Advanced Quantitative Magnetic Resonance Imaging Phantoms for Nonalcoholic Fatty Liver Disease

Calimetrix, Llc, Madison WI

Investigators

Abstract

PROJECT SUMMARY The overall goal of this Phase I proposal is to design and test the feasibility of novel magnetic resonance imaging (MRI) reference standards (“phantoms”) that are urgently needed for comprehensive and standardized quality assurance (QA) of quantitative MRI biomarkers of non-alcoholic fatty liver disease (NAFLD). We propose to develop 1) a quantitative MR elastography (MRE) stiffness phantom, and 2) a combined quantitative MRE and proton density fat fraction (PDFF) phantom that mimics the simultaneous presence of liver fibrosis and fat. Over the past decade, quantitative MRI methods, including MRE to measure stiffness as a biomarker of liver fibrosis and chemical shift encoded MRI (CSE-MRI) to measure PDFF as a biomarker of liver fat, have emerged as the noninvasive standard of care for assessment of NAFLD. The rapid adoption of MRE and PDFF methods at thousands of sites worldwide has created an urgent need for quantitative MRE and PDFF phantoms that enable robust quantitative QA to ensure unbiased and reproducible measurements. Lack of clinical QA can result in misdiagnosis, and inadequate QA in clinical trials can result in errors and inconsistency in the primary trial endpoints (liver stiffness and PDFF) leading to loss of valuable patient data and potentially a failed trial. Currently available single-stiffness MRE phantoms are insufficient for quantitative QA because they mimic only a single stiffness value which drifts over time. These phantoms also require phantom-specific MRE protocols that differ significantly from clinical MRE protocols, leading to technical failures and a cumbersome QA process. Importantly, most clinical MRI protocols evaluating NAFLD measure both MRE-stiffness and PDFF in the same exam. Through market research, Calimetrix has identified the need for two new quantitative phantoms: 1) a multi-stiffness MRE phantom; and 2) a combined MRE/PDFF phantom. Both phantoms must be stable over time and be designed to simplify QA setup, minimizing user and technical errors. In this proposal, we have assembled a team consisting of the primary inventors of both PDFF and MRE including experts from the University of Wisconsin, Calimetrix, the Mayo Clinic, and Resoundant. We propose to design, develop, and validate chemical formulations for gels of varying stiffnesses that span the clinically relevant range of liver stiffness (Aim 1) and emulsions with simultaneously varying stiffness and PDFF values that span the clinically relevant range of liver stiffness and fat (Aim 2). We also propose to design and validate a phantom housing that facilitates accurate quantitative measurements and is efficient and easy-to-use with separate compartments to contain multiple stiffness and/or PDFF values in a single compact unit (Aim 3), and finally, to demonstrate the feasibility of the MRE and MRE/PDFF phantom prototypes, including ease-of-use, high image quality, and utility for QA of clinical MRE and CSE-MRI protocols (Aim 4). If successful, we will have developed and demonstrated the feasibility of truly quantitative MRE and MRE/PDFF phantoms that are urgently needed for quality assurance of quantitative MRI biomarkers of NAFLD.