Assessment of fluid removal using ultrasound, bioimpedance and anthropometry in pediatric dialysis: a pilot study.

BACKGROUND: Fluid overload is associated with morbidity and mortality in children receiving dialysis. Accurate clinical assessment is difficult, and using deuterium oxide (D2O) to measure total body water (TBW) is impractical. We investigated the use of ultrasound (US), bioimpedance spectroscopy (BIS), and anthropometry to assess fluid removal in children receiving maintenance hemodialysis (HD). METHODS: Participants completed US, BIS, and anthropometry immediately before and 1-2 h after HD for up to five sessions. US measured inferior vena cava (IVC) diameter, lung B-lines, muscle elastography, and dermal thickness. BIS measured the volume of extracellular (ECF) and intracellular (ICF) fluid. Anthropometry included mid-upper arm, calf and ankle circumferences, and triceps skinfold thickness. D2O was performed once pre-HD. We assessed the change in study measures pre- versus post-HD, and the correlation of change in study measures with percent change in body weight (%∆BW). We also assessed the agreement between TBW measured by BIS and D2O. RESULTS: Eight participants aged 3.4-18.5 years were enrolled. Comparison of pre- and post-HD measures showed significant decrease in IVC diameters, lung B-lines, dermal thickness, BIS %ECF, mid-upper arm circumference, ankle, and calf circumference. Repeated measures correlation showed significant relationships between %∆BW and changes in BIS ECF (rrm =0.51, 95% CI 0.04, 0.80) and calf circumference (rrm=0.80, 95% CI 0.51, 0.92). BIS TBW correlated with D2O TBW but overestimated TBW by 2.2 L (95% LOA, -4.75 to 0.42). CONCLUSION: BIS and calf circumference may be helpful to assess changes in fluid status in children receiving maintenance HD. IVC diameter, lung B-lines and dermal thickness are potential candidates for future studies.

Utility of contrast-enhanced ultrasound for solid mass surveillance and characterization in children with tuberous sclerosis complex: an initial experience.

BACKGROUND: Patients with tuberous sclerosis complex (TSC) can develop solid kidney masses from childhood. Imaging surveillance is done to detect renal cell carcinoma (RCC) and angiomyolipomas (AML), including AMLs at risk for hemorrhage. Intravenous contrast-enhanced ultrasound (CEUS) may be useful for screening as ultrasound is well tolerated by children and ultrasound contrast agents (UCA) are not nephrotoxic. METHODS: Retrospective review of kidney CEUS exams of pediatric TSC patients. Qualitative CEUS analysis by consensus of 3 radiologists assessed rate, intensity, and pattern of lesion enhancement. Quantitative CEUS analysis was performed using Vuebox®. Where available, abdominal MRI was analyzed qualitatively for the same features and quantitatively by in-house-developed software. Time-intensity curves were generated from both CEUS and MRI where possible. Appearance of lesions were compared between CEUS and MRI and histology where available. RESULTS: Nine masses in 5 patients included one histologically proven RCC and 8 AMLs diagnosed by imaging. Quantitative CEUS of RCC showed malignant features including increased peak enhancement 162%, rapid wash-in rate 162%, and elevated washout rate 156% compared to normal kidney tissue; versus AML which was 68%, 105%, and 125%, respectively. All masses were hypoenhancing on MRI compared to normal kidney tissue; MR dynamic contrast study offered no distinction between RCC and AML. The only MRI feature differentiating RCC from AML was absence of fat. CONCLUSION: Temporal resolution afforded by CEUS was useful to distinguish malignant from benign kidney masses. CEUS may prove useful for screening, characterizing, and follow-up of kidney lesions in pediatric TSC patients.

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.

Pediatric contrast-enhanced ultrasound: optimization of techniques and dosing.

When performing contrast-enhanced ultrasound (CEUS), ultrasound (US) scanner settings, examination technique, and contrast agent dose and administration must be optimized to ensure that high-quality, diagnostic and reproducible images are acquired for qualitative and quantitative interpretations. When carrying out CEUS in children, examination settings should be tailored to their body size and specific indications, similar to B-mode US. This review article details the basic background knowledge that is needed to perform CEUS optimally in children, including considerations related to US scanner settings and US contrast agent dose selection and administration techniques.

