Nathalie H P Claessens

Relation between clinical risk factors, early cortical changes, and neurodevelopmental outcome in preterm infants

Cortical folding mainly takes place in the third trimester of pregnancy and may therefore be influenced by preterm birth. The aim of this study was to evaluate the development of specific cortical structures between early age (around 30weeks postmenstrual age) and term-equivalent age (TEA, around 40weeks postmenstrual age) in 71 extremely preterm infants, and to associate this to clinical characteristics and neurodevelopmental outcome at two years of age. First, analysis showed that the central sulcus (CS), lateral fissure (LF) and insula (INS) were present at early MRI in all infants, whereas the other sulci (post-central sulcus [PCS], superior temporal sulcus [STS], superior [SFS] and inferior [IFS] frontal sulcus) were only seen in part of the infants. Relative growth from early to TEA examination was largest in the SFS. A rightward asymmetry of the surface area was seen in development between both examinations except for the LF, which showed a leftward asymmetry at both time points. Second, lower birth weight z-score, multiple pregnancy and prolonged mechanical ventilation showed negative effects on cortical folding of the CS, LF, INS, STS and PCS, mainly on the first examination, suggesting that sulci developing the earliest were the most affected by clinical factors. Finally, in this cohort, a clear association between cortical folding and neurodevelopmental outcome at two years corrected age was found, particularly for receptive language.

Delayed cortical gray matter development in neonates with severe congenital heart disease

Background:This study aimed to assess cortical gray matter growth and maturation in neonates with congenital heart disease (CHD).Methods:Thirty-one (near) term neonates with severe CHD (8 univentricular heart malformation (UVH), 21 d-transposition of great arteries (d-TGA) and 2 aortic coarctation) underwent cerebral MRI before (postnatal-day 7) and after (postnatal-day 24) surgery. Eighteen controls with similar gestational age had one MRI (postnatal-day 23). Cortical gray matter volume (CGM), inner cortical surface (iCS), and median cortical thickness were extracted as measures of volumetric growth, and gyrification index (GI) as measure of maturation.Results:Over a median of 18 d, CGM increased by 21%, iCS by 17%, thickness and GI both by 9%. Decreased postoperative CGM and iCS were seen for CHD compared to controls (P values < 0.01), however with similar thickness and GI. UVH showed lower postoperative iCS, thickness (P values < 0.05) and GI (P value < 0.01) than d-TGA and controls. Infants requiring preoperative balloon-atrioseptostomy (BAS, 61%) had reduced postoperative CGM, iCS, and GI (P values < 0.05).Conclusion:Infants with severe CHD show reduced cortical volumes compared to controls with gyrification being delayed in UVH, but not in d-TGA. Infants requiring BAS show higher risk of impaired cortical volume and gyrification.

Perioperative neonatal brain injury is associated with worse school-age neurodevelopment in children with critical congenital heart disease

To assess the impact of perioperative neonatal brain injury and brain volumes on neurodevelopment throughout school‐age children with critical congenital heart disease (CHD).

Clinical and neuroimaging characteristics of cerebral sinovenous thrombosis in neonates undergoing cardiac surgery

Objectives: Neonates with congenital heart disease may have an increased risk of cerebral sinovenous thrombosis, but incidence rates are lacking. This study describes the clinical and neuroimaging characteristics of cerebral sinovenous thrombosis in neonates undergoing cardiac surgery. Methods: Forty neonates (78% male) requiring neonatal univentricular or biventricular cardiac repair using cardiopulmonary bypass were included. All underwent preoperative (median postnatal day 7) and postoperative (median postoperative day 7) magnetic resonance imaging of the brain, including venography, to detect cerebral sinovenous thrombosis. Clinical characteristics were compared between cerebral sinovenous thrombosis positive and cerebral sinovenous thrombosis negative neonates. Results: Postoperatively, cerebral sinovenous thrombosis was diagnosed in 11 neonates (28%), with the transverse sinus affected in all, and involvement of multiple sinuses in 10 (91%). Preoperatively, signs of thrombosis were seen in 3 cases (8%). Focal infarction of the basal ganglia was significantly more common in cerebral sinovenous thrombosis positive than cerebral sinovenous thrombosis negative neonates (P = .025). Cerebral sinovenous thrombosis positive neonates spent more time in the intensive care unit preoperatively (P = .001), had lower weight (P = .024) and lower postmenstrual age (P = .030) at surgery, and had prolonged use of a central venous catheter (P = .023) and a catheter placed in the internal jugular vein more often (P = .039). Surgical and postoperative factors were not different between new postoperative cerebral sinovenous thrombosis positive and cerebral sinovenous thrombosis negative neonates. Conclusions: Cerebral sinovenous thrombosis might be more common than previously understood in neonates undergoing cardiac surgery. In our study, cerebral sinovenous thrombosis was associated with a higher risk of additional intra‐parenchymal brain injury.

