3T sodium MR imaging in Alzheimer's disease shows stage-dependent sodium increase influenced by age and local brain volume

Introduction: Application of MRI in clinical routine mainly addresses structural alterations. However, pathological changes at a cellular level are expected to precede the occurrence of brain atrophy clusters and of clinical symptoms. In this context, ²³Na-MRI examines sodium changes in the brain as a potential metabolic parameter. Recently, we have shown that ²³Na-MRI at ultra-high-field (7 T) was able to detect increased tissue sodium concentration (TSC) in Alzheimer's disease (AD). In this work, we aimed at assessing AD-pathology with ²³Na-MRI in a larger cohort and on a clinical 3T MR scanner.

Methods: We used a multimodal MRI protocol on 52 prodromal to mild AD patients and 34 cognitively healthy control subjects on a clinical 3T MR scanner. We examined the TSC, brain volume, and cortical thickness in association with clinical parameters. We further compared TSC with intra-individual normalized TSC for the reduction of inter-individual TSC variability resulting from physiological as well as experimental conditions. Normalized TSC maps were created by normalizing each voxel to the mean TSC inside the brain stem.

Results: We found increased normalized TSC in the AD cohort compared to elderly control subjects both on global as well as on a region-of-interest-based level. We further confirmed a significant association of local brain volume as well as age with TSC. TSC increase in the left temporal lobe was further associated with the cognitive state, evaluated via the Montreal cognitive assessment (MoCA) screening test. An increase of normalized TSC depending on disease stage reflected by the Clinical Dementia Rating (CDR) was found in our AD patients in temporal lobe regions. In comparison to classical brain volume and cortical thickness assessments, normalized TSC had a higher discriminative power between controls and prodromal AD patients in several regions of the temporal lobe.

Discussion: We confirm the feasibility of ²³Na-MRI at 3T and report an increase of TSC in AD in several regions of the brain, particularly in brain regions of the temporal lobe. Furthermore, to reduce inter-subject variability caused by physiological factors such as circadian rhythms and experimental conditions, we introduced normalized TSC maps. This showed a higher discriminative potential between different clinical groups in comparison to the classical TSC analysis. In conclusion, ²³Na-MRI represents a potential translational imaging marker applicable e.g.for diagnostics and the assessment of intervention outcomes in AD even under clinically available field strengths such as 3T. Implication of ²³Na-MRI in association with other metabolic imaging marker needs to be further elucidated.