Starting a pediatric contrast ultrasound service: made simple!

The addition of contrast US to an existing pediatric US service requires several preparatory steps. This overview provides a guide to simplify the process. Initially, it is important to communicate to all stakeholders the justifications for pediatric contrast US, including (1) its comparable or better diagnostic results relative to other modalities; (2) its reduction in procedural sedation or anesthesia by avoiding MRI or CT; (3) its reduction or elimination of radiation exposure by not having to perform fluoroscopy or CT; (4) the higher safety profile of US contrast agents (UCA) compared to other contrast agents; (5) the improved exam comfort and ease inherent to US, leading to better patient and family experience, including bedside US exams for children who cannot be transported; (6) the need for another diagnostic option in light of increasing demand by parents and providers; and (7) its status as an approved and reimbursable exam. It is necessary to have an UCA incorporated into the pharmacy formulary noting that only SonoVue/Lumason is currently approved for pediatric use. In the United States this UCA is approved for intravenous administration for cardiac and liver imaging and for vesicoureteric reflux detection with intravesical application. In Europe and China it is only approved for the intravesical use in children. All other applications are off-label. The US scanner needs to be equipped with contrast-specific software. The UCA has to be prepared just before the exam and it is important to strictly follow the steps as outlined in the packaging inserts in order to prevent premature destruction of the microbubbles. The initial training in contrast US is best focused on the frontline staff actually performing the US studies; these might be sonographers, pediatric or interventional radiologists, or trainees. It is important from the outset to educate the referring physicians about contrast US. It is helpful to participate in existing contrast US courses, particularly those with hands-on components.

Ultrasound Elastography to Quantify Liver Disease Severity in Autosomal Recessive Polycystic Kidney Disease.

OBJECTIVES: To evaluate the diagnostic accuracy of ultrasound elastography with acoustic radiation force impulse (ARFI) to detect congenital hepatic fibrosis and portal hypertension in children with autosomal recessive polycystic kidney disease (ARPKD). STUDY DESIGN: Cross-sectional study of 25 children with ARPKD and 24 healthy controls. Ultrasound ARFI elastography (Acuson S3000, Siemens Medical Solutions USA, Inc, Malvern, Pennsylvania) was performed to measure shear wave speed (SWS) in the right and left liver lobes and the spleen. Liver and spleen SWS were compared in controls vs ARPKD, and ARPKD without vs with portal hypertension. Linear correlations between liver and spleen SWS, spleen length, and platelet counts were analyzed. Receiver operating characteristic analysis was used to evaluate diagnostic accuracy of ultrasound ARFI elastography. RESULTS: Participants with ARPKD had significantly higher median liver and spleen SWS than controls. At a proposed SWS cut-off value of 1.56 m/s, the left liver lobe had the highest sensitivity (92%) and specificity (96%) for distinguishing participants with ARPKD from controls (receiver operating characteristic area 0.92; 95% CI 0.82-1.00). Participants with ARPKD with portal hypertension (splenomegaly and low platelet counts) had significantly higher median liver and spleen stiffness than those without portal hypertension. The left liver lobe also had the highest sensitivity and specificity for distinguishing subjects with ARPKD with portal hypertension. CONCLUSIONS: Ultrasound ARFI elastography of the liver and spleen, particularly of the left liver lobe, is a useful noninvasive biomarker to detect and quantify liver fibrosis and portal hypertension in children with ARPKD.

Influence of contrast-enhanced ultrasound administration setups on microbubble enhancement: a focus on pediatric applications.

