Sulfur Hexafluoride Microbubbles Research Articles

Focused Ultrasound Combined With Microbubbles Attenuate Symptoms in Heroin-Addicted Mice

ObjectiveTo explore the efficacy and mechanisms of stimulating the nucleus accumbens (NAc) in heroin-addicted mice using focused ultrasound and microbubbles (MBs). MethodsThe conditioned place preference (CPP) method was employed to establish a heroin-addicted mice model. Mice were randomized into control (C), heroin (H), heroin + ultrasound (H + U) and H + U + MBs. Ultrasound (2 MHz fundamental frequency, 1.34 MPa peak-negative pressure, 1 MHz pulse repetition frequency, 5% duty cycle, 15 min/d, over 2 d) was applied to stimulate the NAc in the latter 2 groups. Whereas H + U + MBs received an injection of sulfur hexafluoride MBs during the stimulation. Subsequently, CPP scores, open-field test (OFT), and elevated plus-maze test (EPMT) were conducted to assess behavioral changes in addiction memory, anxiety and exercise status. HE staining was performed to detect pathological structures. Neurotransmitters such as dopamine (DA), serotonin (5-HT) and glutamate (Glu) were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Transmission electron microscopy (TEM) was used to observe ultrastructural changes of synapses in NAc. Immunohistochemistry (IHC) was utilized to detect Cleaved Caspase-3 in the NAc region. Western blotting (WB) was used to detect the protein expression of Cleaved Caspase-3, Bax and Bcl-2 in NAc. ResultsHE staining showed small patches of erythrocyte exudation were observed in the NAc and adjacent areas in H + U + MBs. The CPP scores of H + U + MBs were lower (p < 0.05) than H. After ultrasound treatment, all indices of the OFT and EPMT in H + U + MBs were significantly higher than H (p < 0.05). UPLC-MS/MS revealed that the levels of DA, 5-HT and Glu in H + U + MBs were lower than H (p < 0.01). TEM showed decrease the number of synapses (p < 0.05), and noticeable swelling of mitochondria, membrane damage, as well as damage to the cristae. Further detection by IHC and WB showed that the pro-apoptotic proteins Cleaved Caspase-3 and Bax increased and Bcl-2 decreased as anti-apoptotic proteins after ultrasound combined with MBs (p < 0.05). ConclusionFocused ultrasound combined with MBs stimulate the NAc can weaken the addictive memory and improve anxiety of heroin-related mice. The mechanical effect of ultrasound combined with the cavitation effect may be a potential treatment for addiction.

Contrast-Enhanced Intraoperative Ultrasound Shows Excellent Performance in Improving Intraoperative Decision-Making.

The aim of this study was to evaluate the performance and the impact of contrast-enhanced intraoperative ultrasound (CE-IOUS) on intraoperative decision-making, as there is still no standardized protocol for its use. Therefore, we retrospectively analyzed multiple CE-IOUS performed in hepato-pancreatic-biliary surgery with respect to pre- and postoperative imaging and histopathological findings. Data of 50 patients who underwent hepato-pancreatic-biliary surgery between 03/2022 and 03/2024 were retrospectively collected. CE-IOUS was performed with a linear 6-9 MHz multifrequency probe connected to a high-resolution device. The ultrasound contrast agent used was a stabilized aqueous suspension of sulphur hexafluoride microbubbles. In total, all 50 lesions indicated for surgery were correctly identified. In 30 cases, CE-IOUS was used to localize the primary lesion and to define the resection margins. In the remaining 20 cases, CE-IOUS identified an additional lesion. Fifteen of these findings were identified as malignant. In eight of these cases, the additional malignant lesion was subsequently resected. In the remaining seven cases, CE-IOUS again revealed an inoperable situation. In summary, CE-IOUS diagnostics resulted in a high correct classification rate of 95.7%, with positive and negative predictive values of 95.2% and 100.0%, respectively. CE-IOUS shows excellent performance in describing intraoperative findings in hepato-pancreatic-biliary surgery, leading to a substantial impact on intraoperative decision-making.

A retrospective study on adverse events of intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications in 83,778 patients.

To investigate the rate of adverse events (AEs) caused by intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications retrospectively and to explore practical measures for prevention and treatment of them. This study enrolled 83,778 contrast-enhanced ultrasound (CEUS) examinations using sulfur hexafluoride microbubbles intravenously performed during 11 years. Age, gender, and target organs of all CEUS patients were recorded. For cases of AEs, their medical history and laboratory results were also collected. The process of AEs was assessed and categorized. Besides, the management of AEs were recorded. Twenty patients had sulfur hexafluoride microbubbles-related AEs. The AE rate was 0.024%. No significant difference was observed between patients with AEs and the whole group for age and sex distribution. All AEs happened in liver examinations. Among them, 7 (35%) were mild, 8 (40%) were moderate, and 5 (25%) were severe. They were categorized into 15 allergic-like reactions and 5 physiologic reactions. The manifestations of mild and moderate AEs mainly include urticaria, chills, and mild hypoxia, which could be eased by simple management. Severe cases had anaphylactic shock, generalized convulsions, and diffuse erythema with hypotension respectively. They need close monitoring and oxygen inhalation with anti-shock and anti-anaphylactic treatment. Most cases started within 30 min and recovered within 1 day. Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications was safe with rare AEs. AEs were more likely to happen in abdominal applications than superficial ones. A well-designed emergency plan should be available for clinical use of sulfur hexafluoride microbubbles to reduce AEs and to deal with AEs properly. Intravenous administration of sulfur hexafluoride microbubbles in abdominal and superficial applications reported few AEs and could be considered safe but severe AEs are life-threatening. We analyzed the influence factors of AEs and propose some methods for prevention and treatment of them, which can further improve the safety of sulfur hexafluoride microbubbles in clinical practice. • The AE rate of sulfur hexafluoride microbubbles in abdominal and superficial applications was 0.024%. • Patients were more likely to have AEs in abdominal applications than superficial ones. • Severe AEs are life-threatening and need prompt identification and treatment. • We summarized some detailed suggestions for clinical prevention and treatment of AEs.

