Neonatal Brain Imaging Research Articles

Enhanced Neonatal Brain Tissue Analysis via Minimum Spanning Tree Segmentation and the Brier Score Coupled Classifier

Automatic assessment of brain regions in an MR image has emerged as a pivotal tool in advancing diagnosis and continual monitoring of neurological disorders through different phases of life. Nevertheless, current solutions often exhibit specificity to particular age groups, thereby constraining their utility in observing brain development from infancy to late adulthood. In our research, we introduce a novel approach for segmenting and classifying neonatal brain images. Our methodology capitalizes on minimum spanning tree (MST) segmentation employing the Manhattan distance, complemented by a shrunken centroid classifier empowered by the Brier score. This fusion enhances the accuracy of tissue classification, effectively addressing the complexities inherent in age-specific segmentation. Moreover, we propose a novel threshold estimation method utilizing the Brier score, further refining the classification process. The proposed approach yields a competitive Dice similarity index of 0.88 and a Jaccard index of 0.95. This approach marks a significant step toward neonatal brain tissue segmentation, showcasing the efficacy of our proposed methodology in comparison to the latest cutting-edge methods.

MGA-Net: A novel mask-guided attention neural network for precision neonatal brain imaging

In this study, we introduce MGA-Net, a novel mask-guided attention neural network, which extends the U-net model for precision neonatal brain imaging. MGA-Net is designed to extract the brain from other structures and reconstruct high-quality brain images. The network employs a common encoder and two decoders: one for brain mask extraction and the other for brain region reconstruction. A key feature of MGA-Net is its high-level mask-guided attention module, which leverages features from the brain mask decoder to enhance image reconstruction. To enable the same encoder and decoder to process both MRI and ultrasound (US) images, MGA-Net integrates sinusoidal positional encoding. This encoding assigns distinct positional values to MRI and US images, allowing the model to effectively learn from both modalities. Consequently, features learned from a single modality can aid in learning a modality with less available data, such as US. We extensively validated the proposed MGA-Net on diverse and independent datasets from varied clinical settings and neonatal age groups. The metrics used for assessment included the DICE similarity coefficient, recall, and accuracy for image segmentation; structural similarity for image reconstruction; and root mean squared error for total brain volume estimation from 3D ultrasound images. Our results demonstrate that MGA-Net significantly outperforms traditional methods, offering superior performance in brain extraction and segmentation while achieving high precision in image reconstruction and volumetric analysis. Thus, MGA-Net represents a robust and effective preprocessing tool for MRI and 3D ultrasound images, marking a significant advance in neuroimaging that enhances both research and clinical diagnostics in the neonatal period and beyond.

Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency.

Pyruvate dehydrogenase complex deficiency (PDCD) is a disorder of mitochondrial metabolism that is caused by pathogenic variants in multiple genes, including PDHA1. Typical neonatal brain imaging findings have been described, with a focus on malformative and encephaloclastic features. Fetal brain MRI in PDCD has not been comprehensively described. The aims of this study were (1) to further characterize the fetal brain MRI findings in PDCD using comprehensive fetal imaging and genetic testing and (2) to determine whether markers of diagnosis of PDCD could be identified on prenatal imaging. Fetuses with a diagnosis of PDCD related to a genetic etiology that had undergone fetal MRI were included. Fetuses were identified retrospectively from local databases of 4 fetal diagnostic clinics within tertiary pediatric health care centers. Electronic medical records were reviewed retrospectively: demographics, maternal and pregnancy history, fetal outcomes, and neonatal outcomes (if available) were reviewed and recorded. Fetal and neonatal imaging reports were reviewed; source fetal and neonatal brain MRI scans were reviewed by a single pediatric neuroradiologist (J.W.S.) for consistency. Genetic testing strategies and results including variant type, zygosity, inheritance pattern, and pathogenicity were recorded. Deidentified data were combined and reported descriptively. A total of 10 fetuses with a diagnosis of PDCD were included. 8 fetuses had corpus callosum dysgenesis, 6 had an abnormal gyration pattern, 10 had reduced brain volumes, and 9 had cystic lesions. 1 fetus had intraventricular hemorrhages. 1 fetus had a midbrain malformation with aqueductal stenosis and severe hydrocephalus. 6 fetuses imaged in the second trimester had cystic lesions involving the ganglionic eminences (GEs) while GE cysts were not present in the 4 fetuses imaged in the third trimester. Fetuses with PDCD have similar brain MRI findings to neonates described in the literature, although some of these findings are subtle early in pregnancy. Additional features, such as cystic lesions of the GEs, are noted in the second trimester in fetuses with PDCD. These may represent an early diagnostic marker of PDCD, although more data are needed to validate this association. Early diagnosis of PDCD using fetal MRI may inform genetic counseling, pregnancy decision making, and neonatal care planning.

