Longitudinal Changes in Neuromelanin MRI Signal in Parkinson's Disease: A Progression Marker

Abstract

A BS TRACT: Background: Development of reliable and accurate imaging biomarkers of dopaminergic cell neurodegeneration is necessary to facilitate therapeutic drug trials in Parkinson's disease (PD). Neuromelanin-sensitive MRI techniques have been effective in detecting neurodegeneration in the substantia nigra pars compacta (SNpc). The objective of the current study was to investigate longitudinal neuromelanin signal changes in the SNpc in PD patients. Methods: In this prospective, longitudinal, observational case-control study, we included 140 PD patients and 64 healthy volunteers divided into 2 cohorts. Cohort I included 99 early PD patients (disease duration, 1.5 AE 1.0 years) and 41 healthy volunteers analyzed at baseline (V1), where 79 PD patients and 32 healthy volunteers were rescanned after 2.0 AE 0.2 years of follow-up (V2). Cohort II included 41 progressing PD patients (disease duration, 9.3 AE 3.7 years) and 23 healthy volunteers at V1, where 30 PD patients were rescanned after 2.4 AE 0.5 years of follow-up. Subjects were scanned at 3 T MRI using 3-dimensional T1-weighted and neuromelanin-sensitive imaging. Regions of interest were delineated manually to calculate SN volumes, volumes corrected by total intracranial volume, signal-to-noise ratio, and contrast-to-noise ratio. Results: Results showed (1) significant reduction in volume and volume corrected by total intracranial volume between visits, greater in progressing PD than nonsignificant changes in healthy volunteers; (2) no significant effects of visit for signal intensity (signal-to-noise ratio);(3) significant interaction in volume between group and visit; (4) greater volume corrected by total intracranial volume at baseline in female patients and greater decrease in volume and increase in the contrast-to-noise ratio in progressing female PD patients compared with male patients; and (5) correlations between neuromelanin SN changes and disease severity and duration. Conclusions: We observed a progressive and measurable decrease in neuromelanin-based SN signal and volume in PD, which might allow a direct noninvasive

Deep Learning‐Based Neuromelanin MRI Changes of Isolated REM Sleep Behavior Disorder

“…Volumes and signal changes were at an intermediate level between values in HVs and PD patients. All female groups had larger C vol similar to previous HVs 22 and PD 20 studies.…”

“…We calculated SNc volumes (Vol), corrected volume (C vol = Vol/total intracranial volume) to normalize for the subject head size, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) by normalizing the mean signal in SNc relative to the background signal, as described in previous studies (Data S1). 2,20 Statistical analyses were performed using R (R Core Team 2019, v3.6.1) and MATLAB. The between-group comparisons of demographic and clinical variables were performed using the parametric Student's t test.…”

The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson’s disease

“… 64 Inter-visit changes in neuromelanin and iron accumulation were not significant. On neuromelanin-sensitive MRI, neuromelanin SNR was less sensitive than SNc volume measurements (as used here) for detecting changes early in the disease, 65 suggesting that, in early Parkinson’s disease, measurements of neuromelanin residual volume and SNc neuromelanin SNR offer complementary information on Parkinson’s disease-induced temporal changes in neuromelanin.…”

Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review

“…Importantly, multimodal studies employing structural MRI and SPECT imaging showed comparable or better diagnostic performance compared to each parameter of DAT-SPECT and NM-MRI in distinguishing PD from nondegenerative parkinsonian syndrome [ 297 ]. It is worth noting that, unlike DAT imaging, NM-MRI imaging seems to be also effective for measuring disease progression demonstrating to closely correlate with clinical scores, including UPDRS-III, in advanced PD patients [ 105 , 298 ].…”