Combination of HIFU with sulfur hexafluoride microbubbles in the treatment of solitary uterine fibroids: a systematic review and meta-analysis.

To assess the efficacy and safety of sulfur hexafluoride microbubbles on ultrasound-guided high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. Studies that compared HIFU-microbubble combination with HIFU-only in patients with uterine fibroids were searched from inception to April 2022. The standardized mean difference (SMD) or relative risk (RR) with 95% confidence interval (CI) for different outcome parameters was calculated. Seven studies were included, with a total of 901 patients (519 in the combination group and 382 in the HIFU-only group). The energy consumption for treating 1 cm3 of the lesion in the combination group was less than that in the HIFU-only group [SMD = - 2.19, 95%CI (- 3.81, - 0.57), p = 0.008]. The use of microbubbles was associated with shortening the duration of the treatment and sonication [SMD = - 2.60, 95%CI (- 4.09, - 1.10), p = 0.0007; SMD = - 2.11, 95%CI (- 3.30, - 0.92), p = 0.0005]. The rates of significant greyscale changes during HIFU were greater in the combination group, as well as the increase of non-perfused volume ratio [RR = 1.26, 95%CI (1.04, 1.54), p = 0.02; SMD = 0.32, 95%CI (0.03, 0.61), p = 0.03]. The average sonication durations to reach significant greyscale changes and for ablating 1 cm3 of the fibroid lesion were shorter in the combination group [SMD = - 1.24, 95%CI (- 2.02, - 0.45), p = 0.002; SMD = - 0.22, 95%CI (- 0.42, - 0.02), p = 0.03]. The two groups had similar post-HIFU adverse effects, while the combination group had fewer intraprocedural adverse events like abdominal pain, sacrum pain, and leg pain. Sulfur hexafluoride microbubbles can be safely used to enhance and accelerate the ablation effects of HIFU in the treatment of uterine fibroids. The combination of HIFU with sulfur hexafluoride microbubbles offers a promising non-invasive treatment option for patients with uterine fibroids. • Sulfur hexafluoride microbubbles combined with ultrasound-guided high-intensity focused ultrasound (USgHIFU) has potential advantages in the treatment of uterine fibroids. • Sulfur hexafluoride microbubbles not only enhance the effects of USgHIFU treatment for uterine fibroids but also shorten its duration. • Sulfur hexafluoride microbubbles do not increase the incidence of USgHIFU-related adverse events in the treatment of uterine fibroids.

Contrast-enhanced ultrasound with microbubbles containing sulfur hexafluoride and perfluorobutane with Kupffer phase for the detection of colorectal liver metastases.

To compare contrast-enhanced ultrasound (CEUS) with microbubbles containing sulfur hexafluoride (SHF) and perfluorobutane (PFB) for the detection of colorectal liver metastasis (CRLM). In this prospective study, conducted from September to November 2021, patients with colorectal cancer were consecutively recruited and underwent same-day ultrasound, SHF-CEUS, and PFB-CEUS. The reference standard was contrast-enhanced MRI and follow-up imaging. The size, depth, echogenicity, and calcification of each focal liver lesion were recorded. The number and conspicuity of CRLMs, based on washout appearance during the late phase (LP) (> 120 s)/Kupffer phase (KP), were evaluated offsite by two blinded readers. Overall, 230 lesions (CRLMs, n= 219; benign lesions, n= 11) in 78 patients were evaluated. Lesion conspicuity (p= 0.344) and accuracy in the detection of CRLM were comparable for SHF- and PFB-CEUS (0.877 for SHF vs. 0.770 for PFB, p= 0.087). More CRLMs ≥ 10 mm were identified by LP contrast washout in SHF-CEUS than in KP PFB-CEUS (p< 0.001). More CRLMs < 10 mm were identified by KP washout in PFB-CEUS than in LP SHF-CEUS (p< 0.001). Conspicuity was better on PFB-CEUS than on SHF-CEUS (p= 0.027). In hyperechoic lesions, lesions located deeper than 80 mm, and calcified lesions, CRLM conspicuity on PFB-CEUS was inferior to that on SHF-CEUS (p< 0.05). The overall accuracy of detection and conspicuity of washout in CRLMs were comparable between SHF and PFB-CEUS. PFB-CEUS has the advantage of identifying washout in small CRLMs. However, larger, hyperechogenic, deep-seated, or calcified lesions were better identified using SHF-CEUS. Accuracy of detection and conspicuity of washout in CRLMs were comparable between SHF- and PFB-CEUS. PFB-CEUS has the advantage in detecting small CRLMs, whereas SHF-CEUS is better for detecting larger, hyperechogenic, deep-seated, or calcified lesions. Contrast-enhanced ultrasound with sulfur hexafluoride in the late phase and perfluorobutane microbubbles in the Kupffer phase were comparable in terms of accuracy in the detection and conspicuity of colorectal liver metastases. Small colorectal liver metastases (< 10 mm) were more often identified in the Kupffer phase contrast-enhanced ultrasound imaging when using perfluorobutane microbubbles. Larger, hyperechogenic, deep-seated, or calcified lesions were better identified in the late phase contrast-enhanced ultrasound imaging (> 120 s) when using sulfur hexafluoride microbubbles.

