Living on Site While Renovating; Flexible Instructional Design of Post-Graduate Medical Training.

Background: Developing theoretical courses for post-graduate medical training that are aligned to current workplace-based learning practices and adaptive to change in the field is challenging, especially in (sub) specialties where time for re-design is limited and needs to be performed while education continues. Approach: An instructional design method was applied based on flexible co-design to improve post-graduate theoretical courses in child and adolescent psychiatry (CAP) in the Netherlands. In four phases over a period of three years, courses were re-designed at a national level. Evaluation: Once common vision and learning goals were agreed upon and the prototype was developed (phases 1 and 2), the first courses could be tested in daily practice (phase 3). Phase 4 refined these courses in brief iterative cycles and allowed for designing additional courses building on and adding to previous experiences in brief iterative cycles. The resulting national theoretical courses re-allocated resources previously spent on a local level using easily accessible online tools. This allowed trainees to align content with their clinical rotations, personal preferences and training schedules. Reflection: The development of theoretical courses for post-graduate medical training in smaller medical (sub-)specialties with limited resources may profit from a flexible instructional design method. We consider the potential merit of such a method to other medical specialties and other (inter-)national efforts to develop theoretical teaching courses. A longer-term implementation evaluation is needed to show to what extent the investment made in the re-design proves to be future-proof and enables rapid adaptation to changes in the field.

Effects of the neonatal intensive care environment on circadian health and development of preterm infants.

The circadian system in mammals ensures adaptation to the light-dark cycle on Earth and imposes 24-h rhythmicity on metabolic, physiological and behavioral processes. The central circadian pacemaker is located in the brain and is entrained by environmental signals called Zeitgebers. From here, neural, humoral and systemic signals drive rhythms in peripheral clocks in nearly every mammalian tissue. During pregnancy, disruption of the complex interplay between the mother's rhythmic signals and the fetal developing circadian system can lead to long-term health consequences in the offspring. When an infant is born very preterm, it loses the temporal signals received from the mother prematurely and becomes totally dependent on 24/7 care in the Neonatal Intensive Care Unit (NICU), where day/night rhythmicity is usually blurred. In this literature review, we provide an overview of the fetal and neonatal development of the circadian system, and short-term consequences of disruption of this process as occurs in the NICU environment. Moreover, we provide a theoretical and molecular framework of how this disruption could lead to later-life disease. Finally, we discuss studies that aim to improve health outcomes after preterm birth by studying the effects of enhancing rhythmicity in light and noise exposure.

Introduction of ultra-high-field MR brain imaging in infants: vital parameters, temperature and comfort.

Background: Brain MRI in infants at ultra-high-field scanners might improve diagnostic quality, but safety should be evaluated first. In our previous study, we reported simulated specific absorption rates and acoustic noise data at 7 Tesla. Methods: In this study, we included twenty infants between term-equivalent age and three months of age. The infants were scanned on a 7 Tesla MRI directly after their clinically indicated 3 Tesla brain MRI scan. Vital parameters, temperature, and comfort were monitored throughout the process. Brain temperature was estimated during the MRI scans using proton MR spectroscopy. Results: We found no significant differences in vital parameters, temperature, and comfort during and after 7 Tesla MRI scans, compared to 3 Tesla MRI scans. Conclusions: These data confirm our hypothesis that scanning infants at 7 Tesla MRI appears to be safe and we identified no additional risks from scanning at 3 Tesla MRI.

Early Ultrasonic Monitoring of Brain Growth and Later Neurodevelopmental Outcome in Very Preterm Infants.

