Quantitative volumetric analysis of brain magnetic resonance imaging from patients with multiple sclerosis

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Abstract

We compared the volumes of the brain as a whole and of different cerebral structures from patients with multiple sclerosis (MS) and normal subjects. In the patients, we also correlated brain volumes with T2 and T1 lesion loads and disability. A magnetization-prepared rapid acquisition gradient echo (MP RAGE) sequence with subsequent reconstruction of axial 1-mm thick slices and a dual-echo sequence were obtained in 15 patients with relapsing-remitting or secondary progressive MS and 15 sex-, age-, height- and weight-matched normal subjects. The brains and the different cerebral structures studied (cerebral hemispheres, cerebellum and brainstem) were segmented manually by a single observer on the 1-mm MP RAGE scans. The hyperintense lesion volumes seen on dual-echo scans and the hypointense lesion volumes seen on the 1-mm MP RAGE scans were measured using a semi-automated segmentation technique based on local thresholding. Compared to the normal volunteers, patients had significantly lower cerebral (P=0.008), hemispheric (P=0.01) and brainstem (P=0.03) volumes. Cerebral atrophy was detected in seven (47%) MS patients. Patients with brainstem signs had significantly lower mean brainstem volume than the others (P=0.04). No significant correlations were found between the cerebral volumes and the EDSS scores, the hyperintense lesion volumes and the hypointense lesion volumes. We conclude that cerebral atrophy is a relatively frequent finding in MS, but its relationship with physical disability is modest.

Introduction

Change of lesion load on yearly conventional T2-weighted magnetic resonance (MR) scans of the brain is used to monitor long-term multiple sclerosis (MS) evolution, either natural or modified by treatment 5, 21. However, the correlation between changes of disability and T2-weighted lesion load is modest 5, 21. More recently, measures obtained from several other MR techniques 5, 21have been found to correlate better with clinical disability. In particular, there is increasing evidence that atrophy per se is a clinically relevant entity in MS. Several studies have shown strong correlations between physical disability and both spinal cord 6, 9, 18and cerebellar [4]atrophy and between measures of cerebral atrophy and cognitive impairment 13, 25. More recently, moderate correlations between changes of disability and changes of spinal cord cross-sectional area [9]and cerebral white matter volumes [17]have been found.

Previous studies evaluating cerebral atrophy in MS are, however, not free from criticism. First, the large inter-subject variations in normal brain size [3]were not usually taken into account 13, 25, 29. Secondly, arbitrary or inaccurate measures of cerebral atrophy were used by all researchers 13, 17, 25, 29. Cerebral area or volumes were always measured on 2D MR data sets with relatively thick slices and sometimes only a few slices were considered. In the present study, we readdressed the issue of cerebral atrophy in MS, by measuring the volumes of the brain as a whole and of different cerebral structures from patients with MS and sex-, age-, weight- and height-matched normal subjects using a magnetization prepared rapid acquisition gradient-echo (MP RAGE) sequence. This is a three-dimensional MR sequence which gives T1-weighted images with thin slices down to 1 mm [23]. The magnetization is prepared using a 180° inversion pulse to give T1 contrast, before two-dimensional phase encoding in a gradient-recalled echo sequence with low flip angle read-out pulses to give a three-dimensional image volume.

Section snippets

Patients

Patients with either relapsing-remitting or secondary progressive MS [19]were recruited from our MS population. To be included, patients must not have taken immunosuppressive or immunomodulating treatments (including steroids) for at least 6 months prior to the study. In addition, the last relapse must have subsided at least 3 months before the study. At the time MR imaging was performed, each patient was evaluated neurologically, and disability was assessed by a single observer using the

Clinical data

Fifteen patients (nine women and six men; eleven with relapsing-remitting MS and four with secondary progressive MS) and fifteen controls entered the study. The demographic and clinical characteristics of the controls and patients are presented in Table 1. By definition, the female/male ratio, the age, the height and weight of the two groups were similar.

MR measures

In Table 2 and Fig. 1, the volumes of the cerebrum, the left and right cerebral hemispheres, the cerebellum and the brainstem for controls and

Discussion

This study demonstrates that brain atrophy is a frequent finding in patients with MS and that mean volumes of the brain and different cerebral structures are significantly lower in the MS group, compared with matched controls. Despite such reductions, there was no clear relationship between reduction of cerebral volumes and disability.

Axonal loss and severe demyelination are likely to be the most important contributors to the development of atrophy in MS. Several previous studies 5, 21

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