Noninvasive microvascular imaging in newborn rats using high-frequency ultrafast ultrasound

Ultrasound imaging stands as the predominant modality for neonatal health assessment, with recent advancements in ultrafast Doppler (μDoppler) technology offering significant promise in fields such as neonatal brain imaging. Combining μDoppler with high-frequency ultrasound (HF-μDoppler) presents a potential efficient avenue to enhance in vivo microvascular imaging in small animals, notably newborn rats, a crucial preclinical animal model for neonatal disease and development research. It is necessary to verify the imaging performance of HF-μDoppler in preclinical trials. This study investigates the microvascular imaging capabilities of HF-μDoppler using a 30 MHz high-frequency linear array probe in newborn rats. Results demonstrate the clarity of cerebral microvascular imaging in rats aged 1 to 7 postnatal days, extending to whole-body microvascular imaging, encompassing the central nervous system, including the brain and spinal cord. In conclusion, HF-μDoppler technology emerges as a reliable imaging tool, offering a new perspective for preclinical investigations into neonatal diseases and development.

VINNA for Neonates – Orientation Independence through Latent Augmentations

Abstract A robust, fast, and accurate segmentation of neonatal brain images is highly desired to better understand and detect changes during development and disease, specifically considering the rise in imaging studies for this cohort. Yet, the limited availability of ground truth datasets, lack of standardized acquisition protocols, and wide variations of head positioning in the scanner pose challenges for method development. A few automated image analysis pipelines exist for newborn brain MRI segmentation, but they often rely on time-consuming non-linear spatial registration procedures and require resampling to a common resolution, subject to loss of information due to interpolation and down-sampling. Without registration and image resampling, variations with respect to head positions and voxel resolutions have to be addressed differently. In deep-learning, external augmentations such as rotation, translation, and scaling are traditionally used to artificially expand the representation of spatial variability, which subsequently increases both the training dataset size and robustness. However, these transformations in the image space still require resampling, reducing accuracy specifically in the context of label interpolation. We recently introduced the concept of resolution-independence with the Voxel-size Independent Neural Network framework, VINN. Here, we extend this concept by additionally shifting all rigid-transforms into the network architecture with a four degree of freedom (4-DOF) transform module, enabling resolution-aware internal augmentations (VINNA) for deep learning. In this work we show that VINNA (i) significantly outperforms state-of-the-art external augmentation approaches, (ii) effectively addresses the head variations present specifically in newborn datasets, and (iii) retains high segmentation accuracy across a range of resolutions (0.5-1.0mm). Furthermore, the 4-DOF transform module together with internal augmentations is a powerful, general approach to implement spatial augmentation without requiring image or label interpolation. The specific network application to newborns will be made publicly available as VINNA4neonates.

Advances in neonatal brain imaging: A comparative analysis of MRI, CT scans, and ultrasound