BACKGROUND AND PURPOSE: In infants born very preterm, monitoring of early brain growth could contribute to prediction of later neurodevelopment. Therefore, our aim was to investigate associations between 2 early cranial ultrasound markers (corpus callosum-fastigium and corpus callosum length) and neurodevelopmental outcome and the added value of both markers in the prediction of neurodevelopmental outcome based on neonatal risk factors and head circumference in very preterm infants. MATERIALS AND METHODS: This prospective observational study included 225 infants born at <30 weeks' gestational age, of whom 153 were without any brain injury on cranial ultrasound. Corpus callosum-fastigium and corpus callosum length and head circumference were measured at birth, 29 weeks' gestational age, transfer from the neonatal intensive care unit to a level II hospital, and 2 months' corrected age. We analyzed associations of brain markers and their growth with cognitive, motor, language, and behavioral outcome at 2 years' corrected age. RESULTS: In infants without brain injury, greater corpus callosum-fastigium length at 2 months was associated with better cognitive outcome. Corpus callosum length at 2 months was positively associated with cognitive, motor, and language outcome. Faster growth of the corpus callosum length between birth and 2 months was associated with better cognitive and motor function. Prediction of neurodevelopmental outcome based on neonatal risk factors with or without head circumference was significantly improved by adding corpus callosum length. CONCLUSIONS: Both corpus callosum-fastigium and corpus callosum length on cranial ultrasound are associated with neurodevelopmental outcome of very preterm infants without brain injury at 2 years, but only corpus callosum length shows the added clinical utility in predicting neurodevelopmental outcome.

Creating an optimal observational sleep stage classification system for very and extremely preterm infants.

BACKGROUND: Sleep plays a major role in neuronal survival and guiding the fetal brain's development. Preterm infants in the neonatal intensive care unit are exposed to numerous external stimuli that can severely disrupt their sleep/wake patterns. Currently, almost no behavioral classification scales are validated for preterm infants. This study aims to develop a new, easy-to-use, validated visual sleep stage classification system for preterm infants with a gestational age between 25 and 37 weeks. METHODS: The Behavioral Sleep stage classification for Preterm Infants (BeSSPI) consists of four sleep-wake stages; active sleep (AS), quiet sleep (QS), intermediate sleep (IS) and wake (W), which are classified using seven items. Items include eye movements, body movements, facial movements, vocalizations, heart rate, respiratory pattern and activity level. RESULTS: 69 preterm infants were observed (24 + 6-36 + 0 weeks GA at birth; 25 + 2-36 + 6 weeks PMA at observation; 57.3% male). Across all 69 infants, the BeSSPI was based on 10,922 min of observed behavior, with 4264 min AS (38.83%), 2873 min QS (26.16%), 2887 min IS (26.29%), and 957 min W (8.72%). For the final BeSSPI, an interrater agreement of κ = 0.80 was reached. Additionally, construct, content, face validity, and expert validity were carefully assessed and deemed satisfactory. CONCLUSIONS: We developed a method to evaluate sleep-wake stages that is simple for all neonatal healthcare providers to learn and use. The BeSSPI is of high reliability and validity. Furthermore, it can be used in all preterm age-groups. Therefore, this novel instrument may improve rigor and reproducibility for future preterm sleep research.

Radar-based sleep stage classification in children undergoing polysomnography: a pilot-study.

STUDY OBJECTIVES: Unobtrusive monitoring of sleep and sleep disorders in children presents challenges. We investigated the possibility of using Ultra-Wide band (UWB) radar to measure sleep in children. METHODS: Thirty-two children scheduled to undergo a clinical polysomnography participated; their ages ranged from 2 months to 14 years. During the polysomnography, the children's body movements and breathing rate were measured by an UWB-radar. A total of 38 features were calculated from the motion signals and breathing rate obtained from the raw radar signals. Adaptive boosting was used as machine learning classifier to estimate sleep stages, with polysomnography as gold standard method for comparison. RESULTS: Data of all participants combined, this study achieved a Cohen's Kappa coefficient of 0.67 and an overall accuracy of 89.8% for wake and sleep classification, a Kappa of 0.47 and an accuracy of 72.9% for wake, rapid-eye-movement (REM) sleep, and non-REM sleep classification, and a Kappa of 0.43 and an accuracy of 58.0% for wake, REM sleep, light sleep and deep sleep classification. CONCLUSION: Although the current performance is not sufficient for clinical use yet, UWB radar is a promising method for non-contact sleep analysis in children.

Relationship Between Early Functional and Structural Brain Developments and Brain Injury in Preterm Infants.

