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Current pharmacotherapies for depression exhibit slow onset, side effects and limited efficacy. Therefore, identification of novel fast-onset antidepressants is desirable. GLO1 is a ubiquitous cellular enzyme responsible for the detoxification of the glycolytic byproduct methylglyoxal (MG). We have previously shown that MG is a competitive partial agonist at GABA-A receptors. We examined the effects of genetic and pharmacological inhibition of GLO1 in two antidepressant assay models: the tail suspension test (TST) and the forced swim test (FST). We also examined the effects of GLO1 inhibition in three models of antidepressant onset: the chronic FST (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy (OBX). Genetic knockdown of Glo1 or pharmacological inhibition using two structurally distinct GLO1 inhibitors (S-bromobenzylglutathione cyclopentyl diester (pBBG) or methyl-gerfelin (MeGFN)) reduced immobility in the TST and acute FST. Both GLO1 inhibitors also reduced immobility in the cFST after 5 days of treatment. In contrast, the serotonin reuptake inhibitor fluoxetine (FLX) reduced immobility after 14, but not 5 days of treatment. Furthermore, 5 days of treatment with either GLO1 inhibitor blocked the depression-like effects induced by CMS on the FST and coat state, and attenuated OBX-induced locomotor hyperactivity. Finally, 5 days of treatment with a GLO1 inhibitor (pBBG), but not FLX, induced molecular markers of the antidepressant response including brain-derived neurotrophic factor (BDNF) induction and increased phosphorylated cyclic-AMP response-binding protein (pCREB) to CREB ratio in the hippocampus and medial prefrontal cortex (mPFC). Our findings indicate that GLO1 inhibitors may provide a novel and fast-acting pharmacotherapy for depression.

Objective: Nearly all reported parathyroid cancers are >15 mm at presentation. The objective was to identify ultrasound criteria of malignancy in parathyroid lesions of >15 mm in size.Materials and Methods: This study was approved by a local ethics committee. A retrospective review of patients identified from a database from 2004-2009 was performed. All patients underwent ultrasound imaging according to the protocol. Two trained observers categorized findings using the pre-determined features: shape, calcification, pattern of vascularity, local infiltration and internal lesion gray scale appearances.Results: Sixty-nine patients (mean age 54.3 years, range 19-79 years; male = 16, female = 53) fulfilled the criteria of a parathyroid lesion >15 mm; 8/69 (11.6%) with parathyroid cancer and 61/69 (88.4%) with benign solitary parathyroid adenoma. A high positive predictive value (PPV) for cancer was identified for infiltration (PPV 100%) and calcification (PPV 100%), whilst a high negative predictive value (NPV) was found for the absence of suspicious vascularity (NPV 97.6%), a thick capsule (NPV 96.7) and inhomogeneity (NPV 100%).Conclusion: In lesions >15 mm systematic ultrasound assessment of specific features provides a valuable tool to identify parathyroid cancers before surgery. [ABSTRACT FROM AUTHOR]

Objective: To conduct a dose testing analysis of perfluorobutane microbubble (NC100100) contrast-enhanced ultrasound (CEUS) to determine the optimal dose for detection of liver metastases in patients with extra-hepatic primary malignancy.Methods: 157 patients were investigated with conventional US and CEUS. CEUS was performed following intravenous administration of perfluorobutane microbubbles (using one dose of either 0.008, 0.08, 0.12 or 0.36 μL/kg body weight). Three blinded off-site readers recorded the number and locations of metastatic lesions detected by US and CEUS. Contrast enhanced CT and MRI were used as the "Standard Of Reference" (SOR). Sensitivity, specificity and accuracy of liver metastasis detection with US versus CEUS, for each dose group were obtained. Dose group analysis was performed using the Chi-square test.Results: 165 metastases were present in 92 patients who each had 1-7 lesions present on the SOR. Sensitivity of US versus CEUS (for all doses combined) was 38% and 67% (p = 0.0001). The 0.12 dose group with CEUS (78%) had significantly higher sensitivity and accuracy (70%) compared to other dose groups (p < 0.05).Conclusion: The diagnostic performance of CEUS is dose dependent with the 0.12 μL/kg NC100100 dose group showing the greatest sensitivity and accuracy in detection of liver metastases. [ABSTRACT FROM AUTHOR]

