Increase of liver stiffness and altered bile acid metabolism after triple CFTR modulator initiation in children and young adults with cystic fibrosis.

BACKGROUND: Novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (elexacaftor/tezacaftor/ivacaftor-ETI) promise clinically significant and sustained improvements for patients with cystic fibrosis (CF). In this study, we investigated the impact of ETI therapy on liver stiffness and bile acid metabolism in a cohort of children and young adults with CF. METHODS: A prospective observational study (NCT05576324) was conducted from September 2020 to November 2021 enrolling CF patients naive to ETI. Standard laboratory chemistry, sweat test, lung function, share wave velocity (SWV) derived by acoustic radiation force impulse imaging (ARFI) and serum bile acid profiles were assessed before and 6 months after induction of ETI therapy. RESULTS: A total of 20 patients (10 aged <20 years) completed the study. While lung function and BMI improved after ETI therapy, ARFI SWV increased in CF patients <20 years of age (from 1.27 to 1.43 m/s, p = 0.023). Bile acid (BA) profiles revealed a decrease in unconjugated (5.75 vs 1.46, p = 0.007) and increase in glycine-conjugated derivatives (GCDCA) (4.79 vs 6.64 p = 0.016). There was a positive correlation between ARFI SWV values and GCDCA (r = 0.80, p < 0.0001). Glycine-conjugated BA provided high diagnostic accuracy to predict increased ARFI measurements (AUC 0.90) and clinical (Colombo) CFLD grading (AUC 0.97). CONCLUSIONS: ARFI SWV and bile acid profiles provide evidence for early increase in liver stiffness and altered bile acid metabolism in young CF patients after initiation of ETI and may serve as synergistic measures for detection of hepatic complications during ETI therapy.

Transfontanellar Contrast-enhanced US for Intraoperative Imaging of Cerebral Perfusion during Neonatal Arterial Switch Operation.

Background Brain injury and subsequent neurodevelopmental disorders are major determinants for later-life outcomes in neonates with transposition of the great arteries (TGA). Purpose To quantitatively assess cerebral perfusion in neonates with TGA undergoing arterial switch operation (ASO) using transfontanellar contrast-enhanced US (T-CEUS). Materials and Methods In a prospective single-center cross-sectional diagnostic study, neonates with TGA scheduled for ASO were recruited from February 2018 to February 2020. Measurements were performed at five time points before, during, and after surgery (T1-T5), and 11 perfusion parameters were derived per cerebral hemisphere. Neonate clinical characteristics, heart rate, mean arterial pressure, central venous pressure, near-infrared spectroscopy, blood gas analyses, ventilation time, time spent in the pediatric intensive care unit, and time in hospital were correlated with imaging parameters. Analysis of variance or a mixed-effects model were used for groupwise comparisons. Results A total of 12 neonates (mean gestational age, 39 6/7 weeks ± 1/7 [SD]) were included and underwent ASO a mean of 6.9 days ± 3.4 after birth. When compared with baseline values, T-CEUS revealed a longer mean time-to-peak (right hemisphere, 4.3 seconds ± 2.1 vs 17 seconds ± 6.4 [P < .001]; left hemisphere, 4.0 seconds ± 2.3 vs 21 seconds ± 8.7 [P < .001]) and rise time (right hemisphere, 3.5 seconds ± 1.7 vs 11 seconds ± 5.1 [P = .002]; left hemisphere, 3.4 seconds ± 2.0 vs 22 seconds ± 7.8 [P = .004]) in both cerebral hemispheres during low-flow cardiopulmonary bypass and hypothermia (T4) for all neonates. Neonate age at surgery negatively correlated with T-CEUS parameters during ASO, as calculated with the area under the flow curve (AUC) during wash-in (R = -0.60, P = .020), washout (R = -0.82, P = .002), and both wash-in and washout (R = -0.79, P = .004). Mean AUC values were lower in neonates older than 7 days compared with younger neonates during wash-in ([87 arbitrary units {au} ± 77] × 102 vs [270 au ± 164] × 102, P = .049]), washout ([15 au ± 11] × 103 vs [65 au ± 38] × 103, P = .020]) and both wash-in and washout ([24 au ± 18] × 103 vs [92 au ± 53] × 103, P = .023). Conclusion Low-flow hypothermic conditions resulted in reduced cerebral perfusion, as measured with transfontanellar contrast-enhanced US, which inversely correlated with age at surgery. Clinical trial registration no. NCT03215628 © RSNA, 2022 Online supplemental material is available for this article.