BACKGROUND: Recent studies explored the relationship between early brain function and brain morphology, based on the hypothesis that increased brain activity can positively affect structural brain development and that excitatory neuronal activity stimulates myelination. OBJECTIVE: To investigate the relationship between maturational features from early and serial aEEGs after premature birth and MRI metrics characterizing structural brain development and injury, measured around 30weeks postmenstrual age (PMA) and at term. Moreover, we aimed to verify whether previously developed maturational EEG features are related with PMA. DESIGN/METHODS: One hundred six extremely preterm infants received bedside aEEGs during the first 72h and weekly until week 5. 3T-MRIs were performed at 30weeks PMA and at term. Specific features were extracted to assess EEG maturation: (1) the spectral content, (2) the continuity [percentage of spontaneous activity transients (SAT%) and the interburst interval (IBI)], and (3) the complexity. Automatic MRI segmentation to assess volumes and MRI score was performed. The relationship between the maturational EEG features and MRI measures was investigated. RESULTS: Both SAT% and EEG complexity were correlated with PMA. IBI was inversely associated with PMA. Complexity features had a positive correlation with the cerebellar size at 30weeks, while event-based measures were related to the cerebellar size at term. Cerebellar width, cortical grey matter, and total brain volume at term were inversely correlated with the relative power in the higher frequency bands. CONCLUSIONS: The continuity and complexity of the EEG steadily increase with increasing postnatal age. Increasing complexity and event-based features are associated with cerebellar size, a structure with enormous development during preterm life. Brain activity is important for later structural brain development.

Introduction of Ultra-High-Field MR Imaging in Infants: Preparations and Feasibility.

BACKGROUND AND PURPOSE: Cerebral MR imaging in infants is usually performed with a field strength of up to 3T. In adults, a growing number of studies have shown added diagnostic value of 7T MR imaging. 7T MR imaging might be of additional value in infants with unexplained seizures, for example. The aim of this study was to investigate the feasibility of 7T MR imaging in infants. We provide information about the safety preparations and show the first MR images of infants at 7T. MATERIALS AND METHODS: Specific absorption rate levels during 7T were simulated in Sim4life using infant and adult models. A newly developed acoustic hood was used to guarantee hearing protection. Acoustic noise damping of this hood was measured and compared with the 3T Nordell hood and no hood. In this prospective pilot study, clinically stable infants, between term-equivalent age and the corrected age of 3 months, underwent 7T MR imaging immediately after their standard 3T MR imaging. The 7T scan protocols were developed and optimized while scanning this cohort. RESULTS: Global and peak specific absorption rate levels in the infant model in the centered position and 50-mm feet direction did not exceed the levels in the adult model. Hearing protection was guaranteed with the new hood. Twelve infants were scanned. No MR imaging-related adverse events occurred. It was feasible to obtain good-quality imaging at 7T for MRA, MRV, SWI, single-shot T2WI, and MR spectroscopy. T1WI had lower quality at 7T. CONCLUSIONS: 7T MR imaging is feasible in infants, and good-quality scans could be obtained.

Synthetic MRI of Preterm Infants at Term-Equivalent Age: Evaluation of Diagnostic Image Quality and Automated Brain Volume Segmentation.

BACKGROUND AND PURPOSE: Neonatal MR imaging brain volume measurements can be used as biomarkers for long-term neurodevelopmental outcome, but quantitative volumetric MR imaging data are not usually available during routine radiologic evaluation. In the current study, the feasibility of automated quantitative brain volumetry and image reconstruction via synthetic MR imaging in very preterm infants was investigated. MATERIALS AND METHODS: Conventional and synthetic T1WIs and T2WIs from 111 very preterm infants were acquired at term-equivalent age. Overall image quality and artifacts of the conventional and synthetic images were rated on a 4-point scale. Legibility of anatomic structures and lesion conspicuity were assessed on a binary scale. Synthetic MR volumetry was compared with that generated via MANTiS, which is a neonatal tissue segmentation toolbox based on T2WI. RESULTS: Image quality was good or excellent for most conventional and synthetic images. The 2 methods did not differ significantly regarding image quality or diagnostic performance for focal and cystic WM lesions. Dice similarity coefficients had excellent overlap for intracranial volume (97.3%) and brain parenchymal volume (94.3%), and moderate overlap for CSF (75.6%). Bland-Altman plots demonstrated a small systematic bias in all cases (1.7%-5.9%) CONCLUSIONS: Synthetic T1WI and T2WI sequences may complement or replace conventional images in neonatal imaging, and robust synthetic volumetric results are accessible from a clinical workstation in less than 1 minute. Via the above-described methods, volume assessments could be routinely used in daily clinical practice.

The CHOPIn Study: a Multicenter Study on Cerebellar Hemorrhage and Outcome in Preterm Infants.

