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Preterm birth is often associated with impaired brain development. The state and expected progression of preterm brain development can be evaluated using quantitative assessment of MR images. Such measurements require accurate segmentation of different tissue types in those images. This paper presents an algorithm for the automatic segmentation of unmyelinated white matter (WM), cortical grey matter (GM), and cerebrospinal fluid in the extracerebral space (CSF). The algorithm uses supervised voxel classification in three subsequent stages. In the first stage, voxels that can easily be assigned to one of the three tissue types are labelled. In the second stage, dedicated analysis of the remaining voxels is performed. The first and the second stages both use two-class classification for each tissue type separately. Possible inconsistencies that could result from these tissue-specific segmentation stages are resolved in the third stage, which performs multi-class classification. A set of T1- and T2-weighted images was analysed, but the optimised system performs automatic segmentation using a T2-weighted image only. We have investigated the performance of the algorithm when using training data randomly selected from completely annotated images as well as when using training data from only partially annotated images. The method was evaluated on images of preterm infants acquired at 30 and 40 weeks postmenstrual age (PMA). When the method was trained using random selection from the completely annotated images, the average Dice coefficients were 0.95 for WM, 0.81 for GM, and 0.89 for CSF on an independent set of images acquired at 30 weeks PMA. When the method was trained using only the partially annotated images, the average Dice coefficients were 0.95 for WM, 0.78 for GM and 0.87 for CSF for the images acquired at 30 weeks PMA, and 0.92 for WM, 0.80 for GM and 0.85 for CSF for the images acquired at 40 weeks PMA. Even though the segmentations obtained using training data from the partially annotated images resulted in slightly lower Dice coefficients, the performance in all experiments was close to that of a second human expert (0.93 for WM, 0.79 for GM and 0.86 for CSF for the images acquired at 30 weeks, and 0.94 for WM, 0.76 for GM and 0.87 for CSF for the images acquired at 40 weeks). These results show that the presented method is robust to age and acquisition protocol and that it performs accurate segmentation of WM, GM, and CSF when the training data is extracted from complete annotations as well as when the training data is extracted from partial annotations only. This extends the applicability of the method by reducing the time and effort necessary to create training data in a population with different characteristics. [ABSTRACT FROM AUTHOR]

