Liver cirrhosis has been historically classified as a single histopathologic entity, as it is considered to be the latest fibrosis stage; however it is well known that cirrhosis encompasses different degrees of clinical severity. Advanced liver fibrosis and cirrhosis are commonly associated with portal hypertension, which is due to increased hemodynamic resistance of the liver leading to an increase in portal venous pressure. Portal hypertension leads to the development of esophageal varices associated with a high risk of bleeding, ascites and renal dysfunction. The definite diagnosis of portal hypertension is based on the measurement hepatic venous pressure gradient (HVPG), which is an indirect measure of portal pressure. This technique is invasive and not widely available. Portal hypertension may also associated with a decrease in portal venous flow/velocity due to a higher parenchymal resistance to flow, and an increase in hepatic arterial flow secondary to an arterial buffer response that can be measured with phase-contrast magnetic resonance imaging (MRI). According to our recent data, the increased vascular pressure observed in portal hypertension affects liver and spleen stiffness as well as other viscoelastic properties measured with advanced 3D MR elastography, which may potentially be used as biomarkers of portal hypertension. In this proposal, we would like to validate noninvasive imaging biomarkers based on a short multiparametric MRI protocol for the quantification of changes in viscoelastic properties and flow metrics in the liver and spleen in relation with portal hypertension. This protocol could potentially be integrated in routine clinical MRI exams, and could significantly reduce the cost of care by decreasing the need for HVPG measurement, upper gastrointestinal endoscopies, and could provide a novel risk stratification scoring system of liver disease and portal hypertension based on MRI. This will be a highly significant progress in patients with liver disease.

Public Health Relevance

Portal hypertension, a common complication of liver cirrhosis, leads to the development of esophageal varices associated with a high risk of bleeding, ascites and renal dysfunction. The definite diagnosis of portal hypertension is based on the measurement of hepatic venous pressure gradient (HVPG), which involves the placement of a catheter in the internal jugular vein advanced to the level of the hepatic veins, which is invasive. In this proposal, we would like to validate noninvasive advanced magnetic resonance imaging (MRI) techniques (including MR elastography to measure liver and spleen stiffness and advanced viscoelastic properties; and phase-contrast MRI to measure liver and spleen vascular flow) as markers of portal hypertension (HVPG ?5 mm Hg) and clinically significant portal hypertension (HVPG ? 10mm Hg) and degree of scarring in the liver parenchyma. These techniques could be used for diagnosis of portal hypertension, and could decrease the need of portal pressure measurements, which are invasive and not widely available. This could save costs and could benefit a large number of patients with liver disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK113272-02
Application #
9604803
Study Section
Hepatobiliary Pathophysiology Study Section (HBPP)
Program Officer
Sherker, Averell H
Project Start
2017-12-01
Project End
2021-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Wagner, Mathilde; Hectors, Stefanie; Bane, Octavia et al. (2018) Noninvasive prediction of portal pressure with MR elastography and DCE-MRI of the liver and spleen: Preliminary results. J Magn Reson Imaging 48:1091-1103