Cerebellar hemorrhage (CBH) is a frequent complication of preterm birth and may play an important and under-recognized role in neurodevelopment outcome. Association between CBH size, location, and neurodevelopment is still unknown. The main objective of this study was to investigate neurodevelopmental outcome at 2 years of age in a large number of infants with different patterns of CBH. Of preterm infants (≤ 34 weeks) with known CBH, perinatal factors, neuro-imaging findings, and follow-up at 2 years of age were retrospectively collected. MRI scans were reassessed to determine the exact size, number, and location of CBH. CBH was divided into three groups: punctate (≤ 4 mm), limited (> 4 mm but < 1/3 of the cerebellar hemisphere), or massive (≥ 1/3 of the cerebellar hemisphere). Associations between pattern of CBH, perinatal factors, and (composite) neurodevelopmental outcome were assessed. Data of 218 preterm infants with CBH were analyzed. Of 177 infants, the composite outcome score could be obtained. Forty-eight out of 119 infants (40%) with punctate CBH, 18 out of 35 infants (51%) with limited CBH, and 18 out of 23 infants (78%) with massive CBH had an abnormal composite outcome score. No significant differences were found for the composite outcome between punctate and limited CBH (P = 0.42). The risk of an abnormal outcome increased with increasing size of CBH. Infants with limited CBH have a more favorable outcome than infants with massive CBH. It is therefore important to distinguish between limited and massive CBH.

Cerebellar Growth Impairment Characterizes School-Aged Children Born Preterm without Perinatal Brain Lesions.

BACKGROUND AND PURPOSE: Infants born preterm are commonly diagnosed with structural brain lesions known to affect long-term neurodevelopment negatively. Yet, the effects of preterm birth on brain development in the absence of intracranial lesions remain to be studied in detail. In this study, we aim to quantify long term consequences of preterm birth on brain development in this specific group. MATERIALS AND METHODS: Neonatal cranial sonography and follow-up T1-weighted MR imaging and DTI were performed to evaluate whether the anatomic characteristics of the cerebrum and cerebellum in a cohort of school-aged children (6-12 years of age) were related to gestational age at birth in children free of brain lesions in the perinatal period. RESULTS: In the cohort consisting of 36 preterm (28-37 weeks' gestational age) and 66 term-born infants, T1-weighted MR imaging and DTI at 6-12 years revealed a reduction of cerebellar white matter volume (ß = 0.387, P < .001), altered fractional anisotropy of cerebellar white matter (ß = -0.236, P = .02), and a reduction of cerebellar gray and white matter surface area (ß = 0.337, P < .001; ß = 0.375, P < .001, respectively) in relation to birth age. Such relations were not observed for the cerebral cortex or white matter volume, surface area, or diffusion quantities. CONCLUSIONS: The results of our study show that perinatal influences that are not primarily neurologic are still able to disturb long-term neurodevelopment, particularly of the developing cerebellum. Including the cerebellum in future neuroprotective strategies seems therefore essential.

Advanced genomic testing may aid in counseling of isolated agenesis of the corpus callosum on prenatal ultrasound.

OBJECTIVE: Isolated agenesis of the corpus callosum on fetal ultrasound has a varied prognosis. Microarray and exome sequencing (ES) might aid in prenatal counseling. METHOD: This study includes 25 fetuses with apparently isolated complete corpus callosum (cACC) on ultrasound. All cases were offered single nucleotide polymorphism array. Complementary ES was offered postnatally in selected cases. Clinical physical and neurodevelopmental follow-up was collected. RESULTS: Eighteen cases opted for single nucleotide polymorphism array testing, which detected a causal anomaly in 2/18 (11.1%; 95% CI 2.0%-31%). Among ongoing pregnancies without a causal anomaly on microarray, 30% (95% CI 8.5%-60%) showed intellectual disability. Postnatal magnetic resonance imaging and physical examination often (64%; 95% CI 38%-85%, and 64%; 95% CI 38%-85%, respectively) revealed additional physical anomalies in cases without a causal anomaly on microarray. Two cases appeared truly isolated after birth. Postnatal sequencing in 4 of 16 cases without a causal anomaly on microarray but with intellectual disability and/or additional postnatal physical anomalies revealed 2 single-gene disorders. Therefore, the estimated diagnostic yield of ES in chromosomally normal cACC fetuses is between 2/4 (50%; 95% CI 11%-89%) and 2/16 (13.3%; 95% CI 2.4%-36%). CONCLUSION: In accordance with current guidelines, we conclude that microarray should be offered in case of isolated cACC on ultrasound. ES is likely to be informative for prenatal counseling and should be offered if microarray is normal.