To review our experience of placement of a mushroom-cage gastrostomy tube (Entristar, Tyco Healthcare, Mansfield, MA), using radiological guidance, in patients with amyotrophic lateral sclerosis (ALS). All procedures were performed under local anaesthesia without sedation. Complications were recorded as peri-procedural, early (<24 h), late (>24 h), major or minor. Deaths were recorded as related to the underlying ALS or secondary to radiological-inserted gastrostomy (RIG) placement. Replacement RIG tube rate was recorded. Over a 5-year period RIG tubes were placed in 104 patients with ALS (male n = 52, female n = 52), with a median age of 62 years (range 34-86 years). All procedures were technically successful. Of the RIG procedures, 21/104 (20.2%) were performed with respiratory support. The 30-day mortality rate was 7/104 (6.7%); no patient died as a result of the procedure. There were 23/104 (22.1%) complications overall; 20/104 (19.2%) were minor and 3/104 (2.9%) major, requiring surgery (n = 2) and radiological-guided abscess drainage (n = 1). A median interval between replacement RIG procedures in 20/104 (19.2%) patients was 141.5 days (range 43-537 days). A mushroom-cage RIG tube may be safely and effectively inserted in a 'one-step' radiological procedure and may replace endoscopic-inserted gastrostomy tubes in the nutritional management of ALS. [ABSTRACT FROM AUTHOR]

Aim: To determine the prevalence and variation in appearance of the "two-tone" testes artefact. Methods and Materials: Patients attending for a testicular ultrasound, without an intra-testicular lesion, were included. A single operator performed examinations using a 15L8w linear array transducer. When an artefact resembling the "two-tone" testes appearance was seen, the images were recorded prospectively. Two independent observers reviewed the images and identified patterns of the two-tone testis as: partial posterior shadowing from an incompletely identified trans-testicular artery; partial posterior shadowing from a completely identified trans-testicular artery; total posterior shadowing from a completely identified trans-testicular artery. Results: Over a 44-month period 1038 patients were examined. The median age of patients was 32.5 years (range 19-46 years). A total of 17 two-tone testes artefacts of varying appearances were identified in 16 patients, occurring in 1.6% of the selected population. There were six partial posterior shadowing from an incompletely identified trans-testicular artery (0.6%); five partial posterior shadowing from a completely identified trans-testicular artery (0.5%); and five total posterior shadowing from a completely identified trans-testicular artery (0.5%) artefacts present. There was no relationship between the two-tone artefact and clinical symptoms or other ultrasound findings. Conclusion: The two-tone testis artefact is a rare finding and has a variable appearance according to the extent of acoustic shadowing produced. Careful examination of the testis and operator experience is required when the artefact is identified in order that underlying pathological disease is not overlooked. [ABSTRACT FROM AUTHOR]

Aim: To determine whether delayed-phase liver imaging using a destructive imaging mode is able to provide similar information to phase-inversion imaging regarding detection and conspicuity of liver metastases. Material and Methods: Patients with a known primary malignancy with suspected liver metastases were recruited. Ultrasound was performed at baseline, and up to 5 min after the administration of Sonazoid, using phase-inversion imaging at both low and high mechanical indices (MI) and at 10-15 min using destructive imaging. One of four doses of Sonazoid was used: 0.008, 0.08, 0.12, and 0.36 microl/kg of body weight. Two observers documented lesion number and conspicuity subjectively, and divided the patients into group A (no lesions), group B (one to seven lesions), and group C(I-III) (more than eight lesions, subdivided with increasing lesion number) depending on the number of lesions and categories I-IV based on lesion conspicuity. These parameters were compared with contrast-enhanced computed tomography (CECT) as the reference standard. Results: Sixteen patients were examined (six women, 10 men), mean age 67.3 years (range 48-83 years). Based on CECT imaging, the division was as follows: group A n=1, group B n=8, group C(I)n=1, group C(II)n=4, group C(III)n=2. The accuracy of baseline ultrasound versus CECT was 75% (in 12 of the 16 patients the group concurred) and the accuracy for contrast-enhanced ultrasound (CEUS) versus CECT was 93.8% (15/16). There was a significant improvement in lesion conspicuity for both low (p=0.0029) and high MI phase-inversion (p=0.0004) and destructive (p=0.0015) CEUS imaging in comparison with baseline ultrasound. Artefact was noted at higher doses of Sonazoid; and no side effects were recorded. Conclusion: Following a single, intravenous injection of Sonazoid, the properties of this microbubble allow for a and robust examination of the liver using two different techniques with comparable results. [ABSTRACT FROM AUTHOR]

