Contrast efficacy of novel phase convertible nanodroplets for safe CEUS imaging.

Microbubble contrast agents in ultrasound/echocardiography are used to increase the echogenicity of the target tissues, thereby raising the contrast resolution of the resultant image. Recently, the trend has shifted toward the development of phase-convertible nanodroplets as ultrasound contrast agents due to their promising theragnostic potential by switching capability at the active site. Herein, we fabricated pre-PGS- perfluoropentane phase convertible nanodroplets and checked their in vitro and in vivo enhancement and safety profile. For this, we performed experiments on 20 male Wistar rats and 2 dogs. Biochemical assays of both rats and dogs included complete blood profiles, liver function tests, and renal function tests. For rat vitals, monitoring and histopathological analysis were also performed. Converted nanodroplets showed excellent contrast enhancement, better than Sonovue upon in vitro testing, with an enhancement time of up to 14 min. In vivo, experiments showed comparable opacification of the ventricles of both rats and dogs. All biochemical assays remained within the normal range during the study period. The histopathological analysis did not show any signs of drug-induced toxicity, showing the safety of these nanodroplets. Pre-PGS-PFP nanodroplets hold great potential for use in echocardiography and abdominal imaging in both human and veterinary applications after clinical trials.

Intra-individual comparison of Sonazoid contrast-enhanced ultrasound and SonoVue contrast-enhanced ultrasound in diagnosing hepatocellular carcinoma.

PURPOSE: To assess whether the diagnostic performance of Sonazoid contrast-enhanced ultrasound (SZUS) is non-inferior to that of SonoVue contrast-enhanced ultrasound (SVUS) in diagnosing hepatocellular carcinoma (HCC) in individuals with high risk. MATERIALS AND METHODS: This prospective study was conducted from October 2020 to May 2022 and included participants with a high risk of HCC who underwent SZUS and SVUS. All lesions were confirmed by clinical or pathological diagnosis. Each nodule was classified according to the Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System version 2017 (CEUS LI-RADS v2017) for SVUS and SZUS and the modified CEUS LI-RADS (using Kupffer phase defect instead of late and mild washout) for SZUS. The diagnostic performance of both two modalities for all observations was compared. Analysis of the vascular phase and Kupffer phase imaging characteristics of CEUS was performed. RESULTS: One hundred and fifteen focal liver lesions from 113 patients (94 HCCs, 12 non-HCC malignancies, and 9 benign lesions) were analysed. According to CEUS LI-RADS (v2017), SVUS and SZUS showed similar sensitivity (71.3% vs. 72.3%) and specificity (85.7% vs. 81.0%) in HCC diagnosis. However, the modified CEUS LI-RADS did not significantly improve the diagnostic efficacy of Sonazoid compared to CEUS LI-RADS v2017, having equivalent sensitivity (73.4% vs. 72.3%) and specificity (81.0% vs. 81.0%). The agreement between SVUS and SZUS for all observations was 0.610 (95% CI 0.475, 0.745), while for HCCs it was 0.452 (95% CI 0.257, 0.647). CONCLUSION: Using LI-RADS v2017, SZUS and SVUS showed non-inferior efficacy in evaluating HCC lesions. In addition, adding Kupffer phase defects to SZUS does not notably improve its diagnostic efficacy.

Effectiveness of contrast-enhanced duplex ultrasound for detecting renal artery stenosis: A systematic review.

