Resolution of Murine Toxic Hepatic Injury Quantified With Ultrasound Entropy Metrics

Abstract

Image-based classification of liver disease generally lacks specificity for distinguishing between acute, resolvable injury and chronic irreversible injury. We propose that ultrasound radiofrequency data acquired in vivo from livers subjected to toxic drug injury can be analyzed with information theoretic detectors to derive entropy metrics, which classify a statistical distribution of pathologic scatterers that dissipate over time as livers heal. Here we exposed 38 C57BL/6 mice to carbon tetrachloride to cause liver damage, and imaged livers in vivo 1, 4, 8, 12 and 18 d after exposure with a broadband 15-MHz probe. Selected entropy metrics manifested monotonic recovery to normal values over time as livers healed, and were correlated directly with progressive restoration of liver architecture by histologic assessment (r² ≥ 0.95, p < 0.004). Thus, recovery of normal liver microarchitecture after toxic exposure can be delineated sensitively with entropy metrics.

Keywords: Carbon tetrachloride; Entropy; Liver recovery; Liver toxicity; Quantitative ultrasound; Tissue characterization; Ultrasound.