Does age, sex, and area of substantia nigra echogenicity predict the MRI appearance of nigrosome-1?

The appearance of the substantia nigra (SN) can aid diagnosis of Parkinson's disease (PD). The effect of age and sex on the appearance of nigrosome-1 (SN subregion) on magnetic resonance imaging (MRI), and the relationship between nigrosome-1 (viewed with MRI) and SN echogenicity (viewed with transcranial ultrasound) is unknown. The study aimed to address these knowledge gaps. It was hypothesized that age, sex, and area of SN echogenicity predict area of MRI hyperintense signal in nigrosome-1. The cross-sectional study involved a group of healthy adults (n = 105; aged 21-79 years) and adults diagnosed with PD (n = 37; aged 51-80 years). Multilevel mixed-effects regression analysis was used to investigate if age, sex, side, and area of SN echogenicity predict area of nigrosome-1 hyperintense signal. Area of nigrosome-1 hyperintense signal increased by an average of 0.045 mm²/year in healthy adults (p = 0.016) but not in adults living with PD. Sex, side, and area of SN echogenicity did not predict area of nigrosome-1 hyperintense signal in either group. Disease duration predicted area of nigrosome-1 hyperintense signal in the PD group (coefficient = -0.41, p = 0.014). The expected between-group differences (p < 0.001) in median area of nigrosome-1 hyperintense signal (smallest area across sides: healthy = 7.6 mm², PD = 0.0 mm²) and SN echogenicity (largest area across sides: healthy = 14.3 mm², PD = 29.3 mm²) were observed. The results suggest that the MRI appearance of nigrosome-1 can vary with age but not sex or area of SN echogenicity. The results further understanding of the nigrosome-1 biomarker for PD and aid interpretation of nigrosome-1 MRI findings in clinical settings.