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: 10463582
• 负责人: Taylor Marie Cannon
• 金额: $ 4.68万
• 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/10463582
• 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; tissue mapping; 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.

项目概要 更好的基于成像的筛查和监测方法可以改善癌症患者的治疗结果 通常在晚期才被诊断出来，例如食管腺癌（EAC）。虽然成功了—— 诊断患有低度或高度不典型增生的患者可以获得完整的主动治疗选择， 许多高危患者在晚期才被诊断出来，几乎没有有效的治疗选择，导致高危患者 死亡率。不典型增生是根据食管活检的组织学评估来诊断的。 在白光内窥镜 (WLE) 的引导下，其本身不具备检测分辨率 关键的形态变化，即核大小和核质比率（NCR）的增加， 这是发育不良进展的特征。因此，漏诊在 WLE 筛查患者中很常见。 最近，光学相干断层扫描（OCT），一种高速横截面成像技术 因其能够可视化与以下疾病相关的腺体异常而被引入作为 WLE 的替代方案 东非委员会。尽管它提供比 WLE 和次表面组织询问更高的分辨率，但 OCT 仍然存在 无法直接可视化核形态，限制了其捕获或分级低级或高级的能力 发育不良。该提案旨在通过新颖的基于物理的信号亲和力来增强当前的 OCT 能力 处理方法以及随附的定制光学硬件，可可视化早期发育不良变化，同时 保留广阔的视野。 首先，我们将开发一个量化健康切除组织中核大小和 NCR 的框架 基于 OCT 组织光学特性的测量。以前的工作还没有达到跨 将这些特性转化为有意义的发育不良生物标志物，但我们通过新的、更多的方法来实现这一目标 利用额外样本信息和基于硬件的进步的准确方法。不像 与以前的方法相比，我们的新方法将适用于表征具有高 Epi- 的发育异常组织 大细胞核的细胞密度和显着的纤维化。其次，我们将重新设计我们的多项措施 OCT 系统具有临床兼容性，可在 10 分钟内完成完整的食管扫描，并带有 en- 立体成像硬件。概念验证试点研究将评估部署我们的想象的可行性 接受上消化道内窥镜检查的患者的荷兰国际平台。我们的体积组织显微结构 真正的传感平台将不仅限于食管发育不良的调查，而是可推广到 其他有机会根据形态变化进行早期检测的恶性肿瘤。我们预计 我们的技术将比传统的活检引导成像方法提供显着的改进 ，转化为早期诊断、主动治疗疾病的更多机会，以及改善 在高危患者中得到证实的结果。