Preterm Infants off Positive Pressure Respiratory Support Have a Higher Incidence of Occult Cerebral Hypoxia.

OBJECTIVE: To use cerebral near-infrared spectroscopy (NIRS) to quantify occult cerebral hypoxia across respiratory support modes in preterm infants. STUDY DESIGN: In this prospective, longitudinal, observational study, infants ≤32 weeks gestation underwent serial pulse oximetry (oxygen saturation [SpO2]) and cerebral NIRS monitoring (4-6 hours per session) following a standardized recording schedule (daily for 2 weeks, every other day for 2 weeks, then weekly until 35 weeks corrected gestational age). Four calculations were made: median cerebral saturation, median cerebral hypoxia burden (proportion of NIRS samples below the hypoxia threshold [<67%]), median systemic saturation, and median systemic hypoxia burden (proportion of SpO2 samples below the desaturation threshold [<85%]). During each recording session, respiratory support mode was noted (room air, low-flow nasal cannula, high-flow nasal cannula, noninvasive positive pressure ventilation, continuous positive airway pressure, and invasive ventilation). RESULTS: There were 1013 recording sessions made from 174 infants with a median length of 6.9 hours. Although the systemic (SpO2) hypoxia burden was significantly greater for infants on the highest respiratory support (invasive and noninvasive positive pressure ventilation), the cerebral hypoxia burden was significantly greater during recording sessions made on the lowest respiratory support (8% for room air; 29% for low-flow nasal cannula). CONCLUSIONS: Premature infants on the highest levels of respiratory support have less cerebral hypoxia than those on lower respiratory support. These results raise concern about unrecognized cerebral hypoxia during lower acuity periods of neonatal intensive care unit hospitalization and adverse outcomes.

The hidden consequence of intraventricular hemorrhage: persistent cerebral desaturation after IVH in preterm infants.

BACKGROUND: Previous studies describe a short-term decrease in cerebral oxygen saturation (StO2) after intraventricular hemorrhage (IVH) in premature infants; little is known about long-term implications. METHODS: Infants born <30 weeks gestational age (GA) were included. Clinical characteristics, hemoglobin measurements, the highest grade of IVH, and white matter injury (WMI) were noted. NIRS monitoring occurred daily or every other day for 4 weeks; weekly through 36 weeks GA. Recordings were error-corrected before calculation of mean StO2 and fractional tissue oxygen extraction (FTOE). Mean StO2 and FTOE were plotted by postnatal age and injury group (IVH/no IVH; WMI/no WMI). Non-linear regression by locally estimated scatterplot smoothing was used to generate the best-fit line and CI. RESULTS: A total of 1237 recordings from 185 infants were included; mean length = 6.5 h; mean GA = 26.3 w; mean BW = 951 g; overall/severe IVH incidence was 29/8%, WMI incidence was 16%. IVH was independently associated with an acute drop in StO2, which remained lower for 68 d. Severe IVH was associated with lower StO2 values than mild IVH. WMI was associated with early and persistent elevation of FTOE. CONCLUSION: IVH of any grade is associated with a prolonged cerebral desaturation and WMI is associated with prolonged elevation of FTOE. This finding is exacerbated for infants with severe IVH. IMPACT: The longitudinal impact of IVH on cerebral oxygenation has not been previously studied. IVH is associated with persistent cerebral desaturation, months in length, and is independent of anemia. More severe IVH is associated with worsened cerebral hypoxia. Infants later diagnosed with white matter injury have an early and persistent elevation of cerebral oxygen extraction (cFTOE). This cerebral desaturation, below previously identified normative ranges, may provide insight into the mechanistic link between IVH and white matter injury.