New Ultrasound Measurements to Bridge the Gap between Prenatal and Neonatal Brain Growth Assessment.

BACKGROUND AND PURPOSE: Most ultrasound markers for monitoring brain growth can only be used in either the prenatal or the postnatal period. We investigated whether corpus callosum length and corpus callosum-fastigium length could be used as markers for both prenatal and postnatal brain growth. MATERIALS AND METHODS: A 3D ultrasound study embedded in the prospective Rotterdam Periconception Cohort was performed at 22, 26 and 32 weeks' gestational age in fetuses with fetal growth restriction, congenital heart defects, and controls. Postnatally, cranial ultrasound was performed at 42 weeks' postmenstrual age. First, reliability was evaluated. Second, associations between prenatal and postnatal corpus callosum and corpus callosum-fastigium length were investigated. Third, we created reference curves and compared corpus callosum and corpus callosum-fastigium length growth trajectories of controls with growth trajectories of fetuses with fetal growth retardation and congenital heart defects. RESULTS: We included 199 fetuses; 22 with fetal growth retardation, 20 with congenital heart defects, and 157 controls. Reliability of both measurements was excellent (intraclass correlation coefficient ≥ 0.97). Corpus callosum growth trajectories were significantly decreased in fetuses with fetal growth restriction and congenital heart defects (ß = -2.295; 95% CI, -3.320-1.270; P < .01; ß = -1.267; 95% CI, -0.972-0.562; P < .01, respectively) compared with growth trajectories of controls. Corpus callosum-fastigium growth trajectories were decreased in fetuses with fetal growth restriction (ß = -1.295; 95% CI, -2.595-0.003; P = .05). CONCLUSIONS: Corpus callosum and corpus callosum-fastigium length may serve as reliable markers for monitoring brain growth from the prenatal into the postnatal period. The clinical applicability of these markers was established by the significantly different corpus callosum and corpus callosum-fastigium growth trajectories in fetuses at risk for abnormal brain growth compared with those of controls.

Prenatal cerebellar growth trajectories and the impact of periconceptional maternal and fetal factors.

STUDY QUESTION: CAN WE assess human prenatal cerebellar growth from the first until the third trimester of pregnancy and create growth trajectories to investigate associations with periconceptional maternal and fetal characteristics? SUMMARY ANSWER: Prenatal growth trajectories of the human cerebellum between 9 and 32 weeks gestational age (GA) were created using three-dimensional ultrasound (3D-US) and show negative associations with pre-pregnancy and early first trimester BMI calculated from self-reported and standardized measured weight and height, respectively. WHAT IS KNOWN ALREADY: The cerebellum is essential for normal neurodevelopment and abnormal cerebellar development has been associated with neurodevelopmental impairments and psychiatric diseases. Cerebellar development is particularly susceptible to exposures during the prenatal period, including maternal folate status, smoking habit and alcohol consumption. STUDY DESIGN, SIZE, DURATION: From 2013 until 2015, we included 182 singleton pregnancies during the first trimester as a subgroup in a prospective periconception cohort with follow-up until birth. For the statistical analyses, we selected 166 pregnancies ending in live born infants without congenital malformations. PARTICIPANTS/MATERIALS, SETTING, METHODS: We measured transcerebellar diameter (TCD) at 9, 11, 22, 26 and 32 weeks GA on ultrasound scans. Growth rates were calculated and growth trajectories of the cerebellum were created. Linear mixed models were used to estimate associations between cerebellar growth and maternal age, parity, mode of conception, geographic origin, pre-pregnancy and first trimester BMI, periconceptional smoking, alcohol consumption, timing of folic acid supplement initiation and fetal gender. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 166 pregnancies provided 652 (87%) ultrasound images eligible for TCD measurements. Cerebellar growth rates increased with advancing GA being 0.1691 mm/day in the first trimester, 0.2336 mm/day in the second trimester and 0.2702 mm/day in the third trimester. Pre-pregnancy BMI, calculated from self-reported body weight and height, was significantly associated with decreased cerebellar growth trajectories (ß = -0.0331 mm, 95% CI = -0.0638; -0.0024, P = 0.035). A similar association was found between cerebellar growth trajectories and first trimester BMI, calculated from standardized measurements of body weight and height (ß = -0.0325, 95% CI = -0.0642; -0.0008, P = 0.045, respectively). LIMITATIONS, REASONS FOR CAUTION: As the study population largely consisted of tertiary hospital patients, external validity should be studied in the general population. Whether small differences in prenatal cerebellar growth due to a higher pre-pregnancy and first trimester BMI have consequences for neurodevelopmental outcome needs further investigation. WIDER IMPLICATIONS OF THE FINDINGS: Our findings further substantiate previous evidence for the detrimental impact of a higher maternal BMI on neurodevelopmental health of offspring in later life. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Department of Obstetrics and Gynecology, Erasmus MC University Medical Centre and Sophia Children's Hospital Fund, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared.

