The Bipolar Lithium Imaging Scan Study (BLISS): protocol for a 7T lithium-7 magnetic resonance study in bipolar disorder

Abstract

Introduction: Lithium treatment is considered the first-line option in the pharmacological treatment of bipolar disorder. At the same time, individual responses vary greatly, which complicates achieving rapid stabilization in many subjects with bipolar disorder. The neurobiological mechanism of action of lithium remains largely unknown, hindering the development of clinically applicable predictors of individual treatment responses. The recent introduction of ultra-high-field lithium magnetic resonance imaging (MRI) has opened up a promising avenue for better linking brain measures with clinical response to lithium treatment.

Methods and analysis: This is an observational study involving 80 adults with bipolar disorder who begin lithium as part of their regular treatment. Within 4 weeks of reaching stable therapeutic serum lithium concentrations, brain lithium concentrations will be measured by employing a 3D lithium-7 chemical shift imaging (⁷Li CSI) sequence on a 7T MR system. The primary outcome is the clinical response to lithium treatment at 1 year follow-up, assessed using a validated questionnaire. Linear regression analysis will be used to establish correlations between brain lithium concentrations—measured through mean brain, voxel-wise, parcellation, and region-of-interest approaches—and clinical lithium response.

Ethics and dissemination: The BLISS study protocol (NL80214.058.22) has been approved by the Medical Ethics Committee of Leiden, The Hague, and Delft in The Netherlands. Results will be submitted for publication in peer-reviewed journals and shared with the key population.

Registration Online at clinicaltrials.gov (NCT06134349), 20 November 2023.

Keywords

7 Tesla / lithium / bipolar disorder / translational / ultra-high field / chemical shift imaging / clinical treatment response / lithium-7 MR imaging

Study status

Recruitment began in March 2024, and completion of inclusions is expected by March 2027.

Author contributions

Elvira Boere (Conceptualization, Project administration, Writing - original draft), Nic J.A. van der Wee (Conceptualization, Resources, Writing - review & editing), Albert M. van Hemert (Conceptualization, Resources, Writing - review & editing), Andrew G. Webb (Conceptualization, Resources, Software, Visualization, Writing - review & editing), and Max de Leeuw (Conceptualization, Supervision, Writing - review & editing).

Conflict of interests

None to report.

Acknowledgements

The BLISS study is made possible by the participating institutes: the Departments of Psychiatry and Radiology at Leiden University Medical Centre, PsyQ ParnassiaGroup Mental Health Institution, and Rivierduinen Mental Health Institution, all based in the Netherlands.

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