First-in-human diagnostic study of hepatic steatosis with computed ultrasound tomography in echo mode (CUTE)

Abstract Non-alcoholic fatty liver disease is rapidly emerging as the leading global cause of chronic liver disease. Efficient disease management requires low-cost, noninvasive techniques for diagnosing hepatic steatosis accurately. Here we propose quantifying liver speed-of-sound (SoS) with computed US tomography in echo mode (CUTE), a newly developed US imaging modality adapted to clinical pulse-echo systems. CUTE reconstructs the spatial distribution of SoS by measuring local echo phase shifts when probing tissue at different steering angles in transmission and reception. This first-in-human phase II study shows that liver CUTE-SoS estimates correlate strongly (r=-0.84, p=8.27∙10 -13 ) with controlled attenuation parameter values, a commonly used tool for assessing liver steatosis, and have 90.9% (95% confidence interval: 84 - 100%) sensitivity and 95.5% (81 - 100%) specificity for differentiating normal and significantly steatotic livers. Because CUTE offers the same flexibility as conventional US imaging, it can be readily extended to other clinical applications, establishing it as a new quantitative add-on to diagnostic US.