In vivo study of experimental pneumococcal meningitis using magnetic resonance imaging

Christian T Brandt¹^,3 , Helle Simonsen² , Matthew Liptrot² , Lise V Søgaard² , Jens D Lundgren³ , Christian Østergaard¹^,4 , Niels Frimodt-Møller¹ and Ian J Rowland²^,5

¹National Center for Antimicrobials and Infection Control, Statens Serum Institut, Copenhagen, Denmark

²Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark

³CHIP, Faculty of Health Sciences, University of Copenhagen, Denmark

⁴Clinical Microbiological Department, University Hospital Herlev, Copenhagen, Denmark

⁵Radiology, University Wisconsin-Madison, Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA

author email corresponding author email

BMC Medical Imaging 2008, 8:1doi:10.1186/1471-2342-8-1


Published:	14 January 2008

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 ΔSI_(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).

Conclusion

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