Diagnostic utility of 7T neuromelanin imaging of the substantia nigra in Parkinson's disease

Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that presents a diagnostic challenge due to symptom overlap with other disorders. Neuromelanin (NM) imaging is a promising biomarker for PD, but adoption has been limited, in part due to subpar performance at standard MRI field strengths. We aimed to evaluate the diagnostic utility of ultra-high field 7T NM-sensitive imaging in the diagnosis of PD versus controls and essential tremor (ET), as well as NM differences among PD subtypes. A retrospective case-control study was conducted including PD patients, ET patients, and controls. 7T NM-sensitive 3D-GRE was acquired, and substantia nigra pars compacta (SNpc) volumes, contrast ratios, and asymmetry indices were calculated. Statistical analyses, including general linear models and ROC curves, were employed. Twenty-one PD patients, 13 ET patients, and 18 controls were assessed. PD patients exhibited significantly lower SNpc volumes compared to non-PD subjects. SNpc total volume showed 100% sensitivity and 96.8% specificity (AUC = 0.998) for differentiating PD from non-PD and 100% sensitivity and 95.2% specificity (AUC = 0.996) in differentiating PD from ET. Contrast ratio was not significantly different between PD and non-PD groups (p = 0.07). There was also significantly higher asymmetry index in SNpc volume in PD compared to non-PD cohorts (p < 0.001). NM signal loss in PD predominantly involved the inferior, posterior, and lateral aspects of SNpc. Akinetic-rigid subtype showed more significant NM signal loss compared to tremor dominant subtype (p < 0.001). 7T NM imaging demonstrates potential as a diagnostic tool for PD, including potential distinction between subtypes, allowing improved understanding of disease progression and subtype-related characteristics.

Fig. 1. Distribution of measured variables across all groups.

a Total SNpc volume in mm³, (b) average SNpc contrast ratio, and (c) asymmetry index are shown for patients with Parkinson’s disease (PD), including those with the akinetic-rigid subtype (AR), those with the tremor dominant subtype (TD), and those with postural instability/gait disturbance (PIGD), as well as all subjects without PD (non-PD), including those with essential tremor (ET) and control subjects (CTRL). Box plots illustrate the median and 25th and 75th percentiles, while whiskers represent minimum and maximum values. Statistically significant differences are indicated.

Fig. 2. Differentiation of patients with Parkinson’s disease (PD) versus non-PD subjects.

The receiver operating characteristic (ROC) analysis for identifying PD patients in a group consisting of both PD and non-PD subjects using (a) total substantia nigra pars compacta (SNpc) volume, (b) average SNpc contrast ratio (CR), and (c) asymmetry index. A total SNpc volume threshold of <440.6 mm³ yields an area under curve (AUC) of 0.998. An average CR threshold of <0.135 yields an AUC of 0.684. An asymmetry index threshold of >3.44 yields an AUC of 0.962.

Fig. 3. Differentiation of patients with Parkinson’s disease (PD) versus essential tremor (ET) subjects.

The receiver operating characteristic (ROC) analysis for identifying PD patients in a group consisting of PD and ET subjects using (a) total substantia nigra pars compacta (SNpc) volume, (b) average SNpc contrast ratio (CR), and (c) asymmetry index. A total SNpc volume threshold of <432.1 mm³ yields an area under curve (AUC) of 0.996. An average CR threshold of <0.173 yields an AUC of 0.711. An asymmetry index threshold of >3.02 yields an AUC of 0.967.

Fig. 4. Differentiation of Parkinson’s disease (PD) subtypes.

The receiver operating characteristic (ROC) analysis for identifying patients with akinetic-rigid (AR) Parkinson’s disease in a group consisting of AR and tremor dominant (TD) subjects using (a) total substantia nigra pars compacta (SNpc) volume, (b) average SNpc contrast ratio (CR), and (c) asymmetry index. A total SNpc volume threshold of <352.2 mm³ yields an area under curve (AUC) of 0.857. An average CR threshold of >0.134 yields an AUC of 0.619. An asymmetry index threshold of >2.83 yields an AUC of 0.512.

Fig. 5. Normalized group mean substantia nigra pars compacta (SNpc) maps.

a Heatmaps for the SNpc for the PD (green) and control (red–orange). b SNpc subtraction maps showing voxels with greater SNpc in controls (red) and greater SNpc in PD (purple). c Heatmaps for the SNpc for the PD (green) and ET (blue). d SNpc subtraction maps showing voxels with greater SNpc in ET (red) and greater SNpc in PD (purple). Neuromelanin (NM) pigment loss in PD was more pronounced along the lateral and inferior aspect of SNpc compared to both ET and control groups.

Fig. 6. Normalized group mean substantia nigra pars compacta (SNpc) maps.

Heatmaps for the SNpc for the (a) tremor dominant (TD) and (b) akinetic-rigid (AR) subgroups. c Overlay of SNpc maps for TD (orange) and AR (blue) showing greater NM pigment loss in the AR subgroup, most pronounced along the lateral and inferior aspect of SNpc.