Ultrasonic Investigation of Hepatic Mechanical Properties: Quantifying Tissue Stiffness and Deformation with Increasing Portal Venous Pressure

Abstract

In this work, I investigate the mechanical response of the liver to increasing pressure in the portal vein using ultrasonic approaches. In advancing liver disease, portal venous pressure increases lead to severe clinical problems and death. Monitoring these pressure increases can predict patient outcomes and guide treatment. Current methods for measurement of portal venous pressure are invasive, expensive, and therefore are rarely repeated. Ultrasonic methods show promise because they are noninvasive, but traditional ultrasound images and doppler measurements do not yield accurate repeatable measures of hepatic pressure. However, increases in portal venous pressure have been associated with higher estimates of liver stiffness using ultrasound-based shear wave speed estimation algorithms. These quantitative estimates of shear wave speed may provide a mechanism for noninvasive hepatic pressure characterization, but they cannot currently be distinguished from the increases in shear wave speed estimates that are also observed in patients with normal portal venous pressures with advancing liver diseases. Thus, a better understanding of the mechanisms by which hepatic pressure modulates estimates of liver stiffness could provide information needed to distinguish increasing hepatic pressure from advancing brosis stage. This work is devoted to identifying and characterizing the underlying mechanism behind the observed increases in hepatic shear wave speed with pressurization.Two experiments were designed in order to dene the mechanical properties of liver tissue that underlie the observed increase in shear wave speeds with increasing portal venous pressure. First, the behavior of the liver was shown to be nonlinear (or strain-dependent) by comparing stiness estimates in livers that were free to expand and constrained from expansion at increasing hepatic pressures. Shear wave speeds were observed to increase only in the unconstrained case in which the liver was observed to qualitatively deform. Second, the deformation of the liver was quantied using a clinical scanner and 3-D transducer to generate estimates of axial strain during pressurization. Axial strain was found to increase with elevation in portal venous pressure. This axial expansion of the liver also corresponded to increases in shear wave speed estimates with portal venous pressure.The techniques developed herein were used to elucidate mechanical properties of the pressurized liver by concurrent ultrasound-based quantication of hepatic deformation and stiffness. This work shows that increasing shear wave speed estimates with hepatic pressurization are associated with increases in hepatic axial strain measurements. These results provide the basis for quantifying the relationship between pressurization and hepatic strain, laying the foundation for hyperelastic material modeling of the liver. Such nonlinear mechanical models can provide the basis for noninvasive characterization of hepatic pressure using stiffness metrics in the future.