Maternal SARS-CoV-2 infection during pregnancy: possible impact on the infant.

The risk and potential consequences of mother-to-child transmission of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) during pregnancy are still a matter of debate. We studied the impact of SARS-CoV-2 infection on 56 complete households, including 27 newborns whose mothers were pregnant when exposed to the virus. Two PCR-confirmed perinatal SARS-CoV-2 transmissions with mild symptoms in affected neonates were recorded. In addition, we observed a severe eye malformation (unilateral microphthalmia, optic nerve hypoplasia, and congenital retinopathy) associated with maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development. This embryopathy could not be explained by other infectious agents, genetic factors, drug use, or maternal disease during pregnancy. Eight other women with a history of SARS-CoV-2 infection prior to gestational week 12, however, delivered healthy infants.Conclusion: The repeated occurrence of mother-to-child transmission in our cohort with risks that remain incompletely understood, such as long-term effects and the possibility of an embryopathy, should sensitize researchers and stimulate further studies as well as support COVID-19 vaccination recommendations for pregnant women. Trial registration number: NCT04741412. Date of registration: November 18, 2020 What is Known: •Materno-fetal transmission of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) during pregnancy has rarely been reported so far, but was demonstrated in isolated cases. What is New: •In a study of complete households with documented SARS-CoV-2 infection, including a cohort of pregnant women, we observed perinatal coronavirus transmission at a higher frequency than expected. •We also describe a newborn boy with an eye malformation reminiscent of rubella embryopathy but associated with early gestation SARS-CoV-2 infection of his mother. •A coronavirus-related embryopathy, reported here for the first time, is a finding that requires further investigation.

Pediatric Buried Bumper Syndrome: Diagnostic Validity of Transabdominal Ultrasound and Artificial Intelligence.

PURPOSE: Buried bumper syndrome (BBS) is a severe complication of percutaneous endoscopic gastrostomy (PEG) resulting from overgrowth of gastric mucosa and penetration of the inner holding plate into the gastric wall. The aim of this study was to evaluate the diagnostic value of transabdominal ultrasound (US) in comparison to an artificial intelligence (AI) model for the diagnosis of BBS in children. MATERIALS AND METHODS: In this monocentric retrospective study, pediatric US data concerning BBS from a ten-year period (2009-2019) were analyzed. US findings were compared to a clinical multiparameter-based AI model and reference standard endoscopy. Clinical risk factors for the occurrence of pediatric BBS were determined. RESULTS: In n = 121 independent examinations of n = 82 patients, the placement of the inner holding plate of the PEG was assessed by US. In n = 18 cases BBS was confirmed. Recall and precision rates were 100 % for US and 88 % for the AI-based assessment. Risk factors for the occurrence of BBS were mobilization problems of the PEG (rs = 0.66, p < 0.001), secretion/exudation (rs = 0.29, p = 0.002), time between 1st PEG placement and US (rs = 0.38, p < 0.001), and elevated leukocyte count (rs = 0.24, p = 0.016). CONCLUSION: Transabdominal US enables correct, rapid, and noninvasive diagnosis of BBS in pediatric patients. Preceding AI models could aid during diagnostic workup. To avoid unnecessary invasive procedures, US could be considered as a primary diagnostic procedure in suspected BBS. .

Contrast-enhanced ultrasound of the pediatric brain.

Brain contrast-enhanced ultrasound (CEUS) is an emerging application that can complement gray-scale US and yield additional insights into cerebral flow dynamics. CEUS uses intravenous injection of ultrasound contrast agents (UCAs) to highlight tissue perfusion and thus more clearly delineate cerebral pathologies including stroke, hypoxic-ischemic injury and focal lesions such as tumors and vascular malformations. It can be applied not only in infants with open fontanelles but also in older children and adults via a transtemporal window or surgically created acoustic window. Advancements in CEUS technology and post-processing methods for quantitative analysis of UCA kinetics further elucidate cerebral microcirculation. In this review article we discuss the CEUS examination protocol for brain imaging in children, current clinical applications and future directions for research and clinical uses of brain CEUS.

