Advanced Assessment of Hepatic Inflammation and Fibrosis with MR Elastography

利用 MR 弹性成像对肝脏炎症和纤维化进行高级评估

• 批准号: 9039590
• 负责人: Meng Yin
• 金额: $ 35.78万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9039590
• 关键词: 3-Dimensional; Accounting; Acute; Adopted; Animals; Behavior; Biological; Biopsy; Cells; Clinical; Data; Databases; Dependency; Diagnosis; Diffuse; Disease; Disease Progression; Elasticity; Elements; Equation; Evaluation; Fibrosis; Freezing; Frequencies; Goals; Health; Hepatic; Hepatology; Histologic; Histology; Imaging technology; Inflammation; Intercellular Fluid; Isotropy; Liquid substance; Liver; Liver Fibrosis; Liver diseases; Measures; Mechanics; Methods; Modeling; Monitor; Mus; Natural History; Pathologic; Patients; Phase; Predictive Value; Process; Property; Solid; Soy Bean Curd; Techniques; Testing; Time; Tissues; Translating; Viscosity; chronic liver disease; clinical Diagnosis; clinically relevant; disease diagnosis; early onset; elastography; experience; human study; human subject; in vivo; in vivo Model; liver development; mouse model; non-alcoholic fatty liver; non-invasive imaging; nonalcoholic steatohepatitis; pressure; response; soft tissue; success; theories; tool; viscoelasticity

DESCRIPTION (provided by applicant): Mechanical properties are promising surrogates for monitoring and characterizing various pathophysiologic conditions of cells and tissues. For example, we have pioneered the development of liver MR elastography (MRE), a noninvasive imaging technology for measuring liver stiffness, which is beginning to see widespread clinical use for assessing hepatic fibrosis as an alternative to biopsy. Despite this progress, there is a need to further develop hepatic MRE so that it can have the precision necessary to track disease progression and response to therapy. Several intrinsic pathologic conditions of the liver (e.g., inflammation) compromise the positive predictive value of liver stiffness for characterizing hepatic fibrosis alone. These factors cause similar amounts of stiffness augmentation but have different pathophysiological origins and correspond to different architectural changes. Therefore, the major goal of this proposal is to develop advanced hepatic MRE techniques, including poroviscoelastic (PVE) mechanical models, capable of differentiating inflammation and fibrosis while considering the effects of steatosis in the liver tissue. Our basic assumption is that liver tissue can reasonably be modeled using biphasic PVE theory consisting of an intrinsically isotropic incompressible viscoelastic solid matrix phase and an incompressible saturated fluid phase. The hypothesis is that analysis of time-harmonic hepatic MRE data based on such a PVE model will enable the separation of the steatosis- and fibrosis-related solid matrix mechanical responses from that of the inflammation-related pore fluid behavior. In Aim 1, we will implement a PVE analysis method to determine PVE parameters and evaluate the key assumptions of the model in phantom studies. In Aim 2, we will use an acute hepatic inflammation mouse model to evaluate the potential for a PVE model to differentiate and quantify inflammation extent by testing whether noninvasively calculated PVE pore pressure significantly correlates with invasively measured interstitial fluid pressure (IFP), indicating tha it could be used as a surrogate for histology-proven inflammation extent. In Aim 3, we will further evaluate the potential for PVE hepatic MRE to differentiate and quantify coexisting inflammation and fibrosis in mouse models with chronic liver disease (NAFLD/NASH mouse model). We hypothesize that significant correlations can be found among MRE-assessed PVE parameters (elasticity, viscosity & pore pressure) and hepatic histology (fibrosis, steatosis & inflammation). In Aim 4, we will perform a translational human study using existing patient data to determine if there is at least one or a combination of several PVE parameters that can distinguish and quantify progressive steatosis, early onset and ongoing inflammation and subsequently developed hepatic fibrosis in the liver. The success of this proposed study will maximize the clinically relevant information provided by hepatic MRE to substantially advance our understanding and ability to diagnose disease progress in the broad pathophysiologic spectrum of chronic liver diseases.

描述（由申请人提供）：机械性能是有望监测和表征细胞和组织各种病理生理状况的替代物。例如，我们开创了肝MR弹性术（MRE）的发展，这是一种用于测量肝脏僵硬度的无创成像技术，该技术开始看到广泛的临床用途，用于评估肝纤维化作为活检的替代方法。尽管取得了这种进展，但仍需要进一步发展肝MRE，以便它具有跟踪疾病进展和对治疗反应的必要精度。肝脏的几种内在病理条件（例如炎症）损害了肝脏刚度的阳性预测值以表征 仅肝纤维化。这些因素会导致相似的刚度增强，但具有不同的病理生理起源，对应于不同的建筑变化。因此，该提案的主要目的是开发先进的肝MRE技术，包括PorovisCo弹性（PVE）机械模型，能够区分炎症和纤维化，同时考虑脂肪变性在肝组织中的影响。我们的基本假设是，可以使用双相PVE理论对肝组织进行合理的建模，该理论由本质上的各向同性不可压缩的粘粘性固体基质相和不可压缩的饱和液相模拟。假设是，基于这种PVE模型的时谐肝MRE数据分析将使与炎症相关孔隙流体行为的脂肪变性和纤维化相关的固体基质机械响应的分离。在AIM 1中，我们将实施一种PVE分析方法来确定PVE参数并评估幻影研究中模型的关键假设。在AIM 2中，我们将使用急性肝炎症鼠标模型来评估PVE模型通过测试非侵入性计算的PVE孔隙压力是否与侵入性测量的间质流体压力（IFP）显着相关的PVE模型的潜力，以表明THA可以用作替代的替代性促进液含量，以使其用于替代化含量，以使其用于促进液位。在AIM 3中，我们将进一步评估PVE肝MRE的潜力，以分化和量化患有慢性肝病（NAFLD/NASH小鼠模型）的小鼠模型中共存的炎症和纤维化。我们假设可以在MRE评估的PVE参数（弹性，粘度和孔隙压力）和肝组织学（纤维化，脂肪变性和炎症）中发现显着相关性。 在AIM 4中，我们将使用现有的患者数据进行翻译人类研究，以确定几种PVE参数的至少有一个或组合，可以区分和量化进行性脂肪变性，早期发作和持续的炎症，然后在肝脏中产生肝纤维化。这项拟议的研究的成功将最大化肝MRE提供的临床相关信息，从而大大提高我们的理解和诊断慢性肝病的广泛病理生理谱系中疾病进展的能力。