title: Definition and quantification of acute inflammatory white matter injury in the immature brain by MRI/MRS at high magnetic field.
abstract: BACKGROUND
  Lipopolysaccharide (LPS) injection in the corpus callosum (CC) of rat pups results in diffuse white matter injury similar to the main neuropathology of preterm infants. The aim of this study was to characterize the structural and metabolic markers of acute inflammatory injury by high-field magnetic resonance imaging (MRI) magnetic resonance spectroscopy (MRS) in vivo.
  
  
  METHODS
  Twenty-four hours after a 1-mg/kg injection of LPS in postnatal day 3 rat pups, diffusion tensor imaging and proton nuclear magnetic spectroscopy ((1)H NMR) were analyzed in conjunction to determine markers of cell death and inflammation using immunohistochemistry and gene expression.
  
  
  RESULTS
  MRI and MRS in the CC revealed an increase in lactate and free lipids and a decrease of the apparent diffusion coefficient. Detailed evaluation of the CC showed a marked apoptotic response assessed by fractin expression. Interestingly, the degree of reduction in the apparent diffusion coefficient correlated strongly with the natural logarithm of fractin expression, in the same region of interest. LPS injection further resulted in increased activated microglia clustered in the cingulum, widespread astrogliosis, and increased expression of genes for interleukin (IL)-1, IL-6, and tumor necrosis factor.
  
  
  CONCLUSIONS
  This model was able to reproduce the typical MRI hallmarks of acute diffuse white matter injury seen in preterm infants and allowed the evaluation of in vivo biomarkers of acute neuropathology after inflammatory challenge.
authors.affiliation: 1] Department of Pediatrics, Division of Child Development & Growth, University of Geneva, Geneva, Switzerland [2] Department of Pediatrics, Neonatal ICU, Research Center, CHU Sainte-Justine, Montréal, Québec, Canada [3] Montreal Heart Institute, Research Center, University of Montreal, Montréal, Québec, Canada.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Lodygensky
authors.affiliation: 1] Department of Pediatrics, Division of Child Development & Growth, University of Geneva, Geneva, Switzerland [2] Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kunz
authors.affiliation: Department of Pediatrics, Division of Child Development & Growth, University of Geneva, Geneva, Switzerland.
authors.forename: Elodie
authors.initials: E
authors.lastname: Perroud
authors.affiliation: Department of Pediatrics, Division of Child Development & Growth, University of Geneva, Geneva, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Somm
authors.affiliation: Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mlynarik
authors.affiliation: Department of Pediatrics, Division of Child Development & Growth, University of Geneva, Geneva, Switzerland.
authors.forename: Petra S
authors.initials: PS
authors.lastname: Hüppi
authors.affiliation: Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
authors.affiliation: Department of Pediatrics, Division of Child Development & Growth, University of Geneva, Geneva, Switzerland.
authors.forename: Stéphane V
authors.initials: SV
authors.lastname: Sizonenko
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D056324:Diffusion Tensor Imaging; D004660:Encephalitis / Q000175:diagnosis*; D006801:Humans; D007150:Immunohistochemistry; D007234:Infant, Premature; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D056784:Leukoencephalopathies / Q000175:diagnosis*; D008070:Lipopolysaccharides; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid