Volumetric mapping of tissue microstructure with OCT for enhanced dysplasia detection

项目总结 更好的基于成像的筛查和监测方法将改善癌症患者的预后 通常在晚期诊断，如食管腺癌(EAC)。尽管成功了- 被诊断为低级别或高级别异型增生的患者可以选择积极主动的治疗， 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 死亡率。异型增生的诊断是基于对未采取的食道活检的组织学评估。 在白光内窥镜(WLE)的引导下，其本身没有分辨率来检测 主要的形态变化，即核大小和核浆比(NCR)的增加， 这是发育不良进程的特征。因此，在接受WLE筛查的患者中，漏诊很常见。 近年来，光学相干层析成像(OCT)这一高速、横断面成像技术问世。 被介绍为WLE的替代方案，因为它能够可视化与以下疾病相关的腺体异常 EAC。虽然它提供了比WLE和地下组织询问更高的分辨率，但OCT仍然 无法直接显示核形态，限制了其捕获或分级低或高级别的能力 发育不良。这项提议寻求通过基于物理的新信号PRO来放大当前的OCT能力 方法，以及随附的定制光学硬件，以可视化早期发育不良变化 保持广阔的视野。 首先，我们将开发一个框架来量化健康切除组织中的核大小和NCR。 基于OCT对组织光学性质的测量。以前的工作没有达到反式转换的目的。 将这些特性转化为有意义的发育不良生物标记物，但我们通过新的、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高表面积的不典型增生组织。 大核内皮细胞密度大，纤维化明显。其次，我们将重新设计我们的多项措施- Enment OCT系统实现了临床兼容性，可在10分钟内完成完整的食道扫描 剂量镜成像硬件。概念验证试点研究将评估部署我们的映像的可行性- ING平台在上消化道内窥镜检查中的应用。我们的体积组织显微结构- 真传感平台将不再局限于对食道异型增生的研究，而是可以推广到 其他有机会根据形态变化及早发现的恶性肿瘤。我们期待着 我们的技术将大大改进传统的活检引导成像方法- 疾病，转化为更早的诊断，更大的主动治疗疾病的机会，并免疫。 在高危患者中证明了结果。

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.