PT  - JOURNAL ARTICLE
AU  - Bezukladova, Svetlana
AU  - Tuisku, Jouni
AU  - Matilainen, Markus
AU  - Vuorimaa, Anna
AU  - Nylund, Marjo
AU  - Smith, Sarah
AU  - Sucksdorff, Marcus
AU  - Mohammadian, Mehrbod
AU  - Saunavaara, Virva
AU  - Laaksonen, Sini
AU  - Rokka, Johanna
AU  - Rinne, Juha O.
AU  - Rissanen, Eero
AU  - Airas, Laura
TI  - Insights into disseminated MS brain pathology with multimodal diffusion tensor and PET imaging
AID  - 10.1212/NXI.0000000000000691
DP  - 2020 May 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e691
VI  - 7
IP  - 3
4099  - http://nn.neurology.org/content/7/3/e691.short
4100  - http://nn.neurology.org/content/7/3/e691.full
SO  - Neurol Neuroimmunol Neuroinflamm2020 May 01; 7
AB  - Objective To evaluate in vivo the co-occurrence of microglial activation and microstructural white matter (WM) damage in the MS brain and to examine their association with clinical disability.Methods 18-kDa translocator protein (TSPO) brain PET imaging was performed for evaluation of microglial activation by using the radioligand [11C](R)-PK11195. TSPO binding was evaluated as the distribution volume ratio (DVR) from dynamic PET images. Diffusion tensor imaging (DTI) and conventional MRI (cMRI) were performed at the same time. Mean fractional anisotropy (FA) and mean (MD), axial, and radial (RD) diffusivities were calculated within the whole normal-appearing WM (NAWM) and segmented NAWM regions appearing normal in cMRI. Fifty-five patients with MS and 15 healthy controls (HCs) were examined.Results Microstructural damage was observed in the NAWM of the MS brain. DTI parameters of patients with MS were significantly altered in the NAWM compared with an age- and sex-matched HC group: mean FA was decreased, and MD and RD were increased. These structural abnormalities correlated with increased TSPO binding in the whole NAWM and in the temporal NAWM (p < 0.05 for all correlations; p < 0.01 for RD in the temporal NAWM). Both compromised WM integrity and increased microglial activation in the NAWM correlated significantly with higher clinical disability measured with the Expanded Disability Status Scale score.Conclusions Widespread structural disruption in the NAWM is linked to neuroinflammation, and both phenomena associate with clinical disability. Multimodal PET and DTI allow in vivo evaluation of widespread MS pathology not visible using cMRI.AD=axial diffusivity; BPND=binding potential; cMRI=conventional MRI; DMT=disease-modifying therapy; DTI=diffusion tensor imaging; DVR=distribution volume ratio; EDSS=Expanded Disability Status Scale; FA=fractional anisotropy; GM=gray matter; MD=mean diffusivity; MR=magnetic resonance; MSSS=MS severity scale; RD=radial diffusivity; ROI=region of interest; RRMS=relapsing-remitting MS; SPMS=secondary progressive MS; TAC=time-activity curve; TSPO=translocator protein; WM=white matter