Mapping white matter damage distribution in neuromyelitis optica spectrum disorders with a multimodal MRI approach

Abstract

Background: The pathogenetic mechanisms sustaining neuroinflammatory disorders may originate from the cerebrospinal fluid. Objective: To evaluate white matter damage with diffusion tensor imaging and T1/T2-weighted ratio at progressive distances from the ventricular system in neuromyelitis optica spectrum disorders and multiple sclerosis. Methods: Fractional anisotropy, mean, axial, and radial diffusivity and T1/T2-weighted ratio maps were obtained from patients with seropositive neuromyelitis optica spectrum disorders, multiple sclerosis, and healthy controls ( n = 20 each group). White matter damage was assessed as function of ventricular distance within progressive concentric bands. Results: Compared to healthy controls, neuromyelitis optica spectrum disorders patients had similar fractional anisotropy, radial and axial diffusivity, increased mean diffusivity ( p = 0.009–0.013) and reduced T1/T2-weighted ratio ( p = 0.024–0.037) in all bands. In multiple sclerosis, gradient of percentage lesion volume and intra-lesional mean and axial diffusivity were higher in periventricular bands. Compared to healthy controls, multiple sclerosis patients had reduced fractional anisotropy ( p = 0.001–0.043) in periventricular bands, increased mean ( p < 0.001), radial ( p < 0.001–0.004), and axial diffusivity ( p = 0.002–0.008) and preserved T1/T2-weighted ratio in all bands. Conclusion: White matter damage is higher at periventricular level in multiple sclerosis and diffuse in neuromyelitis optica spectrum disorders. Fractional anisotropy preservation, associated with increased mean diffusivity and reduced T1/T2-weighted ratio may reflect astrocyte damage.

Longitudinal analysis of T1w/T2w ratio in patients with multiple sclerosis from first clinical presentation

“…We believe that these effects are minimized in the current cohort for the following reasons: (1) we used CAT12 for segmentation, which corrects for partial volume effects; 34 (2) we reran the analysis using eroded tissue masks and the linear mixed model results remained stable; and (3) we show that, in this cohort, the scaling factor is not influenced by disease factors and that the T1w and T2w gray matter intensities are not sensitive to pathology, confirming previous findings. 14 In addition, the findings that sT1w/T2w are correlated with lesion volume is consistent with recent publications using the conventional T1w/T2w and T1w/T2w corrected using cerebrospinal fluid, 12 , 35 further supporting the similarity of these methods. Nonetheless future studies investigating sT1w/T2w over time in healthy controls as well as studies specifically designed to further investigate the impact of gray matter pathology on the validity of the calibration are necessary to help interpret the results presented here.…”

“…sT1w/T2w is a relatively novel measure of NAWM integrity damage in MS, standardizing the conventional T1w/T2w using the combined image technique, originally developed for contrast enhancement. 13 The conventional T1w/T2w has been shown to be sensitive to MS pathology, both in the cortex 32 and NAWM, 11 , 12 , 15 and is related to reduced EDSS and cognitive impairment. 11 , 32 The main benefit of the conventional T1w/T2w compared to other markers of NAWM damage is that it uses routine clinical images and has relatively simple post-processing steps.…”

“… 10 Originally developed as a marker of myelination, the T1/T2-weighted ratio (T1w/T2w) has been shown to be sensitive to NAWM pathology in RRMS from 2 years disease duration. 11 , 12 T1w/T2w is particularly promising as it is based on scans acquired as part of the clinical routine and the necessary post-processing methods are fast and easily implemented. Recently, standardizing T1w/T2w (sT1w/T2w) using the combined image method, originally developed for contrast enhancement, 13 has been shown to increase sensitivity to NAWM damage in MS compared to the conventional T1w/T2w 14 and T1w/T2w has been shown to correlate with other quantitative measures of NAWM damage in MS. 15 However, longitudinal investigations of NAWM integrity in patients with MS using T1w/T2w, which are critical to evaluate the clinical utility of this measure, are lacking.…”

A window into the future? MRI for evaluation of neuromyelitis optica spectrum disorder throughout the disease course

“… 135 – 137 Diffusion tensor imaging is another advanced MRI technique that has been used to evaluate microstructural changes in the normal-appearing white matter in NMOSD and has demonstrated that the white matter injury in NMOSD is diffuse, compared with MS in which the white matter alterations are predominantly periventricular. 16 , 138 In addition, microstructural white matter changes have been identified in the afferent visual pathway in NMOSD patients with a history of optic neuritis, as well as in NMOSD patients with a history of LETM without optic neuritis. 16 , 139 Diffusion tensor imaging has also been used to explore the differences in microstructural parenchymal damage between NMOSD and MOGAD and has shown that, compared with healthy controls, it is more prominent in MOGAD patients than in NMOSD patients, while brain volume loss is more severe in NMOSD patients.…”

Demyelination and remyelination detected in an alternative cuprizone mouse model of multiple sclerosis with 7.0 T multiparameter magnetic resonance imaging

“…An example of multiparameter MRI is conventional T 2 -weighted imaging (T 2 WI), which is mainly affected by tissue water composition and can sensitivity detect inflammation and edema in tissues 4 , 6 . Moreover, in regions with dense myelin, such as the corpus callosum (CC), the signal intensity of T 2 WI is inversely proportional to the myelin content 7 . Susceptibility-weighted imaging (SWI) mainly reflects the magnetic susceptibility of tissues in a magnetic field 8 , 9 .…”