Assessing Use of Acoustic Radiation Force to Noninvasively Measure Liver Pressure

描述(由申请人提供)：目前评估肝脏疾病进展的黄金标准包括血清检测、肝脏活检和随着疾病进展而进行的肝静脉压力梯度(HVPG)测量。超声提供了评估临床肝病的两个方面的机会，这两个方面传统上是侵入性测量的：肝纤维化和HVPG。第一，肝纤维化的超声特征，通过比较基于活检的纤维化分期和非侵入性获得的肝脏硬度的定量评估，进行了广泛的研究。具体地说，基于声辐射力脉冲(ARFI)的组织硬度定量评估已成功地无创性地区分了重度和中度肝纤维化。最近的研究表明，超声对肝脏硬度的估计也随着肝静脉加压而增加。这些硬度指标与肝脏间质压力的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潜在机制并不是很好地理解，也不能用常用的线弹性力学模型来解释。该方案中设计的项目结合了从体外肝脏样本、非线性组织模拟材料和有限元模拟收集的数据，以更好地理解观察到的肝脏压力依赖的硬化，并评估体内肝脏压力表征的可能性。应变相关的超弹性模型可以为理解加压时观察到的肝脏硬化提供基础。建议的工作包括使用有限元模拟的参数分析和对非线性组织模拟材料的校准来开发和验证该模型。初步数据是使用定制设计的实验装置获得的，该装置允许在受限和非受限条件下对切除的肝脏进行加压。一旦模型得到验证，各种加压状态下基于ARFI的实验性体外肝脏硬度测量将适用于所建立的非线性材料参数。该项目的主要目标是使用非线性肝脏模型来研究使用基于ARFI的剪切刚度度量来非侵入性地表征肝脏压力的方法，以减少基于导管的HVPG测量的需要。非线性组织模拟材料的变形将类似于肝脏加压观察到的应变状态，将使用两个超声换能器来确定是否可以使用基于ARFI的硬度度量和潜在材料属性的知识来确定肝脏的变形状态。该实验装置也可用于临床测试前的体外肝脏加压实验。用两个换能器成像压缩的非线性模体将验证这样的假设，即肝脏在压力下的非线性行为可以被用来无创性地估计HVPG。 公共卫生相关性：拟议的项目将研究一种非侵入性、超声肝脏压力量化的方法。如果成功，这种方法将不再需要侵入性的、基于导管的肝脏压力测量。

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. PUBLIC HEALTH RELEVANCE: The proposed project will investigate a method for noninvasive, ultrasonic hepatic pressure quantification. If successful, this method would obviate the need for invasive, catheter-based hepatic pressure measurements.