DETERMINATION OF THE SEVERITY OF TRAUMATIC BRAIN INJURIES BY METHODS OF RADIATION DIAGNOSTICS.

To study the specificity and sensitivity of X-ray research methods in the diagnosis of traumatic brain injury. Of the 969 injured for various reasons, 444 patients underwent CT, and 34 patients underwent MRI. The obtained results were subjected to a comparative analysis. Traumatic brain injury was diagnosed in 197 people, of whom 192 (97.5%) underwent CT, 28 (14.2%) - MRI. Of these patients, 164 (83.2%) had a combined, 33 (16.8%) patients had an isolated traumatic brain injury. Based on the results of the study, CT can be considered a more effective examination method for detecting combined traumatic brain injuries due to CT sensitivity and specificity, and MRI due to sensitivity in detecting traumatic brain injuries resulting from a car accident. It has been established that multidetector CT is of great importance in the timely and correct diagnosis of traumatic brain injuries.

Shear shock wave injury in vivo: High frame-rate ultrasound observation and histological assessment.

Using high frame-rate ultrasound and ¡1µm sensitive motion tracking we previously showed that shear waves at the surface of ex vivo and in situ brains develop into shear shock waves deep inside the brain, with destructive local accelerations. However post-mortem tissue cannot develop injuries and has different viscoelastodynamic behavior from in vivo tissue. Here we present the ultrasonic measurement of the high-rate shear shock biomechanics in the in vivo porcine brain, and histological assessment of the resulting axonal pathology. A new biomechanical model of brain injury was developed consisting of a perforated mylar surface attached to the brain and vibrated using an electromechanical shaker. Using a custom sequence with 8 interleaved wide beam emissions, brain imaging and motion tracking were performed at 2900 images/s. Shear shock waves were observed for the first time in vivo wherein the shock acceleration was measured to be 2.6 times larger than the surface acceleration ( 95g vs. 36g). Histopathology showed axonal damage in the impacted side of the brain from the brain surface, accompanied by a local shock-front acceleration of >70g. This shows that axonal injury occurs deep in the brain even though the shear excitation was at the brain surface, and the acceleration measurements support the hypothesis that shear shock waves are responsible for deep traumatic brain injuries.

Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment.

Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly understood. Early diagnosis of preterm brain injuries remains a significant challenge. Here, we identified subventricular zone echogenicity (SVE) on cranial ultrasound in preterm infants following intestinal perforations. The development of SVE was significantly associated with motor impairment at 2 years. SVE was replicated in a neonatal mouse model of intestinal perforation. Examination of the murine echogenic subventricular zone (SVZ) revealed NLRP3-inflammasome assembly in multiciliated FoxJ1+ ependymal cells and a loss of the ependymal border in this postnatal stem cell niche. These data suggest a mechanism of preterm brain injury localized to the SVZ that has not been adequately considered. Ultrasound detection of SVE may serve as an early biomarker for neurodevelopmental impairment after inflammatory disease in preterm infants.

Size and Location of Preterm Brain Injury and Associations With Neurodevelopmental Outcomes.

BACKGROUND AND OBJECTIVES: We examined associations of white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI) volume and location with 18-month neurodevelopment in very preterm infants. METHODS: A total of 254 infants born <32 weeks' gestational age were prospectively recruited across 3 tertiary neonatal intensive care units (NICUs). Infants underwent early-life (median 33.1 weeks) and/or term-equivalent-age (median 41.9 weeks) MRI. WMI and PVHI were manually segmented for quantification in 92 infants. Highest maternal education level was included as a marker of socioeconomic status and was defined as group 1 = primary/secondary school; group 2 = undergraduate degree; and group 3 = postgraduate degree. Eighteen-month neurodevelopmental assessments were completed with Bayley Scales of Infant and Toddler Development, Third Edition. Adverse outcomes were defined as a score of less than 85 points. Multivariable linear regression models were used to examine associations of brain injury (WMI and PVHI) volume with neurodevelopmental outcomes. Voxel-wise lesion symptom maps were developed to assess relationships between brain injury location and neurodevelopmental outcomes. RESULTS: Greater brain injury volume was associated with lower 18-month Motor scores (ß = -5.7, 95% CI -9.2 to -2.2, p = 0.002) while higher maternal education level was significantly associated with higher Cognitive scores (group 3 compared 1: ß = 14.5, 95% CI -2.1 to 26.9, p = 0.03). In voxel-wise lesion symptom maps, brain injury involving the central and parietal white matter was associated with an increased risk of poorer motor outcomes. DISCUSSION: We found that brain injury volume and location were significant predictors of motor, but not cognitive outcomes, suggesting that different pathways may mediate outcomes across domains of neurodevelopment in preterm infants. Specifically, assessing lesion size and location may allow for more accurate identification of infants with brain injury at highest risk of poorer motor outcomes. These data also highlight the importance of socioeconomic status in cognitive outcomes, even in preterm infants with brain injury.

