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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.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.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.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.

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.

International audience; 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 (TDC, 3-5 years), brief a 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 TDC (n=24) underwent a 15-minute behavioral-play MRI familiarization followed by a 35-minute 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 TDC (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 (B=0.73, p=.007, exp(B)=3.11, 95% CI [1.36 7.08]) and fewer parental concerns (B=-1.56, p=.02, exp(B)=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.

OBJECTIVES Little is known about cardiac hemodynamics in the fetus with transposition of the great arteries and intact ventricular septum (TGA-IVS). Better understanding of the fetal physiology in TGA-IVS would help to provide insights into specific clinical complications observed after birth, in particular neonatal hypoxia and pulmonary hypertension. The aim of this study was to assess cardiac hemodynamics in fetuses with TGA-IVS by performing systematic longitudinal echocardiographic follow-up from diagnosis to delivery. METHODS This was a longitudinal retrospective study of fetuses referred between 2010 and 2018 to the Sainte-Justine University Hospital Centre. Complete assessment of cardiac hemodynamics was performed in fetuses with TGA-IVS at 18-22, 28-32 and 35-38 weeks' gestation, which were compared with normal fetuses matched for gestational age. The maximum diameter of the foramen ovale was measured using two-dimensional echocardiography under the guidance of color Doppler echocardiography. Fetal cardiac hemodynamics were analyzed according to postnatal preductal transcutaneous oxygen saturation (TcSO2 )

BACKGROUND Plexiform neurofibromas (PN) are observed in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PN but limited data has been reported on its efficacy within a clinical trial. METHODS This ongoing multicenter phase II trial includes patients with pediatric low-grade glioma and PN. Patients received daily oral trametinib (MEK inhibitor) for eighteen 28-day cycles. The volumes of PN were centrally quantified using a new semi-automatic 3D segmentation method. RESULTS As of May 15, 2022, 46 patients with PN were enrolled in the study and the recruitment was completed for this study arm. Thirty-four completed treatment and were available for analysis. For these patients, the median age was 10.5 years (range 0.7-19.8). The median volume of PN at baseline was 51cm3 (range 2.6 to 487.6). Among the 34 patients, 28 (82.4%) completed 18 cycles as planned. Two patients discontinued due to adverse reaction, three patients refused to continue treatment and one patient discontinued treatment based on physician decision. Median duration of treatment was 16.8 months (range 2.8 to 16.8). Median duration of follow-up was 30.4 months (range 8.2 to 42). A total of 38 PN were available for volumetric analysis. Using RECIST evaluation, the overall response rate was 13.1%. Volumetric assessment demonstrated an overall response rate of 64.7% (22/34 patients), and 65.8% (25/38 PN) of PN showed a decrease of more than 20% in volume. Median volume change was -30% (range -93.5 to 14.3). Thirty-one patients (91.1%) had durable response without progression (lasting ≥ 1 year). After discontinuation of treatment, one patient underwent surgery and three patients resumed MEK inhibitor. CONCLUSION We report outcome and volumetric quantification of PN treated with trametinib within a large clinical trial. Based on the current results, trametinib is effective and offers durable response.

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.

We present here an open-source platform capable of simulating Optical Coherence Tomography (OCT) images to be used by the community. Such a simulator can have a variety of applications such as the training of neural networks. Our first-generation Monte Carlo simulator quantifies detected photons path length. The code achieves reasonable runtime by exploiting a bias scattering scheme. The results are then interpreted to produce an OCT A-line. A Github platform was implemented with necessary documentation (e.g. readme file and instructions guide) to allow a variety of application and geometry as well as community-based improvements over time.

BACKGROUND: Plexiform neurofibromas (PN) are found in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PN but limited data has been reported on its efficacy within a clinical trial. METHODS: This ongoing multicenter phase II trial includes patients with pediatric low-grade glioma and PN. The primary objective for PN was to evaluate the overall response rate based on RECIST 1.1 criteria after daily oral trametinib administration for eighteen 28-day cycles. The volumes of PN were centrally quantified using a new semi-automatic 3D segmentation method. RESULTS: As of January 1, 2022, 45 patients with PN were enrolled in the study. Twenty-eight completed treatment and were available for analysis. For these patients, the median age was 11.4 years (range 0.7-19.8) including 16 males (57.1%). The majority did not receive prior systemic therapies (71.4%). The median volume of PN at baseline was 49.5 cm3 (range 2.6 to 469). Among the 28 patients, 25 (89.3%) completed 18 cycles as planned. One patient discontinued due to adverse reaction, one patient refused to continue treatment and one patient discontinued treatment based on physician decision. Median duration of treatment was 15.9 months (range 4.6 to 16.8). Median duration of follow-up was 29.7 months (range 17.7 to 38.1). A total of 32 PN were available for volumetric analysis. Using RECIST evaluation, the overall response rate was 24.1%. Volumetric assessment demonstrated an overall response rate of 60.7% and 62.5% of PN showed a decrease of more than 20% in volume. Median decrease in volume was -30% (range -93.5 to 14.3). Twenty-seven patients (93.1%) had durable response without progression (lasting ≥1 year). CONCLUSION: We report outcome and volumetric quantification of PN treated with trametinib within a large clinical trial. Based on the current results, trametinib appears effective and offers durable response.

