Clinical presentation of 13 children with alkaptonuria.

Until now, only a few studies have focused on the early onset of symptoms of alkaptonuria (AKU) in the pediatric population. This prospective, longitudinal study is a comprehensive approach to the assessment of children with recognized AKU during childhood. The study includes data from 32 visits of 13 patients (five males, eight females; age 4-17 years) with AKU. A clinical evaluation was performed with particular attention to eye, ear, and skin pigmentation, musculoskeletal complaints, magnetic resonance imaging (MRI), and ultrasound (US) imaging abnormalities. The cognitive functioning and adaptive abilities were examined. Molecular genetic analyses were performed. The most common symptoms observed were dark urine (13/13), followed by joint pain (6/13), and dark ear wax (6/13). In 4 of 13 patients the values obtained in the KOOS-child questionnaire were below the reference values. MRI and US did not show degenerative changes in knee cartilages. One child had nephrolithiasis. Almost half of the children with AKU (5/13) presented deficits in cognitive functioning and/or adaptive abilities. The most frequent HGD variants observed in the patients were c.481G>A (p.Gly161Arg) mutation and the c.240A>T (p.His80Gln) polymorphism. The newly described allele of the HGD gene (c.948G>T, p.Val316Phe) which is potentially pathogenic was identified.

Optimization of Mechanical Indices for Clinical Contrast-Enhanced Ultrasound.

The quality of contrast-enhanced ultrasound (CEUS) imaging performed with high-frequency convex and linear transducers is often suboptimal. A common solution to improving the microbubble signal is by increasing the volume of the ultrasound contrast agent being administered. An alternative technique to improve the signal from the contrast agent is to adjust the mechanical index (MI). This study aimed to compare the manufacturer's default MI to an optimal MI (as determined by the best contrast-to-tissue ratio) for improving the CEUS image quality using linear and convex transducers. This study found that in most cases, the default CEUS MI setting by the manufacturer is often suboptimal, and increasing the MI is necessary to improve the contrast-to-tissue ratio and image quality. The MI can be modified by the clinician during the study to improve the quality of the clinical CEUS examination.

Contrast-enhanced ultrasound of pediatric lungs.

In addition to radiography, ultrasound (US) has long proved to be a valuable imaging modality to evaluate the pediatric lung and pleural cavity. Its many inherent advantages, including real-time performance, high spatial resolution, lack of ionizing radiation and lack of need for sedation make it preferable over other imaging modalities such as CT. Since the introduction of ultrasound contrast agents (UCAs), contrast-enhanced ultrasound (CEUS) has become a valuable complementary US technique, with many well-established uses in adults and evolving uses in children. Lung CEUS applications are still not licensed and are performed off-label, although the added value of CEUS in certain clinical scenarios is increasingly reported. The limited evidence of CEUS in the evaluation of pediatric lungs focuses primarily on community-acquired pneumonia and its complications. In this clinical setting, CEUS is used to confidently and accurately diagnose necrotizing pneumonia and to delineate pleural effusions and empyema. In addition to intravenous use, UCAs can be administered directly into the pleural cavity through chest catheters to improve visualization of loculations within a complex pleural effusion, which might necessitate fibrinolytic therapy. The purpose of this paper is to present the current experience on pediatric lung CEUS and to suggest potential additional uses that can be derived from adult studies.

Translational research in pediatric contrast-enhanced ultrasound.

The role of contrast-enhanced ultrasound (CEUS) imaging is being widely explored by various groups for its use in the pediatric population. Clinical implementation of new diagnostic or therapeutic techniques requires extensive and meticulous preclinical testing and evaluation. The impact of CEUS will be determined in part by the extent to which studies are oriented specifically toward a pediatric population. Rather than simply applying principles and techniques used in the adult population, these studies are expected to advance and augment preexisting knowledge with pediatric-specific information. To further develop this imaging modality for use in children, pediatric-focused preclinical research is essential. In this paper we describe the development and implementation of the pediatric-specific preclinical animal and phantom models that are being used to evaluate CEUS with the goal of clinical translation to children.

Contrast-enhanced ultrasound: a comprehensive review of safety in children.