Investigating neuropathological changes and underlying neurobiological mechanisms in the early stages of primary blast-induced traumatic brain injury: Insights from a rat model.

The utilization of explosives and chemicals has resulted in a rise in blast-induced traumatic brain injury (bTBI) in recent times. However, there is a dearth of diagnostic biomarkers and therapeutic targets for bTBI due to a limited understanding of biological mechanisms, particularly in the early stages. The objective of this study was to examine the early neuropathological characteristics and underlying biological mechanisms of primary bTBI. A total of 83 Sprague Dawley rats were employed, with their heads subjected to a blast shockwave of peak overpressure ranging from 172 to 421 kPa in the GI, GII, and GIII groups within a closed shock tube, while the body was shielded. Neuromotor dysfunctions, morphological changes, and neuropathological alterations were detected through modified neurologic severity scores, brain water content analysis, MRI scans, histological, TUNEL, and caspase-3 immunohistochemical staining. In addition, label-free quantitative (LFQ)-proteomics was utilized to investigate the biological mechanisms associated with the observed neuropathology. Notably, no evident damage was discernible in the GII and GI groups, whereas mild brain injury was observed in the GIII group. Neuropathological features of bTBI were characterized by morphologic changes, including neuronal injury and apoptosis, cerebral edema, and cerebrovascular injury in the shockwave's path. Subsequently, 3153 proteins were identified and quantified in the GIII group, with subsequent enriched neurological responses consistent with pathological findings. Further analysis revealed that signaling pathways such as relaxin signaling, hippo signaling, gap junction, chemokine signaling, and sphingolipid signaling, as well as hub proteins including Prkacb, Adcy5, and various G-protein subunits (Gnai2, Gnai3, Gnao1, Gnb1, Gnb2, Gnb4, and Gnb5), were closely associated with the observed neuropathology. The expression of hub proteins was confirmed via Western blotting. Accordingly, this study proposes signaling pathways and key proteins that exhibit sensitivity to brain injury and are correlated with the early pathologies of bTBI. Furthermore, it highlights the significance of G-protein subunits in bTBI pathophysiology, thereby establishing a theoretical foundation for early diagnosis and treatment strategies for primary bTBI.

Whole-brain traumatic controlled cortical impact to the left frontal lobe: Magnetic resonance image-based texture analysis.

This research assesses the capability of texture analysis (TA) derived from high-resolution (HR) T2-weighted magnetic resonance imaging to identify primary sequelae following 1-5 hours of controlled cortical impact mild or severe traumatic brain injury (TBI) to the left frontal cortex (focal impact) and secondary (diffuse) sequelae in the right frontal cortex, bilateral corpus callosum, and hippocampus in rats. The TA technique comprised first-order (histogram-based) and second-order statistics (including gray-level co-occurrence matrix, gray-level run length matrix, and neighborhood gray-level difference matrix). Edema in the left frontal impact region developed within 1 hour and continued throughout the 5-hour assessments. The TA features from HR images confirmed the focal injury. There was no significant difference among radiomics features between the left and right corpus callosum or hippocampus from 1 to 5 hours following a mild or severe impact. The adjacent corpus callosum region and the distal hippocampus region (s), showed no diffuse injury 1-5 hours after mild or severe TBI. These results suggest that combining HR images with TA may enhance detection of early primary and secondary sequelae following TBI.

White Matter Injury on Early-versus-Term-Equivalent Age Brain MRI in Infants Born Preterm.