A number of algorithms for brain segmentation in preterm born infants have been published, but a reliable comparison of their performance is lacking. The NeoBrainS12 study ( http://neobrains12.isi.uu.nl ), providing three different image sets of preterm born infants, was set up to provide such a comparison. These sets are (i) axial scans acquired at 40 weeks corrected age, (ii) coronal scans acquired at 30 weeks corrected age and (iii) coronal scans acquired at 40 weeks corrected age. Each of these three sets consists of three T1- and T2-weighted MR images of the brain acquired with a 3T MRI scanner. The task was to segment cortical grey matter, non-myelinated and myelinated white matter, brainstem, basal ganglia and thalami, cerebellum, and cerebrospinal fluid in the ventricles and in the extracerebral space separately. Any team could upload the results and all segmentations were evaluated in the same way. This paper presents the results of eight participating teams. The results demonstrate that the participating methods were able to segment all tissue classes well, except myelinated white matter. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that color Doppler-measured cerebral blood flow velocity (CD-CBFV) as measured in the three feeding arteries of the brain can be used as an estimator of global cerebral blood flow. Patients and Methods: CD-CBFV was determined as soon as possible after determination of phase-contrast magnetic resonance angiography-measured blood volume flow (PC-MRA BVF) by adding up angle-corrected time-averaged mean flow velocities of both internal carotid arteries and basilar artery. 30 newborns (gestational age ranging from 25 to 42 weeks; actual weight ranging from 1,050 to 5,858 g; postconceptional age ranging from 225 to 369 days) were investigated. Results: Doppler-determined CBFV ranged from 37 to 131 cm/s with a median of 69 cm/s. CD-CBFV showed a positive correlation with actual weight (r = 0.56, p < 0.01) and postconceptional age (r = 0.53, p < 0.01). CD-CBFV correlated positively with PC-MRA-measured BVF (r = 0.51, p < 0.01). Gestational age at birth, mechanical ventilation or gender did not influence this relationship. The limits of agreement, however, are wide, especially at higher CD-CBFV- and PC-MRA-measured BVF. Conclusion: CD-CBFV may be used as a non-invasive trend-monitoring tool to detect gross changes in global cerebral blood flow in the unstable and sick neonate. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Brain injury patterns of preterm infants with perinatal asphyxia (PA) are underreported. We aimed to explore brain magnetic resonance imaging (MRI) findings and associated neurodevelopmental outcomes in these newborns. Methods: Retrospective multicenter study included infants with gestational age (GA) 24.0–36.0 weeks and PA, defined as ≥2 of the following: (1) umbilical cord pH ≤7.0, (2) 5-min Apgar score ≤5, and (3) fetal distress or systemic effects of PA. Findings were compared between GA <28.0 (group 1), 28.0–31.9 (group 2), and 32.0–36.0 weeks (group 3). Early MRI (<36 weeks postmenstrual age or <10 postnatal days) was categorized according to predominant injury pattern, and MRI around term-equivalent age (TEA, 36.0–44.0 weeks and ≥10 postnatal days) using the Kidokoro score. Adverse outcomes included death, cerebral palsy, epilepsy, severe hearing/visual impairment, or neurodevelopment <-1 SD at 18–24 months corrected age. Results: One hundred nineteen infants with early MRI (n = 94) and/or MRI around TEA (n = 66) were included. Early MRI showed predominantly hemorrhagic injury in groups 1 (56%) and 2 (45%), and white matter (WM)/watershed injury in group 3 (43%). Around TEA, WM scores were highest in groups 2 and 3. Deep gray matter (DGM) (aOR 15.0, 95% CI: 3.8–58.9) and hemorrhagic injury on early MRI (aOR 2.5, 95% CI: 1.3–4.6) and Kidokoro WM (aOR 1.3, 95% CI: 1.0–1.6) and DGM sub-scores (aOR 4.8, 95% CI: 1.1–21.7) around TEA were associated with adverse neurodevelopmental outcomes. Conclusion: The brain injury patterns following PA in preterm infants differ across GA. Particularly DGM abnormalities are associated with adverse neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship between sleep stages and neural microstructure – measured using diffusion tensor imaging – of the posterior limb of the internal capsule and corticospinal tract in preterm infants. A retrospective cohort of 50 preterm infants born between 24 + 4 and 29 + 3 weeks gestational age was included in the study. Sleep stages were continuously measured for 5–7 consecutive days between 29 + 0 and 31 + 6 weeks postmenstrual age using an in-house-developed, and recently published, automated sleep staging algorithm based on routinely measured heart rate and respiratory rate. Additionally, a diffusion tensor imaging scan was conducted at term equivalent age as part of standard care. Region of interest analysis of the posterior limb of the internal capsule was performed, and tractography was used to analyze the corticospinal tract. The association between sleep and white matter microstructure of the posterior limb of the internal capsule and corticospinal tract was examined using a multiple linear regression model, adjusted for potential confounders. The results of the analyses revealed an interaction effect between sleep stage and days of invasive ventilation on the fractional anisotropy of the left and right posterior limb of the internal capsule (β = 0.04, FDR-adjusted p = 0.001 and β = 0.04, FDR-adjusted p = 0.02, respectively). Furthermore, an interaction effect between sleep stage and days of invasive ventilation was observed for the radial diffusivity of the mean of the left and right PLIC (β = −4.1e-05, FDR-adjusted p = 0.04). Previous research has shown that, in very preterm infants, invasive ventilation has a negative effect on white matter tract maturation throughout the brain. A positive association between active sleep and white matter microstructure of the posterior limb of the internal capsule, may indicate a protective role of sleep in this vulnerable population. • Active sleep positively influences white matter microstructure in preterm infants. • Interaction between sleep stages and days of invasive ventilation affects brain development. • Active sleep shows a protective role in preterm infants with longer invasive ventilation days. • Increased AS is associated with higher fractional anisotropy in the PLIC. [ABSTRACT FROM AUTHOR]

