Assessing Cerebral Oxygen Metabolism Changes in Patients With Preeclampsia Using Voxel-Based Morphometry of Oxygen Extraction Fraction Maps in Magnetic Resonance Imaging

Abstract

Objective: The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia.

Materials and methods: Forty-nine women with preeclampsia (mean age 32.4 years; range, 18-44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23-40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20-42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups.

Results: Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (all P-values were less than 0.05, after correcting for multiple comparisons). The average OEF values of the preeclampsia group were higher than those of the PHC and NPHC groups. The bilateral superior frontal gyrus/bilateral medial superior frontal gyrus had the largest size of the aforementioned brain regions, and the OEF values in this area were 24.2 ± 4.6, 21.3 ± 2.4, and 20.6 ± 2.8 in the preeclampsia, PHC, and NPHC groups, respectively. In addition, the OEF values showed no significant differences between NPHC and PHC. Correlation analysis revealed that the OEF values of some brain regions (mainly involving the frontal, occipital, and temporal gyrus) were positively correlated with age, gestational week, body mass index, and mean blood pressure in the preeclampsia group (r = 0.361-0.812).

Conclusion: Using whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.

Keywords: Cerebral hypoxia; Magnetic resonance imaging; Oxygen extraction fraction; Preeclampsia; Voxel-based morphometry.

Fig. 1. Schematic pipeline for processing steps. Brain oxygen extraction fraction (OEF) values are computed using a quantitative susceptibility map (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging [qBOLD] or QQ). QSM and OEF images are resliced to T1 resolution and segmented into the T1 anatomical images. The gray matter volume, QSM, and OEF maps are then normalized to the Montreal Neurological Institute (MNI) space and smoothed. GRE = gradient recalled echo, DARTEL = diffeomorphic anatomical registration through exponentiated lie algebra, SPM = statistical parametric mapping, AAL = anatomical automatic labeling, ANOVA = one-way analysis of variance, FDR = false discovery rate

Fig. 2. Whole-brain voxel-based analyses of oxygen extraction fraction (OEF) values between preeclampsia, non-pregnant healthy controls (NPHCs), and pregnant healthy controls (PHCs). Preeclampsia showed significantly higher OEF values than NPHCs and PHCs in the frontal lobe, parahippocampus, calcarine, cuneus, and precuneus.

Fig. 3. Box plot for seven clusters in Table 2. A-G: Oxygen extraction fraction (OEF) values of the seven clusters are significantly different among the three groups. The five lines in the box plot represent (top to bottom) the following values: maximum, 75th quantile, median, 25th quantile, and minimum. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001. NPHC = non-pregnant healthy control, PHC = pregnant healthy control

Fig. 4. Area under the curve (AUC) of oxygen extraction fraction values in seven region of interests for discriminating patients with preeclampsia from controls. A-G: The DeLong test showed that there are significant differences among the AUC values in the bilateral parahippocampal gyrus, which indicated that the bilateral parahippocampal gyrus had a better ability to discriminate participants with and without preeclampsia (P < 0.05).

Fig. 5. Correlation analyses of oxygen extraction fraction (OEF) values in patients with preeclampsia using whole-brain voxel-based OEF. A-D: There are positive correlations between OEF values and blood pressure (BP), age, body mass index (BMI), and gestational week in patients with preeclampsia.

Fig. 6. Correlations between oxygen extraction fraction (OEF) values and clinical parameters in preeclampsia. In Table 4, we selected the brain regions with larger voxels in the brain regions related to the four clinical parameters to draw scatter plots. A: The OEF values of the right superior frontal gyrus/right middle frontal gyrus are positively correlated with age. B: The OEF values of the left middle frontal gyrus are positively correlated with body mass index (BMI). C: The OEF values of the left triangular inferior frontal, right orbital middle frontal, left rectus, right middle occipital, and right inferior occipital gyrus are positively correlated with mean blood pressure (BP). D: The OEF values of the left middle frontal gyrus are positively correlated with gestational week. Significance is set to P < 0.05. Family wise error corrected for multiple comparisons.

Fig. 7. Differences in oxygen extraction fraction (OEF) values among the three groups. Patients with preeclampsia showed significantly higher OEF values than non-pregnant healthy controls (NPHCs) and pregnant healthy controls (PHCs), especially in the bilateral parahippocampal gyrus. NPHCs and PHCs had no difference in OEF values. QSM = quantitative susceptibility map, T1WI = T1-weighted imaging