Optically-Guided Bladder Biopsy Using Polarized Elastic Scattering Spectroscopy

描述(申请人提供)：6.项目摘要/摘要本建议是为了开发一种基于光纤的系统，用于早期膀胱癌的检测和监测。该技术基于偏振弹性散射光谱(PESS)。美国有超过50万人患有膀胱癌。目前的检测依赖于白光膀胱镜的肉眼检查。当患者出现血尿或尿液细胞异常等症状时，通常会进行这种检查。接下来是活组织检查和外科手术。膀胱癌术后复发率高达50%-70%。这会导致多次重复的内窥镜检查和手术，给患者带来持续的不适和压力。膀胱癌也是最昂贵的癌症，在美国每年的估计成本为40亿美元，每个手术患者的终生治疗成本在100-20万美元之间。在癌症达到浸润期之前及早发现往往对长期预后至关重要。这项建议的主要目标是确定使用PESS检测早期膀胱癌的可行性，并将PESS发展为光学引导介入工具以及医生办公室的常规内窥镜筛查工具。在光学和图像引导的内窥镜和外科手术中，活检部位与光谱测量部位的联合配准一直是一个一致的问题。为了解决这个问题，在这个第一阶段计划期间，将开发一种工具，将PESS光纤探头与商业上可获得的活检钳子集成在一起，以确保组织病理学与光谱数据的准确关联。这种光学引导的活检工具将用于30名患者的初步临床研究，以获得从同一部位活检的样本的PESS频谱和组织病理学评估。这些数据将被用来确定PESS频谱特征与组织学之间的初步相关性，用于PESS频谱的经验分类，以指示正常尿路上皮、间质性膀胱炎、低级别膀胱癌或高级别膀胱癌。第一阶段的成功结果将导致更广泛的多中心第二阶段临床研究，组织分类的改进算法，以及集成光学引导活检钳的商业化。PESS具有区分正常组织和病变组织的潜力，具有敏感性和特异性&gt；90%不使用指示性染料、分子标记或其他外源性试剂。与核磁共振、CT和超声等成像手段相比，光学引导的PESS技术简单、成本低、易于使用，只需最少的培训。PESS能够以高灵敏度和高特异性快速检测病变，可以减少不必要的组织活检，更早发现复发，减少术后膀胱镜检查的需要，同时降低医疗保健成本，改善患者的预后和生活质量。OTI在光学制导技术开发方面拥有丰富的经验，以及包括波士顿大学、弗劳恩霍夫研究所和库克泌尿系统公司在内的世界级合作者团队，是成功完成这一计划的唯一条件。7.公共卫生相关性：膀胱癌是美国第五种最常见的恶性肿瘤，其高复发率要求术后频繁进行膀胱镜检查，并在发现新癌症时进行手术。目前的临床方法和实践旨在通过外科手术切除视觉上确定的肿瘤或从视觉上“可疑”区域的活检中切除肿瘤。如果成功，这笔赠款的结果将是一种在膀胱癌显露之前发现它的方法，允许更早地发现和治疗，减少不必要的组织活检，减少对术后随访和干预的需要，同时降低医疗保健成本，改善患者的预后和生活质量。

DESCRIPTION (provided by applicant): 6. Project Summary/Abstract This proposal is for the development of a fiber-optic based system for the detection and surveillance of early stage bladder cancer. The technology is based on Polarized Elastic Scattering Spectroscopy (PESS). Over 500,000 people in the US are afflicted with bladder cancer. Detection currently depends on visual examination by white light cystoscopy. This is generally performed when a patient presents with symptoms like hematuria or abnormal cells in the urine. This is followed by biopsy and surgical intervention. The recurrence rate for bladder cancer after surgery is an onerous 50-70%. This results in multiple repeat endoscopies and surgeries, with continued discomfort and stress to the patient. Bladder cancer is also the most expensive cancer, with an annual estimated cost in the US of $4B and a lifetime treatment cost for each surgical patient in the range of $100-200K. Early detection before the cancer reaches an invasive stage is often critical to long-term prognosis. The primary goals of this proposal are to determine the feasibility of using PESS for detecting early stage bladder cancer and developing PESS into a tool for optically guided interventions as well as a routine endoscopic screening tool for the doctor's office. Co-registration of a biopsy site with the site of spectroscopic measurement has been a consistent problem with optically and image-guided endoscopic and surgical interventions. To address this problem, a tool will be developed during this Phase 1 program that integrates a PESS fiber-optic probe with commercially-available biopsy forceps to ensure accurate correlation of histopathology with spectroscopic data. This optically-guided biopsy tool will be used in a 30-patient preliminary clinical study to acquire PESS spectra and histopathological assessments of samples biopsied from the same site. These data will be used to determine preliminary correlation between PESS spectral features and tissue histology for empirical classification of PESS spectra as indicative of normal urothelium, interstitial cystitis, low-grade bladder carcinoma, or high-grade bladder carcinoma. A successful Phase 1 outcome will lead to a broader multi-center Phase II clinical study, refined algorithms for tissue classification, and commercialization of the integrated optically-guided biopsy forceps. PESS has the potential to differentiate between normal and diseased tissues with sensitivity and specificity >90% using no indicator dyes, molecular markers, or other exogenous agents. Compared to imaging modalities such as NMR, CT and ultrasound, optically-guided PESS technology is simple, low cost, and easy to use with minimal training. PESS' ability to quickly detect lesions with high sensitivity and specificity can lead to fewer unnecessary tissue biopsies, earlier detection of recurrence, and reduced need for post-operative cystoscopic examinations, while reducing the cost of health care and improving patient outcomes and quality of life. OTI, with deep experience in optically- guided technology development, along with a world-class team of collaborators including Boston University, the Fraunhofer Institute, and Cook Urological, Inc. is uniquely equipped to successfully complete this program. 7. PUBLIC HEALTH RELEVANCE: Bladder cancer is the fifth most commonly diagnosed malignancy in the United States, and its high recurrence rate requires frequent post-operative visits for cystoscopic examination and surgery when new cancers are observed. Current clinical methods and practice are directed at surgically removing tumors identified visually or from biopsy of visually `suspicious' areas. If successful, the outcome of this grant will be a method of detecting bladder cancer before it is visible, allowing for earlier detection and treatment with fewer unnecessary tissue biopsies, a reduction in the need for post-operative follow-up and intervention, while reducing the cost of health care and improving patient outcomes and quality of life.