Serena J. Counsell

Probabilistic diffusion tractography of the optic radiations and visual function in preterm infants at term equivalent age

Children born prematurely have a high incidence of visual disorders which cannot always be explained by focal retinal or brain lesions. The aim of this study was to test the hypothesis that visual function in preterm infants is related to the microstructural development of white matter in the optic radiations. We used diffusion tensor imaging (DTI) with probabilistic diffusion tractography to delineate the optic radiations at term equivalent age and compared the fractional anisotropy (FA) to a contemporaneous evaluation of visual function. Thirty-seven preterm infants (19 male) born at median (range) 28(+4) (24(+1)-32(+3)) weeks gestational age, were examined at a post-menstrual age of 42 (39(+6)-43) weeks. MRI and DTI were acquired on a 3 Tesla MR system with DTI obtained in 15 non-collinear directions with a b value of 750 s/mm(2). Tracts were generated from a seed mask placed in the white matter lateral to the lateral geniculate nucleus and mean FA values of these tracts were determined. Visual assessment was performed using a battery of nine items assessing different aspects of visual abilities. Ten infants had evidence of cerebral lesions on conventional MRI. Multiple regression analysis demonstrated that the visual assessment score was independently correlated with FA values, but not gestational age at birth, post-menstrual age at scan or the presence of lesions on conventional MRI. The occurrence of mild retinopathy of prematurity did not affect the FA measures or visual scores. We then performed a secondary analysis using tract-based spatial statistics to determine whether global brain white matter development was related to visual function and found that only FA in the optic radiations was correlated with visual assessment score. Our results suggest that in preterm infants at term equivalent age visual function is directly related to the development of white matter in the optic radiations.

Relationship Between White Matter Apparent Diffusion Coefficients in Preterm Infants at Term-Equivalent Age and Developmental Outcome at 2 Years

OBJECTIVE. The aim of this study was to develop a simple reproducible method for the measurement of apparent diffusion coefficient values in the white matter of preterm infants using diffusion-weighted imaging to test the hypothesis that elevated mean apparent diffusion coefficient values are associated with lower developmental quotient scores at 2 years’ corrected age. METHODS. We obtained diffusion-weighted imaging in 38 preterm infants at term-equivalent age who had no evidence of overt cerebral pathology on conventional MRI. Mean apparent diffusion coefficient values at the level of the centrum semiovale were determined. The children were assessed using a standardized neurologic examination, and the Griffiths Mental Development Scales were administered to obtain a developmental quotient at 2 years’ corrected age. The relationship between mean apparent diffusion coefficient values and developmental quotient was examined. Clinical data relating to postnatal sepsis, antenatal steroid exposure, supplemental oxygen, gender, patent ductus arteriosus, and inotrope requirement were collected, and the mean apparent diffusion coefficient values for each group were compared. RESULTS. The mean (±SD) apparent diffusion coefficient value in the white matter was 1.385 ± 0.07 × 10−3 mm2/second, and the mean developmental quotient was 108.9 ± 11.5. None of the children had a significant neurologic problem. There was a significant negative correlation between mean apparent diffusion coefficient and developmental quotient. CONCLUSION. These findings suggest that higher white matter apparent diffusion coefficient values at term-equivalent age in preterm infants without overt lesions are associated with poorer developmental performance in later childhood. Consequently, apparent diffusion coefficient values at term may be of prognostic value for neurodevelopmental outcome in infants who are born preterm and who have no other imaging indicators of abnormality.

43 Total Cerebral Volume Measurements Following Preterm Birth

Background. Preterm infants have reduced cerebral tissue volumes in adolescence, and relative loss of some brain regions in early childhood, but it is unclear if this is due to perinatal or more prolonged growth failure. We therefore compared total cerebral tissue volume in preterm infants at term equivalent age and term born controls.Methods. Subjects: We studied 89 preterm infants born at median 29.7 weeks GA without parenchymal lesions at median 40.57 weeks, and 20 term born controls (median 40.43 weeks GA). Image acquisition: A 1.5 Tesla MR system was used to acquire T1-weighted volume datasets with a voxel size 1x1x1.6mm, in addition to conventional and diffusion weighted imaging. Image processing: A non-rigid image registration algorithm transformed all images to a reference subject, and transformations were used to propagate region of interest (ROI) labels segmented in the reference anatomy to the corresponding structure in all subjects. The volume change for each ROI relative to the reference was computed, enabling cerebral tissue volume measurements (excluding CSF) to be calculated for each subject.Results. Mean cerebral tissue volume in preterm infants at term was 404.9cm3; and in term controls, 401.1cm3 (p=0.765). Diffuse white matter injury, oxygen requirement at 28 days, and intrauterine growth restriction were not associated with significant reductions in cerebral tissue volume.Conclusions. Despite evidence of regional and later growth failure, total brain tissue volume in preterm infants at term is similar to term born controls.