Safety and Short-Term Outcomes of Therapeutic Hypothermia in Preterm Neonates 34-35 Weeks Gestational Age with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To evaluate the safety and short-term outcomes of preterm neonates born at 34-35 weeks gestation with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. STUDY DESIGN: Medical records of preterm neonates born at 34-35 weeks gestational age with HIE treated with therapeutic hypothermia were retrospectively reviewed. Short-term safety outcomes and the presence, severity (mild, moderate, severe), and patterns of brain injury on magnetic resonance imaging were reviewed using a standard scoring system, and compared with a cohort of term neonates with HIE treated with therapeutic hypothermia. RESULTS: Thirty-one preterm and 32 term neonates were identified. Therapeutic hypothermia-associated complications were seen in 90% of preterm infants and 81.3% of term infants (P = .30). In the preterm infants, hyperglycemia (58.1% vs31.3%, P = .03) and rewarming before completion of therapeutic hypothermia (19.4% vs 0.0%, P = .009) were more likely compared with term infants. All deaths occurred in the preterm group (12.9% vs 0%, P = .04). Neuroimaging showed the presence of injury in 80.6% of preterm infants and 59.4% of term infants (P = .07), with no differences in injury severity. Injury to the white matter was more prevalent in preterm infants compared with term infants (66.7% vs 25.0%, P = .001). CONCLUSIONS: Therapeutic hypothermia in infants born at 34-35 weeks gestational age appears feasible. Risks of mortality and side effects warrant caution with use of therapeutic hypothermia in preterm infants.

Gestational age-dependent relationship between cerebral oxygen extraction and blood pressure.

BackgroundPremature infants may lack mature cerebrovascular autoregulatory function and fail to adapt oxygen extraction to decreasing systemic perfusion.MethodsInfants ≤28 weeks of gestational age (GA) were recruited. Systemic oxygen saturation (SpO2), mean arterial blood pressure (MABP), and cerebral saturation (near-infrared spectroscopy, SctO2) were measured continuously over the first 72 h. Resulting data underwent error-processing. For each remaining 10 m window, the mean MABP and fractional tissue oxygen extraction (FTOE) were calculated. The infants were divided into two groups (23-25 and 26-28 weeks). The median FTOE at low, medium, and high MABP values (empirically defined within each group based on the 25th and 75th centile) were compared between estimated gestational age (EGA) groups.ResultsSample n=68, mean±SD GA=25.5±1.3 weeks, and birthweight (BW)=823±195 g. The median FTOE in the more preterm group vs. more mature group was statistically different at lower value of MABP (P<0.01) and higher values of MABP (P=0.01), but not at medium values (P=0.55).ConclusionThe more mature group (GA 26-28 weeks) displayed an appropriate increase in oxygen extraction during hypotension, steadily decreasing as MABP increased, suggesting mature autoregulation. An opposite response was noted in the more preterm group, suggesting an inability to mount a compensatory response when BP is outside of the physiologic range.

Functional Imaging of the Developing Brain at the Bedside Using Diffuse Optical Tomography.

While histological studies and conventional magnetic resonance imaging (MRI) investigations have elucidated the trajectory of structural changes in the developing brain, less is known regarding early functional cerebral development. Recent investigations have demonstrated that resting-state functional connectivity MRI (fcMRI) can identify networks of functional cerebral connections in infants. However, technical and logistical challenges frequently limit the ability to perform MRI scans early or repeatedly in neonates, particularly in those at greatest risk for adverse neurodevelopmental outcomes. High-density diffuse optical tomography (HD-DOT), a portable imaging modality, potentially enables early continuous and quantitative monitoring of brain function in infants. We introduce an HD-DOT imaging system that combines advancements in cap design, ergonomics, and data analysis methods to allow bedside mapping of functional brain development in infants. In a cohort of healthy, full-term neonates scanned within the first days of life, HD-DOT results demonstrate strong congruence with those obtained using co-registered, subject-matched fcMRI and reflect patterns of typical brain development. These findings represent a transformative advance in functional neuroimaging in infants, and introduce HD-DOT as a powerful and practical method for quantitative mapping of early functional brain development in normal and high-risk neonates.