Contrast-enhanced ultrasound (CEUS) has been increasingly used in pediatric radiology practice worldwide. For nearly two decades, CEUS applications have been performed with the off-label use of gas-containing second-generation ultrasound contrast agents (UCAs). Since 2016, the United States Food and Drug Administration (FDA) has approved the UCA Lumason for three pediatric indications: the evaluation of focal liver lesions and echocardiography via intravenous administration and the assessment of vesicoureteral reflux via intravesical application (contrast-enhanced voiding urosonography, ceVUS). Prior to the FDA approval of Lumason, numerous studies with the use of second-generation UCAs had been conducted in adults and children. Comprehensive protocols for clinical safety evaluations have demonstrated the highly favorable safety profile of UCA for intravenous, intravesical and other intracavitary uses. The safety data on CEUS continue to accumulate as this imaging modality is increasingly utilized in clinical settings worldwide. As of August 2021, 57 pediatric-only original research studies encompassing a total of 4,518 children with 4,906 intravenous CEUS examinations had been published. As in adults, there were a few adverse events; the majority of these were non-serious, although very rarely serious anaphylactic reactions were reported. In the published pediatric-only intravenous CEUS studies included in our analysis, the overall incidence rate of serious adverse events was 0.22% (10/4,518) of children and 0.20% (10/4,906) of all CEUS examinations. Non-serious adverse events from the intravenous CEUS were observed in 1.20% (54/4,518) of children and 1.10% (54/4,906) of CEUS examinations. During the same time period, 31 studies with the intravesical use of UCA were conducted in 12,362 children. A few non-serious adverse events were encountered (0.31%; 38/12,362), but these were most likely attributable to the bladder catheterization rather than the UCA. Other developing clinical applications of UCA in children, including intracavitary and intralymphatic, are ongoing. To date, no serious adverse events have been reported with these applications. This article reviews the existing pediatric CEUS literature and provides an overview of safety-related information reported from UCA uses in children.

Contrast-enhanced ultrasound of the kidneys and adrenals in children.

Pediatric applications of contrast-enhanced ultrasound (CEUS) are growing. Evaluation of the kidneys and adrenal glands in children using intravenous administration of US contrast agents, however, is still an off-label indication. Pediatric CEUS applications for kidneys are similar to those in adults, including ischemic disorders, pseudo- versus real tumors, indeterminate lesions, complex cystic lesions, complicated pyelonephritis, and abscesses. CEUS applications for evaluation of adrenal glands in children are limited, mainly focusing on the assessment and follow-up of adrenal trauma and the differentiation between an adrenal hemorrhage and a mass. This review addresses the current experience in pediatric CEUS of the kidneys and adrenal glands. By extrapolating the established knowledge for US contrast evaluations in the adult kidney to the pediatric context we can note opportunities for CEUS clinical use in children.

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.

Contrast-enhanced voiding urosonography part 2: urethral imaging.

Ultrasound (US) has been increasingly used as an important imaging tool to assess the urethra in children. The earliest reports of pediatric urethral sonography involved imaging the urethra in a non-voiding state, during physiological voiding of urine, and after instillation of saline. The introduction of US contrast agents has continued to improve visualization of urethral anatomy. Contrast-enhanced US of the urethra can be performed during the voiding phase of a standard contrast-enhanced voiding urosonography (ceVUS) exam or with retrograde instillation of a contrast agent, depending on the exam indication. Both techniques are well tolerated by children and provide accurate information about urethral pathology and periurethral soft tissues. This article reviews the technical aspects and imaging findings of urethral pathologies in children using contrast-enhanced US, both by the voiding and retrograde instillation techniques.

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.

Improved Diagnostic Sensitivity of Bowel Disease of Prematurity on Contrast-Enhanced Ultrasound.

Bowel diseases of prematurity, including necrotizing enterocolitis, are dreaded ailments of neonates. Early diagnosis is difficult, with clinical and radiographic findings often inconclusive. We present a novel use of contrast-enhanced ultrasound in detection of pediatric bowel disease. Early identification of compromised blood flow or an at-risk bowel can be quantitatively detected and monitored. This ability has implications for guidance of emerging therapies, allowing targeting of inflammation. These findings represent an advancement in detection of bowel disease in neonates.

Relative Cerebral Blood Transit Time Decline and Neurological Improvement in Patients After Internal Carotid Artery Stenting.

