Abstract
Microstructural changes associated with degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc) in Parkinson's disease (PD) have been studied using Diffusion Tensor Imaging (DTI). However, these studies show inconsistent results, mainly due to methodological variations in delineation of SNc. To mitigate this, our work aims to construct a probabilistic atlas of SNc based on a 3D Neuromelanin Sensitive MRI (NMS‐MRI) sequence and demonstrate its applicability to investigate microstructural changes on a large dataset of PD. Using manual segmentation and deformable registration we created a novel SNc atlas in the MNI space using NMS‐MRI sequences of 27 healthy controls (HC). We first quantitatively evaluated this atlas and then employed it to investigate the micro‐structural abnormalities in SNc using diffusion MRI from 133 patients with PD and 99 HCs. Our results demonstrated significant increase in diffusivity with no changes in anisotropy. In addition, we also observed an asymmetry of the diffusion metrics with a higher diffusivity and lower anisotropy in the left SNc than the right. Finally, a multivariate classifier based on SNc diffusion features could delineate patients with PD with an average accuracy of 71.7%. Overall, from this work we establish a normative baseline for the SNc region of interest using NMS‐MRI while the application on PD data emphasizes on the contribution of diffusivity measures rather than anisotropy of white matter in PD.
Highlights
Parkinson‟s disease (PD) is a chronic, progressive disorder characterized by bradykinesia, rigidity, and tremor
Higher axial diffusivity (AD),mean diffusivity (MD)(left substantia nigra ROIs (snROIs): f=21.40, p=0.000006; right snROI: f=11.43,p=0.00084) and RD(left snROI: f=19.57,p=0.000015; right snROI: f=11.77, p=0.0007) values were obtained in PD patients as compared to controls
Comparative studies(Du et al, 2011; Langley et al, 2015)on contrast generating MR sequence for substantia nigra pars compacta (SNc) have shown that T2w sequences and Neuromelanin sensitive Magnetic Resonance Imaging (MRI) (NMS-MRI) sequences are both sensitive to different sub regions of SNc, hypo-density observed on T2 images in PD could indicate iron deposition apart from dopaminergic loss in the SNc, making it highly unreliable(Deng et al, 2018; Langley et al, 2016; Wypijewska et al, 2010)
Summary
Parkinson‟s disease (PD) is a chronic, progressive disorder characterized by bradykinesia, rigidity, and tremor. Several T1 weighted NMS-MRI based studies in PD have found a reduction in signal intensity, contrast to noise ratio, as well as area and volume of SNc in PD patients as compared to controls (Isaias et al, 2016; Kashihara et al, 2011; Matsuura et al, 2016; Matsuura et al, 2013; Reimao et al, 2015; Sasaki et al, 2006) Majority of these studies have showed a significant correlation of NMS-MRI measures with disease severity and other clinical scores(Isaias et al, 2016; Kashihara et al, 2011; Matsuura et al, 2016; Matsuura et al, 2013; Reimao et al, 2015), indicating a potential neuro-pathological biomarker for disease progression in PD
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