In Vivo MRI Assessment of Hepatic and Splenic Disease in a Murine Model of Schistosmiasis

Abstract

BackgroundSchistosomiasis (or bilharzia), a major parasitic disease, affects more than 260 million people worldwide. In chronic cases of intestinal schistosomiasis caused by trematodes of the Schistosoma genus, hepatic fibrosis develops as a host immune response to the helminth eggs, followed by potentially lethal portal hypertension. In this study, we characterized hepatic and splenic features of a murine model of intestinal schistosomiasis using in vivo magnetic resonance imaging (MRI) and evaluated the transverse relaxation time T2 as a non-invasive imaging biomarker for monitoring hepatic fibrogenesis.Methodology/Principal FindingsCBA/J mice were imaged at 11.75T two, six and ten weeks after percutaneous infection with Schistosoma mansoni. In vivo imaging studies were completed with histology at the last two time points. Anatomical MRI allowed detection of typical manifestations of the intestinal disease such as significant hepato- and splenomegaly, and dilation of the portal vein as early as six weeks, with further aggravation at 10 weeks after infection. Liver multifocal lesions observed by MRI in infected animals at 10 weeks post infection corresponded to granulomatous inflammation and intergranulomatous fibrosis with METAVIR scores up to A2F2. While most healthy hepatic tissue showed T2 values below 14 ms, these lesions were characterized by a T2 greater than 16 ms. The area fraction of increased T2 correlated (rS = 0.83) with the area fraction of Sirius Red stained collagen in histological sections. A continuous liver T2* decrease was also measured while brown pigments in macrophages were detected at histology. These findings suggest accumulation of hematin in infected livers.Conclusions/SignificanceOur multiparametric MRI approach confirms that this murine model replicates hepatic and splenic manifestations of human intestinal schistosomiasis. Quantitative T2 mapping proved sensitive to assess liver fibrogenesis non-invasively and may therefore constitute an objective imaging biomarker for treatment monitoring in diseases involving hepatic fibrosis.

X-ray micro-computed tomography (μCT): an emerging opportunity in parasite imaging

“…The low contrast provided by unstained tissue is also a factor which precludes imaging of soft tissue in vivo at histological resolution. Magnetic resonance imaging (MRI), which is amenable to in vivo imaging, has been used to analyse parasite-induced pathology in whole animals (Voieta et al 2010 ; Masi et al 2015 ). However, MRI has a spatial resolution approaching 25–100 µ m in the most powerful magnetic fields (Shapiro et al 2004 ; de Kemp et al 2010 ), and no meaningful morphological information about tissue structure can be gathered below this threshold.…”

Clinical and Preclinical Imaging of Hepatosplenic Schistosomiasis

“…The first MRI study of S. mansoni infected mice[94] used anatomical MRI and identified a patchy liver pattern assigned to fibrosis at histology. A longitudinal MRI study of this model[95] revealed anatomical signs of PH (liver, spleen and portal vein enlargement) and contrast-enhancement of fibrotic liver lesions. Furthermore, this study proposed that quantitative mapping of the transverse T 2 relaxation time constant could be used to noninvasively assess fibrosis[95].Concluding remarksAssessment of HSS morbidity and treatment monitoring would benefit from non-invasive imaging methods allowing reliable fibrosis staging and estimation of vascular dysfunction (see outstanding questions).…”

“…A longitudinal MRI study of this model[95] revealed anatomical signs of PH (liver, spleen and portal vein enlargement) and contrast-enhancement of fibrotic liver lesions. Furthermore, this study proposed that quantitative mapping of the transverse T 2 relaxation time constant could be used to noninvasively assess fibrosis[95].Concluding remarksAssessment of HSS morbidity and treatment monitoring would benefit from non-invasive imaging methods allowing reliable fibrosis staging and estimation of vascular dysfunction (see outstanding questions). Quantitative methods, which have been successfully evaluated on human fibrotic and cirrhotic liver (USG elastography, MRE, 31 P-MRS, ASL, perfusion PET …) or in experimental schistosomiasis (T 2 mapping) have a potential for clinical/human schistosomiasis assessment provided the equipment is available.…”

Anatomical MRI and [18F]FDG PET/CT imaging of Schistosoma mansoni in a NMRI mouse model

“…Moreover, the characterization of a mouse model of schistosomiasis using MRI demonstrated that this in vivo imaging technique is capable of monitoring liver damage during the course of the disease 26 . The pathological findings obtained in this MRT study were consistent with known characteristics of infected people, confirming the convenience of MRI imaging as an appropriate instrument to detect schistosomiasis and determine the efficacy of new developed therapies 26 . In light of these results, we assume that a combined use of PET/CT and MRI could be a beneficial technique for clinicians and researchers to visualize and characterize the worm load in infected individuals and to evaluate new treatments for schistosomiasis in vivo.…”