This scholarly investigation undertakes a comprehensive comparison of the diagnostic efficacy, precision, and sensitivity associated with neonatal brain Magnetic Resonance Imaging (MRI) in contrast to its counterparts, Computed Tomography (CT) scans and ultrasound. As the medical community has progressively become attuned to the long-term health implications of radiation exposure from CT scans, the imperative of a strategy mitigating this risk has gained prominence. In this context, ultrasound emerges as an alternative modality devoid of ionizing radiation. Employing a methodical approach rooted in systematic literature review, this study synthesizes five pertinent research works to unravel its research objectives. Empirical evidence substantiates that neonatal brain MRI surpasses both neonatal brain CT and ultrasound in diagnostic effectiveness. The underpinning rationale for this phenomenon lies in the heightened accuracy inherent to neonatal brain MRI procedures. To unravel the intricacies associated with disparities between neonatal and adult brain MRI procedures, the study meticulously investigates structural, shape, and size distinctions. This endeavor underscores the necessity for bespoke MRI apparatuses designed to account for these nuances. In pursuit of this objective, the integration of technologically advanced components such as compact scanners and refinements in magnetic and coil technologies has engendered tangible improvements. This innovation confluence bears testimony to the augmentation of patient safety, conferring a cascade effect wherein the precision of acquired MRI data underwrites accurate diagnoses and consequent therapeutic interventions. Conclusively, the study underscores the pivotal role played by recent MRI technological advancements in amplifying its efficacy within the niche domain of neonatal brain imaging. Prospective innovations within the MRI ambit stand poised to recalibrate performance benchmarks, thereby amplifying its diagnostic potency and broadening its scope of application.

The Use of Contrast-Enhanced Ultrasound (CEUS) in the Evaluation of the Neonatal Brain.

In recent years, advancements in technology have allowed the use of contrast-enhanced ultrasounds (CEUS) with high-frequency transducers, which in turn, led to new possibilities in diagnosing a variety of diseases and conditions in the field of radiology, including neonatal brain imaging. CEUSs overcome some of the limitations of conventional ultrasounds (US) and Doppler USs. It allows the visualization of dynamic perfusion even in the smallest vessels in the whole brain and allows the quantitative analysis of perfusion parameters. An increasing number of articles are published on the topic of the use of CEUSs on children each year. In the area of brain imaging, the CEUS has already proven to be useful in cases with clinical indications, such as hypoxic-ischemic injuries, stroke, intracranial hemorrhages, vascular anomalies, brain tumors, and infections. We present and discuss the basic principles of the CEUS and its safety considerations, the examination protocol for imaging the neonatal brain, and current and emerging clinical applications.

Development and characterization of transfontanelle photoacoustic imaging system for detection of intracranial hemorrhages and measurement of brain oxygenation: Ex-vivo

We have developed and optimized an imaging system to study and improve the detection of brain hemorrhage and to quantify oxygenation. Since this system is intended to be used for brain imaging in neonates through the skull opening, i.e., fontanelle, we called it, Transfontanelle Photoacoustic Imaging (TFPAI) system. The system is optimized in terms of optical and acoustic designs, thermal safety, and mechanical stability. The lower limit of quantification of TFPAI to detect the location of hemorrhage and its size is evaluated using in-vitro and ex-vivo experiments. The capability of TFPAI in measuring the tissue oxygenation and detection of vasogenic edema due to brain blood barrier disruption are demonstrated. The results obtained from our experimental evaluations strongly suggest the potential utility of TFPAI, as a portable imaging modality in the neonatal intensive care unit. Confirmation of these findings in-vivo could facilitate the translation of this promising technology to the clinic.

Feasibility of Cerebellar Measurements with Phased Array Sonography through the Anterior Fontanelle in Comparison to MRI.

Cerebral sonography (CS) through the anterior fontanelle is a neonatal brain imaging method that has become an integral part of modern neonatal bedside care for both screening and diagnostic purposes. Premature infants with cognitive delay have a reduction in cerebellar size at term corrected age on magnetic resonance imaging (MRI). We aimed to determine the level of agreement between postnatal MRI and CS for cerebellar biometry and to determine the level of agreement within one and between different examiners. Cerebellar sonography and MRI measurements of the cerebellum from 30 term infants was assessed by Bland-Altman plots. Measurements between both modalities were compared using Wilcoxon's signed rank test. A p-value < 0.01 was considered statistically significant. Intraclass correlation coefficients (ICC) for intra- and interrater reliabilities of CS measurements were calculated. There was no statistically significant difference between CS and MRI for linear measurements, but the measurements of perimeter and surface area differed significantly between the two techniques. There was a systematic bias between both modalities for most measurements except for anterior-posterior (AP) width and vermis height (VH). For measurements that were not statistically different from MRI, we found excellent intrarater ICC for the AP width, VH, and cerebellar width. The interrater ICC was excellent for the AP width and VH, but poor for the transverse cerebellar width. With a strict imaging protocol, cerebellar measurements of the AP width and the VH can be used as an alternative to MRI for diagnostic-screening purposes in a neonatal department where multiple clinicians perform bedside CS. · Abnormal cerebellar growth and injuries affect neurodevelopmental outcome.. · Cerebral sonography through the anterior fontanelle is used for bedside imaging.. · Postnatal sonographic cerebellar measurements are not validated against MRI.. · Measuring vermis height and anterior-posterior width are reliable.. · Measuring transverse cerebellar width through anterior fontanelle is unreliable..

