Optimising Quantitative Susceptibility Mapping for Application In Mild Cognitive Impairment and Early Alzheimer’s Disease

Abstract

Background: Iron plays an essential role in the brain. In a healthy brain, iron levels increase with aging. Previous studies highlighted the potential link between iron deposition and the pathology of Alzheimer's Disease (AD). Quantitative Susceptibility Mapping (QSM), a Magnetic Resonance Imaging (MRI) method, shows some promising results to measure iron in the brain. This study implemented three QSM toolboxes, compared them, and applied two QSM methods to clinical groups with cognitive impairment (CI) and healthy age-matched controls. Methods: Fifty-one participants enrolled in the study included eleven with AD, twenty-two with mild cognitive impairment (MCI), and seventeen healthy controls (CN). The MEDI toolbox and QSMxT toolbox with parameters were used to reconstruct the QSM map. The inverse transform was computed to register a standard space template into the native space of the QSM map for each individual, and pre-defined atlas regions of interest (ROI) results were extracted for comparison. The t-test was used to investigate the relationship between regional susceptibility and group difference (CI versus CN and APOE e4 carrier versus non-carrier). Person coefficient correlation was used to examine the relationship between regional susceptibility and cognitive score. The following was investigated 1) if susceptibility values between the cognitively impaired group (MCI and AD) and healthy controls varied brain regions 2) how regional susceptibility varied between the left and right hemisphere 3) how regional susceptibility varied depending on genetic risk factor for AD (APOE e4 carrier) 4) Association with regional susceptibility and global cognitive score using both different QSM reconstruction methods. Results: Out of all ROIs investigated, the hippocampus was the only region where group-related susceptibility difference was found using both QSM methods. Considering inter-hemispheric difference, significantly higher susceptibility was found in the right pallidum than the left pallidum. A negative correlation was found between susceptibility in the putamen and the cognitive score. The APOE e4 group tends to have higher susceptibility in the putamen. Conclusion: Hippocampus susceptibility may be considered as a biomarker to diagnose Alzheimer’s Disease.