Abstract
Accurate measurement of changes in amyloid-beta (Aβ) deposition over time is important in longitudinal studies, particularly in anti-Aβ therapeutic trials. To achieve this, the optimal reference region (RR) must be selected to reduce variance of Aβ positron emission tomography (PET) measurements, allowing early detection of treatment efficacy. The aim of this study was to determine the RR that allows earlier detection of subtle Aβ changes using 18F florbetaben (FBB) PET. Methods: Forty-five patients with mild cognitive impairment (MCI) (72.69 ± 6.54 years; 29 men/16 women) who underwent up to three FBB scans were included. Baseline scans were visually classified as high (Aβ+) or low (Aβ-) amyloid. Six cortical regions were quantified using a standardized region-of-interest atlas applied to the spatially normalized gray-matter image obtained from segmentation of the baseline T1-weighted volumetric magnetic resonance imaging (MRI). Four RRs (cerebellar gray matter (CGM), whole cerebellum (WCER), pons (PONS), and subcortical white matter (SWM)) were studied. Standardized uptake value ratio (SUVR) for each RR was calculated by dividing cortex activity by RR activity, with a composite SUVR averaged over six cortical regions. SUVR increase from baseline to 1 and 2 years, and percentage Aβ deposition per year, were assessed across Aβ+ and Aβ- groups. Results: SUVs for any RR were not significantly different over time. Percentage Aβ accumulation per year derived from composite SUVR was 0.10±1.72 (Aβ-) and 1.36±1.98 (Aβ+) (P = 0.02) for CGM and 0.13±1.47 and 1.32±1.75 (P = 0.01), respectively, for WCER. Compared with baseline, composite SUVR increase in Aβ+ scans was significantly larger than in Aβ- scans at 1 year (pCGM=0.04; pWCER=0.03) and 2 years (pCGM=0.02, pWCER=0.01) using these two RR. Significant SUVR changes using PONS as RR were detected only at 2 years (p1-yr=0.46, p2-yrs=0.001). SUVR using SWM as RR showed no significant differences at either follow-up (p1-yr=0.39, p2-yrs=0.09). Conclusion: RR selection influences reliable early measurement of Aβ changes over time. Compared with SWM and PONS which do not fulfil the RR requirements and have limited sensitivity to detect Aβ changes, cerebellar RRs are recommended for FBB PET as they allow earlier detection of Aβ accumulation.
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.