AJNR. American journal of neuroradiology · 2026
T1W/T2W Ratio to Assess Brain Microstructural Damage in Multiple Sclerosis: A Multicenter Study.
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Storelli Loredana, Preziosa Paolo, Tedone Nicolò, Gallo Antonio, Altieri Manuela, Pantano Patrizia, Piervincenzi Claudia, De Stefano Nicola, Cortese Rosa, Rocca Maria A, Filippi Massimo, INNI Network
Аннотация
BACKGROUND AND PURPOSE: The T1-weighted/T2-weighted ratio, a proposed surrogate measure of myelin integrity/damage, has debated specificity in multiple sclerosis. We investigated compartment-specific T1-weighted/T2-weighted alterations across multiple sclerosis phenotypes and age at onset, and their associations with disability and cognition.
MATERIALS AND METHODS: In this multicenter study, 918 multiple sclerosis and 272 healthy controls from an Italian neuroimaging initiative underwent standardized 3D T1- and T2-weighted MRI (3D or 2D dual-echo sequences depending on site), together with clinical and cognitive assessments. T1-weighted/T2-weighted ratios were computed using a standardized pipeline and multiple sclerosis z-scores were derived across brain regions using linear mixed-effects models fitted on healthy controls. Associations with disease duration, disability, and Symbol Digit Modalities Test were analyzed.
RESULTS: Compared with healthy controls, patients showed lower T1-weighted/T2-weighted ratios in lesions, normal-appearing white matter, and cortical grey matter (all FDR-adjusted p-values<.001), and higher ratios in the thalamus and deep grey matter (all FDR-adjusted p-values≤.01). Differences were more pronounced in secondary progressive and relapsing-remitting multiple sclerosis (all FDR-adjusted p-values<.001) than clinically isolated syndrome and primary progressive. Pediatric-onset patients showed lower normal-appearing white matter and cortical grey matter ratios (all FDR-adjusted p-values≤.02) than adult- and late-onset patients, which conversely showed higher deep grey matter ratios compared to the other groups (all FDR-adjusted p-values≤.01). Higher disability was associated to lower lesion, normal-appearing white matter, cortical grey matter ratios (all p≤.05) and higher thalamic ratios (p=.006). Longer disease duration correlated with lower lesion (p=.02), normal-appearing white matter ratios (p=.007) and higher deep grey matter ratios (p=.002). Worse cognitive performance was associated with lower cortical (p=.01), and higher thalamic and deep grey matter ratios (all p≤.004).
CONCLUSIONS: T1-weighted/T2-weighted mapping can provide complementary, compartment-specific information on tissue integrity and clinical outcomes across the MS spectrum.
MATERIALS AND METHODS: In this multicenter study, 918 multiple sclerosis and 272 healthy controls from an Italian neuroimaging initiative underwent standardized 3D T1- and T2-weighted MRI (3D or 2D dual-echo sequences depending on site), together with clinical and cognitive assessments. T1-weighted/T2-weighted ratios were computed using a standardized pipeline and multiple sclerosis z-scores were derived across brain regions using linear mixed-effects models fitted on healthy controls. Associations with disease duration, disability, and Symbol Digit Modalities Test were analyzed.
RESULTS: Compared with healthy controls, patients showed lower T1-weighted/T2-weighted ratios in lesions, normal-appearing white matter, and cortical grey matter (all FDR-adjusted p-values<.001), and higher ratios in the thalamus and deep grey matter (all FDR-adjusted p-values≤.01). Differences were more pronounced in secondary progressive and relapsing-remitting multiple sclerosis (all FDR-adjusted p-values<.001) than clinically isolated syndrome and primary progressive. Pediatric-onset patients showed lower normal-appearing white matter and cortical grey matter ratios (all FDR-adjusted p-values≤.02) than adult- and late-onset patients, which conversely showed higher deep grey matter ratios compared to the other groups (all FDR-adjusted p-values≤.01). Higher disability was associated to lower lesion, normal-appearing white matter, cortical grey matter ratios (all p≤.05) and higher thalamic ratios (p=.006). Longer disease duration correlated with lower lesion (p=.02), normal-appearing white matter ratios (p=.007) and higher deep grey matter ratios (p=.002). Worse cognitive performance was associated with lower cortical (p=.01), and higher thalamic and deep grey matter ratios (all p≤.004).
CONCLUSIONS: T1-weighted/T2-weighted mapping can provide complementary, compartment-specific information on tissue integrity and clinical outcomes across the MS spectrum.