Contrast-enhanced ultrasound of benign and malignant liver lesions in children.

Contrast-enhanced ultrasound (CEUS) is increasingly being used in children. One of the most common referrals for CEUS performance is characterization of indeterminate focal liver lesions and follow-up of known liver lesions. In this setting, CEUS is performed with intravenous administration of ultrasound contrast agents (UCAs). When injected into a vein, UCA microbubbles remain confined within the vascular network until they dissipate. Therefore, visualization of UCA within the tissues and lesions corresponds to true blood flow. CEUS enables continuous, real-time observation of the enhancement pattern of a focal liver lesion, allowing in most cases for a definite diagnosis and obviating the need for further cross-sectional imaging or other interventional procedures. The recent approval of Lumason (Bracco Diagnostics, Monroe Township, NJ) for pediatric liver CEUS applications has spurred the widespread use of CEUS. In this review article we describe the role of CEUS in pediatric liver applications, focusing on the examination technique and interpretation of main imaging findings of the most commonly encountered benign and malignant focal liver lesions. We also compare the diagnostic performance of CEUS with other imaging modalities for accurate characterization of focal liver lesions.

Contrast-enhanced ultrasound of the small organs in children.

In pediatric and adult populations, intravenous contrast-enhanced ultrasound (CEUS) remains off-label for imaging of organs other than the liver and heart. This limited scope inhibits potential benefits of the new modality from a more widespread utilization. Yet, CEUS is potentially useful for imaging small organs such as the thyroid gland, lymph nodes, testes, ovaries and uterus, with all having locations and vasculature favorable for this type of examination. In the adult population, the utility of CEUS has been demonstrated in a growing number of studies for the evaluation of these small organs. The aim of this article is to present a review of pediatric CEUS of the thyroid gland, lymph nodes, testes, ovaries and uterus as well as to draw from the adult literature indications for possible applications in children.

Time Tracking of Standard Ultrasound Examinations in Pediatric Hospitals and Pediatric Medical Practices - A Multicenter Study by the Pediatric Section of the German Society of Ultrasound in Medicine (DEGUM).

PURPOSE: Ultrasonography is the primary imaging modality in pediatrics but still lacks sufficient reimbursement in Germany. In this multicenter study, national data for the duration of standard ultrasound in pediatrics were systematically documented in order to specify the actual time required. MATERIALS AND METHODS: N = 10 hospitals (N = 5 university hospitals, N = 5 non-university hospitals) and N = 3 medical practices in Germany recorded the entire process of an ultrasound examination in a special protocol developed by the Pediatric Section of the DEGUM. The duration of each of seven single steps during ultrasonography (from data input to final discussion of the results) of different organ systems was logged. RESULTS: In total, N = 2118 examinations from different organ systems were recorded. N = 10 organ systems were examined frequently (> 30 times). The total duration of an ultrasound examination was statistically significantly longer in hospitals compared to medical practices (median (IQR) 27 min. (18-38) vs. 12 min. (9-17), p < 0.001). The "hands-on" patient time was approximately one half of the total required time in both settings (49.9 % vs. 48.9 %). Ultrasonography of the abdomen and brain lasted longer in university hospitals than in non-university hospitals (p < 0.001, and p = 0.04, respectively). Cooperation and age did not uniformly correlate with the total duration. CONCLUSION: This study provides novel comprehensive national data for the duration of standardized ultrasound examinations of children and adolescents in Germany. These data are essential for a further evaluation of the economic costs and should support better remuneration in the future.

European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB): An Update on the Pediatric CEUS Registry on Behalf of the "EFSUMB Pediatric CEUS Registry Working Group".

The European Federation of Ultrasound in Medicine and Biology (EFSUMB) created the "EFSUMB Pediatric Registry" (EFSUMB EPR) with the purpose of collecting data regarding the intravenous application of pediatric contrast-enhanced ultrasound (CEUS). The primary aim was to document the current clinical practice and usefulness of the technique and secondarily to assess CEUS safety in children. We issue the preliminary results of this database and examine the overall practice of CEUS in children in Europe.

