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.

中文翻译：

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双相情感障碍患者海马体中锂的积累：7 特斯拉的锂 7 磁共振成像研究

背景锂（Li）是双相情感障碍（BD）的一线治疗药物。为了研究其脑分布及其与血浆浓度的关系，我们在使用碳酸锂治疗至少 2 年的心境正常的 BD 患者中使用了 7T 的 7Li 磁共振成像。方法 使用非笛卡尔 k 空间采样方案通过超短回波时间序列采集三维 7Li 磁共振成像扫描 (N = 21)。锂浓度 ([Li]) 是使用体模替换方法估算的，考虑了不同的 T1 和 T2 弛豫效应。除了确定来自 7 个广泛解剖区域的平均区域 [Li] 外，还首次对 7Li 磁共振成像进行了基于体素和分割的组分析。结果 使用前所未有的空间敏感性和特异性，我们能够确认脑 Li 分布的异质性及其个体间变异性，以及血浆和平均脑 [Li] 之间的强相关性（[Li]B ≈ 0.40 × [Li]P，R = .74）。值得注意的是，我们的统计分析导致确定了一个定义明确且显着的簇，与左海马体紧密对应，在我们的队列中始终显示高锂含量。结论 考虑到 1) 海马体在情绪处理和调节中的主要作用，2) 未经治疗的 BD 患者海马体的持续萎缩，以及 3) Li 对灰质体积的正常化作用，这一观察结果可能很有趣。该研究为阐明 Li 脑分布与其治疗反应之间的关系铺平了道路，