Microbubble contrast agent as a minimally invasive pressure sensor at body temperature and reduced concentrations in an ultrasound flow phantom

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): MRC. Background Cardiac catheterisation is the gold standard for assessing cardiac pressures. However, this is an invasive and costly procedure. A minimally invasive alternative may be to use the subharmonic signal of microbubble ultrasound contrast agents to estimate pressure using echocardiography (Sub-Harmonic Assisted Pressure Estimation: SHAPE). Purpose The aim of this work was to investigate the ability of SHAPE to track dynamic diastolic pressures in a flow phantom at body temperature and at reduced microbubble concentrations. Methods A priming dose of 0.4 mL/L of sulphur hexafluoride microbubbles was circulated through a silicone tube using a peristaltic pump at a flow rate of 375 mL/min (generating 376 pressure cycles/min and maximum pressure gradient of 1.9 mmHg/ms; Fig. 1). The ULtrasound Advanced Open Platform (ULA-OP) was used with a cardiac phased array transducer to transmit a pulse-inversion sequence at 2.1 MHz. Radiofrequency data were recorded at five acoustic pressures (71–228 kPa peak-negative). To investigate the effects of temperature, the subharmonic-pressure relationship was measured over 60 min at both room and body temperature (37°C). Microbubble concentration was maintained by regular top-up (0.15 mL/L every 3–5 min). To investigate the effect of lower concentrations on the subharmonic-pressure relationship, a priming dose of 0.4, 0.3 or 0.2 mL/L was administered before a single acquisition was made. The system was immediately purged before testing the next concentration. The subharmonic (1.05 MHz) amplitude of the microbubbles was calculated over a 40% bandwidth. A solid-state catheter recorded ground-truth pressures. Correlation coefficient (r) and sensitivity (dB/mmHg) of the subharmonic signal to the pressure values were calculated. Results The mean correlation coefficient (r = 0.91 ± 0.04; Fig. 2) and sensitivity (0.20 ± 0.04 dB/mmHg) at body temperature (n = 20) were significantly greater than those for the same batch of microbubbles at room temperature (r = 0.81 ± 0.07 and 0.14 ± 0.02; n = 18; p &amp;lt; 0.05) at the optimal acoustic pressure (Fig. 2). No significant differences in the subharmonic-pressure relationship were observed between the three different microbubble concentrations (Correlation: r = 0.96 ± 0.00, 0.96 ± 0.01, 0.97 ± 0.01. Sensitivity: 0.26 ± 0.02, 0.26 ± 0.03, 0.28 ± 0.02 mmHg/dB for 0.4, 0.3 and 0.2 mL/L, respectively; n = 3) at the optimal acoustic pressure. Conclusions SHAPE can accurately track diastolic pressures five times faster than the average resting heart rate at body temperature and with reduced microbubble concentrations. SHAPE is a potential method for assessing cardiac diastolic pressures using ultrasound in a minimally invasive fashion, being suitable for use in patients with faster microbubble clearance or in the event of delayed acquisition. The use of SHAPE fits into routine clinical procedures and has the potential to improve the diagnosis and monitoring of cardiovascular diseases.

Contrast-Enhanced Ultrasound in Distinguishing between Malignant and Benign Peripheral Pulmonary Consolidations: The Debated Utility of the Contrast Enhancement Arrival Time

