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: 8838786
• 负责人: Meng Yin
• 金额: $ 35.06万
• 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/8838786
• 关键词: 3-Dimensional; Accounting; Acute; Adopted; Animals; Behavior; Biological; Biopsy; Cells; Clinical; Data; Databases; Dependency; Development; 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; 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）：机械性能是监测和表征细胞和组织的各种病理生理状况的有前途的替代品。例如，我们率先开发了肝脏磁共振弹性成像 (MRE)，这是一种用于测量肝脏硬度的无创成像技术，该技术已开始在临床上广泛用于评估肝纤维化，作为活检的替代方案。尽管取得了这些进展，但仍需要进一步开发肝脏 MRE，以便其具有跟踪疾病进展和治疗反应所需的精度。肝脏的几种内在病理状况（例如炎症）会影响肝脏硬度表征的阳性预测价值 单纯肝纤维化。这些因素导致相似量的刚度增加，但具有不同的病理生理学起源并对应于不同的结构变化。因此，该提案的主要目标是开发先进的肝脏 MRE 技术，包括多孔粘弹性（PVE）机械模型，能够区分炎症和纤维化，同时考虑肝组织中脂肪变性的影响。我们的基本假设是，可以使用双相 PVE 理论合理地对肝脏组织进行建模，该双相 PVE 理论由本质上各向同性的不可压缩粘弹性固体基质相和不可压缩饱和流体相组成。假设基于这种 PVE 模型对时谐肝脏 MRE 数据进行分析将能够将脂肪变性和纤维化相关的固体基质机械响应与炎症相关的孔隙流体行为分开。在目标 1 中，我们将实施 PVE 分析方法来确定 PVE 参数并评估模型研究中模型的关键假设。在目标 2 中，我们将使用急性肝脏炎症小鼠模型来评估 PVE 模型区分和量化炎症程度的潜力，方法是测试无创计算的 PVE 孔隙压力是否与有创测量的间质液压力 (IFP) 显着相关，表明它可用作组织学证明的炎症程度的替代指标。在目标 3 中，我们将进一步评估 PVE 肝脏 MRE 区分和量化慢性肝病小鼠模型（NAFLD/NASH 小鼠模型）中共存炎症和纤维化的潜力。我们假设 MRE 评估的 PVE 参数（弹性、粘度和孔隙压力）与肝组织学（纤维化、脂肪变性和炎症）之间存在显着相关性。 在目标 4 中，我们将利用现有患者数据进行一项转化性人体研究，以确定是否存在至少一个或多个 PVE 参数的组合，可以区分和量化进行性脂肪变性、早发性和持续性炎症以及随后发生的肝纤维化。肝。这项拟议研究的成功将最大限度地利用肝脏 MRE 提供的临床相关信息，从而大大提高我们对慢性肝病广泛病理生理学范围的疾病进展的理解和诊断能力。