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Objectives: Hemodynamic abnormalities and brain development disorders have been reported previously in fetuses and infants with transposition of the great arteries and intact ventricular septum (TGA‐IVS). A ventricular septal defect (VSD) is thought to be an additional risk factor for adverse neurodevelopment, but literature describing this population is sparse. The objectives of this study were to assess fetal cardiac hemodynamics throughout pregnancy, to monitor cerebral hemodynamics and oxygen metabolism in neonates, and to compare these data between patients with TGA‐IVS, those with TGA‐VSD and age‐matched controls. Methods: Cardiac hemodynamics were assessed in TGA‐IVS and TGA‐VSD fetuses and compared with healthy controls matched for gestational age (GA) during three periods: ≤ 22 + 5 weeks (GA1), 27 + 0 to 32 + 5 weeks (GA2) and ≥ 34 + 5 weeks (GA3). Left (LVO), right (RVO) and combined (CVO) ventricular outputs, ductus arteriosus flow (DAF, sum of ante‐ and retrograde flow in systole and diastole), diastolic DAF, transpulmonary flow (TPF) and foramen ovale diameter were measured. Aortic (AoF) and main pulmonary artery (MPAF) flows were derived as a percentage of CVO. Fetal middle cerebral artery and umbilical artery (UA) pulsatility indices (PI) were measured and the cerebroplacental ratio (CPR) was derived. Bedside optical brain monitoring was used to measure cerebral hemoglobin oxygen saturation (SO2) and an index of microvascular cerebral blood flow (CBFi), along with peripheral arterial oxygen saturation (SpO2), in TGA‐IVS and TGA‐VSD neonates. Using hemoglobin (Hb) concentration measurements, these parameters were used to derive cerebral oxygen delivery and extraction fraction (OEF), as well as an index of cerebral oxygen metabolism (CMRO2i). These data were acquired in the early preoperative period (within 3 days after birth and following balloon atrial septostomy) and compared with those of age‐matched healthy controls, and repeat measurements were collected before discharge when vital signs were stable. Results: LVO was increased in both TGA groups compared with controls throughout pregnancy. Compared with controls, TPF was increased and diastolic DAF was decreased in TGA‐IVS fetuses throughout pregnancy, but only during GA1 and GA2 in TGA‐VSD fetuses. Compared with controls, DAF was decreased in TGA‐IVS fetuses throughout pregnancy and in TGA‐VSD fetuses at GA2 and GA3. At GA2, AoF was higher in TGA‐IVS and TGA‐VSD fetuses than in controls, while MPAF was lower. At GA3, RVO and CVO were higher in the TGA‐IVS group than in the TGA‐VSD group. In addition, UA‐PI was lower at GA2 and CPR higher at GA3 in TGA‐VSD fetuses compared with TGA‐IVS fetuses. Within 3 days after birth, SpO2 and SO2 were lower in both TGA groups than in controls, while Hb, cerebral OEF and CMRO2i were higher. Preoperative SpO2 was also lower in TGA‐VSD neonates than in those with TGA‐IVS. From preoperative to predischarge periods, SpO2 and OEF increased in both TGA groups, but CBFi and CMRO2i increased only in the TGA‐VSD group. During the predischarge period, SO2 was higher in TGA‐IVS than in TGA‐VSD neonates, while CBFi was lower. Conclusions: Fetal cardiac and neonatal cerebral hemodynamic/metabolic differences were observed in both TGA groups compared with controls. Compared to those with TGA‐IVS, fetuses with TGA‐VSD had lower RVO and CVO in late gestation. A higher level of preoperative hypoxemia was observed in the TGA‐VSD group. Postsurgical cerebral adaptive mechanisms probably differ between TGA groups. Patients with TGA‐VSD have a specific physiology that warrants further study to improve neonatal care and neurodevelopmental outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Purpose: The use of trametinib in the treatment of pediatric low-grade gliomas (PLGG) and plexiform neurofibroma (PN) is being investigated in an ongoing multicenter phase II trial (NCT03363217). Preliminary data shows potential benefits with significant response in the majority of PLGG and PN and an overall good tolerance. Moreover, possible benefits of MEK inhibitor therapy on cognitive functioning in neurofibromatosis type 1 (NF1) were recently shown which supports the need for further evaluation., Methods: Thirty-six patients with NF1 (age range 3-19 years) enrolled in the phase II study of trametinib underwent a neurocognitive assessment at inclusion and at completion of the 72-week treatment. Age-appropriate Wechsler Intelligence Scales and the Trail Making Test (for children over 8 years old) were administered at each assessment. Paired t-tests and Reliable Change Index (RCI) analyses were performed to investigate change in neurocognitive outcomes. Regression analyses were used to investigate the contribution of age and baseline score in the prediction of change., Results: Stable performance on neurocognitive tests was revealed at a group-level using paired t-tests. Clinically significant improvements were however found on specific indexes of the Wechsler intelligence scales and Trail Making Test, using RCI analyses. No significant impact of age on cognitive change was evidenced. However, lower initial cognitive performance was associated with increased odds of presenting clinically significant improvements on neurocognitive outcomes., Conclusion: These preliminary results show a potential positive effect of trametinib on cognition in patients with NF1. We observed significant improvements in processing speed, visuo-motor and verbal abilities. This study demonstrates the importance of including neuropsychological evaluations into clinical trial when using MEK inhibitors for patients with NF1., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Advanced magnetic resonance imaging (MRI) techniques indicate that concussion (i.e., mild traumatic brain injury) disrupts brain structure and function in children. However, the functional connectivity of brain regions within global and local networks (i.e., functional connectome) is poorly understood in pediatric concussion. This prospective, longitudinal study addressed this gap using data from the largest neuroimaging study of pediatric concussion to date to study the functional connectome longitudinally after concussion as compared with mild orthopedic injury (OI). Children and adolescents ( n  = 967) 8-16.99 years with concussion or mild OI were recruited from pediatric emergency departments within 48 h post-injury. Pre-injury and 1-month post-injury symptom ratings were used to classify concussion with or without persistent symptoms based on reliable change. Subjects completed a post-acute (2-33 days) and chronic (3 or 6 months via random assignment) MRI scan. Graph theory metrics were derived from 918 resting-state functional MRI scans in 585 children (386 concussion/199 OI). Linear mixed-effects modeling was performed to assess group differences over time, correcting for multiple comparisons. Relative to OI, the global clustering coefficient was reduced at 3 months post-injury in older children with concussion and in females with concussion and persistent symptoms. Time post-injury and sex moderated group differences in local (regional) network metrics of several brain regions, including degree centrality, efficiency, and clustering coefficient of the angular gyrus, calcarine fissure, cuneus, and inferior occipital, lingual, middle occipital, post-central, and superior occipital gyrus. Relative to OI, degree centrality and nodal efficiency were reduced post-acutely, and nodal efficiency and clustering coefficient were reduced chronically after concussion (i.e., at 3 and 6 months post-injury in females; at 6 months post-injury in males). Functional network alterations were more robust and widespread chronically as opposed to post-acutely after concussion, and varied by sex, age, and symptom recovery at 1-month post-injury. Local network segregation reductions emerged globally (across the whole brain network) in older children and in females with poor recovery chronically after concussion. Reduced functioning between neighboring regions could negatively disrupt specialized information processing. Local network metric alterations were demonstrated in several posterior regions that are involved in vision and attention after concussion relative to OI. This indicates that functioning of superior parietal and occipital regions could be particularly susceptibile to the effects of concussion. Moreover, those regional alterations were especially apparent at later time periods post-injury, emerging after post-concussive symptoms resolved in most and persisted up to 6 months post-injury, and differed by biological sex. This indicates that neurobiological changes continue to occur up to 6 months after pediatric concussion, although changes emerge earlier in females than in males. Changes could reflect neural compensation mechanisms.