In this study we hypothesized that the alleviation of neurological symptoms long after internal carotid artery (ICA) stenting may be related to sustained improvement of cerebral perfusion. Thirty-four subjects (F/M; 15/19) with >70% stenosis of a single internal carotid artery and neurological symptoms, who underwent a carotid artery stenting procedure, were studied. Brain computed tomography perfusion (CTP) imaging was performed before and 3 years after ICA stenting. The following relative variables were compared: cerebral blood flow (rCBF), cerebral blood volume (rCBV), mean transit time (rMTT), time to peak (rTTP), and permeability surface area product (rPS). A survey also was conducted to compare the patients' clinical symptoms. Overall, we found that a trend toward rMTT decline was the only persisting change after ICA stenting. We then stratified the patients into the subgroups of <2%, 2-5%, and > 5% rMTT decline and found that those with a rMTT decline >2% reported a prominent reduction in subjective clinical symptoms such as headache, dizziness, tinnitus, blurred vision, transient blindness, a sense of gravity of the head, and pain in the eyeballs. We conclude that a shortened mean rMTT, likely reflecting improved cerebral microcirculation, underlies the improvement of neurological symptoms in patients with ICA stenosis.

Reduction of cortical oxygenation in chronic kidney disease: evidence obtained with a new analysis method of blood oxygenation level-dependent magnetic resonance imaging.

BACKGROUND: Determinations of renal oxygenation by blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in chronic kidney disease (CKD) patients have given heterogeneous results, possibly due to the lack of a reproducible method to analyse BOLD-MRI. It therefore remains uncertain whether patients with CKD have a reduced renal tissue oxygenation. We developed a new method to analyse BOLD-MRI signals and applied it to CKD patients and controls. METHODS: MRI was performed under standardized conditions before and 15 min after IV furosemide in 104 CKD patients, 61 hypertensives and 42 controls. MR images were analysed with the new twelve-layer concentric objects method (TLCO) that divides renal parenchyma in 12 layers of equal thickness. The mean R2* value of each layer was reported, along with the change in R2* between successive layers, as measured by the slope steepness of the relevant curve. RESULTS: Inter-observer variability was 2.3 ± 0.9%, 1.9 ± 0.8% and 3.0 ± 2.3% in, respectively, controls, moderate and severe CKD. The mean R2* of the outer (more cortical) layers was significantly higher in CKD, suggesting lower cortical oxygenation as compared with controls. In CKD patients, the response to furosemide was blunted in the inner (more medullary) layers, and the R2* slope was flatter. In multivariable regression analysis, the R2* slope correlated positively with estimated glomerular filtration rate (eGFR) in patients with an eGFR <90 mL/min/1.73 m2 (P < 0.001). CONCLUSIONS: Using the new TLCO method, we confirm the hypothesis that renal cortical oxygenation is reduced in CKD in humans, and that the level of cortical oxygenation correlates with CKD severity.

Visualizing Carotid Bodies With Doppler Ultrasound Versus CT Angiography: Preliminary Study.

OBJECTIVE: The purpose of this article is to evaluate the utility of ultrasound in identifying carotid bodies (CBs) in patients with drug-resistant arterial hypertension. SUBJECTS AND METHODS: We enrolled 13 patients with drug-resistant hypertension into a trial for surgical CB excision. CT angiography (CTA) and Doppler ultrasound (DUS) of the cervical arteries were performed before surgery. CBs were identified in a blind manner at both CTA and DUS. CBs were defined at CTA as ovoid avidly enhancing structures at the inferomedial aspect of the carotid bifurcation. At DUS, CBs were defined as ovoid solid structures in the inferomedial aspect of the bifurcation. RESULTS: CBs were identified in 12 of 13 patients (23/26 sides) using CTA and in 11 of 13 patients (18/26 sides) using DUS. Identification of CB with DUS and CTA correlated in 17 of 18 cases; in one instance, CB was identified with DUS but not CTA. There was no statistically significant difference in size and volume of CB measured by both methods. CONCLUSION: Noncarcinogenic CBs can be visualized using DUS, with good correlation of size and location compared with CTA. The findings show that DUS can be reliably used to further examine the role of CBs in cardiovascular disorders and can be used in conjunction with therapies that target CBs.

Role of Contrast-Enhanced Ultrasound (CEUS) in Paediatric Practice: An EFSUMB Position Statement.

