RT Journal Article
SR Electronic
T1 Insights into disseminated MS brain pathology with multimodal diffusion tensor and PET imaging
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e691
DO 10.1212/NXI.0000000000000691
VO 7
IS 3
A1 Bezukladova, Svetlana
A1 Tuisku, Jouni
A1 Matilainen, Markus
A1 Vuorimaa, Anna
A1 Nylund, Marjo
A1 Smith, Sarah
A1 Sucksdorff, Marcus
A1 Mohammadian, Mehrbod
A1 Saunavaara, Virva
A1 Laaksonen, Sini
A1 Rokka, Johanna
A1 Rinne, Juha O.
A1 Rissanen, Eero
A1 Airas, Laura
YR 2020
UL http://nn.neurology.org/content/7/3/e691.abstract
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