ECTRIMS eLearning

Diffusivity data suggests progressive lesion-independent demyelination in NAWM of MS patients: a 5 year study
Author(s): ,
A. Klistorner
Affiliations:
Sydney Neuroimaging Analysis Centre; Ophthalmology, The University of Sydney, Save Sight Institute; Australian School of Advanced Medicine, Macquarie University
,
C. Wang
Affiliations:
Sydney Neuroimaging Analysis Centre; Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
,
S. Liu
Affiliations:
Ophthalmology, The University of Sydney, Save Sight Institute; Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
,
L. Graham
Affiliations:
Australian School of Advanced Medicine, Macquarie University
M. Barnett
Affiliations:
Sydney Neuroimaging Analysis Centre; Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
ECTRIMS Learn. Wang C. 10/11/18; 228663; P820
Chenyu Wang
Chenyu Wang
Contributions
Abstract

Abstract: P820

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Introduction and objectives: Recent data suggest that progressive tissue loss in the core of chronic multiple sclerosis (MS) lesions is reflected by increasing diffusivity measured by magnetic resonance imagining (MRI). However, measured diffusivity in the normal appearing white matter (NAWM) remains relatively stable over time, potentially a consequence of short follow-up periods or non-congruency of NAWM ROIs at baseline and follow-up related to progressive brain atrophy. Therefore, in the current study we assessed changes in NAWM diffusivity over a relatively long (5 year) period of follow-up. In addition, NAWM ROIs were topgraphically “linked” to chronic MS lesions, and their position adjusted for brain atrophy.
Methods: Pre- and post-gadolinium T1, T2 FLAIR and DTI images were acquired from 39 consecutive RRMS patients at baseline and 5 years. Baseline lesion masks (excluding gadolinium-enhancing lesions) were identified on T2 FLAIR images. Progressive mean, axial and radial diffusivity (MD, AD and RD) change were analysed in lesion “core”, lesion “rim” and 6 expanding external shells (each 1 voxel thick) 1,2,3,4,5 and 10 voxels from the lesion edge. Perilesional WM ROIs were intersected with the white matter mask to avoid CSF and grey matter contamination.
Results: There was a considerable increase of MD within MS lesions, recapitulating previous work. While longitudinal MD change gradually decreased towards NAWM, it remained significant even in outermost shell. Furthermore, while the observed increase in lesional MD was driven by an equivalent change of RD and AD, the relative contribution of RD progressively increased towards the NAWM. Conversely, the change in AD progressively dropped with increasing distance from lesion, and finally became negligible. The difference between the ΔRD and ΔAD in NAWM increased centrifugally and then stabilised at about 4 mm from the lesion edge.
Conclusions: This study demonstrates a lesion-independent increase of RD in NAWM over 5 years, which may reflect progressive loss of myelin. Despite significant brain atrophy in the study population, AD remained stable, indicating, that parallel diffusivity may not be an adequate measure of axonal loss in NAWM.
Disclosure: Alexander Klistorner: nothing to disclose.Chenyu Wang: nothing to disclose. Sidong Liu: nothing to disclose. Lizzi Graham: nothing to disclose. Michael Barnett has received institutional support for research, speaking and/or participation in advisory boards for Biogen, Merck, Novartis, Roche and Sanofi Genzyme. Dr Barnett is a research consultant at Medical Safety Systems and research director for the Sydney Neuroimaging Analysis Centre.

Abstract: P820

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Introduction and objectives: Recent data suggest that progressive tissue loss in the core of chronic multiple sclerosis (MS) lesions is reflected by increasing diffusivity measured by magnetic resonance imagining (MRI). However, measured diffusivity in the normal appearing white matter (NAWM) remains relatively stable over time, potentially a consequence of short follow-up periods or non-congruency of NAWM ROIs at baseline and follow-up related to progressive brain atrophy. Therefore, in the current study we assessed changes in NAWM diffusivity over a relatively long (5 year) period of follow-up. In addition, NAWM ROIs were topgraphically “linked” to chronic MS lesions, and their position adjusted for brain atrophy.
Methods: Pre- and post-gadolinium T1, T2 FLAIR and DTI images were acquired from 39 consecutive RRMS patients at baseline and 5 years. Baseline lesion masks (excluding gadolinium-enhancing lesions) were identified on T2 FLAIR images. Progressive mean, axial and radial diffusivity (MD, AD and RD) change were analysed in lesion “core”, lesion “rim” and 6 expanding external shells (each 1 voxel thick) 1,2,3,4,5 and 10 voxels from the lesion edge. Perilesional WM ROIs were intersected with the white matter mask to avoid CSF and grey matter contamination.
Results: There was a considerable increase of MD within MS lesions, recapitulating previous work. While longitudinal MD change gradually decreased towards NAWM, it remained significant even in outermost shell. Furthermore, while the observed increase in lesional MD was driven by an equivalent change of RD and AD, the relative contribution of RD progressively increased towards the NAWM. Conversely, the change in AD progressively dropped with increasing distance from lesion, and finally became negligible. The difference between the ΔRD and ΔAD in NAWM increased centrifugally and then stabilised at about 4 mm from the lesion edge.
Conclusions: This study demonstrates a lesion-independent increase of RD in NAWM over 5 years, which may reflect progressive loss of myelin. Despite significant brain atrophy in the study population, AD remained stable, indicating, that parallel diffusivity may not be an adequate measure of axonal loss in NAWM.
Disclosure: Alexander Klistorner: nothing to disclose.Chenyu Wang: nothing to disclose. Sidong Liu: nothing to disclose. Lizzi Graham: nothing to disclose. Michael Barnett has received institutional support for research, speaking and/or participation in advisory boards for Biogen, Merck, Novartis, Roche and Sanofi Genzyme. Dr Barnett is a research consultant at Medical Safety Systems and research director for the Sydney Neuroimaging Analysis Centre.

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