NeoRS: A Neonatal Resting State fMRI Data Preprocessing Pipeline.

Resting state functional MRI (rsfMRI) has been shown to be a promising tool to study intrinsic brain functional connectivity and assess its integrity in cerebral development. In neonates, where functional MRI is limited to very few paradigms, rsfMRI was shown to be a relevant tool to explore regional interactions of brain networks. However, to identify the resting state networks, data needs to be carefully processed to reduce artifacts compromising the interpretation of results. Because of the non-collaborative nature of the neonates, the differences in brain size and the reversed contrast compared to adults due to myelination, neonates can’t be processed with the existing adult pipelines, as they are not adapted. Therefore, we developed NeoRS, a rsfMRI pipeline for neonates. The pipeline relies on popular neuroimaging tools (FSL, AFNI, and SPM) and is optimized for the neonatal brain. The main processing steps include image registration to an atlas, skull stripping, tissue segmentation, slice timing and head motion correction and regression of confounds which compromise functional data interpretation. To address the specificity of neonatal brain imaging, particular attention was given to registration including neonatal atlas type and parameters, such as brain size variations, and contrast differences compared to adults. Furthermore, head motion was scrutinized, and motion management optimized, as it is a major issue when processing neonatal rsfMRI data. The pipeline includes quality control using visual assessment checkpoints. To assess the effectiveness of NeoRS processing steps we used the neonatal data from the Baby Connectome Project dataset including a total of 10 neonates. NeoRS was designed to work on both multi-band and single-band acquisitions and is applicable on smaller datasets. NeoRS also includes popular functional connectivity analysis features such as seed-to-seed or seed-to-voxel correlations. Language, default mode, dorsal attention, visual, ventral attention, motor and fronto-parietal networks were evaluated. Topology found the different analyzed networks were in agreement with previously published studies in the neonate. NeoRS is coded in Matlab and allows parallel computing to reduce computational times; it is open-source and available on GitHub (https://github.com/venguix/NeoRS). NeoRS allows robust image processing of the neonatal rsfMRI data that can be readily customized to different datasets.

Brain Development and Maternal Behavior in Relation to Cognitive and Language Outcomes in Preterm-Born Children

BackgroundChildren born very preterm (≤32 weeks gestational age) show poorer cognitive and language development compared with their term-born peers. The importance of supportive maternal responses to the child’s cues for promoting neurodevelopment is well established. However, little is known about whether supportive maternal behavior can buffer the association of early brain dysmaturation with cognitive and language performance. MethodsInfants born very preterm (N = 226) were recruited from the neonatal intensive care unit for a prospective, observational cohort study. Chart review (e.g., size at birth, postnatal infection) was conducted from birth to discharge. Magnetic resonance imaging, including diffusion tensor imaging, was acquired at approximately 32 weeks postmenstrual age and again at term-equivalent age. Fractional anisotropy, a quantitative measure of brain maturation, was obtained from 11 bilateral regions of interest in the cortical gray matter. At 3 years (n = 187), neurodevelopmental testing (Bayley Scales of Infant and Toddler Development-III) was administered, and parent-child interaction was filmed. Maternal behavior was scored using the Emotional Availability Scale-IV. A total of 146 infants with neonatal brain imaging and follow-up data were included for analysis. Generalized estimating equations were used to examine whether maternal support interacted with mean fractional anisotropy values to predict Cognitive and Language scores at 3 years, accounting for confounding neonatal and maternal factors. ResultsHigher maternal support significantly moderated cortical fractional anisotropy values at term-equivalent age to predict higher Cognitive (interaction term β = 2.01, p = .05) and Language (interaction term β = 1.85, p = .04) scores. ConclusionsFindings suggest that supportive maternal behavior following early brain dysmaturation may provide an opportunity to promote optimal neurodevelopment in children born very preterm.

