Britt J. van Kooij

Cerebellar Volume and Proton Magnetic Resonance Spectroscopy at Term, and Neurodevelopment at 2 Years of Age in Preterm Infants.

Aim To assess the relation between cerebellar volume and spectroscopy at term equivalent age, and neurodevelopment at 24 months corrected age in preterm infants.

Serial MRI and Neurodevelopmental Outcome in 9-to 10-Year-Old Children with Neonatal Encephalopathy

OBJECTIVE To assess the relation between patterns of brain injury on neonatal and childhood magnetic resonance imaging (MRI) and long-term neurodevelopmental outcome. STUDY DESIGN Neonatal (n = 34) and childhood MRIs (n = 77) were analyzed for 80 children with neonatal encephalopathy and for 51 control subjects during childhood. MRIs were graded as normal, mildly abnormal (white matter lesions), or moderately/severely abnormal (watershed injury, lesions in basal ganglia/thalamus or focal infarction). Severity of brain injury was related to different aspects of neurologic outcome: Total impairment score of the Movement Assessment Battery for Children, intelligence quotient score, cerebral palsy, postneonatal epilepsy, and need for special education. Seven children with neonatal encephalopathy required extracorporeal membrane oxygenation treatment. RESULTS Neonatal and childhood MRI were comparable in 25/33 children (75.8%, P < .001). Children with moderate/severe lesions on neonatal or childhood MRI more often had a total impairment score <or= 15th percentile, an intelligence quotient <or= 85, and cerebral palsy, and attended special education. CONCLUSION Different patterns of injury seen on neonatal MRI after neonatal encephalopathy can still be recognized on childhood MRI. Children with moderate to severe brain lesions on neonatal or childhood MRI significantly more often have impaired motor and cognitive outcomes.

Automatic Segmentation of Eight Tissue Classes in Neonatal Brain MRI

Purpose Volumetric measurements of neonatal brain tissues may be used as a biomarker for later neurodevelopmental outcome. We propose an automatic method for probabilistic brain segmentation in neonatal MRIs. Materials and Methods In an IRB-approved study axial T1- and T2-weighted MR images were acquired at term-equivalent age for a preterm cohort of 108 neonates. A method for automatic probabilistic segmentation of the images into eight cerebral tissue classes was developed: cortical and central grey matter, unmyelinated and myelinated white matter, cerebrospinal fluid in the ventricles and in the extra cerebral space, brainstem and cerebellum. Segmentation is based on supervised pixel classification using intensity values and spatial positions of the image voxels. The method was trained and evaluated using leave-one-out experiments on seven images, for which an expert had set a reference standard manually. Subsequently, the method was applied to the remaining 101 scans, and the resulting segmentations were evaluated visually by three experts. Finally, volumes of the eight segmented tissue classes were determined for each patient. Results The Dice similarity coefficients of the segmented tissue classes, except myelinated white matter, ranged from 0.75 to 0.92. Myelinated white matter was difficult to segment and the achieved Dice coefficient was 0.47. Visual analysis of the results demonstrated accurate segmentations of the eight tissue classes. The probabilistic segmentation method produced volumes that compared favorably with the reference standard. Conclusion The proposed method provides accurate segmentation of neonatal brain MR images into all given tissue classes, except myelinated white matter. This is the one of the first methods that distinguishes cerebrospinal fluid in the ventricles from cerebrospinal fluid in the extracerebral space. This method might be helpful in predicting neurodevelopmental outcome and useful for evaluating neuroprotective clinical trials in neonates.

Fiber Tracking at Term Displays Gender Differences Regarding Cognitive and Motor Outcome at 2 Years of Age in Preterm Infants

White matter microstructural changes can be detected with diffusion tensor imaging. It was hypothesized that diffusion parameters in the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) bundles in preterm infants at term equivalent age (TEA) were associated with neurodevelopment at 2 y corrected age. In 67 preterm infants, fiber tracking was performed at TEA for the CC and both PLIC bundles. Volume, length, fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity were determined for the three bundles. These parameters were assessed in relation to outcome on the Bayley Scales of Infant and Toddler Development III. In girls, volume and length of the CC bundle and right PLIC bundle volume were associated with cognition. In boys, volume, FA, mean and radial diffusivity, and length of the left PLIC were associated with fine motor scores. Correction for GA, birth weight, intraventricular hemorrhage, white matter injury, and maternal education did not change the results. Fiber tracking parameters in the PLIC and CC bundles in preterm infants at TEA revealed different associations with neurodevelopment between boys and girls. This study suggested that fiber tracking is a useful method to predict neurodevelopment in preterm infants.