To examine whether accelerometry can quantitate asymmetry of upper limb activity in infants aged 3–12 months at risk for developing unilateral spastic cerebral palsy (USCP). A prospective study was performed in 50 infants with unilateral perinatal brain injury at high risk of developing USCP. Triaxial accelerometers were worn on the ipsilateral and contralesional upper limb during the Hand Assessment for Infants (HAI). Infants were grouped in three age intervals (3–5 months, 5–7.5 months and 7.5 until 12 months). Each age interval group was divided in a group with and without asymmetrical hand function based on HAI cutoff values suggestive of USCP. In a total of 82 assessments, the asymmetry index for mean upper limb activity was higher in infants with asymmetrical hand function compared to infants with symmetrical hand function in all three age groups (ranging from 41 to 51% versus − 2–6%, p < 0.01), while the total activity of both upper limbs did not differ. Upper limb accelerometry can identify asymmetrical hand function in the upper limbs in infants with unilateral perinatal brain injury from 3 months onwards and is complementary to the Hand Assessment for Infants. [ABSTRACT FROM AUTHOR]

Early human brain development constitutes a sequence of intricate processes resulting in the ontogeny of functionally operative neural circuits. Developmental trajectories of early brain network formation are genetically programmed and can be modified by epigenetic and environmental influences. Such alterations may exert profound effects on neurodevelopment, potentially persisting throughout the lifespan. This review focuses on the critical period of fetal and early postnatal brain development. Here we collate findings from neuroimaging studies, with a particular focus on functional MRI research that interrogated early brain network development in both health and high-risk or disease states. First, we will provide an overview of the developmental processes that take place from the embryonic period through early infancy in order to contextualize brain network formation. Second, functional brain network development in the typically developing brain will be discussed. Third, we will touch on prenatal and perinatal risk factors that may interfere with the trajectories of functional brain wiring, including prenatal substance exposure, maternal mental illness and preterm birth. Collectively, studies have revealed the blueprint of adult human brain organization to be present in the neonatal brain. Distinct attributes of human brain architecture have even been detected in the developing fetal brain from as early as 24 postconceptional weeks. During postnatal brain development, the brain's wiring pattern is further sculpted and modulated to become the full facsimile of the adult human brain, with functional brain network refinement being more rigorous than structural brain network maturation. Advances in neuroimaging techniques have paved the way towards a comprehensive understanding of the maturational pathways of brain network development and of how early developmental adversity may affect these trajectories. Such insights are fundamental for our understanding of human brain functioning, for early identification of infants at risk, as well as for future neuroprotective strategies. [ABSTRACT FROM AUTHOR]

B MATERIALS AND METHODOLOGY: b 21 healthy newborn piglets were divided into 3 cohorts to either receive normal saline vehicles (control group A, n=6), bicuculine 4mg/kg IV (seizure group B, n= 7) to induce seizures or bicuculine 4mg/kg IV followed by phenobarbitone loading dose 20mg/kg after 10 min of continuous electrical seizures (treated seizure group C, n=8) over two time points 3h apart. Electrographic seizures were identified in 296 (33.9%) newborns, in which 26 (10.6%) had status epilepticus, 170 (69.7%) repetitive seizures and 48 (19.7%) single seizure. A comparison of treatment pathways for seizures in newborns across rural and non-rural level... B Dickman J b SP 1 sp , Carrasco McCaul M SP 1 sp I SP 1 sp University Of Wisconsin School Of Medicine And Public Health, Madison, United States i B BACKGROUND: b Seizures are more common during the neonatal period than at any other age, occurring at a rate of 1.10-5.5 per 1,000 live births. Amplitude integrated electroencephalography combined with raw electroencephalography and video imaging (video aEEG/EEG) provides real-time screening for seizure detection. The survey collected information regarding the evaluation of neonatal seizures, anti-seizure medication availability, electroencephalogram (EEG) monitoring methods, and if and how an official treatment pathway for neonatal seizure patients was established at their institution. [Extracted from the article]

• Dual-channel quantitative EEG metrics are useful to distinguish between sleep-wake states of preterm neonates in the first postnatal hours. • Combining different qEEG metrics helps develop a sleep-wake state classifier robust against rapid maturational changes in the preterm period. • The complexity features showed the best sleep staging capability and greatest robustness among several quantitative EEG metrics. To investigate the feasibility of automated sleep staging based on quantitative analysis of dual-channel electroencephalography (EEG) for extremely and very preterm infants during their first postnatal days. We enrolled 17 preterm neonates born between 25 and 30 weeks of gestational age. Three-hour behavioral sleep observations and simultaneous dual-channel EEG monitoring were conducted for each infant within their first 72 hours after birth. Four kinds of representative and complementary quantitative EEG (qEEG) metrics (i.e., bursting, synchrony, spectral power, and complexity) were calculated and compared between active sleep, quiet sleep, and wakefulness. All analyses were performed in offline mode. In separate comparison analyses, significant differences between sleep-wake states were found for bursting, spectral power and complexity features. The automated sleep-wake state classifier based on the combination of all qEEG features achieved a macro-averaged area under the curve of receiver operating characteristic of 74.8%. The complexity features contributed the most to sleep-wake state classification. It is feasible to distinguish between sleep-wake states within the first 72 postnatal hours for extremely and very preterm infants using qEEG metrics. Our findings offer the possibility of starting personalized care dependent on preterm infants' sleep-wake states directly after birth, potentially yielding long-run benefits for their developmental outcomes. [ABSTRACT FROM AUTHOR]