Background. Limited studies and observations conducted on a too small number of patients prevent determining the actual clinical utility of pulmonary contrast-enhanced ultrasound (CEUS). The aim of the present study was to examine the efficacy of contrast enhancement (CE) arrival time (AT) and other dynamic CEUS findings for differentiating between malignant and benign peripheral lung lesions. Methods. 317 inpatients and outpatients (215 men, 102 women; mean age: 52 years) with peripheral pulmonary lesions were included in the study and underwent pulmonary CEUS. Patients were examined in a sitting position after receiving an intravenous injection of 4.8 mL of sulfur hexafluoride microbubbles stabilized by a phospholipid shell as ultrasound contrast agent (SonoVue-Bracco; Milan, Italy). Each lesion was observed for at least 5 min in real-time and the following temporal characteristics of enhancement were detected: the arrival time (AT) of microbubbles in the target lesion; the enhancement pattern; the wash-out time (WOT) of microbubbles. Results were then compared in light of the definitive diagnosis of community acquired pneumonia (CAP) or malignancies, which was not known at the time of CEUS examination. All malignant cases were diagnosed by histological results, while pneumonia was diagnosed on the basis of clinical and radiological follow-up, laboratory findings and, in some cases, histology. Results. CE AT has not been shown to differ between benign and malignant peripheral pulmonary lesions. The overall diagnostic accuracy and sensibility of a CE AT cut-off value < 10 s in discriminating benign lesions were low (diagnostic accuracy: 47.6%; sensibility: 5.3%). Poor results were also obtained in the sub-analysis of small (mean diameter < 3 cm) and large (mean diameter > 3 cm) lesions. No differences were recorded in the type of CE pattern showed between benign and malignant peripheral pulmonary lesions. In benign lesions we observed a higher frequency of delayed CE wash-out time (WOT) > 300 s. Anyhow, a CE WOT cut-off value > 300 s showed low diagnostic accuracy (53.6%) and sensibility (16.5%) in discriminating between pneumonias and malignancies. Similar results were also obtained in the sub-analysis by lesion size. Squamous cell carcinomas showed a more delayed CE AT compared to other histopathology subtypes. However, such a difference was statistically significant with undifferentiated lung carcinomas. Conclusions. Due to an overlap of CEUS timings and patterns, dynamic CEUS parameters cannot effectively differentiate between benign and malignant peripheral pulmonary lesions. Chest CT remains the gold standard for lesion characterization and the eventual identification of other pneumonic non-subpleural localizations. Furthermore, in the case of malignancy, a chest CT is always needed for staging purposes.

Risk Factors of Contrast Agent Intravasation With Sulfur Hexafluoride Microbubble During Hysterosalpingo-Contrast Sonography.

To analyze the risk factors of sulfur hexafluoride microbubble contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy), and to explore a simple prediction model by the obvious clinical history. This was a retrospective study included 299 infertility women who had undergone HyCoSy examination from July 1, 2018 to June 31, 2019. The factors were recorded, including age, endometrial thickness, balloon length, infertility type, history of intrauterine surgery, history of pelvic surgery, and tubal patency. The method of multivariate logistic regression analysis was adopted to analyze the risk factors affecting the contrast agent intravasation, and the receiver operating characteristic curves were plotted to test their efficacy. Secondary infertility, a history of intrauterine surgery, thin endometrial thickness, and tubal obstruction were all risk factors of the occurrence of intravasation (P < .05). And the area under the receiver operating characteristic curves of the multifactor-combined prediction model of the intravasation was significantly larger than that of single-factor. Sonographers and gynecologists should be familiar with the risk factors of intravasation and select the appropriate timing of HyCoSy toward reducing the occurrence of intravasation and other complications after thoroughly explaining and communicating with the patients.

Effects of Cavitation from Extracorporeal Shock Wave Combined with Sulfur Hexafluoride Microbubble on Myocardial Ultrastructure in Rats.

In the present study, the effects of extracorporeal cardiac shock waves combined with different concentrations of sulfur hexafluoride ultrasound microbubbles on myocardial ultrastructure in rats were observed. Thirty-six rats were randomly divided into 6 groups: control group (N), extracorporeal cardiac shock wave group, and combined group, i.e., extracorporeal cardiac shock wave combined with different concentrations of sulfur hexafluoride microbubble (0.225 mL/kg/min, 0.45 mL/kg/min, 0.9 mL/kg/min, 1.8 mL/kg/min). The combination of extracorporeal cardiac shock wave combined with sulfur hexafluoride microbubbles of different concentrations had no significant effect on hemodynamic indexes and left ventricular function in rats. There were significant differences in cardiac troponin I (cTnI) and nitricoxide among different groups. Histopathology showed that inflammatory cells infiltrated in the shock wave+microbubble 0.9 and shock wave+microbubble 1.8 groups. The myocardial ultrastructural injury score of shock wave+microbubble1.8 group was significantly higher than that of the N group, shock wave group, shock wave+microbubble 0.225 group, and shock wave+microbubble 0.45 group. The score of shock wave+microbubble 0.9 group was higher than that of the control group (P=.009). Western blot results showed that the expression of vascular endothelial growth factor and endothelial nitricoxide synthase (eNOS) protein in the rats treated with extracorporeal cardiac shock wave combined with sulfur hexafluoride microbubbles of different concentrations was higher than that in the N group and shock wave group, with shock wave+microbubble 0.45 group having the strongest expression. Myocardial ultrastructure damage occurs when high concentrations of sulfur hexafluoride microbubbles are present, but a proper concentration of sulfur hexafluoride microbubbles could promote the cavitation effect of extracorporeal cardiac shock waves. Thus combination therapy may become a new paradigm in coronary heart disease, especially contributing to the treatment of refractory angina. Combination therapy may change coronary heart disease treatment, especially for refractory angina.

Multimodal ultrasound imaging with conventional B-mode, elastography, and parametric analysis of contrast-enhanced ultrasound (CEUS): A novel approach to assess small bowel manifestation in severe COVID-19 disease.

