Total and Regional Brain Volumes in Fetuses With Congenital Heart Disease

Abstract

BackgroundCongenital 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.PurposeTo 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 TypeRetrospective case–control study.PopulationThree 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/SequenceT2‐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.AssessmentImages 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 TestsANOVA 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.ResultsTotal 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 ConclusionTotal 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 Level3Technical EfficacyStage 3

Structural covariance networks in the fetal brain reveal altered neurodevelopment for specific subtypes of congenital heart disease

“…To explore the hypothesis that impaired cerebral substrate delivery plays a major role in the neurodevelopmental abnormalities associated with CHD, we divided the CHD cohort into 4 groups, according to the predicted level of substrate delivery to the developing fetal brain, based on the expected consequence of the underlying cardiac defect as described previously (Cromb et al, 2023).…”

“…For cases where information about the direction of blood flow at the aortic isthmus could not be derived from MRI derived fetal blood flows, and was important for CHD categorization, it was extracted from the clinical fetal echocardiogram report, acquired as per routine clinical care. In cases where a diagnosis could potentially fit into more than one category, depending on severity or underlying hemodynamics, a combination of phase contrast (with metric optimized gating), fetal flow measurements (described in Lloyd et al, 2021, Janz et al, 2010 and/or contemporaneously acquired echocardiographic data were used to assign cases individually, following assessment of the data by a fetal cardiologist (Cromb et al, 2023).…”

“…A wide spectrum of CHD was represented in this cohort, including 40 different diagnoses (Figure 1, 2), which were categorised into 4 groups based on expected cerebral substrate delivery (Cromb et al, 2023), Normal = 232, Mildly reduced = 67, Moderately reduced = 46, Severely reduced = 23. The range of CHD diagnoses within each group is shown in Figure 2.…”

“…It has been hypothesised that aberrant cardiovascular physiology, altering the delivery of oxygen, glucose and other nutrients to the fetal brain during this critical window, impairs brain development (Peyvandi 2021, Lauridsen 2017, Sun 2015. Different types of CHD will affect the pattern of cerebral substrate delivery in different ways, likely having unique implications for brain development (Sun et al, 2021, Rollins et al, 2021, Cromb et al, 2023. There are also a multitude of other interacting factors that may perturb neurodevelopment during the fetal period and manifest as structural brain alterations.…”

“…With recent advances in fetal MRI, it has become possible to study brain development in utero. Previous work has identified deviations from normal brain growth trajectories in fetuses with CHD, including reduced regional brain volumes (Limperopoulos 2010, Clouchoux et al, 2013, Brossard-Racine 2014, Ren et al, 2021, Dovjak et al, 2022, Cromb et al 2023), altered volumes of transient fetal compartments (Rollins et al, 2021, Wu et al, 2021), reduced cortical folding (Ortinau 2019, Jaimes et al, 2020) and a relationship between cerebral oxygen delivery and fetal brain size (Sun et al, 2015, Cromb et al, 2023). These studies demonstrate that abnormal neurodevelopment in the CHD population begins in utero during a period of rapid brain growth, featuring metabolically demanding cellular processes such as gyrification, oligodendrocyte maturation, and synaptogenesis.…”