The heterogeneity of tissue destruction between iron rim lesions and non-iron rim lesions in multiple sclerosis: A diffusion MRI study

Objectives This study aimed to explore the microstructural heterogeneity of different white matter (WM) tissues in relapsing-remitting multiple sclerosis (RRMS) patients by diffusion magnetic resonance imaging (dMRI) and its correlation with disability and cognitive status. Materials and Methods A total of 337 iron rim lesions (IRLs), 337 perilesional white matters of IRLs (IRLs-PLWMs), 330 non-iron rim lesions (non-IRLs), 330 non-IRLs-PLWMs, 42 normal-appearing white matters (NAWMs) in 42 RRMS patients, and 30 white matters in healthy controls (WMs in HCs) were enrolled in the lesion-wise analysis. Diffusion kurtosis imaging (DKI) parameters including kurtosis fractional anisotropy (KFA) and mean kurtosis (MK), and diffusion tensor imaging (DTI) parameters including fractional anisotropy (FA) and mean diffusivity (MD) were measured in the six types of tissues. Subgroup analysis was performed between non-IRLs with QSM hyperintense (non-IRLs-H) and non-IRLs with QSM isointense or hypointense (non-IRLs-I), as well as between non-IRLs-H-PLWMs and non-IRLs-I-PLWMs. Thirty-four out of forty-two patients were enrolled in patient-wise analysis. The relationships between these diffusion metrics of patients and their Kurtzke Expanded Disability Status Scale (EDSS) score and Symbol Digit Modalities Test (SDMT) score were analyzed separately by partial correlation analysis with age and disease duration (DD) as covariates. Results The KFA, FA, MK, and MD values were significantly different among the six types of tissues. The lowest KFA, FA, and MK values and the highest MD values were revealed in IRLs. There were significant differences in all the enrolled diffusion metrics between IRLs and non-IRLs, as well as between IRLs-PLWMs and non-IRLs-PLWMs (p < 0.05). There were no significant differences between NAWMs and WMs in HCs (p = 1.000 for all enrolled diffusion metrics). For all the enrolled diffusion metrics, no significant differences were found in the subgroup analysis. The FA, MK, and MD values of total lesions (including IRLs and non-IRLs) (r = -0.420, p = 0.017; r = -0.472, p = 0.006; r = -0.475, p = 0.006) and the MK values of IRLs (r = -0.438, p = 0.012) were correlated with the EDSS scores. There was no significant correlation between the diffusion parameter values and the SDMT scores. Conclusion Our findings demonstrate that IRLs are more destructive than non-IRLs. Similarly, IRLs-PLWMs are more destructive than non-IRLs-PLWMs. Additionally, diffusion parameter values of MS lesions can reflect the disability degree. These findings contribute to a better understanding of the different evolution of MS lesions and the relationship between the disability level of patients and focal lesion damage degree.