Brain injury resulting from adverse events during pregnancy and delivery is the leading cause of neonatal morbidity and disability. Surviving neonates often suffer long-term motor, sensory, and cognitive impairments. Birth asphyxia is among the most common causes of neonatal encephalopathy. The integration of ultrasound, including Doppler ultrasound, and near-infrared spectroscopy (NIRS) offers a promising approach to understanding the pathology and diagnosis of encephalopathy in this special patient population. Ultrasound diagnosis can be very helpful for the assessment of structural abnormalities associated with neonatal encephalopathy such as alterations in brain structures (intraventricular hemorrhage, infarcts, hydrocephalus, white matter injury) and evaluation of morphologic changes. Doppler sonography is the most valuable method as it provides information about blood flow patterns and outcome prediction. NIRS provides valuable insight into the functional aspects of brain activity by measuring tissue oxygenation and blood flow. The combination of ultrasonography and NIRS may produce complementary information on structural and functional aspects of the brain. This review summarizes the current state of research, discusses advantages and limitations, and explores future directions to improve applicability and efficacy.

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.

Syphilis is caused by treponema pallidum. If untreated, or inadequately treated, during pregnancy, it can result in congenital syphilis (CS), which is classified as early and late. Early CS displays before 2 years of age. We herein describe 2 cases of early CS, whose clinical onset included liver failure, edema, organomegaly, and respiratory distress. We focus on liver, intestinal, and brain ultrasound (US) and other peculiar radiological findings. To date, there are no scientific data on intestinal and brain US findings in patients with early CS whereas data on abdominal US are scarce. Increasing knowledge about US findings in early CS could be useful to improve the diagnostic and therapeutic approach to these patients.

Point-of-care brain ultrasound and transcranial doppler or color-coded doppler is being increasingly used as an essential diagnostic and monitoring tool at the bedside of critically ill neonates and children. Brain ultrasound has already established as a cornerstone of daily practice in the management of the critically ill newborn for diagnosis and follow-up of the most common brain diseases, considering the easiness to insonate the brain through transfontanellar window. In critically ill children, doppler based techniques are used to assess cerebral hemodynamics in acute brain injury and recommended for screening patients suffering from sickle cell disease at risk for stroke. However, more evidence is needed regarding the accuracy of doppler based techniques for non-invasive estimation of cerebral perfusion pressure and intracranial pressure, as well as regarding the accuracy of brain ultrasound for diagnosis and monitoring of acute brain parenchyma alterations in children. This review is aimed at providing a comprehensive overview for clinicians of the technical, anatomical, and physiological basics for brain ultrasonography and transcranial doppler or color-coded doppler, and of the current status and future perspectives of their clinical applications in critically ill neonates and children.
CONCLUSIONS: In critically ill neonates, brain ultrasound for diagnosis and follow-up of the most common cerebral pathologies of the neonatal period may be considered the standard of care. Data are needed about the possible role of doppler techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles. In pediatric critical care, doppler based techniques should be routinely adopted to assess and monitor cerebral hemodynamics. New technologies and more evidence are needed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles.
BACKGROUND: • In critically ill neonates, brain ultrasound for early diagnosis and follow-up of the most common cerebral and neurovascular pathologies of the neonatal period is a cornerstone of daily practice. In critically ill children, doppler-based techniques are more routinely used to assess cerebral hemodynamics and autoregulation after acute brain injury and to screen patients at risk for vasospasm or stroke (e.g., sickle cell diseases, right-to-left shunts).
BACKGROUND: • In critically ill neonates, research is currently focusing on the use of novel high frequency probes, even higher than 10 MHz, especially for extremely preterm babies. Furthermore, data are needed about the role of doppler based techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles, also integrated with a non-invasive assessment of brain oxygenation. In pediatric critical care, new technologies should be developed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. Furthermore, large multicenter studies are needed to clarify role and accuracy of doppler-based techniques to assess cerebral perfusion pressure and its changes after treatment interventions.

