Imaging brain development in preterm and term infants

Abstract

The incidence of preterm birth (at less than 32 weeks of gestation) is estimated at 1-2% of all live births. In Switzerland, over the last ten years, approximately 782 preterm infants per year have been born between 23 and 32 weeks of gestation. Owing to improved neonatal intensive care, the number of very preterm infants surviving into childhood is rising. Indeed, the survival of those extremely low birth weight infants has been increasing over the last decade, especially for the preterm infants born below 26 weeks of gestation. Premature infants are, however, extremely vulnerable to brain injury. Five to 10% of the survivors develop cerebral palsy, and 40–50% develop cognitive and behavioural deficits. Hence, brain injury and its consequences in preterm infants is a serious issue that needs to be addressed. Another population at risk for neurodevelopmental impairment are the infants with congenital heart disease. These infants are known to have a wide range of developmental and neurological difficulties in infancy. The observed cognitive, behavioural and motor deficits can significantly impact daily routine and educational perspectives and lead to a high rate of special schooling and supportive therapies. A recent study reported developmental and functional performance at school entry in children with CHD showing that about one fourth of these children had significant behavioural problems and many had difficulties in socialization, daily living skills, communication or adaptive behaviour. Neuroimaging studies have contributed considerably to our understanding of the maturational changes in gray and white matter during normal and abnormal brain development. Advanced neuroimaging techniques have been increasingly applied to study preterm and term infants in order to further understand the developing brain. This is of importance because as neuroprotective interventions become available robust biomarkers are needed to guide and monitor these interventions. This habilitation discusses quantitative brain MR measures such as T2 relaxation times in preterm infants and diffusion measures such as apparent diffusion coefficient and fractional anisotropy in term infants with congenital heart disease. Further is explores the use of cranial ultrasound in healthy term infants in a low resource setting such as at Mulago University Hospital in Kampala, Uganda. In summary, T2 relaxation times were shown to be longer in the posterior white matter in preterm infants compared to control infants and we found a regional variation in T2 values. T2 provides an objective measure for WM assessment in preterm infants at term; it can be measured easily and rapidly during clinical MR imaging and might serve as a biomarker for later neurodevelopment. In infants with congenital heart disease we demonstrated altered microstructure (DTI) in the corpus callosum with regional variation, with delayed white matter maturation in the genu of the corpus 4 callosum both before and after surgery when compared to the control infants. This altered microstructure might be an explanation later cognitive impairment of these infants. The cUS studies in healthy Ugandan term infants showed a much higher incidence of brain abnormalities compared to other ethnic population. The most common abnormalities were white matter abnormalities, subependymal pseudocysts and choroid plexus cysts. Cerebral cUS measurements were comparable to those of other ethnic populations. They can serve as normative data for comparison with infants with brain malformation and to monitor brain growth of preterm and term infants. This normative cUS data is important for comparison of studies with asphyxiated infants or preterm infants.