Point-of Care MR Device to Estimate T1 Relaxation Time as a Biomarker of Liver Disease (resubmission)

PROJECT SUMMARY LiverScope® is a low cost, easy-to-use, table-top device for use in research and clinical settings to assess quantitative biomarkers of nonalcoholic fatty liver disease (NAFLD). It uses novel, noise-free, advanced magnetic resonance (MR)-based technology, requires no room shielding, and can be sited in a standard clinic room for point-of-care (POC) access or can be operated in a small van for mobile diagnostic delivery. We recently received a Phase 1 SBIR grant (1 R43 DK135225-01) to show feasibility of using LiverScope® to estimate liver PDFF, and are now re-submitting this current Phase 1 SBIR proposal to show feasibility of LiverScope® to estimate liver T1 relaxation times. Emerging data support use of T1 relaxation time as a quantitative biomarker in numerous contexts of use, including diagnosis of ‘at risk NASH’, treatment response, monitoring, stratification, and prognostication. Adding T1 relaxation time estimation capability to LiverScope® has the potential to make it a ‘one-stop’ test, substantially enhancing its clinical, scientific, and commercial value. Demonstration of non-invasive imaging biomarker assessment feasibility of both hepatic steatosis (by PDFF) and fibrosis/inflammation (by T1) will support a follow-on comprehensive Phase 2 trial in which these biomarkers of NASH can be tested prospectively. Our long-term goal is to bring LiverScope® to market. Our focus in this study will be to develop LiverScope® capability and establish feasibility to estimate T1 relaxation time (T1). Our immediate goal in this study is to evaluate T1 precision for two identical LiverScope® devices, and so our primary specific aims are to estimate water T1 intra-device repeatability and inter-device reproducibility in phantoms (Aim 1) and humans (Aim 2). The innovation of this proposed derives from the novel technology used to estimate and verify validity for MR-based quantitative biomarkers of NAFLD at low cost and in POC settings while maintaining the accuracy and precision of full-size MRI scanners. The clinical significance of this work is that widespread implementation of this technology will enable earlier diagnosis, more timely referral to specialists, and greater access to monitoring of NAFLD. If these studies are successful, deployment of LiverScope® in primary care, rural, underserved, and third-world communities will be possible. Offering real-time PDFF and T1 estimation capability, and the potential for future expansions of LiverScope capability to include assessment of liver disease activity and damage, could be transformational to the medical care of patients with known or suspected NAFLD. This technology could support POC and mobile clinical application in numerous contexts of use, including early detection, diagnosis, staging, monitoring, and treatment response assessment; early intervention to prevent downstream hepatic and extrahepatic complications of NAFLD; large-scale epidemiology studies to better understand the prevalence and genetics of NAFLD; and more efficient screening, enrollment, and execution of clinical trials to accelerate drug discovery.