Optically-Guided Bladder Biopsy Using Polarized Elastic Scattering Spectroscopy

描述（由申请人提供）：6。项目摘要/摘要本提案是为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）。在美国有超过50万人患有膀胱癌。目前的检测依赖于通过白色光膀胱镜检查的视觉检查。这通常是当患者出现血尿或尿液中异常细胞等症状时进行的。随后进行活检和手术干预。膀胱癌术后复发率高达50- 70%。这导致多次重复内窥镜检查和手术，给患者带来持续的不适和压力。膀胱癌也是最昂贵的癌症，在美国每年的估计费用为40亿美元，每个手术患者的终身治疗费用在10 - 20万美元之间。在癌症达到侵袭性阶段之前的早期检测通常对长期预后至关重要。该提案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开发为光学引导干预的工具以及医生办公室的常规内窥镜筛查工具。活检部位与光谱测量部位的共配准一直是光学和图像引导的内窥镜和外科手术干预的一个一致问题。为了解决这个问题，将在第一阶段计划中开发一种工具，将PESS光纤探头与市售活检钳集成在一起，以确保组织病理学与光谱数据的准确相关性。该光学引导活检工具将用于30例患者的初步临床研究，以获取PESS光谱和同一部位活检样本的组织病理学评估。这些数据将用于确定PESS光谱特征与组织组织学之间的初步相关性，用于将PESS光谱经验分类为正常尿路上皮、间质性膀胱炎、低度膀胱癌或高度膀胱癌的指示。成功的I期结果将导致更广泛的多中心II期临床研究，用于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具有在不使用指示染料、分子标记或其他外源性试剂的情况下区分正常组织和患病组织的潜力，其灵敏度和特异性>90%。与核磁共振、CT和超声波等成像方式相比，光学引导PESS技术简单、成本低、易于使用，只需很少的培训。PESS以高灵敏度和特异性快速检测病变的能力可以减少不必要的组织活检，早期检测复发，减少术后膀胱镜检查的需求，同时降低医疗保健成本，改善患者的预后和生活质量。OTI在光学引导技术开发方面拥有丰富的经验，沿着世界一流的合作团队，包括波士顿大学、弗劳恩霍夫研究所和库克泌尿外科公司。是唯一能够成功完成这个项目的人7.公共卫生相关性：膀胱癌是美国第五大最常诊断的恶性肿瘤，其高复发率需要频繁的术后访视，以便在观察到新癌症时进行膀胱镜检查和手术。目前的临床方法和实践是针对手术切除肿瘤视觉识别或从活检的视觉“可疑”的地区。如果成功的话，这笔赠款的结果将是一种在膀胱癌可见之前检测膀胱癌的方法，允许早期检测和治疗，减少不必要的组织活检，减少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.