LAUSR

Liver fibrosis plays a critical role in the evolution of most chronic liver diseases and is characterized by a buildup of extracellular matrix, which can progress to cirrhosis, hepatocellular carcinoma, liver failure, or death. Now, there are no noninvasive methods available to accurately assess disease activity (fibrogenesis) to sensitively detect early onset of fibrosis or to detect early response to treatment. Here, we hypothesized that extracellular allysine aldehyde (LysAld) pairs formed by collagen oxidation during active fibrosis could be a target for assessing fibrogenesis with a molecular probe. We showed that molecular magnetic resonance imaging (MRI) using an extracellular probe targeting these LysAld pairs acts as a noninvasive biomarker of fibrogenesis and demonstrated its high sensitivity and specificity in detecting fibrogenesis in toxin- and dietary-induced mouse models, a cholestasis rat model of liver fibrogenesis, and in human fibrotic liver tissues. Quantitative molecular MRI was highly correlated with fibrogenesis markers and enabled noninvasive detection of early onset fibrosis and response to antifibrotic treatment, showing high potential for clinical translation. Description Molecular MR imaging measures liver fibrogenesis in rodent models and human fibrotic liver tissues to enable disease detection and therapy monitoring. Noninvasively monitoring liver fibrosis Current clinical methods for assessing liver fibrosis are all invasive to some degree. Ning et al. used magnetic resonance imaging (MRI) coupled with a specific molecular probe to detect hepatic fibrosis in preclinical animal models. The authors were able to detect changes in fibrosis in the models in response to antifibrotic treatment and demonstrated proof-of-principle fibrosis detection using dissected human liver tissues. Although the method remains to be tested on individuals, this study offers a promising potential avenue for noninvasive detection of liver fibrosis.