Objectives: Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is used to definitively diagnose hepatocellular carcinoma (HCC) in patients at risk. However, the user variability associated with CEUS LI-RADS has not been validated in North American and European patients. This study aims to evaluate the inter-reader agreements of CEUS LI-RADS features for, and final categorization of, HCC in patients at risk., Methods: This retrospective multicenter clinical study used the database of a previous prospective multinational study, evaluating the accuracy of CEUS LI-RADS for HCC diagnosis in patients at risk. All cases were first evaluated by a site physician performing/supervising the CEUS examination. Randomly selected cases were re-evaluated by a blinded central reader. Final diagnosis was confirmed with the reference standard, which was a composite of imaging tests and histology. Cohen's kappa test was used to evaluate inter-reader agreement., Results: This study included 150 liver nodules and 58.0% (87/150) were confirmed as HCC, 4.7% (7/150) non-HCC malignancies, 22.7% (34/150) had no confirmed final diagnosis, and 14.7% (22/150) were nonmalignant. Inter-reader agreements were substantial for CEUS LI-RADS categorization (κ = 0.61; 95% confidence interval [CI]: 0.51-0.71) and major features assessment (ranged κ = 0.64-0.78), LR-5 (κ = 0.65; 95% CI: 0.52-0.77), and LR-M (κ = 0.67; 95% CI: 0.44-0.90), while for LR-1 and LR-2 categorization was almost perfect (κ = 0.85; 95% CI: 0.65-1.00)., Conclusion: Our study reported a substantial inter-reader agreement for overall CEUS LI-RADS categorization, especially for LR-5 and LR-M, and major imaging features of HCC, further confirming CEUS LI-RADS as a valuable and reliable tool for diagnosis of HCC., (© 2024 The Author(s). Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

Purpose: To determine the diagnostic accuracy of combining CEUS and CT/MRI LI-RADS major imaging features for the improved categorization of liver observations indeterminate on both CT/MRI and CEUS., Materials and Methods: A retrospective analysis using a database from a prospective study conducted at 11 centers in North America and Europe from 2018 to 2022 included a total of 109 participants at risk for HCC who had liver observations with indeterminate characterization (LR3, LR-4, and LR-M) on both CEUS and CT/MRI. The individual CEUS and CT/MRI LI-RADS major features were extracted from the original study and analyzed in various combinations. Reference standards included biopsy, explant histology, and follow-up CT/MRI. The diagnostic performance of the combinations of LI-RADS major features for definitive diagnosis of HCC was calculated. A reverse, stepwise logistical regression sub-analysis was also performed., Results: This study included 114 observations indeterminate on both CT/MRI and CEUS. These observations were categorized as LR-3 (n = 37), LR-4 (n = 41), and LR-M (n = 36) on CT/MRI and LR-3 (n = 48), LR-4 (n = 36), LR-M (n = 29), and LR-TIV (n = 1) on CEUS. Of them, 43.0% (49/114) were confirmed as HCC, 37.3% (43/114) non-malignant, and 19.3% (22/114) non-hepatocellular malignancies. The highest diagnostic accuracy among the combinations of imaging features was achieved in CT/MRI LR-3 observations, where the combination of CEUS arterial phase hyper-enhancement (APHE) + CT/MRI APHE had 96.7% specificity, 75.0% positive predictive value (PPV), and 86.5% accuracy for HCC., Conclusion: The combination of LI-RADS major features on CT/MRI and CEUS showed higher specificity, PPV, and accuracy compared to individual modalities' assessments, particularly for CT/MRI LR-3 observations., (© 2024. The Author(s).)

