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A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse
Published on: December 16, 2022
Total and Regional Brain Volumes in Fetuses With Congenital Heart Disease
Daniel Cromb1, Alena Uus1,2, Milou P M Van Poppel2,3,4
1Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
Insights
Congenital heart disease (CHD) in fetuses is linked to smaller brain volumes when cerebral substrate delivery is reduced. However, brain development is unaffected if substrate delivery remains normal.
Area of Science:
- Neuroimaging
- Developmental Biology
- Cardiology
Background:
- Congenital heart disease (CHD) is a common condition affecting fetal development.
- CHD is associated with impaired brain development and neurodevelopmental outcomes.
- The precise mechanisms linking CHD to brain development issues remain unclear.
Purpose of the Study:
- To investigate the association between expected cerebral substrate delivery and fetal brain volumes in fetuses with CHD.
- To compare brain volumes in fetuses with CHD and typically developing fetuses using MRI data.
Main Methods:
- A retrospective case-control study involving 380 fetuses (45 controls, 335 with CHD) scanned between 29-37 weeks gestation.
- MRI data (T2-weighted and balanced steady-state free precession sequences) were acquired on a 1.5T scanner.
- Automated image processing, including motion correction, reconstruction, and segmentation using a convolutional neural network, was employed.
Main Results:
- Fetuses with CHD and reduced cerebral substrate delivery exhibited smaller total and regional brain volumes.
- No significant differences in brain volumes were found between control fetuses and those with CHD but normal substrate delivery.
- Severely reduced cerebral substrate delivery correlated with lower brain-to-body volume ratios.
Conclusions:
- Reduced cerebral substrate delivery in fetuses with CHD is associated with diminished total and regional brain volumes.
- Fetal brain volumes are not significantly affected in CHD cases with normal expected cerebral substrate delivery.
- These findings highlight the critical role of substrate delivery in fetal brain growth in the context of CHD.
Background:
Congenital heart disease (CHD) is common and is associated with impaired early brain development and neurodevelopmental outcomes, yet the exact mechanisms underlying these associations are unclear.
Purpose:
To utilize MRI data from a cohort of fetuses with CHD as well as typically developing fetuses to test the hypothesis that expected cerebral substrate delivery is associated with total and regional fetal brain volumes.
Study Type:
Retrospective case-control study.
Population:
Three hundred eighty fetuses (188 male), comprising 45 healthy controls and 335 with isolated CHD, scanned between 29 and 37 weeks gestation. Fetuses with CHD were assigned into one of four groups based on expected cerebral substrate delivery.
Field Strength/Sequence:
T2-weighted single-shot fast-spin-echo sequences and a balanced steady-state free precession gradient echo sequence were obtained on a 1.5 T scanner.
Assessment:
Images were motion-corrected and reconstructed using an automated slice-to-volume registration reconstruction technique, before undergoing segmentation using an automated pipeline and convolutional neural network that had undergone semi-supervised training. Differences in total, regional brain (cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem) and brain:body volumes were compared between groups.
Statistical Tests:
ANOVA was used to test for differences in brain volumes between groups, after accounting for sex and gestational age at scan. PFDR-values <0.05 were considered statistically significant.
Results:
Total and regional brain volumes were smaller in fetuses where cerebral substrate delivery is reduced. No significant differences were observed in total or regional brain volumes between control fetuses and fetuses with CHD but normal cerebral substrate delivery (all PFDR > 0.12). Severely reduced cerebral substrate delivery is associated with lower brain:body volume ratios.
Data Conclusion:
Total and regional brain volumes are smaller in fetuses with CHD where there is a reduction in cerebral substrate delivery, but not in those where cerebral substrate delivery is expected to be normal.
Evidence Level:
3 TECHNICAL EFFICACY: Stage 3.
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