The aim was to describe the small bowel morphology with conventional B-mode and elastography and additionally to evaluate dynamic effects of COVID-19 associated small bowel microvascularization using CEUS with color coded perfusion parameters.Thirteen patients with severe COVID-19 acute respiratory distress syndrome (ARDS) were investigated. 13 patients required intensive care treatment with mechanical ventilation. Five patients required extracorporeal membrane oxygenation (ECMO). Contrast-enhanced ultrasound (CEUS) was performed by an experienced investigator as a bolus injection of up to 2.4 ml sulfur hexafluoride microbubbles via a central venous catheter. In the parametric analysis of CEUS, the flare of microbubbles over time is visualized with colors. This is the first work using parametric analysis of CEUS to detect perfusion differences in the small bowel.Parametric analysis of CEUS in the intestinal phase was carried out, using DICOM loops for 20 seconds. In 5 patients, parametric analysis revealed intraindividual differences in contrast agent behavior in the small bowel region. Analogous to the computed tomography (CT) images parametric analysis showed regions of simultaneous hyper- and hypoperfusion of the small intestine in a subgroup of patients. In 5 patients, the parametric image of transmural global contrast enhancement was visualized.Our results using CEUS to investigate small bowel affection in COVID-19 suggest that in severe COVID-19 ARDS systemic inflammation and concomitant micro embolisms may lead to disruption of the epithelial barrier of the small intestine.This is the first study using parametric analysis of CEUS to evaluate the extent of small bowel involvement in severe COVID-19 disease and to detect microemboli. In summary, we show that in COVID-19 the small bowel may also be an important interaction site. This is in line with the fact that enterocytes have been shown to a plenitude of angiotensin converting enzyme (ACE)-2 receptors as entry sites of the virus.

Trophoblastic microcirculation occlusion as an adjunct to electric vacuum aspiration for the treatment of endogenous cesarean scar pregnancy

To describe a simple adjunct treatment option, trophoblastic microcirculation occlusion (TMO), which could change subsequent high-risk electric vacuum aspiration in patients with an endogenous cesarean scar pregnancy (CSP) into a routine conventional surgical procedure. Electric vacuum aspiration for the treatment of CSP may be associated with several significant complications, including hemorrhage and tissue remnants. Consequently, a second intervention, such as uterine artery embolization, resectoscopy, or methotrexate, may be required, thus complicating the surgical treatment of CSP. We demonstrate the principle and detailed technique of TMO treatment using animations, video clips, and slides. The study was approved by the institutional review board of Hangzhou Women's Hospital. Tertiary maternity hospital. The video shows a 30-year-old woman with a 5-week endogenous CSP. The procedural steps were repeated in another 6 patients suffering from endogenous CSP (Table1). Written informed consent was obtained from each patient. In patients with a CSP, the syncytiotrophoblastic cells erode the helicine arteries in the inner uterine myometrium. The cytotrophoblastic cells extend as villi tissue into the syncytiotrophoblast. Maternal blood enters the intervillous space between the cytotrophoblast and syncytiotrophoblast. The syncytiotrophoblast, cytotrophoblast, and intervillous space constitute the trophoblastic microcirculation, which subsequently becomes the main blood supply to the gestational sac (Fig.1). During TMO treatment, the trophoblastic microcirculation is identified by contrast-enhanced ultrasound with the cubital vein injected with sulfur hexafluoride microbubbles (Bracco, Switzerland). A 21-gauge needle (200 mm long) was punctured vaginally into the uterine myometrium surrounding the syncytiotrophoblast at 3 different points, and a total of 8 mL sclerosant was injected directly to seal the trophoblastic microcirculation. Complete compression of the helicine arteries for trophoblastic blood supply is the key to TMO treatment (Fig.2, see video interpretation for detailed information). A repeat contrast-enhanced ultrasound was performed after injection to confirm a significant reduction of blood flow in the trophoblast. An electric vacuum aspiration was performed 24 hours after TMO treatment to remove the products of conception completely. Surgical safety was enhanced by deep sedation and concurrent transabdominal ultrasound guidance. The levels of β-human chorionic gonadotropin (β-hCG) were measured weekly until a nonpregnant level was achieved. A follow-up ultrasound then was performed to confirm that the treatment was complete. The clinical value and feasibility of TMO treatment as an adjunct before high-risk electric vacuum aspiration for the management of endogenous CSP. The TMO treatment was performed successfully in all 7 patients; the clinical outcomes are presented in Table2. The TMO treatment significantly reduced the risk of hemorrhage during electric vacuum aspiration. No complications were detected perioperatively. Patients were discharged on day 1 postoperatively. Follow-up ultrasound, performed when the levels of β-hCG had fallen to normal, failed to identify any remnants of the uterine corpus. One patient achieved an intrauterine pregnancy 7 months postoperatively and gave birth to a live baby at 39 weeks of gestation via repeat cesarean section. No cesarean scar dehiscence was observed. Surgical abortion of an endogenous CSP, with a high risk of intraoperative hemorrhage, can be performed with minimal blood loss in a single electric vacuum aspiration when assisted by TMO treatment. This technique provides good results in terms of bleeding reduction that are comparable to those in conventional patients. The TMO treatment can be accomplished via ultrasound-guided needle puncture, a technique that is available widely in the practice of reproductive medicine with a reduced need for consumable resources. The use of a simple adjunct treatment option, TMO, expands the indications of electric vacuum aspiration. This sequential treatment allows for completion of clinical management without the need for uterine artery embolization, resectoscopy, or methotrexate, thus simplifying the originally complicated form of surgical treatment for CSP.

