Publications by authors named "Aikaterini Ntoulia"

34 Publications

Contrast-enhanced ultrasound in children: a first-of-its-kind comprehensive compendium!

Pediatr Radiol 2021 Jul 23. Epub 2021 Jul 23.

Department of Radiology, Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA, 19104, USA.

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http://dx.doi.org/10.1007/s00247-021-05120-wDOI Listing
July 2021

Ultrasound contrast agents: microbubbles made simple for the pediatric radiologist.

Pediatr Radiol 2021 Jun 12. Epub 2021 Jun 12.

Department of Radiology, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA.

The ability to provide prompt, real-time, easily accessible and radiation-free diagnostic assessments makes ultrasound (US) one of the most versatile imaging modalities. The introduction and development of stable microbubble-based ultrasound contrast agents (UCAs) in the early 1990s improved visualization of complex vascular structures, overcoming some of the limitations of B-mode and Doppler imaging. UCAs have been used extensively in the adult population to visualize vasculature and to evaluate perfusion and blood flow dynamics in organs and lesions. Since the first observations that air bubbles within a liquid can generate a strong echogenic effect, to the early makeshift approaches with agitated saline, and later to the development of industrially produced and federally approved UCAs, these agents have evolved to become both clinically and commercially viable. Perhaps the most exciting potential of UCAs is being uncovered by current research that explores the use of these agents for molecular imaging and therapeutic applications. As contrast-enhanced ultrasound (CEUS) becomes more widely available, it is important for pediatric radiologists to understand the physics of the interaction between the US signal and the microbubbles in order to properly utilize them for the highest level of diagnostic imaging and interventions. In this article we introduce the composition of UCAs and the physics of their behavior in US, and we offer a brief history of their development over the last decades.
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http://dx.doi.org/10.1007/s00247-021-05080-1DOI Listing
June 2021

Pediatric contrast-enhanced ultrasound: shedding light on the pursuit of approval in the United States.

Pediatr Radiol 2021 Jun 11. Epub 2021 Jun 11.

Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, USA.

For two decades, pediatric contrast US has been well accepted throughout Europe and other parts of the world outside the United States because of its high diagnostic efficacy and extremely favorable safety profile. This includes intravenous (IV) administration, contrast-enhanced US (CEUS) and the intravesical application, contrast-enhanced voiding urosonography (ceVUS). However, the breakthrough for pediatric contrast US in the United States did not come until 2016, when the U.S. Food and Drug Administration (FDA) approved the first pediatric indication for a US contrast agent. This initial approval covered the use of Lumason (Bracco Diagnostics, Monroe Township, NJ) for the evaluation of focal liver lesions via IV administration in children. A second pediatric indication followed shortly thereafter, when the FDA extended the use of Lumason for assessing known or suspected vesicoureteral reflux via intravesical application in children. Both initial pediatric approvals were granted without prospective pediatric clinical trials, based instead on published literature describing favorable safety and efficacy in children. Three years later, in 2019, the FDA approved Lumason for pediatric echocardiography following a clinical trial involving a total of 12 subjects at 2 sites. The story of how we achieved these FDA approvals spans more than a decade and involves the extraordinary dedication of two professional societies, namely the International Contrast Ultrasound Society (ICUS) and the Society for Pediatric Radiology (SPR). Credit also must be given to the FDA staff for their commitment to the welfare of children and their openness to compelling evidence that contrast US is a safe, reliable, radiation-free imaging option for our pediatric patients. Understanding the history of this approval process will impact the practical application of US contrast agents, particularly when expanding off-label indications in the pediatric population. This article describes the background of the FDA's approval of pediatric contrast US applications to better illuminate the potential pathways to approvals of future indications.
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http://dx.doi.org/10.1007/s00247-021-05102-yDOI Listing
June 2021

Starting a pediatric contrast ultrasound service: made simple!

Pediatr Radiol 2021 May 12. Epub 2021 May 12.

Department of Radiology, Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA, 19104, USA.

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.
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http://dx.doi.org/10.1007/s00247-021-04998-wDOI Listing
May 2021

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

Pediatr Radiol 2021 May 12. Epub 2021 May 12.

Department of Radiology, Medical University of Gdansk, Gdansk, Poland.

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.
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http://dx.doi.org/10.1007/s00247-020-04849-0DOI Listing
May 2021

Contrast-enhanced ultrasound of transplant organs - liver and kidney - in children.

Pediatr Radiol 2021 May 12. Epub 2021 May 12.

Department of Radiology and Medical Imaging, University of Virginia Children's Hospital, Charlottesville, VA, USA.