BACKGROUND AND PURPOSE: White matter injury in infants born preterm is associated with adverse neurodevelopmental outcomes, depending on the extent and location. White matter injury can be visualized with MR imaging in the initial weeks following preterm birth but is more commonly defined at term-equivalent-age MR imaging. Our aim was to see how white matter injury detection in MR imaging compares between the 2 time points. MATERIALS AND METHODS: This study compared white matter injury on early brain MR imaging (30-34 weeks' postmenstrual age) with white matter injury assessment at term-equivalent (37-42 weeks) MR imaging, using 2 previously published and standardized scoring systems, in a cohort of 30 preterm infants born at <33 weeks' gestational age. RESULTS: There was a strong association between the systematic assessments of white matter injury at the 2 time points (P = .007) and the global injury severity (P < .001). CONCLUSIONS: Although the optimal timing to undertake neuroimaging in the preterm infant remains to be determined, both early (30-34 weeks) and term-equivalent MR imaging provide valuable information on white matter injury and the risk of associated sequelae.

Aberrant White Matter Development in Cerebral Visual Impairment: A Proposed Mechanism for Visual Dysfunction Following Early Brain Injury.

BACKGROUND: Cerebral visual impairment (CVI) is a common sequala of early brain injury, damage, or malformation and is one of the leading individual causes of visual dysfunction in pediatric populations worldwide. Although patients with CVI are heterogeneous both in terms of underlying etiology and visual behavioural manifestations, there may be underlying similarities in terms of which white matter pathways are potentially altered. This exploratory study used diffusion tractography to examine potential differences in volume, quantitative anisotropy (QA), as well as mean, axial, and radial diffusivities (mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), respectively) focusing on the dorsal and ventral visual stream pathways in a cohort of young adults with CVI compared to typically sighted and developing controls. METHODS: High angular resolution diffusion imaging (HARDI) data were acquired in a sample of 10 individuals with a diagnosis of CVI (mean age = 17.3 years, 2.97 standard deviation (SD), range 14-22 years) and 17 controls (mean age = 19.82 years, 3.34 SD, range 15-25 years). The inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), vertical occipital fasciculus (VOF), and the three divisions of the superior longitudinal fasciculus (SLF I, II, and III) were virtually reconstructed and average tract volume (adjusted for intracranial volume), MD, AD, and RD were compared between CVI and control groups. As a secondary analysis, an analysis of variance (ANOVA) was carried out to investigate potential differences based on etiology (i.e., CVI due to periventricular leukomalacia (CVI-PVL) and CVI due to other causes (CVI-nonPVL)). RESULTS: We observed a large degree of variation within the CVI group, which minimized the overall group differences in tractography outcomes when examining the CVI sample as a unitary group. In our secondary analysis, we observed significant reductions in tract volume in the CVI-PVL group compared to both controls and individuals with CVI due to other causes. We also observed widespread significant increases in QA, MD, and AD in CVI-PVL compared to the control group, with mixed effects in the CVI-nonPVL group. CONCLUSIONS: These data provide preliminary evidence for aberrant development of key white matter fasciculi implicated in visual perceptual processing skills, which are often impaired to varying degrees in individuals with CVI. The results also indicate that the severity and extent of the white matter changes may be due in part to the underlying cause of the cerebral visual impairments. Additional analyses will need to be done in a larger sample alongside behavioural testing to fully appreciate the relationships between white matter integrity, visual dysfunction, and associated causes in individuals with CVI.

Association of aEEG and brain injury severity on MRI at term-equivalent age in preterm infants.

AIM: Measures to detect and monitor brain injury in preterm infants are amplitude-integrated electroencephalography (aEEG) and magnetic resonance imaging (MRI). To investigate the association between aEEG and MRI in a large cohort of preterm infants. Five hundred and twenty-three preterm infants were included in the study. METHODS: AEEG was interpreted for the total maturation score (TMS) according to Burdjalov. Cerebral MRI was evaluated using a validated scoring system by Kidokoro. RESULTS: One hundred and forty-six infants (27.9%) showed some form of brain injury, with 111 infants (21.2%) showing mild injury and 35 (6.7%) showing severe injury. TMS were significantly higher in infants without injury compared to severe injury. When comparing infants with isolated intraventricular haemorrhage  to infants without brain injury, TMS were significantly lower. CONCLUSION: Prediction of adverse outcome is an important aspect of neonatal care. The combination of diagnostic measures evaluating brain injury might enhance our abilities in neonatal care to provide accurate information about later outcome. Early aEEG is predictive for the severity of brain injury detected by MRI at term-equivalent age. Whether aEEG is also predictive for neurodevelopmental outcome needs to be further investigated in relation to the various patterns of preterm brain injury.