PURPOSE: Contrast-enhanced duplex ultrasound (CEUS) might be a useful tool to diagnosing renal artery stenosis (RAS). We amalgamated and reviewed the evidence assessing the diagnostic accuracy of CEUS on detecting RAS compared to angiography. METHODS: This preregistered systematic review included studies that compared the presence of RAS via CEUS with angiography. Sources were searched in November 2022 and included Scopus, EMBASE, MEDLINE, CINAHL, and Academic Search Premier (n = 1717). The Quality Assessment of Diagnostic Studies 2 tool assessed study quality. Results are presented narratively. RESULTS: The studies included (n = 11) had a total of 447 unique participants (193 females) and average age of 56 ± 9 years. Five of eleven studies investigated CEUS using SonoVue contrast agent and reported an average accuracy (91% ± 2%), sensitivity (91% ± 3%), specificity (90% ± 5%), negative predictive value (86% ± 6%), and positive predictive value (94% ± 1%) with all values >80%. The accuracy of CEUS using other types of contrast agent (n = 6), including Levovsit (n = 3/6), Definity (n = 1/6), perfienapent emulsion (n = 1/6), and perfluorocarbon-exposed sonicated dextrose albumin (n = 1/6) was mixed. These studies detected an average accuracy of 91 ± 11% (n = 2/3% > 80%), sensitivity of 98% ± 4%, (n = 3/3% > 80%), and specificity of 86% ± 10% (n = 2/3% > 80%). Included studies had generally low risk of bias and applicability concerns except for unclear flow and timing (n = 7/11) and applicability of patient selection (n = 4/11). CONCLUSION: Despite being limited by the heterogeneity of included studies, our review indicates a high overall diagnostic accuracy for CEUS to detect RAS compared to angiography, with the largest evidence-base for SonoVue contrast. Radiologists and hospital decision makers should consider CEUS as an acceptable alternative to angiography.

Compared with SonoVue® LR-5, Sonazoid® modified LR-5 has better diagnostic sensitivity for hepatocellular carcinoma: a systematic review and meta-analysis.

Background: The contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) is a standardized system for reporting liver nodules in patients at risk of developing hepatocellular carcinoma (HCC) and is only recommended for pure blood pool agents such as SonoVue®. A modified LI-RADS was proposed for Sonazoid®, a Kupffer cell-specific contrast agent. This meta-analysis was conducted to compare the diagnostic efficiency of the CEUS LI-RADS for SonoVue® and the modified LI-RADS for Sonazoid®. Methods: The PubMed, Medline, Web of Science, Embase, and Cochrane Library databases were systematically searched to retrieve studies on the diagnostic efficiency of the CEUS LI-RADS algorithms in diagnosing HCC using SonoVue® and/or Sonazoid® from January 2016 to June 2023. Histopathology or imaging follow-up served as the reference standards. Only articles published in English on retrospective or prospective studies with full reports were included in the meta-analysis. A bivariate random-effects model was used. Data pooling, meta-regression, and sensitivity analysis were performed for the meta-analysis. Deeks' funnel plot asymmetry test was used to evaluate publication bias, and the QUADAS-2 tool was used to assess the methodological quality of eligible studies. Results: In total, 26 studies comprising 8,495 patients with 9,244 lesions were included in the meta-analysis. The pooled data results for SonoVue® LI-RADS category 5 (LR-5) and Sonazoid® modified LR-5 were as follows: pooled sensitivity: 0.68 [95% confidence interval (CI): 0.64-0.73, I2=89.20%; P<0.01] and 0.82 (95% CI: 0.74-0.87, I2=85.39%; P<0.01) (P<0.05); pooled specificity: 0.93 (95% CI: 0.90-0.96, I2=86.52%; P<0.01) and 0.86 (95% CI: 0.79-0.91, I2=59.91%; P=0.01) (P<0.05); pooled area under the curve (AUC): 0.86 (95% CI: 0.82-0.89) and 0.91 (95% CI: 0.88-0.93) (P<0.05), respectively. The meta-regression analysis revealed that the study design, subject enrollment method, and reference standard contributed to the heterogeneity of SonoVue® LR-5, and the number of lesions was a source of heterogeneity for Sonazoid® modified LR-5. The diagnostic performance of the LI-RADS category M (LR-M) algorithms of SonoVue® and Sonazoid® was comparable. Conclusions: The Sonazoid® modified LR-5 algorithm had a higher diagnostic sensitivity, lower specificity, and higher AUC than SonoVue® LR-5.

Preoperative assessment of fistula-in-ano using SonoVue enhancement during three-dimensional transperineal ultrasound.