Safety findings after intravenous administration of sulfur hexafluoride microbubbles to 463,434 examinations at 24 centers.

We aimed to evaluate the safety of the ultrasound contrast agent sulfur hexafluoride microbubbles in a large group of patients referred for routine contrast-enhanced ultrasound (CEUS). A retrospective assessment was made of all patients that received sulfur hexafluoride microbubbles intravenously for CEUS at 24 centers between January 2006 and April 2019. Patient demographic details, examination type, and the dose of sulfur hexafluoride microbubbles administered were recorded with specific adverse events (AEs) documentation tools at each center. All AEs were recorded as serious or non-serious. Non-serious AEs were classified by intensity as mild, moderate, or severe according to ACR criteria. The frequencies of AEs across patient subgroups were compared using the chi-square test. A total of 463,434 examinations were evaluated. Overall, 157 AEs (153 [0.033%] non-serious; 4 [0.001%] serious) were reported after sulfur hexafluoride microbubbles administration, giving an AE frequency of 0.034% (157/463,434). Among the non-serious AEs, 66 (0.014%) were mild, 70 (0.015%) moderate, and 17 (0.004%) severe in intensity. The liver was the most common examination site, presenting an AE frequency of 0.026%. The highest AE frequency (0.092%) was for patients undergoing CEUS for vascular disease. There were no significant gender differences in either the total number or the severity of non-serious AEs (chi-square = 2.497, p = 0.287). The onset of AEs occurred within 30 min of sulfur hexafluoride microbubbles administration in 91% of cases. The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare, confirming that sulfur hexafluoride microbubbles are appropriate for routine CEUS applications. • The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare.

Evaluation of Takayasu's arteritis activity by ultrasound localization microscopy

Abstract Objectives Use of sulphur hexafluoride microbubbles (MB) with ultrasound can provide arterial wall enhancement. The use of ultrafast imaging with MB super-localization offers the possibility of ultrasound localization microscopy (ULM) and thus a visualization of in vivo carotid vasa vasorum. We aim to perform in vivo Vasa vasorum imaging in the carotid wall in Takayasu's arteritis and to provide a correlation with the disease's activity. Methods Patients with Takayasu arteritis were consecutively included in the national referral centre. Assessment of activity was performed by NIH activity index, with measurement of biological inflammation, morphological evaluation by computed tomography (CT) angiography, and 18-fluorodeoxyglucose CT scan. Ultrafast ultrasound imaging was performed with a 7 MHz central frequency linear probe. A dedicated contrast imaging sequence (plane waves with 8 angles, frame rate 500 Hz, voltage 8 V, duration of 8 s), coupled with the intravenous injection of sulphur hexafluoride MB allow us to store the raw radio frequency data of the MB passage. After a pre-processing step to accumulate frames properly including a frames selection and a movement correction, the MB were localized then tracked, allowing reconstruction of the vasa vasorum. The inflammation was quantified through MB tracked and normalized for inter acquisition comparison. Results 16 patients were included. 5 patients (median age 35.8 [24.5–46.0] years, 3 women) had active disease and 11 patients (37.2 [31.7–47.3] years, 9 women) had quiescent disease. The passage of MB allowed the visualisation of microvessels within the arterial wall for active cases. The number of MB detected per second in the wall was 118 [80–169] for active cases vs. 13 [10–15] for quiescent cases (p=0.0005). Conclusion ULM allows visualization of microvessels within the carotid wall, with significantly greater MB passage in active Takayasu arteritis. ULM provides for the first time a precise visualization in vivo of the vasa vasorum and gives access to quantification of the vascularity of the arterial wall. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Société française de cardiologie

Sulfur hexafluoride microbubbles combined with serology distinguish benign and malignant ovarian tumors

To explore the value of contrast-enhanced ultrasound with Sulfur hexafluoride microbubbles, serum carbohydrate antigen 125, carcinoembryonic antigen and human epididymis protein 4 joint inspection in the differential diagnosis of ovarian tumors. A total of 56 patients with ovarian tumors were chosen as research materials from June 2018 to October 2021. Result show 24 patients of benign tumors and 32 patients of malignant tumors were confirmed by pathological diagnosis. The rise time and time to peak values of malignant tumors were lower than those of benign tumors (p&lt;0.001). However, peak intensity, Time intensity curve -Area under Curve and serum human epididymis protein 4, carcinoembryonic antigen, carbohydrate antigen 125 levels joint inspection in malignant tumors were higher than those in benign tumors (p &lt; 0.001). Rise time, peak intensity and time to peak in benign and malignant ovarian tumors were 0.895 (0.802–0.999, 95% CI), 0.852 (0.804–0.916, 95% CI), 0.907 (0.829–0.925, 95% CI), respectively. Area under Curve were 0.909 (0.846–1.012, 95% CI) and serum carbohydrate antigen 125 and carcinoembryonic antigen and human epididymis protein 4 for diagnosis of benign and malignant ovarian tumors were 0.865 (0.838–0.991, 95% CI), 0.816 (0.702–0.930, 95% CI), 0.903 (0.850–1.007, 95% CI). Contrast-enhanced Ultrasound unite to serum carbohydrate antigen 125 and carcinoembryonic antigen and human epididymis protein 4, the accuracy rate 92.86% (52/56) significantly higher than Contrast-enhanced Ultrasound or serum v diagnosis benign and malignant of ovarian tumor (p&lt;0.01, 92.86% vs. 82.14%, p&lt;0.001, 92.86% vs. 73.21%). Conclusion Contrast-enhanced Ultrasound, carbohydrate antigen 125, carcinoembryonic antigen, human epididymis protein 4 joint inspection can improve the accuracy of early ovarian cancer.

