Related Experiment Video
Updated: Jul 13, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Multimodal MRI study on the relation between WM integrity and connected GM atrophy and its effect on disability in
Merlin M Weeda1, D R van Nederpelt2, J W R Twisk3
1MS Center Amsterdam, Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands. M.Weeda@amsterdamumc.nl.
Background:
Multiple sclerosis (MS) is characterized by pathology in white matter (WM) and atrophy of grey matter (GM), but it remains unclear how these processes are related, or how they influence clinical progression.
Objective:
To study the spatial and temporal relationship between GM atrophy and damage in connected WM in relapsing-remitting (RR) MS in relation to clinical progression.
Methods:
Healthy control (HC) and early RRMS subjects visited our center twice with a 1-year interval for MRI and clinical examinations, including the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores. RRMS subjects were categorized as MSFC decliners or non-decliners based on ΔMSFC over time. Ten deep (D)GM and 62 cortical (C) GM structures were segmented and probabilistic tractography was performed to identify the connected WM. WM integrity was determined per tract with, amongst others, fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), and myelin water fraction (MWF). Linear mixed models (LMMs) were used to investigate GM and WM differences between HC and RRMS, and between MSFC decliners and non-decliners. LMM was also used to test associations between baseline WM z-scores and changes in connected GM z-scores, and between baseline GM z-scores and changes in connected WM z-scores, in HC/RRMS subjects and in MSFC decliners/non-decliners.
Results:
We included 13 HCs and 31 RRMS subjects with an average disease duration of 3.5 years and a median EDSS of 3.0. Fifteen RRMS subjects showed declining MSFC scores over time, and they showed higher atrophy rates and greater WM integrity loss compared to non-decliners. Lower baseline WM integrity was associated with increased CGM atrophy over time in RRMS, but not in HC subjects. This effect was only seen in MSFC decliners, especially when an extended WM z-score was used, which included FA, MD, NDI and MWF. Baseline GM measures were not significantly related to WM integrity changes over time in any of the groups.
Discussion:
Lower baseline WM integrity was related to more cortical atrophy in RRMS subjects that showed clinical progression over a 1-year follow-up, while baseline GM did not affect WM integrity changes over time. WM damage, therefore, seems to drive atrophy more than conversely.
Insights
In relapsing-remitting multiple sclerosis (RRMS), white matter (WM) damage appears to drive grey matter (GM) atrophy more than the reverse. Lower baseline WM integrity predicts increased GM atrophy in patients with clinical progression.
Area of Science:
- Neuroimaging
- Neurology
- Pathophysiology of Multiple Sclerosis
Background:
- Multiple sclerosis (MS) involves both white matter (WM) pathology and grey matter (GM) atrophy.
- The relationship between these processes and their impact on clinical progression in MS remains unclear.
Purpose of the Study:
- To investigate the temporal and spatial relationship between GM atrophy and damage in connected WM in relapsing-remitting MS (RRMS).
- To examine how these relationships influence clinical progression in RRMS patients.
Main Methods:
- Longitudinal MRI and clinical assessments (EDSS, MSFC) over 1 year in 31 RRMS patients and 13 healthy controls (HC).
- Segmentation of deep and cortical GM structures; probabilistic tractography to identify connected WM.
- WM integrity assessed using fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), and myelin water fraction (MWF).
- Linear mixed models (LMMs) analyzed GM/WM differences and associations between GM and WM changes over time, categorizing RRMS patients as MSFC decliners or non-decliners.
Main Results:
- Fifteen RRMS subjects were classified as MSFC decliners, exhibiting higher atrophy rates and greater WM integrity loss compared to non-decliners.
- Lower baseline WM integrity was associated with increased cortical GM (cGM) atrophy over time in RRMS patients, but not in HC.
- This association was significant in MSFC decliners, particularly when using an extended WM integrity score (FA, MD, NDI, MWF). Baseline GM measures did not predict subsequent WM integrity changes.
Conclusions:
- Reduced baseline WM integrity is linked to accelerated cortical GM atrophy in RRMS patients experiencing clinical progression over a one-year period.
- Grey matter changes do not appear to drive white matter integrity alterations over time in this cohort.
- Evidence suggests that white matter damage is a primary driver of grey matter atrophy in the progression of MS.
