Intravenous administration of ultrasound contrast to critically ill pediatric patients.

BACKGROUND: The off-label use of contrast-enhanced ultrasound has been increasingly used for pediatric patients. OBJECTIVE: The purpose of this retrospective study is to report any observed clinical changes associated with the intravenous (IV) administration of ultrasound contrast to critically ill neonates, infants, children, and adolescents. MATERIALS AND METHODS: All critically ill patients who had 1 or more contrast-enhanced ultrasound scans while being closely monitored in the neonatal, pediatric, or pediatric cardiac intensive care units were identified. Subjective and objective data concerning cardiopulmonary, neurological, and hemodynamic monitoring were extracted from the patient's electronic medical records. Vital signs and laboratory values before, during, and after administration of ultrasound contrast were obtained. Statistical analyses were performed using JMP Pro, version 15. Results were accepted as statistically significant for P-value<0.05. RESULTS: Forty-seven contrast-enhanced ultrasound scans were performed on 38 critically ill patients, 2 days to 17 years old, 19 of which were female (50%), and 19 had history of prematurity (50%). At the time of the contrast-enhanced ultrasound scans, 15 patients had cardiac shunts or a patent ductus arteriosus, 25 had respiratory failure requiring invasive mechanical oxygenation and ventilation, 19 were hemodynamically unstable requiring continual vasoactive infusions, and 8 were receiving inhaled nitric oxide. In all cases, no significant respiratory, neurologic, cardiac, perfusion, or vital sign changes associated with IV ultrasound contrast were identified. CONCLUSION: This study did not retrospectively identify any adverse clinical effects associated with the IV administration of ultrasound contrast to critically ill neonates, infants, children, and adolescents.

Microvascular imaging findings in infants with bacterial meningitis: a case series.

Bacterial meningitis is a severe and life-threatening disease that rapidly progresses in neonates and infants; prompt diagnosis and appropriate treatment are lifesaving. Magnetic resonance imaging remains the primary imaging technique for diagnosing meningitis; however, due to its limited availability and cost, ultrasound is often used for initial screening. Microvascular imaging ultrasound (MVI) is an emerging technique that offers insight into the brain microvasculature beyond conventional ultrasound. Here we present three patients with confirmed bacterial meningitis and associated cerebral microvascular findings on brain MVI to instigate further validation of cerebral microvascular imaging markers of bacterial meningitis for early detection and intervention.

Evaluation of the Cerebrospinal Fluid Flow Dynamics with Microvascular Imaging Ultrasound in Infants.

PURPOSE: Microvascular imaging ultrasound (MVI) can detect slow blood flow in small-caliber cerebral vessels. This technology may help assess flow in other intracranial structures, such as the ventricular system. In this study, we describe the use of MVI for characterizing intraventricular cerebrospinal fluid (CSF) flow dynamics in infants. MATERIALS AND METHODS: We included infants with brain ultrasound that had MVI B-Flow cine clips in the sagittal plane. Two blinded reviewers examined the images, dictated a diagnostic impression, and identified the third ventricle, cerebral aqueduct, fourth ventricle, and CSF flow direction. A third reviewer evaluated the discrepancies. We evaluated the association of visualization of CSF flow as detectable with MVI, with the diagnostic impressions. We also assessed the inter-rater reliability (IRR) for detecting CSF flow. RESULTS: We evaluated 101 infants, mean age 40 ± 53 days. Based on brain MVI B-Flow, a total of 49 patients had normal brain US scans, 40 had hydrocephalus, 26 had intraventricular hemorrhage (IVH), and 14 had hydrocephalus+IVH. Using spatially moving MVI signal in the third ventricle, cerebral aqueduct, and fourth ventricle as the criteria for CSF flow, CSF flow was identified in 10.9% (n = 11), 15.8% (n = 16), and 16.8% (n = 17) of cases, respectively. Flow direction was detected in 19.8% (n = 20) of cases; 70% (n = 14) was caudocranial, 15% (n = 3) was craniocaudal, and 15% (n = 3) bidirectional, with IRR = 0.662, p < 0.001. Visualization of CSF flow was significantly associated with the presence of IVH alone (OR 9.7 [3.3-29.0], p < 0.001) and IVH+hydrocephalus (OR 12.4 [3.5-440], p < 0.001), but not with hydrocephalus alone (p = 0.116). CONCLUSION: This study demonstrates that MVI can detect CSF flow dynamics in infants with a history of post-hemorrhagic hydrocephalus with a high IRR.