Hydrocortisone treatment for bronchopulmonary dysplasia and brain volumes in preterm infants.

OBJECTIVE To assess whether there was an adverse effect on brain growth after hydrocortisone (HC) treatment for bronchopulmonary dysplasia (BPD) in a large cohort of infants without dexamethasone exposure. STUDY DESIGN Infants who received HC for BPD between 2005 and 2011 and underwent magnetic resonance imaging at term-equivalent age were included. Control infants born in Geneva (2005-2006) and Utrecht (2007-2011) were matched to the infants treated with HC according to segmentation method, sex, and gestational age. Infants with overt parenchymal pathology were excluded. Multivariable analysis was used to determine if there was a difference in brain volumes between the 2 groups. RESULTS Seventy-three infants treated with HC and 73 matched controls were included. Mean gestational age was 26.7 weeks, and mean birth weight was 906 g. After correction for gestational age, postmenstrual age at time of scanning, the presence of intraventricular hemorrhage, and birth weight z-score, no differences were found between infants treated with HC and controls in total brain tissue or cerebellar volumes. CONCLUSIONS In the absence of associated parenchymal brain injury, no reduction in brain tissue or cerebellar volumes could be found at term-equivalent age between infants with or without treatment with HC for BPD.

Corpus Callosum Size in Relation to Motor Performance in 9-to 10-Year-Old Children with Neonatal Encephalopathy

Magnetic resonance imaging studies have contributed to recognize the patterns of cerebral injury related to neonatal encephalopathy (NE). We assessed whether a smaller corpus callosum (CC) explained the difference in motor performance between school-age children with NE and controls. Frontal, middle, and posterior areas of the CC were measured in 61 9–10-y-old children with NE and in 47 controls. Motor performance was determined using the Movement Assessment Battery for Children (M-ABC). Linear regression was used to assess whether differences in M-ABC between NE children and controls could be explained by CC size. The CC of 11/30 children with NE type I according to Sarnat (NE I) and 19/36 children with NE type II according to Sarnat (NE II) showed generalized or focal thinning, compared with 8/49 controls. Children with NE II had significantly smaller middle and posterior parts and total areas of the CC. Children with NE scored significantly worse on the M-ABC than controls. The reduction in size of the posterior part of the CC partly explained the mean differences on the M-ABC. Children with NE have poorer motor skills than controls, which is partly explained by a smaller size of the CC.

Sequential Cranial Ultrasound and Cerebellar Diffusion Weighted Imaging Contribute to the Early Prognosis of Neurodevelopmental Outcome in Preterm Infants

Objective To evaluate the contribution of sequential cranial ultrasound (cUS) and term-equivalent age magnetic resonance imaging (TEA-MRI) including diffusion weighted imaging (DWI) to the early prognosis of neurodevelopmental outcome in a cohort of very preterm infants (gestational age [GA] <31 weeks). Study design In total, 93 preterm infants (median [range] GA in weeks: 28.3 [25.0–30.9]) were enrolled in this prospective cohort study and underwent early and term cUS as well as TEA-MRI including DWI. Early cUS abnormalities were classified as normal, mild, moderate or severe. Term cUS was evaluated for ex-vacuo ventriculomegaly (VM) and enlargement of the extracerebral cerebrospinal fluid (eCSF) space. Abnormalities on T1- and T2-weighted TEA-MRI were scored according to Kidokoro et al. Using DWI at TEA, apparent diffusion coefficients (ADCs) were measured in four white matter regions bilaterally and both cerebellar hemispheres. Neurodevelopmental outcome was assessed at two years’ corrected age (CA) using the Bayley Scales of Infant and Toddler Development, third edition. Linear regression analysis was conducted to explore the correlation between the different neuroimaging modalities and outcome. Results Moderate/severe abnormalities on early cUS, ex-vacuo VM and enlargement of the eCSF space on term cUS and increased cerebellar ADC values on term DWI were independently associated with worse motor outcome (p<.05). Ex-vacuo VM on term cUS was also related to worse cognitive performance at two years’ CA (p<.01). Conclusion These data support the clinical value of sequential cUS and recommend repeating cUS at TEA. In particular, assessment of moderate/severe early cUS abnormalities and ex-vacuo VM on term cUS provides important prognostic information. Cerebellar ADC values may further aid in the prognostication of gross motor function.