Ultrasound (US) is the first-line imaging tool for evaluating liver and kidney transplants during and after the surgical procedures. In most patients after organ transplantation, gray-scale US coupled with color/power and spectral Doppler techniques is used to evaluate the transplant organs, assess the patency of vascular structures, and identify potential complications. In technically difficult or inconclusive cases, however, contrast-enhanced ultrasound (CEUS) can provide prompt and accurate diagnostic information that is essential for management decisions. CEUS is indicated to evaluate for vascular complications including vascular stenosis or thrombosis, active bleeding, pseudoaneurysms and arteriovenous fistulas. Parenchymal indications for CEUS include evaluation for perfusion defects and focal inflammatory and non-inflammatory lesions. When transplant rejection is suspected, CEUS can assist with prompt intervention by excluding potential underlying causes for organ dysfunction. Intracavitary CEUS applications can evaluate the biliary tract of a liver transplant (e.g., for biliary strictures, bile leak or intraductal stones) or the urinary tract of a renal transplant (e.g., for urinary obstruction, urine leak or vesicoureteral reflux) as well as the position and patency of hepatic, biliary and renal drains and catheters. The aim of this review is to present current experience regarding the use of CEUS to evaluate liver and renal transplants, focusing on the examination technique and interpretation of the main imaging findings, predominantly those related to vascular complications.
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http://dx.doi.org/10.1007/s00247-020-04867-yDOI Listing
May 2021

Contrast-enhanced genitosonography and colosonography: emerging alternatives to fluoroscopy.

Pediatr Radiol 2021 May 12. Epub 2021 May 12.

Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Imaging plays a crucial role in evaluating newborns and infants with cloacal and urogenital malformations. Contrast-enhanced genitosonography (ceGS) and contrast-enhanced colosonography (ceCS) are sensitive and radiation-free alternatives to fluoroscopic genitography and colography for diagnosis and surgical planning. These imaging techniques are performed by instilling a US contrast agent into specific body cavities to define the genitourinary and colorectal anatomy. This review article presents the experience with ceGS and ceCS applications in children, focusing on the background, examination technique, and interpretation of imaging findings, as well as strengths and weaknesses compared to conventional techniques.
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http://dx.doi.org/10.1007/s00247-020-04770-6DOI Listing
May 2021

Contrast-enhanced voiding urosonography, part 1: vesicoureteral reflux evaluation.

Pediatr Radiol 2021 Mar 31. Epub 2021 Mar 31.

Pediatric Ultrasound Center, Thessaloniki, Greece.

Contrast-enhanced voiding urosonography (ceVUS) is a well-established, sensitive and safe ultrasound (US) modality for detecting and grading vesicoureteral reflux (VUR) and urethral imaging in children. Nearly three decades of remarkable advances in US technology and US contrast agents have refined ceVUS's diagnostic potential. The recent approval of Lumason/SonoVue in the United States, Europe and China for pediatric intravesical applications marked the beginning of a new era for this type of contrast US imaging. Consequently, the use of ceVUS in children has expanded to multiple places around the globe. In the first part of this review article, we describe the current experience in the use of ceVUS for VUR evaluation, with an emphasis on historical background, examination technique, image interpretation and diagnostic accuracy. In the second part, we will present the role of ceVUS for urethral imaging in children.
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http://dx.doi.org/10.1007/s00247-020-04906-8DOI Listing
March 2021

Contrast-enhanced ultrasound for musculoskeletal indications in children.

Pediatr Radiol 2021 Mar 30. Epub 2021 Mar 30.

Department of Radiology, Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA, 19104, USA.

The increasing use of contrast-enhanced ultrasound (CEUS) has opened exciting new frontiers for musculoskeletal applications in adults and children. The most common musculoskeletal-related CEUS applications in adults are for detecting inflammatory joint diseases, imaging skeletal muscles and tendon perfusion, imaging postoperative viability of osseous and osseocutaneous tissue flaps, and evaluating the malignant potential of soft-tissue masses. Pediatric musculoskeletal-related CEUS has been applied for imaging juvenile idiopathic arthritis and Legg-Calvé-Perthes disease and for evaluating femoral head perfusion following surgical hip reduction in children with developmental hip dysplasia. CEUS can improve visualization of the capillary network in superficial and deep tissues and also in states of slow- or low-volume blood flow. In addition, measurements of blood flow imaging parameters performed by quantitative CEUS are valuable when monitoring the outcome of treatment interventions. In this review article we present current experience regarding a wide range of CEUS applications in musculoskeletal conditions in adults and children, with emphasis on the latter, and discuss imaging techniques and CEUS findings in musculoskeletal applications.
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http://dx.doi.org/10.1007/s00247-021-04964-6DOI Listing
March 2021

Intracavitary contrast-enhanced ultrasonography in children: review with procedural recommendations and clinical applications from the European Society of Paediatric Radiology abdominal imaging task force.

