Rationale and Objectives
Fibrosis is characterized by progressive replacement of normal tissue by extracellular matrix. Diagnosis relies on biopsies as noninvasive methods for detection and quantification of fibrosis are still limited. This work aimed to address the ability of 2 molecular magnetic resonance (MR) probes, EP-3533 and Gd-Hyd, to identify fibrosis and fibrogenesis, respectively, independently of the presence of underlying inflammation in a mouse model of chronic liver disease caused by infection with Schistosoma mansoni.
Three groups of mice that develop either mild type 2 inflammation and fibrosis (wild type), severe fibrosis with exacerbated type 2 inflammation (Il10−/−Il12b−/−Il13ra2−/−), or minimal fibrosis with marked type 1 inflammation (Il4ra∂/∂) after infection with S. mansoni were imaged using both probes for determination of signal enhancement. Schistosoma mansoni–infected wild-type mice developed chronic liver fibrosis.
The liver MR signal enhancement after either probe administration was significantly higher in S. mansoni–infected wild-type mice compared with naive animals. The S. mansoni–infected Il4ra∂/∂ mice presented with little liver signal enhancement after probe injection despite the presence of substantial inflammation. Schistosoma mansoni–infected Il10−/−Il12b−/−Il13ra2−/− mice presented with marked fibrosis, which correlated to increased signal enhancement after injection of either probe.
Both MR probes, EP-3533 and Gd-Hyd, were specific for fibrosis in this model of chronic liver disease regardless of the presence or severity of the underlying inflammation. These results, in addition to previous findings, show the potential application of both molecular MR probes for detection and quantification of fibrosis from various etiologies.