Patlak analysis of striatal dopamine synthesis capacity in earlier and later-onset psychotic illnesses with ¹⁸F-DOPA brain PET/MR imaging

Abstract

Dysregulation of presynaptic dopamine synthesis capacity (DSC) was reported in “earlier-onset” psychotic illnesses (EOP) on younger patient populations (≤30 years). Nonetheless, lines of evidence indicated “later-onset” (>30 years) psychotic illnesses (LOP) contributing to a significant part of the disorder. In this study, we aimed to assess presynaptic DSC in EOP and LOP groups in a Hong Kong Chinese population using 18F-labeled 6-fluoro-L-DOPA (18F-DOPA). We also aimed to evaluate whether presynaptic DSC was also increased in LOP patients as in EOP patients by using Patlak graphical analysis on dynamic 18F-DOPA PET/MR brain imaging. Finally, the diagnostic parameters defined as influx index K and conventional substriatal-to-cerebellum ratio (SC ratio) would be evaluated for the discriminating ability in separating patients with psychosis from healthy controls using PET/MR imaging modality.

53 Chinese participants, including 11 EOP patients and 7 young controls (age≤30 years, mean age=23.0±3.6 vs 22.0±2.2 years); 24 patients with LOP and 11 old controls (age>30 years, mean age=48.5±8.0 vs 54.2±6.3 years), were referred by the psychiatrists for PET/MR 18F-DOPA brain imaging. The psychotic disease was diagnosed according to the clinical symptom-based criteria from DSM-V and ICD-10. Dynamic 18F-DOPA PET/MR brain imaging began at 30 minutes post injection for a 30-minutes list mode PET acquisition (3D OSEM, 21 subsets, 5 iterations, 256*256 matrix, zoom factor 2.0, 3.0mm-Gaussian filter). Regions of interest (ROIs) including putamen, caudate, occipital lobe and cerebellum were drawn in 3 orthogonal planes on hybrid fusion of PET/MR images generated from simultaneously acquired 3-Tesla MR sequence (3D SAGITTAL T1) and PET acquisition, which created the time-activity curve (TAC) in each ROI (MIM software 6.6). Patlak graphical analysis with occipital lobe as input function was performed to quantify the striatal DSC as index K for both EOP and LOP patients. Another DSC index parameter: SC ratio at 55-60 minutes, was also calculated to index DSC.

There were statistically significant differences in the K values of both the putamen (0.0081±0.0010 vs 0.0070±0.0006, p=0.003, Cohen’s d = 1.33, AUC=0.831) and caudate (0.0072±0.0012 vs 0.0063±0.0007, p=0.034, Cohen’s d = 0.92, AUC=0.761) between the LOP patients and old controls. In contrast, statistically significant difference was only found in the K values of putamen (0.0083±0.0012 vs 0.0069±0.0008, p=0.013, Cohen’s d = 1.37, AUC=0.877) between the EOP patients and young controls, but not in the K values of the caudate (0.0072±0.0016 vs 0.0064±0.0010, p=0.268, Cohen’s d = 0.60, AUC=0.721). Furthermore, there were no statistically significant differences in any of the SC ratios for both the EOP and LOP patients when compared with the age-matched controls.

In conclusion, dynamic 18F-DOPA brain PET/MR imaging with 30-minute list mode PET acquisition was sensitive to assess the striatal DSC between the psychotic patients and the healthy controls by influx index K, which is an imaging bio-parameter showing a high diagnostic accuracy when compared with the conventional SC ratio approach. The elevation in the striatal DSC that is classically associated with the EOP could also be related to LOP patients, which may be the underlying cause of the pathogenesis of psychosis.