The use of contrast-enhanced ultrasound (CEUS) in adults is well established in many different areas, with a number of current applications deemed "off-label", but the use supported by clinical experience and evidence. Paediatric CEUS is also an "off-label" application until recently with approval specifically for assessment of focal liver lesions. Nevertheless there is mounting evidence of the usefulness of CEUS in children in many areas, primarily as an imaging technique that reduces exposure to radiation, iodinated contrast medium and the "patient-friendly" circumstances of ultrasonography. This position statement of the European Federation of Societies in Ultrasound and Medicine (EFSUMB) assesses the current status of CEUS applications in children and makes suggestions for further development of this technique.

Carotid Artery Stenting and Blood-Brain Barrier Permeability in Subjects with Chronic Carotid Artery Stenosis.

Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population. Forty subjects (23 males) with stenosis of >70% within a single internal carotid artery and neurological symptoms who underwent a carotid artery stenting procedure were investigated. Differences in the following computed tomography perfusion (CTP) parameters were compared before and after surgery: global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and PS. PS acquired by CTP is used to measure the permeability of the BBB to contrast material. In all baseline cases, the CBF and CBV values were low, while MTT and TTP were high on both the ipsi- and contralateral sides compared to reference values. PS was approximately twice the normal value. CBF was higher (+6.14%), while MTT was lower (-9.34%) on the contralateral than on the ipsilateral side. All perfusion parameters improved after stenting on both the ipsilateral (CBF +22.66%; CBV +18.98%; MTT -16.09%, TTP -7.62%) and contralateral (CBF +22.27%, CBV +19.72%, MTT -14.65%, TTP -7.46%) sides. PS decreased by almost half: ipsilateral -48.11%, contralateral -45.19%. The decline in BBB permeability was symmetrical on the ipsi- and contralateral sides to the stenosis. Augmented BBB permeability can be controlled by surgical intervention in humans.

Renal tissue oxygenation in children with chronic kidney disease due to vesicoureteral reflux.

BACKGROUND: Vesicoureteral reflux (VUR) is a frequent cause of chronic kidney disease (CKD) in children. Using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), we measured cortical and medullary oxygenation in children with CKD due to VUR and compared the results to those obtained on healthy controls. METHOD: The study population comprised 37 children (19 with CKD due to VUR and 18 healthy age-matched controls). BOLD-MRI was performed before and after furosemide treatment. MR images were analyzed with the region-of-interest (ROI) technique to assess the mean R2* values (=1/T2*) of the cortex and medulla of each kidney and with the concentric object (CO) technique that divides renal parenchyma in 12 equal layers. RESULTS: R2* values were significantly lower (corresponding to higher oxygenation) in the cortex and medulla of kidneys of children with CKD due to VUR than in those of the healthy controls (cortex 16.4 ± 1.4 vs. 17.2 ± 1.6 s(-1) , respectively; medulla 28.4 ± 3.2 vs. 30.3 ± 1.9 s(-1) , respectively; P < 0.05), and furosemide-induced changes in medullary R2* were smaller in the former than in the latter (-5.7 ± 3.0 vs. -6.9 ± 3.4 s(-1), respectively; P < 0.05). Similar results were found with the CO technique. In children with a history of unilateral reflux (n = 9), the non-affected contralateral kidneys presented similar R2* values as the diseased kidneys, but their response to furosemide was significantly larger (-7.4 ± 3.2 vs. -5.7 ± 3.0, respectively; P = 0.05). CONCLUSIONS: Chronic kidney disease due to VUR is not associated with kidney tissue hypoxia in children. The significantly larger furosemide-induced decrease in medullary R2* levels in the healthy group and unaffected contralateral kidneys of the VUR group points towards more intense renal sodium transport in these kidneys.

US not bright but right method of thyroid volume estimation even in large and substernal extended goitres. Comparison of US and three methods of CT thyroid evaluation ­ prospective study.

