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Hippocampal Subfield Susceptibility Alterations in Mild Cognitive Impairment Revealed by 7T MRI
Gaoxing Zheng1, Fang Frank Yu1,2, Yujia Huang1
1From the Advanced Imaging Research Center (G.Z., F.F.Y., Y.H., S.M., S.L.V., J.L.), UT Southwestern Medical Center, Dallas, Texas.
Background And Purpose:
Hippocampal magnetic susceptibility alterations may serve as early neurodegenerative biomarkers of Alzheimer disease (AD), but subfield-level evidence in mild cognitive impairment (MCI) remains limited. This study uses submillimeter high-resolution quantitative susceptibility mapping (QSM) to investigate hippocampal subfield susceptibility changes in MCI.
Materials And Methods:
Thirteen individuals with MCI and 13 cognitively normal controls (NC) underwent 7T MRI scans including MP2RAGE and multiecho gradient echo imaging (for QSM). The visibility of hippocampal strata radiatum, lacunosum, and moleculare (SRLM) was assessed using a visual rating scale. Hippocampal subfields (Cornu Ammonis 1 [CA1], CA2, CA3, dentate gyrus [DG], and subiculums) were segmented, and magnetic susceptibility values (χ) were extracted for each subfield. The susceptibility difference between the DG and other subfields was 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, this pattern was clearly visible exhibiting consistently delineated boundaries, while it appeared blurred or absent in most subjects with MCI. The visual rating results showed that NC had significantly higher scores than subjects with MCI (Hedgesg = 1.43, 95% confidence interval) [95% CI, 0.60-2.35; P = .003], with most NC rating 3-4 and most subjects with MCI rating 1-2. Quantitative analysis of hippocampal subfield susceptibility revealed significantly elevated susceptibility [χ] in the left DG in those with MCI compared with NC (Hedgeg = 0.88, 95% CI, 0.10-1.72; P = .03), leading to reduced susceptibility contrast between the SRLM and adjacent CA1-CA3 or DG. Furthermore, regional differences of susceptibility between key subfields (left CA1 versus DG and subiculum versus 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 individuals with MCI, providing a potential early biomarker for AD.
Insights
Quantitative susceptibility mapping (QSM) reveals altered hippocampal subfield susceptibility in mild cognitive impairment (MCI), offering a potential early biomarker for Alzheimer's disease (AD). These changes correlate with cognitive decline.
Area of Science:
- Neuroimaging
- Biomarkers
- Neurodegeneration
Background:
- Magnetic susceptibility alterations in the hippocampus may indicate early Alzheimer's disease (AD).
- Subfield-level evidence of these changes in mild cognitive impairment (MCI) is limited.
- High-resolution quantitative susceptibility mapping (QSM) can investigate these alterations.
Purpose of the Study:
- To investigate hippocampal subfield susceptibility changes in individuals with MCI using submillimeter high-resolution QSM.
- To assess the potential of these changes as early biomarkers for neurodegeneration in AD.
Main Methods:
- Thirteen MCI patients and thirteen cognitively normal controls (NC) underwent 7T MRI scans.
- Quantitative susceptibility mapping (QSM) was performed, and hippocampal subfields (CA1, CA2, CA3, dentate gyrus (DG), subiculum (Sub)) were segmented.
- Magnetic susceptibility values and differences between subfields were calculated and correlated with cognitive performance.
Main Results:
- A distinct pattern in the hippocampal strata radiatum, lacunosum, and moleculare (SRLM) was visible in NC but blurred or absent in MCI.
- Individuals with MCI showed significantly elevated susceptibility in the left dentate gyrus (DG) compared to NC.
- Reduced susceptibility contrast between hippocampal subfields in MCI was associated with lower cognitive performance.
Conclusions:
- 7T QSM detects significant susceptibility changes in hippocampal substructures in individuals with MCI.
- These findings suggest that QSM-based hippocampal subfield analysis can serve as a potential early biomarker for Alzheimer's disease.
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