Contrast enhanced ultrasonography (CEUS) a novel tool to detect intestinal epithelial barrier dysfunction in severe COVID-19 disease.

Ten patients with confirmed COVID-19 disease were studied. Nine patients required intensive care treatment, among them four needed extracorporeal membrane oxygenation (ECMO). Contrast enhanced ultrasonography (CEUS) was performed by one experienced investigator as a bolus injection of up to 2.4 ml of sulphur hexafluoride microbubbles via a central venous catheter. B-Mode evaluation and strain elastography showed mural edema of the small bowel with a thickness of up to 10 mm in all patients. We applied color coded Doppler sonography (CCDS) and power mode with flow-adapted parameters and early, dynamic capillary arterial contrast enhancement of bowel wall structures <10 s to assess perfusion of the small bowel. In all patients, reactive hyperemia was seen in the entire small bowel. In a subgroup of seven patients microbubbles translocated into the intestinal lumen. Thus, high-grade intestinal barrier disruption secondary to SARSCoV-2 infection can be postulated in these patients.This is the first description of perfusion changes and a disruption of the small bowel epithelial barrier in COVID-19 Patients using contrast ultrasonography and elastography.

Anaphylaxis to ultrasound-enhancing agent with transient elevation in serum tryptase

Ultrasound-enhancing agents (UEA) are used to enhance ultrasound image quality. The UEA that are approved for use by the US Food and Drug Administration (FDA) include perfluorocarbon or sulfur hexafluoride microbubbles, stabilized with “shells” composed of either lipid monolayer or albumin. The lipid based UEA contain polyethylene glycol (PEG).1

Is Hysterosalpingo-Contrast Sonography (HyCoSy) Using Sulfur Hexafluoride Microbubbles (SonoVue) Sufficient for the Assessment of Fallopian Tube Patency? A Systematic Review and Meta-Analysis.

This study aimed to evaluate the diagnostic value of HyCoSy using sulfur hexafluoride microbubbles for fallopian tubal patency assessment in infertile females. Twenty-four studies, including 1358 females with 2661 detected fallopian tubes published from January 2003 to May 2019, were identified. The pooled sensitivity was 93% (95% CI: 90-95%), while the specificity was 90% (95% CI: 87-92%). The area under the receiver-operating characteristic curve was 0.96 (95% CI: 94-98%). The specificity of the four-dimensional HyCoSy subgroup was higher than the 2D/3D subgroup; an increased dose of contrast agent did not affect the specificity, with only a slightly reduced sensitivity.

Dynamic endoluminal contrast enhanced ultrasound (CEUS) for display of drainages in inflammatory abdominal fluid collections1.

To evaluate the additive clinical value of endoluminal contrast enhanced ultrasound (CEUS) after interventional placement of drainages in abdominal fluid collections. Examination of 30 patients using a 1-6 MHz convex probe (Resona 7, Mindray) to locate the fluid collection in B-Mode. Additionally, dynamic endoluminal CEUS with 1 ml sulphur-hexafluoride microbubbles was performed to measure the extent of the percutaneously drained abscesses. Independent assessment of dynamically stored images in PACS in DICOM format. Correlation to reference imaging using computed tomography (CT). A total of 30 patients were examined (17 m, 19-78 years, mean 56.1 years). Drainages were positioned in the liver in 15 cases, in the pelvis after kidney transplantation in 4 cases, close to the spleen in 1 case, and in the abdomen in 10 cases. In all cases abscesses showed marginal hyperaemia with reactive septations in CEUS. The drainage position was assessed by means of B-mode in all cases first and then by CEUS. In 4 cases CEUS showed a fistula to the pleura, in 5 cases to the peritoneum, in 2 cases to the intestine, in 5 cases to the biliary tract, corresponding to the CT. In 2 cases there was a hint of an anastomotic leakage after intestinal anastomosis, which was reliably detected by CT. The drainage was removed in 11 cases within a period of 2 to 5 days after CEUS control, in 9 cases within a period of 5 to 10 days. Another operation was necessary in 3 cases. A new drainage was placed in 2 cases. The required amount of ultrasound contrast medium is 1 ml endoluminally diluted to 9 ml sodium chloride. CEUS facilitates the exact localization and characterization of inflammatory abdominal fluid collections. Furthermore, possible fistulas can be detected that cannot be seen with conventional ultrasound.

