Magnetic resonance imaging markers of Parkinson’s disease nigrostriatal signature

Abstract

One objective of modern neuroimaging is to identify markers that can aid in diagnosis, disease progression monitoring and long-term drug impact analysis. In this study, Parkinson-associated physiopathological modifications were characterized in six subcortical structures by simultaneously measuring quantitative magnetic resonance parameters sensitive to complementary tissue characteristics (i.e. volume atrophy, iron deposition and microstructural damage). Thirty patients with Parkinson's disease and 22 control subjects underwent 3-T magnetic resonance imaging with T₂*-weighted, whole-brain T₁-weighted and diffusion tensor imaging scans. The mean R₂* value, mean diffusivity and fractional anisotropy in the pallidum, putamen, caudate nucleus, thalamus, substantia nigra and red nucleus were compared between patients with Parkinson's disease and control subjects. Comparisons were also performed using voxel-based analysis of R₂*, mean diffusivity and fractional anisotropy maps to determine which subregion of the basal ganglia showed the greater difference for each parameter. Averages of each subregion were then used in a logistic regression analysis. Compared with control subjects, patients with Parkinson's disease displayed significantly higher R₂* values in the substantia nigra, lower fractional anisotropy values in the substantia nigra and thalamus, and higher mean diffusivity values in the thalamus. Voxel-based analyses confirmed these results and, in addition, showed a significant difference in the mean diffusivity in the striatum. The combination of three markers was sufficient to obtain a 95% global accuracy (area under the receiver operating characteristic curve) for discriminating patients with Parkinson's disease from controls. The markers comprising discriminating combinations were R₂* in the substantia nigra, fractional anisotropy in the substantia nigra and mean diffusivity in the putamen or caudate nucleus. Remarkably, the predictive markers involved the nigrostriatal structures that characterize Parkinson's physiopathology. Furthermore, highly discriminating combinations included markers from three different magnetic resonance parameters (R₂*, mean diffusivity and fractional anisotropy). These findings demonstrate that multimodal magnetic resonance imaging of subcortical grey matter structures is useful for the evaluation of Parkinson's disease and, possibly, of other subcortical pathologies.

Advances in the Role of Neuroimaging to Monitor Disease Progression in Parkinson’s Disease

“…73 A multimodal magnetic resonance imaging study of subcortical gray matter structures using 3-T MRI with T2*-weighted, whole-brain T1-weighted and diffusion tensor imaging scans was recently reported in 30 patients with PD and 22 controls. 74 Patients with PD displayed significantly higher R2* values in the substantia nigra (in keeping with the report of Martin et al), lower fractional anisotropy values in the substantia nigra and thalamus, and higher mean diffusivity values in the thalamus. Voxel-based analyses confirmed these results and, in addition, showed a significant difference in the mean diffusivity in the striatum.…”

Diffusion tensor imaging in parkinsonian syndromes

“…Two other studies 10,26 did find reduced FA in SN correlated with disease severity. Studies focusing on the SN and integrating T2* 20,24 or volumetric analysis 15 with DTI reported that this improved their ability to discriminate patients with PD from healthy controls. There is evidence suggesting that neurodegenerative changes occur outside the SN.…”

Imaging insights into basal ganglia function, Parkinson's disease, and dystonia

“…3 A combination of measures of iron content with changes in fractional anisotropy in the substantia nigra resulted in better separation of patients with Parkinson's disease from control individuals compared with each technique separately, with 95% global accuracy. 4 Reduced connectivity of the substantia nigra with the striatum and thalamus was also evidenced in patients with Parkinson's disease using tractography-based methods 5 and resting-state functional connectivity (figure 2). Novel MRI techniques might be helpful for differentiation between Parkinson's disease and atypical parkinsonism (table 1).…”