BACKGROUND: In pediatrics, contrast-enhanced ultrasound offers high-quality imaging with an excellent safety profile. OBJECTIVE: To investigate the effects of varying intravenous administration setups on in vitro enhancement and concentration of two commercially available ultrasound contrast agents, taking into consideration potential pediatric applications. MATERIALS AND METHODS: We quantified in vitro enhancement using a flow phantom (ATS Laboratories, Bridgeport, CT) and Acuson S3000 ultrasound system (Siemens Healthineers, Mountain View, CA) with a 9L4 probe in Cadence pulse sequencing mode. We determined microbubble concentration with an LSRII flow cytometer (BD Biosciences, San Jose, CA). We investigated Optison (GE Healthcare, Princeton, NJ) and Lumason (Bracco, Geneva, Switzerland) ultrasound contrast agents. The ultrasound (US) contrast agent was injected via a 1 mL syringe and flushed with 5 mL of saline through a 22-gauge diffusion catheter (BD Medical, Franklin Lakes, NJ) with the following variations: in-line injection through a 3-way stopcock with and without a neutral displacement connector (ICU Medical, San Clemente, CA), perpendicular through a 3-way stopcock with and without a connector, and without a 3-way stopcock. We also conducted injections through a 22-gauge standard angiocatheter. RESULTS: Injection through the connector and perpendicular injection via the 3-way stopcock resulted in significant decreases in enhancement for both ultrasound contrast agents (P<0.0001). Injection through the connector resulted in significant decrease in concentration for Optison (P<0.05). Neither addition of the 3-way stopcock (P>0.24) nor use of a pediatric diffusion catheter (P>0.28) affected the enhancement. CONCLUSION: Ultrasound contrast agent enhancement depends on the administration route, although some effects appear to be specific to the ultrasound contrast agent used. To avoid loss of enhancement, neutral displacement connectors and perpendicular injection should be avoided.

Contrast-enhanced voiding urosonography (ceVUS) with the intravesical administration of the ultrasound contrast agent Optison™ for vesicoureteral reflux detection in children: a prospective clinical trial.

BACKGROUND: Contrast-enhanced voiding urosonography (ceVUS) is widely used outside the United States to diagnose vesicoureteral reflux (VUR) in children and is highly sensitive while avoiding exposure to ionizing radiation. At the onset of this study, two ultrasound (US) contrast agents were available in the United States. Pediatric safety data for intravenous administration was published for one, Optison™. OBJECTIVE: This study aimed to evaluate the diagnostic performance and safety of ceVUS using Optison™ and compare its diagnostic efficacy with voiding cystourethrogram (VCUG) for VUR detection and grading in children. MATERIALS AND METHODS: The United States Food and Drug Administration and institutional Investigational New Drug authorizations were obtained to conduct a prospective comparative study of ceVUS with Optison™ and VCUG. CeVUS was performed with intravesical administration of 0.2% Optison™/normal saline solution. A standard VCUG followed. Safety assessment included physical examination, and heart rate, pulse oximetry and adverse reactions monitoring before, during and immediately after the examinations. A follow-up questionnaire was completed by telephone 48-h after the studies. RESULTS: Sixty-two pelviureteric units were studied in 30 patients with a mean age of 3.5 years (range: 0.1-17 years) including 21 girls and 9 boys. No severe adverse events occurred. All patients had normal heart rate and blood oxygenation saturation prior to, during and after the studies. At the 48-h follow-up, one patient (3.3%) reported transient dysuria. Taking the VCUG as the reference standard, ceVUS had a sensitivity of 91.7% (95%; confidence interval [CI]: 61.5%-99.8%) and specificity of 98% (95%; CI: 89.4%-99.9%). The concordance between ceVUS and VCUG for VUR detection and grading was 84.3% and 81.8%, respectively. VUR grades were discrepant in 4/11 refluxing pelviureteric units, with VCUG upgrading VUR in 2. CONCLUSION: Detection of VUR with Optison™ ceVUS was comparable to VCUG without exposure to ionizing radiation. CeVUS with Optison™ is a well-tolerated diagnostic procedure with a favorable safety profile.

Contrast-enhanced US Assessment of Focal Liver Lesions in Children.