Ultrasound is being researched as a method to modulate the brain. Studies of the interaction of sound with neurons support the hypothesis that mechanosensitive ion channels play an important role in ultrasound neuromodulation. The response of cells other than neurons (e.g., astrocytes, pericytes and endothelial cells) have not been fully characterized, despite playing an important role in brain function.
To address this gap in knowledge, we examined cultured murine primary cortical neurons, astrocytes, endothelial cells and pericytes in an in vitro widefield microscopy setup during application of a 500 ms burst of 250 kHz focused ultrasound over a pressure range known to elicit neuromodulation. We examined cell membrane health in response to a range of pulses and used optical calcium indicators in conjunction with pharmacological antagonists to selectively block different groups of thermo- and mechanosensitive ion channels known to be responsive to ultrasound.
All cell types experienced an increase in calcium fluorescence in response to ultrasound. Gadolinium (Gad), 2-aminoethoxydiphenyl borate (2-APB) and ruthenium red (RR) reduced the percentage of responding neurons and magnitude of response. The percentage of astrocytes responding was significantly lowered only by Gad, whereas both 2-APB and Gad decreased the amplitude of the fluorescence response. 2-APB decreased the percentage of responding endothelial cells, whereas only Gad reduced the magnitude of responses. Pericytes exposed to RR or Gad were less likely to respond to stimulation. RR had no detectable effect on the magnitude of the pericyte responses while 2-APB and Gad significantly decreased the fluorescence intensity, despite not affecting the percentage responding.
Our study highlights the role of non-neuronal cells during FUS neuromodulation. All of the investigated cell types are sensitive to mechanical ultrasound stimulation and rely on mechanosensitive ion channels to undergo ultrasound neuromodulation.

OBJECTIVE: Stroke is a leading cause of mortality and disability worldwide. This study aimed to assess the prognostic value of serum S100B protein, transcranial color-coded duplex sonography (TCCD), and optic nerve sheath diameter (ONSD) in predicting functional outcomes in critically ill patients with acute ischemic stroke (AIS).
METHODS: In this prospective observational study, 80 adult AIS patients were evaluated. Serum S100B protein levels, ONSD, and middle cerebral artery pulsatility index (MCA PI) were measured on days 1 and 3. Functional outcomes at 90 days were assessed using the modified Rankin Scale (mRS) and categorized into favourable (mRS 0-2) or unfavourable (mRS 3-6) groups. The association of demographic, clinical, laboratory, and imaging parameters with mRS outcomes was analyzed.
RESULTS: Poor mRS outcomes occurred in 82.5 % of patients. Factors significantly associated with poor outcomes were female sex, higher National Institutes of Health Stroke Scale (NIHSS) scores on days 1, 3, and 7, and larger stroke size. Receiver Operating Characteristic (ROC) curve analysis revealed that ONSD at days 1 and 3, serum S100B levels at day 1, and right MCA PI at day 1 had significant predictive value for poor mRS outcome. Multivariate analysis identified female sex, S100B on day 1, and NIHSS on days 1, 3, and 7 as independent predictors of poor mRS outcomes.
CONCLUSIONS: The combination of S100B, ONSD, and MCA PI improved the prediction of functional outcomes in critically ill AIS patients. Early S100B measurement and brain ultrasound evaluation may serve as valuable prognostic tools for guiding therapeutic decision-making. This study provides novel insights into the role of S100B and brain ultrasound in stroke outcome prediction, particularly in critically ill AIS patients.

Point-of-care ultrasound (POCUS) is an essential tool to assess and manage different pathologies in the intensive care unit, and many protocols have been proposed for its application in critical care literature. However, the brain has been overlooked in these protocols.Brain ultrasonography (BU) is easily available, and it allows a goal-directed approach thanks to its repeatability and immediate interpretation and provides a quick management and real time assessment of patients\' conditions. Based on recent studies, the increasing interest from intensivists, and the undeniable benefits of ultrasound, the main goal of this overview is to describe the main evidence and progresses in the incorporation of BU into the POCUS approach in the daily practice, and thus becoming POCUS-BU. This integration would allow a noninvasive global assessment to entail an integrated analysis of the critical care patients.

