Safety and parents´ acceptance of ultrasound contrast agents in children and adolescents - contrast enhanced voiding urosonography and contrast enhanced ultrasound.

AIMS: To evaluate the safety of the contrast enhanced voiding urosonography (ceVUS) and contrast enhanced ultrasound (CEUS) in children and adolescence and to receive data about parents' acceptance of intravesical and intravenous application of sulfur hexafluoride. MATERIAL AND METHODS: In this prospective, single centre study conducted over a 1 year study period, parents of 56 children (f/m=32/24; mean age 3.1 years; range 3 weeks - 15.9 years) with ceVUS and of 30 children (f/m=15/15; mean age 10.5 years; range 2 months - 17.7 years) with CEUS agreed to be included. A standardized telephone survey about the acceptance of the parents during and after the procedure as well as the adverse events (AE) were conducted within three days of the examination. RESULTS: The parents would agree with the use of both ceVUS and CEUS as a diagnostic tool again in 96% (54/56) or 100% (30/30) of the cases, respectively and 92.9% (52/56) would prefer ceVUS to voiding cystourethrography (VCUG). In addition, 83.3% (25/30) would prefer CEUS to CT and 73.3% (22/30) would prefer CEUS to MRI. AE were reported in 3.6% after ceVUS (2/56; skin rash, mild fever) and in 3.3% after CEUS (1/30; vomiting). AE were subacute and self­limited. CONCLUSIONS: The vast majority of parents prefer ceVUS and CEUS to VCUG, CT or MRI because of the safety profile of the contrast agent and diagnostic accuracy.

Quantitative Analysis of Microperfusion in Contrast-Induced Nephropathy Using Contrast-Enhanced Ultrasound: An Animal Study.

OBJECTIVE: To investigate imaging biomarkers of microperfusion in contrast-induced nephropathy (CIN) using contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: The CIN model was fabricated by administering indomethacin (10 mg/kg), L-NAME (15 mg/kg), and iopamidol (10 mL/kg) to Sprague-Dawley rats. After 24 hours, CEUS was performed on CIN (n = 6) and control (n = 6) rats with sulphur hexafluoride microbubbles (SonoVue). From time-intensity curves obtained from the kidney arriving time (AT), acceleration time (AC), time to peak (TTP), and peak enhancement (PE) were measured and compared between the groups. After CEUS, the rats were sacrificed, and cell apoptosis markers were evaluated to confirm the development of CIN. RESULTS: Among CEUS parameters, AT (7.8 ± 1.6 vs. 4.2 ± 0.5 s, p = 0.002), AC (4.7 ± 1.4 vs. 2.0 ± 0.4 s, p = 0.002), and TTP (12.5 ± 2.9 vs. 6.2 ± 0.6 s, p = 0.002) were significantly prolonged in the CIN group compared to controls. PE was significantly higher in the control group than in the CIN group (17.1 ± 1.9 vs. 12.2 ± 2.0 dB, p = 0.004). In kidney tissue, mRNA and protein levels of the apoptotic makers were significantly higher in the CIN group than in the control group (p = 0.003 and p = 0.002). CONCLUSION: CEUS parameters can be used as imaging biomarkers for microperfusion in CIN. In rats with CIN, AT, AC, and TTP were significantly prolonged, while PE was significantly lower compared to controls.

Transcholecystic Contrast-Enhanced Ultrasound-Guided Percutaneous Transhepatic Biliary Drainage for Central Bile Duct Protection During Thermal Tumor Ablation.

Intraductal cooling via a percutaneous transhepatic biliary drainage tube holds great promise in facilitating thermal ablation of liver tumors adjacent to the central bile ducts. However, the difficulties and complications associated with puncturing nondilated bile ducts are greater than those associated with puncturing dilated bile ducts. As reported here, percutaneous transcholecystic contrast-enhanced ultrasound was performed in 7 patients to visualize the nondilated bile ducts and guide percutaneous transhepatic biliary drainage, thus facilitating the intraductal cooling-assisted thermal ablation process. The procedures were technically successful in all 7 patients, and no major complications were recorded during the follow-up period.

The role of multiparametric ultrasound in the diagnosis of paediatric scrotal pathology.

