Neuromelanin-Sensitive MRI of the Locus Coeruleus: Insights into Parkinson's disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder pri- marily characterized by motor symptoms such as tremor, rigidity, and bradykinesia. However, in recent years, the important role of non-motor symptoms such as fatigue, sleep disturbances, and cognitive impairments has emerged, significantly contributing to disease burden and reduced quality of life. In this context, the locus coeruleus (LC), a small neuromelanin-rich structure in the brainstem, has been suggested to be potentially involved in the pathophysiology of these manifestations. Magnetic resonance imaging (MRI) is a key tool for studying disease progression and identifying potential biomarkers of neurodegeneration. The aim of the present work was to investigate whether neuromelanin-sensitive MRI (NM-MRI) sequences can be used to characterize the signal originating from the LC and relate it to clinically relevant indices in PD. The study included 35 patients with PD, who underwent a high-resolution MRI protocol comprising NM-sensitive sequences, T1-weighted structural sequences, and resting-state functional MRI (rs-fMRI). Due to the small size of the LC and the difficulty of direct identification, the structure was segmented using anatomical atlases. From each segmented image, voxel intensities were extracted, applying different normalization methods to make the NM-MRI signal comparable across subjects. Subsequently, correlations between the normalized signal (CNR) and key clinical indices were calculated. For each patient, the rs-fMRI images, initially in the native space, were coregistered to the NM-MRI space. Within the LC, mean values of BOLD signal regional homogeneity, dopamine- and noradrenaline-erniched functional connectivity were extracted. The average values of these three maps within the LC were correlated with the CNR. Results showed lateral dif- ferences in NM-MRI signal in a majority of participants, which were not related to the clinically most affected side. Importantly, CNR was associated with anxiety levels and, to a lesser extent, with fatigue. No significant associations were observed between CNR and LC functional connectivity or regional homogeneity.