Growth trajectories of the human embryonic head and periconceptional maternal conditions.

STUDY QUESTION: Can growth trajectories of the human embryonic head be created using 3D ultrasound (3D-US) and virtual reality (VR) technology, and be associated with second trimester fetal head size and periconceptional maternal conditions? SUMMARY ANSWER: Serial first trimester head circumference (HC) and head volume (HV) measurements were used to create reliable growth trajectories of the embryonic head, which were significantly associated with fetal head size and periconceptional maternal smoking, age and ITALIC! in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) treatment. WHAT IS KNOWN ALREADY: Fetal growth is influenced by periconceptional maternal conditions. STUDY DESIGN, SIZE, DURATION: We selected 149 singleton pregnancies with a live born non-malformed fetus from the Rotterdam periconception cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Bi-parietal diameter and occipital frontal diameter to calculate HC, HV and crown-rump length (CRL) were measured weekly between 9 + 0 and 12 + 6 weeks gestational age (GA) using 3D-US and VR. Fetal HC was obtained from second trimester structural anomaly scans. Growth trajectories of the embryonic head were created with general additive models and linear mixed models were used to estimate associations with maternal periconceptional conditions as a function of GA and CRL, respectively. MAIN RESULTS: A total of 303 3D-US images of 149 pregnancies were eligible for embryonic head measurements (intra-class correlation coefficients >0.99). Associations were found between embryonic HC and fetal HC ( ITALIC! ρ = 0.617, ITALIC! P < 0.001) and between embryonic HV and fetal HC ( ITALIC! ρ = 0.660, ITALIC! P < 0.001) in ITALIC! Z-scores. Maternal periconceptional smoking was associated with decreased, and maternal age and IVF/ICSI treatment with increased growth trajectories of the embryonic head measured by HC and HV (All ITALIC! P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The consequences of the small effect sizes for neurodevelopmental outcome need further investigation. As the study population consists largely of tertiary hospital patients, external validity should be studied in the general population. WIDER IMPLICATIONS OF THE FINDINGS: Assessment of growth trajectories of the embryonic head may be of benefit in future early antenatal care. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre and Sophia Foundation for Medical Research, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared.

A New Ultrasound Marker for Bedside Monitoring of Preterm Brain Growth.

BACKGROUND AND PURPOSE: Preterm neonates are at risk for neurodevelopmental impairment, but reliable, bedside-available markers to monitor preterm brain growth during hospital stay are still lacking. The aim of this study was to assess the feasibility of corpus callosum-fastigium length as a new cranial sonography marker for monitoring of preterm brain growth. MATERIALS AND METHODS: In this longitudinal prospective cohort study, cranial ultrasound was planned on the day of birth, days 1, 2, 3, and 7 of life; and then weekly until discharge in preterm infants born before 29 weeks of gestational age. Reproducibility and associations between clinical variables and corpus callosum-fastigium growth trajectories were studied. RESULTS: A series of 1-8 cranial ultrasounds was performed in 140 infants (median gestational age at birth, 27(+2) weeks (interquartile range, 26(+1) to 28(+1); 57.9% male infants). Corpus callosum-fastigium measurements showed good-to-excellent agreement for inter- and intraobserver reproducibility (intraclass correlation coefficient >0.89). Growth charts for preterm infants between 24 and 32 weeks of gestation were developed. Male sex and birth weight SD score were positively associated with corpus callosum-fastigium growth rate. CONCLUSIONS: Corpus callosum-fastigium length measurement is a new reproducible marker applicable for bedside monitoring of preterm brain growth during neonatal intensive care stay.