Germinal matrix-intraventricular haemorrhage (GMH-IVH) remains a serious problem in the very and extremely preterm infant. This article reviews current methods of diagnosis, treatment and neurodevelopmental outcome in preterm infants with low-grade and severe GMH-IVH. We conclude that there is still no consensus on timing of intervention and treatment of infants with GMH-IVH, whether or not complicated by post-haemorrhagic ventricular dilatation. The discrepancies between the studies underline the need for international collaboration to define the optimal strategy for these infants. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Fetuses with congenital heart defects (CHD) show delayed neurodevelopment, fetal growth restriction (FGR) and placenta related complications. The neurodevelopmental delay may be, partly, attributed to placental factors. As both placental development and fetal aortic flow/oxygenation influence neurodevelopment, placentas were compared within fetal CHD groups based on aortic oxygenation and flow, aiming to unravel the true effects in the developmental processes. Placental tissues of pregnancies with fetal CHD and healthy controls were selected from biobanks of two Dutch academic hospitals (LUMC, UMCU). Additionally, biometry and Dopplers were assessed. CHD cases with reduced oxygenation (RO) towards the fetal brain were compared to cases with reduced flow (RF) in the aortic arch and healthy controls. Genetic abnormalities, termination of pregnancy, fetal demise and/or multiple pregnancies were excluded. Histological outcomes were related to fetal Dopplers and biometry. A placenta severity score was used to assess the severity of placental abnormalities per case. In CHD, significantly more delayed maturation, maternal vascular malperfusion, fetal hypoxia and higher placenta severity scores (median 14 in RO, 14 in RF, 5 in controls, p < 0.001) were observed. Doppler abnormalities (PI UA > p90, PI MCA < p10, CPR < p10) and FGR were more often found in CHD. There were no differences in placental abnormalities, fetal growth and fetal Dopplers between cases with RO and RF. Fetal hemodynamics in the ascending aorta could not be related to placenta characteristics. We hypothesize that placental development influences neurodevelopment in excess of hemodynamics in CHD cases. • Placental features in fetal CHD could not be related to aortic flow and oxygenation. • Next to hemodynamic alterations, alternative contributing factors might play a role. • Abnormal placental development might influence neurodevelopment in these cases. [ABSTRACT FROM AUTHOR]

Background: Sleep is paramount for optimal brain development in infants admitted to the neonatal intensive care unit. Besides (minimally) invasive technical approaches to study sleep in infants, there is currently a large variety of behavioral sleep stage classification methods (BSSCs) that can be used to identify sleep stages in preterm infants born <37 weeks gestational age. However, they operate different criteria to define sleep stages, which limits the comparability and reproducibility of research on preterm sleep. This scoping review aims to: 1) identify and elaborate on existing neonatal BSSCs used for preterm infants, 2) examine the reliability and validity of these BSSCs, and 3) identify which criteria are most used for different ages, ranging from 23 to 37 weeks postmenstrual age at observation.Methods: To map the existing BSSCs, PubMed, EMBASE and Cochrane were searched for studies using a BSSC to identify sleep stages in preterm infants.Results: In total, 36 BSSCs were identified with on average five item categories assessed per BSSC, most frequently: eyes, body movements, facial movements, sounds, and respiratory pattern. Furthermore, validity and reliability of the BSSCs were tested in less than half of the included studies. Finally, BSSCs were used in infants of all ages, regardless the age for which the BSSC was originally developed.Conclusions: Items used for scoring in the different BSSCs were relatively consistent. The age ranges, reliability, and validity of the BSSCs were not consistently reported in most studies. Either validation studies of existing BSSCs or new BSSCs are necessary to improve the comparability and reproducibility of previous and future preterm behavioral sleep studies. [ABSTRACT FROM AUTHOR]

