Abstract
ABSTRACT
High‐resolution quantitative susceptibility mapping (QSM) combined with susceptibility source decomposition provides a powerful approach for investigating the magnetic susceptibility alterations in Alzheimer's disease (AD). In this study, ex vivo three‐dimensional multi‐echo gradient‐echo (mGRE) images of 5xFAD and mouse brains were acquired at 30 isotropic resolution using a 9.4 T MRI scanner. QSM was reconstructed and decomposed into diamagnetic component susceptibility (DCS) and paramagnetic component susceptibility (PCS). Individual amyloid‐beta () plaques were automatically detected and their susceptibility properties were quantitatively characterized. DCS and PCS revealed subvoxel mixtures of diamagnetic and paramagnetic components. Compared with conventional QSM, DCS exhibited clearer plaque visualization and higher plaque detection sensitivity. Histological analysis revealed the coexistence of aggregates and ferritin in both mouse models, with most plaques measuring less than 70 in diameter. To assess the impact of spatial resolution on plaque visualization and susceptibility quantification, the acquired k‐space data were downsampled to isotropic resolutions of 45, 60, and 90 m. As spatial resolution became coarser, plaque visibility degraded progressively, resulting in reductions in both the number of detectable plaques and the estimated plaque burden. Whole‐cortex plaque loading decreased from 8.9% at 30 m to 3.1% at 90 m in 5xFAD and from 6.5% to 2.6% in mice. In both models, detected plaques exhibited predominantly diamagnetic susceptibility, with the diamagnetic component accounting for approximately 80% of the total absolute susceptibility. These findings demonstrate that high‐resolution susceptibility mapping combined with source decomposition enables plaque‐level characterization of diamagnetic and paramagnetic contributions and provides complementary biomarkers for assessing pathology and associated iron dysregulation in preclinical mouse models of AD.