Objective: To develop an imaging protocol for 7 tesla magnetic resonance imaging (MRI) that captures the structural and functional consequences of locus coeruleus (LC) neurodegeneration. Subsequently, to unravel how LC degeneration and noradrenergic (NA) dysfunction contributes to non-motor symptoms in Parkinson’s disease (PD).

Background: PD is a neurodegenerative disease affecting neuromodulatory brainstem nuclei leading to severe neuronal loss in the substantia nigra (SN) and locus coeruleus (LC)[1]. PD can, in addition to the classical triad of motor symptoms, cause heterogeneous non-motor symptoms including sleep disorders, neuropsychiatric and cognitive symptoms (e.g. depression, apathy, anxiety and dementia). NA is involved in modulating sleep, arousal, emotional processing and cognition, and NA loss from LC degeneration might therefore contribute to the development of non-motor symptoms associated with PD. We are exploring changes in the LC and a possible correlation to NA-related non-motor symptoms in PD. So far however, the effects of LC degeneration and NA dysfunction in PD remain largely unknown.

Method: PD related changes in the LC are quantified using 7 tesla structural and functional MRI. Structural changes are assessed using a neuromelanin sensitive, magnetization transfer weighted (MTw) sequence similar to the method developed by Priovoulos et al.[2]. This allows for evaluation of the structural integrity of the LC at sub-millimetre resolution (voxel size 0.4×0.4×1.0mm). Functional MRI (fMRI) is used to evaluate the LC-NA response to emotionally salient visual stimuli in two sessions, on and off PD medication. Non-motor symptoms are assessed using the Non-Motor Symptom Scale, Montreal Cognitive Assessment, Beck’s Depression Inventory and Lille Apathy Rating Scale.

Results: Acquisition of structural data and pilot fMRI experiments are ongoing with 22/60 patients and 4/30 healthy control participants currently enrolled. As a preliminary finding, the LC could be identified visually in 10 of the 16 subjects scanned: Visible L=10 R=7, not visible L=4, R=7, uncertain L=2, R=2 (L, left LC, R, right LC).

Conclusion: We have developed a 7T MRI protocol for assessing structural and functional changes in the LC. Data collection is expected to be completed by March 2020.

References: [1] N. Giguère, S. Burke Nanni, L.-E. Trudeau, On Cell Loss and Selective Vulnerability of Neuronal Populations in Parkinson’s Disease, Front. Neurol. 9 (2018). doi:10.3389/fneur.2018.00455. [2] N. Priovoulos, H.I.L. Jacobs, D. Ivanov, K. Uludag, F.R.J. Verhey, B.A. Poser, High-resolution in vivo imaging of human locus coeruleus by Magnetization Transfer MRI at 3T and 7T, NeuroImage. (2017). doi:10.1016/j.neuroimage.2017.07.045.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/focus-on-the-locus-ultra-high-field-mri-evaluation-of-locus-coeruleus-structure-and-function-in-parkinsons-disease/