Pediatr Radiol 2020 04 13;50(4):596-606. Epub 2020 Feb 13.

Service d'Imagerie Pédiatrique et Prénatale, Hôpital Timone Enfants, Marseille, France.

Contrast-enhanced ultrasonography (US) has become an important supplementary tool in many clinical applications in children. Contrast-enhanced voiding urosonography and intravenous US contrast agents have proved useful in routine clinical practice. Other applications of intracavitary contrast-enhanced US, particularly in children, have not been widely investigated but could serve as a practical and radiation-free problem-solver in several clinical settings. Intracavitary contrast-enhanced US is a real-time imaging modality similar to fluoroscopy with iodinated contrast agent. The US contrast agent solution is administered into physiological or non-physiological body cavities. There is no definitive list of established indications for intracavitary US contrast agent application. However, intracavitary contrast-enhanced US can be used for many clinical applications. It offers excellent real-time spatial resolution and allows for a more accurate delineation of the cavity anatomy, including the internal architecture of complex collections and possible communications within the cavity or with the surrounding structures through fistulous tracts. It can provide valuable information related to the insertion of catheters and tubes, and identify related complications such as confirming the position and patency of a catheter and identifying causes for drainage dysfunction or leakage. Patency of the ureter and biliary ducts can be evaluated, too. US contrast agent solution can be administered orally or a via nasogastric tube, or as an enema to evaluate the gastrointestinal tract. In this review we present potential clinical applications and procedural and dose recommendations regarding intracavitary contrast-enhanced ultrasonography.
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http://dx.doi.org/10.1007/s00247-019-04611-1DOI Listing
April 2020

European Society of Paediatric Radiology abdominal imaging task force: recommendations for contrast-enhanced ultrasound and diffusion-weighted imaging in focal renal lesions in children.

Pediatr Radiol 2020 02 27;50(2):297-304. Epub 2019 Nov 27.

Service d'Imagerie Pédiatrique et Prénatale, Hôpital Timone Enfants, Marseille, France.

Contrast-enhanced ultrasound (CEUS) and diffusion-weighted imaging (DWI) are safe, repeatable imaging techniques. The aim of this paper is to discuss the advantages, technical factors and possible clinical applications of these imaging tools in focal renal lesions in children.
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http://dx.doi.org/10.1007/s00247-019-04552-9DOI Listing
February 2020

Intraoperative Contrast-Enhanced Ultrasound Imaging of Femoral Head Perfusion in Developmental Dysplasia of the Hip: A Feasibility Study.

J Ultrasound Med 2020 Feb 23;39(2):247-257. Epub 2019 Jul 23.

Division of Orthopedic Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Objectives: Developmental dysplasia of the hip (DDH) is one of the most common developmental deformities of the lower extremity. Although many children are successfully treated with a brace or harness, some require intraoperative closed or open reduction and spica casting. Surgical reduction is largely successful to relocate the hip; however, iatrogenic avascular necrosis is a major source of morbidity. Recent research showed that postoperative gadolinium-enhanced magnetic resonance imaging (MRI) can depict hip perfusion, which may predict a future incidence of avascular necrosis. As contrast-enhanced ultrasound (CEUS) assesses blood flow in real time, it may be an effective intraoperative alternative to evaluate femoral head perfusion. Here we describe our initial experience regarding the feasibility of intraoperative CEUS of the hip for the assessment of femoral head perfusion before and after DDH reduction.

Methods: This single-institution retrospective Institutional Review Board-approved study with a waiver of informed consent evaluated intraoperative hip CEUS in children with DDH compared to postoperative contrast-enhanced MRI. Pediatric radiologists, blinded to prior imaging findings and outcomes, reviewed both CEUS and MRI examinations separately and some time from the initial examination both independently and in consensus.

Results: Seventeen patients had 20 intraoperative CEUS examinations. Twelve of 17 (70.6%) had prereduction hip CEUS, postreduction hip CEUS, and postreduction gadolinium-enhanced MRI. Seven of 12 (58.3%) were evaluable retrospectively. All CEUS studies showed blood flow in the femoral epiphysis before and after reduction, and all MRI studies showed femoral head enhancement after reduction. The CEUS and MRI for all 7 patients also showed physeal blood flow.

Conclusions: Contrast-enhanced ultrasound is a feasible intraoperative tool for assessing adequate blood flow after hip reduction surgery in DDH.
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http://dx.doi.org/10.1002/jum.15097DOI Listing
February 2020

Correction to: European Society of Paediatric Radiology abdominal imaging task force: statement on imaging in very early onset inflammatory bowel disease.

Pediatr Radiol 2019 Jun;49(7):975

Department of Radiology and Nuclear Medicine, Unit for Paediatric Radiology, Oslo University Hospital, Oslo, Norway.