BACKGROUND: Ultrasound is nowadays a method of choice for thyroid volume assessment. However, its disadvantage is some inaccuracy, which is said to be higher in huge, especially substernally extended goitres. AIMS: The aim of the study was to compare the US and CT thyroid volumetric measurements: multi-observers (CT MO) and one-observer (CT OO) to CT planimetry results (CT Pl) in patients with large goitres. MATERIALS & METHODS: The study material comprised 70 thyroid imaging examinations obtained from 35 patients with nontoxic goitres, scanned twice before and after radioiodine treatment. Mean thyroid volume was 88·97 ± 60·21 ml. Thirty-three thyroid scans revealed the extension below the jugular notch (mean of 2·46 cm). Thyroid volume in US, CT MO and CT OO was estimated using the ellipsoid formula. CT Pl was established a reference method. RESULTS: The mean thyroid volume in CT Pl was 88·97 ml (median 80·73, range 11·81 to 315·97). US underestimates thyroid volume by 7·55 ml (7·7%) with a sufficient correlation (R(2) = 0·89) and precision (20·37). CT OO is the closest and CT MO the most distant from CT Pl, with US between them in thyroid volume estimation. The percentage US bias is constant through all range of thyroid volume. There is no difference for percentage bias between US and CT Pl for goitres with (8·67%), and without (6·70%) substernal part. CONCLUSION: US examination is sufficient for epidemiological studies, radioiodine activity calculation and goitre size assessment in everyday medical practice. Neither initial size of the goitre nor its substernal extension affects US assessment precision.

Comparative Effect of a Renin Inhibitor and a Thiazide Diuretic on Renal Tissue Oxygenation in Hypertensive Patients.

BACKGROUND/AIMS: The purpose of the present study was to compare the direct renin inhibitor aliskiren to the diuretic hydrochlorothiazide (HCTZ) in their ability to modulate renal tissue oxygenation in hypertensive patients. METHODS: 24 patients were enrolled in this randomized prospective study and 20 completed the protocol. Patients were randomly assigned to receive either aliskiren 150-300 mg/d or HCTZ 12.5 - 25 mg/d for 8 weeks. Renal oxygenation was measured by BOLD-MRI at weeks 0 and 8. BOLD-MRI was also performed before and after an i.v. injection of 20 mg furosemide at week 0 and at week 8. BOLD-MRI data were analyzed by measuring the oxygenation in 12 computed layers of the kidney enabling to asses renal oxygenation according to the depth within the kidney and by the classical method of regions of interest (ROI). RESULTS: The classical ROI analysis of the data showed no difference between the groups at week 8. The analysis of renal oxygenation according to the 12 layers method shows no significant difference between aliskiren and HCTZ at week 8 before administration of furosemide. However, within group analyses show that aliskiren slightly but not significantly increased oxygenation in the cortex and decreased medullary oxygenation whereas HCTZ induced a significant overall decrease in renal tissue oxygenation. With the same method of analysis we observed that the response to furosemide was unchanged in the HCTZ group at week 8 but was characterized by an increase in both cortical and medullary oxygenation in aliskiren-treated patients. Patients responding to aliskiren and HCTZ by a fall in systolic blood pressure of >10 mmHg improved their renal tissue oxygenation when compared to non-responders. CONCLUSION: With the classical method of evaluation using regions no difference were found between aliskiren and HCTZ on renal tissue oxygenation after 8 weeks. In contrast, with our new method that takes into account the entire kidney, within group analyses show that aliskiren slightly increases cortical and medullary renal tissue oxygenation in hypertensive patients whereas HCTZ decreases significantly renal oxygenation at trough.

Radiation safety awareness among medical staff.

BACKGROUND: The common access to imaging methods based on ionizing radiation requires also radiation protection. The knowledge of ionizing radiation exposure risks among the medical staff is essential for planning diagnostic procedures and therapy. Evaluation of the knowledge of radiation safety during diagnostic procedures among the medical staff. MATERIAL/METHODS: The study consisted of a questionnaire survey. The questionnaire consisted of seven closed-ended questions concerning the knowledge of the effects of exposure to ionizing radiation as well as questions related to responder's profession and work experience. The study group included a total of 150 individuals from four professional groups: nurses, doctors, medical technicians, support staff. The study was carried out in the three largest hospitals in Gdansk between July and October 2013. RESULTS: The highest rates of correct answers to questions related to the issue of radiation protection were provided by the staff of radiology facilities and emergency departments with 1-5 years of professional experience. The most vulnerable group in terms of the knowledge of these issues consisted of individuals working at surgical wards with 11-15 years of professional experience. CONCLUSIONS: Education in the field of radiological protection should be a subject of periodic training of medical personnel regardless of position and length of service.