Volumetric mapping of tissue microstructure with OCT for enhanced dysplasia detection

使用 OCT 绘制组织微观结构的体积图，以增强不典型增生检测

• 批准号: 10315026
• 负责人: Taylor Marie Cannon
• 金额: $ 4.6万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10315026
• 关键词: Address; Area; Barrett Esophagus; Biological Markers; Biopsy; Cancer Etiology; Cell Nucleus; Cellular Morphology; Cessation of life; Clinical; Clinical Research; Colorectal; Complex; Custom; Detection; Diagnosis; Disease; Disease Progression; Dysplasia; Early Diagnosis; Endoscopes; Endoscopy; Environment; Epithelial; Esophageal Adenocarcinoma; Esophageal Intraepithelial Neoplasia; Esophagus; Evaluation; Exhibits; Extracellular Matrix; Feasibility Studies; Fibrosis; Follow-Up Studies; Gastrointestinal Endoscopy; Gastrointestinal tract structure; High grade dysplasia; Histologic; Histology; Ice; Image; Imaging Techniques; Intervention; Investigation; Lesion; Light; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Maps; Measurement; Measures; Metaplasia; Methodology; Methods; Monitor; Morphology; Neoplastic Cell Transformation; Nuclear; Optical Coherence Tomography; Optics; Outcome; Output; Pathogenesis; Patient-Focused Outcomes; Patients; Physics; Pilot Projects; Procedures; Property; Research; Resolution; Risk; Sampling; Scanning; Sensitivity and Specificity; Signal Transduction; Speed; Structure; Surface; Surveillance Methods; System; Technology; Tissue Sample; Tissues; Translating; Update; Validation; Visualization; Work; advanced disease; base; clinical Diagnosis; clinical translation; density; effective therapy; experimental study; gastrointestinal; imaging modality; imaging platform; improved; improved outcome; in vivo; mortality; novel; optical imaging; particle; patient screening; premalignant; screening; signal processing; tool; tumor progression

Project summary Better imaging-based screening and surveillance methods stand to improve patient outcomes in cancers that are typically diagnosed at late stages, such as esophageal adenocarcinoma (EAC). Although success- ful proactive treatment options are available to patients diagnosed with low- or high-grade dysplasia, many at-risk patients are diagnosed at later stages with few effective treatment options, leading to high mortality rates. Dysplasia is diagnosed based on histological evaluation of esophageal biopsies taken un- der the guidance of white light endoscopy (WLE), which in itself does not have the resolution to detect the key morphological changes, namely increases in nuclear size and nuclear cytoplasmic ratio (NCR), that characterize dysplastic progression. Thus, missed diagnoses are common in WLE-screened patients. Recently, optical coherence tomography (OCT), a high-speed, cross-sectional imaging technique was in- troduced as an alternative to WLE based on its ability to visualize glandular anomalies associated with EAC. Although it offers higher resolution than WLE and sub-surface tissue interrogation, OCT remains unable to directly visualize nuclear morphology, limiting its ability to capture or grade low- or high-grade dysplasia. This proposal seeks to amplify current OCT capabilities with novel physics-based signal pro- cessing methods, and accompanying custom optical hardware, to visualize early dysplastic change while retaining a wide field of view. Firstly, we will develop a framework for quantifying nuclear size and NCR in healthy excised tissues based on the measurement of tissue optical properties with OCT. Previous work has fallen short of trans- lating these properties into meaningful dysplastic biomarkers, but we accomplish this with new, more accurate methodology leveraging additional sample information and hardware-based advances. Unlike previous approaches, our new methods will be suitable for characterizing dysplastic tissues with high epi- thelial densities of large nuclei and significant fibrosis. Secondly, we will redesign our multi-measure- ment OCT system for clinical compatibility, enabling full esophageal scans in under ten minutes with en- doscopic imaging hardware. A proof-of-concept pilot study will assess feasibility of deploying our imag- ing platform in patients undergoing upper gastrointestinal endoscopy. Our volumetric tissue microstruc- ture sensing platform will not be limited to investigation of esophageal dysplasia, but generalizable to other malignancies with opportunity for early detection based on morphological changes. We anticipate that our technology will offer significant improvement over traditional imaging methods for biopsy guid- ance, translating into earlier diagnoses, greater opportunity for proactive treatment of disease, and im- proved outcomes in at-risk patients.

项目摘要 更好的基于成像的筛查和监视方法可以改善癌症的患者预后 通常在晚期被诊断出来，例如食管腺癌（EAC）。虽然成功 - 可诊断出患有低级或高级发育不良的患者，可以使用积极主动的治疗选择， 许多处于危险的患者在以后的阶段被诊断出，有效的治疗选择很少，导致高 死亡率。根据对未进行的食管活检的组织学评估来诊断出异常 白光内窥镜检查（WLE）的指导本身没有检测到的分辨率 关键的形态变化，即核大小和核细胞质比（NCR）的增加， 这是发育不良进展的特征。因此，遗漏的诊断在WLE筛选的患者中很常见。 最近，光学相干断层扫描（OCT）是一种高速，横截面技术的技术 基于其可视化与与之相关的腺异常的能力，作为WLE的替代方案 EAC。尽管它提供的分辨率高于WLE和地下组织询问，但OCT仍然存在 无法直接可视化核形态，限制其捕获或评分低或高级的能力 发育不良。该建议旨在通过新颖的基于物理的信号促进来扩大当前的OCT功能 限制方法和随附的自定义光学硬件，以可视化早期的异型变化，同时 保持广泛的视野。 首先，我们将开发一个用于量化健康切除组织中核大小和NCR的框架 基于具有OCT的组织光学特性的测量。以前的工作已经不足 将这些特性融入有意义的发育不良生物标志物中，但我们以新的，更多的 准确的方法论利用其他示例信息和基于硬件的进步。与众不同 以前的方法，我们的新方法将适合表征具有高表观的发育不良组织 大核和明显的纤维化的三个密度。其次，我们将重新设计我们的多种测量 - 临床兼容性的OCT系统，可在不到十分钟的情况下进行全面食管扫描 DOSCOPIC成像硬件。概念证明的试点研究将评估部署我们的想象的可行性 接受上胃肠道内窥镜检查的患者中的平台。我们的体积组织微观 感测平台不仅限于研究食管发育不良，但可推广到 其他恶性肿瘤有基于形态变化的早期检测的机会。我们期待 我们的技术将对用于活检指南的传统成像方法提供显着改进 - Ance，转化为早期诊断，积极治疗疾病的机会更大，以及 处于危险患者的结果证明。