Abstract
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.
Glossary
- ANCOVA=
- analysis of covariance;
- ANOVA=
- analysis of variance;
- BPF=
- brain parenchymal fraction;
- CIS=
- clinically isolated syndrome;
- DTI=
- diffusion tensor imaging;
- DVR=
- distribution volume ratio;
- EDSS=
- Expanded Disability Status Scale;
- FA=
- fractional anisotropy;
- GM=
- gray matter;
- MD=
- mean diffusivity;
- MSSS=
- MS severity scale;
- NAWM=
- normal-appearing white matter;
- rm ANCOVA=
- repeated-measures analysis of covariance;
- ROI=
- region of interest;
- RRMS=
- relapsing-remitting MS;
- SPMS=
- secondary progressive MS;
- TPC=
- Turku PET Centre;
- TSPO=
- translocator protein;
- WM=
- white matter;
- WMIC=
- Wolfson Molecular Imaging Centre
Footnotes
Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.
The Article Processing Charge was funded by State Research Funding/TYKS.
- Received September 1, 2017.
- Accepted in final form January 11, 2018.
- Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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