Background: Accurate preoperative evaluation of fistula-in-ano can guide the choice of surgical procedure and may improve healing rates. This prospective study aimed to evaluate the accuracy of conventional 3D transperineal ultrasound (3D-TPUS) compared with SonoVue (SVE)-enhanced 3D-TPUS for the detection and classification of anal fistula. Methods: In this prospective study, 3D-TPUS reconstructions were performed before and after SVE enhancement in 60 patients with fistula-in-ano who intended to undergo surgery at the Department of Anorectal Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University (P. R. China) between January 2021 and October 2021. Accuracies of anal fistula classification, complexity classification, detection of anal fistula branches, and detection of internal opening between 3D-TPUS and SVE 3D-TPUS were compared based on a reference standard-intraoperative findings. Results: This study enrolled 60 patients (mean age, 37.1 ± 11.4 years; mean follow-up, 9 ± 3 months). Intraoperative findings showed that the fistula type was intersphincteric in 23 patients (38.3%), trans-sphincteric in 35 (58.3%; 12 high and 23 low), and suprasphincteric in 2 (3.3%). Moreover, 68 internal openings were found. Compared with the accuracy of 3D-TPUS, that of SVE 3D-TPUS was similar in fistula classification [95.0% (57/60) vs 96.7% (58/60), P = 0.392], but significantly higher in internal opening evaluation [80.9% (55/68) vs 97.1% (66/68), P = 0.001], complexity classification [85.0% (51/60) vs 98.3% (59/60), P = 0.018], and detection of fistula branches [70.4% (19/27) vs 92.6% (25/27), P = 0.031]. Conclusions: SVE 3D-TPUS may be a useful examination for patients with perianal fistulae because of its high accuracy and consistency with intraoperative findings, especially in complex fistula-in-ano and difficult cases.

Clinical Significance of Contrast-Enhanced Ultrasound Galactography in Pre-operative Diagnosis of Patients With Pathologic Nipple Discharge.

OBJECTIVE: The aim of the work described here was to investigate the feasibility and diagnostic value of using contrast-enhanced ultrasound (CEUS) galactography with SonoVue in patients with pathologic nipple discharge (PND). METHODS: Twenty-eight patients who underwent breast surgery for PND from May 2019 to August 2021 were included. Routine ultrasound, ductoscopy and CEUS galactography were performed successively. Lesions were diagnosed and localized. The sensitivity, specificity and pre-operative localization value of each examination method were evaluated on post-operative pathology. RESULTS: CEUS galactography was successfully conducted in all 28 patients and revealed negative ductal ectasia, filling stop and filling defect. Ductoscopy revealed positive nodules in 21 cases and negative nodules in 7 cases. A total of 18 nodules were found by routine ultrasound, and the relationship between all nodules and the discharge duct was confirmed after CEUS galactography. Compared with the other two methods, CEUS galactography had higher sensitivity, positive predictive value and negative predictive value (100%, 81.82% and 100%, respectively), while it has the same specificity as routine ultrasound (both 60%). The pre-operative location of the nipple duct was consistent with the intra-operative findings in 28 patients after CEUS galactography. CONCLUSION: The ultrasound contrast agent SonoVue can be used for CEUS galactography in patients with PND. CEUS galactography can improve the detection of ductal nodules and locate the nipple discharge duct pre-operatively. As the technique does not emit radiation and SonoVue is easily metabolized and safe, CEUS galactography is better than conventional imaging for PND patients.

Mechanistic study of ultrasound and microbubble enhanced cancer therapy in a 3D vascularized microfluidic cancer model.

Accumulating evidence has shown that ultrasound exposure combined with microbubbles can enhance cancer therapy. However, the underlying mechanisms at the tissue level have not been fully understood yet. The conventional cell culture in vitro lacks complex structure and interaction, while animal studies cannot provide micron-scale dynamic information. To bridge the gap, we designed and assembled a 3D vascularized microfluidic cancer model, particularly suitable for ultrasound and microbubble involved mechanistic studies. Using this model, we first studied SonoVue microbubble traveling dynamics in 3D tissue structure, then resolved SonoVue microbubble cavitation dynamics in tissue mimicking agarose gels at a frame rate of 0.675 M fps, and finally explored the impacts of ultrasound and microbubbles on cancer cell spheroids. Our results demonstrate that microbubble penetration in agarose gel was enhanced by increasing microbubble concentration, flow rate and decreasing viscosity of the gel, and little affected by mild acoustic radiation force. SonoVue microbubble exhibited larger expansion amplitudes in 2 %(w/v) agarose gels than in water, which can be explained theoretically by the relaxation of the cavitation medium. The immediate impacts of ultrasound and SonoVue microbubbles to cancer cell spheroids in the 3D tissue model included improved cancer cell spheroid penetration in micron-scale and sparse direct permanent cancer cell damage. Our study provides new insights of the mechanisms for ultrasound and microbubble enhanced cancer therapy at the tissue level.