The above article was published online with incorrect author name. The right spelling should be Damjana Kljucevsek instead of Damjana Kjucevsek. The correct name is presented here.
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http://dx.doi.org/10.1007/s00247-019-04421-5DOI Listing
June 2019

European Society of Paediatric Radiology abdominal imaging task force: statement on imaging in very early onset inflammatory bowel disease.

Pediatr Radiol 2019 05;49(6):841-848

Department of Radiology and Nuclear Medicine, Unit for Paediatric Radiology, Oslo University Hospital, Oslo, Norway.

Very early onset inflammatory bowel disease (VEO-IBD) is defined as disease presenting before the age of 6. These children require a tailored imaging approach because conventional imaging studies can be difficult to perform at such a young age. Unlike inflammatory bowel disease in older children and adults, colonic disease predominates in VEO-IBD, and small-bowel disease is rare. Distinguishing Crohn disease from ulcerative colitis is challenging both clinically and on histology. Radiology offers the greatest utility for detecting small-bowel disease because it helps to distinguish the two main disease entities and guide clinical management. Small-bowel ultrasound is recommended as the first-line investigation because it requires relatively little preparation, is readily available and is generally well tolerated in young children. We present these recommendations, based on the current evidence for radiologic management in this group, and propose an imaging algorithm for investigating VEO-IBD.
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http://dx.doi.org/10.1007/s00247-019-04375-8DOI Listing
May 2019

3D/4D contrast-enhanced urosonography (ceVUS) in children - is it superior to the 2D technique?

J Ultrason 2018 ;18(73):120-125

Department of Pediatric Radiology, Medical University of Lublin, Lublin, Poland.

Background: By now, two-dimensional contrast-enhanced voiding urosonography (ceVUS) has become a well-established method for the diagnosis and treatment monitoring of vesicoureteral reflux in children, particularly after the recent approval for this application in children in the USA and in Europe. The introduction of three-dimensional static (3D) and real-time (4D) techniques with ultrasound contrast agents opens up new diagnostic opportunities for this imaging modality.

Objective: To analyze whether 3D and 4D ceVUS is a superior technique compared to standard 2D ceVUS in diagnosing vesicoureteral reflux in children.

Material And Methods: The study included 150 patients (mean age 3.7 years) who underwent 2D and 3D/4D ceVUS for the diagnosis and grading of vesicoureteral reflux.

Results: 2D ceVUS and 3D/4D ceVUS diagnosed the same number of vesicoureteral refluxes, however, there was a statistically significant difference in grading between the two methods. Performing 3D/4D ceVUS resulted in changing the initial grade compared to 2D ceVUS in 19 out of 107 refluxing units (17.76%) diagnosed. The 4D technique enabled a more conspicuous visualization of vesicoureteral reflux than the 3D technique.

Conclusions: 2D ceVUS and 3D/4D ceVUS diagnosed the same number of vesicoureteral refluxes, however, there was a statistically significant difference in grading between the two methods. Thus 3D/4D ceVUS appears at least a valid, if not even a more conspicuous technique compared to 2D ceVUS.
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http://dx.doi.org/10.15557/JoU.2018.0017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440503PMC
January 2018

European Society of Paediatric Radiology Abdominal Imaging Task Force recommendations in paediatric uroradiology, part X: how to perform paediatric gastrointestinal ultrasonography, use gadolinium as a contrast agent in children, follow up paediatric testicular microlithiasis, and an update on paediatric contrast-enhanced ultrasound.

Pediatr Radiol 2018 09 23;48(10):1528-1536. Epub 2018 May 23.

Department of Radiology and Nuclear Medicine, Unit for Paediatric Radiology, Oslo University Hospital, Oslo, Norway.

At the European Society of Paediatric Radiology (ESPR) annual meeting 2017 in Davos, Switzerland, the ESPR Abdominal (gastrointestinal and genitourinary) Imaging Task Force set out to complete the suggestions for paediatric abdominal imaging and its procedural recommendations. Some final topics were addressed including how to perform paediatric gastrointestinal ultrasonography. Based on the recent approval of ultrasound (US) contrast agents for paediatric use, important aspects of paediatric contrast-enhanced US were revisited. Additionally, the recent developments concerning the use and possible brain deposition of gadolinium as a magnetic resonance imaging contrast agent were presented. The recommendations for paediatric use were reissued after considering all available evidence. Recent insights on the incidence of neoplastic lesions in children with testicular microlithiasis were discussed and led to a slightly altered recommendation.
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http://dx.doi.org/10.1007/s00247-018-4147-3DOI Listing
September 2018

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.

Pediatr Radiol 2018 02 27;48(2):216-226. Epub 2017 Nov 27.