Brain injury is the main factor leading to the decline of the quality of life in premature infants. The clinical manifestations of such diseases are often diverse and complex, lacking obvious neurological symptoms and signs, and the disease progresses rapidly. Due to missed diagnosis, it is easy to miss the best treatment opportunity. Brain ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and other imaging methods can help clinicians diagnose and assess the type and extent of brain injury in premature infants to some extent, but the three methods have their own characteristics. This article briefly reviews the diagnostic value of these three methods for brain injury in premature infants.

OBJECTIVE: Infants who require extracorporeal membrane oxygenation (ECMO) therapy have an increased risk of neurological complications and mortality. Microvascular imaging (MVI) is an advanced Doppler technique that allows high-resolution visualization of microvasculature in the brain. We describe the feasibility and utility of MVI for the evaluation of cerebral microvascular perfusion in patients undergoing ECMO.
METHODS: We retrospectively analyzed brain MVI scans of neonates undergoing ECMO. Two pediatric radiologists qualitatively assessed MVI scans to determine the presence or absence of tortuosity, symmetry, heterogeneity, engorgement, and hypoperfusion of the basal ganglia-thalamus (BGT) region, as well as the presence or absence of white matter vascular engorgement and increased peri-gyral flow in the cortex. We tested the association between the presence of the aforementioned brain MVI features and clinical outcomes.
RESULTS: We included 30 patients, 14 of which were male (46.7%). The time of ECMO duration was 11.8 ± 6.9 days. The most prevalent microvascular finding in BGT was lenticulostriate vessel tortuosity (26/30, 86.7%), and the most common microvascular finding in the cortex was increased peri-gyral flow (10/24, 41.7%). Cortical white matter vascular engorgement was significantly associated with the presence of any poor outcome as defined by death, seizure, and/or cerebrovascular events on magnetic resonance imaging (p = 0.03).
CONCLUSIONS: MVI is a feasible modality to evaluate cerebral perfusion in infants undergoing ECMO. Additionally, evidence of white matter vascular engorgement after ECMO cannulation could serve as a predictor of poor outcomes in this population.

OBJECTIVE: To evaluate the use of transtemporal brain contrast-enhanced ultrasound (CEUS) to assess cerebral blood perfusion in a cohort of children without neurological disorders.
METHODS: We included pediatric patients who were undergoing a clinically-indicated CEUS study. Brain scans were performed with a Siemens Sequoia scanner and a 4V1 transducer, that was placed on the left transtemporal bone. Brain scans were performed simultaneously with the images of the clinically-indicated organ of interest. Qualitative and quantitative analysis was performed to evaluate the hemispherical blood flow at the level of the midbrain during the wash-in and wash-out phases of the time-intensity curve. Clinical charts were reviewed to evaluate post-CEUS adverse events.
RESULTS: Five patients were evaluated (mean age 5.8 ± 5.1 years). Qualitatively, more avid enhancement in the midbrain than the cortex was observed. Structures depicted ranged between the centrum semiovale at the level of the lateral ventricles and the midbrain. A quantitative analysis conducted on four patients demonstrated less avid perfusion on the contralateral (i.e. right) side, with a mean left/right ratio ranging between 1.51 and 4.07. In general, there was a steep positive wash-in slope starting at approximately 10 s after contrast injection, reaching a peak intensity around 15-26 s on the left side, and 17-29 s on the right side. No adverse events were reported.
CONCLUSIONS: Transtemporal brain CEUS is feasible and safe in the pediatric population and allows qualitative and quantitative assessment of cerebral perfusion.