Assessment of arterial-phase hyperenhancement and late-phase washout of hepatocellular carcinoma-a meta-analysis of contrast-enhanced ultrasound (CEUS) with SonoVue® and Sonazoid®.

OBJECTIVES: The recognition of arterial phase hyperenhancement (APHE) and washout during the late phase is key for correct diagnosis of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS). This meta-analysis was conducted to compare SonoVue®-enhanced and Sonazoid®-enhanced ultrasound in the assessment of HCC enhancement and diagnosis. METHODS: Studies were included in the analysis if they reported data for HCC enhancement in the arterial phase and late phase for SonoVue® or in the arterial phase and Kupffer phase (KP) for Sonazoid®. Forty-two studies (7502 patients) with use of SonoVue® and 30 studies (2391 patients) with use of Sonazoid® were identified. In a pooled analysis, the comparison between SonoVue® and Sonazoid® CEUS was performed using chi-square test. An inverse variance weighted random-effect model was used to estimate proportion, sensitivity, and specificity along with 95% confidence interval (CI). RESULTS: In the meta-analysis, the proportion of HCC showing APHE with SonoVue®, 93% (95% CI 91-95%), was significantly higher than the proportion of HCC showing APHE with Sonazoid®, 77% (71-83%) (p < 0.0001); similarly, the proportion of HCC showing washout at late phase/KP was significantly higher with SonoVue®, 86% (83-89%), than with Sonazoid®, 76% (70-82%) (p < 0.0001). The sensitivity and specificity for the detection of APHE plus late-phase/KP washout detection in HCC were also higher with SonoVue® than with Sonazoid® (sensitivity 80% vs 52%; specificity 80% vs 73% in studies within unselected patient populations). CONCLUSION: APHE and late washout in HCC are more frequently observed with SonoVue® than with Sonazoid®. This may affect the diagnostic performance of CEUS in the diagnosis of HCCs. CLINICAL RELEVANCE STATEMENT: Meta-analysis data show the presence of key enhancement features for diagnosis of hepatocellular carcinoma is different between ultrasound contrast agents, and arterial hyperenhancement and late washout are more frequently observed at contrast-enhanced ultrasound with SonoVue® than with Sonazoid®. KEY POINTS: • Dynamic enhancement features are key for imaging-based diagnosis of HCC. • Arterial hyperenhancement and late washout are more often observed in HCCs using SonoVue®-enhanced US than with Sonazoid®. • The existing evidence for contrast-enhanced US may need to be considered being specific to the individual contrast agent.

A review of contrast-enhanced ultrasound using SonoVue® and Sonazoid™ in non-hepatic organs.

Contrast-enhanced ultrasound (CEUS) is a dependable modality for the diagnosis of various clinical conditions. A judicious selection of ultrasound contrast agent (UCA) is imperative for optimizing imaging and improving diagnosis. Approved UCAs for imaging the majority of organs include SonoVue, a pure blood agent, and Sonazoid, which exhibits an additional Kupffer phase. Despite the fact that the two UCAs are increasingly being employed, there is a lack of comparative reviews between the two agents in different organs diseases. This review represents the first attempt to compare the two UCAs in non-hepatic organs, primarily including breast, thyroid, pancreas, and spleen diseases. Through comparative analysis, this review provides a comprehensive and objective evaluation of the performance characteristics of SonoVue and Sonazoid, with the aim of offering valuable guidance for the clinical application of CEUS. Overall, further clinical evidences are required to compare and contrast the dissimilarities between the two UCAs in non-hepatic organs, enabling clinicians to make an appropriate selection based on actual clinical applications.

Safety of Lumason® (SonoVue®) in special populations and critically ill patients.

