title: Magnetic Resonance Imaging Is Sensitive to Pathological Amelioration in a Model for Laminin-Deficient Congenital Muscular Dystrophy (MDC1A).
abstract: OBJECTIVE
  To elucidate the reliability of MRI as a non-invasive tool for assessing in vivo muscle health and pathological amelioration in response to Losartan (Angiotensin II Type 1 receptor blocker) in DyW mice (mouse model for Laminin-deficient Congenital Muscular Dystrophy Type 1A).
  
  
  METHODS
  Multiparametric MR quantifications along with histological/biochemical analyses were utilized to measure muscle volume and composition in untreated and Losartan-treated 7-week old DyW mice.
  
  
  RESULTS
  MRI shows that DyW mice have significantly less hind limb muscle volume and areas of hyperintensity that are absent in WT muscle. DyW mice also have significantly elevated muscle levels (suggestive of inflammation and edema). Muscle T2 returned to WT levels in response to Losartan treatment. When considering only muscle pixels without T2 elevation, DyW T2 levels are significantly lower than WT (suggestive of fibrosis) whereas Losartan-treated animals do not demonstrate this decrease in muscle T2. MRI measurements suggestive of elevated inflammation and fibrosis corroborate with increased Mac-1 positive cells as well as increased Picrosirius red staining/COL1a gene expression that is returned to WT levels in response to Losartan.
  
  
  CONCLUSIONS
  MRI is sensitive to and tightly corresponds with pathological changes in DyW mice and thus is a viable and effective non-invasive tool for assessing pathological changes.
authors.affiliation: Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL, United States of America.
authors.forename: Ravneet
authors.initials: R
authors.lastname: Vohra
authors.affiliation: Department of Health Sciences, Sargent College, Boston University, Boston, MA, United States of America.
authors.forename: Anthony
authors.initials: A
authors.lastname: Accorsi
authors.affiliation: Department of Health Sciences, Sargent College, Boston University, Boston, MA, United States of America.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL, United States of America.
authors.forename: Glenn
authors.initials: G
authors.lastname: Walter
authors.affiliation: Department of Health Sciences, Sargent College, Boston University, Boston, MA, United States of America.
authors.forename: Mahasweta
authors.initials: M
authors.lastname: Girgenrath
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007797:Laminin / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015203:Reproducibility of Results
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007797:Laminin; D019808:Losartan