Development of a Randomized Trial Comparing ICP-Monitor-Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring-Research Algorithms.

BACKGROUND AND OBJECTIVES: The efficacy of our current approach to incorporating intracranial pressure (ICP) data into pediatric severe traumatic brain injury (sTBI) management is incompletely understood, lacking data from multicenter, prospective, randomized studies. The National Institutes of Health-supported Benchmark Evidence from Latin America-Treatment of Raised Intracranial Pressure-Pediatrics trial will compare outcomes from pediatric sTBI of a management protocol based on ICP monitoring vs 1 based on imaging and clinical examination without monitoring. Because no applicable comprehensive management algorithms for either cohort are available, it was necessary to develop them. METHODS: A consensus conference involving the 21 intensivists and neurosurgeons from the 8 trial sites used Delphi-based methodology to formulate management algorithms for both study cohorts. We included recommendations from the latest Brain Trauma Foundation pediatric sTBI guidelines and the consensus-based adult algorithms (Seattle International Brain Injury Consensus Conference/Consensus Revised Imaging and Clinical Examination) wherever relevant. We used a consensus threshold of 80%. RESULTS: We developed comprehensive management algorithms for monitored and nonmonitored cohort children with sTBI. We defined suspected intracranial hypertension for the nonmonitored group, set minimum number and timing of computed tomography scans, specified minimal age-adjusted mean arterial pressure and cerebral perfusion pressure targets, defined clinical neuroworsening, described minimal requisites for intensive care unit management, produced tiered management algorithms for both groups, and listed treatments not routinely used. CONCLUSION: We will study these protocols in the Benchmark Evidence from Latin America-Treatment of Raised Intracranial Pressure-Pediatrics trial in low- and middle-income countries. Second, we present them here for consideration as prototype pediatric sTBI management algorithms in the absence of published alternatives, acknowledging their limited evidentiary status. Therefore, herein, we describe our study design only, not recommended treatment protocols.

Magnetic Resonance Imaging-Based Reference Values for Two-Dimensional Quantitative Brain Metrics in a Cohort of Extremely Preterm Infants.

INTRODUCTION: Cerebral magnetic resonance imaging (cMRI) is an important diagnostic tool in neonatology. In addition to qualitative analysis, quantitative measurements may help identify infants with impaired brain growth. This study aimed to create reference values for brain metrics of various brain areas in neonates without major brain injuries born before 28 weeks of gestation. METHODS: This retrospective study analyzes cMRI imaging data of high-risk patients without severe brain pathologies at term-equivalent age, collected over 4 years since November 2017. Nineteen brain areas were measured, reference values created, and compared to published values from fetal and postnatal MRI. Furthermore, correlations between brain metrics and gestational age at birth were evaluated. RESULTS: A total of 174 cMRI examinations were available for analysis. Reference values including cut-offs for impaired brain growth were established for different gestational age groups. There was a significant correlation between gestational age at birth and larger "tissue" parameters, as well as smaller "fluid" parameters, including intracerebral and extracerebral spaces. DISCUSSION: With quantitative brain metrics infants with impaired brain growth might be detected earlier. Compared to preexisting reference values, these are the first of a contemporary collective of extremely preterm neonates without severe brain injuries. Measurements can be easily performed by radiologists as well as neonatologists without specialized equipment or computational expertise. CONCLUSION: Two-dimensional cMRI brain measurements at term-equivalent age represent an easy and reliable approach for the evaluation of brain size and growth in infants at high risk for neurodevelopmental impairment.

