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Neuromelanin-sensitive MRI for mechanistic research and biomarker development in psychiatry

Neuropsychopharmacology (2024)Cite this article

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Abstract

Neuromelanin-sensitive MRI is a burgeoning non-invasive neuroimaging method with an increasing number of applications in psychiatric research. This MRI modality is sensitive to the concentration of neuromelanin, which is synthesized from intracellular catecholamines and accumulates in catecholaminergic nuclei including the dopaminergic substantia nigra and the noradrenergic locus coeruleus. Emerging data suggest the utility of neuromelanin-sensitive MRI as a proxy measure for variability in catecholamine metabolism and function, even in the absence of catecholaminergic cell loss. Given the importance of catecholamine function to several psychiatric disorders and their treatments, neuromelanin-sensitive MRI is ideally positioned as an informative and easy-to-acquire catecholaminergic index. In this review paper, we examine basic aspects of neuromelanin and neuromelanin-sensitive MRI and focus on its psychiatric applications in the contexts of mechanistic research and biomarker development. We discuss ongoing debates and state-of-the-art research into the mechanisms of the neuromelanin-sensitive MRI contrast, standardized protocols and optimized analytic approaches, and application of cutting-edge methods such as machine learning and artificial intelligence to enhance the feasibility and predictive power of neuromelanin-sensitive-MRI-based tools. We finally lay out important future directions to allow neuromelanin-sensitive-MRI to fulfill its potential as a key component of the research, and ultimately clinical, toolbox in psychiatry.

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Fig. 1: Anatomy of catecholaminergic nuclei, neuromelanin synthesis, and neuromelanin-sensitive MRI.
Fig. 2: Clinical applications of SN-VTA NM-MRI.
Fig. 3: Measurement of LC NM-MRI contrast and its clinical and behavioral correlates.
Fig. 4: A lab-to-clinic pipeline for NM-MRI-based biomarkers.

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Funding

CC was supported by NSERC grant RGPIN-1502. GH was supported by NIMH grants R01 MH117323 and R01 MH114965.

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Authors and Affiliations

  1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Kenneth Wengler

  2. Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Kenneth Wengler

  3. Department of Neurology, Vanderbilt University Medical Center, Vanderbilt, TN, USA

    Paula Trujillo

  4. Department of Psychiatry and Behavioral Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA

    Clifford M. Cassidy

  5. New York State Psychiatric Institute, New York, NY, USA

    Guillermo Horga

  6. Department of Psychiatry, Columbia University, New York, NY, USA

    Guillermo Horga

Authors
  1. Kenneth Wengler
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  2. Paula Trujillo
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  3. Clifford M. Cassidy
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  4. Guillermo Horga
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Contributions

KW, PT, CMC, GH: Conceptualization, literature review, writing of original and revised drafts. All authors contributed to drafting and approved the final version of the manuscript.

Corresponding author

Correspondence to Guillermo Horga.

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Competing interests

KW, CMC, and GH are inventors on filed patents for the analysis and use of neuromelanin-sensitive MRI in central nervous system disorders licensed to Terran Biosciences, with no royalties received. GH and PT reported investigator-initiated sponsored research agreements with Terran Biosciences outside the submitted work.

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Wengler, K., Trujillo, P., Cassidy, C.M. et al. Neuromelanin-sensitive MRI for mechanistic research and biomarker development in psychiatry. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01934-y

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  • DOI: https://doi.org/10.1038/s41386-024-01934-y

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