Parkinson's disease (PD) is a progressive neurological disorder that has no reliable biomarkers. The aim of this study was to explore the potential of semi-automated sub-regional analysis of the striatum with magnetic resonance imaging (MRI) to distinguish PD patients from controls (i.e., as a diagnostic biomarker) and to compare PD patients at different stages of disease.With 3 Tesla MRI, diffusion- and T1-weighted scans were obtained on two occasions in 24 PD patients and 18 age-matched, healthy controls. PD patients completed one session on and the other session off dopaminergic medication. The striatum was parcellated into seven functionally disparate sub-regions. The segmentation was guided by reciprocal connections to distinct cortical regions. Volume, surface-based morphometry, and integrity of white matter connections were calculated for each striatal sub-region.Test-retest reliability of our volume, morphometry, and white matter integrity measures across scans was high, with correlations ranging from r = 0.452, p < 0.05 and r = 0.985, p < 0.001. Global measures of striatum such as total striatum, nucleus accumbens, caudate nuclei, and putamen were not significantly different between PD patients and controls, indicating poor sensitivity of these measures, which average across sub-regions that are functionally heterogeneous and differentially affected by PD, to act as diagnostic biomarkers. Further, these measures did not correlate significantly with disease severity, challenging their potential to serve as progression biomarkers. In contrast, a) decreased volume and b) inward surface displacement of caudal-motor striatum—the region first and most dopamine depleted in PD—distinguished PD patients from controls. Integrity of white matter cortico-striatal connections in caudal-motor and adjacent striatal sub-regions (i.e., executive and temporal striatum) was reduced for PD patients relative to controls. Finally, volume of limbic striatum, the only striatal sub-region innervated by the later-degenerating ventral tegmental area in PD, was reduced in later-stage compared to early stage PD patients a potential progression biomarker.Segmenting striatum based on distinct cortical connectivity provided highly sensitive MRI measures for diagnosing and staging PD.

Purpose Deep brain stimulation (DBS) is a common treatment for Parkinson's disease (PD) and involves the use of brain atlases or intrinsic landmarks to estimate the location of target deep brain structures, such as the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi). However, these structures can be difficult to localize with conventional clinical magnetic resonance imaging (MRI), and thus targeting can be prone to error. Ultra-high-field imaging at 7T has the ability to clearly resolve these structures and thus atlases built with these data have the potential to improve targeting accuracy. Methods T1 and T2-weighted images of 12 healthy control subjects were acquired using a 7T MR scanner. These images were then used with groupwise registration to generate an unbiased average template with T1w and T2w contrast. Deep brain structures were manually labelled in each subject by two raters and rater reliability was assessed. We compared the use of this unbiased atlas with two other methods of atlas-based segmentation (single-template and multi-template) for subthalamic nucleus (STN) segmentation on 7T MRI data. We also applied this atlas to clinical DBS data acquired at 1.5T to evaluate its efficacy for DBS target localization as compared to using a standard atlas. Results The unbiased templates provide superb detail of subcortical structures. Through one-way ANOVA tests, the unbiased template is significantly (p < 0.05) more accurate than a single-template in atlas-based segmentation and DBS target localization tasks. Conclusion The generated unbiased averaged templates provide better visualization of deep brain nuclei and an increase in accuracy over single-template and lower field strength atlases.