Advanced a/LCI systems for improved clinical utility

Barrett‘s食道患者体内异型增生的迫切需要尚未得到满足 (BE)，一种由慢性酸反流引起的肿瘤组织状态。BE与心脏病风险增加有关 食道癌是一种发病率较高的疾病。BE患者定期接受内窥镜检查 通过系统活检进行监测，以寻找癌前病变、发育不良组织，在这一点上可以治愈 需要通过热消融或手术治疗。这些手术是由白光内窥镜检查指导的。 但由于在组织表面没有肉眼可见的证据，检测异型增生的效果有限。 因此，即使BE患者接受定期的内窥镜监测，异型增生仍未被发现。 光学诊断技术已经显示出评估体内组织健康的能力，但还没有得到广泛的应用 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 区域是否有效或缺乏足够的敏感性和特异性来实时检测异型增生。例如, 角度分辨低相干干涉测量(a/LCI)使用核形态测量作为生物标记物 发育不良改变，经证实具有体内检测发育不良BE组织的敏感性和特异性。然而， A/LCI是一种点探头方式，一次只能检查一个点的组织。在这里，我们寻求合并a/lci 到一个多模式光学成像平台，从而能够实际检测BE中的异型增生。 该研究项目的目标是设计、实施和测试先进的多模式光学成像系统 以便能够诊断BE组织中的异型增生。提出了以下具体目标。1)更新a/lci 具有图像制导的系统。A/lci系统将被重新设计，利用关键光谱仪的进步。 组件，以提高实用性。光纤探头将进行更新，以纳入使用 光学相干层析成像(OCT)，这将提高可用性。2)实现实时反馈。软件 将被更新，以包括组织定向和健康状态的实时指导。3)测试新设计 临床研究。临床研究将证实a/LCI在显示时检测异型增生的准确性 提高新硬件和软件的效率。这项研究的一个子目标是评估OCT 指导A/LCI测量，同时还检测残留的亚鳞状腺体 仍然存在癌症风险的治疗。4)研制多点a/lci探头。演示广域扫描原理 使用a/lci，无需重新定位即可实现多个测量。进一步的进展将整合这个探测器 进入治疗性探头的外形因素，特别是Barrx Halo 90，一个安装在 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 通过与该项目的第一次试用进行比较，得出了新的外形系数。终点将是决定收益率的 进行发育不良的阳性活检，同时评估覆盖组织所需的时间。完成 这些目标将产生一种临床上精辟的诊断工具，适合广泛采用。

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.