title: In vivo study of experimental pneumococcal meningitis using magnetic resonance imaging.
abstract: BACKGROUND
  Magnetic Resonance Imaging (MRI) methods were evaluated as a tool for the study of experimental meningitis. The identification and characterisation of pathophysiological parameters that vary during the course of the disease could be used as markers for future studies of new treatment strategies.
  
  
  METHODS
  Rats infected intracisternally with S. pneumoniae (n = 29) or saline (n = 13) were randomized for imaging at 6, 12, 24, 30, 36, 42 or 48 hours after infection. T1W, T2W, quantitative diffusion, and post contrast T1W images were acquired at 4.7 T. Dynamic MRI (dMRI) was used to evaluate blood-brain-barrier (BBB) permeability and to obtain a measure of cerebral and muscle perfusion. Clinical- and motor scores, bacterial counts in CSF and blood, and WBC counts in CSF were measured.
  
  
  RESULTS
  MR images and dMRI revealed the development of a highly significant increase in BBB permeability (P < 0.002) and ventricle size (P < 0.0001) among infected rats. Clinical disease severity was closely related to ventricle expansion (P = 0.024). Changes in brain water distribution, assessed by ADC, and categorization of brain 'perfusion' by cortex DeltaSI(bolus) were subject to increased inter-rat variation as the disease progressed, but without overall differences compared to uninfected rats (P > 0.05). Areas of well-'perfused' muscle decreased with the progression of infection indicative of septicaemia (P = 0.05).
  
  
  CONCLUSIONS
  The evolution of bacterial meningitis was successfully followed in-vivo with MRI. Increasing BBB-breakdown and ventricle size was observed in rats with meningitis whereas changes in brain water distribution were heterogeneous. MRI will be a valuable technique for future studies aiming at evaluating or optimizing adjunctive treatments.
authors.affiliation: National Center for Antimicrobials and Infection Control, Statens Serum Institut, Copenhagen, Denmark. ctb@ssi.dk
authors.forename: Christian T
authors.initials: CT
authors.lastname: Brandt
authors.forename: Helle
authors.initials: H
authors.lastname: Simonsen
authors.forename: Matthew
authors.initials: M
authors.lastname: Liptrot
authors.forename: Lise V
authors.initials: LV
authors.lastname: Søgaard
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Christian
authors.initials: C
authors.lastname: Ostergaard
authors.forename: Niels
authors.initials: N
authors.lastname: Frimodt-Møller
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Rowland
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology*; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008586:Meningitis, Pneumococcal / Q000175:diagnosis*; D051381:Rats; D017208:Rats, Wistar