Changes in carotid blood flow after unilateral perinatal arterial ischemic stroke

Introduction:Little is known about changes in carotid blood flow after perinatal arterial ischemic stroke (PAIS). The aim of this study was to assess the blood flow in the internal carotid arteries (ICAs) after unilateral PAIS.Methods:The carotid flow (ml/min) was measured noninvasively by means of two-dimensional phase-contrast magnetic resonance angiography (2D PC-MRA) in 25 full-term infants who had unilateral PAIS within 10 d after birth. In 17 infants a second 2D PC-MRA was carried out at the age of 3 mo. Asymmetry of carotid blood flow was calculated at both time points, and the circle of Willis (CoW) was assessed with a three-dimensional (3D) time-of-flight MRA.Results:On the early magnetic resonance imaging (MRI), a significant increase in ipsilateral blood flow was observed (7.7%, 95% confidence interval (CI) 3.0–14.9%), which persisted after correcting for CoW configuration. At 3 mo, this asymmetry was no longer observed. No relationship was found between the asymmetry in blood flow and either stroke size or postnatal age at scan.Discussion:A higher blood flow in the ipsilateral ICA was observed during the acute phase after unilateral PAIS, and this disappeared after 3 mo. Further research into the role of hyperperfusion after PAIS may suggest new approaches to neuroprotection.

Preterm brain injury on term-equivalent age MRI in relation to perinatal factors and neurodevelopmental outcome at two years

Objectives First, to apply a recently extended scoring system for preterm brain injury at term-equivalent age (TEA-)MRI in a regional extremely preterm cohort; second, to identify independent perinatal factors associated with this score; and third, to assess the prognostic value of this TEA-MRI score with respect to early neurodevelopmental outcome. Study design 239 extremely preterm infants (median gestational age [range] in weeks: 26.6 [24.3–27.9]), admitted to the Wilhelmina Children’s Hospital between 2006 and 2012 were included. Brain abnormalities in white matter, cortical and deep grey matter and cerebellum and brain growth were scored on T1- and T2-weighted TEA-MRI using the Kidokoro scoring system. Neurodevelopmental outcome was assessed at two years corrected age using the Bayley Scales of Infant and Toddler Development, third edition. The association between TEA-MRI and perinatal factors as well as neurodevelopmental outcome was evaluated using multivariable regression analysis. Results The distribution of brain abnormalities and brain metrics in the Utrecht cohort differed from the original St. Louis cohort (p < .05). Mechanical ventilation >7 days (β [95% confidence interval, CI]: 1.3 [.5; 2.0]) and parenteral nutrition >21 days (2.2 [1.2; 3.2]) were independently associated with higher global brain abnormality scores (p < .001). Global brain abnormality scores were inversely associated with cognitive (β in composite scores [95% CI]: -.7 [-1.2; -.2], p = .004), fine motor (β in scaled scores [95% CI]: -.1 [-.3; -.0], p = .007) and gross motor outcome (β in scaled scores [95% CI]: -.2 [-.3; -.1], p < .001) at two years corrected age, although the explained variances were low (R2 ≤.219). Conclusion Patterns of brain injury differed between cohorts. Prolonged mechanical ventilation and parenteral nutrition were identified as independent perinatal risk factors. The prognostic value of the TEA-MRI score was rather limited in this well-performing cohort.

Unmyelinated White Matter Loss in the Preterm Brain Is Associated with Early Increased Levels of End-Tidal Carbon Monoxide

Objective Increased levels of end-tidal carbon monoxide (ETCOc) in preterm infants during the first day of life are associated with oxidative stress, inflammatory processes and adverse neurodevelopmental outcome at 2 years of age. Therefore, we hypothesized that early ETCOc levels may also be associated with impaired growth of unmyelinated cerebral white matter. Methods From a cohort of 156 extremely and very preterm infants in which ETCOc was determined within 24 h after birth, in 36 infants 3D-MRI was performed at term-equivalent age to assess cerebral tissue volumes of important brain regions. Results Linear regression analysis between cerebral ventricular volume, unmyelinated white matter/total brain volume-, and cortical grey matter/total brain volume-ratio and ETCOc showed a positive, negative and positive correlation, respectively. Multivariable analyses showed that solely ETCOc was positively related to cerebral ventricular volume and cortical grey matter/total brain volume ratio, and that solely ETCOc was inversely related to the unmyelinated white matter/total brain volume ratio, suggesting that increased levels of ETCOc, associated with oxidative stress and inflammation, were related with impaired growth of unmyelinated white matter. Conclusion Increased values of ETCOc, measured within the first 24 hours of life may be indicative of oxidative stress and inflammation in the immediate perinatal period, resulting in impaired growth of the vulnerable unmyelinated white matter of the preterm brain.