Prediction of cognitive and motor outcome of preterm infants based on automatic quantitative descriptors from neonatal MR brain images

This study investigates the predictive ability of automatic quantitative brain MRI descriptors for the identification of infants with low cognitive and/or motor outcome at 2–3 years chronological age. MR brain images of 173 patients were acquired at 30 weeks postmenstrual age (PMA) (n = 86) and 40 weeks PMA (n = 153) between 2008 and 2013. Eight tissue volumes and measures of cortical morphology were automatically computed. A support vector machine classifier was employed to identify infants who exhibit low cognitive and/or motor outcome (<85) at 2–3 years chronological age as assessed by the Bayley scales. Based on the images acquired at 30 weeks PMA, the automatic identification resulted in an area under the receiver operation characteristic curve (AUC) of 0.78 for low cognitive outcome, and an AUC of 0.80 for low motor outcome. Identification based on the change of the descriptors between 30 and 40 weeks PMA (n = 66) resulted in an AUC of 0.80 for low cognitive outcome and an AUC of 0.85 for low motor outcome. This study provides evidence of the feasibility of identification of preterm infants at risk of cognitive and motor impairments based on descriptors automatically computed from images acquired at 30 and 40 weeks PMA.

Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease

This review integrates data on brain dysmaturation and acquired brain injury using fetal and neonatal magnetic resonance imaging (MRI), including the contribution of cardiovascular physiology to differences in brain development, and the relationship between brain abnormalities and subsequent neurological impairments in infants with congenital heart disease (CHD). The antenatal and neonatal period are critical for optimal brain development; the developing brain is particularly vulnerable to haemodynamic disturbances during this time. Altered cerebral perfusion and decreased cerebral oxygen delivery in the antenatal period can affect functional and structural brain development, while postnatal haemodynamic fluctuations may cause additional injury. In critical CHD, brain dysmaturation and acquired brain injury result from a combination of underlying cardiovascular pathology and surgery performed in the neonatal period. MRI findings in infants with CHD can be used to evaluate potential clinical risk factors for brain abnormalities, and aid prediction of functional outcomes at an early stage. In addition, information on timing of brain dysmaturation and acquired brain injury in CHD has the potential to be used when developing strategies to optimize neurodevelopment.

Severe retinopathy of prematurity is associated with reduced cerebellar and brainstem volumes at term and neurodevelopmental deficits at 2 years

BackgroundTo evaluate the association between severe retinopathy of prematurity (ROP), measures of brain morphology at term-equivalent age (TEA), and neurodevelopmental outcome.MethodsEighteen infants with severe ROP (median gestational age (GA) 25.3 (range 24.6–25.9 weeks) were included in this retrospective case–control study. Each infant was matched to two extremely preterm control infants (n=36) by GA, birth weight, sex, and brain injury. T2-weighted images were obtained on a 3 T magnetic resonance imaging (MRI) at TEA. Brain volumes were computed using an automatic segmentation method. In addition, cortical folding metrics were extracted. Neurodevelopment was formally assessed at the ages of 15 and 24 months.ResultsInfants with severe ROP had smaller cerebellar volumes (21.4±3.2 vs. 23.1±2.6 ml; P=0.04) and brainstem volumes (5.4±0.5 ml vs. 5.8±0.5 ml; P=0.01) compared with matched control infants. Furthermore, ROP patients showed a significantly lower development quotient (Griffiths Mental Development Scales) at the age of 15 months (93±15 vs. 102±10; P=0.01) and lower fine motor scores (10±3 vs. 12±2; P=0.02) on Bayley Scales (Third Edition) at the age of 24 months.ConclusionSevere ROP was associated with smaller volumes of the cerebellum and brainstem and with poorer early neurodevelopmental outcome. Follow-up through childhood is needed to evaluate the long-term consequences of our findings.