Effects of ulinastatin on renal perfusion evaluated by Doppler ultrasonography in a porcine model of septic shock.

The present study aimed to evaluate the effect of ulinastatin (UTI) on renal perfusion using Doppler ultrasonography in a porcine model of septic shock induced by smoking inhalation and live methicillin-resistant Staphylococcus aureus instillation. A total of 32 healthy Landrace pigs were randomly assigned into the following four groups: Sham group (SH; n=5), septic shock group (SS; n=9), septic shock treated with vancomycin (15 mg/kg) group (VAN; n=9) and septic shock treated with UTI (50,000 U/kg) + vancomycin (UTI; n=9) group. Renal perfusion was evaluated by contrast-enhanced ultrasound (CEUS) at baseline and at the end of the protocol (24 h). The spectrum of interlobar or arcuate artery was selected to calculate the corrected resistive index (cRI). Sulphur hexafluoride microbubbles were bolus injected via a venous catheter. The peak intensity (Pi) and area under curve (AUC) were calculated using a time-intensity curve. Compared with the baseline group, cRI was increased significantly at the end of the protocol, except for that in the SH group, whereas Pi decreased significantly after injury in all experimental groups but was higher in the UTI group compared with that in the SS and VAN groups (both P<0.001). Linear correlation was found between the cardiac output (CO) and Pi (R2=0.752; P<0.001). The AUC was significantly decreased after injury in the SS and VAN groups compared with the baseline group. All parameters detected by CEUS were improved in the UTI group, and significant differences were found between the UTI and SS or VAN group (all P<0.05). In conclusion, acute renal injury, which occasionally occurs during septic shock, is accompanied with a significantly lower perfusion rate in the renal microcirculation. By contrast, UTI can significantly improve renal perfusion, which can be reliably evaluated using CEUS.

Quantification of dynamic contrast-enhanced ultrasound (CEUS) in non-cystic breast lesions using external perfusion software

The aim of this present clinical pilot study is the display of typical perfusion results in patients with solid, non-cystic breast lesions. The lesions were characterized using contrast enhanced ultrasound (CEUS) with (i) time intensity curve analyses (TIC) and (ii) parametric color maps. The 24 asymptomatic patients included were genetically tested for having an elevated risk for breast cancer. At a center of early detection of familial ovary and breast cancer, those patients received annual MRI and grey-scale ultrasound. If lesions remained unclear or appeared even suspicious, those patients also received CEUS. CEUS was performed after intravenous application of sulfur hexafluoride microbubbles. Digital DICOM cine loops were continuously stored for one minute in PACS (picture archiving and communication system). Perfusion images and TIC analyses were calculated off-line with external perfusion software (VueBox). The lesion diameter ranged between 7 and 15 mm (mean 11 ± 3 mm). Five hypoechoic irregular lesions were scars, 6 lesions were benign and 12 lesions were highly suspicious for breast cancer with irregular enhancement at the margins and a partial wash out. In those 12 cases, histopathology confirmed breast cancer. All the suspicious lesions were correctly identified visually. For the perfusion analysis only Peak Enhancement (PE) and Area Under the Curve (AUC) added more information for correctly identifying the lesions. Typical for benign lesions is a prolonged contrast agent enhancement with lower PE and prolonged wash out, while scars are characterized typically by a reduced enhancement in the center. No differences (p = 0.428) were found in PE in the center of benign lesions (64.2 ± 28.9 dB), malignant lesions (88.1 ± 93.6 dB) and a scar (40.0 ± 17.0 dB). No significant differences (p = 0.174) were found for PE values at the margin of benign lesions (96.4 ± 144.9 dB), malignant lesions (54.3 ± 86.2 dB) or scar tissue (203.8 ± 218.9 dB). Significant differences (p < 0.001) were found in PE of the surrounding tissue when comparing benign lesions (33.6 ± 25.2 dB) to malignant lesions (15.7 ± 36.3 dB) and scars (277.2 ± 199.9 dB). No differences (p = 0.821) were found in AUC in the center of benign lesions (391.3 ± 213.7), malignant lesions (314.7 ± 643.9) and a scar (213.1 ± 124.5). No differences (p = 0.601) were found in AUC values of the margin of benign lesions (313.3 ± 372.8), malignant lesions (272.6 ± 566.4) or scar tissue (695.0 ± 360.6). Significant differences (p < 0.01) were found in AUC of the surrounding tissue for benign lesions (151.7 ± 127.8), malignant lesions (177.9 ± 1345.6) and scars (1091 ± 693.3). There were no differences in perfusion evaluation for mean transit time (mTT), rise time (RT) and time to peak (TTP) when comparing the center to the margins and the surrounding tissue. The CEUS perfusion parameters PE and AUC allow a very good assessment of the risk of malignant breast lesions and thus a downgrading of BI-RADS 4 lesions. The use of the external perfusion software (VueBox, Bracco, Milan, Italy) did not lead to any further improvement in the diagnosis of suspicious breast lesions and does appears not to have any additional diagnostic value in breast lesions.