Ultrasonography (US) is often the first line of imaging for the examination of children suspected of having liver lesions. However, gray-scale US with color Doppler imaging has limitations. The use of US contrast agents has recently been approved by the U.S. Food and Drug Administration (FDA). Compared with other imaging modalities, contrast material-enhanced US (CEUS) enables the assessment of contrast enhancement patterns with a higher temporal resolution and is therefore becoming a valuable alternative imaging technique. CEUS is advantageous owing to its high safety profile; lower cost, compared with the costs of conventional contrast-enhanced computed tomographic and magnetic resonance imaging examinations; reliability; and reproducibility. Furthermore, US examinations obviate the use of sedation, ionizing radiation, and iodinated or gadolinium-based contrast agents. All of these are desirable attributes for an imaging examination for children, the most vulnerable of patients. Focal liver lesions in children are commonly discovered incidentally, and this can pose a dilemma in terms of diagnosis and management. Owing to the FDA's recent approval of the use of a specific US contrast agent for evaluation of focal liver lesions in pediatric patients, CEUS can now be used as a problem-solving tool that complements conventional imaging examinations and aids in the follow-up of lesions. The temporal resolution with CEUS enables US images to readily depict the real-time internal vascularity of a lesion. The characterization of a lesion during different phases of enhancement improves diagnostic confidence and treatment. In this article, the authors review the composition, physiologic properties, and safety profile of CEUS; describe the technique for performing CEUS; and highlight the utility of this examination in the assessment of common focal liver lesions in children. Online supplemental material is available for this article. ©RSNA, 2017.

Evaluation of galectin-3 and intestinal fatty acid binding protein as serum biomarkers in autosomal recessive polycystic kidney disease.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) causes fibrocystic kidney disease, congenital hepatic fibrosis, and portal hypertension. Serum galectin-3 (Gal-3) and intestinal fatty acid binding protein (I-FABP) are potential biomarkers of kidney fibrosis and portal hypertension, respectively. We examined whether serum Gal-3 associates with kidney disease severity and serum I-FABP associates with liver disease severity in ARPKD. METHODS: Cross-sectional study of 29 participants with ARPKD (0.2-21 years old) and presence of native kidneys (Gal-3 analyses, n = 18) and/or native livers (I-FABP analyses, n = 21). Serum Gal-3 and I-FABP were analyzed using enzyme linked immunosorbent assay. Kidney disease severity variables included estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV). Liver disease severity was characterized using ultrasound elastography to measure liver fibrosis, and spleen length and platelet count as markers of portal hypertension. Simple and multivariable linear regression examined associations between Gal-3 and kidney disease severity (adjusted for liver disease severity) and between I-FABP and liver disease severity (adjusted for eGFR). RESULTS: Serum Gal-3 was negatively associated with eGFR; 1 standard deviation (SD) lower eGFR was associated with 0.795 SD higher Gal-3 level (95% CI - 1.116, - 0.473; p < 0.001). This association remained significant when adjusted for liver disease severity. Serum Gal-3 was not associated with htTKV in adjusted analyses. Overall I-FABP levels were elevated, but there were no linear associations between I-FABP and liver disease severity in unadjusted or adjusted models. CONCLUSIONS: Serum Gal-3 is associated with eGFR in ARPKD, suggesting its value as a possible novel biomarker of kidney disease severity. We found no associations between serum I-FABP and ARPKD liver disease severity despite overall elevated I-FABP levels.

Hands-On Ultrasound Training for Radiology Residents: The Impact of an Ultrasound Scanning Curriculum.

RATIONALE AND OBJECTIVES: Radiologists are responsible for interpreting ultrasound (US) images accurately, troubleshooting, aiding sonographers, and advancing technology and research. Despite this, most radiology residents do not feel confident performing US independently. The purpose of this study is to evaluate the impact of an abdominal US scanning rotation and digital curriculum on radiology residents' confidence and skills in performing US. MATERIALS AND METHODS: All residents who were rotating in pediatric US at our institution for the first time were included (PGY 3-5). Those who agreed to participate were recruited sequentially from July 2018 to 2021 into (A) control and (B) intervention. B had a 1-week US scanning rotation and US digital course. Both groups completed a pre-and post-confidence self-assessment. Pre-and post-skills were objectively assessed by an expert technologist while participants scanned a volunteer. At completion, B completed an evaluation of the tutorial. Descriptive statistics summarized the demographics and closed questions. Pre-and post-test results were compared using paired-T tests, and effect size (ES) with Cohen's d. Open-ended questions were thematically analyzed. RESULTS: PGY-3 and 4 residents participated, and were enrolled in A (N = 39) and B (N = 30). Scanning confidence significantly improved in both groups, with a greater ES in B (p < 0.01). Scanning skills significantly improved in B (p < 0.01) but not A. Eighty per cent of questionnaire responders used the integrative US tutorial and found it helpful. Free text responses were grouped into themes: 1) Technical issues, 2) Didn't complete course, 3) Didn't understand project, 4) Course was detailed and thorough. CONCLUSIONS: Our scanning curriculum improved residents' confidence and skills in pediatric US and may encourage consistency in training, thus promoting stewardship of high-quality US.

