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Published on: June 8, 2017
In vivo study of experimental pneumococcal meningitis using magnetic resonance imaging
Christian T Brandt1, Helle Simonsen, Matthew Liptrot
1National Center for Antimicrobials and Infection Control, Statens Serum Institut, Copenhagen, Denmark. ctb@ssi.dk
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).
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.
Insights
Magnetic Resonance Imaging (MRI) effectively tracked experimental meningitis in rats. The study identified increased blood-brain-barrier permeability and ventricle size as key markers of disease progression.
Area of Science:
- Neuroimaging
- Infectious Diseases
- Experimental Medicine
Background:
- Experimental meningitis studies require robust methods to track disease progression.
- Identifying pathophysiological markers is crucial for evaluating new treatment strategies.
Purpose of the Study:
- To evaluate Magnetic Resonance Imaging (MRI) methods for studying experimental meningitis.
- To identify and characterize pathophysiological parameters that change during meningitis progression.
Main Methods:
- Rats with S. pneumoniae meningitis underwent various MRI sequences (T1W, T2W, diffusion, contrast-enhanced) at multiple time points.
- Dynamic MRI (dMRI) assessed blood-brain-barrier (BBB) permeability and perfusion.
- Clinical scores, bacterial, and white blood cell (WBC) counts were also measured.
Main Results:
- MRI revealed significant increases in BBB permeability and ventricle size in infected rats.
- Clinical disease severity correlated with ventricle expansion.
- Muscle perfusion decreased, indicating sepsis, while brain water distribution showed heterogeneous changes.
Conclusions:
- In-vivo MRI successfully monitored the evolution of bacterial meningitis in rats.
- Increasing BBB breakdown and ventricle size were key MRI findings.
- MRI is a valuable tool for future studies evaluating adjunctive meningitis treatments.
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