Enlarged Perivascular Spaces Linked to Disease Duration and Motor Severity in Parkinson’s Disease
Poster No:
216
Submission Type:
Abstract Submission
Authors:
Dimuthu Hemachandra1, Kyan Younes1, Joseph Winer1, Yann Cobbigo5, Howard J. Rosen5, Christina B. Young1, Alena M. Smith1, Tilman Schulte3,4, Kathleen L. Poston1,2, Eva M. Müller-Oehring1,3
Institutions:
1Dept. of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA; 2Dept. of Neurosurgery, Stanford University School of Medicine, Stanford, CA; 3Biosciences Division, SRI International, Menlo Park, CA; 4Dept. of Psychology, Palo Alto University, Palo Alto, CA; 5Dept. of Neurology, University of California San Francisco, San Francisco, CA
First Author:
Co-Author(s):
Introduction:
Perivascular spaces (PVS) are fluid-filled channels surrounding brain vessels, which play a crucial part in the brain waste clearance system [Fig.1A]. Enlarged PVS (ePVS) are visible in magnetic resonance imaging (MRI) and could link to aging and neurodegeneration (Ramirez et al., 2016). ePVS may reflect impaired interstitial fluid drainage and clearance of metabolic waste, including α-synuclein, which could contribute to pathology in Parkinson's disease (PD) (Lin et al., 2022). Despite their significance, the relationship between ePVS and motor symptoms in PD is not yet well understood. We developed an automated pipeline utilizing MRI images to quantify the burden of ePVS, enabling a more comprehensive investigation of the contribution of ePVS to PD motor symptom severity. Studying ePVS in PD could provide insights into disease mechanisms and potential biomarkers for disease progression.
Methods:
Forty-one mild/moderate PD and 36 healthy control participants underwent structural MRI scans, comprehensive motor assessments using the MDS-UPDRS (part II, III performed off dopaminergic medications). Preprocessed 3 Tesla GE T1- and T2-weighted images were combined to enhance PVS contrast (Younes et al., 2023). An unsupervised learning algorithm was used to generate a subject specific probability map of presence of ventricular signal (likely related to the flow of CSF) within white matter (WM). By applying a Frangi filter (Frangi et al., 1998) to these maps, we generated vesselness maps for PVS delineation. A morphological constraint algorithm was used to threshold these maps by size, linearity and location and created a labeled map of potential ePVS clusters as described in (Boespflug et al., 2018) [Fig.1B]. Quality control of these clusters were performed by a single trained rater. The total ePVS burden in WM was calculated as the total ePVS volume divided by the total WM volume. Subsequently, T1w images were registered to the MNI 1 mm space using both rigid and nonlinear registration, and the same transformation was applied to transfer cluster label maps to MNI space. An atlas comprising 20 fiber bundles (JHU DTI-based white matter atlases) was utilized as a mask to quantify the ePVS clusters within each fiber bundle, which we referred to as bundle ePVS burden. The relationship between ePVS burden and disease-associated symptoms was analyzed using a multiple linear regression model accounting for age variability and sex.
Results:
PD participants exhibited higher values and a larger standard deviation compared to healthy controls in both total and bundle ePVS burden measures; however, their means did not differ statistically [Figure2A]. Within the PD group, ePVS ratio correlated with both years since diagnosis (r=0.53, p=.0009, p*<.05) and motor symptom severity (MDS-UPDRS-II, III), particularly bradykinesia in the off-medication state (r=0.47, p<.0076, p*<.05) [Figure2B]. The ePVS ratio did not show a significant relationship with age (r=0.13, p=.46). Furthermore, the bundle ePVS burden of inferior fronto-occipital fasciculus (IFO) exhibited the highest correlation with the off-medication MDS-UPDRS-III score (r=0.52, p<.003, p*=.06). This bundle also showed a significantly elevated ePVS burden (p=.017) compared to the left hemisphere [Fig.2C].
Conclusions:
Our findings reveal a significant correlation between the ePVS ratio and PD-specific motor severity scores in PD participants. The absence of correlation with general aging suggests that ePVS may serve as a specific marker for motor dysfunctions associated with PD. Previous studies utilizing diffusion MRI have demonstrated decreased white matter integrity in the IFO in PD (Yang et al., 2023). Our observation of elevated ePVS burden within IFO, along with its correlation with motor symptom severity, may connect these findings to dysfunctions in the waste clearance system. Further research is warranted to investigate the potential of ePVS as a biomarker for disease progression PD.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Classification and Predictive Modeling
Motor Behavior:
Motor Behavior Other
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 2
Keywords:
Aging
Astrocyte
Cerebro Spinal Fluid (CSF)
DISORDERS
Machine Learning
Movement Disorder
MRI
Neurological
STRUCTURAL MRI
White Matter
1|2Indicates the priority used for review
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Provide references using APA citation style.
Frangi, A. F., Niessen, W. J., Vincken, K. L., & Viergever, M. A. (1998). Multiscale vessel enhancement filtering. In Medical Image Computing and Computer-Assisted Intervention — MICCAI’98 (pp. 130–137). 1st International Conference on Medical Image Computing and Computer-Assisted Intervention, MICCAI 1998. Springer Berlin Heidelberg.
Lin, F., Yang, B., Chen, Y., Zhao, W., Li, B., & Jia, W. (2022). Enlarged perivascular spaces are linked to freezing of gait in Parkinson’s disease. Frontiers in Neurology, 13, 985294.
Ramirez, J., Berezuk, C., McNeely, A. A., Gao, F., McLaurin, J., & Black, S. E. (2016). Imaging the perivascular space as a potential biomarker of neurovascular and neurodegenerative diseases. Cellular and Molecular Neurobiology, 36(2), 289–299.
Yang, K., Wu, Z., Long, J., Li, W., Wang, X., Hu, N., Zhao, X., & Sun, T. (2023). White matter changes in Parkinson’s disease. NPJ Parkinson’s Disease, 9(1), 150.
Younes, K., Cobbigo, Y., Tsuie, T., Wang, E., Wolf, A., Joie, R. L., Soleimani-Meigooni, D. N., Asken, B., Tosun, D., Kramer, J. H., Ferguson, A. R., Miller, B. L., Mormino, E. C., Schwartz, D., Silbert, L. C., Rabinovici, G., Rosen, H. J., & Elahi, F. M. (2023). Divergent enlarged perivascular spaces volumes in early versus late age-of-onset Alzheimer’s disease. https://doi.org/10.1101/2023.08.01.23293514