A validated clinical MRI injury scoring system in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Deep nuclear gray matter injury in neonatal hypoxic-ischemic encephalopathy (HIE) is associated with worse neurodevelopmental outcomes. We previously published a qualitative MRI injury scoring system utilizing serial T1-weighted, T2-weighted and diffusion-weighted imaging (DWI), weighted for deep nuclear gray matter injury. OBJECTIVES: To establish the validity of the MRI scoring system with neurodevelopmental outcome at 18-24 months. MATERIALS AND METHODS: MRI scans from neonates with moderate to severe HIE treated with therapeutic hypothermia were evaluated. Signal abnormality was scored on T1-weighted, T2-weighted and DWI sequences and assessed using an established system in five regions: (a) subcortical: caudate nucleus, globus pallidus and putamen, thalamus and the posterior limb of the internal capsule; (b) white matter; (c) cortex, (d) cerebellum and (e) brainstem. MRI injury was graded as none, mild, moderate or severe. Inter-rater reliability was tested on a subset of scans by two independent and blinded neuroradiologists. Surviving infants underwent the Bayley Scales of Infant and Toddler Development-III (Bayley-III) at 18-24 months. Data were analyzed using univariate and multivariate linear and logistic regression. RESULTS: Fifty-seven eligible neonates underwent at least one MRI scan in the first 2 weeks of life. Mean postnatal age at scan 1 was 4±2 days in 50/57 (88%) neonates and 48/54 (89%) surviving infants underwent scan 2 at 10±2 days. In 54/57 (95%) survivors, higher MRI injury grades were significantly associated with worse outcomes in the cognitive, motor and language domains of the Bayley-III. CONCLUSION: A qualitative MRI injury scoring system weighted for deep nuclear gray matter injury is a significant predictor of neurodevelopmental outcome at 18-24 months in neonates with HIE.

A novel method for assessing cerebral autoregulation in preterm infants using transfer function analysis.

BACKGROUND: Autoregulatory dysfunction is an important contributor to brain injury in premature infants, particularly intraventricular hemorrhage (IVH). The autoregulatory system acts as a filter that dampens the systemic blood flow to follow a normal cerebral perfusion profile. METHODS: Simultaneous arterial blood pressure and cerebral near-infrared spectroscopy (NIRS) data were collected from infants born before 28 wk estimated gestational age. The resulting data were preprocessed and then divided into nonoverlapping 20-min epochs. The transfer function estimate was calculated to determine dampening ability. RESULTS: Sixty-two infants were prospectively recruited with a mean estimated gestational age of 25.4 ± 1.3 wk and birth weight of 832 ± 199 g. 67% were male, 24/62 had IVH, 17/62 received dopamine, 47/62 had antenatal steroid exposure, and 22/62 received fentanyl.Advancing estimated gestational age and birth weight z-score predicted stronger dampening while African-American race and IVH of any grade predicted weaker dampening. CONCLUSION: This preliminary report suggests an impairment in dampening ability associated with immaturity, decreased birth weight z-score, and African-American race. Decreased dampening is also associated with IVH, although these results cannot distinguish between decreased dampening as an antecedent or sequela of IVH. These observations should be studied in a larger sample.

Bedside optical imaging of occipital resting-state functional connectivity in neonates.

Resting-state networks derived from temporal correlations of spontaneous hemodynamic fluctuations have been extensively used to elucidate the functional organization of the brain in adults and infants. We have previously developed functional connectivity diffuse optical tomography methods in adults, and we now apply these techniques to study functional connectivity in newborn infants at the bedside. We present functional connectivity maps in the occipital cortices obtained from healthy term-born infants and premature infants, including one infant with an occipital stroke. Our results suggest that functional connectivity diffuse optical tomography has potential as a valuable clinical tool for the early detection of functional deficits and for providing prognostic information on future development.

WU-NEAT: A clinically validated, open-source MATLAB toolbox for limited-channel neonatal EEG analysis.

BACKGROUND: Limited-channel EEG research in neonates is hindered by lack of open, accessible analytic tools. To overcome this limitation, we have created the Washington University-Neonatal EEG Analysis Toolbox (WU-NEAT), containing two of the most commonly used tools, provided in an open-source, clinically-validated package running within MATLAB. METHODS: The first algorithm is the amplitude-integrated EEG (aEEG), which is generated by filtering, rectifying and time-compressing the original EEG recording, with subsequent semi-logarithmic display. The second algorithm is the spectral edge frequency (SEF), calculated as the critical frequency below which a user-defined proportion of the EEG spectral power is located. The aEEG algorithm was validated by three experienced reviewers. Reviewers evaluated aEEG recordings of fourteen preterm/term infants, displayed twice in random order, once using a reference algorithm and again using the WU-NEAT aEEG algorithm. Using standard methodology, reviewers assigned a background pattern classification. Inter/intra-rater reliability was assessed. For the SEF, calculations were made using the same fourteen recordings, first with the reference and then with the WU-NEAT algorithm. Results were compared using Pearson's correlation coefficient. RESULTS: For the aEEG algorithm, intra- and inter-rater reliability was 100% and 98%, respectively. For the SEF, the mean±SD Pearson correlation coefficient between algorithms was 0.96±0.04. CONCLUSION: We have demonstrated a clinically-validated toolbox for generating the aEEG as well as calculating the SEF from EEG data. Open-source access will enable widespread use of common analytic algorithms which are device-independent and unlikely to become outdated as technology changes, thereby facilitating future collaborative research in neonatal EEG.

