​Background
Lithium (Li) is a first line treatment for bipolar disorders (BD). In order to study its cerebral distribution and association with plasmatic concentrations, we used ⁷Li MRI at 7T in euthymic patients with BD treated with Li carbonate for at least 2 years.
Methods
3D ⁷Li MRI (n=21) were acquired using an ultra-short echo-time sequence using a non-Cartesian k-space sampling scheme. Lithium concentrations ([Li]) were estimated using a phantom replacement approach accounting for differential T₁ and T₂ relaxation effects. In addition to the determination of mean regional [Li] from seven broad anatomical areas, a voxel and a parcellation-based group analysis were conducted for the first time for ⁷Li MRI.
Results
Using unprecedented spatial sensitivity and specificity, we were able to confirm the heterogeneity of the brain Li distribution and its inter-individual variability as well as the strong correlation between plasma and average brain [Li] ([Li]_B ≈ 0.40 * [Li]_P, R=0.74). Remarkably, our statistical analysis led to the identification of a well-defined and significant cluster corresponding closely to the left hippocampus for which high Li content was displayed consistently across our cohort.
Conclusions
This observation could be of interest considering (i) the major role of the hippocampus in emotion processing and regulation, (ii) the consistent atrophy of the hippocampus in untreated patients with BD and (iii) the normalization effect of Li on grey matter volumes. This study paves the way for the elucidation of the relationship between Li cerebral distribution and its therapeutic response, notably in newly diagnosed BD patients.
Keywords
Lithium-7 (⁷Li) ; Bipolar disorder (BD) ; magnetic resonance imaging (MRI) ; Brain ; Hippocampus ; High magnetic field