TY - JOUR T1 - Striatal acetylcholine-dopamine imbalance in Parkinson's disease: in vivo neuroimaging study with dual-tracer PET and dopaminergic PET-informed correlational tractography JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.121.261939 SP - jnumed.121.261939 AU - Carlos Sanchez-Catasus AU - Nicolaas I. Bohnen AU - Nicholas D'Cruz AU - Martijn Muller Y1 - 2021/07/01 UR - http://jnm.snmjournals.org/content/early/2021/07/16/jnumed.121.261939.abstract N2 - Previous studies of animal models of Parkinson's disease (PD) suggest an imbalance between striatal acetylcholine (ACh) and dopamine (DA), although other studies have questioned this. To our knowledge, there are no previous in vivo neuroimaging studies examining striatal ACh-DA imbalance in PD patients. Using cholinergic and dopaminergic PET (18F-FEOBV and 11C-DTBZ, respectively) and correlational tractography, our aim was to investigate the ACh-DA interaction at two levels of dopaminergic loss in PD subjects: integrity loss of the nigrostriatal dopaminergic white matter tract; and loss at the presynaptic-terminal level. Methods: The study involved 45 subjects with mild to moderate PD (36 men, 9 women; mean age, 66.3 ± 6.3 years, disease duration, 5.8 ± 3.6; Hoehn and Yahr stage, 2.2 ± 0.6) and 15 control subjects (9 men, 6 women; mean age, 69.1 ± 8.6 years). PET imaging was performed using standard protocols. We first estimated the integrity of the dopaminergic nigrostriatal white matter tracts in PD subjects by incorporating molecular information from striatal 11C-DTBZ PET into the fiber tracking process using correlational tractography (based on quantitative anisotropy, QA; a measure of tract integrity). Subsequently, we used voxel-based correlation to test the association of the mean QA of the nigrostriatal tract of each cerebral hemisphere with striatal 18F-FEOBV distribution volume ratio (DVR) in PD subjects. The same analysis was performed for 11C-DTBZ DVR in 12 striatal subregions (presynaptic-terminal level). Results: Unlike 11C-DTBZ DVR in striatal subregions, the mean QA of the nigrostriatal tract of the most affected (MA) hemisphere showed a negative correlation with a striatal cluster of 18F-FEOBV DVR in PD subjects (p corrected= 0.039). We also found that the mean 18F-FEOBV DVR within this cluster was higher in the PD group compared to the control group (P = 0.01). Cross-validation analyses confirmed these findings. We also found an increase of bradykinesia ratings associated with increased ACh-DA imbalance in the MA hemisphere (r=0.41, P = 0.006). Conclusion: Our results provide evidence for the existence of striatal ACh-DA imbalance in early PD and may provide an avenue for testing in vivo effects of therapeutic strategies aimed at restoring striatal ACh-DA imbalance in PD. ER -