title: Effects of acute levodopa challenge on resting cerebral blood flow in Parkinson's Disease patients assessed using pseudo-continuous arterial spin labeling.
abstract: Introduction. Levodopa is the gold-standard for treatment of Parkinson's disease (PD) related motor symptoms. In this study, we used pseudo-continuous arterial spin labeling (pCASL) to quantify changes in cerebral blood flow (CBF) after acute oral administration of levodopa in PD patients. Materials and Methods. Thirteen patients (3 females, age 66.2 ± 8.7 years) with moderately advanced PD (Hoehn and Yahr stage >2 (median 2.5), disease duration >3 years) were scanned on a 3T Siemens MR scanner before and after oral levodopa administration. Statistical parametric mapping was used to detect drug-induced changes in CBF and its correlation to clinical severity scales. Images were normalized and flipped in order to examine effects on the more affected (left) and less affected (right) cerebral hemispheres across the cohort. Results. Levodopa did not change global CBF but increased regional CBF in dorsal midbrain, precuneus/cuneus, more affected inferior frontal pars opercularis and triangularis, bilateral pre- and postcentral gyri, more affected inferior parietal areas, as well as less affected putamen/globus pallidus by 27-74% (p < 0.05, FWE corrected for multiple comparisons). CBF change was negatively correlated with improvement in bradykinesia UPDRS-III subscore in the more affected precentral gyrus, and total predrug UPDRS-III score in the mid-cingulate region. Drug-induced CBF change in a widespread network of regions including parietal and postcentral areas was also negatively correlated with the predrug rigidity UPDRS-III subscore. Conclusion. These findings are in line with prior reports of abnormal activity in the nigrostriatal pathway of PD patients and demonstrate the feasibility of pCASL as a neuroimaging tool for investigating in vivo physiological effects of acute drug administration in PD.
authors.affiliation: Department of Radiology, Feinberg School of Medicine, Northwestern University , Chicago, IL , USA.
authors.forename: Yufen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California , San Francisco, CA , USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Pressman
authors.affiliation: Department of Neurology, Feinberg School of Medicine, Northwestern University , Chicago, IL , USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Simuni
authors.affiliation: Department of Radiology, Feinberg School of Medicine, Northwestern University , Chicago, IL , USA.
authors.forename: Todd B
authors.initials: TB
authors.lastname: Parrish
authors.affiliation: Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Medicine, Advocate Lutheran General Hospital, Park Ridge, IL, USA; Department of Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Gitelman
keywords: Arterial spin labeling; Cerebral blood flow; Levodopa; Parkinson’s disease; Pharmacological MRI