Abstract
PurposeAlthough cerebral perfusion alterations have long been acknowledged in multiple sclerosis (MS), the relationship between measurable perfusion changes and the status of highly active MS has not been examined. We hypothesized that alteration of perfusion can be detected in normal appearing white matter and is increased in high inflammatory patients.Materials and MethodsThirty-three patients with relapsing-remitting MS underwent four monthly 3T MRI scans including dynamic susceptibility contrast perfusion-weighted MRI. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured in normal appearing white matter. Patients were stratified in a high- and low-inflammatory group according to the number of new contrast enhancing lesions.ResultsThirteen patients were classified as high-inflammatory. Compared to low-inflammatory patients, the high-inflammatory group demonstrated significantly higher CBV (p = 0.001) and CBF (p = 0.014) values. A mixed model analysis to assess independent variables associated with CBV and CBF revealed that white matter lesion load and atrophy measurements had no significant influence on CBF and CBV.ConclusionThis work provides evidence that high inflammatory lesion load is associated with increased CBV and CBF, underlining the role of global modified microcirculation prior to leakage of the blood-brain barrier in the pathophysiology of MS. Perfusion changes might therefore be sensitive to active inflammation apart from lesion development without local blood–brain barrier breakdown, and could be utilized to further assess the metabolic aspect of current inflammation.
Highlights
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and white matter (WM) lesions are visualized using T2w magnetic resonance imaging (MRI) in most patients
A mixed model analysis to assess independent variables associated with cerebral blood volume (CBV) and cerebral blood flow (CBF) revealed that white matter lesion load and atrophy measurements had no significant influence on CBF and CBV
Studying ongoing inflammatory processes in normal-appearing white matter (NAWM) by use of structural MRI has been challenging. These processes are not associated with a clear break-down of the blood–brain barrier (BBB) which can be detected as regions of gadolinium contrast enhancement in highly inflammatory lesions [7]
Summary
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and white matter (WM) lesions are visualized using T2w magnetic resonance imaging (MRI) in most patients. Studying ongoing inflammatory processes in NAWM by use of structural MRI has been challenging. These processes are not associated with a clear break-down of the blood–brain barrier (BBB) which can be detected as regions of gadolinium contrast enhancement in highly inflammatory lesions [7]. Previous imaging studies have used perfusion-weighted MRI (PWI) techniques to measure cerebral perfusion in MS patients. These studies have identified both decrease [8,9,10] and increase [11,12] of perfusion in WM. The relationship between measurable perfusion alteration and visible inflammation in structural MRI has not been examined so far
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