Evidence for the safe use of Lumason® (SonoVue®), an ultrasound enhancing agent (UEA), in special patient populations is critical to enable healthcare professionals to make informed decisions concerning its use in such patients. Herein, we provide insight on the safety and tolerability of Lumason® in special patient populations. Findings are presented from clinical pharmacology studies conducted in patients with compromised cardiopulmonary conditions, from a retrospective study performed in critically ill patients, and from post-marketing surveillance data from over 20 years of market use of Lumason® (SonoVue®). No detrimental effects of Lumason® on cardiac electrophysiology were observed in patients with coronary artery disease (CAD), and no significant effects on pulmonary hemodynamics were noted in patients with pulmonary hypertension or congestive heart failure. Similarly, no effects on several assessments of pulmonary function (e.g., FVC) were observed in patients with chronic obstructive pulmonary disease (COPD), and no clinically meaningful changes in O2 saturation or other safety parameters were observed after administration of Lumason® to patients with diffuse interstitial pulmonary fibrosis (DIPF). The retrospective study of critically ill patients revealed no significant difference for in-hospital mortality between patients administered Lumason® for echocardiography versus those who had undergone echocardiography without contrast agent. Post-marketing surveillance revealed very low reporting rates (RR) for non-serious and serious adverse events and that serious hypersensitivity reactions were rare. These findings confirm that Lumason® is a safe and well tolerated UEA for use in special populations and critically ill patients.

Sonazoid-enhanced ultrasonography for noninvasive imaging diagnosis of hepatocellular carcinoma: special emphasis on the 2022 KLCA-NCC guideline.

Contrast-enhanced ultrasonography (CEUS) is a noninvasive imaging modality used to diagnose hepatocellular carcinoma (HCC) based on specific imaging features, without the need for pathologic confirmation. Two types of ultrasound contrast agents are commercially available: pure intravascular agents (such as SonoVue) and Kupffer agents (such as Sonazoid). Major guidelines recognize CEUS as a reliable imaging method for HCC diagnosis, although they differ depending on the contrast agents used. The Korean Liver Cancer Association-National Cancer Center guideline includes CEUS with either SonoVue or Sonazoid as a second-line diagnostic technique. However, Sonazoid-enhanced ultrasound is associated with several unresolved issues. This review provides a comparative overview of these contrast agents regarding pharmacokinetic features, examination protocols, diagnostic criteria for HCC, and potential applications in the HCC diagnostic algorithm.

Contrast-enhanced ultrasound-guided sentinel lymph node biopsy in early-stage breast cancer: a prospective cohort study.

OBJECTIVE: This study evaluated the identification efficiency of contrast-enhanced ultrasound (CEUS) for sentinel lymph nodes (SLN) to accurately represent the axillary node status in early-stage breast cancer. METHOD: In total, 109 consecutive consenting patients with clinically node-negative and T1-2 breast cancer were included in this study. All patients received CEUS to identify SLN before surgery, and a guidewire was deployed to locate SLN in those who were successfully explored by CEUS. The patients underwent sentinel lymph node biopsy (SLNB), and the blue dye was used to trace SLN during the surgery. The decision to perform axillary lymph node dissection (ALND) depended on the intraoperative pathological identification of SLN by CEUS (CE-SLN). The concordance rate of pathological status between CE-SLN and dyed SLN was calculated. RESULT: The CEUS detection rate was 96.3%; CE-SLN failed in 4 patients. Among the remaining 105 successful identifications, 18 were CE-SLN positive by intraoperative frozen section, and one with CE-SLN micrometastasis was diagnosed by paraffin section. No additional lymph node metastases were found in CE-SLN-negative patients. The concordance rate of pathological status between CE-SLN and dyed SLN was 100%. CONCLUSION: CEUS can accurately represent the status of axillary lymph nodes in patients with clinically node-negative and small tumor burden breast cancer.

Trans-intrauterine contrast-enhanced ultrasound (CEUS) can be an effective approach for the diagnosis of vesicouterine fistula (VUF), especially for patients with fistulas flowing unidirectionally from the uterine cavity.