IntroductionMild 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 analysesKOALA 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 disseminationThe 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.

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.

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 (CrSO2) and preductal peripheral perfusion index (PI), capillary oxygen saturation (SpO2) 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 (CrSO2 and oximetry (PI, SpO2 and HR) as well as in-phase semblance and gain between CrSO2 and HR were significantly lower while anti-phase semblance between CrSO2 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.

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.

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.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.Every patient demonstrated a significant increase in overall spectral power from the interictal to preictal and ictal periods (p0.01). 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.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.

This work describes the development of optical instrumentation and data processing methods to image the retina in the mouse pup with optical coherence tomography. These developments will be used to better understand in vivo vascular retinal changes due to retinopathy of prematurity.

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.

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.

BACKGROUND Assessment of hemodynamics during the transitional period in preterm infants is challenging. OBJECTIVES We aimed to describe the relationship between cerebral regional tissue oxygenation saturation (CrSO2), preductal perfusion index (PI), echocardiographic and clinical parameters in extremely preterm infants in their first 72 hours of life. DESIGN/METHODS This single center prospective observational study was conducted in the level 3 neonatal intensive care unit of Sainte-Justine Hospital between July 2015 and May 2016. Twenty newborns born at RESULTS Median gestational age and birth weight were 25.0 weeks (24–26) and 750 g (655–920) respectively. Table 1 describes the measures over the 72 hours of the study period. CrSO2 and preductal PI were weakly correlated with mean blood pressure, PaCO2, lactates and haemoglobin. Fifteen patients had at least one episode of low left and/or right ventricular output (RVO) measured and showed strong correlation between CrSO2 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 flowat H6 and showed strong correlation between PI and RVO (r=0.98). CONCLUSION CrSO2 and preductal PI were weakly correlated with clinical parameters in the preterm infants. However, CrSO2 and PI showed stronger correlation with RVO and SVC flow during low cardiac output states.

Haemodynamic assessment during the transitional period in preterm infants is challenging. We aimed to describe the relationships between cerebral regional tissue oxygen saturation (CrSO2), perfusion index (PI), echocardiographic, and clinical parameters in extremely preterm infants in their first 72 h of life. Twenty newborns born at

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.

BACKGROUND Extremely premature infants born OBJECTIVES To explore time-frequency relationships between cerebral oxygenation and peripheral oximetry. DESIGN/METHODS Near infrared spectroscopy cerebral regional haemoglobin oxygen saturation (CrSO2), preductal peripheral perfusion index (PI), heart rate (HR), capillary oxygen saturation (SpO2), and blood pressure (BP) were monitored in the first 72h of life. Patients were grouped in infants with PH and/or IVH (n=8) and controls (n=10). Signals were decomposed in wavelets allowing the analysis of localized variations of power. This approach allowed to quantify the common power and determine the duration of significant cross-correlation, phase and coherence between each pair of signals. Groups were compared with Wilcoxon tests. RESULTS Figure 1 shows an example of CrSO2 and PI, and their cross-correlation, phase (semblance) and coherence in a control (left column) and a PH-IVH patient (right column). Durations of significant cross-correlation between CrSO2 and HR (p CONCLUSION This study is the first to apply time-frequency analysis to simultaneous NIRS and preductal peripheral oximetry in extremely preterm infants early in life. Significantly lower durations of cross-correlation (CrSO2 with HR and SpO2), anti-phase (CrSO2, SpO2) and coherence (PI, BP) in PH-IVH patients may reflect early abnormal circulation. Our results show the potential of non-invasive monitoring to identify premature infants at-risk of early PH-IVH.

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 SO2remained unchanged after the therapy. Thus, FDNIRS–DCS can provide information complimentary to SO2and 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.

Time-domain near infrared spectroscopy was used to quantify hemodynamic signals during physical exercise and rest. Changes in extra-cerebral hemodynamics relative to rest are significant and their quantification may prevent data interpretation bias.