Here, we present MCOCT, a Monte Carlo simulator for optical coherence tomography (OCT), incorporating a Gaussian illumination scheme and bias to increase backscattered event collection. MCOCT optical fluence was numerically compared and validated to an established simulator (MCX) and showed concordance at the focus while diverging slightly with distance to it. MCOCT OCT signals were experimentally compared and validated to OCT signals acquired in tissue-mimicking phantoms with known optical properties and showed a similar attenuation pattern with increasing depth while diverging beyond 1.5 mm and proximal to layer interfaces. MCOCT may help in the design of OCT systems for a wide range of applications., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

Rationale and Objectives: Plexiform neurofibromas (PNs) are peripheral nerve tumors that occur in 25-50 % of patients with neurofibromatosis type 1. PNs may have complex, diffused, and irregular shapes. The objective of this work was to develop a volumetric quantification method for PNs as clinical assessment is currently based on unidimensional measurement., Materials and Methods: A semi-automatic segmentation technique based on mean magnetic resonance imaging (MRI) intensity thresholding (SSTMean) was developed and compared to a similar and previously published technique based on minimum image intensity thresholding (SSTMini). The performance (volume and computation time) of the two techniques was compared to manual tracings of 15 tumors of different locations, shapes, and sizes. Performance was also assessed using different MRI sequences. Reproducibility was assessed by inter-observer analysis., Results: When compared to manual tracing, quantification performed with SSTMean was not significantly different (mean difference: 1.2 %), while volumes computed by SSTMini were significantly different (p < .0001, mean difference: 13.4 %). Volumes quantified by SSTMean were also significantly different than the ones assessed by SSTMini (p < .0001). Using SSTMean, volumes quantified with short TI inversion recovery, T1-, and T2-weighted imaging were not significantly different. Computation times used by SSTMean and SSTMini were significantly lower than for manual segmentation (p < .0001). The highest difference measured by two users was 8 cm 3 ., Conclusion: Our method showed accuracy compared to a current gold standard (manual tracing) and reproducibility between users. The refined segmentation threshold and the possibility to define multiple regions-of-interest to initiate segmentation may have contributed to its performance. The versatility and speed of our method may prove useful to better monitor volumetric changes in lesions of patients enrolled in clinical trials to assessing response to therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

A few-mode optical coherence tomography (FM-OCT) system was developed around a 2 × 1 modally-specific photonic lantern (MSPL) centered at 1310 nm. The MSPL allowed FM-OCT to acquire two coregistered images with uncorrelated speckle patterns generated by their specific coherent spread function. Here, we showed that averaging such images in vitro and in vivo reduced the speckle contrast by up to 28% and increased signal-to-noise ratio (SNR) by up to 48% with negligible impact on image spatial resolution. This method is compatible with other speckle reduction techniques to further improve OCT image quality., Competing Interests: C.B.: Castor Optics, inc. (I,P). The other authors have no conflicts to disclose., (© 2023 Optica Publishing Group.)

Patients with congenital heart disease (CHD) requiring cardiac surgery in infancy are at high risk for neurodevelopmental impairments. Neonatal imaging studies have reported disruptions of brain functional organization before surgery. Yet, the extent to which functional network alterations are present after cardiac repair remains unexplored. This preliminary study aimed at investigating cortical functional connectivity in 4-month-old infants with repaired CHD, using resting-state functional near-infrared spectroscopy (fNIRS). After fNIRS signal frequency decomposition, we compared values of magnitude-squared coherence as a measure of connectivity strength, between 21 infants with corrected CHD and 31 healthy controls. We identified a subset of connections with differences between groups at an uncorrected statistical level of p  < .05 while controlling for sex and maternal socioeconomic status, with most of these connections showing reduced connectivity in infants with CHD. Although none of these differences reach statistical significance after FDR correction, likely due to the small sample size, moderate to large effect sizes were found for group-differences. If replicated, these results would therefore suggest preliminary evidence that alterations of brain functional connectivity are present in the months after cardiac surgery. Additional studies involving larger sample size are needed to replicate our data, and comparisons between pre- and postoperative findings would allow to further delineate alterations of functional brain connectivity in this population.