Introduction: ElaTION is a large multi-centre pragmatic randomised controlled trial, performed in 18 secondary/tertiary hospitals across England, comparing elastography ultrasound-guided fine needle aspiration cytology (EUS-FNAC) with ultrasound-guided FNAC (US-FNAC) alone in the diagnostic assessment of thyroid nodules. Secondary trial outcomes, reported here, assessed the accuracy of ultrasound-alone (US) compared with US-guided FNAC to inform and update current practice guidelines., Methods: Adults with single or multiple thyroid nodules who had not undergone previous FNAC were eligible. Radiologists assessed all thyroid nodules using US alone, thereby enabling assessment of its accuracy (sensitivity and specificity) versus US-FNAC., Results: Of the 982 participants, a final definitive diagnosis was obtained in 688, who were included in the final analyses. The sensitivity of US-alone was the same as US-FNAC (0.91, [95% CI 0.85, 0.97] vs 0.87 [95%CI 0.80-0.95], p=0.37). US alone had statistically significant lower specificity than US-FNAC alone (0.48 vs 0.67 respectively, p<0.0001). The malignancy rate on histology in a nodule classified as benign on ultrasound (U2) was 9/263 (3.42%) and on cytology (Thy2) was 15/353 (4.25%), whereas the malignancy rate in a nodule that was benign on both (U2, Thy2) was 3/210 (1.43%). Malignancy risk for U3, U4, and U5 nodules was 68/304 (22.4%), 43/83 (51.8%), and 29/38 (76.3%) respectively (p<0.0001). Yet 80/982 (8%) patients were discharged despite having U3-U5 scans with Thy1 (non-diagnostic) FNAC and no definitive diagnosis.Malignancy risk was higher in smaller nodules: <10mm 23/60 (38.3%), 10-20mm 46/162 (28.4 %), and >20mm 80/466 (17.2%) (p<0.0001). Nodules with indeterminate cytology with atypical features (Thy3a) carried a similar malignancy risk to those with indeterminate cytology (Thy3/3f): 27/95 (28.4%) versus 42/113 (37.2%) respectively (p=0.18)., Conclusion: Ultrasound alone appears to be an effective diagnostic modality in thyroid nodules, confirming the recommendations of recent guidelines and the BTA classification. However, findings also suggest caution regarding existing recommendations for conservative management of non-diagnostic (Thy1/Bethesda I) and atypical (Thy3a/Bethesda III) nodules. In those cases, ultrasound (U3-5) features may help identify high-risk subgroups for more proactive management., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background There is variable evidence and no randomized trials on the benefit of US elastography-guided fine-needle aspiration cytology (FNAC) over conventional US-guided FNAC alone for thyroid nodules. Purpose To compare the efficacy of US elastography-guided FNAC versus US-guided FNAC in reducing nondiagnostic rates for thyroid nodules. Materials and Methods A pragmatic, multicenter randomized controlled trial was performed at 18 secondary and tertiary hospitals across England between February 2015 and September 2018. Eligible adults with single or multiple thyroid nodules who had not previously undergone FNAC were randomized (1:1 ratio) to US elastography FNAC (intervention) or conventional US FNAC (control). The primary outcome was the proportion of patients who have a nondiagnostic cytologic Thy1 (British Thyroid Association system) result following the first FNAC. Results A total of 982 participants (mean age, 51.3 years ± 15 [SD] [IQR, 39-63]; male-to-female ratio, 1:4) were randomized. Of the 493 participants who underwent US elastography, 467 (94.7%) were examined with strain US elastography. There was no difference between the two arms in the nondiagnostic (Thy1) rate following the first FNAC (19% vs 16%; risk difference [RD], 0.03 [95% CI: -0.01, 0.07]; P = .11) or in the median time to reach the final definitive diagnosis (3.3 months [IQR, 1.5-6.4] for US elastography FNAC vs 3.4 months [IQR, 1.5-6.2] for US FNAC). All sensitivity analyses supported the primary analysis. Fewer participants in the US elastography FNAC arm underwent diagnostic hemithyroidectomy than in the US FNAC arm (183 of 493 [37%] vs 196 of 489 [40%]), but this was not statistically significant (adjusted RD, 0.02 [95% CI: -0.06, 0.01]; P = 0.15). There was no evidence of a difference in malignancy rates between the two arms: 70 of 493 (14%) in US elastography FNAC arm versus 79 of 489 (16%) in US FNAC arm ( P = .39). There was also no difference in the rate of benign histologic findings between the groups (RD, -0.01 [95% CI: -0.04, 0.03]; P = .7). Conclusion Strain US elastography does not appear to have additional benefit over conventional US FNAC in the diagnosis of malignancy in thyroid nodules. Clinical trial registration no. ISRCTN18261857 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Isikbay and Harwin in this issue.

The innovative techniques in ultrasound have added a new dimension to investigating superficially located areas such as the contents of the scrotal sac. High frequency transducers, improved technology with the addition of elastography, contrast enhanced ultrasound and microvascular imaging has resulted in a further improvement in diagnostic capabilities. The ability to clearly demonstrate the presence or absence of vascularity within the area under investigation adds an additional dimension to operator confidence in establishing the presence of infarction, global or segmental, or the walls and cavity of an abscess in the testis or epididymis. Increased vascularity of a tumor aids the differential diagnosis based on the flow dynamics of the microbubble contrast, benign lesions likely to retain contrast. Elastography has the ability to ascertain the stiffness of tissue, and when used in conjunction with other ultrasound methods adds to the understanding of the likelihood of a malignant abnormality being present. All the different techniques come under the umbrella term 'multiparametric ultrasound', with the application in the scrotal sac detailed in this article., (© 2024. The Author(s).)

