Advanced a/LCI systems for improved clinical utility

先进的 a/LCI 系统可提高临床实用性

• 批准号: 9261900
• 负责人: NICHOLAS J SHAHEEN
• 金额: $ 50.11万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-13 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9261900
• 关键词: Acids; Adopted; Adoption; Advocate; Affect; Aftercare; Area; Barrett Esophagus; Biological; Biological Markers; Biophotonics; Biopsy; Catheters; Cell Nucleus; Cell Size; Cervical; Chronic; Clinical; Clinical Research; Clinical Trials; Columnar Epithelium; Computer software; Conduct Clinical Trials; Confocal Microscopy; Data; Deglutition; Detection; Developed Countries; Developing Countries; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Dysplasia; Dysplasia in Barrett' s Esophagus; Endoscopes; Endoscopy; Epithelial; Epithelium; Esophageal; Esophageal Diseases; Esophagus; Feedback; Fiber; Future; Gastroesophageal reflux disease; Gland; Goals; Health; Health Status; Image; Incidence; Interferometry; Intestines; Light; Malignant Neoplasms; Malignant neoplasm of esophagus; Manuals; Measurement; Measures; Metaplasia; Methods; Modality; Morbidity - disease rate; Morphology; Multi-modal optical imaging; North Carolina; Nuclear; Operative Surgical Procedures; Optical Coherence Tomography; Optics; Outcome Study; Patients; Pattern; Performance; Periodicity; Phase; Physicians; Predictive Value; Premalignant; Procedures; Protocols documentation; Public Health; Radiofrequency Interstitial Ablation; Reflux; Research; Research Project Grants; Residual state; Resolution; Risk; Risk Factors; Sampling; Sampling Errors; Scanning; Sensitivity and Specificity; Spottings; Squamous Epithelium; Stratum Basale; Surface; System; Techniques; Technology; Testing; Therapeutic; Thermal Ablation Therapy; Time; Tissues; Universities; Update; Validation; Visual; base; cancer risk; clinical practice; design; image guided; imaging approach; imaging platform; imaging system; improved; in vivo; instrument; light scattering; mortality; neoplastic; novel; optical fiber; response; screening; tool; usability

There is a critical unmet need for in vivo detection of dysplasia in patients with Barrett's esophagus (BE), a neoplastic tissue state resulting from chronic acid reflux. BE is associated with an increased risk of esophageal cancer, a disease with a high morbidity rate. Patients with BE undergo periodic endoscopic surveillance with systematic biopsy to search for pre-cancerous, dysplastic tissues, at which point therapeutic treatment by thermal ablation or surgery is indicated. These procedures are guided by white-light endoscopy but since there is no visual evidence of at the tissue surface, efficacy for detecting dysplasia is limited. Consequently, dysplasia goes undetected even though BE patients undergo regular endoscopic surveillance. Optical diagnostic techniques have shown the ability to assess tissue health in vivo but none has been widely adopted. Physicians have not taken up these techniques because they typically do not cover enough tissue area to be effective or lack sufficient sensitivity and specificity for real-time dysplasia detection. For example, angle-resolved low coherence interferometry (a/LCI) uses nuclear morphology measurements as a biomarker of dysplastic change, with proven sensitivity and specificity for in vivo detection of dysplastic BE tissues. However, a/LCI is a point probe modality, only examining tissues in one spot at a time. Here we seek to incorporate a/LCI into a multimodal optical imaging platform that enables practical detection of dysplasia in BE. The goal of this research project is to design, implement and test advanced multimodal optical imaging systems to enable diagnosis of dysplasia in BE tissues. The following specific aims are proposed. 1) Update a/LCI system with image guidance. The a/LCI system will be redesigned, capitalizing on advances in key spectrometer components to improve utility. The optical fiber probe will be updated to incorporate image guidance using optical coherence tomography (OCT), which will improve usability. 2) Implement real time feedback. Software will be updated to include real time guidance of tissue orientation and health status. 3) Test new designs in clinical study. Clinical study will confirm accuracy of a/LCI for detecting dysplasia while demonstrating improvements in efficiency of new hardware and software. A sub-aim of this study will be to evaluate OCT for guiding a/LCI measurements while also detecting residual sub-squamous BE glands which may persist after therapy that remain a cancer risk. 4) Develop multipoint a/LCI probe. Demonstrate principle of wide area scans using a/LCI, enabling multiple measurements without repositioning. Further advances will integrate this probe into the form factor of a therapeutic probe, specifically the Barrx Halo 90, a 2 cm2 “paddle” that is mounted on the outside of a standard endoscope. 5) Conduct clinical trial of multipoint probe. This final clinical study will test the new form factor by comparing with the first trial in this project. Endpoints will be to determine the yield of dysplastic positive biopsies while also assessing the amount of time needed to cover the tissue. Completion of these aims will yield a clinically incisive diagnostic tool suitable for widespread adoption.

在Barrett食管患者体内检测异型增生的需求尚未得到满足 (BE)一种由慢性胃酸反流引起的肿瘤组织状态。BE与以下风险增加相关： 食管癌是一种发病率很高的疾病。BE患者定期接受内镜检查 通过系统性活检进行监测，以寻找癌前病变、发育异常组织， 需要通过热消融或外科手术进行治疗。这些程序是由白光内窥镜引导的 但是由于在组织表面没有可见的证据，检测发育异常的功效是有限的。 因此，即使BE患者接受定期内镜监测，发育不良也未被发现。 光学诊断技术已经显示出评估体内组织健康的能力，但还没有一种被广泛应用。 领养的医生们还没有采用这些技术，因为它们通常不能覆盖足够的组织 区域是有效的或缺乏足够的灵敏度和特异性的实时异型增生检测。比如说， 角分辨低相干干涉术（a/LCI）使用核形态学测量作为 发育异常变化，对于发育异常BE组织的体内检测具有已证实的灵敏度和特异性。然而，在这方面， a/LCI是一种点探针模式，一次仅检查一个点的组织。在这里，我们寻求纳入/LCI 多模式光学成像平台，能够实际检测BE中的发育异常。 本研究项目的目标是设计、实现和测试先进的多模态光学成像系统 从而能够诊断BE组织中的发育异常。提出了以下具体目标。1)更新a/LCI 图像引导系统。a/LCI系统将重新设计，利用关键光谱仪的进步 组件以提高实用性。将更新光纤探头，以纳入图像引导， 光学相干断层扫描（OCT），这将提高可用性。2)实施真实的时间反馈。软件 将进行更新，以包括组织定向和健康状态的真实的实时指导。3)测试新设计 临床研究临床研究将证实a/LCI检测异型增生的准确性，同时证明 提高新硬件和软件的效率。本研究的子目标是评价OCT 指导a/LCI测量，同时还检测残留的鳞状下BE腺体， 治疗仍然有癌症风险。4)开发多点a/LCI探头。演示广域扫描原理 使用/LCI，无需重新定位即可进行多次测量。进一步的发展将把这个探测器 进入治疗探头的形状因子，特别是Barrx Halo 90，一个2 cm 2的“桨”，安装在 标准内窥镜的外部。5)进行多点探头的临床试验。这项最终的临床研究将测试 通过与该项目中的第一次试验进行比较，确定了新的形状因子。终点将是确定 发育异常阳性活检，同时还评估覆盖组织所需的时间量。完成 这些目标将产生适合广泛采用的临床上敏锐的诊断工具。