Brain Targeted Xenon Protects Cerebral Vasculature After Traumatic Brain Injury.

Abstract Cerebrovascular dysfunction following traumatic brain injury (TBI) is a well-characterized phenomenon. Given the therapeutic potential of xenon, we aimed to study its effects after localized delivery to the brain using microbubbles. We designed xenon-containing microbubbles stabilized by dibehenoylphosphatidylcholine (DBPC) and polyethylene glycol (PEG) attached to saturated phospholipid (DPSE-PEG5000). Using a pig model of TBI, these microbubbles were intravenously injected, and ultrasound was used to release xenon at the level of the carotid artery. The control group received perfluorobutane containing microbubbles. Diffusion tensor imaging (DTI) showed areas of higher fractional anisotropy for pigs receiving xenon microbubbles compared to the control group at 1 day after injury. Radial diffusivity analysis showed that this effect was mainly the result of acute edema. Pigs were euthanized at 5 days, and the brain tissues of xenon-treated animals showed reduction of perivascular inflammation and blood-brain barrier disruption. Endothelial cell culture experiments showed that glutamate reduces tight junction protein zona occludens-1 (ZO-1), but treatment with xenon microbubbles attenuates this effect. Xenon treatment protects cerebrovasculature and reduces astroglial reactivity after TBI. Further, these data support the future use of localized delivery of various therapeutic agents for brain injury using microbubbles in order to limit systemic side effects and reduce costs.

A Template for Translational Bioinformatics: Facilitating Multimodal Data Analyses in Preclinical Models of Neurological Injury.

Background: Pediatric neurological injury and disease is a critical public health issue due to increasing rates of survival from primary injuries (e.g., cardiac arrest, traumatic brain injury) and a lack of monitoring technologies and therapeutics for the treatment of secondary neurological injury. Translational, preclinical research facilitates the development of solutions to address this growing issue but is hindered by a lack of available data frameworks and standards for the management, processing, and analysis of multimodal data sets. Methods: Here, we present a generalizable data framework that was implemented for large animal research at the Children's Hospital of Philadelphia to address this technological gap. The presented framework culminates in an interactive dashboard for exploratory analysis and filtered data set download. Results: Compared with existing clinical and preclinical data management solutions, the presented framework accommodates heterogeneous data types (single measure, repeated measures, time series, and imaging), integrates data sets across various experimental models, and facilitates dynamic visualization of integrated data sets. We present a use case of this framework for predictive model development for intra-arrest prediction of cardiopulmonary resuscitation outcome. Conclusions: The described preclinical data framework may serve as a template to aid in data management efforts in other translational research labs that generate heterogeneous data sets and require a dynamic platform that can easily evolve alongside their research.

Current understanding and future potential applications of cerebral microvascular imaging in infants.

Microvascular imaging is an advanced Doppler ultrasound technique that detects slow flow in microvessels by suppressing clutter signal and motion-related artifacts. The technique has been applied in several conditions to assess organ perfusion and lesion characteristics. In this pictorial review, we aim to describe current knowledge of the technique, particularly its diagnostic utility in the infant brain, and expand on the unexplored but promising clinical applications of microvascular imaging in the brain with case illustrations.

Can Ultrasound-Guided Xenon Delivery Provide Neuroprotection in Traumatic Brain Injury?

Traumatic brain injury (TBI) is associated with high mortality and morbidity in children and adults. Unfortunately, there is no effective management for TBI in the acute setting. Rodent studies have shown that xenon, a well-known anesthetic gas, can be neuroprotective when administered post-TBI. Gas inhalation therapy, however, the approach typically used for administering xenon, is expensive, inconvenient, and fraught with systemic side effects. Therapeutic delivery to the brain is minimal, with much of the inhaled gas cleared by the lungs. To bridge major gaps in clinical care and enhance cerebral delivery of xenon, this study introduces a novel xenon delivery technique, utilizing microbubbles, in which a high impulse ultrasound signal is used for targeted cerebral release of xenon. Briefly, an ultrasound pulse is applied along the carotid artery at the level of the neck on intravenous injection of xenon microbubbles (XeMBs) resulting in release of xenon from microbubbles into the brain. This delivery technique employs a hand-held, portable ultrasound system that could be adopted in resource-limited environments. Using a high-fidelity porcine model, this study demonstrates the neuroprotective efficacy of xenon microbubbles in TBI for the first time.