Accurate Point of Care Liver Disease Diagnostics

PROJECT SUMMARY Our long-term goal is to obtain FDA 510(k) clearance and to bring to market LiverScope®, a low cost, easy- to-use, table-top, point-of-care device for use in research and clinical settings to assess quantitative biomarkers of nonalcoholic fatty liver disease (NAFLD). LiverScope® 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 access or can be operated in a small van for mobile diagnostic delivery. Our initial focus is on the estimation of proton-density fat fraction (PDFF), a standardized MRI-based biomarker of hepatic steatosis. Our immediate goal (and the focus of this application) is to perform Phase 1 studies in phantoms and humans to verify that PDFF estimated by LiverScope® (LiverScope®-PDFF) meets conformance standards developed by the Quantitative Imaging Biomarkers Alliance. The primary specific aims of this Phase 1 proposal are to verify that PDFF estimated by LiverScope® agrees with ground-truth phantom PDFF values (Aim 1) and is repeatable and reproducible in humans (Aim 2). Successful demonstration of quantitative milestones of success in Aims 1 and 2 will support the design, planning, and execution of a future, larger, multi-center Phase 2 proposal to obtain FDA 510(k) clearance. Likelihood of success is leveraged by prior conversations with FDA, patents to protect Livivos’ intellectual property, and supportive preliminary data. After LiverScope is FDA cleared to estimate PDFF, we will investigate its capability to assess other potential biomarkers of NAFLD, such as T1 relaxation, T2 relaxation, and diffusivity (proposed biomarkers of liver disease activity and damage).The innovation of the proposed work resides in the creation of novel technology to estimate MR-based quantitative biomarkers of NAFLD at low cost and in point- of-care settings while maintaining the accuracy and precision of full-size MRI scanners. The clinical significance of the proposed 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 the goals of this Phase 1 SBIR proposal are met, and if a follow-on comprehensive Phase 2 SBIR studies result in FDA 510(k) clearance of LiverScope for PDFF estimation, deployment in primary care, rural, underserved, and third- world communities will be possible. 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 point-of-care 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 NAFLD; and more efficient screening, enrollment, and execution of clinical trials to accelerate drug discovery.