Microbubbles in macrocysts - Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report.

BACKGROUND: Congenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application. CASE PRESENTATION: Here we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432. CONCLUSIONS: Contrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

Intrauterine Growth Restriction (IUGR) Induces Signs of Subclinical Atherosclerosis in 6-Year-Old Infants Despite Absence Of Excessive Growth.

Background Postnatal catch-up growth and rapid weight gain after intrauterine growth restriction (IUGR) seem to increase the risk for later disease. This study aimed to compare features of the metabolic syndrome early in life between IUGR and appropriate for gestational age (AGA) infants. Patients Data for 9 infants with IUGR defined by a birth weight<10th percentile and ultrasound-proven placental insufficiency and 11 AGA children were available. Method Postnatal growth, auxological, cardiovascular, and metabolic parameters up to a chronological age of 6 years were assessed: Fasting serum concentrations of LDL-cholesterol, insulin, leptin, IGF-I, DHEAS, skinfold thicknesses, blood pressure, and mean carotid intima-media thickness (cIMT). Results All IUGR infants showed catch-up growth, although mean BMI SDS and total subcutaneous fat mass at the age of 6 years were still slightly lower compared to the AGA cohort. Reduced serum leptin concentrations were observed in IUGR infants (p=0.02), whereas no significant difference was found for IGF-I, insulin, LDL-cholesterol and DHEAS concentrations. Mean cIMT was significantly higher in IUGR infants (p<0.05). Mean arterial pressure did no differ. Discussion and Conclusion In 6-year-old IUGR infants with catch-up growth, who still had a slightly reduced BMI SDS compared to the AGA group, signs of subclinical atherosclerosis were detectable suggesting that cardiovascular risk in IUGR may be present even in the absence of excessive growth.

Ultrasound in Pediatric Inflammatory Bowel Disease-A Review of the State of the Art and Future Perspectives.

Inflammatory bowel disease (IBD) comprises a group of relapsing, chronic diseases of the gastrointestinal tract that, in addition to adults, can affect children and adolescents. To detect relapses of inflammation, these patients require close observation, frequent follow-up, and therapeutic adjustments. While reference standard diagnostics include anamnestic factors, laboratory and stool sample assessment, performing specific imaging in children and adolescents is much more challenging than in adults. Endoscopic and classic cross-sectional imaging modalities may be invasive and often require sedation for younger patients. For this reason, intestinal ultrasound (IUS) is becoming increasingly important for the non-invasive assessment of the intestine and its inflammatory affection. In this review, we would like to shed light on the current state of the art and provide an outlook on developments in this field that could potentially spare these patients more invasive follow-up procedures.

Monitoring spinal muscular atrophy with three-dimensional optoacoustic imaging.

BACKGROUND: Spinal muscular atrophy is a progressive neuromuscular disorder and among the most frequent genetic causes of infant mortality. While recent advancements in gene therapy provide the potential to ameliorate the disease severity, there is currently no modality in clinical use to visualize dynamic pathophysiological changes in disease progression and regression after therapy. METHODS: In this prospective diagnostic clinical study, ten pediatric patients with spinal muscular atrophy and ten age- and sex-matched controls have been examined with three-dimensional optoacoustic imaging and clinical standard examinations to compare the spectral profile of muscle tissue and correlate it with motor function (ClinicalTrials.gov: NCT04115475). FINDINGS: We observed a reduced optoacoustic signal in muscle tissue of pediatric patients with spinal muscular atrophy. The reduction in signal intensity correlated with disease severity as assessed by grayscale ultrasound and standard motor function tests. In a cohort of patients who received disease-modifying therapy prior to the study, the optoacoustic signal intensity was similar to healthy controls. CONCLUSIONS: This translational study provides early evidence that three-dimensional optoacoustic imaging could have clinical implications in monitoring disease activity in spinal muscular atrophy. By visualizing and quantifying molecular changes in muscle tissue, disease progression and effects of gene therapy can be assessed in real time. FUNDING: The project was funded by ELAN Fonds (P055) at the University Hospital of the Friedrich-Alexander-Universität (FAU) Erlangen-Nurnberg to A.P.R.

