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Abstract BACKGROUND The survival benefit in maximizing resection in glioblastomas (GBMs) has been demonstrated by numerous studies. The true limit of infiltration of GBMs has been an overwhelming obstacle, and several technological advances have been introduced to improve the identification of residual tumors. OBJECTIVE To evaluate whether the integration of 5-aminolevulinic acid (5-ALA) with microbubble contrast-enhanced ultrasound (CEUS) improves residual tumor identification and has an impact on the extent of resection (EOR), overall survival (OS), and progression-free survival (PFS). METHODS A total of 230 GBM procedures were retrospectively studied. Cases were stratified according to the surgical procedure into 4 groups: 5-ALA- and CEUS-guided surgeries, 5-ALA-guided surgeries, CEUS-guided surgeries, and conventional microsurgical procedures. RESULTS Patients undergoing conventional microsurgical procedures showed the worst EORs compared to the assisted techniques (5-ALA and CEUS procedures). Both 5-ALA and CEUS techniques improved the EOR compared to conventional microsurgical procedures. However, their combination gave the best results in terms of the EOR (P = .0003). The median EOR% and the number of supramarginal resections are hence superior in the 5-ALA + CEUS + group compared to the others; this observation had consequences on PFS and OS in our series. CONCLUSION In terms of the EOR, the best results can be achieved through a combination of both techniques, where the 5-ALA-guided procedure is followed by a final survey with CEUS. Compared with other intraoperative imaging techniques, CEUS is a real-time, readily repeatable, safe, and inexpensive technique that provides valuable information to the surgeon before, during, and after resection. Graphical Abstract Graphical Abstract

PurposeRenal cysts comprise benign and malignant entities. Risk assessment profits from CT/MRI imaging using the Bosniak classification. While Bosniak-IIF, -III, and -IV cover complex cyst variants, Bosniak-IIF and -III stand out due to notorious overestimation. Contrast-enhanced ultrasound (CEUS) is promising to overcome this deficit but warrants standardization. This study addresses the benefits of a combined CEUS and CT/MRI evaluation of renal cysts. The study provides a realistic account of kidney tumor boards' intricacies in trying to validate renal cysts.Methods247 patients were examined over 8 years. CEUS lesions were graded according to CEUS-Bosniak (IIF, III, IV). 55 lesions were resected, CEUS-Bosniak- and CT/MRI-Bosniak-classification were correlated with histopathological diagnosis. Interobserver agreement between the classifications was evaluated statistically. 105 lesions were followed by ultrasound, and change in CEUS-Bosniak-types and lesion size were documented.Results146 patients (156 lesions) were included. CEUS classified 67 lesions as CEUS-Bosniak-IIF, 44 as CEUS-Bosniak-III, and 45 as CEUS-Bosniak-IV. Histopathology of 55 resected lesions revealed benign cysts in all CEUS-Bosniak-IIF lesions (2/2), 40% of CEUS-Bosniak-III and 8% of CEUS-Bosniak-IV, whereas malignancy was uncovered in 60% of CEUS-Bosniak-III and 92% of CEUS-Bosniak-IV. Overall, CEUS-Bosniak-types matched CT/MRI-Bosniak types in 58% (fair agreement, κ = 0.28). CEUS-Bosniak resulted in higher stages than CT/MRI-Bosniak (40%). Ultrasound follow-up of 105 lesions detected no relevant differences between CEUS-Bosniak-types concerning cysts size. 99% of lesions showed the same CEUS-Bosniak-type.ConclusionThe CEUS-Bosniak classification is an essential tool in clinical practice to differentiate and monitor renal cystic lesions and empowers diagnostic work-up and patient care.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Abstract Background and aims The postoperative course of Crohn's disease (CD) is best predicted by ileocolonoscopy. Ultrasonography (US) has been proposed as indicator for postsurgical recurrence (PSR), but further confirmation is needed. We performed a systemic review with meta-analysis to assess the pooled diagnostic accuracy of US in the evaluation of PSR. Methods The systematic review was performed in PubMed/MEDLINE, EMBASE, SCOPUS, and Cochrane databases to identify studies assessing the US accuracy in PSR diagnosis. A sub-analysis between bowel sonography (BS), small-intestine contrast ultrasound (SICUS), and contrast-enhanced ultrasound (CEUS) was performed. Pooling was performed using diagnostic fixed or random-effect model according with heterogeneity. Results Ten studies (536 patients) met the inclusion criteria. There was no publication bias. Pooled sensitivity and specificity of US in detecting PSR were 0.94 (95% CI, 0.86-0.97) and 0.84 (95% CI, 0.62-0.94; diagnostic accuracy 90%), respectively. At sub-analysis, pooled sensitivity and specificity were 0.82 (95% CI, 0.76-0.88) and 0.88 (95% CI, 0.74-0.95) respectively for BS, with 0.99 (95% CI, 0.99-1.00) and 0.74 (95% CI, 0.73-0.74) for SICUS. Finally, an SROC curve was built to establish the best bowel wall thickness (BWT) cutoff able to predict the presence of severe PSR (Rutgeerts ≥3): a BWT ≥5.5 mm at US revealed sensitivity of 83.8% (95% CI, 73.6%-90.6%), specificity of 97.7% (95% CI, 93%-99%). Conclusions US shows high sensitivity and specificity for the diagnosis of PSR. SICUS appears more sensitive-but less specific-than BS, while the role of CEUS needs further investigation. A cutoff value of BWT ≥5.5 mm is strongly indicative of severe PSR. 10.1093/ibd/izy012_video1 izy012.video1 5775249754001

