White matter T1 relaxation time histograms and cerebral atrophy in multiple sclerosis
Introduction
Conventional T2-weighted magnetic resonance imaging (MRI) provides a sensitive measure of lesion load in multiple sclerosis (MS), but lacks histopathological specificity for the presumed substrates of irreversible disability, severe demyelination and axonal loss [1]. T1-hypointense lesions have been shown to reflect axonal loss and demyelination [2], [3], and to correlate with disability [4]. However, the qualitative nature of T1-weighted images makes the assessment of T1-hypointense lesion load both subjective and sequence dependent [5]. By contrast, T1 relaxation time (T1) provides a quantitative MRI parameter that can be used to assess tissue damage in discrete lesions [6], [7], [8] and in the normal-appearing white matter (NAWM) [9], [10].
T1 increases as tissue water becomes more mobile and less organized [11]. Experimental models and clinical studies have demonstrated that prolongation of T1 reflects extracellular space expansion [12], [13]. Ultrastructural analyses of chronic MS plaques and the surrounding tissue have shown variable expansion of the extracellular space relating to differing degrees of axonal loss [6], [14]. The wide range of T1 values observed in MS plaques and in NAWM may therefore be an indication of this pathological heterogeneity [6], [7], [8], [10].
Previous quantitative studies of T1 in MS have been performed with varying accuracy and precision using different imaging techniques, the majority in a single-slice mode and requiring protracted acquisition times [15]. T1 analyses have therefore been limited to sampling small regions of NAWM or discrete lesions. We have acquired T1 values for the whole brain using a novel, rapid, multi-slice inversion recovery sequence and segmented the white matter to generate total white matter T1 histograms. Our objectives were: (i) to compare total white matter T1 values in MS patients and controls using histogram analysis, (ii) to understand the significance of the histogram parameters in relation to NAWM T1, and (iii) determine the relationships between total white matter T1 and more established MRI parameters, including cerebral atrophy, T2 lesion load and clinical parameters.
Section snippets
Subjects
Twenty-six patients with clinically definite relapsing–remitting MS were recruited. All subjects had at least two documented relapses as defined by Poser et al. [16] in the 2 years prior to study entry, and had been exacerbation free for at least 1 month. No patient had received previous treatment with immunosuppressive or immunomodulatory drugs, or corticosteroids within the last 1 month. None of the subjects had any significant medical condition, past or present, which could confound the
Total white matter T1 histograms
All histogram-derived measures in the MS patients were significantly different from controls (Table 1, Fig. 2), with the median and peak position shifted to higher T1 values. The patients' histograms showed marked variability in both peak height and ‘spread’ (represented by the SD).
The peak position of the total white matter T1 histograms showed a linear correlation with the NAWM T1 histograms' peak position (r=0.996, p<0.0001) (Fig. 3).
T2 lesion load
The median T2 lesion volume in patients was 3.4 cm3
Discussion
Our study has demonstrated that total white matter T1 values in MS patients are significantly different from controls, and correlate with measures of brain atrophy and the visible lesion burden. We have also shown that the peak position (mode) of total white matter T1 histograms predominantly reflects pathology in the NAWM.
In MS patients, the median and peak of the histograms were significantly shifted to higher T1, the peak height was lower and the spread of values greater than in controls.
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