Background: Vesicouterine fistula (VUF) is a rare complication after cesarean section. It is challenging to diagnose VUF correctly. Case presentation: A 34-year-old woman complained of recurrent hematuria and urinary tract infection for more than 4 years after cesarean delivery, mostly during menstruation, without vaginal leakage and with a normal menstrual cycle. Conventional transabdominal ultrasound showed no abnormal findings in bilateral kidneys and ureters, bladder and uterus, and transvaginal ultrasound showed that the scar at the lower part of the anterior uterine wall was closely adhered to the posterior wall of the bladder. Considering that the patient had hematuria but no vaginal leakage, we assumed that the fistula was flowing unidirectionally from the uterine cavity to the bladder cavity. Therefore, we chose to inject SonoVue (ultrasound contrast agent) into the uterine cavity rather than into the bladder. After intrauterine injection of SonoVue, the ultrasound contrast agent was seen flowing from the uterine cavity into the bladder cavity through the fistula, showing a hyperechoic fistula between the posterior wall of the bladder and the uterine wall, confirming the diagnosis of VUF. The accuracy of this diagnosis was then further confirmed by both MRI and cystoscopy. Conclusions: Trans-intrauterine CEUS provides a new effective imaging method for the diagnosis of VUF, especially for patients with fistulas that flow unidirectionally from the uterine cavity.

Contrast-Enhanced Ultrasound With SonoVue and Sonazoid for the Diagnosis of Colorectal Liver Metastasis After Chemotherapy.

PURPOSE: To compare the diagnostic efficacy of SonoVue and Sonazoid contrast-enhanced ultrasound (CEUS) in correctly detecting and characterizing colorectal liver metastasis (CRLM) after chemotherapy. MATERIALS AND METHODS: Patients with CRLMs treated with chemotherapy and subsequently scheduled for hepatic resection were prospectively enrolled from April 2020 to January 2021. Lesions detected by SonoVue or Sonazoid CEUS were recorded as and characterized as metastases or non-metastatic lesions respectively. Histopathology or intraoperative ultrasound with MRI were the reference standard. RESULTS: A total of 348 focal liver lesions in 42 patients were investigated, including 297 CRLMs and 51 non-metastatic lesions. SonoVue showed significantly higher diagnostic accuracy (64.7% versus 54.0%; P < .001) and sensitivity (63.3% versus 50.5%; P < .001) in the diagnosis of CRLMs than Sonazoid, both methods presented with similar specificity (72.5% versus 74.5%; P = 1.0). Forty metastases appeared non-hypoenhancing (hyperenhancing or isoenhancing) in the late phase and postvascular phase of Sonazoid CEUS and were mischaracterized as benign lesions. CONCLUSION: SonoVue performed significantly better than Sonazoid in the diagnosis of CRLMs after chemotherapy.

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.

High frame-rate contrast enhanced ultrasound (HIFR-CEUS) in the characterization of small hepatic lesions in cirrhotic patients.