103 Serial Magnetic Resonance Imaging of the Preterm Brain: The Natural History of Early Lesions, Abnormalities at Term Age and Relation to Outcome

Background. The neural substrate for adverse neurodevelopmental outcome in extremely preterm infants remains incompletely determined.Aims. To determine the spectrum of brain abnormalities in the preterm population using serial magnetic resonance (MR) imaging from birth to term age and make preliminary correlations with neurodevelopmental outcome.Methods. Serial MR brain scans were acquired prospectively from birth until term age from a consecutive cohort of preterm infants. Neurodevelopmental assessments were made after 18 months of age using Griffiths Mental Development Scales with calculation of a developmental quotient.Results. Three hundred and twenty seven MR studies were obtained from 119 surviving infants born at 23 to 29 weeks gestation. Initial MR scan acquisition was at a median of 2 days after delivery. Four infants had major destructive brain lesions (haemorrhagic parenchymal infarction, n=2; cystic periventricular leucomalacia, n=2); tissue loss was seen at term in the two survivors. Fifty one infants had haemorrhage (germinal layer, n=47; intraventricular (IVH), n=29; extracerebral, n=6) with 42% of survivors having ventricular dilatation at term. Twenty six infants had punctate white matter lesions, 40% of which persisted to term. Cerebellar haemorrhage occurred in 8 infants and basal ganglia lesions occurred in 17 infants. At term 53% of infants without prior haemorrhage had ventricular dilatation and 80% of infants had diffuse excessive high signal intensity (DEHSI) within the white matter. Complete follow-up is available in 67% of infants. Adverse outcome, characterized by low developmental quotient, is associated with major destructive lesions, cerebellar haemorrhage, DEHSI and ventricular dilatation after IVH, but not with punctate white matter lesions, haemorrhage or ventricular dilatation without IVH.Conclusions. Diffuse white matter abnormalities and post-haemorrhagic ventricular dilatation are common at term and correlate with reduced developmental quotient. Early lesions, except for cerebellar haemorrhage and major destructive lesions, do not show clear relationships with outcome.

106 Cortical Growth and Neurocognitive Impairment in Preterm Infants

Background. Neurocognitive impairment after preterm birth is common and directly related to increasing prematurity. The neural substrate for this dysfunction is unknown, but cannot be wholly accounted for by major destructive brain lesions.Aims. To test the hypothesis that the timing of premature delivery is associated with a dose-dependent reduction in the rate of growth of the cerebral cortex which parallels the increase in neurocognitive impairment.Methods. MR images were obtained from a consecutive cohort of extremely preterm infants serially from soon after delivery until term corrected age and neurodevelopment was assessed using the Griffiths Developmental Scales at median 24 months corrected age. Total cerebral volume and cortical surface area were measured semi-interactively, and their rate of growth found to be related by a power law, the scaling exponent of which gives a direct measure of the growth rate of cortical surface area relative to cerebral volume. A generalized least squares random effects regression model was constructed to test the effect of gestational age at birth and potential confounding variables on the scaling exponent, and the relation to neurodevelopmental outcome was tested.Results. 113 infants born at 23–29 weeks gestation were imaged providing 274 images without major destructive lesions for analysis. Complete neurodevelopmental data are available on 63 infants. Increasing prematurity was associated with a reduced rate of cortical growth (p<0.0001) which was independent of intrauterine or postnatal somatic growth. There was a significant relation between reduced cortical growth and the Griffiths Developmental Quotient (p<0.05), seen with all subscales except the locomotor.Conclusions. Reduced rate of growth of the cerebral cortex parallels the dose-dependent effect of prematurity on neurodevelopmental function. Cortical growth failure may be a neural substrate for the high rate of non-locomotor neurocognitive impairment seen in preterm infants.