HAI Book 2025 - Flipbook - Page 371
McLachlan, Max
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FDG reference region selection using PiB amyloid status-guided
iterative normalization in a Down syndrome cohort
Max McLachlan1, David Keator2, Julie Price3, Dana Tudorascu4, Charles Laymon4, Annie
Cohen4, Patrick Lao5, Ben Handen4, Tim Fryer6, Beau Ances7, Shahid Zaman6, Elizabeth Head2,
Mark Mapstone2, Brecca Bettcher1, Jose Guerrero Gonzalez1, Lisette LeMerise1, Andrew
McVea1, Alexandra DiFillipo1, Matthew Zammit1, Sigan Hartley1, Bradley Christian1
1
University of Wisconsin - Madison, Madison, WI, US
University of California, Irvine, Irvine, CA, US
3
MGH Martinos Center, Harvard, Boston, MA, US
4
University of Pittsburgh, Pittsburgh, PA, US
5
Columbia University Irving Medical Center, New York, NY, US
6
University of Cambridge, Cambridge, GB
7
Washington University in St. Louis, St. Louis, MO, US
2
Background: Individuals with Down syndrome (DS) carry a genetic risk for Alzheimer9s Disease, resulting in an
accelerated AT[N] timeline. The heterogeneity of glucose metabolism and definition of a suitable FDG reference
region has not been fully characterized in DS. In the neurotypical population, many FDG PET studies implement
whole brain (WB) intensity normalization, despite evidence for underestimation of metabolic change. Yakushev et
al. (2008) proposed a data-driven method for reference region selection by leveraging false-positive
hypermetabolism generated from WB normalization. The goal of this work is to investigate the data-driven
method in a DS cohort, using amyloid status as a general predictor for metabolism.
Methods: Cross-sectional FDG scans were acquired in a cohort of 92 participants with DS. Each participant
completed cognitive consensus testing at time of FDG scan and amyloid (A´) PiB PET imaging ~1.5 years prior.
FDG scans were realigned, summed 30-60min, smoothed by 6mm, spatially normalized to a DS-specific template,
and intensity-normalized using WB average. Participants were grouped by A´ status (Table 1). Voxel-level
statistics were performed in SPM12, using Welch9s t-test as the statistical comparison between groups. The Tmap for the A´+ > A´- contrast (hypermetabolism) was thresholded to p