Abstract. Objective. To investigate whether or not postasphyctic cerebral hypoperfusion and decreased cerebral metabolism occur in the perinatally asphyxiated neonate, as has been reported in adults and newborn animals. Methods. Using near-infrared spectroscopy, we monitored changes in oxyhemoglobin (HbO[sub 2]), deoxyhemoglobin (HbR), total hemoglobin (HbO[sub 2] + HbR, which represents changes in cerebral blood volume [CBV]), and cytochrome oxidase (Cytaa[sub 3], which indicates changes in oxidation level of this intracerebral mitochondrial enzyme). Thirty-one neonates (gestational age >34 weeks), divided into three groups, were monitored between 2 and 12 hours or between 12 and 24 hours of life. Group I consisted of healthy newborns: N = 8 (2 to 12 hours) and N = 5 (12 to 24 hours). Patients in group II were moderately asphyxiated newborns but neurologically normal in the first 24 hours of life: N = 6 (2 to 12 hours) and N = 3 (12 to 24 hours). Group III consisted of severely asphyxiated newborns with an abnormal neurologic behavior within 24 hours after birth: N = 5 (2 to 12 hours) and N = 4 (12 to 24 hours). Results. From 2 to 12 h, CBV levels in groups I and ii were stable. In group III CBV decreased in all infants. This decrease in CBV was associated with a drop in both HbO[sub 2] and HbR. Cytaa[sub 3] was stable in groups I and II, but showed a marked decrease in two of the five infants of group III. There was a positive relationship between CBV and mean arterial blood pressure in groups II and III. Between 12 and 24 hours, all groups showed stable CBV and Cytaa[sub 3] patterns. A positive relation existed now between transcutaneous Pco[sub 2] and CBV in groups II and III. Conclusions. CBV,... [ABSTRACT FROM AUTHOR]

• The neonatal brain can generate epileptic high-frequency oscillations (HFOs), though their occurrence is not common. • Neonatal ripples and fast ripples co-occur with ictal and interictal sharp transients. • Our data on neonatal HFOs could not yet support their potential value for outcome prediction. Neonatal seizures are often the first symptom of perinatal brain injury. High-frequency oscillations (HFOs) are promising new biomarkers for epileptogenic tissue and can be found in intracranial and surface EEG. To date, we cannot reliably predict which neonates with seizures will develop childhood epilepsy. We questioned whether epileptic HFOs can be generated by the neonatal brain and potentially predict epilepsy. We selected 24 surface EEGs sampled at 2048 Hz with 175 seizures from 16 neonates and visually reviewed them for HFOs. Interictal epochs were also reviewed. We found HFOs in thirteen seizures (7%) from four neonates (25%). 5025 ictal ripples (rate 10 to 1311/min; mean frequency 135 Hz; mean duration 66 ms) and 1427 fast ripples (rate 8 to 356/min; mean frequency 298 Hz; mean duration 25 ms) were marked. Two neonates (13%) showed interictal HFOs (285 ripples and 25 fast ripples). Almost all HFOs co-occurred with sharp transients. We could not find a relationship between neonatal HFOs and outcome yet. Neonatal HFOs co-occur with ictal and interictal sharp transients. The neonatal brain can generate epileptic ripples and fast ripples, particularly during seizures, though their occurrence is not common and potential clinical value not evident yet. [ABSTRACT FROM AUTHOR]