Quantitative ultrasound (QUS) and ultrasound-based elastography techniques are emerging as non-invasive effective methods for assessing chronic liver disease. They are more accurate than B-mode imaging alone and more accessible than MRI as alternatives to liver biopsy. Early detection and monitoring of diffuse liver processes such as steatosis, inflammation, and fibrosis play an important role in guiding patient management. The most widely available and validated techniques are attenuation-based QUS techniques and shear-wave elastography techniques that measure shear-wave speed. Other techniques are supported by a growing body of evidence and are increasingly commercialized. This review explains general physical concepts of QUS and ultrasound-based elastography techniques for evaluating chronic liver disease. The first section describes QUS techniques relying on attenuation, backscatter, and speed of sound. The second section discusses ultrasound-based elastography techniques analyzing shear-wave speed, shear-wave dispersion, and shear-wave attenuation. With an emphasis on clinical implementation, each technique's diagnostic performance along with thresholds for various clinical applications are summarized, to provide guidance on analysis and reporting for radiologists. Measurement methods, advantages, and limitations are also discussed. The third section explores developments in quantitative contrast-enhanced and vascular ultrasound that are relevant to chronic liver disease evaluation.

Background: Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive., Methods: A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3)., Results: 75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct., Conclusion: CEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging., Clinicaltrials: gov number, NCT03318380., (© 2024. The Author(s).)

Objective: To determine whether small, incidentally detected testicular lesions can be safely followed up, by assessing growth rate and volume threshold for benign vs. malignant lesions., Methods: This retrospective observational study includes a consecutive series of 130 testicular incidentalomas < 1 cm and with negative tumour markers identified from October 2001 to November 2022, which were initially followed up with ultrasound. A total of 39 cases proceeded to surgery during the study period, either due to lesion growth (n = 28) or patient preference/recommendation by the referring urologist (n = 11). For the lesions that were growing, specific growth rate (SGR) and doubling time (DT) were calculated assuming an exponential growth pattern. In addition, the velocity of increase of the average diameter (∆D av ) and of the maximum diameter (∆D max ) were calculated., Results: Of the 130 nodules that were initially followed up, six disappeared, eight were reduced in size, eighty-eight were stable, and twenty-eight increased in size. For operated nodules all 18 malignant tumours, 8/9 benign tumours, and 2/12 surgically proved non-neoplastic lesions were growing. The best cut-off values of the growth indicators to differentiate between malignant and non-malignant histology were 3.47 × 10 -3 %volume/day, ≤ 179 days, > 10 × 10 -3  mm/day, and > 5 × 10 -3  mm/day for SGR, DT, ∆D max , ∆D av , respectively., Conclusions: Malignant and non-malignant small incidentalomas can be effectively differentiated based on growing parameters, even though overlap exists. An increase of the maximum diameter of about 1 mm and 2 mm in three months and in six months, respectively, suggests malignancy., Clinical Relevance Statement: Growing parameters allow an educated assessment of benign and malignant small testicular incidentalomas. Non-aggressive management is justified and safe when follow-up includes self-examination and tumour marker assessment to reduce the risk of interval tumour growth., Key Points: Small, non-palpable and asymptomatic testicular nodules < 1 cm are unexpectedly discovered during scrotal ultrasound. Growth indicators estimate the potential malignancy, even though overlap with non-malignant lesions exists. Non-growing incidentalomas can be safely followed up., (© 2024. The Author(s).)

Conventional ultrasonography (US), including greyscale imaging and colour Doppler US (CDUS), is pivotal for diagnosing scrotal pathologies, but it has limited specificity. Historically, solid focal testicular abnormalities often led to radical orchidectomy. This retrospective study evaluated the utilisation of contrast-enhanced ultrasound (CEUS) and strain elastography (SE) in investigating intratesticular focal abnormalities. A total of 124 cases were analysed. This study underscored the superior diagnostic capabilities of CEUS in detecting vascular enhancement in all malignant cases, even those with undetectable vascularity by CDUS. It also highlighted the potential of CEUS in identifying distinctive vascular patterns in benign vascular tumours. Definitive confirmation of benignity could be obtained when the absence of enhancement was demonstrated on CEUS. While SE alone offered no distinctive advantage in differentiating between benign and malignant pathologies, we demonstrated that incorporating a combination of CEUS and SE into the evaluation of focal testicular abnormalities could improve diagnostic performance metrics over conventional CDUS. Our findings underscore the role of advanced ultrasound techniques in enhancing the evaluation of focal testicular abnormalities in clinical practice and could aid a shift towards testis-sparing management strategies.