Department of Radiology, The Children's Hospital of Philadelphia, 34th Street & Civic Center Boulevard, Philadelphia, PA, 19104, USA.

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.
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http://dx.doi.org/10.1007/s00247-017-4026-3DOI Listing
February 2018

Standardization of pediatric uroradiological terms: A multidisciplinary European glossary.

J Pediatr Urol 2017 Dec 13;13(6):641-650. Epub 2017 Jul 13.

Pediatric Nephrology, Centro Hospitalar São João, Porto, Portugal.

To promote the standardization of nephro-uroradiological terms used in children, the European Society of Pediatric Radiology uroradiology taskforce wrote a detailed glossary. This work has been subsequently submitted to European experts in pediatric urology and nephrology for discussion and acceptance to improve the quality of radiological reports and communication among different clinicians involved in pediatric urology and nephrology.
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http://dx.doi.org/10.1016/j.jpurol.2017.05.026DOI Listing
December 2017

Standardization of pediatric uroradiological terms: a multidisciplinary European glossary.

Pediatr Radiol 2018 02 15;48(2):291-303. Epub 2017 Nov 15.

Pediatric Nephrology, Centro Hospitalar São João, Porto, Portugal.

To promote the standardization of nephro-uroradiological terms used in children, the European Society of Paediatric Radiology uroradiology taskforce wrote a detailed glossary. This work has been subsequently submitted to European experts in pediatric urology and nephrology for discussion and acceptance to improve the quality of radiological reports and communication between different clinicians involved in pediatric urology and nephrology.
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http://dx.doi.org/10.1007/s00247-017-4006-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790858PMC
February 2018

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

Radiographics 2017 Oct;37(6):1632-1647

From the Department of Radiology, The Children's Hospital of Philadelphia, University of Pennsylvania, Perelman School of Medicine, 3401 Civic Center Blvd, Philadelphia, PA 19104.

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.
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http://dx.doi.org/10.1148/rg.2017170073DOI Listing
October 2017

Applications of contrast-enhanced ultrasound in the pediatric abdomen.

Abdom Radiol (NY) 2018 04;43(4):948-959

Department of Radiology, Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.

Contrast-enhanced ultrasound (CEUS) is a radiation-free, safe, and in specific clinical settings, highly sensitive imaging modality. Over the recent decades, there is cumulating experience and a large volume of published safety and efficacy data on pediatric CEUS applications. Many of these applications have been directly translated from adults, while others are unique to the pediatric population. The most frequently reported intravenous abdominal applications of CEUS in children are the characterization of focal liver lesions, monitoring of solid abdominal tumor response to treatment, and the evaluation of intra-abdominal parenchymal injuries in selected cases of blunt abdominal trauma. The intravesical CEUS application, namely contrast-enhanced voiding urosonography (ceVUS), is a well-established, pediatric-specific imaging technique entailing the intravesical administration of ultrasound contrast agents for detection and grading of vesicoureteral reflux. In Europe, all pediatric CEUS applications remain off-label. In 2016, the United States Food and Drug Administration (FDA) approved the most commonly used worldwide second-generation ultrasound contrast SonoVue®/Lumason® for pediatric liver and intravesical applications, giving new impetus to pediatric CEUS worldwide.
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http://dx.doi.org/10.1007/s00261-017-1315-0DOI Listing
April 2018

Role of magnetic resonance urography in pediatric renal fusion anomalies.

Pediatr Radiol 2017 Dec 24;47(13):1707-1720. Epub 2017 Aug 24.

Division of Body Imaging, Department of Radiology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Renal fusion is on a spectrum of congenital abnormalities that occur due to disruption of the migration process of the embryonic kidneys from the pelvis to the retroperitoneal renal fossae. Clinically, renal fusion anomalies are often found incidentally and associated with increased risk for complications, such as urinary tract obstruction, infection and urolithiasis. These anomalies are most commonly imaged using ultrasound for anatomical definition and less frequently using renal scintigraphy to quantify differential renal function and assess urinary tract drainage. Functional magnetic resonance urography (fMRU) is an advanced imaging technique that combines the excellent soft-tissue contrast of conventional magnetic resonance (MR) images with the quantitative assessment based on contrast medium uptake and excretion kinetics to provide information on renal function and drainage. fMRU has been shown to be clinically useful in evaluating a number of urological conditions. A highly sensitive and radiation-free imaging modality, fMRU can provide detailed morphological and functional information that can facilitate conservative and/or surgical management of children with renal fusion anomalies. This paper reviews the embryological basis of the different types of renal fusion anomalies, their imaging appearances at fMRU, complications associated with fusion anomalies, and the important role of fMRU in diagnosing and managing children with these anomalies.
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http://dx.doi.org/10.1007/s00247-017-3927-5DOI Listing
December 2017

Intravenous and Intracavitary Use of Contrast-Enhanced Ultrasound in the Evaluation and Management of Complicated Pediatric Pneumonia.

