Abstract Details

To define the histopathological substrate of the ratio of T1-weighted (T1w) and T2-weighted (T2w) sequences (i.e., T1w/T2w-ratio) in normal-appearing and demyelinated cortices of patients with multiple sclerosis (PwMS) by performing a combined post-mortem MRI/histopathology study.

Fifteen PwMS and ten age- and sex-matched non-neurological controls (nNC) underwent post-mortem in situ 3T MRI with 3D T1w and T2w sequences, followed by brain dissection. One hundred and five paraffin-embedded tissue blocks (n=49 from PwMS, n=56 from nNC) were collected. Tissue regions were matched to T1w/T2w-ratio maps to obtain regional cortical T1w/T2w-ratio. Using immunohistochemistry and silver staining, cortical density of myelin and neurites were evaluated. Correlates of T1w/T2w-ratio alterations with histological markers were assessed through linear mixed-effects models.

Twenty-six cortical lesions (85% subpial) were found in 24/49 (51%) cortical regions from PwMS. Compared to nNC’s cortex, PwMS’ normal-appearing and demyelinated cortices had a significantly lower T1w/T2w-ratio (p=0.045 and 0.001). In PwMS, T1w/T2w-ratio was significantly lower in demyelinated vs normal-appearing cortex (p=0.007). In PwMS, neurite density was significantly lower in both normal-appearing and demyelinated cortices vs nNC (p=0.041 and 0.001), and in demyelinated vs normal-appearing cortex (p=0.048). Demyelinated cortex showed also significant lower myelin density vs normal-appearing cortex in both nNC and PwMS (p<0.001). Cortical T1w/T2w-ratio was positively associated with neurite density (β=3.464×10^-2, p=0.004), whereas only a trend for myelin density was found (p=0.082).

T1w/T2w-ratio is sensitive to MS cortical damage. Although both demyelination and neurite loss occur in MS cortex, T1w/T2w-ratio seems more strongly associated to cortical neurite than myelin density. T1w/T2w-ratio could be useful to investigate cortical damage in MS.