Magnetic resonance imaging (MRI) may be time-consuming, expensive, or poorly tolerated by patients with liver lesions. This is a prospective clinical trial designed to evaluate if contrast-enhanced ultrasound (CEUS) can be used to differentiate focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA) with similar accuracy compared with hepatobiliary agent MRI.Institutional review board approval was obtained (1805450097), and the trial was registered with ClinicalTrials.gov (NCT03652636). From 2018 through 2023, 40 patients who had lesions consistent with FNH or HCA on HBA-MRI underwent 1-time prospective CEUS of up to 2 hepatic lesions. Sonographic images obtained before and after intravenous administration of 2 mL sulfur hexafluoride lipid-type A microspheres (Lumason) per lesion totaling 59 lesions (27 FNHs/32 HCAs). Two blinded radiologists provided a diagnosis of FNH or HCA.Thirty-eight female and 2 male patients (age 36.7 ± 9.9) were scanned. Radiologists provided diagnosis of FNH or HCA with respective sensitivity (66.7/64.0%), specificity (71.9/90.6%), and accuracy (69.5/78.0%). For 38 lesions greater than or equal to 2 cm in size (17 FNHs/21 HCAs), readers had sensitivity (70.6/84.2%), specificity (70.6/84.2%), and accuracy (81.5/86.8%). Interobserver agreement for all lesions was fair (κ = 0.34), whereas agreement for lesions 2 cm or larger was substantial (κ = 0.67).Contrast-enhanced ultrasound can differentiate FNH from HCA with accuracy approaching that of hepatobiliary agent MRI for lesions 2 cm or greater. Interobserver agreement is improved with larger lesions. CEUS may have utility as an alternate diagnostic tool for FNH/HCA, especially in patients who cannot or do not desire to undergo MRI.

Hepatocellular adenomas (HCA) are acquired focal liver lesions, that occur mainly in young-to-middle-aged women who are on long-term estrogen-containing contraceptives or young men after prolonged use of anabolic steroids. Furthermore, distinct underlying diseases, such as obesity, metabolic dysfunction-associated steatotic liver disease, glycogen storage disease, etc. are considered risk factors. The 2017 Bordeaux classification, in particular Nault et al, divided HCAs into eight subtypes according to their pheno- and genotypic characteristics. This includes HCAs with hepatocyte-nuclear-factor (HNF1-alpha mutation), HCAs with β-catenin mutation, and HCAs without either of these genetic mutations, which are further subdivided into HCAs with and without inflammatory cells. HCAs should no longer be classified as purely benign without histologic workup since three of the eight subtypes are considered high-risk lesions, requiring adequate management: malignant transformation of the pure (ßex3-HCA) and mixed inflammatory/β-catenin exon 3 (ßex3-IHCA) adenomas, as well as potential bleeding of the sonic hedgehog HCA and pure (ßex7/8-HCA) and mixed inflammatory/β-catenin exon 7/8 (ßex7/8-IHCA). Elective surgery is recommended for any HCA in a male, or for any HCA exceeding 5 cm. Although MRI can classify up to 80% of adenomas, if findings are equivocal, biopsy remains the reference standard for adenoma subtype.

Suspicious tumors of the lung require specific staging, intraoperative detection, and histological confirmation. We performed an intrathoracic, intraoperative contrast-enhanced ultrasound (Io-CEUS) for characterization of lung cancer.

Retrospective analysis of prospectively collected data on the application of Io-CEUS in thoracic surgery for patients with operable lung cancer. Analysis of the preoperative chest CT scan and FDG-PET/CT findings regarding criteria of malignancy. Immediately before lung resection, the intrathoracic Io-CEUS was performed with a contrast-enabled T-probe (6-9 MHz-L3-9i-D) on a high-performance ultrasound machine (Loqic E9, GE). In addition to intraoperative B-mode, color-coded Doppler sonography (CCDS), or power Doppler (macrovascularization) of the lung tumor, contrast enhancement (Io-CEUS) was used after venous application of 2.4-5 mL sulfur hexafluoride (SonoVue, Bracco, Italy) for dynamic recording of microvascularization. The primary endpoint was the characterization of operable lung cancer with Io-CEUS. Secondly, the results of Io-CEUS were compared with the preoperative staging.

