Parametric estimation of reference signal intensity in the quantification of amyloid-beta deposition: an 18F-AV-45 study.

Background Positron emission tomography (PET) with the radiotracer florbetapir (18F-AV-45) allows the pathophysiology of Alzheimer's disease (AD) to be tracked in vivo. The semi-quantification of amyloid-beta (Aβ) has been extensively evaluated with the standardized uptake value ratio (SUVR) but is susceptible to disturbance from the candidate reference region and the partial volume effect (PVE). In the present study, we applied the parametric estimation of reference signal intensity (PERSI) method to 18F-AV-45 PET images for intensity normalization. Methods We enrolled 479 people with 18F-AV-45 images from the Alzheimer's Disease Neuroimaging Initiative database: 261 healthy controls (HCs), 102 patients with mild cognitive impairment (MCI), and 116 AD patients. We used white matter post-processed by PERSI (PERSI-WM) as the reference region and compared our proposed method with the traditional method for semi-quantification. SUVRs were calculated for eight regions of interest: the frontal lobe, the parietal lobe, the temporal lobe, the occipital lobe, the anterior cingulate cortex, the posterior cingulate cortex, the precuneus, and the global cortex. The SUVRs derived from PERSI-WM and other reference regions were evaluated by effect size and receiver-operator characteristic curve analyses. Results The SUVRs derived from PERSI-WM showed significantly higher trace retention in the frontal, parietal, temporal, and occipital lobes, as well as in the anterior cingulate, posterior cingulate, precuneus, and global cortex in the AD Aβ-positive (+) group (mean: +43.3%±5.4%, P<0.01) and MCI Aβ+ group (mean: +29.6%±5.3%, P<0.01). For the global cortex, PERSI-WM had the greatest Cohen's d effect size compared with the HC Aβ-negative (-) group (AD Aβ+ and MCI Aβ+: 3.02, AD Aβ+: 3.56, MCI Aβ+: 2.34), and the highest area under the curve (AUC) between the HC Aβ- and AD Aβ+ groups (AUC: 0.983, 95% confidence interval: 0.978-0.998). Conclusions PERSI-WM could mitigate the influence of PVE and improve the semi-quantification of 18F-AV-45 images; therefore, it could be used for large-scale clinical application in the nuclear medicine domain.