Poverty and Excess Length of Hospital Stay in Neonatal Opioid Withdrawal Syndrome.

OBJECTIVES: To study the impact of sociodemographic factors on length of stay (LOS) for infants with neonatal opioid withdrawal syndrome (NOWS) secondary to fetal opioid exposure. METHODS: In this retrospective cohort study, we included term infants with NOWS, excluding those with other significant medical issues. Comprehensive clinical and sociodemographic data were collected. Multivariate regression modeling was used to identify factors which contributed to excess LOS, which was defined as the number of days beyond the standard monitoring and/or treatment protocol. RESULTS: In all, 129 infants were identified; mean gestational age of 37.9 ±â€Š1.3 weeks and mean body weight of 2880 ±â€Š496 g. Among them, 68% of infants were exposed to opioids; 27% were exposed to methadone; and 67% required pharmacologic treatment. The degree of poverty was assessed using the Area Deprivation Index (ADI) based on the mother's address at the time of birth. Median LOS for treated infants was 23 days versus 8 days for those who did not need pharmacologic treatment. The median excess LOS was 4 days (range 0-24).Excess hospital days were strongly correlated with degree of deprivation in the mother's community (r = 0.55, P < 0.01). ADI remained a strong predictor of excess LOS, even when controlling for pharmacologic treatment, placement in state's custody, race, and gestational age at birth. CONCLUSIONS: These results suggest poverty is associated with excess LOS and that early allocation of resources for at-risk families may help to reduce overall length of hospital stay.

Delayed cord clamping is associated with improved dynamic cerebral autoregulation and decreased incidence of intraventricular hemorrhage in preterm infants.

Delayed cord clamping (DCC) improves neurologic outcomes in preterm infants through a reduction in intraventricular hemorrhage (IVH) incidence. The mechanism behind this neuroprotective effect is not known. Infants born <28 wk gestation were recruited for longitudinal monitoring. All infants underwent 72 h of synchronized near-infrared spectroscopy (NIRS) and mean arterial blood pressure (MABP) recording within 24 h of birth. Infants with DCC were compared with control infants with immediate cord clamping (ICC), controlling for severity of illness [clinical risk index for babies (CRIB-II) score], chorioamnionitis, antenatal steroids, sedation, inotropes, and delivery mode. Autoregulatory dampening was calculated as the transfer function gain coefficient between the MABP and NIRS signals. Forty-five infants were included (DCC; n = 15, paired 2:1 with ICC controls n = 30). ICC and DCC groups were similar including gestational age (25.5 vs. 25.2 wk, P = 0.48), birth weight (852.3 vs. 816.6 g, P = 0.73), percent female (40 vs. 40%, P = 0.75), and dopamine usage (27 vs. 23%, P = 1.00). There was a significant difference in IVH incidence between the DCC and ICC groups (20 vs. 50%, P = 0.04). Mean MABP was not different (35.9 vs. 35.1 mmHg, P = 0.44). Compared with the DCC group, the ICC group had diminished autoregulatory dampening capacity (-12.96 vs. -15.06 dB, P = 0.01), which remained significant when controlling for confounders. Dampening capacity was, in turn, strongly associated with decreased risk of IVH (odds ratio = 0.14, P < 0.01). The results of this pilot study demonstrate that DCC is associated with improved dynamic cerebral autoregulatory function and may be the mechanism behind the decreased incidence of IVH. NEW & NOTEWORTHY The neuroprotective mechanism of delayed cord clamping in premature infants is unclear. Delayed cord clamping was associated with improved cerebral autoregulatory function and a marked decrease in intraventricular hemorrhage (IVH). Improved dynamic cerebral autoregulation may decrease arterial baroreceptor sensitivity, thereby reducing the risk of IVH.

Late failure of cerebral autoregulation in hypoxic-ischemic encephalopathy is associated with brain injury: a pilot study.

