Human brain 7Li-MRI following low-dose lithium dietary supplementation in healthy participants

Abstract

Background: Lithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging (⁷Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose.

Methods: Lithium orotate supplements were taken by nine healthy adult male subjects (5 mg daily) for up to 28 days, providing 2-7 % of the lithium content of a typical therapeutic lithium carbonate dose. One-dimensional ⁷Li-images were acquired on a 3.0 T MRI scanner. All subjects were scanned on day 14 or 28; seven were scanned on both, one at baseline and one after 7-days washout.

Results: ⁷Li-MR signal amplitude was broadly stable between days 14 and 28. Two subjects had notably higher ⁷Li-signal intensities (approximately 2-4×) compared to other study participants.

Limitations: Lithium adherence was self-reported by all participants without formal validation. The coarse spatial resolution necessary for detection of low concentrations of ⁷Li exhibits imperfect spatial separation of signal from adjacent pixels.

Conclusions: ⁷Li-MRI performed using a clinical 3T scanner demonstrated detection of lithium in the brain at very low concentration, in the range of approximately 10-60 mM. The methods are suited to studies assessing low dose lithium administration in psychiatric and neurodegenerative disorders, and permit the comparison of different lithium salt preparations at a time of emerging interest in the field.

Keywords: (7)Li; Lithium; Low dose; MRI; Multinuclear; Orotate.