Multispectral optoacoustic tomography enables assessment of disease activity in paediatric inflammatory bowel disease.

Multispectral optoacoustic tomography (MSOT) allows non-invasive molecular disease activity assessment in adults with inflammatory bowel disease (IBD). In this prospective pilot-study, we investigated, whether increased levels of MSOT haemoglobin parameters corresponded to inflammatory activity in paediatric IBD patients, too. 23 children with suspected IBD underwent MSOT of the terminal ileum and sigmoid colon with standard validation (e.g. endoscopy). In Crohn`s disease (CD) and ulcerative colitis (UC) patients with endoscopically confirmed disease activity, MSOT total haemoglobin (HbT) signals were increased in the terminal ileum of CD (72.1 ± 13.0 a.u. vs. 32.9 ± 15.4 a.u., p = 0.0049) and in the sigmoid colon of UC patients (62.9 ± 13.8 a.u. vs. 35.1 ± 16.3 a.u., p = 0.0311) as compared to controls, respectively. Furthermore, MSOT haemoglobin parameters correlated well with standard disease activity assessment (e.g. SES-CD and MSOT HbT (rs =0.69, p = 0.0075). Summarizing, MSOT is a novel technology for non-invasive molecular disease activity assessment in paediatric patients with inflammatory bowel disease.

Premature birth associated with a favorable course in gestational alloimmune liver disease (GALD): A case report.

Gestational alloimmune liver disease (GALD) is a rare neonatal disorder with high mortality and morbidity. The patients come to caregivers' attention aged a few hours or days. The disease manifests as acute liver failure with or without siderosis. The differential diagnosis of neonatal acute liver failure (NALF) is broad, including mainly immunologic, infectious, metabolic and toxic disorders. The most common cause, however, is GALD followed by herpes simplex virus (HSV) infection. The best suited pathophysiological paradigm of GALD is that of a maternofetal alloimmune disorder. State of the art treatment combines intravenously administered immunoglobulin (IVIG) with exchange transfusion (ET). We report an infant born at 35 + 2 weeks' gestation in whom GALD had a favorable course, of interest because premature birth in our patient may have exerted protective aspects and lessened morbidity in that intrauterine exposure to maternal complement-fixing antibodies was shortened. The diagnosis of GALD was challenging and difficult. We suggest a modified diagnostic algorithm combining clinical findings with histopathologic findings in liver and lip mucosa and, if available, on abdominal magnetic resonance imaging-study focusing on the liver, spleen, and pancreas. This diagnostic workup must be followed by ET and subsequent administration of IVIG without delay.

Hybrid reflected-ultrasound computed tomography versus B-mode-ultrasound for muscle scoring in spinal muscular atrophy.

BACKGROUND AND PURPOSE: Novel light- and sound-based technologies like multispectral optoacoustic tomography (MSOT) with co-registered reflected-ultrasound computed tomography (RUCT) could add additional value to conventional ultrasound (US) for disease phenotyping in pediatric spinal muscular atrophy (SMA). The aim of this study was to investigate the quality of RUCT compared to US for qualitative and quantitative assessment of imaging neuromuscular disorders. METHODS: Subanalyzing the MSOT SMA study, 288 RUCT and 276 US images from 10 SMA patients (mean age 9.0 ± 3.7) and 10 gender- and age-matched healthy volunteers (HV; mean age 8.7 ± 4.3) were analyzed for quantitative (grayscale levels [GSLs]) and qualitative (echogenicity, distribution pattern, Heckmatt scale, and muscle texture) muscle changes. RUCT and US measures were further correlated with clinical standard motor outcomes. RESULTS: Quantitative agreement using GSLs revealed significantly higher GSLs in muscles of SMA patients compared to healthy muscles in both techniques (US mean GSL [SD] SMA vs. HV: 110.70 [27.8] vs. 68.85 [19.2], p < .0001; RUCT mean GSL [SD] SMA vs. HV: 91.81 [21.8] vs. 59.86 [8.2], p < .0001) with good correlation with motor outcome tests, respectively. Qualitative agreement between methods for muscle composition was excellent for differentiation of pathological versus healthy muscles, echogenicity, and distribution pattern, moderate for Heckmatt scale, and poor for muscle texture. CONCLUSIONS: The data suggest that RUCT may allow the assessment of basic qualitative and quantitative measures for muscular diseases with comparable results to conventional US.

