Contribution of cortical lesion volume detected with 7T MRI to cortical thinning, thalamic and callosal atrophy in multiple sclerosis
Tobias Granberg1,2,3,4, Russell Ouellette1,2, Constantina Andrada Treaba1,2, Celine Louapre1,2, Sindhuja T Govindarajan1,2, Costanza Giannì1,2, Elena Herranz1,2, Revere P Kinkel5, and Caterina Mainero1,2

1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States, 2Harvard Medical School, Boston, MA, United States, 3Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden, 4Department of Radiology, Karolinska University Hospital, Stockholm, Sweden, 5Department of Neurosciences, University of California, San Diego, CA, United States


Grey matter pathology contributes to disability in multiple sclerosis (MS), but in vivo sensitivity for cortical lesions is low with conventional MRI. The role of cortical pathology in the dynamic atrophy processes in MS is, therefore, uncertain. Using 7T MRI and longitudinal 3T imaging (mean follow-up 1.9 years), we showed, in a small MS cohort, that cortical lesion volumes at follow-up correlated with cortical thinning in areas known to be predilection sites for cortical demyelination in MS, while thalamic atrophy was more strongly associated with white matter lesions. No effect of cortical lesions was found on corpus callosal atrophy.


Cortical pathology is an early event in the course of multiple sclerosis (MS) and an important contributor to physical disability and cognitive impairment.1,2 The sensitivity for cortical MS lesions in vivo, although limited at conventional magnetic resonance imaging (MRI), is improved at ultra-high field strengths.3,4 Cortical lesions are associated with lower grey matter volumes, and cortical lesions detected at 3T are an independent predictor of whole-brain grey matter atrophy and accumulation of physical disability.2 It remains unknown, however, if cortical lesions are longitudinally correlated with cortical thinning and atrophy of strategic landmarks in MS, the thalami and corpus callosum that are known to be markedly influenced by MS pathology from the very early disease stages, and well-correlated with disability.5-7

We present initial findings, in a small and heterogeneous MS cohort, aimed at assessing whether higher rates of atrophy within and outside the cortex (corpus callosum, thalami) were associated with cross-sectional 7T estimates of cortical MS lesion volumes at follow-up. We further investigated the role of white matter (WM) lesions on these structural changes.


Participants: This longitudinal cohort study consisted of 16 MS patients (10 females, 6 males; median Expanded Disability Status Scale score 2.5; average age 41.8±10 years; mean follow-up time 1.9±0.7 years) and 7 healthy matched controls (4 females, 3 males; average age 38.1±9.0 years; mean follow-up time 1.8±0.6 years).

Image acquisition: Longitudinal T1-weighted 3D multi-echo magnetization prepared rapid acquisition gradient echo sequences (0.9x0.9x0.9 mm3, flip angle 7°, TE=1.7/3.6/5.4/7.3, TI=1200, TR=2530 ms) were acquired at 3T (Siemens Tim Trio scanners, 32-channel head coil). A 7T scanner (32-channel head coil) was used to obtain T2*-weighted spoiled gradient-echo images (0.33x0.33x1.0 mm3 resolution) at follow-up.

Image analysis: Cortical lesions were manually segmented on T2*-weighted images using Slicer 4.8 Examples of cortical lesions are shown in Figure 1. Cortical thinning (mean thickness averaged across hemispheres) and corpus callosum atrophy were assessed using the longitudinal pipeline of FreeSurfer Initial anatomical reconstructions with FreeSurfer were obtained in 12 patients for cortical thickness measurements, and in 16 patients for corpus callosum volume estimation. Thalamic and intracranial volumes (ICV) were segmented using volBrain in all participants.10,11 All volumetric measurements were normalized to ICV. Segmentation examples are seen in Figure 2. Time-dependent changes were calculated as the symmetric annual percent change: $$$\frac{(Measurement 1-Measurement 2)}{Average (Measurement1 and 2)}\div{FollowUpTime}$$$

Statistical analyses: SPSS 22.0 was used for group comparisons (independent samples t-test) and partial correlation analyses. An α-level of 0.05 (two-tailed, equal variances not assumed) was considered statistically significant.


Cross-sectionally, there were no significant differences between the groups, although MS patients tended to have thinner cortices and lower tissue fractions of the corpus callosum and thalami than controls. Longitudinally, however, corpus callosal atrophy was greater in patients than in controls and the trend for thalamic atrophy became clearer. Cortical thinning remained statistically insignificant (Table 1).

As detailed in Table 2, thalamic atrophy was associated with WM lesions while there was a trend with cortical lesions. Only cortical lesions were associated with cortical thinning. The association of cortical lesions with cortical thinning remained robust after correcting for the WM volume. The thinning related with cortical lesions mainly occurred in the primary motor and sensory areas and the temporal lobes, illustrated in Figure 3.


We report the exploratory association of cortical lesions detected at ultra-high field strength with longitudinal changes in cortical thickness and thalamic atrophy. Cortical thinning related with cortical lesions, independent of WM pathology, were mainly found in primary motor and sensory cortices, areas that have been shown to be affected by demyelination.12 In contrast, thalamic atrophy was more dependent on WM than on cortical lesions, suggesting that the neurodegenerative processes occurring in cortex and deep GM may not share the same pathogenetic mechanisms. Neither WM nor cortical lesions proved to be significantly correlated with callosal atrophy, possibly due to a type II error related to the limited sample size.


Cortical MS lesions detected at ultra-high-field MRI are associated with higher rates of cortical thinning but not with corpus callosal atrophy. Thalamic atrophy was mainly associated with WM lesions. Future studies will include larger sample size and will also investigate the impact of cortical lesions on clinical changes over time.


This study was supported by the National MS Society (NMSS 4281 RG-A), Stockholm City Council and Karolinska Institutet (ALF-20120213).


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Figure 1. Cortical lesions (arrows) and moderate atrophy in a 33-year-old male (A) and severe in a 59-year-old female MS patient (B), both with secondary progressive MS, EDSS 4.5 and 7 respectively.

Figure 2. Thalamic and corpus callosum segmentations in a 23-year-old female MS patient with an EDSS score of 4, cortical lesion volume of 2.2 mL, a thalamic fraction of 0.61% and a corpus callosal fraction of 0.12%.

Table 1. Comparison of cross-sectional and longitudinal imaging metrics between MS patients and controls.

Table 2. Correlations of the WM and cortical lesion volumes with longitudinal brain tissue measurements.

Figure 3. Areas with significant associations between the cortical lesion volume and annual cortical thinning in MS patients. The results are corrected for age, sex with a threshold at 0.05 using a Monte Carlo null-z simulation. The clusters are mainly found around the primary motor and sensory areas and the temporal lobes.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)