Quantitative Susceptibility Mapping of the Hippocampal Fimbria in Alzheimer's Disease

Abstract

Background: The fimbria is a small white matter bundle that connects the hippocampus to the rest of the brain. Damage to the hippocampal gray matter is established in Alzheimer's disease (AD), but the hippocampal fimbrial status in the pathogenesis of AD is unclear. AD-related demyelination and iron deposition alter the diamagnetic and paramagnetic composition of tissues, which can be measured by quantitative susceptibility mapping (QSM).

Hypothesis: AD is associated with microstructural changes in the fimbria that might be detected by QSM.

Study type: Retrospective cross-sectional study.

Subjects: In all, 53 adults comprised of controls (n = 30), subjects with early stage AD (n = 13), and late stage AD (n = 10) who were classified according to their amyloid and tau status and presence of hippocampal atrophy.

Field strength / sequence: 3T; 3D fast-field echo sequence for QSM analysis and 3D T₁ -weighted MP-RAGE sequence for anatomical analysis.

Assessment: Segmentation of the left hippocampal fimbria subfield was performed on T₁ -weighted images and was applied to the coregistered QSM map for extraction of the mean, median, minimum, and maximum values of QSM.

Statistical tests: Group comparison of QSM values using analysis of variance (ANOVA) with post-hoc Tukey's test, accuracy of binary differentiation using receiver operating characteristic (ROC), and individual classification using discriminant analysis.

Results: QSM_mean and QSM_median values were significantly different among the three groups (P < 0.05) and showed a shifting from negative in the control group to positive in the AD group. The control and early AD subjects, who have normal hippocampal volumes, were differentiated by the QSM_mean value (area under the curve [AUC] 0.744, P < 0.05) and the QSM_median value (AUC 0.782, P < 0.05). Up to 76% of subjects (inclusive of 26 controls and six with early AD) were correctly classified using a model incorporating clinical and radiologic data.

Data conclusion: The fimbria showed higher magnetic susceptibility in AD compared with controls.

Level of evidence: 2 TECHNICAL EFFICACY STAGE: 3.

Keywords: Alzheimer's disease; MRI; hippocampal fimbria; quantitative susceptibility mapping.