BACKGROUND: To show the effectiveness of plane wave HighFrame-Rate CEUS (HiFR-CEUS) compared with "conventional" (plane wave) CEUS (C-CEUS) in the characterization of small (< 2 cm) focal liver lesions (FLLs) not easily detected by CT in cirrhotic patients. HiFR-CEUS exploit an ultra-wideband nonlinear process to combine fundamental, second and higher-order harmonic signals generated by ultrasound contrast agents to increase the frame rate. C-CEUS is limited by the transmission principle, and its frame-rate is around 10 FPS. With HiFR-CEUS (Shenzhen Mindray Bio-Medical Electronics Co., China), the frame-rate reached 60 FPS. MATERIAL AND METHODS: Ultrasound detected small FLLs (< 2 cm) in 63 cirrhotic patients during follow-up (June 2019-February 2020); (7 nodules < 1 cm and were not evaluable by spiral CT). Final diagnosis was obtained with MRI (47) or fine needle aspiration (16 cases) C-CEUS was performed and HiFR-CEUS was repeated after 5 min; 0.8-1.2 ml of contrast media (SonoVue, Bracco, Italy) was used. 57 nodules were better evaluable with HiFR-CEUS; 6 nodules were equally evaluable by both techniques; final diagnosis was: 44 benign lesions (29 hemangiomas, 1 amartoma, 2 hepatic cysts; 2 focal nodular hyperplasias, 3 regenerative macronodules, 3 AV-shunts, 3 hepatic sparing areas and 1 focal steatosis) and 19 malignant one (17 HCCs, 1 cholangioca, 1 metastasis); statistical evaluation for better diagnosis with X2 test (SPSS vers. 26); we used LI-RADS classification for evaluating sensitivity, specificity PPV, NPV and diagnostic accuracy of C- and HFR-CEUS. Corrispective AU-ROC were calculated. RESULTS: C-CEUS and HiFR-CEUS reached the same diagnosis in 29 nodules (13 nodules > 1 < 1.5 cm; 16 nodules > 1.5 < 2 cm); HiFR-CEUS reached a correct diagnosis in 32 nodules where C-CEUS was not diagnostic (6 nodules < 1 cm; 17 nodules > 1 < 1.5 cm; 9 nodules > 1.5 < 2 cm); C-CEUS was better in 2 nodules (1 < 1 cm and 1 > 1 < 1.5 cm). Some patient's (sex, BMI, age) and nodule's characteristics (liver segment, type of diagnosis, nodule's dimensions (p = 0.65)) were not correlated with better diagnosis (p ns); only better visualization (p 0.004) was correlated; C-CEUS obtained the following LI-RADS: type-1: 18 Nodules, type-2: 21; type-3: 7, type-4: 7; type-5: 8; type-M: 2; HiFR-CEUS: type-1: 38 Nodules, type-2: 2; type-3:4, type-4: 2; type-5: 15; type-M: 2; In comparison with final diagnosis: C-CEUS: TP: 17; TN: 39; FP: 5; FN:2; HIFR-CEUS: TP: 18; TN: 41; FP: 3; FN:1; C-CEUS: sens: 89.5%; Spec: 88.6%, PPV: 77.3%; NPV: 95.1%; Diagn Acc: 88.6% (AU-ROC: 0.994 ± SEAUC: 0.127; CI: 0.969-1.019); HiHFR CEUS: sens: 94.7%; Spec: 93.2%, PPV: 85.7%; NPV: 97.6%; Diagn Acc: 93.2% (AU-ROC: 0.9958 ± SEAUC: 0.106; CI: 0.975-1.017) FLL vascularization in the arterial phase was more visible with HiFR-CEUS than with C-CEUS, capturing the perfusion details in the arterial phase due to a better temporal resolution. With a better temporal resolution, the late phase could be evaluated longer with HiFR-CEUS (4 min C-CEUS vs. 5 min HiFR-CEUS). CONCLUSION: Both C-CEUS and HIFR-CEUS are good non invasive imaging system for the characterization of small lesions detected during follow up of cirrhotic patients. HiFR-CEUS allowed better FLL characterization in cirrhotic patients with better temporal and spatial resolution capturing the perfusion details that cannot be easily observed with C-CEUS.

Analysis of the Predictive Capacity of the Clinical Variables That Indicate the Performance of Voiding Urosonography in the Study of Vesicoureteral Reflux in Children.

INTRODUCTION: Voiding urosonography (VUS) is a dynamic imaging technique which evaluates the lower urinary tract by introducing sonographic contrast into the bladder, preferably used in the diagnosis of vesicoureteral reflux (VUR). Our goals were to describe the clinical indications for performing a VUS for VUR's diagnosis and analyse its diagnostic reliability. MATERIAL AND METHODS: Cross-sectional study carried on patients under 15 years old with a VUS taken between November 2013-2020. Sex, age, indications (lower urinary tract infection-LUTI; dilatated lower urinary tract-DLUT; duplex collecting system-DCS), results (presence/absence of VUR, score and side) and complications were analysed. U Mann-Whitney and Chi-squared tests were used and 2 predictive capacity models for the indications used to detect VUR were employed (logistic binomial regression and multilayer perceptron neural network). Statistical significance p < 0.05. RESULTS: 415 VUS were completed correctly (male 51.8%, median age 7.3 (3.1-15.3) months). Indications were: LUTI (67.5%), DLUT (33.5%) and DCS (10.2%); presenting 1, 2 and 3 indications in 86.5%, 12.8% and 0.7% respectively. VUR was diagnosed in 34.7% cases. A tendency towards statistically significance was showed related to male sex (p = 0.052) and the only significative clinical indication for VUR was DCS (p = 0.007). Patients with 2 simultaneous indications had higher probability of VUR (p = 0.012). DCS presence or male sex were the only predictive variables of VUR: DCS = OR 1.89 (1.54-6.52) (p = 0.006) and male sex = OR 1.56 (1.03-2.35) (p = 0.035). CONCLUSIONS: VUS is a thriving technique, radiation free and with a low complications rate. Presence of DCS, male sex or 2 simultaneous indications for VUS increase the probability of presenting VUR.

