Second Harmonic Generation analysis of the ECM in idiopathic pulmonary fibrosis

特发性肺纤维化 ECM 的二次谐波产生分析

• 批准号: 9122490
• 负责人: Paul J Campagnola
• 金额: $ 18.28万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9122490
• 关键词: Architecture; Area; Biological Markers; Biomedical Engineering; Cessation of life; Cicatrix; Classification; Clinical; Clinical Markers; Collagen; Computer Vision Systems; Computers; Diagnostic; Disease; Disease Progression; Elastin; Equilibrium; Extracellular Matrix; Fibrosis; Future; Generations; Hamman-Rich syndrome; Health; Histologic; Image; Individual; Label; Lung; Maintenance; Methods; Microscope; Microscopy; Modality; Modeling; Monitor; Morphology; Normal tissue morphology; Pathologic; Patients; Pharmaceutical Preparations; Physicians; Process; Protein Isoforms; Resolution; Sampling; Scheme; Scientist; Sensitivity and Specificity; Severities; Signal Transduction; Specimen; Staging; Structure; Survival Rate; System; Techniques; Texture; Thick; Three-Dimensional Imaging; Tissue Sample; Tissues; Vision; base; improved; in vivo imaging; interdisciplinary approach; prognostic; prognostic tool; second harmonic; tool

 DESCRIPTION (provided by applicant): Second Harmonic Generation analysis of the ECM in idiopathic pulmonary fibrosis Idiopathic pulmonary fibrosis (IPF) is a disorder characterized by unrelenting scarring and stiffening of the lungs that leads to the death of an estimated 34,000 individuals in the U.S. each year. Unfortunately, individuals with IPF have extremely limited treatment options, as no effective drugs have been identified to halt the progression of fibrosis. Despite the importance of collagens to the structural organization both normal and remodeled ECM, little is known about how collagen structure in IPF differs from that of normal tissue architecture. There is a clear need to develop highly specific/sensitive techniques to probe collagen structure and organization in IPF tissues. In this project we will implement new collagen specific analyses using the high resolution microscopy technique of Second Harmonic Generation (SHG). This method is sensitive to both the fibrillar organization and also sub-resolution aspects of macro and supramolecular assembly. Here we will utilize SHG microscopy to: 1) determine the how pathologic collagen organization (seen in IPF) differs from normal tissue; 2) identify and quantify areas of active fibrosis (enriched in collagen III) from "old" or mature fibrosis (high in collagen I) in IPF lung specimens; 3) assess changes in elastin and collagen distribution during disease progression; and 4) correlate areas of high collagen III/I signal in IPF histologic samples with clinical markers of disease activity. As part of the project, we will develop customized automated machine vision routines to automatically classify tissues in terms of severity. We will specifically focus all of our efforts on studying structure around fibroblastic foci, which will be identified by other microscope modalities. These foci are thought to be at the leading edge of ECM remodeling but the dynamics of their formation in relationship to the overall fibrotic process remain unclear. We hypothesize that these structural changes will serve as label- free biomarkers of IPF and further hypothesize that the collagen is altered specifically around foci in a manner which is associated with disease progression. The information gained may form the basis of future prognostic/diagnostic schemes. We propose 2 Aims: Aim 1 Polarization resolved SHG to determine distribution of Col I/III and other ECM changes in different stages of IPF. Aim 2. Develop classification system of morphological changes in IPF visualized by SHG.

 描述（由适用提供）：特发性肺纤维化特发性肺纤维化（IPF）中ECM的第二次谐波生成分析是一种疾病，其特征是肺部无情的疤痕和僵硬，导致美国估计的34,000名患者死亡。不幸的是，患有IPF的人的治疗选择极为有限，因为尚未发现有效的药物可以停止纤维化的进展。尽管胶原蛋白对正常和重塑ECM的结构组织的重要性，但对于IPF中IPF的结构与正常组织结构的胶原蛋白结构如何不同。显然需要开发高度特异性/敏感的技术来探测IPF组织中的胶原蛋白结构和组织。在这个项目中，我们将使用第二次谐波生成（SHG）的高分辨率显微镜技术实施新的胶原蛋白特定分析。该方法对宏观和超分子组装的纤维组织以及子分辨率方面都很敏感。在这里，我们将利用SHG显微镜为：1）确定病理胶原蛋白组织（请参阅IPF中）与正常组织的不同； 2）在IPF肺标本中，从“旧”或成熟的纤维化（胶原蛋白I）中识别和量化活性纤维化区域（富含胶原蛋白III）； 3）评估疾病进展过程中弹性蛋白和胶原蛋白分布的变化； 4）与IPF组织学样本中高胶原蛋白III/I信号的区域与疾病活性的临床标记相关联。作为项目的一部分， 我们将开发自定义的自动化机器视觉程序，以自动根据严重性对时间进行分类。我们将专门将所有精力集中在研究围绕成纤维细胞灶的结构上，这些结构将由其他显微镜模态识别。这些焦点被认为是ECM重塑的前沿，但它们与整体纤维化过程的形成动力学尚不清楚。我们假设这些结构性变化将作为IPF的无标记生物标志物，并进一步假设胶原蛋白会以与疾病进展相关的方式特异性改变。获得的信息可能构成未来预后/诊断方案的基础。我们提出了2个目标：目标1极化解决了SHG，以确定Col I/III的分布和IPF不同阶段的其他ECM变化。 AIM 2。开发SHG可视化IPF形态变化的分类系统。

项目成果

3D texture analysis for classification of second harmonic generation images of human ovarian cancer.

• DOI: 10.1038/srep35734
• 发表时间: 2016-10-21
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Wen B;Campbell KR;Tilbury K;Nadiarnykh O;Brewer MA;Patankar M;Singh V;Eliceiri KW;Campagnola PJ
• 通讯作者: Campagnola PJ