Introduction: Prediction of neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy remains an important challenge. Various studies have shown that the predictive ability of different modalities changed after the introduction of therapeutic hypothermia. This paper reviews the diagnostic test accuracy of the different modalities that are being used to predict neurodevelopmental outcomes following therapeutic hypothermia. Methods: A systematic literature search was performed using Embase and PubMed. Two reviewers independently included eligible studies and extracted data. The quality of the studies was assessed using the Quality in Prognosis Studies Tool. Meta-analyses were performed where possible. Results: Forty-seven articles and 3 conference abstracts were included, reporting on 3,072infants of whom 39% died or had an adverse neurodevelopmental outcome. A meta-analysis could be performed using 37 articles on (amplitude-integrated) electroencephalography (EEG), conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and proton magnetic resonance spectroscopy (1H-MRS). Amplitude-integrated EEG (aEEG) at 24 and 72 h showed similar high diagnostic OR, while aEEG at 6 h and EEG performed less, both due to a low specificity. For MRI, most studies reported scoring systems in which early (<8 days) MRI performed better than late (≥8 days) MRI. Injury to the posterior limb of the internal capsule on MRI or to the thalami on DWI were strong individual predictors, as was an increased lactate/N-acetylaspartate peak on 1H-MRS. Conclusions: In the era of therapeutic hypothermia, the different modalities remain good predictors of neurodevelopmental outcome. However, timing should be taken into account. aEEG may initially be false positive and gets more reliable after 24 h. In contrast, MRI should be used during the first week, as its predictive value decreases afterwards. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate whether a new MRI scoring system for preterm non-haemorrhagic white matter injury (WMI), derived from the analysis of the natural evolution of WMI throughout the neonatal period until term-equivalent age, can be used for outcome prediction. Methods: Eighty-two infants <36 weeks gestation with WMI diagnosed from sequential cranial ultrasound and confirmed on neonatal MRI were retrospectively included. WMI was classified in four grades of severity. Neurodevelopmental data at a median age of 24 months were analysed. Results: In 74 surviving children WMI severity was strongly associated with the presence and severity of cerebral palsy (CP) and other neurodevelopmental impairments (Spearman's rank correlation 0.88, p < 0.001). Only 3 children with grade I WMI (9%) developed CP (all ambulant) and their developmental scores were not different to those from the controls, although they started walking significantly later (p = 0.036). Of the 6 children with grade II, 83% developed CP (mild in most), whereas 91% of the 34 children with grade III had CP (moderate-severe in 76%) and all had some degree of neurodevelopmental impairment. Three children with grade III WMI did not develop CP; their imaging showed, in contrast to children who developed CP, that the cysts did not affect the corticospinal tracts; also, myelin in the posterior limb of the internal capsule appeared normal in 2 children and suboptimal in 1. Conclusions: This MRI scoring system for preterm WMI can be used to predict neurodevelopmental outcomes. Individualized assessment of the site of lesions and the progression of myelination improves prognostic accuracy. [ABSTRACT FROM AUTHOR]

Highlights • "Rodent studies support an important role of social play in the development of brain and behavior". • "Children with a chronic disease are at risk for physical, social, emotional and cognitive problems". • "Facilitating (social) play may improve the developmental outcome of chronical diseased children". • "All children may benefit from knowledge about the impressive resilience of young patients". • "Interactive technology/games can help patients to play with peers, fostering social inclusion". Abstract Play is of vital importance for the healthy development of children. From a developmental perspective, play offers ample physical, emotional, cognitive, and social benefits. It allows children and adolescents to develop motor skills, experiment with their (social) behavioural repertoire, simulate alternative scenarios, and address the various positive and negative consequences of their behaviour in a safe and engaging context. Children with a chronic or life-threatening disease may face obstacles that negatively impact play and play development, possibly impeding developmental milestones, beyond the actual illness itself. Currently, there is limited understanding of the impact of (1) aberrant or suppressed play and (2) play-related interventions on the development of chronic diseased children. We argue that stimulating play behaviour enhances the adaptability of a child to a (chronic) stressful condition and promotes cognitive, social, emotional and psychomotor functioning, thereby strengthening the basis for their future health. Systematic play research will help to develop interventions for young patients, to better cope with the negative consequences of their illness and stimulate healthy development. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) is the standard neuroimaging technique to assess perinatal asphyxia-associated brain injury in full-term infants. Diffusion-weighted imaging (DWI) is most informative when assessed during the first week after the insult. Objectives: To study the DWI abnormalities of the thalamus and basal ganglia in full-term infants with perinatal asphyxia. Methods: Fifty-five (near) term infants (normothermia n = 23; hypothermia n = 32) with thalamus and/or basal ganglia injury were included. MRI findings were assessed visually and quantitatively calculating apparent diffusion coefficient (ADC) values. Thalamus/basal ganglia ADC ratios were calculated to analyze the differences between these areas. Infants with an early MRI (days 1–3) or later MRI (days 4–7) were compared. Results: Isolated extensive thalamic injury was seen early, and focal thalamic and basal ganglia injury was seen later. On the early MRI, visual assessment underestimated abnormalities in the basal ganglia (59% abnormal vs. 90% abnormal on quantitative assessment; p = 0.015), suggesting the need for quantitative assessment. In infants treated with hypothermia, the thalamus/basal ganglia ADC ratio was lower. Conclusions: Both visual analysis and quantitative evaluation of cerebral MRI after perinatal asphyxia are needed, especially during the first few days after birth. Timing of ADC changes is influenced by therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