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., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background and Aims: The objective of this study is to determine the diagnostic accuracy of the American College of Radiology Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System LR-5 characterization for HCC diagnosis in North American or European patients., Approach and Results: A prospective multinational cohort study was performed from January 2018 through November 2022 at 11 academic and nonacademic centers in North America and Europe. Patients at risk for HCC with at least 1 liver observation not previously treated, identified on ultrasound (US), or multiphase CT or MRI performed as a part of standard clinical care were eligible for the study. All participants were examined with CEUS of the liver within 4 weeks of CT/MRI or tissue diagnosis to characterize up to 2 liver nodules per participant using ACR CEUS Liver Imaging Reporting and Data System. Definite HCC diagnosis on the initial CT/MRI, imaging follow-up, or histology for CT/MRI-indeterminate nodules were used as reference standards. A total of 545 nodules had confirmed reference standards in 480 patients, 73.8% were HCC, 5.5% were other malignancies, and 20.7% were nonmalignant. The specificity of CEUS LR-5 for HCC was 95.1% (95% CI 90.1%-97.7%), sensitivity 62.9% (95% CI 57.9%-67.7%), positive predictive value 97.3% (95% CI 94.5%-98.7%), and negative predictive value 47.7% (95% CI 41.7%-53.8%). In addition, benign CEUS characterization (LR-1 or LR-2) had 100% specificity and 100% positive predictive value for nonmalignant liver nodules., Conclusions: CEUS Liver Imaging Reporting and Data System provides an accurate categorization of liver nodules in participants at risk for HCC., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Ultrasound practice is a longstanding tradition for radiology departments, being part of the family of imaging techniques. Ultrasound is widely practiced by non-radiologists but becoming less popular within radiology. The position of ultrasound in radiology is reviewed, and a possible long-term solution to manage radiologist expectations is proposed. An international group of experts in the practice of ultrasound was invited to describe the current organisation of ultrasound within the radiology departments in their own countries and comment on the interaction with non-radiologists and training arrangements. Issues related to regulation, non-medical practitioners, and training principles are detailed. A consensus view was sought from the experts regarding the position of ultrasound within radiology, with the vision of the best scenario for the continuing dominance of radiologists practising ultrasound. Comments were collated from nine different countries. Variable levels of training, practice, and interaction with non-radiologist were reported, with some countries relying on non-physician input to manage the service. All experts recognised there was a diminished desire to practice ultrasound by radiologists. Models varied from practising solely ultrasound and no other imaging techniques to radiology departments being central to the practice of ultrasound by radiologists and non-radiologist, housed within radiology. The consensus view was that the model favoured in select hospitals in Germany would be the most likely setup for ultrasound radiologist to develop and maintain practice. The vision for 20 years hence is for a central ultrasound section within radiology, headed by a trained expert radiologist, with non-radiologist using the facilities.Critical relevance statement The future of ultrasound within the radiology department should encompass all ultrasound users, with radiologists expert in ultrasound, managing the ultrasound section within the radiology department. The current radiology trainees must learn of the importance of ultrasound as a component of the 'holistic' imaging of the patient.Key points: 1. Ultrasound imaging within radiology departments precedes the introduction of CT and MR imaging and was first used over 50 years ago.2. Non-radiology practitioners deploy ultrasound examinations to either 'problem solve' or perform a comprehensive ultrasound examination; radiologists provide comprehensive examinations or use ultrasound to direct interventional procedures.3. Radiology does not 'own' ultrasound, but radiologists are best placed to offer a comprehensive patient-focused imaging assessment.4. A vision of the future of ultrasound within the radiology department is encompassing all ultrasound users under radiologists who are experts in ultrasound, positioned within the radiology department.5. The current radiology trainee must be aware of the importance of ultrasound as a component of the 'holistic' imaging of the patient., (© 2023. The Author(s).)

Background: Ultrasonography (US) represents the gold standard imaging method for the assessment of testicular lesions (TL). The gray-scale (GSUS) and color-Doppler (CDUS) ultrasound examination allow sonographers to investigate the size, margins, echotexture, and vascular features of TLs with the aim to differentiate benign from malignant lesions. Recently, the use of contrast-enhanced US (CEUS) and sonoelastography (SE) has led to further improvements in the differential diagnosis of TL. Although GSUS and CDUS are often sufficient to suggest the benign or malignant nature of the TL, CEUS can be decisive in the differential diagnosis of unclear findings, while SE can help to strengthen the diagnosis. The contemporary combination of GSUS, CDUS, CEUS, and SE has led to a new diagnostic paradigm named multiparametric US (mp-US), which is able to provide a more detailed characterization of TLs than single techniques alone. This narrative and pictorial review aimed to describe the mp-US appearance of several TLs., Methods: An extensive Medline search was performed to identify studies in the English language focusing on the mp-US evaluation of TLs., Results: A practical mp-US "identity card" and iconographic characterization of several benign and malignant TLs is provided herein., Conclusions: The mp-US characterization of TL reported herein can be useful in daily clinical practice.

