Comparison of MRI-based and PET-based image pre-processing for quantification of C-PBB3 uptake in human brain.

Purpose: Quantification of tau load using C-PBB3-PET has the potential to improve diagnosis of neurodegenerative diseases. Although MRI-based pre-processing is used as a reference method, not all patients have MRI. The feasibility of a PET-based pre-processing for the quantification of C-PBB3 tracer was evaluated and compared with the MRI-based method.

Materials And Methods: Fourteen patients with decreased recent memory were examined with C-PBB3-PET and MRI. The PET scans were visually assessed and rated as either PBB3(+) or PBB3(-). The image processing based on the PET-based method was validated against the MRI-based approach. The regional uptakes were quantified using the Mesial-temporal/Temporoparietal/Rest of neocortex (MeTeR) regions. SUVR values were calculated by normalizing to the cerebellar reference region to compare both methods within the patient groups.

Results: Significant correlations were observed between the SUVRs of the MRI-based and the PET-based methods in the MeTeR regions (r=0.91; r=0.98; r=0.96; p<0.0001). However, the Bland-Altman plot showed a significant bias between both methods in the subcortical Me region (bias: -0.041; 95% CI: -0.061 to -0.024; p=0.003). As in the MRI-based method, the C-PBB3 uptake obtained with the PET-based method was higher for the PBB3(+) group in each of the cortical regions and for the whole brain than for the PBB3(-) group (PET-based: 1.11 vs. 0.96; Cliff's Delta (d)=0.68; p=0.04; MRI-based: 1.11 vs. 0.97; d=0.70; p=0.03). To differentiate between positive and negative scans, Youden's index estimated the best cut-off of 0.99 from the ROC curve with good accuracy (AUC: 0.88±0.10; 95% CI: 0.67-1.00) and the same sensitivity (83%) and specificity (88%) for both methods.

Conclusion: The PET-based pre-processing method developed to quantify the tau burden with C-PBB3 provided comparable SUVR values and effect sizes as the MRI-based reference method. Furthermore, both methods have a comparable discrimination accuracy between PBB3(+) and PBB3(-) groups as assessed by visual rating. Therefore, the presented PET-based method can be used for clinical diagnosis if no MRI image is available.