Fig 1.
MRI signs of organomegaly and portal hypertension.
(A) Comparison of contrast-enhanced anatomical MRI covering liver and spleen in a representative infected and a control mouse at 2, 6, and 10 weeks post infection. Two images are shown for each mouse, one centered on the liver and the portal vein (left image for each couple of images), and another one showing the spleen (right image). A multifocal liver and spleen damage is observable at 10 weeks. Spleen (vertical arrows), portal vein (oblique arrows), liver multifocal hyperintensities (arrowheads). The circular object is the external reference tube. Progressive increases in hepatic volume (B), spleen volume (C) and portal vein cross section (D) are detected from week 6 to10 after infection. (*P<0.05, **P<0.01), filled squares = infected animals, empty squares = control animals. Abbreviations: L = liver, PV = portal vein, S = spleen.
Fig 2.
Quantitative T2 and T2* mapping at 10 weeks post infection.
(A) Non contrast-enhanced anatomical acquisitions, T2 and T2* maps for two representative mice from the control and the schistosomiasis group (color bar range: 0 to 50 ms for T2 maps, 0 to 20 ms for T2* maps). Spatial patterns of increased T2 and decreased T2* can be observed in the infected mouse. The external reference has an average T2 of 21.55 ± 0.25 ms (2 weeks: 21.74±0.22 ms, 6 weeks 21.64 ± 0.65 ms, 10 weeks: 21.26±0.60 ms, P = 0.1139). Regions of interest (ROI) in the liver used for analysis are shown on the anatomical acquisitions. (B) At 10 weeks post infection the T2 distribution is enlarged (P < 0.01) in infected (n = 4) compared to control livers (n = 6) with a fraction of values exceeding 16 ms. (C) The area fraction with T2 ϵ [16 ms;26 ms] is significantly increased at 10 weeks post infection compared with control mice (Dunn’s Multiple Comparison Test P < 0.05). The overlay (D) shows that hepatic regions with increased T2 co-localize with hyperintensities seen in the anatomical images prior to Gd-DOTA injection. These hyperintense lesions further enhance after Gd-DOTA injection, but organ displacement prevents pixelwise comparison with T2 maps. (E) Distributions of hepatic T2* values at 10 weeks post infection showing decreased T2* values (P < 0.01) in the infected mice (n = 4) compared to controls (n = 5).
Fig 3.
Relaxometry of collagen solutions.
This figure shows the absence of significant variation of relaxation time-constants with collagen concentration.
Fig 4.
Liver granulomatous pathology and fibrosis.
(A) Intravascular adult parasite at 6 weeks post infection (HE, scale bar 100 μm). (B) to (H): 10 weeks post infection. (B) Granuloma centred on one egg (HE, scale bar 50 μm). (C) Focal hepatocellular necrosis (HE, scale bar 100 μm). (D) Periportal eosinophilic inflammation (red arrow) around a bile duct (blue arrow) (HE, scale bar 100 μm). (E) and (F) Liver lobe allowing assessment of the extent of granulomatous chronic inflammation and hepatitis (arrows pointing at granulomas) in HE staining (E) and portal fibrosis with collagen deposition assessed with Sirius Red staining (F) (bar 500 μm). Sirius Red facilitates quantification of extracellular matrix deposition of collagen within granulomas (zoom in F, bar 100 μm). (G) and (H) Intergranulomatous fibrosis in HE staining (G) and Sirius Red staining (H) (arrowhead pointing at granuloma and arrow at intergranulomatous fibrosis) (scale bar 500 μm). HE = Hematoxylin-Eosin.
Fig 5.
Correlation between relaxometric and histological markers of disease severity.
Disease severity as assessed by the METAVIR score (A) and the area fraction stained with Sirius Red for collagen (B) increases mainly 6 weeks after infection. The area fraction of liver T2 values between 16 and 26 ms obtained at 10 weeks after infection correlates with the METAVIR grading (C) and fibrosis quantification with Sirius Red staining (D). A 95% bivariate normal density ellipse is represented on each scatterplot. (The correlations obtained for the values measured at 6 and 10 weeks are shown in S2A and S2B Fig).