Structural Brain Injury on Brain Magnetic Resonance Imaging in Acute Respiratory Distress Syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is an acute inflammatory respiratory failure condition that may be associated with brain injury. We aimed to describe the types of structural brain injuries detected by brain magnetic resonance imaging (MRI) among patients with ARDS. METHODS: We retrospectively reviewed and collected data on brain injuries as detected by brain MRI during index hospitalization of all patients with ARDS at a single tertiary center in the United States from January 2010 to October 2018 (pre-COVID era). Structural brain injuries were classified as cerebral ischemia (ischemic infarct and hypoxic-ischemic brain injury) or cerebral hemorrhage (intraparenchymal hemorrhage, cerebral microbleeds, subarachnoid hemorrhage, and subdural hematoma). Descriptive statistics were conducted. RESULTS: Of the 678 patients with ARDS, 66 (9.7%) underwent brain MRI during their ARDS illness. The most common indication for brain MRI was encephalopathy (45.4%), and the median time from hospital admission to MRI was 10 days (interquartile range 4-17). Of 66 patients, 29 (44%) had MRI evidence of brain injury, including cerebral ischemia in 33% (22 of 66) and cerebral hemorrhage in 21% (14 of 66). Among those with cerebral ischemia, common findings were bilateral globus pallidus infarcts (n = 7, 32%), multifocal infarcts (n = 5, 23%), and diffuse hypoxic-ischemic brain injury (n = 3, 14%). Of those with cerebral hemorrhage, common findings were cerebral microbleeds (n = 12, 86%) and intraparenchymal hemorrhage (n = 2, 14%). Patients with ARDS with cerebral hemorrhage had significantly greater use of rescue therapies, including prone positioning (28.6% vs. 5.8%, p = 0.03), inhaled vasodilator (35.7% vs. 11.5%, p = 0.046), and recruitment maneuver (14.3% vs. 0%, p = 0.04). CONCLUSIONS: Structural brain injury was not uncommon among selected patients with ARDS who underwent brain MRI. The majority of brain injuries seen were bilateral globus pallidus infarcts and cerebral microbleeds.

Point-of-care brain ultrasound and transcranial doppler or color-coded doppler in critically ill neonates and children.

Point-of-care brain ultrasound and transcranial doppler or color-coded doppler is being increasingly used as an essential diagnostic and monitoring tool at the bedside of critically ill neonates and children. Brain ultrasound has already established as a cornerstone of daily practice in the management of the critically ill newborn for diagnosis and follow-up of the most common brain diseases, considering the easiness to insonate the brain through transfontanellar window. In critically ill children, doppler based techniques are used to assess cerebral hemodynamics in acute brain injury and recommended for screening patients suffering from sickle cell disease at risk for stroke. However, more evidence is needed regarding the accuracy of doppler based techniques for non-invasive estimation of cerebral perfusion pressure and intracranial pressure, as well as regarding the accuracy of brain ultrasound for diagnosis and monitoring of acute brain parenchyma alterations in children. This review is aimed at providing a comprehensive overview for clinicians of the technical, anatomical, and physiological basics for brain ultrasonography and transcranial doppler or color-coded doppler, and of the current status and future perspectives of their clinical applications in critically ill neonates and children. CONCLUSION: In critically ill neonates, brain ultrasound for diagnosis and follow-up of the most common cerebral pathologies of the neonatal period may be considered the standard of care. Data are needed about the possible role of doppler techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles. In pediatric critical care, doppler based techniques should be routinely adopted to assess and monitor cerebral hemodynamics. New technologies and more evidence are needed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. WHAT IS KNOWN: • In critically ill neonates, brain ultrasound for early diagnosis and follow-up of the most common cerebral and neurovascular pathologies of the neonatal period is a cornerstone of daily practice. In critically ill children, doppler-based techniques are more routinely used to assess cerebral hemodynamics and autoregulation after acute brain injury and to screen patients at risk for vasospasm or stroke (e.g., sickle cell diseases, right-to-left shunts). WHAT IS NEW: • In critically ill neonates, research is currently focusing on the use of novel high frequency probes, even higher than 10 MHz, especially for extremely preterm babies. Furthermore, data are needed about the role of doppler based techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles, also integrated with a non-invasive assessment of brain oxygenation. In pediatric critical care, new technologies should be developed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. Furthermore, large multicenter studies are needed to clarify role and accuracy of doppler-based techniques to assess cerebral perfusion pressure and its changes after treatment interventions.

Distinct manifestations and potential mechanisms of seizures due to cortical versus white matter injury in children.

