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.

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.

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 (MRI) 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=0.30). In the preterm infants, hyperglycemia (58.1% vs.31.3%, p=0.03) and rewarming before completion of therapeutic hypothermia (19.4% vs. 0.0%, p=0.009) were more likely compared with term infants. All deaths occurred in the preterm group (12.9% vs. 0%, p=0.04). Neuroimaging showed the presence of injury in 80.6% of preterm infants and 59.4% of term infants (p=0.07), 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=0.001). 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.

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.

Objective: To evaluate the association between early (within 10d) pRBC transfusion and the development of severe ROP. Study Design and Methods: This was a single-center retrospective study. Inclusion criteria were preterm infants born ≤ 32 weeks gestation or weighing ≤ 1500g. Severe ROP was defined as infants requiring retinal laser ablation or bevacizumab injection. Logistic regression was used to identify the association between transfusions and severe ROP. Results: A total of 1635 infants were included in the final analysis. The severe ROP incidence was 8% (126/1635). Ninety-one percent (115/126) of infants who developed severe ROP received a pRBC transfusion in the first 10d. Early transfusion was associated with severe ROP; adjusted odds ratio of 3.8 (95% CI: 1.8-8.1). Conclusion: pRBC transfusions in the first 10 days of life are associated with an almost four-fold increased risk of severe ROP, independent of gestational age at birth or bronchopulmonary dysplasia (BPD) status.