Project: Research project

Project Details


This proposal addresses the topic Hepatitis C in the areas of encouragement – develop reliable, non-invasive, hepatitis-related liver disease and hepatocellular carcinoma (HCC) early detection; and promote reversal of liver fibrosis and/or assess the associated clinical and pathological outcomes. Hepatitis C virus (HCV) infection remains a crucial concern for the Military Health System (MHS). Given recent pharmaceutical advances, reliable noninvasive biomarkers are critical for early detection and treatment monitoring.Our major goal is to develop an advanced multiparametric liver magnetic resonance elastography (MRE) imaging technology to detect and monitor HCV/HCC disease progression or regression. Such imaging products have a variety of applications for military personnel, Veterans, and their families — including those with other chronic liver diseases. Our short-term goals are: (1) early hepatitis-related liver disease detection and monitoring, such as early onset of inflammation before fibrosis and (2) early identification of HCC involvement, differentiation, and microvascular invasion risk. Our long-term goals are: (1) establishing MRE parameters for viral hepatitis treatment initiation and duration; (2) timely monitoring of inflammation, fibrosis, and HCC for accurate treatment efficacy evaluation; and (3) understanding hepatitis progression’s natural history and changes in multiple MRE parameters from inactive chronic infection to active hepatitis, eventually to HCC development.Developing necessary technologies and confirming performance in pilot patient studies can accelerate liver MRE use as a practical tool to monitor chronic liver disease progression and advancing the basic imaging science. Our central hypothesis and final product is the development of advanced multiparametric 3D liver MRE acquisition and inversion methods with improved and new mechanical parameters, including shear attenuation, volumetric strain, and slip interface imaging (SII), which will more fully characterize the pathophysiologic state of HCV during the long disease progression period. Rigorous evaluations and preliminary translational validations of these new mechanical parameters will be conducted in clinical patients.Aim 1: Investigate MRE-assessed mechanical properties to assess hepatitis activity in HCV.Aim 1.1: A retrospective study to evaluate shear attenuation in assessing hepatitis activity: Mayo Clinic has collected more than 8,000 clinical cases since 2007. We expect to find ~90 clinical patients with biopsy in this full cohort. We will perform a retrospective study to evaluate changes in shear attenuation with HCV activities.Aim 1.2: A prospective study to evaluate technical repeatability and longitudinal monitoring of hepatitis:Before this advanced 3D hepatic imaging protocol can be implemented widely in clinical settings, we will perform repeated longitudinal MRE exams on a prospective cohort (10 inactive HCV, 10 active HCV, and 10 healthy volunteers). Shear attenuation measurement precision will be assessed twice on the same day separated by a 5- to 10-minute break. HCV activity progress will be evaluated every 6 months. For each subject, we expect to have one baseline MRE exam with biopsy-proven HCV infection and three follow-up exams within 18 months.Aim 2: Investigate MRE-assessed boundary conditions and tissue pressure for assessing HCC.Aim 2.1: A retrospective study to evaluate volumetric strain and SII in HCC characterization: We have collected more than 1,000 clinical cases with advanced 3D MRE since 2007. A prior analysis on patients with HCC shows that 81% of them have HCV infection. We expect to find ~20 pathologically proven HCC after surgery or transplant for evaluating the diagnostic accuracy of volumetric strain and SII in grade differentiation of HCC and risk prediction of microvascular invasion.Aim 2.2: A prospective study to evaluate technical repeatability of SII and volumetric strain in longitudinal monitoring HCC: We will perform a repeatability study to evaluate within-day measurement precision and a longitudinal study to characterize HCC development. We plan to follow up 30 patients with HCC who are in the waitlist of liver transplantation. 3D MRE will be performed every 3 months to evaluate volumetric strain and SII for characterizing HCC progression or recurrence (transplantation may occur in 50% of these patients within 1 year). The longitudinal monitoring with other tests will follow the standard patient care.This proposal will advance hepatic MRE as a practical imaging tool to qualitatively and quantitatively monitor HCV progression/regression. MRE may detect key focal and diffuse disease processes and provide capabilities unavailable with other imaging techniques. Mayo Clinic’s integrated clinical and collaborative environment is excellent for technological development on tangible clinical problems while conducting pilot clinical studies.

Effective start/end date9/1/198/31/22


  • Congressionally Directed Medical Research Programs: $2,970,690.00


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