PURPOSE: To study seizure manifestations and outcomes in children with cortical versus white matter injury, differences potentially explaining variability of epilepsy in children with cerebral palsy. METHODS: In this population-based retrospective cohort study, MRIs of children with cerebral palsy due to ischemia or haemorrhage were classified according to presence or absence of cortical injury. MRI findings were then correlated with history of neonatal seizures, seizures during childhood, epilepsy syndromes, and seizure outcomes. RESULTS: Of 256 children studied, neonatal seizures occurred in 57 and seizures during childhood occurred in 93. Children with neonatal seizures were more likely to develop seizures during childhood, mostly those with cortical injury. Cortical injury was more strongly associated with (1) developing seizures during childhood, (2) more severe epilepsy syndromes (infantile spasms syndrome, focal epilepsy, Lennox-Gastaut syndrome), and (3) less likelihood of reaching > 2 years without seizures at last follow-up, compared to children without cortical injury. Children without cortical injury, mainly those with white matter injury, were less likely to develop neonatal seizures and seizures during childhood, and when they did, epilepsy syndromes were more commonly febrile seizures and self-limited focal epilepsies of childhood, with most achieving > 2 years without seizures at last follow-up. The presence of cortical injury also influenced seizure occurrence, severity, and outcome within the different predominant injury patterns of the MRI Classification System in cerebral palsy, most notably white matter injury. CONCLUSIONS: Epileptogenesis is understood with cortical injury but not well with white matter injury, the latter potentially related to altered postnatal white matter development or myelination leading to apoptosis, abnormal synaptogenesis or altered thalamic connectivity of cortical neurons. These findings, and the potential mechanisms discussed, likely explain the variability of epilepsy in children with cerebral palsy and epilepsy following early-life brain injury in general.

NEURAL PROTEINS AS MARKERS FOR DIAGNOSING STRUCTURAL DAMAGE TO BRAIN MATTER IN POST-TRAUMATIC NEUROCOGNITIVE DISORDERS.

Objectives to determine the role of neural markers for brain matter damage in cognitive dysfunction after severe traumatic brain injury. A comprehensive study included clinical and laboratory examination, neuropsychological testing, MRI. To identify markers of structural changes in brain substance, neural proteins were identified: glial fibrillary acidic protein and neural cell adhesion molecule. Neural proteins quantification was performed using an enzyme-linked immunosorbent assay. 280 patients with severe traumatic brain injuries and moderate neurocognitive disorders (MND) (DSM-V) were examined and divided into two groups according to the pathogenetic mechanisms and neuropsychological profiles. The first group included subjects with MNDs of a primary dysmnestic type (73 persons), the second group presented MNDs of a neurodynamic-dysregulatory type (207 persons). The follow-up period was 6 months, 1 year and 3 years. By the third year, progression of cognitive disorders in the first group was detected in 5% of cases, in the second group - in 10% of cases. The revealed NP dynamic disturbances and their quantitative assessment in clinical groups during the examination allowed specifying structural and functional brain changes to characterize mechanisms of neurocognitive disorder development in traumatic brain injuries. The findings have demonstrated neural proteins can be considered as markers for not only structural, but also neurodynamic processes.

Predicting neurologic recovery after severe acute brain injury using resting-state networks.

OBJECTIVE: There is a lack of reliable tools used to predict functional recovery in unresponsive patients following a severe brain injury. The objective of the study is to evaluate the prognostic utility of resting-state functional magnetic resonance imaging for predicting good neurologic recovery in unresponsive patients with severe brain injury in the intensive-care unit. METHODS: Each patient underwent a 5.5-min resting-state scan and ten resting-state networks were extracted via independent component analysis. The Glasgow Outcome Scale was used to classify patients into good and poor outcome groups. The Nearest Centroid classifier used each patient's ten resting-state network values to predict best neurologic outcome within 6 months post-injury. RESULTS: Of the 25 patients enrolled (mean age = 43.68, range = [19-69]; GCS ≤ 9; 6 females), 10 had good and 15 had poor outcome. The classifier correctly and confidently predicted 8/10 patients with good and 12/15 patients with poor outcome (mean = 0.793, CI = [0.700, 0.886], Z = 2.843, p = 0.002). The prediction performance was largely determined by three visual (medial: Z = 3.11, p = 0.002; occipital pole: Z = 2.44, p = 0.015; lateral: Z = 2.85, p = 0.004) and the left frontoparietal network (Z = 2.179, p = 0.029). DISCUSSION: Our approach correctly identified good functional outcome with higher sensitivity (80%) than traditional prognostic measures. By revealing preserved networks in the absence of discernible behavioral signs, functional connectivity may aid in the prognostic process and affect the outcome of discussions surrounding withdrawal of life-sustaining measures.

