MRI Tract-Based Quantitative Susceptibility Mapping of Limbic White Matter Alterations in Preeclampsia

Preeclampsia is associated with long-term cerebrovascular and cognitive risk, but tract-level white matter (WM) involvement remains incompletely characterized.

To investigate whether preeclampsia is associated with tract-level WM susceptibility alterations on quantitative susceptibility mapping (QSM) and whether these alterations are related to circulating hypoxia-and brain injury-associated proteins.

Prospective cohort study with exploratory postpartum follow-up in a small subset.

350 women (152 with preeclampsia, 73 pregnant healthy controls, and 125 nonpregnant healthy controls).

1.5-T MRI; multiecho gradient-echo sequence for QSM, and 3D T1-weighted turbo field echo, T2-weighted turbo spin echo, T2-weighted fluid-attenuated inversion recovery imaging, and diffusion-weighted echo-planar imaging.

Quantitative susceptibility maps were reconstructed using MEDI+0. Mean susceptibility was extracted from 42 XTRACT-defined WM tracts. Plasma hypoxia-inducible factor-1α, amyloid-β1-42, total tau, and phosphorylated tau181 were measured using enzyme-linked immunosorbent assays. Follow up MRI was performed after 1-3 years in 32 women with preeclampsia.

Group differences were assessed using analysis of variance with Tukey post hoc testing and false discovery rate correction. Multivariable regression, partial Spearman correlation, and exploratory cross-lagged panel modeling were performed.

Significant group differences in susceptibility were concentrated in limbic pathways, including the bilateral anterior thalamic radiations, right dorsal and perigenual cingulum, bilateral temporal cingulum, and bilateral fornix (FDR-adjusted p < 0.05). Compared with pregnant healthy controls, women with preeclampsia had higher susceptibility in the bilateral temporal cingulum (left: 15.75 ± 13.37 vs. 9.95 ± 11.16 ppb, p < 0.05; right: 14.86 ± 14.39 vs. 8.48 ± 11.18 ppb, p < 0.05) and left fornix (5.07 ± 10.12 vs. 1.14 ± 6.65 ppb, p < 0.05). These associations persisted in pregnancy-restricted models after extended adjustment (β = 0.246-0.386; p < 0.05). Higher susceptibility correlated weakly with HIF-1α and total tau (ρ≈0.22-0.27). The exploratory follow-up analyses of 32 women with preeclampsia suggested that baseline biomarker levels were associated with later limbic tract susceptibility.

Tract-based QSM demonstrated preeclampsia-associated limbic WM susceptibility alterations, mainly involving the temporal cingulum and left fornix compared with pregnant healthy controls. Exploratory postpartum findings require confirmation in larger longitudinal cohorts.

Stage 2.