Objective: To investigate the neuromelanin (NM) signal changes in Parkinson’s disease (PD) patients associated with disease progression.

Background: PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Dopaminergic neurons contain NM pigment, which results in high T1-weighted (T1-w) signal on MRI [1]. The NM signal is reduced early in the SNpc in PD [2]. MRI-NM could be used to monitor disease progression and response to therapies, which requires characterizing the longitudinal NM signal variations in the SN.

Method: We prospectively studied two cohorts of early PD (Iceberg) and advanced PD (Nucleipark) and their respective healthy volunteers (HV). Subjects were scanned at 3T MRI (Iceberg: PRISMA, Nucleipark: TRIO, Siemens) using 3D T1-w and NM-sensitive images, acquired using 2D axial turbo spin echo [table1]. SN regions of interest (ROI) were manually delineated by two independent examiners using FreeView as the hyperintense area dorsal to the cerebral peduncle and ventral to the red nucleus [figure1] [3]. Signal using the manually traced background region and volumes of NM ROI normalized using total intracranial volume (TIV) were calculated.

Results: Clinical characteristics. 51 patients and 20 age-matched HV had NM-imaging for Iceberg whereas 30 patients were compared with the 23 HV for Nucleipark [table2]. Volume measurements. There was excellent reproducibility between the ROI segmentations for both Iceberg (DICE inter-observer: 0.82, ICC for volume: 0.78) and Nucleipark (DICE inter-observer: 0.77, ICC for volume: 0.84). Early PD demonstrated a statistically significant effect for both factors with a significant reduction in SN volume between V1 and V2 (p<0.001) compared to the HV. Longitudinal changes were not significantly different for signal intensity whereas advanced PD demonstrated a significant reduction between V1 and V2 in both SN volume (p<0.005) and signal intensity (p<0.005) [table3] [figure5]. The average annual rate of decline for volume corrected by TIV was 10.3% in advanced PD, 4.0% in early PD, and 1.9% in HV.

Conclusion: There was a progressive and measurable decrease in NM-SN signal and volume in PD patients over time. NM imaging might allow a direct noninvasive assessment of progression of SN cellular loss in PD and a potential target for disease modification biomarker in drug trials.

References: 1. Sulzer, David, et al. “Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson’s disease.” NPJ Parkinson’s disease 4.1 (2018). 2. Pyatigorskaya, N. et al. “Magnetic Resonance Imaging Biomarkers to Assess Substantia Nigra Damage in Idiopathic Rapid Eye Movement Sleep Behavior Disorder. Sleep 40, (2017). 3. Pyatigorskaya, N. et al. Comparative study of MRI biomarkers in the substantia nigra to discriminate idiopathic Parkinson disease. Am. J. Neuroradiol. 39, 1460–1467 (2018).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/changes-in-neuromelanin-mri-signal-in-parkinsons-disease-a-longitudinal-study/