Optimal reference region to measure longituDinal amyloid-b change with 18F-Florbetaben PET

Abstract

Accurate measurement of changes in amyloid-b (Ab) deposition over time is important in longituDinal stuDies, particularly in anti-Ab therapeutic trials. To achieve this, the optimal reference region (RR) must be selected to reduce variance of Ab PET measurements, allowing early detection of treatment efficacy. The aim of this study was to determine the RR that allows earlier detection of subtle Ab changes using 18Fflorbetaben PET. Methods: Forty-five patients with mild cognitive impairment (mean age 6 SD, 72.69 6 6.54 y; 29 men/16 women) who underwent up to 3 18F-florbetaben scans were included. Baseline scans were visually classified as high (Ab1) or low (Ab2) amyloid. Six cortical regions were quantified using a standarDized region-ofinterest atlas applied to the spatially normalized gray matter image obtained from segmentation of the baseline T1-weighted volumetric MRI. Four RRs (cerebellar gray matter [CGM], whole cerebellum [WCER], pons, and subcortical white matter [SWM]) were stuDied. The SUV ratio (SUVR) for each RR was calculated by DiviDing cortex activity by RR activity, with a composite SUVR averaged over 6 cortical regions. SUVR increase from baseline to 1 and 2 y, and percentage Ab deposition per year, were assessed across Ab1 and Ab2 groups. Results: SUVs for any RR were not significantly Different over time. Percentage Ab accumulation per year derived from composite SUVR was 0.10 6 1.72 (Ab2) and 1.36 6 1.98 (Ab1) (P 5 0.02) for CGM and 0.13 6 1.47 and 1.32 6 1.75 (P 5 0.01), respectively, for WCER. Compared with baseline, the composite SUVR increase in Ab1 scans was significantly larger than in Ab2 scans at 1 y (P 5 0.04 [CGM]; P 5 0.03 [WCER]) and 2 y (P 5 0.02 [CGM]; P 5 0.01 [WCER]) using these 2 RRs. Significant SUVR changes using the pons as the RR were detected only at 2 y (P 5 0.46 [1 y], P 5 0.001 [2 y]). SUVR using the SWM as the RR showed no significant Differences at either followup (P 5 0.39 [1 y], P 5 0.09 [2 y]). Conclusion: RR selection influences reliable early measurement of Ab changes over time. Compared with SWM and pons, which do not fulfil the RR requirements and have limited sensitivity to detect Ab changes, cerebellar RRs are recommended for 18F-florbetaben PET because they allow earlier detection of Ab accumulation.