BACKGROUND: Post-resuscitation reperfusion following hypoxic-ischemia (HIE) is associated with secondary brain injury in neonates. OBJECTIVE: To quantify the association between perfusion exceeding autoregulatory limits and brain injury. APPROACH: Continuous mean arterial blood pressure (MABP) and cerebral near-infrared spectroscopy (NIRS) data were prospectively collected from infants with HIE. Cerebral oximetry index (COx) was calculated as a moving correlation coefficient between MABP and NIRS. Upper and lower limits of autoregulation were identified by transition from negative to positive correlation. The proportion of time MABP above (hyperperfusion) and below (hypoperfusion) autoregulatory limits was calculated during therapeutic hypothermia (days 1-3). MAIN RESULTS: Sixteen infants were included; injury was noted in 7/16. There was no significance in hyperperfusion burden between injured and uninjured infants during day one (7% versus 10%, p = 0.88) or two (4% versus 2%, p = 0.88), but there was a marked increase for injured infants on day three (54% versus 14%, p = 0.02). There was a corollary decrease in hypoperfusion for injured versus uninjured infants on day 3 (6% versus 24%, p = 0.05). SIGNIFICANCE: HIE infants with brain injury have a late failure of cerebral autoregulation, manifested as a hyperperfusion burden, suggesting pathologic events are active on day 3 of hypothermia. This finding may help to identify infants which might need additional neuroprotection.

Re-examining the arterial cord blood gas pH screening criteria in neonatal encephalopathy.

OBJECTIVE: Screening criteria for neonatal encephalopathy remain a complex combination of subjective and objective criteria. We examine the utility of universal cord blood gas testing and mandatory encephalopathy evaluation for infants with pH ≤7.10 on umbilical cord arterial blood gas (cABG) as a single screening measure for timely identification of moderate/severe encephalopathy. DESIGN, SETTING, PATIENTS: Infants born at a single centre between 2008 and 2015, who were ≥36 weeks, had no congenital anomalies and had a cABG pH ≤7.10 were identified for a retrospective cohort study. Maternal/perinatal and patient factors were collected. RESULTS: 27 028 infants were born during the study period; 412 met all inclusion criteria. Of those, 35/85 infants with pH <7.00 and 34/327 infants with pH between 7.00 and 7.10 had moderate/severe encephalopathy. Encephalopathy was identified on the basis of pH and examination alone (no other perinatal criteria present) in 5/35 and 13/34 infants in the two pH groups, respectively.A cABG pH threshold of ≤7.10 was associated with a sensitivity of 74.2% and a specificity of 98.7% for detection of moderate/severe encephalopathy. Based on these data, 25 infants with cABG pH between 7.00 and 7.10 will need to be screened to identify one neonate with moderate/severe encephalopathy, who might have otherwise been missed using conventional screening, a 15% increase in appropriate selection and treatment over current methods. CONCLUSION: Universal cord blood gas screening with a pH threshold ≤7.10 and mandatory encephalopathy examination results in greater detection of infants with moderate/severe encephalopathy and timely initiation of therapeutic hypothermia.

Term-equivalent functional brain maturational measures predict neurodevelopmental outcomes in premature infants.

BACKGROUND: Term equivalent age (TEA) brain MRI identifies preterm infants at risk for adverse neurodevelopmental outcomes. But some infants may experience neurodevelopmental impairments even in the absence of neuroimaging abnormalities. OBJECTIVE: Evaluate the association of TEA amplitude-integrated EEG (aEEG) measures with neurodevelopmental outcomes at 24-36 months corrected age. METHODS: We performed aEEG recordings and brain MRI at TEA (mean post-menstrual age of 39 (±2) weeks in a cohort of 60 preterm infants born at a mean gestational age of 26 (±2) weeks. Forty-four infants underwent Bayley Scales of Infant Development, 3rd Edition (BSID-III) testing at 24-36 months corrected age. Developmental delay was defined by a score greater than one standard deviation below the mean (<85) in any domain. An ROC curve was constructed and a value of SEF90 < 9.2, yielded the highest sensitivity and specificity for moderate/severe brain injury on MRI. The association between aEEG measures and neurodevelopmental outcomes was assessed using odds ratio, then adjusted for confounding variables using logistic regression. RESULTS: Infants with developmental delay in any domain had significantly lower values of SEF90. Absent cyclicity was more prevalent in infants with cognitive and motor delay. Both left and right SEF90 < 9.2 were associated with motor delay (OR left: 4.7(1.2-18.3), p = 0.02, OR right: 7.9 (1.8-34.5), p < 0.01). Left SEF90 and right SEF90 were associated with cognitive delay and language delay respectively. Absent cyclicity was associated with motor and cognitive delay (OR for motor delay: 5.8 (1.3-25.1), p = 0.01; OR for cognitive delay: 16.8 (3.1-91.8), p < 0.01). These associations remained significant after correcting for social risk index score and confounding variables. CONCLUSIONS: aEEG may be used at TEA as a new tool for risk stratification of infants at higher risk of poor neurodevelopmental outcomes. Therefore, a larger study is needed to validate these results in premature infants at low and high risk of brain injury.

