Assessment of cortical damage in early multiple sclerosis with quantitative T₂ relaxometry

Abstract

T2 relaxation time is a quantitative MRI in vivo surrogate of cerebral tissue damage in multiple sclerosis (MS) patients. Cortical T2 prolongation is a known feature in later disease stages, but has not been demonstrated in the cortical normal appearing gray matter (NAGM) in early MS. This study centers on the quantitative evaluation of the tissue parameter T2 in cortical NAGM in a collective of early MS and clinically isolated syndrome (CIS) patients, hypothesizing that T2 prolongation is already present at early disease stages and variable over space, in line with global and focal inflammatory processes in MS. Additionally, magnetization transfer ratio (MTR) mapping was performed for further characterization of the expected cortical T2 alteration. Quantitative T2 and MTR maps were acquired from 12 patients with CIS and early MS, and 12 matched healthy controls. The lesion-free part of the cortical volume was identified, and the mean T2 and MTR values and their standard deviations within the cortical volume were determined. For evaluation of spatial specificity, cortical lobar subregions were tested separately for differences of mean T2 and T2 standard deviation. We detected significantly prolonged T2 in cortical NAGM in patients. T2 prolongation was found across the whole cerebral cortex and in all individual lobar subregions. Significantly higher standard deviations across the respective region of interest were found for the whole cerebral cortex and all subregions, suggesting the occurrence of spatially inhomogeneous cortical damage in all regions studied. A trend was observed for MTR reduction and increased MTR variability across the whole cortex in the MS group, suggesting demyelination. In conclusion, our results suggest that cortical damage in early MS is evidenced by spatially inhomogeneous T2 prolongation which goes beyond demyelination. Iron deposition, which is known to decrease T2, seems less prominent.

Longitudinal quantitative MRI assessment of cortical damage in multiple sclerosis: A pilot study

“…These patients were scored on the Expanded Disability Status Scale (EDSS) before the first scan . The patient pool comprised participants who had previously been included in cross‐sectional analyses, and we also used data obtained from a previous study into white matter …”

“…These patients were scored on the Expanded Disability Status Scale (EDSS) before the first scan. 14 The patient pool comprised participants who had previously been included in cross-sectional analyses, [5][6][7]15 and we also used data obtained from a previous study into white matter. 4 Written informed consent was given, and this study was approved by the Ethics Committee of the State Medical Association of Rhineland-Palatine.…”

“…A separate study confirmed a relationship between cortical T 1 and the degree of disability in a relapsing‐remitting MS (RRMS) patient group, covering a range of disability severity and disease duration . Cortical demyelination at early MS stages can also be assessed with T 2 relaxometry, providing an alternative to the technically challenging T 1 and PD mapping …”

“…6 Cortical demyelination at early MS stages can also be assessed with T 2 relaxometry, providing an alternative to the technically challenging T 1 and PD mapping. 7 Several previous approaches using qMRI techniques to assess longitudinal changes in tissue microarchitecture were undertaken, but yielded conflicting results:…”

Iron deposition quantification: Applications in the brain and liver

“…These authors found that T 2 hypointensities seen in GM could be linked to physical disability, cognitive dysfunction, and brain atrophy and that they may be caused by increased brain iron. A more recent study revealed that even in CIS, using T 2 relaxometry, there was an increase in T 2 in cortical GM and that this was nonuniformly distributed leading to an increase in standard deviation of the signal as well …”