title: In Vivo MRI Assessment of Hepatic and Splenic Disease in a Murine Model of Schistosomiasis [corrected].
abstract: BACKGROUND
  Schistosomiasis (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.
  
  
  RESULTS
  CBA/J mice were imaged at 11.75 T 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
  Our 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.
authors.affiliation: Génétique et Immunologie des Maladies Parasitaires-Unité Mixte de Recherche S_906, Aix-Marseille Université, Marseille, France; Unité 906, Institut National de la Santé et de la Recherche Médicale, Marseille, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Masi
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale-Unité Mixte de Recherche 7339, Aix-Marseille Université, Marseille, France; Unité Mixte de Recherche 7339, Centre National de la Recherche Scientifique, Marseille, France.
authors.forename: Teodora-Adriana
authors.initials: TA
authors.lastname: Perles-Barbacaru
authors.affiliation: Laboratoire VET-HISTO, Marseille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Laprie
authors.affiliation: Génétique et Immunologie des Maladies Parasitaires-Unité Mixte de Recherche S_906, Aix-Marseille Université, Marseille, France; Unité 906, Institut National de la Santé et de la Recherche Médicale, Marseille, France.
authors.forename: Helia
authors.initials: H
authors.lastname: Dessein
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale-Unité Mixte de Recherche 7339, Aix-Marseille Université, Marseille, France; Unité Mixte de Recherche 7339, Centre National de la Recherche Scientifique, Marseille, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Bernard
authors.affiliation: Génétique et Immunologie des Maladies Parasitaires-Unité Mixte de Recherche S_906, Aix-Marseille Université, Marseille, France; Unité 906, Institut National de la Santé et de la Recherche Médicale, Marseille, France; Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire Timone, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Dessein
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale-Unité Mixte de Recherche 7339, Aix-Marseille Université, Marseille, France; Unité Mixte de Recherche 7339, Centre National de la Recherche Scientifique, Marseille, France.
authors.forename: Angèle
authors.initials: A
authors.lastname: Viola
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006651:Histocytochemistry; D008103:Liver Cirrhosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008808:Mice, Inbred CBA; D011860:Radiography, Abdominal; D012550:Schistosoma mansoni / Q000254:growth & development; D012552:Schistosomiasis / Q000473:pathology*; D013158:Splenic Diseases / Q000473:pathology*