Both things appear before the immune infiltration and the demyelination and are thought to be the primary cause of the MS lesions. If finally activated microglia is the cause of NAWM would be a good notice, because microglia can be tamed [http://multiple-sclerosis-research.blog ... oglia.html]
Microglial activation, white matter tract damage, and disability in MS
Objective: To investigate the relationship of in vivo microglial activation to clinical and MRI parameters in MS.
Methods: Patients with secondary progressive MS (n = 10) or relapsing-remitting MS (n = 10) and age-matched healthy controls (n = 17) were studied. Microglial activation was measured using PET and radioligand [11C](R)-PK11195. Clinical assessment and structural and quantitative MRI including diffusion tensor imaging (DTI) were performed for comparison.
Results: [11C](R)-PK11195 binding was significantly higher in the normal-appearing white matter (NAWM) of patients with secondary progressive vs relapsing MS and healthy controls, in the thalami of patients with secondary progressive MS vs controls, and in the perilesional area among the progressive compared with relapsing patients. Higher binding in the NAWM was associated with higher clinical disability and reduced white matter (WM) structural integrity, as shown by lower fractional anisotropy, higher mean diffusivity, and increased WM lesion load. Increasing age contributed to higher microglial activation in the NAWM among patients with MS but not in healthy controls.
Conclusions: PET can be used to quantitate microglial activation, which associates with MS progression. This study demonstrates that increased microglial activity in the NAWM correlates closely with impaired WM structural integrity and thus offers one rational pathologic correlate to diffusion tensor imaging (DTI) parameters.
http://orca-mwe.cf.ac.uk/120683/1/Manus ... sion_3.pdf
Quantifying white matter damage in vivo is becoming increasingly important for investigating the effects of neuro- protective and repair strategies in multiple sclerosis (MS). While various approaches are available, the relationship between MRI-based metrics of white matter microstructure in the disease, i.e. to what extent the metrics provide complementary vs redundant information, remains largely unexplored.
We obtained four microstructural metrics from 123 MS patients: fractional anisotropy (FA), radial diffusivity (RD), myelin water fraction (MWF), and magnetisation transfer ratio (MTR). Co-registration of maps of these four indices allowed quantification of microstructural damage through voxel-wise damage scores relative to healthy tissue, as assessed in a group of 27 controls. We considered three white matter tissue-states, which were expected to vary in microstructural damage: normal appearing white matter (NAWM), T2-weighted hyperintense lesional tissue without T1-weighted hypointensity (T2L), and T1-weighted hypointense lesional tissue with corresponding T2-weighted hyperintensity (T1L).
All MRI-indices suggested significant damage in all three tissue-states, the greatest damage being in T1L. The correlations between indices ranged from r=.18 to r=.87. MWF was most sensitive when differentiating T2L from NAWM , while MTR was most sensitive when differentiating T1L
from NAWM and from T2L.
Combining the four metrics into one, through a principal component analysis, did not yield a measure more sensitive to damage than any single measure.
Our findings suggest that the metrics are (at least partially) correlated with each other, but sensitive to different aspects of pathology. Leveraging these differences could be beneficial in clinical trials testing the effects of therapeutic interventions
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