Contrast-enhanced ultrasound liver imaging reporting and data system: clinical validation in a prospective multinational study in North America and Europe.

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.

Multiparametric Ultrasound for Diagnosing Testicular Lesions: Everything You Need to Know in Daily Clinical Practice.

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.

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.

Ultrasonic Sound Speed Estimation for Liver Fat Quantification: A Review by the AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative.

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.

Comparison Between Different Manufacturers' 2-D and Point Shear Wave Elastography Techniques in Staging Liver Fibrosis in Chronic Liver Disease Using Liver Biopsy as the Reference Standard: A Prospective Study.

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.

Multiparametric ultrasound imaging characteristics of multiple testicular adrenal rest tumours in congenital adrenal hyperplasia.

INTRODUCTION: Testicular adrenal rest cell tumours (TART) are rare benign adrenocorticotropic hormone-dependent testicular tumours, which can develop in patients with congenital adrenal hyperplasia. If left untreated, they can cause testicular tissue damage and infertility. Ultrasound is the imaging modality of choice allowing for non-invasive diagnosis provided that characteristic features are seen. In recent times, magnetic resonance imaging characteristics have also been described to aid diagnosis. CASE REPORT: This case describes the imaging features of multiple bilateral TART in a young patient with congenital adrenal hyperplasia. Traditional greyscale and colour Doppler ultrasound demonstrated intratesticular, predominantly hypoechoic areas, with increased surrounding colour Doppler flow. In addition, contrast-enhanced ultrasound and strain elastography were performed, showing increased TART vascularisation and increased stiffness in the hypoechoic areas. Subsequent magnetic resonance imaging confirmed bilateral lobulated, well demarcated, intratesticular lesions, which appeared predominantly isointense on T1-weighted imaging, hypointense on T2-weighted imaging, with heterogeneous enhancement following gadolinium administration. DISCUSSION: This case illustrates the sonographic features including greyscale, colour Doppler, contrast and elastography ultrasound of TART in a patient with congenital adrenal hyperplasia. Both contrast-enhanced ultrasound and elastography can provide information about tissue properties not normally derived from conventional ultrasound and aid accurate diagnosis. Additional magnetic resonance imaging is not normally required with typical ultrasound appearances. The unusual findings seen on the ultrasound examination were likely secondary to poor compliance with treatment. CONCLUSION: Familiarity and recognition of characteristic and uncommon imaging features of these tumours are important to avoid misdiagnosis and surgical intervention.

Development of and Gathering Validity Evidence for a Theoretical Test in Contrast-Enhanced Ultrasound.

Contrast-enhanced ultrasound (CEUS) is an imaging modality applied in a broad field of medical specialties for diagnostic uses, guidance during biopsy procedures and ablation therapies and sonoporation therapy. Appropriate training and assessment of theoretical and practical competencies are recommended before practicing CEUS, but no validated assessment tools exist. This study was aimed at developing a theoretical multiple-choice question-based test for core CEUS competencies and gathering validity evidence for the test. An expert team developed the test via a Delphi process. The test was administered to medical doctors with varying CEUS experience, and the results were used to evaluate test items, internal-consistency reliability, ability to distinguish between different proficiency levels and to establish a pass/fail score. Validity evidence was gathered according to Messick's framework. The final test with 47 test items could distinguish between operators with and without CEUS experience with acceptable reliability. The pass/fail score led to considerable risk of false positives and negatives. The test may be used as an entry test before learning practical CEUS competencies but is not recommended for certification purposes because of the risk of false positives and negatives.

Paediatric focal nodular hyperplasia: A case study of typical contrast-enhanced ultrasound findings with quantitative analysis and correlated with magnetic resonance imaging.

INTRODUCTION: Focal nodular hyperplasia, a benign liver tumour, is the second most common focal benign liver lesion, after a cavernous haemangioma. Contrast-enhanced ultrasound is used increasingly for the diagnostic work up and follow-up of focal liver lesions in adults, but is particularly valuable in the paediatric population, with the ability to reduce radiation and the nephrotoxic contrast agents used in computed tomography or magnetic resonance imaging. Confident recognition of focal nodular hyperplasia is important; it is benign, usually asymptomatic, of no clinical significance, of no clinical consequence or malignant potential. We present a case of focal nodular hyperplasia of the liver with its characteristic findings on conventional ultrasound, contrast-enhanced ultrasound with quantitative analysis and correlated with magnetic resonance imaging.Case presentation: A 15-year-old female with right upper quadrant abdominal pain was referred for liver ultrasound. A focal liver lesion was detected on B-mode ultrasound examination, and colour Doppler demonstrated no specific features. Contrast-enhanced ultrasound examination demonstrated early arterial enhancement, with a characteristic spoke-wheel pattern, centrifugal uniform filling of the lesion on the late arterial phase and sustained enhancement on the portal venous phase. Quantitative contrast-enhanced ultrasound has been performed, showing a typical curve of enhancement, as well as characteristic parametric images, supporting the interpretation of contrast-enhanced ultrasound and assisting the diagnosis. Magnetic resonance imaging demonstrated a central T2 hyperintense scar and similar enhancement characteristics as contrast-enhanced ultrasound on T1 gadolinium-enhanced sequences. CONCLUSION: Contrast-enhanced ultrasound is a useful technique for the differentiation of benign from malignant liver lesions and has the potential to establish the diagnosis of focal nodular hyperplasia, based on the enhancement pattern, which is similar to that observed on magnetic resonance imaging but can be better appreciated with superior temporal, contrast and spatial resolution of contrast-enhanced ultrasound.

