Unraveling the contributions to the neuromelanin-MRI contrast
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ORIGINAL ARTICLE
Unraveling the contributions to the neuromelanin‑MRI contrast Nikos Priovoulos1 · Stan C. J. van Boxel1 · Heidi I. L. Jacobs1,2,3 · Benedikt A. Poser2 · Kamil Uludag4,5 · Frans R. J. Verhey1 · Dimo Ivanov2 Received: 20 April 2020 / Accepted: 1 October 2020 © The Author(s) 2020
Abstract The Locus Coeruleus (LC) and the Substantia Nigra (SN) are small brainstem nuclei that change with aging and may be involved in the development of various neurodegenerative and psychiatric diseases. Magnetization Transfer (MT) MRI has been shown to facilitate LC and the SN visualization, and the observed contrast is assumed to be related to neuromelanin accumulation. Imaging these nuclei may have predictive value for the progression of various diseases, but interpretation of previous studies is hindered by the fact that the precise biological source of the contrast remains unclear, though several hypotheses have been put forward. To inform clinical studies on the possible biological interpretation of the LC- and SN contrast, we examined an agar-based phantom containing samples of natural Sepia melanin and synthetic Cys-Dopa-Melanin and compared this to the in vivo human LC and SN. T1 and T2* maps, MT spectra and relaxation times of the phantom, the LC and the SN were measured, and a two-pool MT model was fitted. Additionally, Bloch simulations and a transient MT experiment were conducted to confirm the findings. Overall, our results indicate that Neuromelanin-MRI contrast in the LC likely results from a lower macromolecular fraction, thus facilitating interpretation of results in clinical populations. We further demonstrate that in older individuals T1 lengthening occurs in the LC. Keywords Neuromelanin · Neuromelanin-MRI · Locus coeruleus · Substantia nigra · Magnetization transfer
Introduction The Locus Coeruleus (LC) and the Substantia Nigra (SN) are small, neuromelanin (NM)-rich gray matter nuclei in the brainstem that show alterations in several neurodegenerative and psychiatric diseases, such as Parkinson’s and Alzheimer’s (AD) disease or depressive disorder (Braak et al. Nikos Priovoulos and Stan C. J. van Boxel contributed equally. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00429-020-02153-z) contains supplementary material, which is available to authorized users. * Nikos Priovoulos [email protected] * Dimo Ivanov [email protected] 1
School for Mental Health and Neuroscience, Alzheimer Center Limburg, Faculty of Health, Medicine and Life Science, Maastricht University, Maastricht, Netherlands
Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
2
2011; Busch et al. 1997; Liu et al. 2017; Marcyniuk et al. 1986; Sara 2009). Because of their critical modulating role in cognition and behavior, as well as being part of the pathophysiology of several neurodegenerative diseases, there is an increasing interest in imaging the LC and th
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