Abstract
BACKGROUND AND PURPOSE: Hippocampal magnetic susceptibility alterations may serve as early neurodegenerative biomarkers of Alzheimer's disease (AD), but subfield-level evidence in mild cognitive impairment (MCI) remains limited. This study utilizes submillimeter high-resolution quantitative susceptibility mapping (QSM) to investigate hippocampal subfield susceptibility changes in MCI. MATERIALS AND METHODS: Thirteen individuals with MCI and thirteen cognitively normal controls (NC) underwent 7T MRI scans including Magnetization-Prepared Two Rapid Acquisition Gradient Echoes (MP2RAGE) and multi-echo Gradient Echo (GRE) imaging (for QSM). Visibility of hippocampal strata radiatum, lacunosum, and moleculare (SRLM) was assessed using a visual rating scale. Hippocampal subfields (CA1, CA2, CA3, dentate gyrus (DG), and subiculum (Sub)) were segmented, and magnetic susceptibility values (ꭓ) were extracted for each subfield. The susceptibility difference (Δꭓ) between DG and other subfields were also calculated. Associations between subfield susceptibility measures and cognitive performance were then assessed. RESULTS: Qualitative analysis revealed a distinct hyperintense curved pattern in the hippocampus on the 7T QSM image, corresponding to the SRLM. In NC subjects, this pattern was clearly visible exhibiting consistently delineated boundaries, while it appeared blurred or absent in most MCI subjects. The visual rating results showed that NC subjects had significantly higher scores than MCI subjects (Hedges' g = 1.43, 95% confidence interval [CI; 0.60, 2.35], p = 0.003), with most NC subjects rated 3-4 and most MCI subjects rated 1-2. Quantitative analysis of hippocampal subfield susceptibility revealed significantly elevated susceptibility (ꭓ) in the left DG in MCI compared to NC (Hedge' g = 0.88, 95% CI [0.10, 1.72], p = 0.03), leading to reduced susceptibility contrast between SRLM and adjacent CA1-CA3 or DG. Furthermore, regional differences of susceptibility (Δꭓ) between key subfields (left CA1 vs. DG and Sub vs. DG) were significantly reduced in MCI, reflecting a loss of subfield contrast. These quantitative changes were significantly associated with lower cognitive performance, even when controlling for age. CONCLUSIONS: 7T QSM reveals susceptibility changes in hippocampal substructures in MCI individuals, providing a potential early biomarker for AD. ABBREVIATIONS: AD = Alzheimer's disease; Aβ = amyloid-beta; DG = dentate gyrus; HSF = Hippocampal Segmentation Factory; MCI = mild cognitive impairment; NC = normal controls; QSM = quantitative susceptibility mapping; SRLM = hippocampal strata radiatum, lacunosum, and moleculare; Sub = Subiculum.