Background and Objectives: This prospective, longitudinal cohort study examined trajectories of brain gray matter macrostructure after pediatric mild traumatic brain injury (mTBI)., Methods: Children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) were recruited from 5 pediatric emergency departments. Reliable change between preinjury and 1 month postinjury symptom ratings was used to classify mTBI with or without persistent symptoms. Children completed postacute (2-33 days) and/or chronic (3 or 6 months) postinjury T1-weighted MRI, from which macrostructural metrics were derived using automated segmentation. Linear mixed-effects models were used, with multiple comparisons correction., Results: Groups ( N = 623; 407 mTBI/216 OI; 59% male; age mean = 12.03, SD = 2.38 years) did not differ in total brain, white, or gray matter volumes or regional subcortical gray matter volumes. However, time postinjury, age at injury, and biological sex-moderated differences among symptom groups in cortical thickness of the angular gyrus, basal forebrain, calcarine cortex, gyrus rectus, medial and posterior orbital gyrus, and the subcallosal area all corrected p < 0.05. Gray matter macrostructural metrics did not differ between groups postacutely. However, cortical thinning emerged chronically after mTBI relative to OI in the angular gyrus in older children ( d [95% confidence interval] = -0.61 [-1.15 to -0.08]); and in the basal forebrain (-0.47 [-0.94 to -0.01]), subcallosal area (-0.55 [-1.01 to -0.08]), and the posterior orbital gyrus (-0.55 [-1.02 to -0.08]) in females. Cortical thinning was demonstrated for frontal and occipital regions 3 months postinjury in males with mTBI with persistent symptoms vs without persistent symptoms (-0.80 [-1.55 to -0.05] to -0.83 [-1.56 to -0.10]) and 6 months postinjury in females and younger children with mTBI with persistent symptoms relative to mTBI without persistent symptoms and OI (-1.42 [-2.29 to -0.45] to -0.91 [-1.81 to -0.01])., Discussion: These findings signal little diagnostic and prognostic utility of postacute gray matter macrostructure in pediatric mTBI. However, mTBI altered the typical course of cortical gray matter thinning up to 6 months postinjury, even after symptoms typically abate in most children. Collapsing across symptom status obscured the neurobiological heterogeneity of discrete clinical outcomes after pediatric mTBI. The results illustrate the need to examine neurobiology in relation to clinical outcomes and within a neurodevelopmental framework., (© 2023 American Academy of Neurology.)

Advanced diffusion-weighted imaging techniques have increased understanding of the neuropathology of paediatric mild traumatic brain injury (i.e. concussion). Most studies have examined discrete white-matter pathways, which may not capture the characteristically subtle, diffuse and heterogenous effects of paediatric concussion on brain microstructure. This study compared the structural connectome of children with concussion to those with mild orthopaedic injury to determine whether network metrics and their trajectories across time post-injury differentiate paediatric concussion from mild traumatic injury more generally. Data were drawn from of a large study of outcomes in paediatric concussion. Children aged 8-16.99 years were recruited from five paediatric emergency departments within 48 h of sustaining a concussion ( n = 360; 56% male) or mild orthopaedic injury ( n = 196; 62% male). A reliable change score was used to classify children with concussion into two groups: concussion with or without persistent symptoms. Children completed 3 T MRI at post-acute (2-33 days) and/or chronic (3 or 6 months, via random assignment) post-injury follow-ups. Diffusion-weighted images were used to calculate the diffusion tensor, conduct deterministic whole-brain fibre tractography and compute connectivity matrices in native (diffusion) space for 90 supratentorial regions. Weighted adjacency matrices were constructed using average fractional anisotropy and used to calculate global and local (regional) graph theory metrics. Linear mixed effects modelling was performed to compare groups, correcting for multiple comparisons. Groups did not differ in global network metrics. However, the clustering coefficient, betweenness centrality and efficiency of the insula, cingulate, parietal, occipital and subcortical regions differed among groups, with differences moderated by time (days) post-injury, biological sex and age at time of injury. Post-acute differences were minimal, whereas more robust alterations emerged at 3 and especially 6 months in children with concussion with persistent symptoms, albeit differently by sex and age. In the largest neuroimaging study to date, post-acute regional network metrics distinguished concussion from mild orthopaedic injury and predicted symptom recovery 1-month post-injury. Regional network parameters alterations were more robust and widespread at chronic timepoints than post-acutely after concussion. Results suggest that increased regional and local subnetwork segregation (modularity) and inefficiency occurs across time after concussion, emerging after post-concussive symptom resolve in most children. These differences persist up to 6 months after concussion, especially in children who showed persistent symptoms. While prognostic, the small to modest effect size of group differences and the moderating effects of sex likely would preclude effective clinical application in individual patients., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Mild traumatic brain injury (mTBI) sustained in early childhood affects the brain at a peak developmental period and may disrupt sensitive stages of skill acquisition, thereby compromising child functioning. However, due to the challenges of collecting non-sedated neuroimaging data in young children, the consequences of mTBI on young children's brains have not been systematically studied. In typically developing preschool children (of age 3-5years), a brief behavioral-play familiarization provides an effective alternative to sedation for acquiring awake magnetic resonance imaging (MRI) in a time- and resource-efficient manner. To date, no study has applied such an approach for acquiring non-sedated MRI in preschool children with mTBI who may present with additional MRI acquisition challenges such as agitation or anxiety., Objective: The present study aimed to compare the effectiveness of a brief behavioral-play familiarization for acquiring non-sedated MRI for research purposes between young children with and without mTBI, and to identify factors associated with successful MRI acquisition., Materials and Methods: Preschool children with mTBI (n=13) and typically developing children (n=24) underwent a 15-minutes behavioral-play MRI familiarization followed by a 35-minutes non-sedated MRI protocol. Success rate was compared between groups, MRI quality was assessed quantitatively, and factors predicting success were documented., Results: Among the 37 participants, 15 typically developing children (63%) and 10 mTBI (77%) reached the MRI acquisition success criteria (i.e., completing the two first sequences). The success rate was not significantly different between groups (p=.48; 95% CI [-0.36 14.08]; Cramer's V=.15). The images acquired were of high-quality in 100% (for both groups) of the structural images, and 60% (for both groups) of the diffusion images. Factors associated with success included older child age (Β=0.73, p=.007, exp(B)=3.11, 95% CI [1.36 7.08]) and fewer parental concerns (Β=-1.56, p=.02, exp(Β)=0.21, 95% CI [0.05 0.82]) about the MRI procedure., Conclusion: Using brief behavioral-play familiarization allows acquisition of high-quality non-sedated MRI in young children with mTBI with success rates comparable to those of non-injured peers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Infants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA)., Methods: Preterm infants ( N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO 2 ). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO 2 i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA., Results: Steeper increases in CBF i ( p < 0.0001) and CMRO 2 i ( p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO 2 i from birth to TEA were not associated with neurological examination at TEA., Conclusion: In this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO 2 i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Côté-Corriveau, Simard, Beaulieu, Chowdhury, Gagnon, Gagnon, Ledjiar, Bernard, Nuyt, Dehaes and Luu.)