Changes in brain morphology and microstructure in relation to early brain activity in extremely preterm infants

Background and ObjectiveTo investigate the relation of early brain activity with structural (growth of the cortex and cerebellum) and white matter microstructural brain development.MethodsA total of 33 preterm neonates (gestational age 26±1 weeks) without major brain abnormalities were continuously monitored with electroencephalography during the first 48 h of life. Rate of spontaneous activity transients per minute (SAT rate) and inter-SAT interval (ISI) in seconds per minute were calculated. Infants underwent brain magnetic resonance imaging ∼30 (mean 30.5; min: 29.3–max: 32.0) and 40 (41.1; 40.0–41.8) weeks of postmenstrual age. Increase in cerebellar volume, cortical gray matter volume, gyrification index, fractional anisotropy (FA) of posterior limb of the internal capsule, and corpus callosum (CC) were measured.ResultsSAT rate was positively associated with cerebellar growth (P=0.01), volumetric growth of the cortex (P=0.027), increase in gyrification (P=0.043), and increase in FA of the CC (P=0.037). ISI was negatively associated with cerebellar growth (P=0.002).ConclusionsIncreased early brain activity is associated with cerebellar and cortical growth structures with rapid development during preterm life. Higher brain activity is related to FA microstructural changes in the CC, a region responsible for interhemispheric connections. This study underlines the importance of brain activity for microstructural brain development.

Amplitude-Integrated Electroencephalography for Early Recognition of Brain Injury in Neonates with Critical Congenital Heart Disease

Objective To study perioperative amplitude‐integrated electroencephalography (aEEG) as an early marker for new brain injury in neonates requiring cardiac surgery for critical congenital heart disease (CHD). Study design This retrospective observational cohort study investigated 76 neonates with critical CHD who underwent neonatal surgery. Perioperative aEEG recordings were evaluated for background pattern (BGP), sleep‐wake cycling (SWC), and ictal discharges. Spontaneous activity transient (SAT) rate, inter‐SAT interval (ISI), and percentage of time with an amplitude <5 &mgr;V were calculated. Routinely obtained preoperative and postoperative magnetic resonance imaging of the brain were reviewed for brain injury (moderate‐severe white matter injury, stroke, intraparenchymal hemorrhage, or cerebral sinovenous thrombosis). Results Preoperatively, none of the neonates showed an abnormal BGP (burst suppression or worse) or ictal discharges. Postoperatively, abnormal BGP was seen in 18 neonates (24%; 95% CI, 14%‐33%) and ictal discharges was seen in 13 neonates (17%; 95% CI, 8%‐26%). Abnormal BGP and ictal discharges were more frequent in neonates with new postoperative brain injury (P = .08 and .01, respectively). Abnormal brain activity (ie, abnormal BGP or ictal discharges) was the single risk factor associated with new postoperative brain injury in multivariable logistic regression analysis (OR, 4.0; 95% CI, 1.3‐12.3; P = .02). Postoperative SAT rate, ISI, or time <5 &mgr;V were not associated with new brain injury. Conclusion Abnormal brain activity is an early, bedside marker of new brain injury in neonates undergoing cardiac surgery. Not only ictal discharges, but also abnormal BGP, should be considered a clear sign of underlying brain pathology.

Automatic segmentation of the intracranial volume in fetal MR images

MR images of the fetus allow non-invasive analysis of the fetal brain. Quantitative analysis of fetal brain development requires automatic brain tissue segmentation that is typically preceded by segmentation of the intracranial volume (ICV). This is challenging because fetal MR images visualize the whole moving fetus and in addition partially visualize the maternal body. This paper presents an automatic method for segmentation of the ICV in fetal MR images. The method employs a multi-scale convolutional neural network in 2D slices to enable learning spatial information from larger context as well as detailed local information. The method is developed and evaluated with 30 fetal T2-weighted MRI scans (average age