Accumulation of Lithium in the Hippocampus of Patients With Bipolar Disorder: A Lithium-7 Magnetic Resonance Imaging Study at 7 Tesla

Abstract

Background: Lithium (Li) is a first-line treatment for bipolar disorder (BD). To study its cerebral distribution and association with plasma concentrations, we used ⁷Li magnetic resonance imaging at 7T in euthymic patients with BD treated with Li carbonate for at least 2 years.

Methods: Three-dimensional ⁷Li magnetic resonance imaging scans (N = 21) were acquired with 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 7 broad anatomical areas, voxel- and parcellation-based group analyses were conducted for the first time for ⁷Li magnetic resonance imaging.

Results: Using unprecedented spatial sensitivity and specificity, we were able to confirm the heterogeneity of the brain Li distribution and its interindividual variability, as well as the strong correlation between plasma and average brain [Li] ([Li]_B ≈ 0.40 × [Li]_P, R = .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 1) the major role of the hippocampus in emotion processing and regulation, 2) the consistent atrophy of the hippocampus in untreated patients with BD, and 3) the normalization effect of Li on gray 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 patients with BD.

Keywords: Bipolar disorder (BD); Brain; High magnetic field; Hippocampus; Lithium-7 ((7)Li); Magnetic resonance imaging (MRI).