In the largest sample studied to date, white matter microstructural trajectories and their relation to persistent symptoms were examined after pediatric mild traumatic brain injury (mTBI). This prospective, longitudinal cohort study recruited children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) from five pediatric emergency departments. Children's pre-injury and 1-month post-injury symptom ratings were used to classify mTBI with or without persistent symptoms. Children completed diffusion-weighted imaging at post-acute (2-33 days post-injury) and chronic (3 or 6 months via random assignment) post-injury assessments. Mean diffusivity (MD) and fractional anisotropy (FA) were derived for 18 white matter tracts in 560 children (362 mTBI/198 OI), 407 with longitudinal data. Superior longitudinal fasciculus FA was higher in mTBI without persistent symptoms relative to OI, d (95% confidence interval) = 0.31 to 0.37 (0.02, 0.68), across time. In younger children, MD of the anterior thalamic radiations was higher in mTBI with persistent symptoms relative to both mTBI without persistent symptoms, 1.43 (0.59, 2.27), and OI, 1.94 (1.07, 2.81). MD of the arcuate fasciculus, -0.58 (-1.04, -0.11), and superior longitudinal fasciculus, -0.49 (-0.90, -0.09) was lower in mTBI without persistent symptoms relative to OI at 6 months post-injury. White matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6 months post injury in children with mTBI, especially in younger children with persistent symptoms, relative to OI. White matter microstructure appears more organized in children without persistent symptoms, consistent with their better clinical outcomes., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Therapeutic hypothermia (TH) without sedation may lead to discomfort, which may be associated with adverse consequences in neonates with hypoxic-ischemic encephalopathy (HIE). The aim of this study was to assess the association between level of exposure to opioids and temperature, with electroencephalography (EEG) background activity post-TH and magnetic resonance imaging (MRI) brain injury in neonates with HIE., Methods: Thirty-one neonates with mild-to-moderate HIE who underwent TH were identified. MRIs were reviewed for presence of brain injury. Quantitative EEG background features including EEG discontinuity index and spectral power densities were calculated during rewarming and post-rewarming periods. Dose of opioids administered during TH and temperatures were collected from the medical charts. Multivariable linear and logistic regression analyses were conducted to assess the associations between cumulative dose of opioids and temperature with EEG background and MRI while adjusting for markers of HIE severity., Results: Higher opioid doses (β = -0.21, p = 0.02) and reduced skin temperature (β = 0.14, p < 0.01) were associated with lower EEG discontinuity index recorded post-TH. Higher opioid doses (β = 0.75, p = 0.01) and reduced skin temperature (β = -0.39, p = 0.02) were also associated with higher EEG Delta power post-TH. MRI brain injury was observed in 14 patients (45%). In adjusted regression analyses, higher opioid doses (OR = 0.00; 95%CI: 0-0.19; p = 0.01), reduced skin temperature (OR = 41.19; 95%CI: 2.27-747.86; p = 0.01) and reduced cooling device output temperature (OR = 1.91; 95%CI: 1.05-3.48; p = 0.04) showed an association with lower odds of brain injury., Conclusions: Higher level of exposure to opioids and reduced skin temperature during TH in mild-to-moderate HIE were associated with improved EEG background activity post-TH. Moreover, higher exposure to opioids, reduced skin temperature and reduced device output temperature were associated with lower odds of brain injury on MRI., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Purpose: The purpose of this study was to develop an in vivo optical coherence tomography (OCT) system capable of imaging the developing mouse retina and its associated morphometric and microstructural changes., Methods: Thirty-four wild-type mice (129S1/SvlmJ) were anesthetized and imaged between postnatal (P) day 7 and P21. OCT instrumentation was developed to optimize signal intensity and image quality. Semi-automatic segmentation tools were developed to quantify the retinal thickness of the nerve fiber layer (NFL), inner plexiform layer (IPL), inner nuclear layer (INL), and the outer retinal layers (ORL), in addition to the total retina. The retinal maturation was characterized by comparing layer thicknesses between consecutive time points., Results: From P7 to P10, the IPL increased significantly, consistent with retinal synaptogenesis. From P10 to P12, the IPL and ORL also increased, which is coherent with synaptic connectivity and photoreceptor maturation. In contrast, during these periods, the INL decreased significantly, consistent with cellular densification and selective apoptotic "pruning" of the tissue during nuclear migration. Thereafter from P12 to P21, the INL continued to thin (significantly from P17 to P21) whereas the other layers remained unchanged. No time-dependent changes were observed in the NFL. Overall, changes in the total retina were attributed to those in the IPL, INL, and ORL. Regions of the retina adjacent to the optic nerve head were thinner than distal regions during maturation., Conclusions: Changes in retinal layer thickness are consistent with retinal developmental mechanisms. Accordingly, this report opens new horizons in using our system in the mouse to characterize longitudinally developmental digressions in models of human diseases.

Optical coherence tomography (OCT) was recently performed using a few-mode (FM) fiber to increase contrast or improve resolution using a sequential time-domain demultiplexing scheme isolating the different interferometric signals of the mode-coupled backscattered light. Here, we present an all-fiber FM-OCT system based on a parallel modal demultiplexing scheme exploiting a novel modally-specific photonic lantern (MSPL). The MSPL allows for maximal fringe visibility for each fiber propagation mode in an all-fiber assembly which provides the robustness required for clinical applications. The custom-built MSPL was designed for OCT at 930 nm and is wavelength-independent over the broad OCT spectrum. We further present a comprehensive coupling model for the interpretation of FM-OCT images using the first two propagation modes of a few-mode fiber, validate its predictions, and demonstrate the technique using in vitro microbead phantoms and ex vivo biological samples., Competing Interests: CB, NG: Castor Optics, inc. (I,P), MPdSH, SBB (P), (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Purpose : This retrospective study aims to describe the gross motor development of children aged 4 to 24 months with congenital heart disease (CHD) enrolled in a systematic developmental follow-up program and to describe the frequency of physical therapy sessions they received between 4 and 8 months of age. Methods : Twenty-nine infants with CHD underwent motor evaluations using the AIMS at 4 months, and the Bayley-III at 12 and 24 months. Results : Based on AIMS, 79% of 4-month-old infants had a gross motor delay and required physical therapy. Among these, 56.5% received one to two physical therapy sessions, and 43.5% received three to six sessions. Infants who benefited from regular interventions tended to show a better improvement in motor scores from 12 to 24 months. Conclusion : This study highlights the importance of early motor screening in infants with CHD and suggests a potential benefit of early physical therapy in at-risk children. Abbreviations: CHD: Congenital heart disease; AIMS: Alberta Infant Motor Scales; Bayley-III: Bayley Scales of Infant and Toddler Development, Third edition; Bayley-III/GM: Gross Motor section of the Bayley Scales of Infant and Toddler Development, Third edition.

