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Published on: March 10, 2020
Hippocampal morphometry is altered in infants with congenital heart disease
Barat Gal-Er1, Alexandra F Bonthrone1, Emily S Nichols2,3
1Centre for the Developing Brain, Research Department of Early Life Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London SE1 7EH, UK.
Insights
Infants with congenital heart disease (CHD) show altered hippocampal morphometry, with specific subfield volume and gyrification differences compared to typically developing infants. These changes were not linked to cerebral oxygen delivery or neurodevelopmental outcomes.
Area of Science:
- Neuroscience
- Pediatric Cardiology
- Developmental Biology
Background:
- Congenital heart disease (CHD) is linked to impaired brain development and neurodevelopmental issues.
- Previous research indicates smaller hippocampal volumes in individuals with CHD, but subfield-specific analysis is lacking.
- Understanding hippocampal morphometry in infants with CHD is crucial for assessing neurodevelopmental risks.
Purpose of the Study:
- To investigate hippocampal morphometry deviations in infants with CHD using normative modeling.
- To analyze relationships between hippocampal measures, cerebral oxygen delivery, and neurodevelopmental outcomes in infants with CHD.
Main Methods:
- Brain MRI (T1- and T2-weighted imaging) was performed on infants with CHD (pre- and postoperative) and typically developing controls.
- Hippocampal subfield volumes and gyrification were quantified using the HippUnfold method.
- Normative curves were generated from control data, and z-scores were calculated for CHD infants.
Main Results:
- Infants with CHD exhibited reduced relative volume in the cornu ammonis 4 and dentate gyrus, and increased volume in the left subiculum.
- Reduced hippocampal gyrification was observed in bilateral subiculum, cornu ammonis 1-4, and dentate gyrus in infants with CHD.
- No significant correlation was found between hippocampal morphometric z-scores and preoperative cerebral oxygen delivery or 22-month neurodevelopmental outcomes.
Conclusions:
- Hippocampal morphometry is altered in infants with CHD, with specific subfield variations in volume and gyrification.
- These observed morphometric changes are not uniformly distributed across the hippocampus.
- Further research is needed to understand the long-term implications of these findings on neurodevelopment.
Abstract:
Congenital heart disease (CHD) is associated with impaired early brain development and an increased risk of adverse neurodevelopmental outcomes. Previous studies have reported smaller hippocampal volumes in infants, children and adolescents with CHD. However, it is unclear whether specific subfields are differentially sensitive as hippocampal subfield morphometry has not been assessed in this population. The aims of this study were to test the hypothesis that infants with CHD deviate from typical hippocampal morphometry, using a normative modelling approach with reference data from 217 typically developing infants, and characterize the relationship between hippocampal morphometric measures and both cerebral oxygen delivery and neurodevelopmental outcomes in infants with CHD. Infants with CHD [60 preoperative and 29 postoperative, gestational age at birth median (range) 38.43 (36.71-40.57) weeks, postmenstrual age at scan 39.86 (37.14-45.71) weeks] and typically developing infants underwent brain MRI on a 3T scanner, and T2-weighted and inversion recovery T1-weighted imaging were acquired. Phase-contrast angiography was acquired in 53 infants with CHD before surgery, and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 52) using the Bayley Scales of Infant and Toddler Development-Third Edition. Volumes of the whole hippocampus, subiculum, cornu ammonis 1-4, dentate gyrus, and stratum radiatum lacunosum and moleculare were obtained by segmenting T1-weighted MRI data using a U-net model trained on infant data using HippUnfold. Normative curves were generated from the typically developing infants using two models: one for relative hippocampal volumes and one for hippocampal gyrification. Models accounted for the infant's postmenstrual age at scan, postnatal age at scan and sex. The hippocampal gyrification model also accounted for hippocampal subfield volume. Z-scores representing the degree of positive or negative deviation from the normative mean were generated for infants with CHD. Relative volume z-scores were reduced for the bilateral cornu ammonis 4 and dentate gyrus (median Z-scores -0.45 to -0.82) and were increased for the left subiculum (mean Z-scores: preoperative 0.44; postoperative 0.51) in infants with CHD. Hippocampal gyrification was reduced in the bilateral subiculum, cornu ammonis 1-4 and dentate gyrus both pre- and postoperatively (mean Z-scores, -0.50 to -1.33). There was no significant relationship between preoperative hippocampal morphometric Z-scores and cerebral oxygen delivery or neurodevelopmental outcomes. Our findings suggest that hippocampal morphometry is altered in infants with CHD; however these effects are not uniform across the hippocampus.
