HAI Book 2025 - Flipbook - Page 434
Chen, Charles
110
Two distinct sources of 18F-MK-6240 off-target signal identified by
individualized head modeling and PET kinetics
Charles Chen1, Jessie Fanglu Fu1, Oula Puonti1, Emma Thibault2, Keith Johnson2, Julie Price1
1
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, US
Gordon Center for Medical Imaging, Massachusetts General Hospital, Boston, MA, US
2
Background: 18F-MK-6240 PET is a powerful tool for visualizing neurofibrillary tangles (NFTs) in aging and
Alzheimer disease (AD). However, 18F-MK-6240 PET off-target signal (OTS) in the meninges can spill into brain
parenchyma. Partial volume correction of OTS spill-in is challenging due to the thin structure of the meninges;
prior approaches have used the FreeSurfer-defined skull mask to approximate the meningeal OTS, as this is a
readily available parcellation. Herein, we describe an approach that uses individualized head modeling and PET
kinetics to more precisely identify meningeal OTS.
Methods: We applied the Complete Head Anatomy Reconstruction Method (CHARM, Puonti et al. NeuroImage
2020) to segment the whole head from T1-weighted (T1w), T2w, and T2w FLAIR MRI in our test-retest dataset of
dynamic (0-120 minutes) 18F-MK-6240 PET/MRI in seven older adults (one diagnosed with AD; Table 1). We use the
T1w/T2w ratio to separate meninges from CSF. This enables us to generate time-activity curves (TACs) for
cerebral and cerebellar cortices, CSF, meninges, and skull (cortical and cancellous bone), and compare these to
TACs generated using FreeSurfer-defined skull. The Diebold-Mariano test was used to determine which
CHARM+T1w/T2w-defined TAC (meningeal or cortical bone) is a more accurate predictor of FreeSurfer-defined
skull TAC.
Results: FreeSurfer-defined skull overlaps inconsistently with CHARM+T1w/T2w-defined meninges, especially
near the tentorium (Fig.1). CHARM+T1w/T2w-defined meningeal and bone TACs show differing kinetics: the
meninges/bone show high/low initial uptake that increases/decreases over time (Fig.2A). FreeSurfer-defined
skull TAC is more similar to the CHARM+T1w/T2w-defined cortical bone than meningeal TAC (Diebold-Mariano pvalues