Multispectral optoacoustic tomography of the human intestine - temporal precision and the influence of postprandial gastrointestinal blood flow.

Multispectral optoacoustic tomography (MSOT) holds great promise as a non-invasive diagnostic tool for inflammatory bowel diseases. Yet, reliability and the impact of physiological processes during fasting and after food intake on optoacoustic signals have not been studied. In the present investigator initiated trial (NCT05160077) the intestines of ten healthy subjects were examined by MSOT at eight timepoints on two days, one fasting and one after food intake. While within-timepoint and within-day reproducibility were good for single wavelength 800 nm and total hemoglobin (ICC 0.722-0.956), between-day reproducibility was inferior (ICC -0.137 to 0.438). However, temporal variability was smaller than variation between individuals (coefficients of variation 8.9%-33.7% vs. 17.0%-48.5%). After food intake and consecutive increased intestinal circulation, indicated by reduced resistance index of simultaneous Doppler ultrasound, optoacoustic signals did not alter significantly. In summary, this study demonstrates high reliability and temporal stability of MSOT for imaging the human intestine during fasting and after food intake.

Contrast-Enhanced Multispectral Optoacoustic Tomography for Functional Assessment of the Gastrointestinal Tract.

Real-time imaging and functional assessment of the intestinal tract and its transit pose a significant challenge to conventional clinical diagnostic methods. Multispectral optoacoustic tomography (MSOT), a molecular-sensitive imaging technology, offers the potential to visualize endogenous and exogenous chromophores in deep tissue. Herein, a novel approach using the orally administered clinical-approved fluorescent dye indocyanine green (ICG) for bedside, non-ionizing evaluation of gastrointestinal passage is presented. The authors are able to show the detectability and stability of ICG in phantom experiments. Furthermore, ten healthy subjects underwent MSOT imaging at multiple time points over eight hours after ingestion of a standardized meal with and without ICG. ICG signals can be visualized and quantified in different intestinal segments, while its excretion is confirmed by fluorescent imaging of stool samples. These findings indicate that contrast-enhanced MSOT (CE-MSOT) provides a translatable real-time imaging approach for functional assessment of the gastrointestinal tract.

Equal cerebral perfusion during extended aortic coarctation repair.

OBJECTIVES: Aortic coarctation with distal aortic arch hypoplasia can be effectively addressed by coarctation resection with extended end-to-end-anastomosis (REEEA). Particularly, when unilateral cerebral perfusion (UCP) is established by clamping of left-sided supra-aortic vessels, the extent of cerebral blood flow distribution during repair remains undetermined, so far. Transfontanellar contrast-enhanced ultrasound (T-CEUS) can be utilized for real-time visualization and quantitative evaluation of cerebral blood flow. This study quantitatively evaluates cerebral perfusion during REEEA by using intraoperative T-CEUS. METHODS: In a prospective study, 9 infants with open fontanelle undergoing REEEA [median age: 13 days (range 1-34) and median weight 3.1 kg (range 2.2-4.4)] were intraoperatively examined with T-CEUS at 3 consecutive time-points: before skin incision, during UCP and after skin suture. A software-based analysis of 11 parameters was used for data evaluation. Absolute and relative blood flow in contralateral hemispheres was measured in side-by-side comparison, and referenced to baseline measurements. RESULTS: No side-depend absolute or relative cerebral perfusion differences were found during REEEA, except for an increased relative 'wash-out-rate' (P = 0.0013) in favour of the right hemisphere after surgery. Compared to ipsilateral baseline levels, 'rise time' was transiently increased in right (P = 0.0277) and 'time-to-peak' in both hemispheres (right: P = 0.0403 and left: P = 0.0286), all during UCP. CONCLUSIONS: The use of T-CEUS provided evidence for homogenous distribution of contrast agent in both hemispheres during UCP. T-CEUS can be utilized for the postprocedural evaluation of cerebral perfusion during congenital cardiac surgery. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov Unique, Identifier: NCT03215628.