Reliability and Reproducibility of Neuromelanin-Sensitive Imaging of the Substantia Nigra: A Comparison of Three Different Sequences

Background: Neuromelanin-sensitive MRI (NM-MRI) of the substantia nigra provides a noninvasive way to acquire an indirect measure of dopamine functioning. Despite the potential of NM-MRI as a candidate biomarker for dopaminergic pathology, studies about its reproducibility are sparse.

Purpose: To assess the test-retest reproducibility of three commonly used NM-MRI sequences and evaluate three analysis methods.

Study type: Prospective study.

Population: A total of 11 healthy participants age between 20-27 years.

Field strength/sequence: 3.0T; NM-MRI gradient recalled echo (GRE) with magnetization transfer (MT) pulse; NM-MRI turbo spin echo (TSE) with MT pulse; NM-MRI TSE without MT pulse.

Assessment: Participants were scanned twice with a 3-week interval. Manual analysis, threshold analysis, and voxelwise analysis were performed for volume and contrast ratio (CR) measurements.

Statistical tests: Intraclass correlation coefficients (ICCs) were calculated for test-retest and inter- and intrarater variability.

Results: The GRE sequence achieved the highest contrast and lowest variability (4.9-5.7%) and showed substantial to almost perfect test-retest ICC (0.72-0.90) for CR measurements. For volume measurements, the manual analysis showed a higher variability (10.7-17.9%) and scored lower test-retest ICCs (-0.13-0.73) than the other analysis methods. The threshold analysis showed higher test-retest ICC (0.77) than the manual analysis for the volume measurements.

Data conclusion: NM-MRI is a highly reproducible measure, especially when using the GRE sequence and CR measurements. Volume measurements appear to be more sensitive to inter/intrarater variability and variability in placement and orientation of the NM-MRI slab. The threshold analysis appears to be the best alternative for volume analysis.

Level of evidence: 2 TECHNICAL EFFICACY STAGE: 1.