J Ultrasound Med 2017 Sep 19;36(9):1943-1954. Epub 2017 Jun 19.

Department of Radiology, King's College London, King's College Hospital, London, England.

Pediatric pneumonia can be complicated by necrotizing pneumonia or a parapneumonic effusion either in the form of an empyema or a clear effusion. Ultrasonography (US) and computed tomography represent well-established modalities for evaluation of complicated pediatric pneumonia. Contrast-enhanced ultrasound (CEUS) was recently introduced and is gaining increasing acceptance in pediatric imaging. In this case series, we present our initial experience with both intravenous and intracavitary use of CEUS in children with complicated pneumonia. Intravenous CEUS accurately and confidently showed necrotizing pneumonia and delineated pleural effusions, whereas intracavitary CEUS accurately identified the chest catheter location and patency and showed the presence of loculations, suggesting the use of fibrinolytics.
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http://dx.doi.org/10.1002/jum.14269DOI Listing
September 2017

Diffusion-Tensor Imaging of the Physes: A Possible Biomarker for Skeletal Growth-Experience with 151 Children.

Radiology 2017 07 2;284(1):210-218. Epub 2017 Feb 2.

From the Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pa (M.A.B., J.D., J.I.B., N.A.C., R.R.G., A.N.); Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pa (J.I.B., N.A.C., M.A.B.); Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Mass (D.Z.); and Department of Radiology, Stanford University School of Medicine, Lucile Packard Children's Hospital, 725 Welch Rd, Palo Alto, CA 94304 (D.J.).

Purpose To determine the changes of diffusion-tensor imaging (DTI) and tractography in the distal femur and proximal tibia related to age, sex, and height. Materials and Methods Following institutional review board approval, with waiver of consent and with HIPAA compliance, the authors retrospectively analyzed DTI images of the knee in 151 children, 73 girls (median age, 14.1 years; range, 6.5-17.8 years) and 78 boys (median age, 16.6 years; range, 6.9-17.9 years), studied from January 2013 to October 2014. At sagittal echo-planar DTI (20 directions, b values of 0 and 600 sec/mm), regions of interest were placed in the tibial and femoral physes. Using a fractional anisotropy threshold of 0.15 and an angle threshold of 40°, the authors performed tractography and measured apparent diffusion coefficient (ADC) and tract length and volume. Changes related to age, sex, and height were evaluated by using fitted nonlinear polynomial functions on bootstrapped samples. Results Femoral tract volume and length increased and then decreased with age (P < .001); the peaks of femoral tract volume are consistent with the growth spurt, occurring earlier in girls (10.8 years) than in boys (13.0 years) (P < .001). Girls had smaller tract volumes in comparison to boys (P = .013). ADC peaks 2 years earlier than tract volume (girls at 9.3 years, boys at 11.0 years). Girls with greater than 50th percentile of height had longer tracts and greater tract volumes compared with girls with less than 50th percentile (P < .020). DTI parameters of boys do not correlate with percentile of height (P > .300). Conclusion DTI of the physis and metaphysis shows greater tract length and volumes in subjects who are at ages when the growth is fastest. ADC and tract length and volume have an earlier and smaller peak in girls than in boys. Femoral tract length and volume are larger in taller girls. RSNA, 2017.
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http://dx.doi.org/10.1148/radiol.2017160681DOI Listing
July 2017

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

Ultraschall Med 2017 Jan 14;38(1):33-43. Epub 2016 Jul 14.

National Centre for Ultrasound in Gastronterology, Haukeland University Hospital, Bergen and Department of Clinical Medicine, University of Bergen, Norway.

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.
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http://dx.doi.org/10.1055/s-0042-110394DOI Listing
January 2017

Failed Intussusception Reduction in Children: Correlation Between Radiologic, Surgical, and Pathologic Findings.

AJR Am J Roentgenol 2016 Aug 25;207(2):424-33. Epub 2016 May 25.

1 The Children's Hospital of Philadelphia, 324 S 34th St, Philadelphia, PA 19104.

Objective: The objective of this study was to identify causes of irreducible intussusception after contrast enema and to correlate imaging findings with surgical and histopathologic findings.

Materials And Methods: Between 2005 and 2013, a total of 543 children underwent reduction of intussusception with the use of an enema technique (hereafter referred to as "enema reduction"). The medical records of 72 children (56 boys [mean age, 24.8 months; range, 3.8 months to 10.9 years] and 16 girls [mean age, 14.2 months; range, 1.5 months to 6.9 years) who underwent unsuccessful reduction and were treated surgically were retrospectively analyzed. The data collected included information on the cause of intussusception, the risk factors noted on ultrasound, operative management, outcome, and the length of the hospital stay. The imaging findings for these patients were compared with findings for statistically similar age-matched control subjects.

