Liver Biomarker Quantification

MR imaging presents unique opportunities to perform non-invasive quantitative mapping of biomarkers in tissue. Our research seeks to leverage these advantages in the liver to overcome challenges in the current clinical gold standard, liver biopsy, an invasive technique ill-suited to repeated measurements needed for monitoring disease/treatment and prone to sampling errors from the local nature of biopsy.


Hepatic Steatosis

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease of both adults and children in the United States. Early detection and treatment may halt or reverse progression to liver injury, inflammation, fibrosis and, ultimately, cirrhosis, which has dreaded complications including liver failure, portal hypertension and hepatocellular carcinoma. LIRP currently focuses on the validation of proton density fat fraction measurements as compared to other invasive and non-invasive methods like MR Spectroscopy, Computer Tomography and Biopsy. Since fatty infiltration is known to be inhomogeneous throughout the liver, LIRP focuses also on establishing techniques evaluating the entire liver instead of single samples like MRS or biopsy.

Hepatic Iron Overload

Surplus iron accumulation in the liver, affecting both adult and pediatric populations, is toxic and requires treatment aimed at reducing body iron stores. Measurement of liver iron is critical for the detection and staging of iron overload, and for the monitoring of iron-reducing chelating therapies, which are expensive and have significant side effects. MRI is a widely available, accessible, and safe technology, with excellent sensitivity to the presence of iron in tissue.  MRI-based techniques for liver iron quantification include relaxometry (measuring the rate of decay of the signal) and susceptometry (estimating the magnetic susceptibility of tissue based on its effects on the magnetic field). We are developing and validating novel relaxometry and susceptometry techniques for rapid, accurate, precise, robust, and reproducible MRI-based liver iron quantification.

Perfusion in Liver Tumors

Increasingly, tumors are being treated with anti-angiogenic agents such as bevacizumab and soranfenib. Although effective in many patients, these agents may not demonstrate a detectable treatment response for many months when using conventional CT and MRI methods. By quantifying blood flow to liver tumors accurately, we aim to detect changes in blood flow to tumors in 2-3 days, as an early biomarker of tumor response. To accomplish this we are developing and validating novel Cartesian and non-Cartesian based methods for more accurate quantification of perfusion in liver tumors.

Signal fat‐fraction maps with full dynamic range (0%–100%) can be calculated on a pixel‐by‐pixel basis, when complex‐based fat‐water separation methods are used to provide separate fat‐only and water‐only images. The signal fat‐fraction map may not accurately reflect the concentration of fat within the liver unless all confounding factors are addressed. Reeder S, et al. Journal of Magnetic Resonance Imaging. 2011;34(4):729-749.
Both MRI‐based R2* mapping and quantitative susceptibility mapping are sensitive to the presence of iron in the liver. Sharma S, et al. Magnetic Resonance in Medicine. 2017 aug;78(1):264-270.

Selected Publications

  • Horng D, Hernando D and Reeder S. Quantification of liver fat in the presence of iron overload. Journal of Magnetic Resonance Imaging. 2017 jul;45(2):428-439. DOI PMID
  • Sharma S, Fischer R, Schoennagel B, Nielsen P, Kooijman H, Yamamura J, Adam G, Bannas P, Hernando D and Reeder S. MRI-based quantitative susceptibility mapping (QSM) and R2* mapping of liver iron overload: Comparison with SQUID-based biomagnetic liver susceptometry. Magnetic Resonance in Medicine. 2017 aug;78(1):264-270. DOI PMID
  • Reeder S, Cruite I, Hamilton G and Sirlin C. Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy. Journal of Magnetic Resonance Imaging. 2011;34(4):729-749. DOI PMID
  • Hines C, Bley T, Lindstrom M and Reeder S. Repeatability of magnetic resonance elastography for quantification of hepatic stiffness. Journal of Magnetic Resonance Imaging. 2010;31(3):725-731. DOI PMID
  • Yu H, Shimakawa A, McKenzie C, Brodsky E, Brittain J and Reeder S. Multiecho water-fat separation and simultaneous R*2 estimation with multifrequency fat spectrum modeling. Magnetic Resonance in Medicine. 2008;60(5):1122-1134. DOI PMID
  • Reeder S, Pineda A, Wen Z, Shimakawa A, Yu H, Brittain J, Gold G, Beaulieu C and Pelc N. Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL): Application with fast spin-echo imaging. Magnetic Resonance in Medicine. 2005;54(3):636-644. DOI PMID