瘤区域。诊断算法将使用这些相关的光学数据进行训练和测试。将从几个来源收集用于鉴定FEC生物标志物的数据，以排除可能的混杂因素。

 DESCRIPTION (provided by applicant): The central objective of this proposal is to demonstrate the benefits of optical spectroscopy for the screening, management, and prevention of colorectal cancer (CRC) as compared to current standard practices. Two complementary applications will be tested using the same platform: Using elastic-scattering spectroscopy (ESS) to distinguish reliably between neoplastic and non-neoplastic polyps, and using ESS, low- coherence enhanced backscattering spectroscopy (LEBS), and partial wave spectroscopy (PWS) for sensing the field effect of carcinogenesis (FEC). The specific objectives are: 1. To conduct a prospective clinical study using ESS for real-time histological assessment of polyps. We will prospectively test and validate algorithms that we have designed for ESS classification of polyps, using the ASGE-PIVI guidelines as performance benchmarks. 2. Clinical studies of field effect, and combined applications study. We will concurrently collect algorithm-training and validation data for sensing of FEC with ESS, during routine colonoscopy procedures. With the same patients and at the same procedure, we will look at ESS as a CRC risk assessment tool and its relationship, if any, with improvements in efficiency and success rate of finding neoplastic polyps for polypectomy. In addition, we will use optical measurements obtained with LEBS and rectal brushings analyzed with PWS to cross-validate FEC sensing results obtained with ESS. 3. Instrumentation: Implement system enhancements and tool design for clinical friendliness. We will establish standardization and calibration procedures to make instruments robust to variations in clinical environment, and develop next-generation clinical hardware and software interfaces. This will ensure that comparable results are obtained among different operators and sites. Integration of ESS and LEBS into a single hybrid system box will be enabled as required. Endoscope-mediated tools for guiding polypectomy and FEC-sensing will be designed to be low-cost and disposable. Methodology: Candidate subjects for this study will be drawn from an extant pool of patients who are scheduled for routine or surveillance colonoscopy by their physician or as the result of a prior clinical evaluation or a pre-existing condition. Upon obtaining a signed Informed Consent, all patients will receive standard treatment. The main deviation from the normal examination and biopsy procedure will be to take an optical measurement prior to each biopsy and of surrounding colonic mucosa, and a rectal sample for brush cytology during the colonoscopy. When biopsy is required, prior to the standard physical biopsy, an optical biopsy will be taken of the exact same tissue with the ESS optical forceps. The biopsy will be sent for histopathology, as per standard of care, and reviewed by three independent pathologists blinded to the spectroscopic results. Measurements of normal colonic mucosa will also be taken along several segments of the colon with ESS. Additionally, optical measurements of rectal mucosa will be obtained with LEBS, as well as rectal brushings that will be analyzed with PWS. ESS spectra from polyps will be correlated to the majority diagnosis from the pathologists. ESS, LEBS, and PWS measurements from normal colonic tissue will be assigned as to belonging to a neoplastic or non-neoplastic field based on findings during the procedure. Diagnostic algorithms will be trained and tested using these correlated optical data. Data for identification of FEC biomarkers will be collected from several sources to rule out possible confounders.