Assessing Use of Acoustic Radiation Force to Noninvasively Measure Liver Pressure

描述（由申请方提供）：目前用于评价肝脏疾病进展的金标准包括血清检测、肝活检和随着疾病进展的肝静脉压梯度（HVPG）测量的组合。超声提供了一个机会，以评估两个方面的临床肝脏疾病，传统上测量的侵入性：肝纤维化和HVPG。第一，肝纤维化的超声表征，已经广泛研究了与比较基于活检的纤维化阶段与非侵入性获得的肝硬度的定量估计有关的问题。具体而言，基于声辐射力脉冲（ARFI）的组织硬度定量估计已经成功地无创区分了中度和晚期肝纤维化。最近的研究表明，基于超声的肝硬度估计也随着肝静脉加压而增加。硬度指标与肝间质压力的这些变化可能会混淆基于硬度的肝纤维化分期预测。这种观察到的加压硬化行为的基本机制还没有很好地理解，并且没有用常用的线弹性力学模型来解释。本提案中设计的项目结合了从离体肝脏样本、非线性组织模拟材料和有限元模拟中收集的数据，以更好地了解观察到的肝脏压力依赖性硬化，并评估体内肝脏压力表征的潜力。应变依赖性超弹性模型可以为理解加压时观察到的肝硬化提供基础。拟议的工作涉及开发和验证这个模型，使用有限元模拟和校准的非线性组织模仿材料的参数分析。使用定制设计的实验装置获得了初步数据，该装置允许在约束和非约束条件下对切除的肝脏加压。一旦该模型得到验证，基于ARFI的实验离体肝脏硬度测量在各种加压状态下将适合建立非线性材料参数。拟议项目的主要目标是使用非线性肝脏模型研究使用基于ARFI的剪切刚度指标无创表征肝脏压力的方法，以减少对基于导管的HVPG测量的需求。非线性组织模拟材料将变形类似于肝脏加压观察到的应变状态，两个超声换能器将用于确定是否可以使用基于ARFI的刚度度量和基础材料特性的知识来找到肝脏的变形状态。该实验装置也可用于临床试验前的离体肝脏加压实验。用两个换能器对压缩的非线性体模进行成像，将检验压力下肝脏的非线性行为可用于无创估计HVPG的假设。

DESCRIPTION (provided by applicant): The current gold standard for evaluating the progression of liver diseases includes a combination of serum testing, liver biopsy, and, as the disease progresses, hepatic venous pressure gradient (HVPG) measurement. Ultrasound provides an opportunity to evaluate two aspects of clinical hepatic disease that are traditionally mea- sured invasively: liver fibrosis and HVPG. The first, ultrasound characterization of liver fibrosis, has been ex- tensively studied with relation to comparing biopsy-based fibrosis stage to noninvasively obtained quantitative estimates of liver stiffness. Specifically, Acoustic Radiation Force Impulse (ARFI) based quantitative estimation of tissue stiffness has successfully distinguished advanced from moderate hepatic fibrosis noninvasively. Recent studies have suggested that ultrasound-based estimates of liver stiffness also increase with hepatic venous pressurization. These changes in stiffness metrics with hepatic interstitial pressure may confound stiffness-based predictions of liver fibrosis stage. The underlying mechanism for this observed stiffening behavior with pressurization is not well understood, and is not explained with commonly used linear elastic mechanical models. The project designed in this proposal combines data collected from ex-vivo liver samples, nonlinear tissue-mimicking materials, and finite element simulations to better understand the observed hepatic pressure-dependent stiffening and evaluate the potential for hepatic pressure characterization in-vivo. A strain-dependent hyperelastic model can provide the basis for understanding observed hepatic stiffening with pressurization. The proposed work involves development and validation of this model using parametric analyses of finite element simulations and calibration to nonlinear tissue-mimicking materials. Preliminary data have been obtained using a custom designed experimental setup that allows pressurization of excised livers under both constrained and unconstrained conditions. Once the model has been validated, ARFI-based experimental ex-vivo hepatic stiffness measures under various pressurization states will be fit to established nonlinear material parameters. The primary goal of the proposed project is to use the nonlinear hepatic model to investigate methods to noninvasively characterize liver pressures using ARFI-based shear stiffness metrics in order to reduce the need for catheter-based HVPG measurements. Nonlinear tissue-mimicking materials will be deformed similarly to the strain state observed with hepatic pressurization and two ultrasound transducers will be used to determine whether ARFI-based stiffness metrics and knowledge of underlying material properties can be used to find the deformation state of the liver. This experimental setup can also be used on ex-vivo hepatic pressurization experiments prior to clinical testing. Imaging compressed nonlinear phantoms with two transducers will test the hypothesis that the nonlinear behavior of the liver under pressure can be exploited to noninvasively estimate HVPG.