Multiparametric ultrasound (MPUS), combining conventional techniques (greyscale and colour Doppler ultrasound), ultrasound strain elastography, and contrast-enhanced ultrasound (CEUS), has been successfully used in the assessment of adult scrotal pathology. Contrast-enhanced ultrasound can confidently establish testicular tissue vascularity even in the small-volume paediatric testis. Elastography provides further assessment of tissue stiffness, potentially adding useful diagnostic information. In children, ultrasonography is particularly advantageous, being safe, radiation-free and negating the need for sedation or general anaesthesia during the imaging evaluation. In this review article, we aim to familiarise readers with the MPUS scanning protocol used for paediatric scrotal examination and provide an overview of scrotal MPUS features, with particular focus to clinical indications where MPUS may be advantageous over conventional ultrasonography.

Planning, Execution, and Follow-up for Endovascular Aortic Aneurysm Repair Using a Highly Restrictive Iodinated Contrast Protocol in Patients with Severe Renal Disease.

BACKGROUND: The cumulative amount of iodinated contrast medium necessary for endovascular repair (EVAR) planning, operative procedure, and subsequent follow-up is a threat for the onset of end-stage renal disease in patients with preoperative impaired kidney function. The purpose of this study was to describe a mini-invasive approach aimed to minimize the exposure of these patients to iodinated contrast medium and the subsequent risk of renal function worsening. METHODS: From 2012 to 2015, all patients with abdominal aortic aneurysm (AAA) at high surgical risk and fit for standard EVAR (simple aortic-iliac anatomy: proximal and distal neck length ≥15 mm, no severe angulation), underwent EVAR through the following "near-zero contrast" approach, if their glomerular filtration rate (GFR) was <30 mL/min: preoperative planning was performed by noncontrast-enhanced computed tomography and duplex ultrasound (DU); the origin of renal/hypogastric arteries and aortic bifurcation was evaluated and matched with vertebral bone landmarks and the endograft deployed accordingly, using <20 cc of isotonic iodinate contrast medium and contrast-enhancement DU (CEUS). Follow-up was by DU/CEUS at 1, 6, and 12 months. Primary end points were technical success (TS: renal/hypogastric artery patency, absence of type I/III endoleaks, iliac stenosis/kinking, intraoperative mortality, and conversion), 30-day mortality, and new onset of permanent dialysis with renal function evaluation at 1, 6, and 12 months. Secondary end points were type II endoleaks, reinterventions, AAA, and renal-related mortality during the follow-up. RESULTS: Eighteen patients (median age: 74 years, interquartile range [IQR]: 6, male: 78%, American Society of Anaesthesiologists [ASA] IV: 100%) were enrolled. The median AAA diameter and preoperative GFR were 66 mm (IQR: 13) and 22 mL/min (IQR: 4), respectively. Infrarenal (n = 10) and suprarenal fixation (n = 8) endografts were implanted, with a mean dose of iodinate contrast medium injection of 18 mL (IQR) and 100% TS rate. Two type II endoleaks were detected at the completion CEUS. The median postoperative GFR was 22 mL/min (IQR: 5). No patients had GFR worsening ≥30% at 1 day and 30 days. The 30-day mortality was 11% (2 deaths for heart failure). At a median follow-up of 16 months (IQR: 8), no patients needed hemodialytic treatment and no endoleaks were detected. One patient died at 6 months for cancer and one at 13 months for myocardial infarction. No reinterventions or AAA and renal-related mortality occurred during the follow-up. CONCLUSIONS: A "near-zero contrast" approach is feasible in EVAR for patients with simple aorto-iliac anatomy. Patients with very poor renal function may still undergo to successful procedures, avoiding renal function impairment.

Incidence and Factors Influencing Retinal Displacement in Eyes Treated for Rhegmatogenous Retinal Detachment With Vitrectomy and Gas or Silicone Oil.

Purpose: The purpose of this study was to study the incidence and factors influencing retinal displacement in eyes treated for rhegmatogenous retinal detachment (RRD) with pars plana vitrectomy (PPV) and gas or silicone oil. Methods: This was a prospective observational case series. One hundred twenty-five eyes with macula-off RRD from 125 patients underwent 25-gauge PPV at two vitreoretinal institutional practices. Eyes without proliferative vitreoretinopathy (PVR) or PVR grade A were tamponated with sulfur hexafluoride (SF6) gas, whereas eyes with PVR grade B received 1000 centistokes silicone oil (SO). The patients postured face-down immediately after surgery. Blue-fundus autofluorescence (B-FAF) pictures were obtained at each follow-up examination. Main outcome measures were incidence and direction of retinal displacement. Results: Ninety-seven eyes (77.6%) were tamponated with SF6 and 28 eyes (22.4%) with SO. After retinal reattachment, displacement was observed in 44 of 125 (35.2%) eyes (40 eyes in the SF6 group and 4 eyes in the SO group, respectively). The type of tamponade, specifically gas, was the only significant predictor of retinal displacement (P = 0.007). The displacement was downward in 39 (88.6%) eyes (36 tamponated with SF6 and 3 with SO) and upward in 5 (11.4%) eyes (4 tamponated with SF6 and 1 with SO). Conclusions: Displacement of the retina after repair of macula-off RRD with PPV is observed using either SF6 gas or SO. Downward and upward displacements may occur with both tamponades, but downward dislocation is more common. Of the factors potentially implicated in favoring displacement that were studied, only the type of tamponade, specifically the gas, was significant.

