Brain tissue integrity in neuromyelitis optica spectrum disorder through T1-w/T2-w ratio, MTR and DTI

The presence of diffuse brain damage in normal-appearing white matter (NAWM) and gray matter (NAGM) in neuromyelitis optica spectrum disorder (NMOSD) remains controversial. We aimed to address this controversy by applying a multiparametric MRI approach. Additionally, the association between MRI metrics and clinical variables was explored.

In this cross-sectional study, we prospectively evaluated aquaporin-4-IgG positive NMOSD patients and healthy controls (HC) matched for age and sex. The clinical variables of interest were collected for each participant. The mean values of T1-w/T2-w ratio, magnetization transfer ratio (MTR), fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were obtained in NAWM, NAGM, as well as in global and hypointense lesion masks. Global lesions refer to those typically associated with aquaporin-4-IgG positive NMOSD. Hypointense lesions were defined as areas of hypointense signal in both T1-w and fluid-attenuated inversion recovery (FLAIR) images.

In total, we included 105 participants (59 NMOSD patients and 46 HC). T1-w/T2-w ratio was lower in NAWM of NMOSD patients versus HC (1.83 ± 0.14 vs 1.89 ± 0.14; p = 0.029), while no significant differences were found in NAWM or NAGM across the other metrics: (p range: 0.079 to 0.973). Hypointense lesions showed lower T1-w/T2-w ratio, MTR, and FA, and higher diffusivity metrics as compared to global lesion masks (p < 0.001). T1-w/T2-w ratio in NAWM was inversely correlated with time to start immunosuppressive therapy (r =  - 0.278; p = 0.036) and with MD (r =  - 0.325; p = 0.014).

Microstructural integrity loss seems to be confined to focal tissue damage in NMOSD. Decreased T1-w/T2-w ratio in NAWM may reflect subclinical water accumulation due to astrocyte and blood-brain barrier dysfunction. Hypointense lesions have shown a severe degree of microstructural damage.