Patlak analysis of striatal dopamine synthesis capacity in earlier and later-onset psychotic illnesses

Abstract

Objectives: Patlak analysis of striatal dopamine synthesis capacity in earlier and later-onset psychotic illnesses with 18F-DOPA brain PET/MR Introduction: The majority of studies on schizophrenia or related psychotic disorders have been focused on younger patients (<30 years), coined as “earlier-onset” psychosis (EOP). However, there is evidence that “later-onset” (>30 years) psychosis (LOP) also constitutes a significant proportion of the disorder. EOP patients were found to have elevated presynaptic striatal dopamine synthesis capacity (DSC), as documented by 18F-labeled 6-fluoro-L-DOPA (18F-DOPA) PET. In this study, we aim to evaluate whether DSC is also increased in LOP patients by using Patlak analysis on dynamic 18F-DOPA brain modeling with PET/MR. Methods: 53 Chinese subjects, 11 EOP patients with 7 age-matched controls (age<=30 years, mean age=23.0±3.6 vs 22.0±2.2 years) and 24 LOP patients with 11 age-matched controls (age>30 years, mean age=48.5±8.0 vs 54.2±6.3 years), were recruited by the psychiatrists for 18F-DOPA brain PET/MR. The diagnosis of psychotic illness was based on the criteria specified by DSM-V and ICD-10. 18F-DOPA brain PET/MR imaging began at 30 minutes post injection for a 30-minute list-mode dynamic PET acquisition (3D OSEM, 21 subsets, 5 iterations, 256[asterisk]256 matrix, zoom factor 2.0, 3.0mm-Gaussian filter). The regions of interest (ROIs) of putamen, caudate, occipital lobe and cerebellum were drawn on simultaneously acquired 3-Tesla MRI (3D SAGITTAL T1) in 3 orthogonal planes, which were then fused with the corresponding 18F-DOPA PET images to generate the time-activity curve (TAC) for each ROI (MIM software 6.6). Patlak parametric analysis with occipital lobe as the reference region was performed to calculate the 18F-DOPA influx index (K) of striatal DSC for both EOP and LOP patients. Another parameter, striatal-to-cerebellum (SC) ratio at 55-60 minutes, was also calculated to evaluate its potential to measure DSC. Result: For the LOP patients and their controls, there was statistically significant difference in the K values of the putamen (0.0081±0.0010 vs 0.0070±0.0006, P=0.003, AUC=0.831) and caudate (0.0072±0.0012 vs 0.0063±0.0007, P=0.034, AUC=0.761). For the EOP patients, however, statistically significant difference in the K values was only found in the putamen (0.0083±0.0012 vs 0.0069±0.0008, P=0.013, AUC=0.877) but not in the caudate (0.0072±0.0016 vs 0.0064±0.0010, P=0.268, AUC=0.721). Moreover, there was no statistically significant difference in any of the SC ratios for both the EOP and LOP patients when compared with the respective normal controls. Conclusions: Dynamic 18F-DOPA brain PET/MR imaging with 30-minute list mode acquisition could be used to assess the striatal dopamine synthesis capacity by Patlak analysis. The 18F-DOPA influx constant K is a quantitative index capable of identifying the psychotic patients from the age-matched controls. Up-regulation of striatal DSC is not just classically associated with the EOP patients but also with the LOP patients. A larger study to evaluate any pathophysiology difference between the 2 groups of patients is warranted.