Different from the Beginning: WM Maturity of Female and Male Extremely Preterm Neonates-A Quantitative MRI Study.

Former preterm born males are at higher risk for neurodevelopmental disabilities compared with female infants born at the same gestational age. This retrospective study investigated sex-related differences in the maturity of early myelinating brain regions in infants born <28 weeks' gestational age using diffusion tensor- and relaxometry-based MR imaging. Quantitative MR imaging sequence acquisitions were analyzed in a sample of 35 extremely preterm neonates imaged at term-equivalent ages. Quantitative MR imaging metrics (fractional anisotropy; ADC [10-3mm2/s]; and T1-/T2-relaxation times [ms]) of the medulla oblongata, pontine tegmentum, midbrain, and the right/left posterior limbs of the internal capsule were determined on diffusion tensor- and multidynamic, multiecho sequence-based imaging data. ANCOVA and a paired t test were used to compare female and male infants and to detect hemispheric developmental asymmetries. Seventeen female (mean gestational age at birth: 26 + 0 [SD, 1 + 4] weeks+days) and 18 male (mean gestational age at birth: 26 + 1 [SD, 1 + 3] weeks+days) infants were enrolled in this study. Significant differences were observed in the T2-relaxation time (P = .014) of the pontine tegmentum, T1-relaxation time (P = .011)/T2-relaxation time (P = .024) of the midbrain, and T1-relaxation time (P = .032) of the left posterior limb of the internal capsule. In both sexes, fractional anisotropy (P [♀] < .001/P [♂] < .001) and ADC (P [♀] = .017/P [♂] = .028) differed significantly between the right and left posterior limbs of the internal capsule. The combined use of various quantitative MR imaging metrics detects sex-related and interhemispheric differences of WM maturity. The brainstem and the left posterior limb of the internal capsule of male preterm neonates are more immature compared with those of female infants at term-equivalent ages. Sex differences in WM maturation need further attention for the personalization of neonatal brain imaging.

Towards an integrated neonatal brain and cardiac examination capability at 7 T: electromagnetic field simulations and early phantom experiments using an 8-channel dipole array

ObjectiveNeonatal brain and cardiac imaging would benefit from the increased signal-to-noise ratio levels at 7 T compared to lower field. Optimal performance might be achieved using purpose designed RF coil arrays. In this study, we introduce an 8-channel dipole array and investigate, using simulations, its RF performances for neonatal applications at 7 T.MethodsThe 8-channel dipole array was designed and evaluated for neonatal brain/cardiac configurations in terms of SAR efficiency (ratio between transmit-field and maximum specific-absorption-rate level) using adjusted dielectric properties for neonate. A birdcage coil operating in circularly polarized mode was simulated for comparison. Validation of the simulation model was performed on phantom for the coil array.ResultsThe 8-channel dipole array demonstrated up to 46% higher SAR efficiency levels compared to the birdcage coil in neonatal configurations, as the specific-absorption-rate levels were alleviated. An averaged normalized root-mean-square-error of 6.7% was found between measured and simulated transmit field maps on phantom.ConclusionThe 8-channel dipole array design integrated for neonatal brain and cardiac MR was successfully demonstrated, in simulation with coverage of the baby and increased SAR efficiency levels compared to the birdcage. We conclude that the 8Tx-dipole array promises safe operating procedures for MR imaging of neonatal brain and heart at 7 T.

Feasibility and Safety of Contrast-Enhanced Ultrasound of the Neonatal Brain: A Prospective Study Using MRI as the Reference Standard.