Introduction: Mild traumatic brain injury (mTBI) is highly prevalent, especially in children under 6 years. However, little research focuses on the consequences of mTBI early in development. The objective of the Kids' Outcomes And Long-term Abilities (KOALA) study is to document the impact of early mTBI on children's motor, cognitive, social and behavioural functioning, as well as on quality of life, stress, sleep and brain integrity., Methods and Analyses: KOALA is a prospective, multicentre, longitudinal cohort study of children aged 6 months to 6 years at the time of injury/recruitment. Children who sustain mTBI (n=150) or an orthopaedic injury (n=75) will be recruited from three paediatric emergency departments (PEDs), and compared with typically developing children (community controls, n=75). A comprehensive battery of prognostic and outcome measures will be collected in the PED, at 10 days, 1, 3 and 12 months postinjury. Biological measures, including measures of brain structure and function (magnetic resonance imaging, MRI), stress (hair cortisol), sleep (actigraphy) and genetics (saliva), will complement direct testing of function using developmental and neuropsychological measures and parent questionnaires. Group comparisons and predictive models will test the a priori hypotheses that, compared with children from the community or with orthopaedic injuries, children with mTBI will (1) display more postconcussive symptoms and exhibit poorer motor, cognitive, social and behavioural functioning; (2) show evidence of altered brain structure and function, poorer sleep and higher levels of stress hormones. A combination of child, injury, socioenvironmental and psychobiological factors are expected to predict behaviour and quality of life at 1, 3 and 12 months postinjury., Ethics and Dissemination: The KOALA study is approved by the Sainte-Justine University Hospital, McGill University Health Centre and University of Calgary Conjoint Health Research Ethics Boards. Parents of participants will provide written consent. Dissemination will occur through peer-reviewed journals and an integrated knowledge translation plan., Competing Interests: Competing interests: CL’s spouse is an employee of General Electric Healthcare. The other authors report no biomedical financial interests or potential conflicts of interest., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: There are no published studies examining resting state networks (RSNs) and their relationship with neurodevelopmental metrics in tuberous sclerosis complex (TSC). We aimed to identify major resting-state functional magnetic resonance imaging (rs-fMRI) networks in infants with TSC and correlate network analyses with neurodevelopmental assessments, autism diagnosis, and seizure history., Methods: Rs-fMRI data from 34 infants with TSC, sedated with propofol during the scan, were analyzed to identify auditory, motor, and visual RSNs. We examined the correlations between auditory, motor, and visual RSNs at approximately 11.5 months, neurodevelopmental outcome at approximately 18.5 months, and diagnosis of autism spectrum disorders at approximately 36 months of age., Results: RSNs were obtained in 76.5% (26/34) of infants. We observed significant negative correlations between auditory RSN and auditory comprehension test scores (p = .038; r = -.435), as well as significant positive correlations between motor RSN and gross motor skills test scores (p = .023; r = .564). Significant positive correlations between motor RSNs and gross motor skills (p = .012; r = .754) were observed in TSC infants without autism, but not in TSC infants with autism, which could suggest altered motor processing. There were no significant differences in RSNs according to seizure history., Conclusions: Negative correlation between auditory RSN, as well as positive correlation between motor RSN and developmental outcome measures might reflect different brain mechanisms and, when identified, may be helpful in predicting later function. A larger study of TSC patients with a healthy control group is needed before auditory and motor RSNs could be considered as neurodevelopmental outcome biomarkers., (© 2019 by the American Society of Neuroimaging.)

Brain imaging offers a valuable tool to observe functional brain plasticity by showing how sensory inputs reshape cortical activations after a visual impairment. Following a unilateral post-chiasmatic lesion affecting the visual cortex, patients may suffer a contralateral visual loss referred to homonymous hemianopia. Nevertheless, these patients preserve the ability to unconsciously detect, localize and discriminate visual stimuli presented in their impaired visual field. To investigate this paradox, known as blindsight, we conducted a study using functional magnetic resonance imaging (fMRI) to evaluate the structural and functional impact of such lesion in a 33-year old patient (ML), who suffers a complete right hemianopia without macular sparing and showing strong evidences of blindsight. We thus performed whole brain and sliced thalamic fMRI scan sequences during an event-related motion detection task. We provided evidence of the neuronal fingerprint of blindsight by acquiring and associating neural correlates, specific structures and functional networks of the midbrain during blindsight performances which may help to better understand this condition. Accurate performance demonstrated the presence of residual vision and the ability to unconsciously perceive motion presented in the blind hemifield, although her reaction time was significantly higher in her blind-field. When the normal hemifield was stimulated, we observed significant contralateral activations in primary and secondary visual areas as well as motion specific areas, such as the supramarginal gyrus and middle temporal area. We also demonstrated sub-thalamic activations within the superior colliculi (SC) and the pulvinar. These results suggest a role of secondary subcortical structures in normal spontaneous motion detection. In a similar way, when the lesioned hemifield was stimulated, we observed contralateral activity in extrastriate areas with no activation of the primary lesioned visual cortex. Moreover, we observed activations within the SC when the blind hemifield was stimulated. However, we observed unexpected ipsilateral activations within the same motion specific areas, as well as bilateral frontal activations. These results highlight the importance of abnormal secondary pathways bypassing the primary visual area (V1) in residual vision. This reorganization in the structure and function of the visual pathways correlates with behavioral changes, thus offering a plausible explanation for the blindsight phenomenon. Our results may potentially impact the development of rehabilitation strategies to target subcortical pathways., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Neonatal brain injury suffered by preterm infants and newborns with some medical conditions can cause significant neurodevelopmental disabilities. MRI is a preferred method to detect these accidents and perform in vivo evaluation of the brain. However, the commercial availability and optimality of receive coils for the neonatal brain is limited, which in many cases leads to images lacking in quality. As extensively demonstrated, receive arrays closely positioned around the scanned part provide images with high signal-to-noise ratios (SNRs). The present work proposes a pneumatic-based MRI receive array that can physically adapt to infant head dimensions from 27-week premature to 1.5 months old. Average SNR increases of up to 68% in the head region and 122% in the cortex region, compared with a 32-channel commercial head coil, were achieved at 3 T. The consistent SNR distribution obtained through the complete coil size range, specifically in the cortex, allows the acquisition of images with similar quality across a range of head dimensions, which is not possible with fixed-size coils due to the variable coil-to-head distance. The risks associated with mechanical pressure on the neonatal head are minimal and the head motion is restricted. The method could be used in coil designs for other age groups, body parts and subjects., (Copyright © 2018 John Wiley & Sons, Ltd.)

