Quantative image analysis models of IPF pathogenesis

（申请人的摘要）最近，血管生成的不平衡、血管生成的调节异常、血管生成的抑制、 细胞外基质和纤维增生而不是炎症 被假定为使IPF中的肺纤维化永久化。肺泡炎检测 因此在评估中几乎没有预后或致病相关性 这些案件。UIP的病理学异质性导致BAL和经支气管 活检（TBBx）受采样误差复合尝试的影响 来阐明致病途径一种非侵入性机制， 在整体和区域基础上对整个肺进行“形态测量”评估 会很理想HRCT数据的定量图像分析（QIA）显示， 与炎症、血管生成和纤维化相关， 全球和区域范围内IPF的这些独立表现， 可能通过支气管镜检查或HRCT目视检查。假设是： CT-QIA可以更好地检测炎症的存在、程度和进展， 血管生成和纤维化，因此可用于 无法区分UIP、DIP、NSIP或NSIP伴纤维化的患者 通过常规临床、放射学和生理学评估或 采样限制BAL和TBBx。具体目标是：1）制定CT-QIA 在能够评估肺纤维化的小鼠模型中， 肺纤维化的发展和进展2）开发CT-QIA模型， IPF能够区分炎症、血管生成和纤维化， 更好地描述临床诊断ILD患者的特征， 病理学定义的UIP、DIP、NSIP和NSIP伴纤维化，以及3） 确定炎症、血管生成和纤维化的相对进展 在接受泼尼松单药治疗的经临床评估的IPF患者中，或 IFN-γ和低剂量泼尼松或硫唑嘌呤加泼尼松。主要 该项目的目的是区分血管生成、炎症 和纤维化在IPF发病机制中的作用，以便更好地表征其 与IPF发病机制的关系以及区分UIP患者， DIP、NSIP或NSIP伴纤维化不可能使用常规技术。

(Applicant's Abstract) Recently, imbalance in angiogenesis, dysregulation of the extra cellular matrix and fibroproliferation rather than inflammation has been postulated to perpetuate lung fibrosis in IPF. Detection of alveolitis may therefore have little prognostic or pathogenic relevance in the assessment of these cases. The heterogeneous pathology of UIP results in BAL and trans-bronchial biopsy (TBBx) to be subject to sampling errors compounding attempts to elucidate pathogenic pathways. A noninvasive mechanism to provide a "morphometric" assessment of the whole lung on a global and regional basis would be ideal. Quantitative Image Analysis (QIA) of HRCT data has shown a correlation with inflammation, angiogenesis and fibrosis and can identify these independent manifestations of IPF on a global and regional basis not possible with bronchoscopy or visual inspection of HRCT. The hypothesis is: CT-QIA can better detect the presence, extent and progression of inflammation, angiogenesis and fibrosis in patients with ILD and so can be used to distinguish patients with UIP, DIP, NSIP or NSIP with fibrosis not possible with conventional clinical, radiographic and physiologic assessment or with sampling limited BAL and TBBx. The specific aims are to 1) develop a CT-QIA model of pulmonary fibrosis in a murine model capable of assessing the development and progression of pulmonary fibrosis 2) develop a CT-QIA model of IPF capable of distinguishing inflammation, angiogenesis and fibrosis to better characterize patients with clinically diagnosed ILD with respect to pathologically defined UIP, DIP, NSIP and NSIP with fibrosis and 3) to determine the relative progression of inflammation, angiogenesis and fibrosis in patients with clinically assessed IPF treated with Prednisone alone, or IFN-gamma and low-dose prednisone or azathioprine plus prednisone. The main objective of this project is to distinguish between angiogenesis, inflammation and fibrosis in the pathogenesis of IPF in order to better characterize their relationship to the pathogenesis of IPF and to distinguish patients with UIP, DIP, NSIP or NSIP with fibrosis not possible with conventional techniques.