The study included 18 patients with operable lung cancer, who received Io-CEUS during minimally invasive thoracic surgery immediately prior to lung resection. In the chest CT scan, the mean size of the lung tumors was 2.54 cm (extension of 0.7-4.5 cm). The mean SUV in the FDG-PET/CT was 7.6 (1.2-16.9). All lung cancers were detected using B-mode and power Doppler confirmed macrovascularization (100%) of the tumors. In addition, Io-CEUS showed an early wash-in with marginal and mostly simultaneous central contrast enhancement.

The intrathoracic application of Io-CEUS demonstrated a peripheral and simultaneous central contrast enhancement in the early phase, which seems to be characteristic of lung cancer. In comparison to preoperative imaging, Io-CEUS was on par with the detection of malignancy and offers an additional tool for the intraoperative assessment of lung cancer before resection.

Due to the trend towards increased use of imaging and rising awareness among high-risk patients, gastroenterologists and hepatologists are more frequently confronted with patients with focal liver lesions. In the differentiation of these lesions, CT and MRI have increasingly found their way into primary diagnostic steps in everyday clinical practice. Contrast-enhanced sonography, on the other hand, is a very effective and cost-efficient method for assessing focal liver lesions. The success of the method is not only based on the visualisation of microvascularisation in real time. If sonography is performed by the treating physician, he can use the exact knowledge of history and clinical findings to specifically adapt the examination procedure and to interpret the sonographic findings with greater accuracy ("clinical sonography"). At the same time, the method enables the practitioner to combine diagnostics and management decisions in his or her own hands. To achieve excellent results with contrast-enhanced sonography-as with any other imaging method-it is necessary that the examiner is sufficiently qualified.This article systematically presents the sonographic characteristics of the most common liver lesions and clearly shows their contrast patterns using videos (available via QR code). The article illustrates that CEUS could-and from the authors' point of view, should-have an even greater significance in the future.

Improvements in understanding the pathophysiology of the different benign liver nodules have refined their nosological classification. New criteria have been identified using imaging, histology and molecular analyses for a precise diagnosis of these tumours. Improvement in the classification of liver tumours provides a more accurate prediction of disease progression and has modified patient management. Haemangioma and focal nodular hyperplasia, the most common benign liver tumours that develop in the absence of chronic liver disease, are usually easy to diagnose on imaging and do not require specific treatment. However, hepatocellular adenomas and cirrhotic macronodules can be difficult to discriminate from hepatocellular carcinoma. The molecular subtyping of hepatocellular adenomas in five major subgroups defined by HNF1A inactivation, β-catenin mutation in exon 3 or exon 7/8, and activation of inflammatory or Hedgehog pathways helps to identify the tumours at risk of malignant transformation or bleeding. New clinical, biological and molecular tools have gradually been included in diagnostic and treatment algorithms to classify benign liver tumours and improve patient management. This Review aims to explain the main pathogenic mechanisms of benign liver tumours and how this knowledge could influence clinical practice.

Incidental liver lesions are identified in children without underlying liver disease or increased risk of hepatic malignancy in childhood. Clinical and imaging evaluation of incidental liver lesions can be complex and may require a multidisciplinary approach. This review aims to summarize the diagnostic process and follow-up of incidental liver lesions based on review of the literature, use of state-of-the-art imaging, and our institutional experience. Age at presentation, gender, alpha fetoprotein levels, tumor size, and imaging characteristics should all be taken into consideration to optimize diagnosis process. Some lesions, such as simple liver cyst, infantile hemangioma, focal nodular hyperplasia (FNH), and focal fatty lesions, have specific imaging characteristics. Recently, contrast-enhanced ultrasound (CEUS) was Food and Drug Administration (FDA)-approved for the evaluation of pediatric liver lesions. CEUS is most specific in lesions smaller than 3 cm and is most useful in the diagnosis of infantile hemangioma, FNH, and focal fatty lesions. The use of hepatobiliary contrast in MRI increases specificity in the diagnosis of FNH. Recently, lesion characteristics in MRI were found to correlate with subtypes of hepatocellular adenomas and associated risk for hemorrhage and malignant transformation. Biopsy should be considered when there are no specific imaging characteristics of a benign lesion. Surveillance with imaging and alpha fetoprotein (AFP) should be performed to confirm the stability of lesions when the diagnosis cannot be determined, and whenever biopsy is not feasible.