The Effect of Postnatal Cytomegalovirus Infection on (Micro)structural Cerebral Development in Very Preterm Infants at Term-Equivalent Age.

INTRODUCTION: There are some data indicating a negative impact of postnatal cytomegalovirus (CMV) infection on long-term neurodevelopmental outcome of preterm infants. So far, there is only little knowledge about a cerebral imaging correlate of these neurodevelopmental alterations induced by postnatal CMV infection in preterm infants. The aim of the current study was to investigate the effect of postnatal CMV infection on the incidence of brain injury and on microstructural brain maturation in very preterm infants at term-equivalent age. METHODS: Infants <32 gestational weeks (02/2011-11/2018) received cerebral MRI including axial diffusion-weighted images at term-equivalent age. All infants were screened for CMV infection using urine/saliva samples, and infection was regarded as acquired postnatal if a sample became positive >5 postnatal days. We compared brain injury as well as fractional anisotropy and apparent diffusion coefficient in 14 defined cerebral regions between infants with and without postnatal CMV infection. RESULTS: 401 infants were eligible, of whom 18 (4.5%) infants had a postnatal CMV infection. There were no significant differences in rates of brain injury or in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks. CONCLUSION: Although infants with postnatal CMV infection were born more immature and more frequently suffered from complications related to immaturity, we neither observed a higher rate of preterm brain injury nor disadvantageous alterations in microstructural brain maturation at term-equivalent age.

Neonatal cortical activity organizes into transient network states that are affected by vigilance states and brain injury.

Early neurodevelopment is critically dependent on the structure and dynamics of spontaneous neuronal activity; however, the natural organization of newborn cortical networks is poorly understood. Recent adult studies suggest that spontaneous cortical activity exhibits discrete network states with physiological correlates. Here, we studied newborn cortical activity during sleep using hidden Markov modeling to determine the presence of such discrete neonatal cortical states (NCS) in 107 newborn infants, with 47 of them presenting with a perinatal brain injury. Our results show that neonatal cortical activity organizes into four discrete NCSs that are present in both cardinal sleep states of a newborn infant, active and quiet sleep, respectively. These NCSs exhibit state-specific spectral and functional network characteristics. The sleep states exhibit different NCS dynamics, with quiet sleep presenting higher fronto-temporal activity and a stronger brain-wide neuronal coupling. Brain injury was associated with prolonged lifetimes of the transient NCSs, suggesting lowered dynamics, or flexibility, in the cortical networks. Taken together, the findings suggest that spontaneously occurring transient network states are already present at birth, with significant physiological and pathological correlates; this NCS analysis framework can be fully automatized, and it holds promise for offering an objective, global level measure of early brain function for benchmarking neurodevelopmental or clinical research.

Microstructural Brain Development and Neurodevelopmental Outcome of Very Preterm Infants of Mothers with Gestational Diabetes Mellitus.

INTRODUCTION: There are data linking gestational diabetes mellitus (GDM) with adverse neurodevelopmental outcome in the offspring. We investigated the effect of GDM on microstructural brain development and neurodevelopmental outcome of very preterm infants. MATERIALS AND METHODS: Preterm infants <32 gestational weeks of mothers with GDM obtained cerebral magnetic resonance imaging (MRI) including diffusion-tensor imaging at term-equivalent age. For every infant, two gestational age-, sex-, and MRI scanner type-matched controls were included. Brain injury was assessed and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measured in 14 defined cerebral regions. Neurodevelopmental outcome was quantified at the corrected age of 24 months using the Bayley Scales of Infant Development. RESULTS: We included 47 infants of mothers with GDM and 94 controls. There were no differences in neonatal morbidity between the groups, nor in any type of brain injury. The GDM group showed significantly higher FA values in the centrum semiovale, the posterior limb of the internal capsule and the pons bilaterally, in the corpus callosum and the right occipital white matter, as well as lower ADC values in the right centrum semiovale, the right occipital white matter and the corpus callosum. Neurodevelopmental outcome did not differ between the groups. CONCLUSION: We found no impairment of brain development in GDM-exposed infants compared to matched controls, but differences in white matter microstructure in specific regions indicating an enhanced maturation. However, neurodevelopmental outcome was equal in both groups. Further studies are needed to better understand brain maturation in preterm infants exposed to GDM.