Steve M. Liao

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.

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.

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.

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.

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.

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.

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.

Head position change is not associated with acute changes in bilateral cerebral oxygenation in stable preterm infants during the first 3 days of life

OBJECTIVE Several recent intraventricular hemorrhage prevention bundles include midline head positioning to prevent potential disturbances in cerebral hemodynamics. We aimed to study the impact of head position change on regional cerebral saturations (SctO2) in preterm infants (< 30 weeks gestational age) during the first 3 days of life. STUDY DESIGN Bilateral SctO2 was measured by near-infrared spectroscopy. The infants head was turned sequentially to each side from midline (baseline) in 30-minute intervals while keeping the body supine. Bilateral SctO2 before and after each position change were compared using paired t-test. RESULTS In relatively stable preterm infants (gestational age 26.5 ± 1.7 weeks, birth weight 930 ± 220 g; n = 20), bilateral SctO2 remained within normal range (71.1-75.3%) when the head was turned from midline position to either side. CONCLUSION Stable preterm infants tolerated brief changes in head position from midline without significant alternation in bilateral SctO2; the impact on critically ill infants needs further evaluation.

Cerebral maturation on amplitude-integrated electroencephalography and perinatal exposures in preterm infants

To determine the associations between perinatal exposures, cerebral maturation on amplitude‐integrated encephalography (aEEG) and outcome.

Response to dopamine in prematurity: a biomarker for brain injury?

Objective:To identify factors associated with responsiveness to dopamine therapy for hypotension and the relationship to brain injury in a cohort of preterm infants.Study Design:The pharmacy database at St Louis Children’s Hospital was retrospectively queried to identify infants who (a) were born <28 weeks gestation between 2012 and 2014, (b) received dopamine and (c) had blood pressure measurements from an umbilical arterial catheter. A control group was constructed from contemporaneous infants who did not receive dopamine. Mean arterial blood pressure (MABP) at baseline, 1 h and 3 h after initiating dopamine were obtained for each dopamine-exposed infant. MABP measurements at matched time points were obtained in the control group.Result:Sixty-nine dopamine-treated and 45 control infants were included. Mean ΔMABP at 3 h was 4.5±6.3 mm of Hg for treated infants vs 1±2.9 for the control. Median dopamine starting dose was 2.5 μg kg−1 min−1. Dopamine-treated infants were less mature and of lower birth weight while also more likely to be intubated at 72 h, diagnosed with intraventricular hemorrhage (IVH) and to die. Failure to respond to dopamine was associated with greater likelihood of developing IVH (odds ratio (OR) 5.8, 95% confidence interval (CI) 1.1–42.3), while a strong response (ΔMABP>10 mm Hg) was associated with a reduction in risk of IVH (OR 0.1, 95% CI 0.01–0.8).Conclusion:Low–moderate dose dopamine administration results in modest blood pressure improvements. A lack of response to dopamine is associated with a greater risk of IVH, whereas a strong response is associated with a decreased risk. Further research into underlying mechanisms and management strategies is needed.