Non-alcoholic fatty liver disease (NAFLD) is a significant cause of diffuse liver disease, morbidity and mortality worldwide. Early and accurate diagnosis of NALFD is critical to identify patients at risk of disease progression. Liver biopsy is the current gold standard for diagnosis and prognosis. However, a non-invasive diagnostic tool is desired because of the high cost and risk of complications of tissue sampling. Medical ultrasound is a safe, inexpensive and widely available imaging tool for diagnosing NAFLD. Emerging sonographic tools to quantitatively estimate hepatic fat fraction, such as tissue sound speed estimation, are likely to improve diagnostic accuracy, precision and reproducibility compared with existing qualitative and semi-quantitative techniques. Various pulse-echo ultrasound speed of sound estimation methodologies have been investigated, and some have been recently commercialized. We review state-of-the-art in vivo speed of sound estimation techniques, including their advantages, limitations, technical sources of variability, biological confounders and existing commercial implementations. We report the expected range of hepatic speed of sound as a function of liver steatosis and fibrosis that may be encountered in clinical practice. Ongoing efforts seek to quantify sound speed measurement accuracy and precision to inform threshold development around meaningful differences in fat fraction and between sequential measurements., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Penile traumatic injuries are rare with potentially severe consequences, with clinical assessment challenging due to pain and swelling. Ultrasound is the primary imaging modality for assessing the penis. It has a high spatial resolution and rapid availability and is portable. Contrast enhanced ultrasound is an advanced ultrasound technique that adds real-time dynamic vascular imaging safely, increasing diagnostic precision and confidence, allowing for better therapeutic management of traumatic penile injuries. Contrast enhanced ultrasound helps to delineate the extent of a haematoma, distinguishing this from the herniated corpus cavernosum, detecting the point of rupture of the tunica albuginea, showing vascular abnormalities, localising a dislocated penis and determining penile viability. The integrity of the urethra may be assessed with intracavitary contrast enhanced ultrasound. Additionally, contrast enhanced ultrasound allows monitoring of the response to endovascular and surgical treatment. This review aims to detail the anatomy and pathogenesis of penile trauma, to give guidance on optimising the contrast enhanced ultrasound technique and to obtain diagnostic examinations. Illustration of the spectrum of aspects of penile trauma will be complemented with a literature review.Critical relevance statement Contrast enhanced ultrasound is a safe and efficient imaging modality that allows for highly accurate diagnoses, helping achieve more successful and conservative treatments of penile trauma complications.Key points• Ultrasound is an accurate and safe imaging test for penile trauma.• CEUS adds dynamic vascular imaging in real-time increasing diagnostic confidence.• CEUS can delineate penile haematomas, locate fractures and demonstrate vessel integrity.• CEUS potentially allows for more conservative treatment of penile trauma complications., (© 2023. European Society of Radiology (ESR).)

Aim: To enhance ultrasound teaching delivery to radiology trainees using a simulation course matched to the 2021 Royal College of Radiologists (RCR) curriculum., Material and Methods: An ultrasound simulation training course was designed for specialty trainees (ST) 1 in radiology, which was based on the 2021 RCR curriculum and covered the top ultrasound training priorities. The course was piloted initially on two occasions in a 1-day format to the August 2021 and the March 2022 ST1 intake trainees. Based on the feedback, a comprehensive 4-day course was developed and delivered between October and December 2022 for the August 2022 ST1 intake, funded by Health Education England. The outcomes measured were subjective trainee feedback using numerical scores and free text., Results: All King's College Hospital NHS Foundation Trust radiology ST1 trainees from the August 2021 to the August 2022 intake participated in ultrasound simulation training. The training matched the RCR curriculum and increased the trainees' confidence and competency in medical ultrasound., Conclusions: Ultrasound simulation training can be successfully delivered to ST1 trainees to match the 2021 RCR curriculum and enhance training in medical ultrasound for radiologists., (Copyright © 2023. Published by Elsevier Ltd.)

