Impact of florbetaben acquisition timing on continuous and dichotomous measures of amyloid burden: implications for real‐world amyloid PET interpretation

Abstract

AbstractBackgroundThe magnitude of Standardized Uptake Value Ratios (SUVRs) and Centiloid (CL) values increase at later acquisition windows for Florbetaben (FBB). As amyloid PET is anticipated to be utilized for treatment decisions with anti‐amyloid therapeutics (van Dyck, 2022), it is important to understand acquisition factors that influence PET quantification.MethodWe analyzed 120 FBB scans from the Stanford Alzheimer’s Disease Research Center with 5‐minute frame data spanning 70‐110 minutes post‐injection (Table 1). Frame data were motion corrected, summed into 70‐90 and 90‐110‐minute files, and processed through an MRI‐Free pipeline. A global cortical target region and whole cerebellum reference region from the GAAIN atlas were used to create SUVRs and CLs (Klunk, 2014). SUVRs and CLs computed across the two acquisition windows were compared using linear regression to understand the effects of timing acquisition on magnitude. Gaussian Mixture Models (GMM) were used to convert SUVRs to a probability scale separately for 70‐90 and 90‐110 datasets. 10,000 bootstrapped mixed timing datasets were created by randomly selecting either 70‐90 or 90‐110 SUVRs for a given participant, which was then used to understand the impact of GMM‐based classification into A‐ and A+ groups when acquisition time varies within dataset.ResultCLs were systematically lower during the earlier acquisition window (2.01 CL for the CL<10 group, ΔCL range = ‐8.83,9.16; 2.89 CL for the 10‐25 group, ΔCL range = ‐2.18,9.33; 3.62 CL for the 25‐50 group, ΔCL range = ‐0.04,11.34; and 10.94 for the >50 group, ΔCL range = 1.81,26.98) (Fig. 1). GMM classification into A‐ and A+ groups was consistent across the two acquisition windows and in the mixed timing datasets (Table 2).ConclusionGMM is a robust quantitative method that can be used to characterize amyloid PET scans into A‐ and A+ groups when acquisition time varies. However, given the inconsistent impact of acquisition time on CL magnitude, comparison of CL values before and after anti‐amyloid treatments will require adjustment for scan acquisition time. Future work is needed to establish methods that can measure amyloid PET change when acquisition times vary within an individual patient. This is especially important for evaluating the efficacy of currently approved anti‐amyloid therapeutic approaches.