Quantitative histopathology for cancer prognosis using quantitative phase imaging on stained tissues

项目摘要 大约八分之一的美国女性会在一生中患上浸润性乳腺癌。早期诊断 和预后是改善健康结果的关键。组织活检的预后标记物有助于临床医生 做出治疗决定，完善患者风险分层。新的研究扩展了目前的 预后标志，以更好地提供个性化治疗方案。然而，分析前的可变性 各种因素(活检采集、处理和储存)可能对生物标志物的评估产生重大影响 这可能会在病人护理方面导致潜在的严重后果。有一种公认的需要 开发与生物样品制剂不变的临床相关生物标记物。 该项目提出了一种提取固有组织形态信息的技术解决方案，不受 组织染色、切片厚度或切片错误的可变性。空间光干涉显微镜 (SLIM)被证明提供了来自肿瘤微环境的预后标记物 邻近癌细胞的非恶性组织的纳米级组织，即基质对 癌症。初步结果表明，SLIM可以区分匹配的患者对(好与 不良结果)，并且能够消除假阳性并帮助临床医生分配适当的 治疗。 对于此项目，我们将验证超薄色彩(CSLIM)功能作为现有、 染色的组织病理学切片。CSLIM将同时呈现亮场和量化相 图像，在一次扫描中。CSLIM将在具有颜色的整个幻灯片成像(WSI)仪器中实施 病理医生熟悉的明亮视野图像，同时保持与染色无关的信号，该信号完整 预后价值。WSI仪器对基质和胶原纤维的高度敏感性将用于开发 乳房预后的可靠标记物，与组织切片厚度、颜色变异性无关 相同的染色类型(例如，H&E)和交叉染色(H&E，各种免疫化学染色等)。有了这个新的 仪器，我们将测试196例TMA的染色不变性，并用300例进行验证 活组织检查。这项工作是将成像、病理学和图像处理方面的专业知识结合在一起的结果 四个站点：UIUC Beckman Institute、Urbana的Mills乳腺癌研究所、UIC病理和U。 威斯康星州。

Project Summary About 1 in 8 U.S. women will develop invasive breast cancer over the course of her lifetime. Early diagnosis and prognosis are key to improving health outcomes. Prognostic markers in tissue biopsies help clinicians make treatment decisions and refine the patient risk stratification. New research expands the current prognostic markers to better deliver personalized treatment regimens. However, the variability of preanalytical factors (biopsy collection, processing and storage) can have a significant impact on biomarkers evaluation which can result in potentially serious consequences in terms of patient care. There is an identified need for developing clinically relevant biomarkers that are invariant to biospecimen preparation. This project proposes a technical solution to extracting intrinsic tissue morphology information, unaffected by variability in tissue staining, slice thickness, or sectioning errors. Spatial Light Interference Microscopy (SLIM) was shown to provide prognostic markers derived from tumor microenvironment using nanoscale organization of the non-malignant tissue adjacent to cancer cells, i.e., the stromal response to cancer. Preliminary results indicate that SLIM can distinguish between pairs of “matched” patients (good vs. bad outcome) and has the capability to eliminate false positives and help the clinician assign the appropriate treatment. For this project, we will validate color SLIM (cSLIM) capabilities as a prognostic tool for existing, stained histopathology slides. cSLIM will render simultaneously bright field and quantitative phase images, in a single scan. cSLIM will be implemented in a whole slide imaging (WSI) instrument with the color bright field image familiar to pathologists, while maintaining a stain-independent signal, which has intact prognosis value. The WSI instrument’s high sensitivity to stroma and collagen fibers will be used to develop robust markers for breast prognosis, which are independent of tissue slice thickness, color variability within the same stain type (say, H & E), and across stains (H & E, various immunochemical stains, etc). With this new instrument, we will test the staining-invariance performance on 196 TMA cases and validate with 300 biopsies. The work is the results of combining expertise in imaging, pathology, and image processing across four sites: UIUC Beckman Institute, the Mills Breast Cancer Institute in Urbana, UIC Pathology, and U. Wisconsin.