High-Spatial-Resolution Diffusion MRI in Parkinson Disease: Lateral Asymmetry of the Substantia Nigra

Abstract

NEURORADIOLOGY Parkinson disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN), leading to abnormalities of movement and other functions. Motor symptoms in PD onset and progression have exhibited lateral asymmetry (1), which suggests that the neuronal loss in the SN can be asymmetric, as reported in a neuropathologic study (2). In a majority of patients, symptoms begin on the side of the dominant hand (1). SPECT has demonstrated left hemispheric predominance of nigrostriatal dysfunction in patients with PD who are right handed, providing further evidence that dopaminergic denervation in the SN can be asymmetric (3). Furthermore, signal lateral asymmetry in the SN was indicated in an anatomic MRI study at 7.0 T (4) and considered in a susceptibility-weighted imaging study at 3.0 T (5). Neuroimaging evidence of underlying tissue Purpose: To investigate lateral asymmetry in the SN of patients with PD by using diffusion MRI with both Gaussian and non-Gaussian models. Materials and Methods:In this cross-sectional study conducted from March 2015 to March 2017, 27 participants with PD and 27 age-matched healthy control (HC) participants, all right handed, underwent MRI at 3.0 T. High-spatial-resolution diffusion images were acquired with a reduced field of view by using seven b values up to 3000 sec/mm 2 . A continuous-time random-walk (CTRW) non-Gaussian diffusion model was used to produce anomalous diffusion coefficient (D m ) and temporal (a) and spatial (b) diffusion heterogeneity indexes followed by a Gaussian diffusion model to yield an apparent diffusion coefficient (ADC). Individual or linear combinations of diffusion parameters in the SN were unilaterally and bilaterally compared between the PD and HC groups. Results:In the bilateral comparison between the PD and HC groups, differences were observed in b (0.67 6 0.06 [standard deviation] vs 0.64 6 0.04, respectively; P = .016), ADC (0.48 mm 2 /msec 6 0.08 vs 0.53 mm 2 /msec 6 0.06, respectively; P = .03), and the combination of CTRW parameters (P = .02). In the unilateral comparison, differences were observed in all diffusion parameters on the left SN (P , .03), but not on the right (P . .20). In a receiver operating characteristic (ROC) analysis to delineate left SN abnormality in PD, the combination of D m , a, and b produced the best sensitivity (sensitivity, 0.78); the combination of D m and b produced the best specificity (specificity, 0.85); and the combination of a and b produced the largest area under the ROC curve (area under the ROC curve, 0.73). Conclusion:These results suggest that quantitative diffusion MRI is sensitive to brain tissue changes in participants with Parkinson disease and provide evidence of substantia nigra lateral asymmetry in this disease.

[Retracted] Measuring Subthalamic Nucleus Volume of Parkinson’s Patients and Evaluating Its Relationship with Clinical Scales at Pre‐ and Postdeep Brain Stimulation Treatment: A Magnetic Resonance Imaging Study

“…Histopathologic studies have shown that 50%–70% of SN neurons have undergone apoptosis by the time motor symptoms appear. Asymmetric loss of dopaminergic neurons in bilateral SN may explain the symptom asymmetry [ 5 , 36 ]. Over half of PD patients show obvious differences in UPDRS III scores between the left and right limbs.…”

“…Parkinson's disease (PD) is a common movement disorder and neurodegenerative disease [1] characterized by the loss of dopaminergic neurons [2][3][4][5] mainly in the substantia nigra (SN). Drugs and invasive treatments are the main therapeutic options for PD.…”

Reduced cerebral blood flow in an α-synuclein transgenic mouse model of Parkinson’s disease

“…Indeed, MRI studies have revealed only slight or no gray matter atrophy in early to moderate stage PD patients, 7,56 although cortical CBF was decreased. 7 Although we did not observe significant changes in brain volume, ADC, or FA between α-synuclein and control mice, we did find, as reported for patients with PD, 57 a significant reduction in the ADC value in the substantia nigra of α-synuclein mice, highlighting the selective vulnerability of this region. Together, previous reports and the current data suggest that functional changes precede overt structural changes in PD.…”

Modern Brainstem MRI Techniques for the Diagnosis of Parkinson's Disease and Parkinsonisms

“…Fractional Anisotropy (FA) in the posterior part seems to be the most discriminant feature ( 51 , 52 ). With the ADC for the whole SN, Zhong et al ( 53 ) found accuracy of 0.72, which is not sufficient in routine diagnosis. Interestingly, DTI metrics have also been used in a longitudinal approach, providing precious information on structural changes in the SN over the years ( 53 – 56 ).…”