Paratesticular lesions: Aetiology and appearances on ultrasound.

BACKGROUND: Ultrasound (US) is the primary modality for the investigation of scrotal pathology, including both intra- and paratesticular abnormalities. OBJECTIVE: To describe the abnormalities of the paratesticular space. MATERIALS/METHODS: The paratesticular space contains the epididymis, spermatic cord and the tunica vaginalis cavity and is affected by a variety of inflammatory or tumoral entities. Differential diagnosis based on US criteria is frequently problematic, as the findings are non-specific. RESULTS: Some general rules apply: (i) unlike testicular lesions, extra-testicular entities are usually benign in the adult, (ii) the first steps to accurate diagnosis include careful localization of the lesion and assessment of its consistency (solid or cystic) and (iii) magnetic resonance imaging can be useful for further tissue characterization of lesions suspected to contain fat, but surgical biopsy will often provide the definite diagnosis. Contrast-enhanced ultrasound (CEUS) has been applied with limited experience indicating a narrow role, primarily for the differential diagnosis of echogenic cystic entities and the delineation of a necrotic abscess from a solid neoplasm. DISCUSSION: The various abnormalities are discussed and illustrated. CONCLUSION: This manuscript summarizes the literature on paratesticular lesions and the value of US in diagnosis.

A Systematic Review on the Use of Qualitative and Quantitative Contrast-enhanced Ultrasound in Diagnosing Testicular Abnormalities.

Greyscale and color doppler ultrasound are the standard when investigating testicular lesions. However, they cannot provide information on the microvasculature. As such, differentiating benign from malignant tumors is challenging. Contrast-enhanced ultrasound (CEUS) uses ultrasound contrast agents that are exclusively intravascular to image the microvasculature. This review assessed CEUS outcomes in investigating intratesticular lesions and concluded that qualitative CEUS provides the most advantage by confirming vascularity, thus differentiating non-neoplastic from neoplastic lesions with added confidence, allowing for appropriate management. Whilst results for quantitative CEUS are promising in distinguishing malignant from benign neoplasms, further research on its benefits is required.

A pictorial review of the utility of CEUS in thoracic biopsies.

Lung cancer is one of the commonest malignancies worldwide and necessitates both early and personalised treatment. A key requirement is histological sampling with immunohistochemistry obtained usually from percutaneous biopsy. Conventionally thoracic biopsies are performed using CT guidance, but more recently, there has been development of physician led ultrasound biopsy for pleural lesions. Contrast-enhanced ultrasound (CEUS) has been increasingly used in interventional procedures and is able to offer benefits for thoracic biopsies including improving lesional visualisation and characterisation, targeting viable tissue and avoiding critical vascular structures as well as evaluating for the presence of post-procedural complications. This educational review aims to benefits of the role of CEUS in thoracic biopsies.

Contrast-Enhanced Ultrasound Quantification Assessment of Focal Fatty Variations in Liver Parenchyma: Challenging the Traditional Qualitative Paradigm of Uniform Enhancement With Adjacent Parenchyma.

OBJECTIVES: The purpose of this study was to quantify contrast-enhanced ultrasound enhancement of focal fatty sparing (FFS) and focal fatty infiltration (FFI) and compare it with adjacent liver parenchyma. METHODS: This was a retrospective observational study yielding 42 cases in the last 4 years. Inclusion criteria were a focal liver lesion, adequate video availability, and an established diagnosis of FFS or FFI based on clinical or imaging follow-up or a second modality. Contrast-enhanced ultrasound examinations were performed with a standard low-mechanical index technique. Commercially available software calculated quantitative parameters for a focal liver lesion and a reference area of liver parenchyma, producing relative indices. RESULTS: In total, 42 patients were analyzed (19 male) with a median age of 18 (interquartile range, 42) years and a median lesion diameter of 30 (interquartile range, 16) mm. The cohort included 26 with FFS and 16 with FFI. Subjectively assessed, 27% of FFS and 25% of FFI were hypoenhancing in the arterial phase, and 73% of FFS and 75% of FFI were isoenhancing. In the venous and delayed phases, all lesions were isoenhancing. The peak enhancement (P = .001), wash-in area under the curve (P < .01), wash-in rate (P = .023), and wash-in perfusion index (P = .001) were significantly lower in FFS compared with adjacent parenchyma but not the mean transit time. In the FFI subgroup, no significant difference was detected. Comparing relative parameters, only the wash-in rate was significantly (P = .049) lower in FFS than FFI. The mean follow-up was 2.8 years. CONCLUSIONS: Focal fatty sparing shows significantly lower and slower enhancement than the liver parenchyma, whereas FFI enhances identically. Focal fatty sparing had a significantly slower enhancement than FFI.

