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.

Emerging contrast-enhanced ultrasound applications in children.

Ultrasound contrast agent (UCA) use in radiology is expanding beyond traditional applications such as evaluation of liver lesions, vesicoureteral reflux and echocardiography. Among emerging techniques, 3-D and 4-D contrast-enhanced ultrasound (CEUS) imaging have demonstrated potential in enhancing the accuracy of voiding urosonography and are ready for wider clinical adoption. US contrast-based lymphatic imaging has been implemented for guiding needle placement in MR lymphangiography in children. In adults, intraoperative CEUS imaging has improved diagnosis and assisted surgical management in tumor resection, and its translation to pediatric brain tumor surgery is imminent. Because of growing interest in precision medicine, targeted US molecular imaging is a topic of active preclinical research and early stage clinical translation. Finally, an exciting new development in the application of UCA is in the field of localized drug delivery and release, with a particular emphasis on treating aggressive brain tumors. Under the appropriate acoustic settings, UCA can reversibly open the blood-brain barrier, allowing drug delivery into the brain. The aim of this article is to review the emerging CEUS applications and provide evidence regarding the feasibility of these applications for clinical implementation.

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

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.

Range of Neurological Signs in Cynomolgus Monkeys After Intrathecal Bolus Administration of Antisense Oligonucleotides.

Intrathecal (IT) dosing (ie, injection into the subarachnoidal space at the lumbar region) is a common route of administration in cynomolgus monkey preclinical safety studies conducted for antisense oligonucleotides (ASO) that target central nervous system diseases. Herein we report on neurological signs that have been observed in 28 IT studies conducted in 1,016 cynomolgus monkeys. Neurological signs were classified into 5 groups: (1) A nonadverse transient absence of lower spinal reflexes. This observation occurred at low incidence in nontreated animals and in those that were injected artificial cerebrospinal fluid. The incidence increased in animals that were injected an ASO. Reflexes were present again at 24 hours or 48 hours after dosing. The incidence appeared to increase with dose. (2) Test-article-related adverse muscle tremor or muscle spasticity occurring during the injection procedure or immediately thereafter. In one-third of animals this finding responded to treatment with diazepam, in two-third it required euthanasia. (3) Neurological findings occurring between 30 minutes and 4 hours after dosing were characterized by any combination of ataxia, paresis, nystagmus, urinary incontinence, or muscle tremor. Those conditions either spontaneously resolved or they slowly worsened, eventually resulting in a poor general condition. (4) Neurological findings due to spinal cord injury were characterized by rapidly progressing paralysis of hind limbs. Magnetic resonance imaging revealed a focal hyperintense lesion, indicative of spinal cord necrosis. (5) Test-article-related adverse hind limb paresis or paralysis that occurred between 2 and 18 days after dosing. Those findings were rare and resulted in a poor general condition requiring euthanasia.

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.

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.

Ultrasound screening for neoplasms in children up to 6 years old.

The aim of the ultrasound (US) screening program was to detect neoplastic lesions in children, together with other pathologies of the developmental age in the area of the neck, abdomen, female pelvis, and scrotum in boys.US screening scans, including cervical, abdominal, pelvical, and scrotal US, were performed in the population of asymptomatic children aged from 9 months to 6 years. The children were scanned in Mobile Pediatric US Unit, consisting of 2 independent consulting rooms.The scans of 14,324 children were analyzed, 7247 boys and 7077 girls. Totally 42,538 US examinations were performed, including 14,187 cervical scans, 14,259 abdominal scans, 6942 female pelvical scans, and 7150 scrotal scans. Totally 5426 abnormalities were detected, which represent 12.7% of all examinations and 30% of patients. Three tumors were recognized, which are renal malignant tumor diagnosed as Wilms tumor, neurogenic tumor of the rib, and teratoma of the testis.US screening in pediatric population can be used to reveal lesions inaccessible to clinical examination, like tumors or other pathologies of developmental age before the onset of clinical symptoms. Due to the large number of detected abnormalities it should be recommended to the whole population of certain age.

Color Doppler dynamic tissue perfusion measurement: a novel tool in the assessment of renal parenchymal perfusion in children with vesicoureteral reflux.

INTRODUCTION: Vesicoureteral reflux (VUR) occurs in 20-50% of children suffering from recurrent urinary tract infections (UTIs) and is associated with an increased risk of renal scarring and impaired renal function. Early detection of renal perfusion deterioration would allow for the implementation of more aggressive treatment and potentially prevent further damage to the renal parenchyma. The aim of the study was to assess renal parenchymal perfusions in children with recurrent UTIs with and without coexisting VUR, and compare the findings with the results of healthy patients. MATERIAL AND METHODS: Color Doppler sonographic dynamic renal parenchymal perfusion measurements were performed with PixelFlux (Chameleon-Software, Germany) software in 77 children with recurrent UTIs and coexisting VUR and in 30 children with UTIs without VUR. The findings were compared with the results of 53 healthy children. RESULTS: Cortical parenchymal perfusion of children suffering from UTIs and VUR was significantly reduced when compared to the control group. Statistically significant differences (p < 0.05) were found in all perfusion parameters (i.e. mean velocity (v mix ), mean perfused area (A mix ), mean perfusion intensity (I mix ), tissue pulsatility index (TPI), and tissue resistance index (TRI)) between the control group and children suffering from UTIs and VUR, particularly VUR grades III and IV. There were no significant differences between the UTI group and the control group. No differences were found between the controls and VUR grade II. CONCLUSIONS: Renal parenchymal perfusion decreases significantly with higher grades of VUR.

CsI-detector-based dual-exposure dual energy in chest radiography for lung nodule detection: results of an international multicenter trial.

To assess both sensitivity and specificity of digital chest radiography alone and in conjunction with dual-exposure dual-energy chest radiography for the detection and classification of pulmonary nodules. One hundred patients with a total of 149 lung nodules (3-45 mm; median, 11 mm) confirmed by CT were included in this study. Dual-exposure dual-energy chest radiographies of each patient were obtained using a CsI detector system. Experienced board-certified chest radiologists from four different medical centers in Europe reviewed standard chest radiographs alone and in conjunction with dual-energy images blinded and in random order. The reviewers rated the probability of presence, calcification and malignancy of all lung nodules on a five-point rating scale. Lesions detected were identified by applying a specific coordinate system to enable precise verification by the study leader. A receiver-operating characteristic (ROC) analysis was performed. In addition to the 149 true-positive CT proven lesions, 236 false-positive lung nodules were described in digital chest radiographies in conjunction with dual-energy chest radiographies. The cumulative sensitivity of chest radiography in conjunction with dual energy was 43%, specificity was 55%. For digital radiography alone, sensitivity was 35% and specifity was 83%. For the dual energy system, positive predictive value was 58%, and negative predictive value was 66% compared to the digital radiography with a positive predictive value of 59% and a negative predictive value of 65%. Areas under the curve in a ROC analysis resulted in 0.631 (95% confidence interval =0.61 to 0.65) for radiography with dual energy and 0.602 (95% confidence interval =0.58 to 0.63) for digital radiography alone. This difference was not statistically significant. For the detection of lesion calcification or the determination of malignancy, ROC analysis also failed to show significant differences. CsI-based flat-panel dual-exposure dual-energy imaging added to standard chest radiography did not show statistically significant improvement for the detection of pulmonary nodules, nor the identification of calcifications, nor the determination of malignancy.