Sonazoid™ versus SonoVue® for Diagnosing Hepatocellular Carcinoma Using Contrast-Enhanced Ultrasound in At-Risk Individuals: A Prospective, Single-Center, Intraindividual, Noninferiority Study.

OBJECTIVE: To determine whether Sonazoid-enhanced ultrasound (SZUS) was noninferior to SonoVue-enhanced ultrasound (SVUS) in diagnosing hepatocellular carcinoma (HCC) using the same diagnostic criteria. MATERIALS AND METHODS: This prospective, single-center, noninferiority study (NCT04847726) enrolled 105 at-risk participants (71 male; mean age ± standard deviation, 63 ± 11 years; range, 26-86 years) with treatment-naïve solid hepatic nodules (≥ 1 cm). All participants underwent same-day SZUS (experimental method) and SVUS (control method) for one representative nodule per participant. Images were interpreted by three readers (the operator and two independent readers). All malignancies were diagnosed histopathologically, while the benignity of other lesions was confirmed by follow-up stability or pathology. The primary endpoint was per-lesion diagnostic accuracy for HCC pooled across three readers using the conventional contrast-enhanced ultrasound diagnostic criteria, including arterial phase hyperenhancement followed by mild (assessed within 2 minutes after contrast injection) and late (≥ 60 seconds with a delay of 5 minutes) washout. The noninferiority delta was -10%p. Furthermore, different time delays were compared as washout criteria in SZUS, including delays of 2, 5, and > 10 minutes. RESULTS: A total of 105 lesions (HCCs [n = 61], non-HCC malignancies [n = 19], and benign [n = 25]) were evaluated. Using the 5-minutes washout criterion, per-lesion accuracy of SZUS pooled across the three readers (72.4%; 95% confidence interval [CI], 64.1%-79.3%) was noninferior to that of SVUS (71.4%; 95% CI, 63.1%-78.6%), meeting the statistical criterion for non-inferiority (difference of 0.95%p; 95% CI, -3.8%p-5.7%p). The arterial phase hyperenhancement combined with the 5-minutes washout criterion showed the same sensitivity as that of the > 10-minutes criterion (59.0% vs. 59.0%, p = 0.989), and the specificities were not significantly different (90.9% vs. 86.4%, p = 0.072). CONCLUSION: SZUS was noninferior to SVUS for diagnosing HCC in at-risk patients using the same diagnostic criteria. No significant improvement in HCC diagnosis was observed by extending the washout time delay from 5 to 10 minutes.

A Comparison of the Sensitivity of Contrast-Specific Imaging Modes on Clinical and Preclinical Ultrasound Scanners.

Ultrasonic contrast agents are used routinely to aid clinical diagnosis. All premium- and mid-range scanners utilise contrast-specific imaging techniques to preferentially isolate and display the nonlinear signals generated from the microbubbles when insonated with a series of ultrasound pulses. In this manuscript the abilities of four premium ultrasound scanners to detect and display the ultrasound signal from two commercially available contrast agents-SonoVue and DEFINITY®-are compared. A flow phantom was built using tubes with internal diameters of 1.6 mm and 3.2 mm, suspended at depths of 1, 5 and 8 cm and embedded in tissue-mimicking material. Dilute solutions of SonoVue and DEFINITY® were pumped through the phantom at 0.25 mL/s and 1.5 mL/s. Four transducers were used to scan the tubes-a GE Logiq E9 (C2-9) curvilinear probe, a Philips iU22 L9-3 linear array probe, an Esaote MyLab Twice linear array LA523 (4-13 MHz) and a Fujifilm VisualSonics Vevo3100 MX250 (15-30 MHz) linear array probe. We defined a new parameter to compare the ability of the ultrasound scanners to display the contrast enhancement. This was defined as the ratio of grey-scale intensity ratio in contrast-specific imaging mode relative to the B-mode intensity from the same region-of-interest within the corresponding B-mode image. The study demonstrated that the flow rates used in this study had no effect on the contrast-specific imaging mode to B-mode (CSIM-BM) ratio for the three clinical scanners studied, with SonoVue demonstrating broadly similar CSIM-BM ratios across all 3 clinical scanners. DEFINITY® also displayed similar results to SonoVue except when insonated with the Esaote MyLab Twice LA523 transducer, where it demonstrated significantly higher CSIM-BM ratios at superficial depths.