Neonatal disorders of germinal matrix.

The germinal matrix (GM) is a richly vascularized, transient layer near the ventricles. It produces neurons and glial cells, and is present in the foetal brain between 8 and 36 weeks of gestation. At 25 weeks, it reaches its maximum volume and subsequently withers. The GM is vulnerable to haemorrhage in preterm infants. This selective vulnerability is explained by limited astrocyte end-feet coverage of microvessels, reduced expression of fibronectin and immature tight junctions. Focal lesions in the neonatal period include haemorrhage, germinolysis and stroke. Such lesions in transient layers interrupt normal brain maturation and induce neurodevelopmental sequelae.

Choice of diffusion tensor estimation approach affects fiber tractography of the fornix in preterm brain.

BACKGROUND AND PURPOSE: Neonatal DTI enables quantitative assessment of microstructural brain properties. Although its use is increasing, it is not widely known that vast differences in tractography results can occur, depending on the diffusion tensor estimation methodology used. Current clinical work appears to be insufficiently focused on data quality and processing of neonatal DTI. To raise awareness about this important processing step, we investigated tractography reconstructions of the fornix with the use of several estimation techniques. We hypothesized that the method of tensor estimation significantly affects DTI tractography results. MATERIALS AND METHODS: Twenty-eight DTI scans of infants born <29 weeks of gestation, acquired at 30-week postmenstrual age and without intracranial injury observed, were prospectively collected. Four diffusion tensor estimation methods were applied: 1) linear least squares; 2) weighted linear least squares; 3) nonlinear least squares, and 4) robust estimation of tensors by outlier rejection. Quality of DTI data and tractography results were evaluated for each method. RESULTS: With nonlinear least squares and robust estimation of tensors by outlier rejection, significantly lower mean fractional anisotropy values were obtained than with linear least squares and weighted linear least squares. Visualized quality of tract reconstruction was significantly higher by use of robust estimation of tensors by outlier rejection and correlated with quality of DTI data. CONCLUSIONS: Quality assessment and choice of processing methodology have considerable impact on neonatal DTI analysis. Dedicated acquisition, quality assessment, and advanced processing of neonatal DTI data must be ensured before performing clinical analyses, such as associating microstructural brain properties with patient outcome.

Optimal timing of cerebral MRI in preterm infants to predict long-term neurodevelopmental outcome: a systematic review.

SUMMARY: Advances in neonatal neuroimaging have improved detection of preterm brain injury responsible for abnormal neuromotor and cognitive development. Increasingly sophisticated MR imaging setups allow scanning during early preterm life. In this review, we investigated how brain MR imaging in preterm infants should be timed to best predict long-term outcome. Given the strong evidence that structural brain abnormalities are related to long-term neurodevelopment, MR imaging should preferably be performed at term-equivalent age. Early MR imaging is promising because it can guide early intervention studies and is indispensable in research on preterm brain injury.

Recent advancements in diffusion MRI for investigating cortical development after preterm birth-potential and pitfalls.

Preterm infants are born during a critical period of brain maturation, in which even subtle events can result in substantial behavioral, motor and cognitive deficits, as well as psychiatric diseases. Recent evidence shows that the main source for these devastating disabilities is not necessarily white matter (WM) damage but could also be disruptions of cortical microstructure. Animal studies showed how moderate hypoxic-ischemic conditions did not result in significant neuronal loss in the developing brain, but did cause significantly impaired dendritic growth and synapse formation alongside a disturbed development of neuronal connectivity as measured using diffusion magnetic resonance imaging (dMRI). When using more advanced acquisition settings such as high-angular resolution diffusion imaging (HARDI), more advanced reconstruction methods can be applied to investigate the cortical microstructure with higher levels of detail. Recent advances in dMRI acquisition and analysis have great potential to contribute to a better understanding of neuronal connectivity impairment in preterm birth. We will review the current understanding of abnormal preterm cortical development, novel approaches in dMRI, and the pitfalls in scanning vulnerable preterm infants.