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 30 weeks postmenstrual age) and term-equivalent age (TEA, around 40 weeks 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. [ABSTRACT FROM AUTHOR]

Background and aim Disturbances in cerebral oxygenation saturation (SO 2 ) have been linked to adverse outcome in adults, children, and neonates. In intensive care, the cerebral SO 2 is increasingly being monitored by Near-InfraRed Spectroscopy (NIRS). Unfortunately NIRS has a limited penetration depth. The “modified T 2 -prepared Blood Imaging of Oxygen Saturation” (T 2 -BIOS) MR sequence provides a step towards full brain SO 2 measurement. Materials and methods Tissue SO 2 , and venous SO 2 (S v O 2 ) were obtained simultaneously by T 2 -BIOS during a respiratory challenge in ten healthy volunteers. These two measures were compared to SO 2 that was obtained by a single probe MR-compatible NIRS setup, and to cerebral blood flow and venous SO 2 that were obtained by arterial spin labelling and T 2 -TRIR, respectively. Results SO 2-T2-BIOS and SO 2-NIRS had a mean bias of − 4.0% (95% CI − 21.3% to 13.3%). S v O 2-T2-BIOS correlated with SO 2-NIRS (R 2 = 0.41, p = 0.002) and S v O 2-T2-TRIR (R 2 = 0.87, p = 0.002). In addition, SO 2-NIRS correlated with S v O 2-T2-TRIR (R 2 = 0.85, p = 0.003) Frontal cerebral blood flow correlated with SO 2-T2-BIOS (R 2 = 0.21, p = 0.04), but was not significant in relation to SO 2-NIRS . Discussion/conclusion Full brain SO 2 assessment by any technique may help validating NIRS and may prove useful in guiding the clinical management of patient populations with cerebral injury following hypoxic-ischaemic events. The agreement between NIRS and T 2 -BIOS provides confidence in measuring cerebral SO 2 by either technique. As it stands now, the T 2 -BIOS represents a novel idea and future work will focus on improvements to make it a reliable tool for SO 2 assessment. [ABSTRACT FROM AUTHOR]

Objective: Cranial magnetic resonance imaging (MRI) is associated with neurodevelopmental outcome in full-term infants with neonatal encephalopathy (NE) following presumed perinatal asphyxia. The aim of this study is to relate 2-dimensional measurements of the basal ganglia and thalami (BGT) and cerebellum in the first week after birth and after 3 months with neurodevelopmental outcome at 18 months. Methods: Retrospectively, 29 full-term infants with NE following presumed perinatal asphyxia who had a cranial MRI in the first week after birth were studied serially. One- and 2-dimensional measurements were obtained and related to different patterns of brain injury, and neurodevelopmental outcome at 18 months. A Griffiths developmental quotient <85 or cerebral palsy was considered adverse. Results: On the first MRI, the adverse outcome group showed increased basal ganglia width (42.1 ± 0.1 vs. 40.3 ± 0.3 mm, p < 0.001), thalamic width (40.3 ± 0.1 vs. 39.3 ± 1.0 mm, p < 0.001), and basal ganglia surface (1,230 ± 21 vs. 1,199 ± 36 mm2, p = 0.007) compared to the favorable outcome group. In the BGT lesions group, basal ganglia width and thalamic width were increased compared to the watershed infarction group (42.1 ± 0.1 vs. 40.9 ± 0.8 mm, p < 0.001, and 40.3 ± 0.1 vs. 39.9 ± 0.5 mm, p = 0.01, respectively). On the second MRI, cerebellar width was larger in the favorable outcome group (p = 0.025). There was a greater increase in dimensions between both MRI time points for basal ganglia width (p = 0.014), basal ganglia surface (p = 0.028) and thalamic width (p = 0.012) in the favorable outcome group. Conclusions: One- and 2-dimensional measurements for basal ganglia surface, BGT width and cerebellar width are associated with neurodevelopmental outcome at 18 months. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) is frequently used to assess brain development in preterm infants. This study investigates maturational changes in diffusivity measures in 122 regions of the brain between 30 and 40 weeks postmenstrual age (PMA) using the neonatal atlas of Oishi and colleagues (Oishi et al., 2011). Forty infants without cerebral injury and with normal neurodevelopmental outcome were selected from a cohort of preterm infants (gestational age < 28 weeks), scanned longitudinally at 30 and 40 weeks PMA. Fractional anisotropy (FA) changed significantly in 84 brain regions, with the largest increase in the central brain regions; by contrast, the cortical brain regions showed a decrease in FA. Mean, radial and axial diffusivity all showed a clear decrease in the majority of brain regions. This study provides longitudinal reference diffusivity values in a cohort of extremely preterm infants, showing a central to peripheral and posterior to anterior directed gradient, in line with our current understanding of brain maturation, and adding to this knowledge. This study further elucidates brain maturation in preterm infants during the last 10 weeks prior to term equivalent age. The presented values can be used as a reference for assessing brain development in other cohorts, when investigating the effects of brain injury in this vulnerable period, and to evaluate the effect of future neuroprotective strategies. [ABSTRACT FROM AUTHOR]