Results: Ultrasound detected 56 of 57 cases of intussusception, but it failed to detect the lead point in three cases and failed to detect ischemic necrosis in seven cases. Positive predictors of failed enema reduction were the presence of a distal mass and observation of the dissecting sign. Of the 72 patients who underwent surgical treatment of intussusception, 26 (36.1%) underwent laparoscopy, 38 (52.8%) underwent laparotomy, and eight (11.1%) underwent conversion from laparoscopy to laparotomy. Surgical reduction was performed in 61.1% of cases, small bowel resection in 19.4%, ileocecectomy in 12.5%, and self-reduction in 69%. Pathologic lead points (noted in 25% of cases) included lymphoid hyperplasia (n = 7), Meckel diverticulum (n = 3), Burkitt lymphoma (n = 3), enteric duplication cyst (n = 2), juvenile polyp (n = 2), and adenovirus appendicitis (n = 1). The length of the hospital stay was significantly longer after laparotomy.

Conclusion: The distalmost location of the intussusception mass and presence of the dissecting sign on images obtained during contrast enema have a higher positive predictive value for failed reduction. Screening ultrasound decreases the number of unnecessary contrast enemas performed; however, classic pathologic lead points, such as Burkitt lymphoma and Meckel diverticulum, may be difficult to diagnose with the use of ultrasound. Laparotomy and laparoscopy are equally safe and efficacious in reducing intussusception, with the length of the hospital stay after laparoscopy significantly shorter than that noted after laparotomy. Most failed enema reductions are idiopathic, and pathologic lead points are noted in 25% of cases.
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http://dx.doi.org/10.2214/AJR.15.15659DOI Listing
August 2016

ESPR Uroradiology Taskforce--imaging recommendations in paediatric uroradiology, part VIII: retrograde urethrography, imaging disorder of sexual development and imaging childhood testicular torsion.

Pediatr Radiol 2015 Dec 1;45(13):2023-8. Epub 2015 Dec 1.

Department of Radiology, Kantonsspital Baden AG, Baden, Switzerland.

Three new consensus-based recommendations of the European Society of Paediatric Radiology Uroradiology Taskforce and the European Society of Urogenital Radiology Paediatric Working Group on paediatric uroradiology are presented. One deals with indications and technique for retrograde urethrography, one with imaging in the work-up for disorders of sexual development and one with imaging workflow in suspected testicular torsion. The latter is subdivided to suggest a distinct algorithm to deal with testicular torsion in neonates. These proposals aim to outline effective imaging algorithms to optimise diagnostic accuracy and to harmonize diagnostic imaging among institutions and practitioners.
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http://dx.doi.org/10.1007/s00247-015-3452-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666898PMC
December 2015

Contrast-enhanced voiding urosonography with intravesical administration of a second-generation ultrasound contrast agent for diagnosis of vesicoureteral reflux: prospective evaluation of contrast safety in 1,010 children.

Pediatr Radiol 2014 Jun 18;44(6):719-28. Epub 2014 Jan 18.

Department of Radiology, Medical School of University of Ioannina, Ioannina, Greece,

Background And Objective: To evaluate the safety of intravesical administration of a second-generation ultrasound (US) contrast agent for the diagnosis of vesicoureteral reflux in children.

Materials And Methods: One thousand and ten children (563 girls, 447 boys; mean age: 2.9 years, range: 15 days-17.6 years) with 2,043 pelvi-ureter-units underwent contrast-enhanced voiding urosonography (ce-VUS) to rule out vesicoureteral reflux. A second-generation US contrast agent (SonoVue®, Bracco, Milan) was administered intravesically through transurethral bladder catheterization at a dose of 0.5 ml/bladder filling. Possible adverse events were monitored during the examination and followed up for 7 days after ce-VUS by phone calls. Urine analysis and culture were performed 3-5 days before ce-VUS in all children and 24-48 h in any patient who reported with adverse events.

Results: No case of serious adverse event was recorded. Minor events were reported in 37 children (3.66% of the study population). These included dysuria (n = 26, 2.57%), urinary retention (n = 2, 0.2%), abdominal pain (n = 2, 0.2%), anxiety (n = 1, 0.1%) and crying (n = 1, 0.1%) during micturition, blood and mucous discharge (n = 1, 0.1%), increased frequency of micturition (n = 1, 0.1%), vomiting (n = 1, 0.1%), perineal irritation (n = 1, 0.1%), and an episode of urinary tract infection 10 days after ce-VUS (n = 1, 0.1%). Of these adverse events, 91.9% were subacute in onset and 8.1% were delayed. All events were self-limited and none required hospitalization.

