Multimodal quantitative magnetic resonance imaging of thalamic development and aging across the human lifespan: implications to neurodegeneration in multiple sclerosis

Abstract

The human brain thalami play essential roles in integrating cognitive, sensory, and motor functions. In multiple sclerosis (MS), quantitative magnetic resonance imaging (qMRI) measurements of the thalami provide important biomarkers of disease progression, but late development and aging confound the interpretation of data collected from patients over a wide age range. Thalamic tissue volume loss due to natural aging and its interplay with lesion-driven pathology has not been investigated previously. In this work, we used standardized thalamic volumetry combined with diffusion tensor imaging, T2 relaxometry, and lesion mapping on large cohorts of controls (N = 255, age range = 6.2-69.1 years) and MS patients (N = 109, age range = 20.8-68.5 years) to demonstrate early age- and lesion-independent thalamic neurodegeneration.

Figure 1.

Spatial distribution of lesions or lesion probability map viewed in standard Montreal Neurological Institute (MNI) space on CIS (A), SPMS (B), and RRMS (C, D). Note the areas of high lesion frequency (posterior corona radiata, optic radiations) and regions with low lesions (e.g., thalamus proper).

Figure 2.

Representative illustration and analysis of age dependence of thalamic qMRI metrics in all controls and patients using scatter plots and linear regression. A–D, Volume percentage of the thalamus proper (A) and corresponding T2 relaxation time values (B), fractional anisotropy (× 1000.0) (C), and mean or average diffusivity (D_av) (D). Note the rise in normalized thalamic volume in healthy children and consequent rapid decrease in both healthy adults and patients. Note the curvilinear age-expected thalamic volumes in healthy controls. E, F, The variation of thalamic volume percentage with whole-brain lesion volume-to-ICV percentage (LVp) (E) and the scatter and regression of NTV with EDSS (F).