Extremely preterm infants are at higher risk of pulmonary (PH) and intraventricular (IVH) haemorrhage during the transitioning physiology due to immature cardiovascular system. Monitoring of haemodynamics can detect early abnormal circulation that may lead to these complications. We described time-frequency relationships between near infrared spectroscopy (NIRS) cerebral regional haemoglobin oxygen saturation (CrSO 2 ) and preductal peripheral perfusion index (PI), capillary oxygen saturation (SpO 2 ) and heart rate (HR) in extremely preterm infants in the first 72 h of life. Patients were sub-grouped in infants with PH and/or IVH (N H  = 8) and healthy controls (N C  = 11). Data were decomposed in wavelets allowing the analysis of localized variations of power. This approach allowed to quantify the percentage of time of significant cross-correlation, semblance, gain (transfer function) and coherence between signals. Ultra-low frequencies (<0.28 mHz) were analyzed as slow and prolonged periods of impaired circulation are considered more detrimental than transient fluctuations. Cross-correlation between CrSO 2 and oximetry (PI, SpO 2 and HR) as well as in-phase semblance and gain between CrSO 2 and HR were significantly lower while anti-phase semblance between CrSO 2 and HR was significantly higher in PH-IVH infants compared to controls. These differences may reflect haemodynamic instability associated with cerebrovascular autoregulation and hemorrhagic complications observed during the transitioning physiology.

Haemodynamic assessment during the transitional period in preterm infants is challenging. We aimed to describe the relationships between cerebral regional tissue oxygen saturation (CrSO 2 ), perfusion index (PI), echocardiographic, and clinical parameters in extremely preterm infants in their first 72 h of life. Twenty newborns born at < 28 weeks of gestation were continuously monitored with CrSO 2 and preductal PI. Cardiac output was measured at H6, H24, H48, and H72. The median gestational age and birth weight were 25.0 weeks (24-26) and 750 g (655-920), respectively. CrSO 2 and preductal PI had r values < 0.35 with blood gases, lactates, haemoglobin, and mean blood pressure. Cardiac output significantly increased over the 72 h of the study period. Fifteen patients had at least one episode of low left and/or right ventricular output (RVO), during which there was a strong correlation between CrSO 2 and superior vena cava (SVC) flow (at H6 (r = 0.74) and H24 (r = 0.86)) and between PI and RVO (at H6 (r = 0.68) and H24 (r = 0.92)). Five patients had low SVC flow (≤ 40 mL/kg/min) at H6, during which PI was strongly correlated with RVO (r = 0.98)., Conclusion: CrSO 2 and preductal PI are strongly correlated with cardiac output during low cardiac output states. What is Known: • Perfusion index and near-infrared spectroscopy are non-invasive tools to evaluate haemodynamics in preterm infants. • Pre- and postductal perfusion indexes strongly correlate with left ventricular output in term infants, and near-infrared spectroscopy has been validated to assess cerebral oxygenation in term and preterm infants. What is New: • Cerebral regional tissue oxygen saturation and preductal perfusion index were strongly correlated with cardiac output during low cardiac output states. • The strength of the correlation between cerebral regional tissue oxygen saturation, preductal perfusion index, and cardiac output varied in the first 72 h of life, reflecting the complexity of the transitional physiology.

The purpose of this work was to develop an optimized transmit/receive birdcage coil to extend the possibilities of a 7T preclinical MRI system to conduct improved full body imaging in medium-sized animals, such as large New Zealand rabbits. The coil was designed by combining calculation and electromagnetic simulation tools. The construction was based on precise mechanical design and careful building practice. A 16-leg, 20 cm long, 16 cm inner diameter, shielded quadrature hybrid structure was selected. Coil parameters were assessed on the bench and images were acquired on phantoms and rabbits. The results were compared to simulations and data obtained with an available commercial coil. An inexpensive assembly with an increase of 2 cm in useful inner diameter and 50 Ω matching with larger animals was achieved. A reduction in radiofrequency (RF) power demand of 31.8%, an improvement in image uniformity of 18.5 percentage points and an increase in signal-to-noise ratio of up to 42.2% were revealed by phantom image acquisitions, which was confirmed by in vivo studies. In conclusion, the proposed coil extended the possibilities of a preclinical 7T system as it improved image studies in relatively large animals by reducing the RF power demand, and increasing image uniformity and signal-to-noise ratio. Shorter scans and time under anesthesia or reduced RF exposure, resulting in better images and lower animal health risk during in vivo experiments, were achieved.

