The presence of infratentorial lesions early in the disease has been shown to have prognostic value for future disability in multiple sclerosis (MS). Quantitative imaging metrics such as T1 relaxometry might contribute to understanding the relationship between supratentorial (ST), infratentorial (IT), and spinal cord (SC) pathology.
Our aim was to explore the association between ST, IT and SC pathology and microstructural tissue alterations assessed with T1 relaxometry in T2-hyperintense lesions as well as cerebral and cerebellar normal-appearing white matter (NAWM) in patients with recently diagnosed MS with- and without IT lesions.
Microstructural tissue alterations were assessed in 42 patients (mean age 33.6±8.0 years, median MS duration 0.2 years (0-2.3)) as deviations from normative T1 times, both obtained from the MP2RAGE sequence at 3T (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). The normative T1 values were voxel-wise modelled via a study-specific atlas based on spatially normalized data from 102 healthy individuals (21-59 years). Relationship between normalized IT volumes (mesencephalon, pons, medulla oblongata, cerebellum), SC volume, ST and IT lesion loads estimated by the Morphobox prototype, Scanview and LemanPV prototype, respectively and the deviations from normative T1 times expressed as z-score-derived metrics (volumes and means of voxels with z-scores above z-score 2 and below z-score 2) in lesions, cerebral and cerebellar NAWM were studied by partial correlations adjusted for age and brain lesion volume.
Patients with IT lesions (n=23, 33.0±8.5 years) had larger lesion load, higher volumes of voxels with positive z-scores (> 2), higher mean of z-scores above 2 in lesions, and larger thalami than patients without IT lesions (n=19, 34.3±7.7 years). The remaining volumes and z-scores derived metrics did not differ between groups. Cerebellar volume correlated negatively with volume of voxels with negative z-scores (< 2) in cerebellar NAWM (partial correlation coefficient r=-.437, p=.005) only in patients with IT lesions. In patients without IT lesions, SC and pons volumes correlated negatively with volume of voxels with positive z-scores corresponding to areas of supratentorial T2 lesions (SC: r=-.669, p=.003, pons: r=-0.606, p=0.01).
Microstructural alterations identified as T1 z-scores relate differently to IT and SC volumes in MS patients with and without IT lesions. In the presence of IT lesions, changes in cerebellar NAWM (T1 shortening relative to healthy controls) are associated with lower cerebellar volume. In the absence of IT lesions, the association of cerebellar NAWM and cerebellar volume is not present. In patients without IT lesions, microstructural alterations in ST lesions (T1 prolongation) that might indicate the extent of tissue damage in lesions, are associated with lower pontine and SC volumes regardless of the T2 lesion load.