BACKGROUND. MRI is the reference standard for neonatal brain imaging, but it is expensive, time-consuming, potentially limited by availability and accessibility, and contraindicated in some patients. Transfontanelle neonatal head ultrasound is an excellent alternative but may be less sensitive and specific than MRI. Contrast-enhanced ultrasound (CEUS) has the potential to improve the capabilities of ultrasound. OBJECTIVE. The purpose of this study is to prospectively evaluate the feasibility, safety, and diagnostic performance of transfontanelle neonatal brain CEUS, with MRI used as the reference standard. METHODS. Neonates in the institutional neonatal ICU who were undergoing MRI as part of their clinical care were prospectively recruited to undergo portable brain ultrasound and CEUS for research purposes. Brain ultrasound and CEUS were performed portably without moving the patient from the isolette or crib in the neonatal ICU. Adverse events were recorded. Two radiologists independently evaluated ultrasound and CEUS images for abnormalities and then reached consensus regarding discrepancies. A separate radiologist reviewed MRI examinations. Sensitivity, specificity, and interreader agreement were evaluated, with MRI used as the reference. Qualitative post hoc image review was performed. RESULTS. Twenty-six neonates (nine boys and 17 girls; mean [± SD] age, 15.2 ± 14.0 days) were included. No significant alteration in patient vital signs or adverse reaction to the ultrasound contrast agent (UCA) occurred. The mean duration of the examination was significantly shorter for combined ultrasound and CEUS than for MRI (21.1 ± 4.7 vs 74.2 ± 34.8 minutes; p < .001). Interrater agreement for any abnormality was almost perfect for both ultrasound and CEUS (κ = 0.92 and 0.85, respectively). Sensitivity for any abnormality was 86.7% for ultrasound and 93.3% for CEUS; specificity was 100.0% for both. CEUS had sensitivity of 87.5% for acute or subacute ischemia and 100.0% for chronic ischemia; its specificity was 100.0% for acute or subacute ischemia and chronic ischemia. For both ultrasound and CEUS, sensitivity for subdural and intraparenchymal hemorrhage was poor (22.2-50.0%). On CEUS but not on MRI, post hoc review showed a case of postischemic hyperperfusion, which was confirmed by subsequently performed contrast-enhanced CT. CONCLUSION. The use of portable brain CEUS in neonates is feasible, safe, and more rapid than MRI. CLINICAL IMPACT. The potential diagnostic utility of brain neonatal CEUS relative to conventional ultrasound, particularly for ischemia, warrants further investigation.

The dimensions of white matter injury in preterm neonates

White matter injury (WMI) represents a frequent form of parenchymal brain injury in preterm neonates. Several dimensions of WMI are recognized, with distinct neuropathologic features involving a combination of destructive and maturational anomalies. Hypoxia-ischemia is the main mechanism leading to WMI and adverse white matter development, which result from injury to the oligodendrocyte precursor cells. Inflammation might act as a potentiator for WMI. A combination of hypoxia-ischemia and inflammation is frequent in several neonatal comorbidities such as postnatal infections, NEC and bronchopulmonary dysplasia, all known contributors to WMI. White matter injury is an important predictor of adverse neurodevelopmental outcomes. When WMI is detected on neonatal brain imaging, a detailed characterization of the injury (pattern of injury, severity and location) may enhance the ability to predict outcomes. This clinically-oriented review will provide an overview of the pathophysiology and imaging diagnosis of the multiple dimensions of WMI, will explore the association between postnatal complications and WMI, and will provide guidance on the signification of white matter anomalies for motor and cognitive development.

Incidental findings on brain MR imaging of asymptomatic term neonates in the Developing Human Connectome Project.