INCIDENCE, RISK FACTORS, AND CLINICAL CHARACTERISTICS OF UNEXPLAINED VISUAL LOSS AFTER INTRAOCULAR SILICONE OIL FOR MACULA-ON RETINAL DETACHMENT.

PURPOSE: To investigate the incidence, risk factors, and clinical characteristics of unexplained visual loss after macula-on rhegmatogenous retinal detachment (RRD). METHODS: Retrospective cohort of patients with primary macula-on rhegmatogenous retinal detachment treated by vitrectomy with gas or silicone oil (SO) tamponade in 2011 and 2012. Outcome was unexplained visual loss (>2 Snellen lines) 2 months after the last vitrectomy. RESULTS: Incidence of unexplained visual loss was 0.7% (1/151) in patients treated by gas and 29.7% (11/37) in patients treated by SO (P = 0.001). Visual loss occurred both during SO tamponade and after removal. Cases underwent optical coherence tomography, perimetry, microperimetry, fluorescein angiography, and visual evoked potentials. Patients with unexplained visual loss after SO tamponade showed a small scotoma within the central 2° on microperimetry. Duration of SO tamponade was the only statistically significant factor related to the incidence of unexplained visual loss (P = 0.001). CONCLUSION: Incidence of SO-related visual loss was 30% with duration of tamponade as the only risk factor. This study is the first to apply microperimetry in these patients, which showed a distinct pattern of a small central scotoma. Therefore, microperimetry can be of great value in the diagnostic workup of patients with unexplained visual loss after vitrectomy.

[Can Postoperative Accelerated Lens Opacification be Limited by Lying in "Face-Down Position" after Vitrectomy with Gas as Tamponade?]. / Kann eine postoperativ beschleunigte Linsentrübung nach einer Pars-plana-Vitrektomie mit Gas als Tamponade durch eine konsequente "Gesicht-nach-unten-Lagerung" vermieden werden?

BACKGROUND: Developing a post-operative cataract after pars-plana vitrectomy (ppV) or core pars-plana vitrectomy (cppV) with gas as tamponade within 6 to 12 months is a common complication and is mostly accepted as unavoidable. Often a combined cataract-ppV surgery in the first place is recommended. The main goal of this study was to analyse the effects of a "face-down positioning" ("fdp") on the lens transparency and the phaco rate. By using the positive experience of an ergonomic body positioning it should be possible to improve the compliance during the period of "fdp" after surgery. METHODS: During the study period of up to 24 months, we observed in a prospective, controlled, clinical and randomised pilot study 30 patients who all had undergone a ppV/cppV with sulfur hexafluoride gas tamponade (SF6 25 %). All patients of the supported group (SG) and the control group (CG) were requested to keep their face consequently downwards until the gas bubble was resorbed completely in order to avoid a direct contact with the lens. The real time in "fdp" in hours per day (24 hours) and the grade of lens opacification was documented pre- and postoperatively using a Pentacam HR (Oculus, Wetzlar). RESULTS: The compliance of patients tested measuring the real time of "fdp" in hours per day varied largely (SG: 19.5/24; CG: 5.5/24; p < 0,0001). Cataract development was found to be directly related to the real time of "fdp". A cataract surgery was necessary mainly in the non-supported group (SG: 4/15; CG:12/15; p = 0.012). There was no lens opacification in the supported group after performing the "fdp" for at least 20 hours daily until the resorption of the gas bubble was completed. This result did not correlate with the age of the patient. CONCLUSION: With the help of sufficient support at the disposal of the patients, it is possible to significantly improve the compliance during the period of "fdp" after surgery. In order to get a safe and painless "fdp" in bed, an ergonomic body positioning is necessary (Schaefer 2012). By practicing the "fdp" until the gas bubble is completely resorbed, the risk of developing a postoperative cataract can be reduced significantly. Provided there is a good compliance to "fdp", the gas bubble can cause the desired tamponade effect even when using shorter acting gases. By performing a consistent "fdp" it is possible to accelerate the healing process and avoid reoperations. Hereby it should even be possible to use an SF6-air mix or optionally simply air as tamponade.