Probe position sensor to track image location in 2D ultrasound.

BACKGROUND: Two-dimensional ultrasounds (2D US) have low reproducibility of given images in later sessions and often depend on the operator's experience. PURPOSE: Due to difficulties in reproducing images in 2D US separated in time, a device to track the position of the ultrasound probe was created. This device aims to measure the probe position angle in two axes for 2D US to provide accurate repositioning of the 2D US probe for repeatability of the desired imaging plane. MATERIALS AND METHODS: The device uses an inclinometer with an Arduino microprocessor to determine the angle of the ultrasound probe to subsequently establish the specific position coordinates of the probe. To test the effectiveness of this device, a 2D US probe was placed on a frontal burr hole of a neonatal swine to image the brain. RESULTS: When fixing the point of contact, using the probe with the angle sensing device helped the operator reproduce images that were both visually and positionally similar. This attachment allows the probe to return to the same image with at least 95% similarity in between different sessions, based on evaluations using an image analysis Matlab program. The sensor can return images of the same location with landmarks within the tolerance of 1.400°. CONCLUSION: This device could potentially improve 2D US image reproducibility such that accuracy of images between sessions is increased, thereby increasing the reproducibility of 2D US in diagnostic and interventional procedures.

Brain Contrast-Enhanced Ultrasound Evaluation of a Pediatric Swine Model.

ABSTRACT: Brain injury remains a leading cause of morbidity and mortality in children. We evaluated the feasibility of using a pediatric swine model to develop contrast-enhanced ultrasound (CEUS)-based measures of brain perfusion for clinical application in various types of brain injury monitoring. Six-week-old, 10-kg swine (N = 10) were anesthetized, and an acoustic window was created in the right frontal cranium to provide visualization of an oblique coronal plane and bilateral thalami. Ultrasound contrast agent was administered via a femoral venous catheter as a weight-based (0.03 mL/kg) bolus. After localization of the imaging plane, CEUS cine clips were acquired for 90 seconds. Bolus injection of contrast agent provided global visualization of cerebral perfusion and highlighted microvasculature in the brain. Preliminary evaluation of bolus kinetics in piglets showed a central gray nuclei-to-cortex ratio similar to human infants with a steep wash-in that crossed and remained above the 1.0 threshold for most of the enhancement period. We demonstrated the similarity in brain perfusion between piglets and human infants, specifically central gray nuclei-to-cortex ratio, showing preliminary feasibility of its use as a pediatric model of brain perfusion. Contrast-enhanced ultrasound can be performed at the bedside as a minimally invasive procedure, and quantitative CEUS may provide critical information regarding changes in brain perfusion as a result of injury or as a response to therapy.

A Low-Cost, Durable and Re-Usable Bladder Phantom: Teaching Intravesical Ultrasound Contrast Administration.

Contrast-enhanced voiding urosonography (ceVUS) is a radiation-free and highly sensitive examination for detecting vesicoureteral reflux and imaging the urethra in children. This examination is performed with ultrasound and intravesical administration of a gas-filled microbubble US contrast agent. The U.S. Food and Drug Administration recently approved the use of a US contrast agent for ceVUS in children. Because of the growing interest among physicians and US technologists in using ceVUS in children, a urinary bladder phantom was developed to teach intravesical ultrasound contrast administration to perform ceVUS procedures. Described here are the preparation and utility of a low-cost, durable and re-usable phantom that simulates the administration, distribution and effects of different US parameters on US contrast agent appearance in the bladder during ceVUS in children.