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Abstract
The nigrosome-1 region of the substantia nigra (SN) undergoes the greatest and earliest dopaminergic neuron loss in Parkinson's disease (PD). As T2-weighted magnetic resonance imaging (MRI) scans are often collected with routine clinical MRI protocols, this investigation aims to determine whether T2-imaging changes in the nigrosome-1 are related to clinical measures of PD and to assess their potential as a more clinically accessible biomarker for PD. Voxel intensity ratios were calculated for T2-weighted MRI scans from 47 subjects from the Parkinson's Progression Markers Initiative database. Three approaches were used to delineate the SN and nigrosome-1: (1) manual segmentation, (2) automated segmentation, and (3) area voxel-based morphometry. Voxel intensity ratios were calculated from voxel intensity values taken from the nigrosome-1 and two areas of the remaining SN. Linear regression analyses were conducted relating voxel intensity ratios with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sub-scores for each subject. For manual segmentation, linear regression tests consistently identified the voxel intensity ratio derived from the dorsolateral SN and nigrosome-1 (IR2) as predictive of nBehav (p = 0.0377) and nExp (p = 0.03856). For automated segmentation, linear regression tests identified IR2 as predictive of Subscore IA (nBehav) (p = 0.01134), Subscore IB (nExp) (p = 0.00336), Score II (mExp) (p = 0.02125), and Score III (mSign) (p = 0.008139). For the voxel-based morphometric approach, univariate simple linear regression analysis identified IR2 as yielding significant results for nBehav (p = 0.003102), mExp (p = 0.0172), and mSign (p = 0.00393). Neuroimaging biomarkers may be used as a proxy of changes in the nigrosome-1, measured by MDS-UPDRS scores as an indicator of the severity of PD. The voxel intensity ratio derived from the dorsolateral SN and nigrosome-1 was consistently predictive of non-motor complex behaviors in all three analyses and predictive of non-motor experiences of daily living, motor experiences of daily living, and motor signs of PD in two of the three analyses. These results suggest that T2 changes in the nigrosome-1 may relate to certain clinical measures of PD. T2 changes in the nigrosome-1 may be considered when developing a more accessible clinical diagnostic tool for patients with suspected PD.
Highlights
There has been recent interest in determining a reliable in vivo biomarker for Parkinson’s disease (PD), a neurodegenerative disorder characterized by motor and non-motor symptoms
In contrast to these studies, we aimed to determine whether the nigrosome-1 could serve as a more readily accessible, potential biomarker for PD using T2-weighted images, in that changes in the nigrosome-1 correspond with signs of PD progression as assessed by the MDS-UPDRS
Whereas the majority of studies investigating the nigrosome-1 and its degeneration in PD have focused on its direct visualization with 7 or 3 T T2*-weighted SWI sequences, we demonstrated positive findings even when using T2-weighted images
Summary
There has been recent interest in determining a reliable in vivo biomarker for Parkinson’s disease (PD), a neurodegenerative disorder characterized by motor and non-motor symptoms. An ideal imaging marker is expected to reflect progressive loss of dopaminergic neurons For such purpose, the nigrosomes within the substantia nigra (SN) region are of particular interest, because they have the highest density of dopaminergic neurons [3]. Using T2-weighted images from both PD subjects and healthy controls, we related voxel intensity ratios derived from the nigrosome-1 and two other regions of the SN with clinical measures of PD to determine whether the nigrosome-1 can serve as a more readily accessible, potential biomarker for PD, thereby serving as an indicator of disease progression. As T2-weighted magnetic resonance imaging (MRI) scans are often collected with routine clinical MRI protocols, this investigation aims to determine whether T2-imaging changes in the nigrosome-1 are related to clinical measures of PD and to assess their potential as a more clinically accessible biomarker for PD
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