ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Combined Educational & Scientific Session: Quantitative Biomarkers of Diffuse Liver Disease

Skill Level: Intermediate

Organizers: Ivan Pedrosa, M.D., Lorenzo Mannelli, M.D., Ph.D., Scott B. Reeder, M.D., Ph.D. & Edwin J.R. van Beek, M.D., Ph.D., M.Ed., FRCR

Tuesday 10 May 2016

This two-hour course focuses on the foundations of quantitative MRI biomarkers of diffuse liver disease. State-of-the-art approaches for quantification of hepatic steatosis, iron overload and fibrosis will be described. Emphasis will be made on understanding the basic principles applied to these quantification methods as well as understanding how to interpret the results of these MRI examinations and how to include these results in an MRI report. Didactic presentations and scientific abstracts on each area of interest will be presented to enhance the educational and scientific value of this course on each specific area of interest.

Target Audience
This course is aimed at radiologists, imaging scientists and MR technologists who wish to review the state-of-art MRI methods for quantification of diffuse liver disease, and learn how to incorporate these methods in routine clinical practice.

Educational Objectives
Upon completion of this course, participants should be able to:

  • Illustrate the role of MRI biomarkers of liver disease in clinical practice;
  • Demonstrate how to implement these methods into clinical protocols;
  • Convey practical approaches to interpret quantitative biomarkers of liver disease; and
  • Integrate approaches to reporting quantitative biomarkers of liver disease.

Moderators: Claude Sirlin, Takeshi Yokoo
Introduction by Moderator
Fat Quantification & Composition
Mustafa Bashir1
1Duke University Medical Center
The use of MRI measures of fatty liver as well as intraabdominal fat will be discussed, particularly as pertain to Nonalcoholic Steatohepatitis and the metabolic syndrome.

Non-invasive quantification and characterisation of liver fat in non-alcoholic fatty liver disease (NAFLD) using automated analysis of MRS correlated with histology
Robert Flintham1, Peter Eddowes2, Scott Semple3, Natasha McDonald4, Jonathan Fallowfield4, Tim Kendall5, Stefan Hübscher6, Philip Newsome2, Gideon Hirschfield2, and Nigel Paul Davies1,7
1Medical Physics, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, 2Centre for Liver Research, NIHR Biomedical Research Unit, University of Birmingham, Birmingham, United Kingdom, 3Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom, 4MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom, 5MRC Human Genetics Unit, University of Edinburgh, Edinburgh, United Kingdom, 6Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom, 7Institute of Cancer and Genomics, University of Birmingham, Birmingham, United Kingdom
MRS is proven to accurately measure liver fat fraction (FF), but its potential to differentiate steatohepatitis from simple steatosis in non-alcohol related fatty liver disease (NAFLD) is unexplored. MRS was acquired in 60 patients with suspected NAFLD across two centres prior to biopsy. Automated analysis was developed using TARQUIN to estimate FF, lipid chain length (CL) and number of double-bonds per chain (nDB) revealing strong correlations between FF, nDB, CL and steatosis grade. nDB also negatively correlated with hepatocyte ballooning assessed by histopathology. Further investigation of the relationship between MRS-derived lipid composition measurements and disease severity in NAFLD is warranted.

Accuracy and optimal proton density fat fraction threshold of magnitude- and complex-based magnetic resonance imaging for diagnosis of hepatic steatosis in obese patients using histology as reference
Tydus Thai1, William Haufe1, Yesenia Covarrubias1, Alexandria Schlein1, Curtis N. Wiens2, Alan McMillan2, Nathan S. Artz2,3, Rashmi Agni4, Michael Peterson5, Luke Funk6, Guilherme M. Campos7, Jacob Greenberg6, Santiago Horgan8, Garth Jacobson8, Tanya Wolfson1, Jeffrey Schwimmer9, Scott Reeder2,10,11,12,13, and Claude Sirlin1
1Liver Imaging Group, Radiology, University of California-San Diego, San Diego, CA, United States, 2Radiology, University of Wisconsin-Madison, Madison, WI, United States, 3Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, United States, 4Pathology, University of Wisconsin-Madison, Madison, WI, United States, 5Western Washington Pathology and Multicare Health System, Tacoma, WA, United States,6Surgery, University of Wisconsin-Madison, Madison, WI, United States, 7Surgery, Virginia Commonwealth University, Richmond, VA, United States, 8Surgery, University of California-San Diego, San Diego, CA, United States, 9Pediatrics, University of California-San Diego, San Diego, CA, United States, 10Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, 11Biomedical Engineering, Madison, WI, United States, 12Medicine, Madison, WI, United States, 13Emergency Medicine, Madison, WI, United States
The purpose of this prospective cross-sectional study was to determine the accuracy of optimal MRI-M- and MRI-C-determined PDFF thresholds for diagnosis of hepatic steatosis using contemporaneous histology as reference in obese adults without previously known NAFLD. The excellent performance parameters of the Youden-index PDFF thresholds for MRI-M and MRI-C (5.3% and 7.7%, respectively) further support the use of these techniques for the quantitative and non-invasive diagnosis of HS. If validated by additional prospective studies, these PDFF thresholds could be used for diagnosing HS in obese adults non-invasively.