Hepatocellular benign liver tumours are mainly developed on normal liver and include hepatic hemangioma, focal nodular hyperplasia and hepatocellular adenoma from the most frequent to the less frequent. The diagnosis of hepatic hemangioma and of simple hepatic biliary cysts can be performed using non-invasive criteria using liver ultrasonography or contrast enhanced MRI. Most of the time the diagnosis of focal nodular hyperplasia can be achieved using contrast-enhanced ultrasonography or contrast enhanced MRI with an additional value of hepatobiliary contrast-agent in this setting. Rarely, if a doubt persists, a tumour and non-tumour liver biopsy can be required in order to establish the diagnosis. As hepatic hemangioma, simple hepatic biliary cysts and focal nodular hyperplasia are not associated with complications, they don't require any treatments or follow-up. Hepatocellular adenomas are mainly diagnosed at histology on surgical samples or liver biopsy even if some radiological features are highly suggestive of several subtypes of hepatocellular adenomas. Finally, the management of hepatocellular adenomas should be guided according to the tumour size, gender but also to the molecular subtypes.

Early diagnosis of hepatocellular carcinoma (HCC) is very important for the prognosis of patients. However, there are very few studies that compared the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) and B-mode ultrasonography for early HCC in cirrhotic patients.

This retrospective study included cirrhotic patients, who were suspected of early HCC between January 2020 and June 2021. The diagnosis of patients was based on the pathology results of surgery or biopsy. Demographic and clinical characteristics of included patients were recorded. The diagnoses of suspected lesions using both types of ultrasonography were recorded, and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of early HCC in cirrhotic patients were calculated.

Eventually, 137 patients with solitary lesions in the liver were included in this study, including 89 patients diagnosed with HCC and 48 patients diagnosed with non-HCC. The median diameter of suspected lesions was 26 mm, and the median level of alpha fetoprotein (AFP) was 37.2 ng/mL. When comparing the demographic and clinical characteristics of cirrhotic patients with HCC and non-HCC, it was found that patients with HCC had significantly higher levels of AFP than those with non-HCC (P=0.03). The sensitivity, specificity, PPV, NPV, and accuracy of CEUS in early HCC were 73%, 93.8%, 95.6%, 65.2% and 80.3%, respectively. In CEUS, all of these parameters were much higher than those in B-mode ultrasonography, i.e., 64%, 75%, 82.6%, 52.9%, and 67.9%. It was also found that the diagnostic accuracy of CEUS was much higher than that of B-mode ultrasonography especially regarding lesions <20 mm. To further improve the sensitivity of CEUS in early HCC, AFP was combined with CEUS for the diagnosis of early HCC. As a result, the sensitivity, specificity, PPV, NPV, and accuracy of CEUS combined with AFP level were 83.1%, 87.5%, 92.5%, 73.7%, and 84.7%, respectively.

Our study confirmed that CEUS' diagnostic accuracy for early HCC in cirrhotic patients was significantly higher than that of B-mode ultrasonography. However, the sensitivity of CEUS needs to be improved further, and the combination of CEUS and AFP level may be a potential solution.