EFSUMB 2020 Proposal for a Contrast-Enhanced Ultrasound-Adapted Bosniak Cyst Categorization - Position Statement.

The well-established Bosniak renal cyst classification is based on contrast-enhanced computed tomography determining the malignant potential of cystic renal lesions. Ultrasound has not been incorporated into this pathway. However, the development of ultrasound contrast agents coupled with the superior resolution of ultrasound makes it possible to redefine the imaging of cystic renal lesions. In this position statement, an EFSUMB Expert Task Force reviews, analyzes, and describes the accumulated knowledge and limitations and presents the current position on the use of ultrasound contrast agents in the evaluation of cystic renal lesions.

Nonscrotal Causes of Acute Scrotum.

Acute scrotum is characterized by intense acute scrotal pain, which may be associated with other symptoms and signs such as abdominal pain, inflammation, and fever. Many pathologic conditions can present in this way, most which involve the scrotal contents. Nonscrotal conditions, however, can rarely present clinically only as acute scrotum: among them, renal colic, aneurysm rupture or other causes of retroperitoneal hemorrhage, primary abdominal or pelvic tumors and metastases, pancreatitis, pelvic inflammation, and muscle injuries. The pathophysiologic characteristics of the clinical presentation, clues for diagnosis, and imaging features of a series of nonscrotal lesions presenting clinically with acute scrotal pain are herein reported and illustrated. In patients presenting with acute scrotal symptoms and normal scrotal ultrasound findings, nonscrotal causes of acute scrotal pain should be considered in the differential diagnosis. Therefore, an ultrasound investigation of the abdomen, groin, and thighs is indicated.

Vascularity of Intra-testicular Lesions: Inter-observer Variation in the Assessment of Non-neoplastic Versus Neoplastic Abnormalities After Vascular Enhancement With Contrast-Enhanced Ultrasound.

The aim of this study is to assess the additional benefit of contrast-enhanced ultrasound (CEUS) over conventional ultrasonography (US) in identifying intra-testicular abnormalities among observers of different experiences. In this study, 91 focal testicular lesions (46 neoplastic, 45 non-neoplastic) imaged with gray-scale US/Doppler US and CEUS were classified using a 5-point scale. Three experienced and four inexperienced observers rated each lesion using gray-scale/color Doppler US alone and then with the addition of CEUS. Improved diagnostic specificity and accuracy with the addition of CEUS was observed for both experienced (specificity: 71.1% vs. 59.3%, p = 0.005; accuracy: 83.5% vs. 76.9%, p = 0.003) and inexperienced observers (specificity: 75.6% vs. 51.7%, p = 0.005; accuracy: 80.2% vs. 72.0%, p < 0.001). Significant inter-observer variability between the experienced and inexperienced observers when assessing conventional US alone was eliminated with the addition of CEUS. CEUS improves diagnostic accuracy of focal intra-testicular lesions for both experienced and inexperienced observers and reduces inter-observer variability in inexperienced operators.

Ultrasound-based liver elastography: current results and future perspectives.

Chronic liver disease affects 185 million population worldwide. It encompasses a heterogenous disease spectrum, but all can lead to the development of liver fibrosis. The degree of liver fibrosis is not only a prognosticator, but has also been used to guide the treatment strategy and to evaluate treatment response. Traditionally, staging of liver fibrosis is determined on histological analysis using samples obtained from an invasive liver biopsy. Ultrasound-based liver elastography is a non-invasive method of assessing diffuse liver disease in patients with known chronic liver disease. The use of liver elastography has led to a significant reduction in the number of liver biopsies performed to assess the severity of liver fibrosis and a liver biopsy is now reserved for only select sub-groups of patients. The aim of this review article is to discuss the key findings and current evidence for ultrasound-based elastography in diffuse liver disease as well as the technical challenges and to evaluate the potential research direction.

Guidelines and Good Clinical Practice Recommendations for Contrast-Enhanced Ultrasound (CEUS) in the Liver-Update 2020 WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast-enhanced ultrasound, first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology. The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications. The 2012 guideline requires updating as, previously, the differences in the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including U.S. Food and Drug Administration approval and the extensive Asian experience, to produce a truly international perspective. These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCAs) and are intended to create standard protocols for the use and administration of UCAs in liver applications on an international basis to improve the management of patients.