Near infrared optical technologies to illuminate the status of the neonatal brain.

The neurodevelopmental outcome of at-risk infants in the neonatal intensive care unit (NICU) is concerning despite steady improvement in the survival rate of these infants. Our current management is often complicated by delayed realization of cerebral deficits due to late manifestation and lack of effective screening tools and neuroimaging/monitoring techniques that are suitable for sick neonates at the bedside. Near infrared specstrocopy (NIRS) is a noninvasive, safe, and portable technique providing a wide range of cerebral hemodynamic contrasts for evaluating the brain. The current state of NIRS technology can be devided into three generations. The first generation represents conventional trend monitoring oximeters that are currently the most widely used in the clinical settings, while the second generation focuses on improving the quantitive accuracy of NIRS measurements by advanced optical techniques. The emergence of diffuse optical imaging (DOI) represents a third generation which opens up more potential clinical applications by providing regional comparisons of brain oximetry and functions either at rest or in response to interventions. Successful integration of NIRS/DOI into the clinical setting requires matching the different capabilities of each instrument to specific clinical goals.

High-density diffuse optical tomography of term infant visual cortex in the nursery.

Advancements in antenatal and neonatal medicine over the last few decades have led to significant improvement in the survival rates of sick newborn infants. However, this improvement in survival has not been matched by a reduction in neurodevelopmental morbidities with increasing recognition of the diverse cognitive and behavioral challenges that preterm infants face in childhood. Conventional neuroimaging modalities, such as cranial ultrasound and magnetic resonance imaging, provide an important definition of neuroanatomy with recognition of brain injury. However, they fail to define the functional integrity of the immature brain, particularly during this critical developmental period. Diffuse optical tomography methods have established success in imaging adult brain function; however, few studies exist to demonstrate their feasibility in the neonatal population. We demonstrate the feasibility of using recently developed high-density diffuse optical tomography (HD-DOT) to map functional activation of the visual cortex in healthy term-born infants. The functional images show high contrast-to-noise ratio obtained in seven neonates. These results illustrate the potential for HD-DOT and provide a foundation for investigations of brain function in more vulnerable newborns, such as preterm infants.

Neonatal hemodynamic response to visual cortex activity: high-density near-infrared spectroscopy study.

The neurodevelopmental outcome of neonatal intensive care unit (NICU) infants is a major clinical concern with many infants displaying neurobehavioral deficits in childhood. Functional neuroimaging may provide early recognition of neural deficits in high-risk infants. Near-infrared spectroscopy (NIRS) has the advantage of providing functional neuroimaging in infants at the bedside. However, limitations in traditional NIRS have included contamination from superficial vascular dynamics in the scalp. Furthermore, controversy exists over the nature of normal vascular, responses in infants. To address these issues, we extend the use of novel high-density NIRS arrays with multiple source-detector distances and a superficial signal regression technique to infants. Evaluations of healthy term-born infants within the first three days of life are performed without sedation using a visual stimulus. We find that the regression technique significantly improves brain activation signal quality. Furthermore, in six out of eight infants, both oxy- and total hemoglobin increases while deoxyhemoglobin decreases, suggesting that, at term, the neurovascular coupling in the visual cortex is similar to that found in healthy adults. These results demonstrate the feasibility of using high-density NIRS arrays in infants to improve signal quality through superficial signal regression, and provide a foundation for further development of high-density NIRS as a clinical tool.