Children with congenital heart disease (CHD) are at increased risk of neurodevelopmental disorders (NDDs) and psychiatric conditions. These include cognitive, adaptive, motor, speech, behavioural, and executive functioning deficits, as well as autism spectrum disorder and psychiatric conditions. Structural and functional neuroimaging have demonstrated brain abnormalities in young children with CHD before undergoing surgical repair, likely as a result of an in utero developmental insult. Surgical factors do not seem to play a significant role in neurodevelopmental outcomes. Specific genetic abnormalities, particularly copy number variants, have been increasingly implicated in both CHD and NDDs. Variations in genes involved in apolipoprotein E (APOE) production, the Wnt signalling pathway, and histone modification, as well as in the 1q21.1, 16p13.1-11, and 8p23.1 genetic loci, have been associated with CHD and NDDs and are important targets for future research. Understanding these associations is important for risk stratification, disease classification, improved screening, and pharmacologic management of individuals with CHD., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Paediatric mild traumatic brain injury (mTBI) is a public health burden. Clinicians urgently need evidence-based guidance to manage mTBI, but gold standards for diagnosing and predicting the outcomes of mTBI are lacking. The objective of the Advancing Concussion Assessment in Pediatrics (A-CAP) study is to assess a broad pool of neurobiological and psychosocial markers to examine associations with postinjury outcomes in a large sample of children with either mTBI or orthopaedic injury (OI), with the goal of improving the diagnosis and prognostication of outcomes of paediatric mTBI., Methods and Analysis: A-CAP is a prospective, longitudinal cohort study of children aged 8.00-16.99 years with either mTBI or OI, recruited during acute emergency department (ED) visits at five sites from the Pediatric Emergency Research Canada network. Injury information is collected in the ED; follow-up assessments at 10 days and 3 and 6 months postinjury measure a variety of neurobiological and psychosocial markers, covariates/confounders and outcomes. Weekly postconcussive symptom ratings are obtained electronically. Recruitment began in September 2016 and will occur for approximately 24 months. Analyses will test the major hypotheses that neurobiological and psychosocial markers can: (1) differentiate mTBI from OI and (2) predict outcomes of mTBI. Models initially will focus within domains (eg, genes, imaging biomarkers, psychosocial markers), followed by multivariable modelling across domains. The planned sample size (700 mTBI, 300 OI) provides adequate statistical power and allows for internal cross-validation of some analyses., Ethics and Dissemination: The ethics boards at all participating institutions have approved the study and all participants and their parents will provide informed consent or assent. Dissemination will follow an integrated knowledge translation plan, with study findings presented at scientific conferences and in multiple manuscripts in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Seizures are common in critically ill neonates. Both seizures and antiepileptic treatments may lead to short term complications and worsen the outcomes. Predicting the risks of seizure reoccurrence could enable individual treatment regimens and better outcomes. We aimed to identify EEG signatures of seizure reoccurrence by investigating periictal electrographic features and spectral power characteristics in hypothermic neonates with hypoxic-ischemic encephalopathy (HIE) with or without reoccurrence of seizures on rewarming., Methods: We recruited five consecutive HIE neonates, submitted to continuous EEG monitoring, with high seizure burden (>20% per hour) while undergoing therapeutic hypothermia. Two of them had reoccurrence of seizures on rewarming. We performed quantitative analysis of fifteen artifact-free consecutive seizures to appreciate spectral power changes between the interictal, preictal and ictal periods, separately for each patient. Visual analysis allowed description of electrographic features associated with ictal events., Results: Every patient demonstrated a significant increase in overall spectral power from the interictal to preictal and ictal periods (p<0.01). Alpha power increase was more pronounced in the two patients with reoccurrence of seizures on rewarming and significant when comparing both interictal-to-preictal and interictal-to-ictal periods. This alpha activity increase could be also appreciated using visual analysis and distinguished neonates with and without seizure reoccurrence., Conclusion: This distinct alpha activity preceding ictal onset could represent a biomarker of propensity for seizure reoccurrence in neonates. Future studies should be performed to confirm whether quantitative periictal characteristics and electrographic features allow predicting the risks of seizure reoccurrence in HIE neonates and other critically ill patients., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation ( SO 2 ) in young adults at rest and during incremental intensity exercise. In extra-cerebral tissue, an increase in deoxy-hemoglobin ( HbR ) and a decrease in SO 2 were observed while only cerebral HbR increased at high intensity exercise. Results in extra-cerebral tissue are consistent with thermoregulatory mechanisms to dissipate excess heat through skin blood flow, while cerebral changes are in agreement with cerebral blood flow ( CBF ) redistribution mechanisms to meet oxygen demand in activated regions during exercise. No significant difference was observed in oxy- ( HbO 2 ) and total hemoglobin ( HbT ). In addition HbO 2 , HbR and HbT increased with subject's peak power output (equivalent to the maximum oxygen volume consumption; VO 2 peak) supporting previous observations of increased total mass of red blood cells in trained individuals. Our results also revealed known gender differences with higher hemoglobin in men. Our approach in quantifying both extra-cerebral and cerebral absolute hemoglobin during exercise may help to better interpret past and future continuous-wave NIRS studies that are prone to extra-cerebral contamination and allow a better understanding of acute cerebral changes due to physical exercise.

Background and Purpose: Perfusion-weighted imaging in adults with acute stroke often reveals hypoperfusion in the ischemic core and in a surrounding area of nondiffusion-restricted penumbral tissue. Perinatal stroke is common, but the perfusion pattern is rarely documented. We aimed to describe the perfusion pattern in newborns with perinatal stroke., Methods: Neonates with clinical features of acute stroke underwent magnetic resonance imaging. Perfusion data were obtained using pseudocontinuous arterial spin labeling. Strokes were classified as arterial, venous, or both. Core infarction was determined by the presence of restricted diffusion on diffusion-weighted imaging. Perfusion-weighted imaging and susceptibility-weighted imaging signal in the ischemic area were visually compared with the homologous region in the contralesional hemisphere. Electroencephalogram data were evaluated for seizure activity., Results: In 25 neonates with acute stroke, 8 of 11 (73%) with arterial ischemic stroke demonstrated hyperperfusion, 1 of 9 (11%) with venous stroke, and 4 of 5 (80%) with both. Hypoperfusion was observed in 3 of 9 (33%) with venous and none with arterial ischemic stroke. Perfusion was normal in 4 of 9 (45%) with venous and 1 of 5 (20%) with both. Twenty-one of 24 patients (88%) with electroencephalogram data had either electrographic seizures or focal sharp waves in the ipsilesional hemisphere (11/11 arterial ischemic stroke, 6/9 venous, and 4/5 both)., Conclusions: Perfusion-weighted imaging can be obtained in neonates with acute stroke and often reveals hyperperfusion in the infarct core. Penumbra in arterial ischemic stroke is seldom found. Hyperperfusion may be caused by poststroke reperfusion or to neuronal hyperexcitability of stroke-associated seizure. Its identification may be useful for consideration of therapy for acute neonatal stroke., (© 2016 American Heart Association, Inc.)

