There is an expected increased incidence of chronic hepatitis C virus infection (HCV) in the Unites States within the next years, with subsequent increased risks of liver damage, including fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma and end-stage liver disease requiring liver transplantation. This disease is/will be the source of enormous health care costs and morbidity/mortality. Most hepatologists still rely on liver biopsy findings in patients newly diagnosed with HCV, which enables the assessment of liver damage (fibrosis and inflammation). Liver biopsy has limitations, including cost, invasiveness, poor patient acceptance, limited sampling, inter-observer variability and is difficult to repeat. Non invasive tests to capture the extent of liver damage at a larger scale are urgently needed. These will gain more acceptance among patients and hepatologists. In this proposal, we would like to test and validate non invasive magnetic resonance imaging (MRI) methods based on advanced diffusion (intravoxel incoherent motion diffusion MRI: IVIM DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) for the detection of fibrosis and cirrhosis in HCV patients. Based on our recent preliminary data, we believe that the combination of IVIM DW- and DCE-MRI has potential for detection of fibrosis and cirrhosis with excellent accuracy, while enabling coverage of the whole liver. In order to improve the diagnostic performance of MRI, we would like to build and validate a predictive model based on advanced functional MRI metrics (diffusion and perfusion). If validated, this novel non invasive algorithm will not only decreases the number of liver biopsies, but also enable earlier diagnosis of liver fibrosis when antiviral treatment is more effective, and enable a comprehensive evaluation of the liver (to assess for cirrhosis, portal hypertension and hepatocellular cancer). This could significantly reduce the cost of care, could become a useful tool for testing new antifibrogenic and antiviral drugs in HCV, and could be used to follow patients for detection of progression to cirrhosis. This will be a highly significant progress in liver diseases given the increased burden of HCV in this country, and would benefit a large number of Americans over the next decade.

Public Health Relevance

Patients with hepatitis C virus infection (HCV) are at high risk of developing liver scarring (fibrosis), with ultimate risks of cirrhosis and liver cancer that may require liver transplant. We would like to develop non invasive advanced MRI techniques (diffusion and dynamic contrast-enhanced MRI) to assess the degree of liver damage in HCV. These techniques combined could reach high diagnostic performance for detection of liver fibrosis;and could decrease the number of necessary liver biopsies, which have risks and sample only a small portion of the liver.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK087877-03
Application #
8322069
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Doo, Edward
Project Start
2010-08-01
Project End
2015-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$337,178
Indirect Cost
$131,885
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
Kennedy, Paul; Wagner, Mathilde; Castéra, Laurent et al. (2018) Quantitative Elastography Methods in Liver Disease: Current Evidence and Future Directions. Radiology 286:738-763
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
Bane, Octavia; Hectors, Stefanie J; Wagner, Mathilde et al. (2018) Accuracy, repeatability, and interplatform reproducibility of T1 quantification methods used for DCE-MRI: Results from a multicenter phantom study. Magn Reson Med 79:2564-2575
Bane, Octavia; Peti, Steven; Wagner, Mathilde et al. (2018) Hemodynamic measurements with an abdominal 4D flow MRI sequence with spiral sampling and compressed sensing in patients with chronic liver disease. J Magn Reson Imaging :
Taouli, Bachir; Hoshida, Yujin; Kakite, Suguru et al. (2017) Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma: preliminary results. Eur Radiol 27:4472-4481
Hectors, Stefanie J; Wagner, Mathilde; Bane, Octavia et al. (2017) Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging. Sci Rep 7:2452
Wagner, Mathilde; Corcuera-Solano, Idoia; Lo, Grace et al. (2017) Technical Failure of MR Elastography Examinations of the Liver: Experience from a Large Single-Center Study. Radiology 284:401-412
Dyvorne, Hadrien A; Jajamovich, Guido H; Bane, Octavia et al. (2016) Prospective comparison of magnetic resonance imaging to transient elastography and serum markers for liver fibrosis detection. Liver Int 36:659-66
Bane, Octavia; Wagner, Mathilde; Zhang, Jeff L et al. (2016) Assessment of renal function using intravoxel incoherent motion diffusion-weighted imaging and dynamic contrast-enhanced MRI. J Magn Reson Imaging 44:317-26
Wagner, Mathilde; Besa, Cecilia; Bou Ayache, Jad et al. (2016) Magnetic Resonance Elastography of the Liver: Qualitative and Quantitative Comparison of Gradient Echo and Spin Echo Echoplanar Imaging Sequences. Invest Radiol 51:575-81

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