Background: Impairment of gas and substrate exchange through the placenta leads to fetal hypoxia and growth restriction. Oxygenation of vital organs is maintained with preferential perfusion at the expense of less vital organs, challenging the fetal cardiovascular system. Objectives: To identify cardiovascular compromise in preterm small for gestational age (SGA) infants using the cardiac biomarker B-type natriuretic peptide (BNP), which indicates the workload of the myocardium. Methods: In this retrospective case-control study, 26 SGA infants born at less than 32 weeks of gestation from October 2009 to October 2010 were matched for gestational age and month of birth with 26 appropriate for gestational age (AGA) infants. Antenatal Doppler ultrasound was used to identify fetal hemodynamic changes by determination of the pulsatility index (PI) of the middle cerebral artery (MCA-PI), umbilical artery (UA-PI) and veins of the ductus venosus (DV-PIV). These indices were compared with BNP levels obtained within 6 h after birth. Results: Antenatal PIs of MCA, UA and DV were significantly related to elevated BNP levels after birth in SGA infants, but not in AGA infants (SGA: MCA-PI = r2 0.23, p < 0.05; UA-PI = r2 0.46, p < 0.01; DV-PIV = r2 0.31, p < 0.05). Furthermore, signs of perinatal (chronic) asphyxia coincided with elevated levels of BNP. SGA was related to more postnatal cardiocirculatory complications. No significant relations between postnatal cardiac ultrasound measurements, placenta size and BNP were found. Conclusion: BNP levels were elevated early after birth in SGA infants and corresponded positively with Doppler indices of circulatory compromise. This suggests an increased workload of the myocardium. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The purpose of this study was to evaluate if non-invasive Arterial Spin Labeling MR imaging can be used to assess changes in brain perfusion with age which reflect neonatal brain development. For this purpose regional perfusion values obtained with ASL MR imaging were evaluated as a function of postmenstrual age. Materials and methods: Pulsed ASL imaging was performed in 33 neonates with a postmenstrual age from 30 to 53 weeks. Whole brain cerebral blood flow (wbCBF), CBF in the basal ganglia and thalamus (BGT-CBF), in the occipital cortex (OC-CBF) and the frontal cortex (FC-CBF) were measured. Regional CBF values were expressed quantitatively (in ml/100gmin) and relative as a percentage of the wbCBF. Results: Mean wbCBF increased significantly from 7±2ml/100gmin (mean±sd) at 31±2 weeks postmenstrual age to 12±3ml/100gmin at term-equivalent age (TEA) and 29±9ml/100gmin at 52±1 weeks postmenstrual age. Relative regional CBF was highest in the BGT at all time-points. Relative OC-and FC-CBF increased significantly from 31±2 weeks postmentrual age to TEA. A significant difference in relative BGT-CBF and OC-CBF was shown between infants at 31±2 weeks postmenstrual age and infants scanned at 52±1 weeks postmenstrual age. Relative perfusion in the BGT measured at TEA was significant different compared to 52±1 weeks postmenstrual age. Conclusion: In conclusion, regional differences in CBF and changes with postmenstrual age could be detected with ASL in neonates. This suggests that ASL can be used as a non-invasive tool to investigate brain maturation in neonates. [Copyright &y& Elsevier]