Near-Infrared Spectroscopy (NIRS) measures the functional hemodynamic response occurring at the surface of the cortex. Large pial veins are located above the surface of the cerebral cortex. Following activation, these veins exhibit oxygenation changes but their volume likely stays constant. The back-reflection geometry of the NIRS measurement renders the signal very sensitive to these superficial pial veins. As such, the measured NIRS signal contains contributions from both the cortical region as well as the pial vasculature. In this work, the cortical contribution to the NIRS signal was investigated using (1) Monte Carlo simulations over a realistic geometry constructed from anatomical and vascular MRI and (2) multimodal NIRS-BOLD recordings during motor stimulation. A good agreement was found between the simulations and the modeling analysis of in vivo measurements. Our results suggest that the cortical contribution to the deoxyhemoglobin signal change ( Δ HbR) is equal to 16–22% of the cortical contribution to the total hemoglobin signal change ( Δ HbT). Similarly, the cortical contribution of the oxyhemoglobin signal change ( Δ HbO) is equal to 73–79% of the cortical contribution to the Δ HbT signal. These results suggest that Δ HbT is far less sensitive to pial vein contamination and therefore, it is likely that the Δ HbT signal provides better spatial specificity and should be used instead of Δ HbO or Δ HbR to map cerebral activity with NIRS. While different stimuli will result in different pial vein contributions, our finger tapping results do reveal the importance of considering the pial contribution.

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. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.

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.

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.

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.

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 12 h 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.

Introduction: Perfusion magnetic resonance imaging (pMRI) in adults reveals a hypoperfused region, the ischemic penumbra, related to the fixed ischemic injury shown by diffusion weighted imaging (DWI) in acute stroke. Neonatal stroke has pathophysiology and optimum treatment that remain elusive. We hypothesized that altered regional perfusion accompanies the ischemic injury in focal neonatal stroke. Methods: Neonates (0-28 days of life) underwent MR imaging at 3T fieldstrength. pMRI employed a pseudocontinuous arterial spin labeling (PCASL) sequence with multi-slice echo planar readouts at 3x3x5mm3 resolution with TE/TR = 12ms/3.5s, labeling time = 1.6s, a post-labeling delay = 1.5s, 9 axial slices acquired, scan time ~5 min. Forty label/control image pairs were acquired, subtracted and averaged to obtain contrast maps proportional to quantified cerebral blood flow (CBF). DWI, susceptibility weighted imaging and T2-weighted series were obtained with standard protocols. Acute stroke was classified as arterial or venous. Core infarction was considered to lie in hypointense regions on DWI apparent diffusion coefficient maps. Regional perfusion signal was compared to the ischemic core on DWI and to the homologous uninvolved region in the contralesional hemisphere. Results: Data were collected on 20 neonates, (13 males; median/mean gestational age=38/38.5 weeks) with acute stroke (11 arterial ischemic stroke (AIS); 9 venous) scanned at median postnatal age=1.5 days. Evidence of regional hyperperfusion existed in 10/11 (91%) neonates with AIS and 4/9 (44%) with venous stroke. Hyperperfusion was part of a heterogeneous pattern of hypo- and hyperperfusion in 4 infants with AIS and 3 infants with venous infarct. Electroencephalography data obtained at presentation were available for 19 (95%) of the neonates. Fourteen infants (70%) had either electrographic seizure or focal sharp waves in the same hemisphere as the acute infarction. Conclusion: Arterial spin labeling pMRI can be successfully obtained in acute neonatal stroke. Unlike adults, pMRI often reveals hyperperfusion rather than hypoperfusion in neonates. This hyperperfusion may be due to early spontaneous reperfusion or to the neuronal hyperexcitability of stroke-associated seizure.

In order to better understand the injured neonatal brain, we quantify cerebral oxygenation, blood flow, and oxygen metabolism in healthy neonates during the first days of life using non-invasive optical spectroscopies.

Frequency domain near infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) can provide noninvasive means to study cerebral hemodynamics in neonates with congenital heart disease (CHD). Using these advanced optical technologies, our preliminary data shows that neonates with CHD have lower cerebral oxygen metabolism than healthy neonates.

By using noninvasive optical techniques, we detected lower cerebral blood flow and metabolism in extremely premature neonates with low-grade intraventricular hemorrhage at the age of 4 to 8 weeks.

Frequency domain near-infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) use near-infrared light to quantify static and dynamic properties of brain tissue. We present a novel FDNIRS-DCS system and characterize its performance.