University of Wisconsin–Madison

(BOLD Liver) Feasibility of Using MR Relaxometry and 4D Flow MRI for Assessment of Early Alterations in Oxygen Consumption in Patients with Fatty Liver Disease

September 2017 to January 2019

Magnetic Resonance (MR) Imaging is a non-invasive diagnostic imaging modality with an unprecedented combination of high spatial resolution and superior soft tissue contrast, but without the need for ionizing radiation. It can provide a vast array of tissue information and features of disease, including morphology, oxygen concentration, blood flow, diffusion of water within tissue, and allow for quantification of important tissue components such as fat, iron, various other metabolites, or tissue perfusion. In order to translate new imaging methods for disease detection into clinical care, we need a cycle of technical development and continuous validation in different settings, meaning to test and evaluate such new techniques or imaging biomarkers in preclinical experiments as well as under clinical conditions, in the presence of actual pathology.

One relevant example, and the subject of this study, is non-alcoholic fatty liver disease (NAFLD), which has emerged as the most common cause of chronic liver disease in the US and records a globally rising prevalence. One of the greatest challenges with this disease remains the timely differentiation between NAFLD and its aggressive sub-form, non-alcoholic steatohepatitis (NASH), which can eventually progress to end stage cirrhosis. Currently, serum markers of liver disease are notoriously non-specific and more definitive evaluation often requires biopsy. Biopsy however is expensive, invasive, and relatively risky, with a risk of death of up to 1:10,000 and a risk of 1:4 of hospitalization. Therefore, the ability to accurately measure important disease features of NAFLD/NASH with non-invasive methods such as MRI would be of tremendous value. Such non-invasive biomarkers are urgently needed for many areas of clinical investigation and clinical care, in order to detect disease preemptively, track disease longitudinally during treatment monitoring, and also as surrogate biomarkers in drug development.

Our group at UW-Madison has previously developed methods for assessment of chronic liver disease and accurate quantification of liver fat content with advanced chemical shift based imaging methods to measure liver triglyceride concentrations (i.e. fat). However, further noninvasive methods that enable the discrimination between “simple steatosis” and progressive tissue damage are crucial for screening, monitoring, clinical decision making, and overall patient outcome. Initial data suggest, that changes in tissue oxygen consumption, which requires both, measurements of tissue oxygen content (blood and tissue oxygenation) as well as oxygen delivery (blood flow), might be eligible markers to measure early alterations in fatty liver disease.

In particular, T1 and T2* MR-mapping techniques that exploit the tissue oxygen level dependent (TOLD) or blood oxygen level dependent (BOLD) effects respectively, are promising tools to indicate alterations in tissue and blood oxygenation. Moreover, new velocity-sensitive 4D flow MRI methods were shown to accurately quantify hemodynamic alterations in portal venous flow of patients with progressive cirrhosis, before and in response to a meal challenge. Recently, unpublished data in obese patients undergoing weight loss surgery at the University of Wisconsin suggest that even in non-cirrhotic NAFLD alterations in hepatic blood flow can be detected.

Therefore, the goal of this pilot study is to assess the feasibility of BOLD/TOLD and 4D-flow MR-imaging techniques as potential biomarkers for the detection of early alterations in liver oxygen consumption in patients with NAFLD/NASH in comparison to healthy volunteers.

This project led by: Scott B Reeder, MD, PhD