OBJECTIVE. The purpose of this article is to compare contrast-enhanced sonography (CEUS) with sulfur hexafluoride with MRI with the liver-specific contrast agent gadobenate dimeglumine in the diagnosis of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) in a cohort of consecutive patients. MATERIALS AND METHODS. Patients referred to a tertiary center for hepatobiliary disease who had suspected HCA or FNH on MRI performed with an extracellular gadolinium-based contrast agent underwent a prospective workup including CEUS and MRI with a liver-specific contrast agent. Diagnosis was definite when the findings of CEUS and MRI with a liver-specific contrast agent were concordant; histopathologic examination (HPE) was performed for cases with discordant findings. Descriptive statistics and the association between categoric variables were presented as numbers and percentages and were assessed using the Fisher exact test. The primary analysis was patient based. Sensitivity, specificity, and AUC and predictive values for the diagnosis of HCA and FNH were calculated separately for CEUS and MRI with a liver-specific contrast agent. RESULTS. A total of 181 patients were selected for the first analysis. Findings from CEUS and MRI with a liver-specific contrast agent were concordant for 132 patients (73%) and discordant for 49 (27%). HPE was performed for 26 of the 49 patients with discordant findings (53%), with findings indeterminate for two of these patients, the findings of MRI with a liver-specific contrast agent correct for 21 of the remaining 24 patients (87.5%), and the findings of CEUS correct for three of these 24 patients (12.5%) (p < 0.05). For further analysis, 156 patients with concordant findings or HPE-proven cases were included. For CEUS, the sensitivity and specificity for the diagnosis of HCA and FNH were 85% and 87%, respectively; the ROC AUC value was 0.856; and the positive predictive value and negative predictive value were 79% and 90%, respectively. For MRI with a liver-specific contrast agent, the sensitivity and specificity were 95% each, the ROC AUC value was 0.949, and the positive predictive value and negative predictive value were 92% and 97%, respectively, for the diagnosis of HCA and FNH. CONCLUSION. The findings of CEUS and MRI with a liver-specific contrast agent showed fair agreement for the diagnosis of HCA and FNH. MRI with a liver-specific contrast agent is diagnostically correct significantly more often than CEUS in cases with discordant findings that are HPE proven.

To evaluate the lesion-to-liver visual signal intensity ratio (SIR) before and at the hepatobiliary phase MRI (HBP-MRI) after gadobenate dimeglumine (Gd-BOPTA) injection, using several T1-weighted images (T1-WI), for the characterization of benign hepatocellular lesions.

Patients with histologically proven focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), who underwent Gd-BOPTA-enhanced HBP-MRI from 2009 to 2017, were retrospectively identified. The lesion-to-liver SIR was visually assessed by two radiologists on HBP (post-HBP analysis) and compared with that of unenhanced sequences (pre/post-HBP analysis) on T1-WI in-phase (T1-IP), out-of-phase (T1-OP), and fat suppression (T1-FS). Lesions were classified as hyper-, iso-, or hypointense on post-HBP, and as decreasing, stable, or increasing SIR on pre/post-HBP analyses. The performance of the different T1-WI sequences for the diagnostic of FNH was evaluated on post-HBP analysis.

Twenty-nine FNHs and 33 HCAs were analyzed. On post-HBP analysis, FNHs appeared hyper-/isointense in 89.7% of all T1-WI. HCAs appeared hypointense in 93.9%, 63.6%, and 69.7% of T1-IP, T1-OP, and T1-FS, respectively. FNHs exhibited an increasing SIR in 55.2-58.6%, a stable SIR in 44.8-58.6%, and a decreasing SIR in 0%, whereas HCAs exhibited a decreasing SIR in 66.7-93.9%, a stable SIR in 6.1-33.3%, and an increasing SIR in 0% (p < 0.0001). The specificity of T1-IP was significantly higher than that of T1-OP (p = 0.015) and T1-FS (p = 0.042).

T1-IP is the most reliable sequence due to misleading tumor/liver signal ratio in the case of fatty liver when using T1-FS or T1-OP. The pre/post-HBP lesion-to-liver SIR is accurate to classify benign hepatocellular lesions and contributes to avoid biopsy.

•The T1-weighted images in-phase should be systematically included in the HBP-MRI protocol, as it is the most reliable sequence especially in the case of fatty liver. •The comparison between lesion-to-liver signal intensity ratios on unenhanced and at the hepatobiliary phase sequences is useful to classify benign hepatocellular lesions in three categories without misclassification: FNH (increasing signal intensity ratio), HCA (decreasing signal intensity ration), and indeterminate lesions (stable signal intensity ratio).

Hepatobiliary phase (HBP) Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has increased the accuracy in differentiating focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). However, the ability of this technique to distinguish HCA subtypes remains controversial. The aim of this study was to investigate the expression of hepatocyte transporters (OATPB1/B3, MRP2, MRP3) in HCA subtypes, hence to understand their MRI signal intensity on HBP Gd-EOB-DTPA-enhanced MRI.

