Quantitative magnetic resonance imaging biomarkers for cortical pathology in multiple sclerosis at 7 T

Abstract

Substantial cortical gray matter tissue damage, which correlates with clinical disease severity, has been revealed in multiple sclerosis (MS) using advanced magnetic resonance imaging (MRI) methods at 3 T and the use of ultra-high field, as well as in histopathology studies. While clinical assessment mainly focuses on lesions using $T_1$ - and $T_2$ -weighted MRI, quantitative MRI (qMRI) methods are capable of uncovering subtle microstructural changes. The aim of this ultra-high field study is to extract possible future MR biomarkers for the quantitative evaluation of regional cortical pathology. Because of their sensitivity to iron, myelin, and in part specifically to cortical demyelination, $T_1$ , $T_2$ , $R_2^{*}$ , and susceptibility mapping were performed including two novel susceptibility markers; in addition, cortical thickness as well as the volumes of 34 cortical regions were computed. Data were acquired in 20 patients and 16 age- and sex-matched healthy controls. In 18 cortical regions, large to very large effect sizes (Cohen's d ≥ 1) and statistically significant differences in qMRI values between patients and controls were revealed compared with only four regions when using more standard MR measures, namely, volume and cortical thickness. Moreover, a decrease in all susceptibility contrasts ( $\chi$ , ${\chi }^{+}$ , ${\chi }^{-})$ and $R_2^{*}$ values indicates that the role of cortical demyelination might outweigh inflammatory processes in the form of iron accumulation in cortical MS pathology, and might also indicate iron loss. A significant association between susceptibility contrasts as well as $R_2^{*}$ of the caudal middle frontal gyrus and disease duration was found (adjusted R² : 0.602, p = 0.0011). Quantitative MRI parameters might be more sensitive towards regional cortical pathology compared with the use of conventional markers only and therefore may play a role in early detection of tissue damage in MS in the future.

Keywords: cortical pathology; multiple sclerosis; quantitative MRI; quantitative susceptibility mapping; relaxometry; ultra-high field.