Advanced a/LCI systems for improved clinical utility

先进的 a/LCI 系统可提高临床实用性

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

在巴雷特食管患者中，对体内检测不典型增生的不满意需要（BE），是由慢性酸反射X引起的肿瘤组织状态。与增加的风险有关食管癌，一种发病率较高的疾病。患有周期性内窥镜患者通过系统的活检进行监测，以寻找癌前的，发育不良的组织，此时治疗。指示通过热消融或手术治疗。这些过程以白光内窥镜指导但是，由于在组织表面没有视觉证据，因此检测发育不良的有效性受到限制。因此，即使患者接受定期的内窥镜监测，发育不良也没有发现。光学诊断技术表明能够在体内评估组织健康的能力，但没有一个广泛的采用。医师没有接受这些技术，因为它们通常没有覆盖足够的组织对实时发育不良检测有效或缺乏足够的敏感性和特异性的区域。例如，角度分辨的低相干干扰（A/LCI）使用核形态测量作为生物标志物发育不良的变化，具有证实的敏感性和特异性，可在体内检测失调是组织。然而， A/LCI是一种点探针方式，一次仅在一个位置检查时间。在这里，我们试图合并A/LCI 进入一个多模式光学成像平台，该平台可以实际检测BE中的发育异常。该研究项目的目的是设计，实施和测试高级多模式光学成像系统使BE组织中发育不良的诊断。提出了以下特定目标。 1）更新A/LCI 带有图像指导的系统。 A/LCI系统将重新设计，利用关键光谱仪的进步改善效用的组件。光纤探针将进行更新，以使用光学相干断层扫描（OCT）将提高可用性。 2）实现实时反馈。软件将更新以包括组织取向和健康状况的实时指导。 3）测试新设计临床研究。临床研究将确认A/LCI在证明发育异常的同时证明的准确性提高新硬件和软件的效率。这项研究的子将是评估OCT 引导A/LCI测量值，同时还检测出残留仍然是癌症风险的治疗。 4）开发多点A/LCI探针。展示大区域扫描原理使用A/LCI，启用多次测量而无需重新定位。进一步的进步将整合这一证明进入治疗性探针的外形，特别是Barrx Halo 90，一个安装在上面的2 cm2“桨” 标准内窥镜的外部。 5）进行多点探针的临床试验。这项最终的临床研究将测试通过与该项目的第一个试验进行比较，新的外形。终点将是确定的产量发育不良的正活检同时还评估覆盖组织所需的时间。完成这些目标将产生适合采用宽度的临床尖锐诊断工具。