Prashob Porayette

Reduced Fetal Cerebral Oxygen Consumption is Associated With Smaller Brain Size in Fetuses With Congenital Heart Disease

Background— Fetal hypoxia has been implicated in the abnormal brain development seen in newborns with congenital heart disease (CHD). New magnetic resonance imaging technology now offers the potential to investigate the relationship between fetal hemodynamics and brain dysmaturation. Methods and Results— We measured fetal brain size, oxygen saturation, and blood flow in the major vessels of the fetal circulation in 30 late-gestation fetuses with CHD and 30 normal controls using phase-contrast magnetic resonance imaging and T2 mapping. Fetal hemodynamic parameters were calculated from a combination of magnetic resonance imaging flow and oximetry data and fetal hemoglobin concentrations estimated from population averages. In fetuses with CHD, reductions in umbilical vein oxygen content (P<0.001) and failure of the normal streaming of oxygenated blood from the placenta to the ascending aorta were associated with a mean reduction in ascending aortic saturation of 10% (P<0.001), whereas cerebral blood flow and cerebral oxygen extraction were no different from those in controls. This accounted for the mean 15% reduction in cerebral oxygen delivery (P=0.08) and 32% reduction cerebral VO2 in CHD fetuses (P<0.001), which were associated with a 13% reduction in fetal brain volume (P<0.001). Fetal brain size correlated with ascending aortic oxygen saturation and cerebral VO2 (r=0.37, P=0.004). Conclusions— This study supports a direct link between reduced cerebral oxygenation and impaired brain growth in fetuses with CHD and raises the possibility that in utero brain development could be improved with maternal oxygen therapy.

MRI shows limited mixing between systemic and pulmonary circulations in foetal transposition of the great arteries: a potential cause of in utero pulmonary vascular disease.

Objectives To investigate the relationship between foetal haemodynamics and postnatal clinical presentation in patients with transposition of the great arteries using phase-contrast cardiovascular magnetic resonance. Background A severe and irreversible form of persistent pulmonary hypertension of the newborn occurs in up to 5% of patients with transposition and remains an important cause of morbidity and mortality in these infants. Restriction at the foramen ovale and ductus arteriosus has been identified as a risk factor for the development of pulmonary hypertension, and this can now be studied with magnetic resonance imaging using a new technique called metric optimised gating. Methods Blood flow was measured in the major vessels of four foetuses with transposition with intact ventricular septum (gestational age range: 35–38 weeks) and compared with values from 12 normal foetuses (median gestational age: 37 weeks; range: 34–40 weeks). Results We found significantly reduced flows in the ductus arteriosus (p<0.01) and foramen ovale (p=0.03) and increased combined ventricular output (p=0.01), ascending aortic (p=0.001), descending aortic (p=0.03), umbilical vein (p=0.03), and aorto-pulmonary collateral (p<0.001) flows in foetuses with transposition compared with normals. The foetus with the lowest foramen ovale shunt and highest aorto-pulmonary collateral flow developed fatal pulmonary vascular disease. Conclusions We found limited mixing between the systemic and pulmonary circulations in a small group of late-gestation foetuses with transposition. We propose that the resulting hypoxia of the pulmonary circulation could be the driver behind increased aorto-pulmonary collateral flow and contribute to the development of pulmonary vascular disease in some foetuses with transposition.

Interplay of brain structure and function in neonatal congenital heart disease.

To evaluate whether structural and microstructural brain abnormalities in neonates with congenital heart disease (CHD) correlate with neuronal network dysfunction measured by analysis of EEG connectivity.

MRI reveals hemodynamic changes with acute maternal hyperoxygenation in human fetuses with and without congenital heart disease

Background Maternal hyperoxygenation (MH) has been used for intrauterine growth restriction and proposed as a way to improve ventricular growth in the setting of congenital heart disease (CHD)[1,2]. Fetal lamb experiments reveal increases in the SaO2 of umbilical venous (UV) blood and a reduction in pulmonary vascular resistance during MH [3]. Doppler suggests that MH increases the human fetal pulmonary blood flow (PBF) [4]. The combination of fetal phase contrast (PC) MRI and MR oximetry using T2 mapping offers the potential for a comprehensive hemodynamic assessment of late gestation fetal circulation [5]. We investigated the physiologic impact of MH in human fetuses with and without CHD using MRI to explore the potential therapeutic benefits of chronic MH.