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease from fatty accumulation (steatosis), necro-inflammation though to fibrosis. It is of increasing global prevalence as a hepatic manifestation of the metabolic syndrome. Although accurate histopathology and magnetic resonance imaging techniques for hepatic fat quantification exist, these are limited by invasiveness and availability, respectively. Ultrasonography is potentially ideal for assessing and monitoring hepatic steatosis given the examination is rapid and readily available. Traditional ultrasound methods include qualitative B-mode for imaging markers, such as increased hepatic parenchymal echogenicity compared to adjacent renal cortex are commonplace; however, there is acknowledged significant interobserver variability and they are suboptimal for detecting mild steatosis. Recently quantitative ultrasound metrics have been investigated as biomarkers for hepatic steatosis. These methods rely on changes in backscatter, attenuation, and speed of sound differences encountered in a steatotic liver. Prospective studies using quantitative ultrasound parameters show good diagnostic performance even at low steatosis grades and in NAFLD. This review aims to define the clinical need for ultrasound-based assessments of liver steatosis, to describe briefly the physics that underpins the various techniques available, and to assess the evidence base for the effectiveness of the techniques that are available commercially from various ultrasound vendors., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aims:  To evaluate the evidence and produce a summary and recommendations for the most common heart and lung applications of point-of-care ultrasound (PoCUS)., Methods:  We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendation were produced, including assignment of levels of evidence (LoE) and grading of the recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement regarding the summary and recommendation for each question (using a 5-point Likert scale), which was approved if a level of agreement of greater than 75 % was reached. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses., Findings and Recommendations:  One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1). The remaining 9 questions achieved broad agreement with one assigned an LoE of 4 and weak GRADE recommendation (question 2), three achieving an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8), and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10)., Conclusion:  These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings., Competing Interests: A number of authors have declared potential conflicts of interest from the past three years:Bøetker, M.T. [royalties received from e-learning platform USabcd.org]; Connolly, J. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare, Terason Ultrasound, EchoNous]; Gargani, L. [honoraria received from GE Healthcare, Philips Healthcare & Caption Health]; Jarman, R.D. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare]; Kim, D. [medical advisor for Clarius Mobile Health]; Liu, R. [honoraria received from Philips Healthcare]; Olusanya, O. [honoraria received from GE Healthcare & Sonosite FujiFilm UK]; Peck, M. [honoraria received from GE Healthcare]., (Thieme. All rights reserved.)

Objective:  To evaluate the evidence and produce a summary and recommendations for the most common heart and lung point-of-care ultrasound (PoCUS)., Methods:  We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendations were produced, including assigning levels of evidence (LoE) and grading of recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement of the summary and recommendation for each question (using a 5-point Likert scale), which was approved in the case of a level of agreement of greater than 75 %. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses., Findings and Recommendations:  One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1), the remaining 9 questions achieved broad agreement with an assigned LoE of 4 and a weak GRADE recommendation (question 2), three achieved an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8) and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10)., Conclusion:  These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings., Competing Interests: A number of authors have declared potential conflicts of interest from the past three years.Bøetker, M.T. [royalties received from e-learning platform USabcd.org];Connolly, J. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare, Terason Ultrasound, EchoNous]; Gargani, L. [honoraria received from GE Healthcare, Philips Healthcare & Caption Health]; Jarman, R.D. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare];Kim, D. [medical advisor for Clarius Mobile Health]; Liu, R. [honoraria received from Philips Healthcare];Olusanya, O. [honoraria received from GE Healthcare & Sonosite FujiFilm UK];Peck, M. [honoraria received from GE Healthcare]., (Thieme. All rights reserved.)

The purpose of this study was to assess the utility of 2-D shear wave elastography (SWE) in assessing liver fibrosis in patients with chronic liver disease by comparing its performance with that of point shear wave elastography (pSWE) using liver histological staging as the reference standard. In this ethics committee-approved, single-institution prospective study, pSWE and 2-D SWE velocity measurements were obtained in 121 adult patients (age: 18-70 y, median: 45 y) immediately before a liver biopsy for chronic liver disease. Shear wave velocity (SWV) and Ishak scores were compared using the Kruskal-Wallis test, Spearman's correlation and receiver operating characteristic (ROC) curve analysis. Youden's index was used to determine the optimal cutoff point. There was no technical failure using pSWE and 2-D SWE. The mean difference for SWV between pSWE and 2-D SWE was 0.0223 (limits of agreement: -1.1009, 1.1145). Values for both pSWE and 2-D SWE were significantly correlated with fibrosis stage (Spearman's ρ = 0.606, p < 0.0001; ρ = 0.722, p < 0.001 respectively). The area under the ROC curve differentiating F ≥3 was 0.855 (95% confidence interval: 0.778-0.932) for pSWE and 0.884 (95% CI: 0.817-0.951) for 2-D SWE. The AUC for differentiating F ≥5 was 0.890 (95% CI: 0.826-0.954) for pSWE and 0.926 (95% CI: 0.88-0.973) for 2-D SWE. This study indicates that 2-D SWE provides feasible and accurate assessment of liver fibrosis, comparable to that provided by pSWE from two different manufacturers' machines., Competing Interests: Conflict of interest disclosure The authors declare no competing interests., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Online supplemental material is available for this article.