BackgroundInterpretation of incidental findings on term neonatal MRI brain imaging can be challenging as there is a paucity of published normative data on asymptomatic term neonates. Reporting radiologists and clinicians need to be familiar with these incidental findings to avoid over-investigation and misinterpretation particularly in relation to neurodevelopmental outcome. This study aimed to determine the prevalence of incidental findings in a large group of asymptomatic term neonates participating in the Developing Human Connectome Project (dHCP) who were invited for neurodevelopmental assessment at 18 months.MethodsWe retrospectively reviewed MRI brain scans performed on 500 term neonates enrolled in the dHCP study between 2015 and 2019 with normal clinical examination. We reviewed the results of the Bayley Scales of Infant and Toddler Development (Bayley III) applied to participants who attended for neurodevelopmental follow-up at 18 months. Scores considered “delayed” if <70 on language, cognitive or motor scales.FindingsIncidental findings were observed in 47% of term infants. Acute cerebral infarcts were incidentally noted in five neonates (1%). More common incidental findings included punctate white matter lesions (PWMLs) (12%) and caudothalamic subependymal cysts (10%). The most frequent incidental finding was intracranial haemorrhage (25%), particularly subdural haemorrhage (SDH). SDH and PWMLs were more common in infants delivered with ventouse-assistance versus other delivery methods.Neurodevelopmental results were available on 386/500 (77%). 14 infants had a language score < 70 (2 SD below the mean). Of the 386 infants with neurodevelopmental follow up at 18 months, group differences in motor and language scores between infants with and without incidental findings were not significant (p = 0·17 and p = 0·97 respectively). Group differences in cognitive scores at 18 months between infants with (median (interquartile range) -100 (95–105)) and without (100 (95–110)) incidental findings were of small effect size to suggest clinical significance (Cliff's d = 0·15; p<0·05).InterpretationIncidental findings are relatively common on brain MRI in asymptomatic term neonates, majority are clinically insignificant with normal neurodevelopment at 18 months.FundingThis work was supported by the European Research Council under the European Union's Seventh Framework Programme (FP7/20072013/ERC grant agreement no. [319456] dHCP project), by core funding from the Wellcome/EPSRC Centre for Medical Engineering [WT203148/Z/16/Z] and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust and King's College London and/or the NIHR Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Three-Dimensional Magnetic Resonance Fingerprinting in Neonates: Quantifying Regional Difference and Maturation in the Brain.

Magnetic resonance fingerprinting (MRF) allows the simultaneous measurement of multiple tissue properties in a single acquisition. Three-dimensional (3D) MRF with high spatial resolution can be used for neonatal brain imaging. The aim of this study is to apply 3D MRF to neonates and show regional differences and maturation in the brain. In this prospective study, 3D MRF using hybrid radial-interleaved acquisition was performed on phantoms and neonates from December 2019 to October 2020. For the reconstruction of 3D MRF, singular value decomposition was applied to reduce reconstruction time, and the iterative reconstruction technique was applied to improve image quality. The accuracies of T1 and T2 values derived from 3D MRF were evaluated in a phantom experiment. Regional T1 and T2 values were obtained from neonates' brain T1 and T2 maps derived from 3D MRF. Regional T1 and T2 values were compared, and their changes according to corrected gestational age were evaluated. The acquisition time for 3D MRF with a spatial resolution of 0.7 × 0.7 × 2 mm3 was less than 5 minutes. The phantom study showed high correlation between T1 and T2 values derived from 3D MRF and those from conventional spin echo sequences (T1, R2 = 0.998, P < 0.001; T2, R2 = 0.998, P < 0.001). Three-dimensional MRF was performed in 25 neonates (15 boys, 10 girls; median corrected gestational age, 263 days; interquartile range, 10 days). In neonates, T1 and T2 values differed in the frontal (median [interquartile range], 2785 [2684-2888] milliseconds and 189.8 [176.7-222.9] milliseconds), parietal (2849 [2741-2950] milliseconds and 191.6 [167.5-232.9] milliseconds), and occipital white matter (2621 [2513-2722] milliseconds and 162.9 [143.5-186.1] milliseconds), showing lower values in occipital white matter (P < 0.001). Regional T1 values showed a negative relationship with corrected gestational age (coefficient, -0.775 to -0.480; P < 0.05). Fast and high spatial resolution 3D MRF was applied to neonates. T1 and T2 maps derived from 3D MRF enabled the quantification of regional differences and maturation in the neonatal brain.

Brain Development and Maternal Behavior in Relation to Cognitive and Language Outcomes in Preterm-Born Children