Conclusion: There were no serious adverse events. Only a few minor events were reported, most likely due to the catheterization process. Thus, ce-VUS with intravesical administration of the second-generation US contrast agent (SonoVue®) for vesicoureteral reflux detection or exclusion had a favorable safety profile in our study group.
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http://dx.doi.org/10.1007/s00247-013-2832-9DOI Listing
June 2014

The PCL index is correlated with the control of rotational kinematics that is achieved after anatomic anterior cruciate ligament reconstruction.

Am J Sports Med 2014 Mar 11;42(3):665-74. Epub 2013 Dec 11.

Franceska Zampeli, Orthopaedic Sports Medicine Center, Department of Orthopaedic Surgery, University of Ioannina, Papanastasiou, Arta, 47100, Greece.

Background: The posterior cruciate ligament (PCL) index quantifies the curvature of the PCL seen on magnetic resonance imaging (MRI) that is caused by a change in tibiofemoral alignment in the anterior cruciate ligament (ACL)-deficient knee. It has been proposed that the PCL index may be useful in assessing the success of ACL reconstruction (ACLR). Hypothesis/

Purpose: The purpose of this study was to test if the PCL index is predictive of in vivo rotational kinematics and joint laxity measures in knees of patients after single-bundle ACLR. The hypothesis was that the PCL index is predictive of rotational knee kinematics and objective laxity scores.

Study Design: Controlled laboratory study.

Methods: At a mean of 18.1 months postoperatively, the PCL index was defined on MRI in 16 patients prospectively followed up after anatomic single-bundle ACLR and in 16 matched controls. The patients were evaluated with 3-dimensional motion analysis during (1) descending and pivoting as well as (2) landing and pivoting tasks. The side-to-side difference in tibial rotation range of motion between the reconstructed knee and the contralateral intact knee was calculated. The side-to-side difference in anterior tibial translation was measured with a KT-1000 arthrometer. Linear regression models were used with the PCL index as a predictor of the side-to-side difference in tibial rotation for each task and the side-to-side difference in anterior tibial translation.

Results: The PCL index of the reconstructed knees was significantly lower compared with that of the control knees (P < .001). The index was predictive of the side-to-side difference in tibial rotation during both tasks (R (2) = 0.472 and 0.477, P = .003), with a lower index being indicative of increased rotational laxity. It was not predictive of anterior tibial translation (at 134 N: R (2) = 0.13, P = .17; at maximum force: R (2) = 0.009, P = .726).

Conclusion: The PCL index after anatomic single-bundle ACLR using a bone-patellar tendon-bone graft is predictive of rotational kinematics during in vivo dynamic pivoting activities. The results show that the PCL index is correlated with the postoperative ability to control rotational kinematics of the knee joint.

Clinical Relevance: This study provides evidence regarding the interplay between restoration of the native ACL's anatomy and the PCL's appearance and suggests that the effective restoration of tibiofemoral alignment after ACLR that is reflected in the PCL index translates into better functional outcomes as measured by tibial rotation during pivoting activities.
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http://dx.doi.org/10.1177/0363546513512780DOI Listing
March 2014

Safety of contrast-enhanced ultrasound in children for non-cardiac applications: a review by the Society for Pediatric Radiology (SPR) and the International Contrast Ultrasound Society (ICUS).

Pediatr Radiol 2013 Sep 11;43(9):1063-73. Epub 2013 Jul 11.

Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

The practice of contrast-enhanced ultrasound in children is in the setting of off-label use or research. The widespread practice of pediatric contrast-enhanced US is primarily in Europe. There is ongoing effort by the Society for Pediatric Radiology (SPR) and International Contrast Ultrasound Society (ICUS) to push for pediatric contrast-enhanced US in the United States. With this in mind, the main objective of this review is to describe the status of US contrast agent safety in non-cardiac applications in children. The five published studies using pediatric intravenous contrast-enhanced US comprise 110 children. There is no mention of adverse events in these studies. From a European survey 948 children can be added. In that survey six minor adverse events were reported in five children. The intravesical administration of US contrast agents for diagnosis of vesicoureteric reflux entails the use of a bladder catheter. Fifteen studies encompassing 2,951 children have evaluated the safety of intravesical US contrast agents in children. A European survey adds 4,131 children to this group. No adverse events could be attributed to the contrast agent. They were most likely related to the bladder catheterization. The existing data on US contrast agent safety in children are encouraging in promoting the widespread use of contrast-enhanced US.
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http://dx.doi.org/10.1007/s00247-013-2746-6DOI Listing
September 2013
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