Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET

Abstract

Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [¹¹C]UCB-J PET. Methods: Participants included 31 older adults with AD and 16 with normal cognition. The distribution volume ratio (DVR) using simplified reference tissue model 2 was compared with SUVR at short scan windows using a whole-cerebellum reference region. Results: Synaptic density was reduced in AD participants using DVR or SUVR. SUVR using later scan windows (60-90 or 70-90 min) was minimally biased, with the strongest correlation with DVR. Effect sizes using SUVR at these late time windows were minimally reduced compared with effect sizes with DVR. Conclusion: A simplified tissue-to-reference method may be useful for multicenter and longitudinal studies seeking to measure synaptic density in AD.

Keywords: Alzheimer disease; PET; SUVR; [11C]UCB-J; synaptic density.

Graphical abstract

FIGURE 1.

Correlations between DVR and SUVR at 30–60 min (A), 60–90 min (B), 30–50 min (C), and 70–90 min (D) for all participants and for CN and AD groups in all regions of interest.

FIGURE 2.

Correlations between effect sizes (Cohen d) in all regions of interest as measured by DVR and SUVR at 30–60 min (A), 60–90 min (B), 30–50 min (C), and 70–90 min (D).

FIGURE 3.

Effect size (Cohen d) maps of DVR (A), SUVR at 30–50 min (B), and SUVR at 70–90 min (C) for comparison between CN and AD groups. Effect size statistics are displayed for all analyzed regions and overlaid on MNI template T1-weighted MR images.

FIGURE 4.

Simulation of group difference in mean SUVR (A) and Cohen d (B) for various perfusion changes.