Background: Children born very preterm (<=32 weeks gestational age) show poorer cognitive and language development compared to their term-born peers. The importance of positive maternal-child interactions for promoting neurodevelopment is well-established. However, little is known about whether sensitive maternal behaviors can buffer the association of early brain dysmaturation with cognitive and language performance. Methods: Infants born very preterm were recruited from the neonatal intensive care unit for a prospective, observational cohort study. Chart review was conducted prospectively from birth to discharge. MRI was acquired at ~32 weeks postmenstrual age and again at term-equivalent age, including diffusion tensor imaging. Fractional anisotropy, a quantitative measure of brain maturation, was obtained from 11 bilateral regions of interest in the cortical gray matter. At 3 years corrected age, neurodevelopmental testing (Bayley Scales of Infant & Toddler Development, Third Edition [Bayley-III]) was administered, and parent-child interaction was filmed. One hundred and forty-six infants with neonatal brain imaging and follow-up data were included for analysis. We examined whether maternal sensitivity interacted with mean fractional anisotropy values to predict Cognitive and Language scores at 3 years corrected age. Findings: Higher maternal sensitivity significantly moderated cortical fractional anisotropy values at term-equivalent age to predict higher Bayley-III Cognitive (s=1.72, P=0.05, R2=0.23), and Language Scores (s=1.91, P=0.03, R2=0.25). Interpretation: This suggests that positive parenting following early brain dysmaturation may provide an opportunity to support more optimal neurodevelopment in children born very preterm. Funding Information: Canadian Institutes for Health Research operating grant MOP-79262 (SPM) and MOP-86489 (REG). Declaration of Interests: The authors have no competing interests to disclose. Ethics Approval Statement: This study was approved by the Clinical Research Ethics Board at the University of British Columbia and BC Children’s and Women’s Hospitals. Parent written informed consent was obtained according to the Declaration of Helsinki.

Role of Cranial Ultrasound in High-Risk Full-Term Neonates

Background: Critically ill full-term infants are at risk for brain injury.The improvement of the survival of the “High-Risk Neonate” requires early detection of neurological abnormalities. Cranial ultrasonography (CUS) is the preferred tool to study the neonatal brain. Objective: This study aimed to evaluate the diagnostic role of cranial US in high-risk full-term neonates. Patients and Methods: This observational study was conducted on 60 high-risk full-term neonates randomly selected from the Neonatal Intensive Care Unit, Pediatric Department, Benha University Hospitals. Detailed history, clinical examination, appropriate investigations and cranial ultrasound were done. Results: The cranial ultrasound findings were normal in 58 cases (96.7%) and abnormal only in 2 cases (3.3%). The cranial ultrasound abnormalities found in the first case that was diagnosed as hypoxic ischemic encephalopathy and congenital malformation were hypoplasia of the cerebellar hemispheres, dilated fourth ventricle and prominent cisterna magna with Dandy walker malformation. The second case who was diagnosed as pneumonia and neonatal sepsis, cranial sonography showed cystic leukomalacia and communicating hydrocephalus. Conclusion: Although we found only 2 cases (3.3%) with abnormal CUS among the studied high-risk full-term neonates, cranial ultrasound is considered an important noninvasive method for brain imaging in neonates especially in those presented with neurological manifestations or exposed to hypoxia. It enables screening and follow up of the brain by serial imaging.

Role of Cranial Ultrasound in High-Risk Full-Term Neonates

Background: Critically ill full-term infants are at risk for brain injury.The improvement of the survival of the “High-Risk Neonate” requires early detection of neurological abnormalities. Cranial ultrasonography (CUS) is the preferred tool to study the neonatal brain. Objective: This study aimed to evaluate the diagnostic role of cranial US in high-risk full-term neonates. Patients and Methods: This observational study was conducted on 60 high-risk full-term neonates randomly selected from the Neonatal Intensive Care Unit, Pediatric Department, Benha University Hospitals. Detailed history, clinical examination, appropriate investigations and cranial ultrasound were done. Results: The cranial ultrasound findings were normal in 58 cases (96.7%) and abnormal only in 2 cases (3.3%). The cranial ultrasound abnormalities found in the first case that was diagnosed as hypoxic ischemic encephalopathy and congenital malformation were hypoplasia of the cerebellar hemispheres, dilated fourth ventricle and prominent cisterna magna with Dandy walker malformation. The second case who was diagnosed as pneumonia and neonatal sepsis, cranial sonography showed cystic leukomalacia and communicating hydrocephalus. Conclusion: Although we found only 2 cases (3.3%) with abnormal CUS among the studied high-risk full-term neonates, cranial ultrasound is considered an important noninvasive method for brain imaging in neonates especially in those presented with neurological manifestations or exposed to hypoxia. It enables screening and follow up of the brain by serial imaging.