Response to Letter Regarding Article, "Reduced Fetal Cerebral Oxygen Consumption Is Associated With Smaller Brain Size in Fetuses With Congenital Heart Disease".

We are grateful to Dr Rudolph for his careful review of our article. Dr Rudolph’s extensive work on the fetal lamb circulation was the principle reference for our research. In our article, we present MRI data showing how the obstructions to flow and abnormal connections that characterize various congenital cardiac malformations result in desaturation of ascending aortic blood because of failure of the normal preferential streaming of umbilical venous blood.1 In addition, we observed reductions in umbilical venous Sao2, and in fetuses with single ventricle physiology, reductions in umbilical blood flow resulting in further desaturation across the fetal circulation. The majority of fetuses with heart disease showed no evidence of increased cerebral blood flow or cerebral oxygen extraction to compensate for the hypoxemia, resulting in a trend toward reduced cerebral oxygen delivery (CDo2) and a significant reduction in cerebral oxygen consumption. In a more recent analysis with …

Serial prenatal and post-natal brain MRI demonstrates impact of congenital heart disease and cardiac surgery on brain growth and maturity

Methods Post-natal brain MRI were performed without sedation in 24 infants with common CHD before and after the cardiac surgery on a Siemens Avanto 1.5T system (Erlangen) after hospital IRB approval. 18 of 24 subjects also had fetal MRI using previously described technique [5] and BV and fetal weight were calculated [3]. The normal brain weights were obtained from published autopsy data [6] and converted to BV [7]. T2 mapping and diffusion weighted imaging were performed to measure T2 and apparent diffusion coefficient (ADC), respectively [2]. The mean T2 and ADC were measured in postnatal brains using 12 regions of interest located bilaterally at frontal and posterior white matter (WM) at inferior basal ganglia level; superior frontal and parietal WM at level of horns of lateral ventricles; and frontal and posterior centrum semiovale level. Cerebral oxygen delivery (CDO2) was also measured [1]. The daily change in BV, T2, and ADC were calculated by dividing the difference in values by days between the scans. The correlation between BV, T2, and ADC was examined using Pearson’s Correlation. Results The cohort (n = 24) consisted of patients with transposition of the great arteries (TGA) with intact ventricular septum (IVS; n = 5); TGA with ventricular septal defect (VSD; n = 7), hypoplastic left heart syndrome (HLHS; n = 4); tricuspid atresia (TA; n = 5), pulmonary atresia (PA, n = 3). The TGA/IVS group had normal brain growth after birth and surgery (Figure 1A). However, in TGA/VSD patients, the brain growth plateaus or drops after birth and do not revert immediately after surgery (Figure 1B). TGA/VSD had lower daily brain growth compared to normals (Figure 1C). HLHS showed similar decline in BV after surgery (Figure 1D). The infants with TA and PA had normal BV growth. The mean T2 and ADC values had excellent correlation (r = 0.96, p < 0.0001; Figure 2A). T2 (r=-0.79, p < 0.0001) and ADC (r=-0.7, p < 0.0001) also correlated with BV. Children with TGA physiology showed opposite change in T2 and ADC to expected values (Figure 2B). The mean CDO2/ml of brain was relatively lower in TGA/VSD (4 ml O2/min/ml BV; n = 3) compared to TGA/IVS (6 ml O2/min/ml BV; n = 3).

The absolute and relative sizes of the brains and bodies of fetuses with different forms of congenital heart disease and intrauterine growth restriction

Background Congenital heart disease(CHD) is associated with in utero brain dysmaturation, abnormal cerebral vasculature and decreased brain size.(1,2) Intrauterine growth restriction is associated with increased relative brain size, smaller birth weight and neurological impairment later in life.(3) A large cohort of CHD and IUGR fetuses allows for more definitive study as to the extent these conditions effect the absolute and relative sizes of the brain and body.