Abstract
PURPOSE: To investigate the physiological influence of tissue perfusion and permeability on O-(2-[(18)F]-fluoroethyl)-L-tyrosine ([(18)F]FET) uptake in gliomas by simultaneous MRI dynamic contrast enhanced (DCE) perfusion imaging and the impact of vascular contributions on diagnostic accuracy. METHODS: Dynamic [(18)F]FET PET/MRI scans from 50 patients with glioma WHO grade 2-4 were analysed. In each patient multiple subvolumes were delineated to account for intra-patient heterogeneity. Associations of 20-40 min. [(18)F]FET tumour-to-background ratio (TBR(med)) with median blood volume (CBV), blood flow (F), and permeability (Ki) within 134 lesion subvolumes were investigated in linear mixed models. Also, associations with initial area under curve (iAUC(120)), time to peak (TTP) and slope (Slope(20 - 40)) from time activity curve were investigated. The influence of adjusting TBR(med) for microvascular physiological parameters on the diagnostic accuracy for tumour recurrences was assessed in an independent dataset (n = 61 lesions from 48 patients). RESULTS: CBV, F and Ki individually accounted for 42%, 36% and 26%, respectively, of the overall variance in TBR(med). DCE metrics combined accounted for 49% of the total variance and for 65% of the regional variance in TBR(med). All DCE metrics were associated positively with iAUC(120) and negatively with both Slope(20 - 40) and TTP (p < 0.001 for all). Adjusting TBR(med) for microvascular effects lowered TBR by 24% on average and reduced the diagnostic accuracy (ROC AUC) from 0.90 to 0.77 in the test dataset. CONCLUSION: Microvascular properties may contribute to a considerable fraction of the clinical [(18)F]FET measures in patients with gliomas, and contribute positively to diagnostic performance of [(18)F]FET PET imaging.