Prospective randomized trial: outcomes of SF6 versus C3F8 in macular hole surgery.

OBJECTIVE: To compare macular hole (MH) closure and visual acuity improvement after vitrectomy using SF6 versus C3F8 gas tamponade. The secondary purposes were to report the cumulative incidence of cataract development at 1 year after MH surgery and the proportion of complications. DESIGN: Prospective, randomized study. PARTICIPANTS: Thirty-one patients were prospectively randomized to the SF6 group and 28 patients to the C3F8 group. METHODS: Preoperative data included MH minimum diameter, Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA), cataract staging, and intraocular pressure (IOP) measurement. Postoperative data included optical coherence tomography confirmation of the closure at 6 weeks and 1 year, and ETDRS BCVA and cataract development/extraction, both 1 year after the MH surgery. RESULTS: Primary MH closure was achieved in 93.3% in the SF6 group and 92.9% in the C3F8 group. Mean ETDRS BCVA improved by 17.7 letters in the SF6 and 16.9 letters in the C3F8 group. The difference in cumulative incidence of cataract development and extraction between both groups was not statistically significant. Regardless of the dye used, similar results were achieved. Finally, the proportion of adverse events was similar in both groups. CONCLUSIONS: MH surgery with SF6 gas achieves results similar to C3F8 in terms of visual acuity improvement, MH closure, cataract development/extraction, and adverse events.

Contrast-enhanced ultrasound for evaluation of high-intensity focused ultrasound treatment of benign uterine diseases: retrospective analysis of contrast safety.

As a noninvasive treatment technique, ultrasound-guided high-intensity focused ultrasound (HIFU) has been considered as a routine treatment for uterine fibroids and adenomyosis in China. Contrast-enhanced ultrasound (CEUS) has been proposed as another option to assess the treatment efficacy during HIFU treatment. The aim of this investigation is to evaluate the adverse effects of HIFU ablation for benign uterine diseases in a group of patients studied with ultrasound contrast agent (UCA), in comparison with a group of patients not exposed to UCA. From November 2010 to December 2013, 2604 patients with benign uterine diseases were treated with HIFU. Among them, 1300 patients were exposed to an UCA, whereas 1304 patients were not.During HIFU procedure, the incidences of leg pain, sacral/buttock pain, groin pain, treatment area pain, and the discomfort "hot" sensation on skin were higher in the patients who were exposed to SonoVue (Bracco, Milan, Italy) than those who were not (20.5% vs 11.7%, 52.5% vs 42.3%, 6.5% vs 4.5%, 68.9% vs 55.4%, and 48.1% vs 42.9%, respectively). Among the postoperative adverse effects, the incidence of lower abdominal pain was significantly higher in patients who were exposed to an UCA than those who were not (51.2% vs 39.9%, P < 0.05). Two patients who were exposed to an UCA had acute renal function failure.In conclusion, UCA may increase the incidences of some common HIFU-related adverse effects during HIFU treatment for benign uterine diseases, but most of which were acceptable and self-limited. After HIFU treatment, renal function should be monitored in patients with a history of hypertension or taking nonsteroidal anti-inflammatory drugs.

Safety of intravenous application of second-generation ultrasound contrast agent in children: prospective analysis.

The goal of the work described here was to assess the safety profile of intravenous second-generation ultrasound contrast agents (UCAs) containing sulfur hexafluoride in pediatric contrast-enhanced ultrasound. Between 2010 and 2013, a total of 167 examinations were performed in 137 children referred by the Oncology Department. Approval by an Independent Ethical Review Board on Scientific Research for the intravenous use of an UCA containing sulfur hexafluoride in children with oncologic diseases was obtained. Consent for UCA administration was acquired from the parents or legal guardians. Severe anaphylactic reaction was observed in 0.6% (n = 1). No other adverse events during or after intravenous administration of contrast were observed in the examined group (no changes in heart rate and rhythm, blood pressure, oxygen saturation or respiratory rate). There were no reports of subjective flushing, nausea, transient headaches or altered taste. Although second-generation ultrasound contrast agents are considered potentially safe, all investigators should be prepared for the development of adverse reactions and have provisions in place for all pediatric intravenous contrast-enhanced ultrasound examinations. More multicenter studies are essential to determination of an accurate UCA safety profile.

Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS.

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

Efficacy and safety of recombinant tissue plasminogen activator and gas versus bevacizumab and gas for subretinal haemorrhage.

PURPOSE: To report the 12 months efficacy of initial intravitreal bevacizumab or intravitreal recombinant tissue plasminogen activator (rtPA) combined with expansile gas in patients with subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD). METHODS: Forty-five eyes of 45 patients with subretinal haemorrhage (1-5 disc diameters) involving the fovea secondary to neovascular AMD were evaluated retrospectively consecutively. Thirty-two eyes underwent treatment with rtPA (50 µg/0.05 ml) combined with intravitreal sulphur hexafluoride (SF6). The other 13 eyes were treated with bevacizumab (1.25 mg/0.05 ml) and SF6. Thereafter, all patients received Vascular Endothelial Growth Factor (anti-VEGF) treatment according to modified PrONTO criteria. Main outcome was change of best-corrected visual acuity (VA) at 12 months as determined by Early Treatment Diabetic Retinopathy (ETDRS). RESULTS: There was more improvement in patients initially treated with rtPA and gas (14 letters; bevacizumab and gas eight letters) and not suffering from adverse events. The incidence of vitreous haemorrhages was significantly higher in the rtPA group (nine of 32 versus one of 13, p < 0.01). In both groups, an average of 3.5 anti-VEGF injections were performed per patient during 12 months (no difference between both groups). CONCLUSION: Both initial treatment regimen lead to improved functional results after 1 year. However, patients, not suffering from adverse events, who underwent initial treatment with rtPA and gas showed better results. To maintain VA, controlling neovascular AMD by anti-VEGF treatment regime after initial treatment with rtPA+gas is important for all cases.

[New aspects in sonography of the liver]. / Neue Horizonte bei der Lebersonographie.

Ultrasound-based technologies are competing more and more success-fully against computerized tomography and magnetic resonance based imaging procedures. This thanks to technological improvements as well as accumulating evidence, stemming from properly conducted controlled clinical studies. The reduced cost and radiation safety issues are additional arguments in its favor. This article reviews new developments in ultrasound medicine as applied to the liver. Emphasis lies on new data related to contrast-ultrasound (Sulphur Hexafluoride SonoVue®) which allows a dynamic analysis of liver perfusion and hence improved characterization of focal liver lesions, such as metastases of extrahepatic tumors, regenerative nodules in patients with liver cirrhosis, focal nodular hyperplasia, hepatocellular carcinoma, liver hemangioma, liver adenoma and or focal hypo-respectively hypersteatosis. This article also deals with important new techniques, which allow assessment of liver stiffness such as transient elastography (Fibroscan), ARFI (Acoustic Radiation Force Impulse) or real-time-tissue elastography. These new techniques will help us to assess and quantify the levels of liver steatosis with more precision and permit accurate follow-up measurements.

Calcification in hydrophilic intraocular lenses associated with injection of intraocular gas.

PURPOSE: To report a distinct type of calcification in hydrophilic intraocular lenses in complicated, traumatized eyes with a history of intraocular gas use. DESIGN: Observational case series. METHODS: Three cases of hydrophilic intraocular lens (IOL) opacification confined to the pupillary area are reported from clinical practice in London, UK. Clinical details and analysis of the explanted intraocular lenses are provided with environmental scanning electron microscopy images and x-ray energy-dispersive spectroscopy results. RESULTS: All cases were associated with use of intraocular gas in complicated traumatized eyes, and had central areas of IOL opacification over the pupillary zone, confined to the anterior surface of the IOL. Analysis of the lenses showed the opacified areas to be composed of calcium and phosphate. CONCLUSION: The areas of opacification in all 3 hydrophilic IOLs were attributable to calcification. We postulate that intraocular gas use and the altered blood-aqueous barrier of these complicated traumatized eyes co-act to trigger secondary IOL calcification. Further experimental testing is needed to confirm this clinical association.

Intravenous application of second-generation ultrasound contrast agents in children: a review of the literature.

CEUS examinations using second-generation ultrasound contrast agents (UCA) are conducted in children, despite not being registered for individuals less than 18 years of age. We searched the Medline® database through Pubmed® and Scopus database, in order to find articles in which UCA were administered intravenously in patients under the age of 18. We analyzed in detail 9 papers (7 case reports, 2 original research studies), describing the examinations with intravenous administration of the UCA in children, and 23 original papers, in which the study group included at least one individual under the age of 18. Neither of the analyzed studies included any reports of adverse effects after UCA administration.