ECTRIMS eLearning

White matter diffusion and myelin integrity improvement after 6 months of fingolimod treatment in relapsing-remitting multiple sclerosis
Author(s): ,
S. Bezukladova
Affiliations:
Åbo Akademi University
,
J. Tuisku
Affiliations:
Turku PET Centre
,
M. Sucksdorff
Affiliations:
Turku PET Centre; Division of Clinical Neurosciences, Turku University Hospital and University of Turku
,
V. Saunavaara
Affiliations:
Turku PET Centre; Department of Medical physics, Turku University Hospital
,
T. Paavilainen
Affiliations:
Medical Imaging Centre of Southwest Finland, Turku University Hospital and University of Turku, Turku, Finland
,
E. Rissanen
Affiliations:
Turku PET Centre; Division of Clinical Neurosciences, Turku University Hospital and University of Turku
,
J.O. Rinne
Affiliations:
Turku PET Centre; Division of Clinical Neurosciences, Turku University Hospital and University of Turku
L. Airas
Affiliations:
Division of Clinical Neurosciences, Turku University Hospital and University of Turku
ECTRIMS Learn. Bezukladova S. 10/10/18; 229513; EP1676
Svetlana Bezukladova
Svetlana Bezukladova
Contributions
Abstract

Abstract: EP1676

Type: Poster Sessions

Abstract Category: Therapy - Tools for detecting therapeutic response

Background: Conventional magnetic resonance imaging (cMRI) is mainly used for evaluation of lesional inflammatory activity and diffuse atrophy in diagnosis and follow-up of MS (multiple sclerosis). However, diffusion tensor imaging (DTI) can reveal microstructural alterations in the normal appearing white matter (NAWM), undetectable in conventional MRI.
Objectives: To evaluate structural brain changes, using DTI, in patients with relapsing-remitting multiple sclerosis (RRMS) during 6 months of fingolimod treatment.
Methods: 10 RRMS patients (28-53 years, 10 female, 1 male) and 15 healthy controls (HC, 21-51 years, 9 female, 6 male), were imaged with 3T Philips Achieva MRI scanner. Scanning protocol included 3D T1-weighted and T2-weighted fluid-attenuated inversion recovery sequences and DTI with 64 directions (resolution 2x2x2 mm). T2 hyperintense lesions were segmented with Lesion Segmentation Tool and extracted from WM to yield NAWM masks. The mean values of diffusion scalars, fractional anisotropy (FA), mean (MD), axial (AD) and radial (RD) diffusivities, were calculated with ExploreDTI within whole NAWM and segmented white matter WM regions (deep WM, cingulate, frontal, temporal, occipital, parietal). The extent of white matter damage was also analyzed using tract-based spatial statistics (TBSS). Voxel-wise TBSS analysis was implemented with threshold-free cluster enhancement method (TFCE), with family-wise error correction and threshold of p < 0.05.
Results: After 6 months of fingolimod treatment, mean FA was significantly increased (p =0.02) and mean RD decreased (p=0.04) in cingulate WM of RRMS patients. TBSS analysis showed that 18.1% of NAWM skeleton voxels of RRMS subjects had significantly decreased FA at baseline imaging compared to HC. This number decreased to 3.7% of voxels after 6 months of fingolimod treatment, compared to HC. The extent of voxels with significantly increased RD was 17.7% and 11.1%, respectively. Meanwhile, there were no significant changes in the T2 lesion, NAWM or GM (grey matter) volumes during the 6 months.
Conclusion: The results suggest improvement in microstructural white matter integrity in RRMS patients after 6 months of fingolimod treatment with concomitantly unchanged cMRI parameters. This indicates, that DTI could be used as a sensitive imaging biomarker in longitudinal studies to evaluate treatment response in the NAWM in MS.
Disclosure: Svetlana Bezukladova, Jouni Tuisku, Marcus Sucksdorff, Virva Saunavaara, Teemu Paavilainen, Juha O. Rinne have nothing to disclose. Eero Rissanen has received speaker honoraria from Teva, Biogen and Roche, a consultational fee from Merck and personal reserach grants from Turku University Hospital and the Finnish MS Foundation. Laura Airas has received honoraria from Biogen, F. Hoffmann-La Roche Ltd, Genzyme, Merck Serono and Teva, and institutional research grant support from Biogen, Genzyme, Merck Serono and Novartis.

Abstract: EP1676

Type: Poster Sessions

Abstract Category: Therapy - Tools for detecting therapeutic response

Background: Conventional magnetic resonance imaging (cMRI) is mainly used for evaluation of lesional inflammatory activity and diffuse atrophy in diagnosis and follow-up of MS (multiple sclerosis). However, diffusion tensor imaging (DTI) can reveal microstructural alterations in the normal appearing white matter (NAWM), undetectable in conventional MRI.
Objectives: To evaluate structural brain changes, using DTI, in patients with relapsing-remitting multiple sclerosis (RRMS) during 6 months of fingolimod treatment.
Methods: 10 RRMS patients (28-53 years, 10 female, 1 male) and 15 healthy controls (HC, 21-51 years, 9 female, 6 male), were imaged with 3T Philips Achieva MRI scanner. Scanning protocol included 3D T1-weighted and T2-weighted fluid-attenuated inversion recovery sequences and DTI with 64 directions (resolution 2x2x2 mm). T2 hyperintense lesions were segmented with Lesion Segmentation Tool and extracted from WM to yield NAWM masks. The mean values of diffusion scalars, fractional anisotropy (FA), mean (MD), axial (AD) and radial (RD) diffusivities, were calculated with ExploreDTI within whole NAWM and segmented white matter WM regions (deep WM, cingulate, frontal, temporal, occipital, parietal). The extent of white matter damage was also analyzed using tract-based spatial statistics (TBSS). Voxel-wise TBSS analysis was implemented with threshold-free cluster enhancement method (TFCE), with family-wise error correction and threshold of p < 0.05.
Results: After 6 months of fingolimod treatment, mean FA was significantly increased (p =0.02) and mean RD decreased (p=0.04) in cingulate WM of RRMS patients. TBSS analysis showed that 18.1% of NAWM skeleton voxels of RRMS subjects had significantly decreased FA at baseline imaging compared to HC. This number decreased to 3.7% of voxels after 6 months of fingolimod treatment, compared to HC. The extent of voxels with significantly increased RD was 17.7% and 11.1%, respectively. Meanwhile, there were no significant changes in the T2 lesion, NAWM or GM (grey matter) volumes during the 6 months.
Conclusion: The results suggest improvement in microstructural white matter integrity in RRMS patients after 6 months of fingolimod treatment with concomitantly unchanged cMRI parameters. This indicates, that DTI could be used as a sensitive imaging biomarker in longitudinal studies to evaluate treatment response in the NAWM in MS.
Disclosure: Svetlana Bezukladova, Jouni Tuisku, Marcus Sucksdorff, Virva Saunavaara, Teemu Paavilainen, Juha O. Rinne have nothing to disclose. Eero Rissanen has received speaker honoraria from Teva, Biogen and Roche, a consultational fee from Merck and personal reserach grants from Turku University Hospital and the Finnish MS Foundation. Laura Airas has received honoraria from Biogen, F. Hoffmann-La Roche Ltd, Genzyme, Merck Serono and Teva, and institutional research grant support from Biogen, Genzyme, Merck Serono and Novartis.

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