Confounders to Iron Quantification in the Liver
Diego Hernando1
1University of Wisconsin-Madison, WI, United States
This presentation will provide an overview of current techniques for liver iron quantification, with a focus on relevant confounding factors which may decrease the accuracy and reproducibility of LIC estimates.  The effect of these confounders, as well as recent efforts to address them, will be presented. 

Iron overload quantification using UTE Imaging at 3T
Eamon K Doyle, MS1,2, Jonathan M Chia, MS3, and John C Wood, MD, PhD1,2
1Biomedical Engineering, University of Southern California, Los Angeles, CA, United States, 2Cardiology, Children's Hospital of Los Angeles, Los Angeles, CA, United States, 3Philips Healthcare, Cleveland, OH, United States
Estimate of R2* in high-iron patients has many challenges at 3T and above.  UTE imaging shows promise as method to perform iron quantitation in heavily iron-loaded tissues.  We demonstrate feasibility of using a 3D radial UTE sequence at 3T to estimate R2* relaxation rates in iron-loaded human subjects and fast-decay phantoms.

Comparing Magnitude versus Complex Data Fitting in Liver R2* Relaxometry
Arthur Peter Wunderlich1,2, Stefan Andreas Schmidt1, Meinrad Beer1, Armin Michael Nagel1,2, and Holger Cario3
1Clinic for Diagnsotic and Interventional Radiology, Ulm University, Medical Center, Ulm, Germany, 2Section for Experimental Radiology, Ulm University, Medical Center, Ulm, Germany, 3Department of Pediatrics and Adolescent Medicine, Ulm University, Medical Center, Ulm, Germany
Relaxometry of patient data was performed comparing the use of magnitude versus complex data. 94 patients suspected for liver iron overload were scanned with mulit-contrast GRE-MRI at 1.5 T, involving multiple TE, TR and FA. Analysis was performed as conjoined fit incorporating effects of fat/water dephasing. One fit was based on magnitude images modeling noise as free fit parameter, the other on complex data. Magnitude fit yielded similar results, but showed superior convergence and lower result uncertainty compared to the approach involving complex data.

Fibrosis: MRI vs US Elastography
Meng Yin
Liver stiffness now a well-established biomarker for assessing fibrosis in chronic liver disease, as an alternative to biopsy. MRI-based and ultrasound-based dynamic elastography methods have been introduced for clinical staging of fibrosis. Some of the methods are commercially available. However, each have their inherent strengths and weaknesses. The published literature generally indicates that MR elastography has higher diagnostic performance and fewer technical failures than ultrasound-based elastography in assessing hepatic fibrosis. There is significant potential to further develop elastography techniques to implement multiparametric methods that have promise for distinguishing between process such as inflammation, fibrosis, venous congestion, etc. 

Discrimination of Hepatic Inflammation and Fibrosis with Magnetic Resonance Elastography
Meng Yin1, Kevin J. Glaser1, Harmeet Malhi2, Amy Mauer2, Anuradha Krishnan2, Taofic Mounajjed3, Jason Bakeberg4, Christopher Ward4, Ruisi Wang2, Douglas Simonnetto2, Shennen Mao5, Jaime Glorioso5, Faysal Elgilani6, Vijay Shah2, Scott Nyberg6, Armando Manduca1, and Richard L. Ehman1
1Radiology, Mayo Clinic, Rochester, MN, United States, 2Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States, 3Pathology, Mayo Clinic, Rochester, MN, United States, 4Nephrology and Hypertension Research, Mayo Clinic, Rochester, MN, United States, 5Surgery, Mayo Clinic, Rochester, MN, United States, 6Transplant Center, Mayo Clinic, Rochester, MN, United States
To investigate the utility of MRE-derived mechanical properties in discriminating hepatic inflammation and fibrosis in early-stage of chronic liver diseases, we performed multifrequency 3D MRE on five different in vivo animal models with chronic liver diseases. Liver stiffness and phase angle derived from complex shear modulus were selected for evaluation. Results demonstrated distinct and potentially characteristic changes in these mechanical properties with hepatic inflammation, fibrosis and increased portal pressure. The findings offer preliminary evidence of the potential to extend MRE to distinguish and independently assess necroinflammatory and fibrotic processes in the early phase of chronic liver diseases.

Multifrequency MR elastography for assessing hepatic fibrosis in pediatric non-alcoholic fatty liver disease
Jing Guo1, Christian Hudert2, Heiko Tzschätzsch1, Andreas Fehlner1, Florian Dittmann1, Jürgen Braun3, and Ingolf Sack1
1Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany, 2Charité - Universitätsmedizin Berlin, Berlin, Germany, 3Department of Medical Informatics, Charité - Universitätsmedizin Berlin, Berlin, Germany
Multifrequency MR elastography (MMRE) was applied to 32 obese pediatric patients with non-alcoholic fatty liver disease (NAFLD). Magnitude shear modulus |G*| which relates to liver stiffness is sensitive to differentiate mild fibrosis (F0-2) from severe fibrosis (F3) with an AUROC of 0.93. The liver stiffness was positively correlated with serum alanine aminotransferase  (ALT) and can potentially serve as a quantitative imaging marker for the noninvasive assessment of liver fibrosis in patients with NAFLD.

Adjournment & Meet the Teachers


The International Society for Magnetic Resonance in Medicine is accredited by the Accreditation Council for
Continuing Medical Education to provide continuing medical education for physicians.