Hepatic Steatosis Quantification with Ultrasound

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PROJECT SUMMARY Quantification of liver steatosis has weighty implications in management of Nonalcoholic Fatty Liver Disease (a condition affecting 75-100 million Americans), diabetes mellitus, and cardiovascular disease. Serum biomarkers, computed tomography, and existing ultrasound methods have low sensitivity or specificity for steatosis staging. Proton Density Fat Fraction (PDFF) measured by MRI has high accuracy, but is limited by accessibility and cost. Here we propose a novel ultrasound technology, Spectrum Normalization Attenuation Imaging (SNAI), to quantify ultrasound attenuation coefficient for accurate liver steatosis staging. SNAI does not require a calibration phantom, and is robust to rib shadowing as well as phase aberration and reverberation clutter from the body wall. Accuracy of SNAI for steatosis staging is demonstrated by a promising correlation coefficient of 0.91 with MRI-PDFF in 50 patients. In this project, we will prototype, optimize, and evaluate SNAI on a low-cost, pocket-sized, wireless ultrasound probe, which can be conveniently used for screening and follow-up at the point-of-care setting such as the office of a family doctor or hepatologist. Specific Aim 1: Technical Development. We will use phantom and patient studies to advance and optimize SNAI on the the wireless ultrasound probe. Acquisition parameters and post processing algorithms will be optimized for both fundamental and harmonic SNAI imaging. We will suppress reverberation clutter and correct for sound speed mismatch in liver for more accurate steatosis quantification. Specific Aim 2: Patient study. We will use the SNAI prototypes optimized in Aim 1 to study 250 steatosis patients with clinically indicated MRI-PDFF to investigate the efficacy of SNAI for steatosis quantification. Correlation analysis will be performed to assess the association of SNAI with MRI-PDFF. Steatosis will also be categorized as S0, S1, and S2/S3 according to PDFF. Receiver operating characteristic analyses will be performed to evaluate performance of SNAI for detecting ≥S1 and ≥S2. The agreement between SNAI and PDFF classification will be evaluated using the Kappa statistic. Fibroscan CAP will be used for benchmarking. Specific Aim 3: Reproducibility study. Two sonographers and two hepatology residents will repeatedly scan a subset of subjects (50 patients) studied in Aim 2. Intraclass correlation coefficients will be used to evaluate the inter-operator agreement for SNAI measurements. The within patient variance component from the model will provide an estimate of the inter-operator variance, which represents a lower bound for the minimum detectable difference for longitudinal follow-ups. Successful completion of this project will result in a safe, cost-effective, and easily accessible ultrasound solution for accurate quantification of liver steatosis for diagnosis and frequent follow-up of this very large patient population at point-of-care settings such as the office of a hepatologist or family doctor.