Objective: To investigate how rewarming impacts the evolution of EEG background in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH)., Methods: We recruited a retrospective cohort of 15 consecutive newborns with moderate (9) and severe (6) HIE monitored with a continuous EEG during TH and at least 12h after its end. EEG background was analyzed using conventional visual and quantitative EEG analysis methods including EEG discontinuity, absolute and relative spectral magnitudes. One patient with seizures on rewarming was excluded from analyses., Results: Visual and quantitative analyses demonstrated significant changes in EEG background from pre- to post-rewarming, characterized by an increased EEG discontinuity, more pronounced in newborns with severe compared to moderate HIE. Neonates with moderate HIE also had an increase in the relative magnitude of slower delta and a decrease in higher frequency theta and alpha waves with rewarming., Conclusions: Rewarming affects EEG background in HIE newborns undergoing TH, which may represent a transient adaptive response or reflect an evolving brain injury., Significance: EEG background impairment induced by rewarming may represent a biomarker of evolving encephalopathy in HIE newborns undergoing TH and underscores the importance of continuously monitoring the brain health in critically ill neonates., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Congenital heart disease (CHD) patients are at risk for neurodevelopmental delay. The etiology of these delays is unclear, but abnormal prenatal cerebral maturation and postoperative hemodynamic instability likely play a role. A better understanding of these factors is needed to improve neurodevelopmental outcome. In this study, we used bedside frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to assess cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle (SV) CHD undergoing surgery and compared them to controls. Our goals were 1) to compare cerebral hemodynamics between unanesthetized SV and healthy neonates, and 2) to determine if FDNIRS-DCS could detect alterations in cerebral hemodynamics beyond cerebral hemoglobin oxygen saturation (SO 2). Eleven SV neonates were recruited and compared to 13 controls. Preoperatively, SV patients showed decreased cerebral blood flow (CBFi ), cerebral oxygen metabolism (CMRO 2i ) and SO 2; and increased oxygen extraction fraction (OEF) compared to controls. Compared to preoperative values, unstable postoperative SV patients had decreased CMRO 2i and CBFi , which returned to baseline when stable. However, SO 2 showed no difference between unstable and stable states. Preoperative SV neonates are flow-limited and show signs of impaired cerebral development compared to controls. FDNIRS-DCS shows potential to improve assessment of cerebral development and postoperative hemodynamics compared to SO 2 alone.

Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS-DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS-DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization.

Near infrared spectroscopy (NIRS) is a functional imaging technique allowing measurement of local cerebral oxygenation. This modality is particularly adapted to critically ill neonates, as it can be used at the bedside and is a suitable and noninvasive tool for carrying out longitudinal studies. However, NIRS is sensitive to the imaged medium and consequently to the optical properties of biological tissues in which photons propagate. In this study, the effect of the neonatal fontanel was investigated by predicting photon propagation using a probabilistic Monte Carlo approach. Two anatomical newborn head models were created from computed tomography and magnetic resonance images: (1) a realistic model including the fontanel tissue and (2) a model in which the fontanel was replaced by skull tissue. Quantitative change in absorption due to simulated activation was compared for the two models for specific regions of activation and optical arrays simulated in the temporal area. A correction factor was computed to quantify the effect of the fontanel and defined by the ratio between the true and recovered change. The results show that recovered changes in absorption were more precise when determined with the anatomical model including the fontanel. The results suggest that the fontanel should be taken into account in quantification of NIRS responses to avoid misinterpretation in experiments involving temporal areas, such as language or auditory studies., (Copyright © 2011 Wiley Periodicals, Inc.)

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO₂). Thus, measures of CMRO₂ are reflective of neuronal viability and provide critical diagnostic information, making CMRO₂ an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO₂) as a surrogate for cerebral oxygen consumption. However, SO₂ is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO₂ are not sensitive enough to detect brain injury hours after the insult, because oxygen consumption and delivery reach equilibrium after acute transients. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO₂ (CMRO₂i). With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

Understanding the evolution of regional and hemispheric asymmetries in the early stages of life is essential to the advancement of developmental neuroscience. By using 2 noninvasive optical methods, frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy, we measured cerebral hemoglobin oxygenation (SO(2)), blood volume (CBV), an index of cerebral blood flow (CBF(i)), and the metabolic rate of oxygen (CMRO(2i)) in the frontal, temporal, and parietal regions of 70 premature and term newborns. In concordance with results obtained using more invasive imaging modalities, we verified both hemodynamic (CBV, CBF(i), and SO(2)) and metabolic (CMRO(2i)) parameters were greater in the temporal and parietal regions than in the frontal region and that these differences increased with age. In addition, we found that most parameters were significantly greater in the right hemisphere than in the left. Finally, in comparing age-matched males and females, we found that males had higher CBF(i) in most cortical regions, higher CMRO(2i) in the frontal region, and more prominent right-left CBF(i) asymmetry. These results reveal, for the first time, that we can detect regional and hemispheric asymmetries in newborns using noninvasive optical techniques. Such a bedside screening tool may facilitate early detection of abnormalities and delays in maturation of specific cortical areas.

In patients presenting with cerebral ischemic injury, the outcome of injured brain tissue quantified as decreased apparent diffusion coefficient (ADC) may depend on associated alterations in cerebral blood perfusion (CBP). This study proposes a non-biased method to quantify associations between ADC and CBP in newborns with global or focal cerebral ischemia. The study population consisted of nine neonates (age: 0 to 3 days) presenting with clinical and imaging evidence of ischemia (seven with global hypoxic ischemia, and two with focal arterial ischemic stroke) with decreased ADC. Six newborns without diffusion abnormalities on magnetic resonance (MR) imaging served as a comparative cohort (age: 0 days to 4 weeks). All patients underwent MR imaging including diffusion weighted imaging (DWI) to determine ADC and axial arterial spin labeling (ASL) to determine CBP. An algorithm was developed that uses the B0 volume from the DWI raw data as a reference, co-registers the ADC and ASL-CBP data to the B0, generates mask filters, and finally performs a statistical analysis to automatically select regions of interest (ROIs) with ADC or ASL-CBP values that deviate significantly from the rest of the brain. If ROIs are identified in this analysis, the algorithm then evaluates correlation based on ROI location and volume. A significant correlation was found between decreased ADC and elevated ASL-CBP with regions of elevated ASL-CBP typically larger than the corresponding ADC abnormality. The association between decreased diffusivity and increased ASL-CBP suggests that, for this cohort, cerebral ischemia is associated with hyperperfusion., (Copyright © 2012 Elsevier Inc. All rights reserved.)