Quantitative analysis of 6,150 real-world amyloid Positron Emission Tomography (PET) scans from the Imaging Dementia–Evidence for Amyloid Scanning (IDEAS) study

Abstract

BackgroundAmyloid-PET had been widely used and validated in research settings, using highly selected samples, harmonized acquisition protocols, co-registration with MRI, and central interpretation by highly experienced experts. In contrast, in clinical settings, more heterogeneous acquisition, reconstruction, and interpretation may compromise the accuracy of the imaging. We quantitatively analyzed real-world amyloid-PET scans to assess their validity.MethodIDEAS acquired 18,295 amyloid PET scans at 343 PET facilities in patients with MCI or dementia using 18F-florbetapir, 18F-florbetaben, or 18F-flutemetamol. Scans were visually interpreted at each site as either negative or positive for cortical tracer retention. Scans from consenting patients were archived. As of December 1, 2021, amyloid-PET scans from 6,263 unique participants were available for analysis. Exclusion for lack of valid images or clinical data and failure of quality checks resulted in 6,150 (98.2%) valid scans. We analyzed the scans using a recently validated PET-only processing pipeline designed to process heterogeneous amyloid-PET scans (Iaccarino et al, 2022) and quantified cortical uptake in Centiloid (CL) units. A previously established neuropathology-based threshold of 24.4 CL was used to define amyloid-PET positivity independent of visual reads.ResultMean CL was higher in dementia (mean±SD = 53±51) than in MCI (40±48) (mean difference: 13; 95%CI: 10-15). Mean CL of visually negative scans (3±27) was very close to 0, as expected for patients without amyloid accumulation, and significantly lower than visually positive scans (72±41) (mean difference: 69; 95%CI: 67-70) (table 1). High concordance was found between local visual reads and CL-based positivity (86.5%, Cohen’s κ=0.72, figure 1). CL exhibited a bimodal distribution, with most scans clearly positive or negative, and a minority of visual-quantitative discordant scans surrounding the positivity threshold (figure 2). CL negatively correlated with MMSE (r=-0.19, p<.001, figure 3). CL further correlated with the level of confidence in the diagnosis of Alzheimer’s Disease (AD), as was indicated by clinicians before the performance of PET (r=0.13, p<.001, figure 4).ConclusionA large heterogeneous dataset of real-world amyloid-PET scans analyzed quantitatively, shows high concordance with visual reads, and expected relationships with clinical and neuropsychological measures of AD.