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测方法可以改善癌症患者的预后 通常在晚期诊断，如食管腺癌（EAC）。虽然成功- 对于诊断为低度或高度异型增生的患者， 许多高危患者在晚期被诊断出来，几乎没有有效的治疗选择，导致高风险。 死亡率。不典型增生的诊断是基于组织学评价的食管活检采取非- 在白色光内窥镜（WLE）的引导下，WLE本身不具有检测的分辨率 关键的形态学变化，即核大小和核质比（NCR）增加， 发育不良的特征因此，漏诊在WLE筛查的患者中很常见。 最近，光学相干断层扫描（OCT），一种高速，横截面成像技术，在- 作为WLE的替代方案，基于其可视化与以下疾病相关的腺体异常的能力， EAC.虽然它提供了比WLE和次表面组织询问更高的分辨率，但OCT仍然是一种有效的方法。 无法直接观察核形态，限制了其捕获或分级低或高级别的能力 发育不良该提案旨在通过新的基于物理的信号处理来放大当前的OCT功能， 切割方法和伴随的定制光学硬件，以可视化早期发育异常变化， 保持广阔的视野。 首先，我们将开发一个框架，用于量化健康切除组织中的细胞核大小和NCR 基于OCT测量生物组织光学特性的研究， 将这些特性转化为有意义的异型增生生物标志物，但我们用新的、更多的 准确的方法利用额外的样本信息和基于硬件的进步。不像 以前的方法，我们的新方法将适用于表征具有高epi的发育不良组织， 大细胞核的上皮密度和显著的纤维化。其次，我们将重新设计我们的多措施- 增强型OCT系统具有临床兼容性，能够在10分钟内完成完整的食管扫描， 剂量成像硬件。一项概念验证试点研究将评估部署我们的imag的可行性， 在接受上消化道内窥镜检查的患者中使用平台。我们的体积组织显微结构- 真实感测平台将不限于食管发育不良的研究，而是可推广到 其他恶性肿瘤，根据形态学变化有机会早期发现。我们预计 我们的技术将为活检引导提供比传统成像方法更大的改进， 早期诊断，积极主动治疗疾病的机会更大， 在高危患者中得到证实的结果。