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Updated: Dec 27, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Insights into disseminated MS brain pathology with multimodal diffusion tensor and PET imaging
Svetlana Bezukladova1, Jouni Tuisku1, Markus Matilainen1
1From the Turku PET Centre (S.B., J.T., M. Matilainen, A.V., M.N., S.S., M.S., M. Mohammadian, V.S., S.L., J.R., J.O.R., E.R., L.A.), University of Turku and Turku University Hospital; Division of Clinical Neurosciences (A.V., M.N., S.S., M.S., S.L., E.R., L.A.), Turku University Hospital; and Department of Medical Physics (V.S.), Division of Medical Imaging, Turku University Hospital, Finland.
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.
Insights
Microglial activation and white matter damage in multiple sclerosis (MS) brains are linked. This neuroinflammation and structural disruption correlate with increased clinical disability in MS patients.
Area of Science:
- Neuroimaging
- Neurology
- Radiology
Background:
- Multiple Sclerosis (MS) is characterized by neuroinflammation and white matter (WM) damage.
- Current imaging techniques may not fully capture the extent of MS pathology in normal-appearing white matter (NAWM).
Purpose of the Study:
- To investigate the in vivo co-occurrence of microglial activation and microstructural WM damage in MS.
- To determine the association between these pathologies and clinical disability.
Main Methods:
- Positron Emission Tomography (PET) with [11C](R)-PK11195 to assess microglial activation (TSPO binding).
- Diffusion Tensor Imaging (DTI) to evaluate white matter microstructure (FA, MD, RD).
- Conventional MRI (cMRI) and clinical disability assessment (EDSS) in 55 MS patients and 15 healthy controls (HCs).
Main Results:
- MS patients showed significant microstructural damage in NAWM compared to HCs (decreased FA, increased MD and RD).
- Increased TSPO binding in NAWM correlated with DTI-derived WM abnormalities.
- Both compromised WM integrity and microglial activation in NAWM were significantly associated with higher clinical disability (EDSS scores).
Conclusions:
- Widespread structural disruption and neuroinflammation in NAWM are linked in MS.
- These in vivo findings highlight the association between MS pathology and clinical disability.
- Multimodal PET and DTI imaging offer valuable insights into MS pathology beyond conventional MRI.
