Longitudinal evaluation of demyelinated lesions in a multiple sclerosis model using ultrashort echo time magnetization transfer (UTE-MT) imaging

Abstract

Alterations in myelin integrity are involved in many neurological disorders and demyelinating diseases, such as multiple sclerosis (MS). Although magnetic resonance imaging (MRI) is the gold standard method to diagnose and monitor MS patients, clinically available MRI protocols show limited specificity for myelin detection, notably in cerebral grey matter areas. Ultrashort echo time (UTE) MRI has shown great promise for direct imaging of lipids and myelin sheaths, and thus holds potential to improve lesion detection.In this study, we used a sequence combining magnetization transfer (MT) with UTE (“UTE-MT”, TE ​= ​76 ​μs) and with short TE (“STE-MT”, TE ​= ​3000 ​μs) to evaluate spatial and temporal changes in brain myelin content in the cuprizone mouse model for MS on a clinical 7 ​T scanner. During demyelination, UTE-MT ratio (UTE-MTR) and STE-MT ratio (STE-MTR) values were significantly decreased in most white matter and grey matter regions. However, only UTE-MTR detected cortical changes. After remyelination in subcortical and cortical areas, UTE-MTR values remained lower than baseline values, indicating that UTE-MT, but not STE-MT, imaging detected long-lasting changes following a demyelinating event.Next, we evaluated the potential correlations between imaging values and underlying histopathological markers. The strongest correlation was observed between UTE-MTR and percent coverage of myelin basic protein (MBP) immunostaining (r2 ​= ​0.71). A significant, although lower, correlation was observed between STE-MTR and MBP (r2 ​= ​0.48), and no correlation was found between UTE-MTR or STE-MTR and gliosis immunostaining. Interestingly, correlations varied across brain substructures.Altogether, our results demonstrate that UTE-MTR values significantly correlate with myelin content as measured by histopathology, not only in white matter, but also in subcortical and cortical grey matter regions in the cuprizone mouse model for MS. Readily implemented on a clinical 7 ​T system, this approach thus holds great potential for detecting demyelinating/remyelinating events in both white and grey matter areas in humans. When applied to patients with neurological disorders, including MS patient populations, UTE-MT methods may improve the non-invasive longitudinal monitoring of brain lesions, not only during disease progression but also in response to next generation remyelinating therapies.