By means of immunohistochemistry (IHC), we scored the expression of OATPB1/B3, MRP2 and MRP3, in resected specimens of FNH (n = 40), subtyped HCA (n = 58) and HCA with focal malignant transformation (HCA-HCC, n = 4). Results were validated on a supplementary set of FNH (n = 6), subtyped HCA (n = 17) and HCA-HCC (n = 1) with Gd-EOB-DTPA MR images.

All FNH showed a preserved expression of hepatocytes transporters. Beta-catenin-activated HCA (at highest risk of malignant transformation) and HCA-HCC were characterized by preserved/increased OATPB1/B3 expression (predictor of hyperintensity on HBP), as opposed to other HCA subtypes (P < 0.01) that mostly showed OATPB1/B3 absence (predictor of hypointensity on HBP). HCA-HCC showed an additional MRP3 overexpressed profile (P < 0.01). On HBP Gd-EOB-DTPA-enhanced MRI, FNH and HCA signal intensity reflected the profile predicted by their specific OATPB1/B3 tissue expression. The hyperintense vs hypointense HBP signal criterion was able to distinguish all higher risk HCA and HCA-HCC (100% accuracy).

OATPB1/B3 and MRP3 IHC and signal intensity on HBP Gd-EOB-DTPA-enhanced MRI can help to stratify HCA according to their risk of malignant transformation.

Focal nodular hyperplasia and hepatic adenoma are rare liver tumors in which specific features on contrast-enhanced ultrasound (US) have been reported but are little known in children.

To assess the interobserver agreement in diagnosing and differentiating focal nodular hyperplasia and hepatic adenoma in children using established adult contrast-enhanced US characteristics.

Thirty children with a definite or probable diagnosis of focal nodular hyperplasia or hepatic adenoma on magnetic resonance imaging (MRI)/histology who underwent contrast-enhanced US studies were included. Typical and additional contrast-enhanced US features of focal nodular hyperplasia and hepatic adenoma were included. The lesions were classified as definite/probable focal nodular hyperplasia, definite/probably hepatic adenoma or unclassified. The interobserver kappa of contrast-enhanced US characteristics was calculated.

Focal nodular hyperplasia and hepatic adenoma in children demonstrate contrast-enhanced US characteristics similar to those in adults. Among the nine lesions with confirmed histological diagnosis, correct diagnosis was made in 7 (77.8%) based on contrast-enhanced US criteria. Two lesions were unclassified by both observers due to a mixed arterial filling pattern. Interobserver kappa for contrast-enhanced US diagnosis was 0.64 (P<0.0001).

There is a good interobserver kappa for separating focal nodular hyperplasia from hepatic adenoma in children using established adult contrast-enhanced US features.

Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are liver tumors that require different management. We assessed the potential of point shear wave elastography (pSWE) to differentiate FNH from HCA and the interobserver and intraobserver reliability of pSWE in the examination of these lesions and of native liver tissue (NLT).

The study included 88 patients (65 FNH, 23 HCA). pSWE was performed by two experienced liver sonographers (observers 1 [O1] and 2 [O2]) and acquired within the lesion of interest and NLT. Group differences, optimal cutoff for characterization and interobserver reliability was assessed with Mann-Whitney-U, area under the ROC curce (AUROC) and intraclass correlation coefficient (ICC). Intraobserver reliability in NLT was assessed in 20 healthy subjects using ICC.

Median stiffness was significantly higher in FNH than in HCA (7.01 kPa vs 4.98 kPa for O1 (P = 0.017) and 7.68 kPa vs 6.00 kPa for O2 (P = 0.031)). A cutoff point for differentiation between the two entities could not be determined with an AUROC of 0.67 (O1) and 0.69 (O2). Interobserver reliability was good for lesion- stiffness (ICC = 0.86) and poor for NLT stiffness (ICC = 0.09). In healthy subjects, intraobserver reliability for NLT-stiffness was poor for O1 (ICC = 0.23) and moderate for O2 (ICC = 0.62).

This study shows that pSWE cannot reliably differentiate FNH from HCA. Interobserver and intraobserver reliability for pSWE in NLT were insufficient. Interpretation of results gained with this method should be done with great caution.