Contrast-enhanced ultrasound (CEUS) is a radiation-free, safe, and in specific clinical settings, highly sensitive imaging modality. Over the recent decades, there is cumulating experience and a large volume of published safety and efficacy data on pediatric CEUS applications. Many of these applications have been directly translated from adults, while others are unique to the pediatric population. The most frequently reported intravenous abdominal applications of CEUS in children are the characterization of focal liver lesions, monitoring of solid abdominal tumor response to treatment, and the evaluation of intra-abdominal parenchymal injuries in selected cases of blunt abdominal trauma. The intravesical CEUS application, namely contrast-enhanced voiding urosonography (ceVUS), is a well-established, pediatric-specific imaging technique entailing the intravesical administration of ultrasound contrast agents for detection and grading of vesicoureteral reflux. In Europe, all pediatric CEUS applications remain off-label. In 2016, the United States Food and Drug Administration (FDA) approved the most commonly used worldwide second-generation ultrasound contrast SonoVue®/Lumason® for pediatric liver and intravesical applications, giving new impetus to pediatric CEUS worldwide.

Abstract Objective Our goal in this multicentric prospective study was 2-fold: first, to test the diagnostic accuracy of ultrasound, color Doppler imaging (CDI), and contrast-enhanced ultrasound (CEUS) in identifying disease activity in patients with Crohn’s disease (CD) compared with endoscopy as the reference standard; and, second, to construct a sonographic score that allows disease activity to be detected. Materials and methods Seventy-two patients with CD from 3 hospitals underwent within a 30-day period both colonoscopy and ultrasound (US), including mural thickness, CDI, and CEUS, prospectively as part of clinical care. A multivariate analysis was carried out to assess the influence of each of the ultrasound variables in predicting endoscopic activity. We then developed a predictive ultrasound score for disease activity, and a receiver operating characteristic (ROC) curve was constructed to determine the area under the ROC curve (AUC) and the best cut-off score value to discriminate between active and inactive disease. Results Sonographic findings that were independent predictors of the presence of active disease at endoscopy were wall thickness, color grade, and contrast parameters. A score based on those variables showed high accuracy in predicting active disease, with an area under the ROC curve of 0.972. A simpler index, without contrast parameters, also showed high accuracy in detecting disease activity (AUC, 0.923). Conclusion A score based on wall thickness, color Doppler grade, and contrast parameters showed high accuracy in predicting active disease. A score without including the use of contrast agent had practically similar results and is easier to use in monitoring response to treatment. Wall thickness, color Doppler grade, and contrast parameters are independent predictors of active disease at endoscopy. A score based on those variables is highly accurate in predicting active disease and may provide an objective measure of the therapeutic response.

Contrast-enhanced ultrasound (CEUS) is a specialized form of ultrasound (US) performed with an intravenous injection of microbubble contrast agents. It has been successfully used for a variety of applications including characterization of liver tumors. In April 2014, the American College of Radiology (ACR) convened a working group of international experts to develop ACR CEUS Liver Imaging Reporting and Data System (CEUS LI-RADS). An initial version of CEUS LI-RADS was published in August 2016. Although the CEUS LI-RADS concept and principles for liver lesion characterization, using dynamic contrast enhancement features, are similar to those for CT or MRI, there are significant differences between CT/MRI and CEUS LI-RADS. Therefore, CEUS LI-RADS has different diagnostic features and a unique characterization algorithm. The size of a lesion, the type and degree of arterial phase enhancement, the presence of washout, and the timing and degree of washout are the major features used for categorization. This paper describes key differences between CT/MRI and CEUS, and provides a diagnostic algorithm of CEUS LI-RADS with detailed, step-by-step instructions and imaging examples of CEUS LI-RADS categories.

Contrast-enhanced ultrasound (CEUS) has become an established modality in various clinical indications for liver diseases. SonoVue®, a pure blood pure agent, and Sonazoid®, which exhibits an additional Kupffer phase, are contrast agents approved for liver imaging. This review discusses and compares the current clinical evidence for these two ultrasound contrast agents in the characterization and detection of focal liver lesions in the non-cirrhotic and cirrhotic liver, as well as for the use in interventional procedures such as liver biopsy guidance, and local ablation treatment monitoring. Reference is made to clinical studies which evaluated the accuracy of CEUS using a standard of reference, its safety, or to comparative studies of these two agents.

Ultrasound has been established as a baseline imaging technique for thyroid nodules. The main advantage of adding CEUS is the ability to assess the sequence and intensity of vascular perfusion and hemodynamics in the thyroid nodule, thus providing real-time characterization of nodule features, considered a valuable new approach in the determination of benign vs. malignant nodules. Original studies, reviews and six meta-analyses were included in this article. A total of 624 studies were retrieved, and 107 were included in the study. As recognized for thyroid nodule malignancy risk stratification by US, for acceptable accuracy in malignancy a combination of several CEUS parameters should be applied: hypo-enhancement, heterogeneous, peripheral irregular enhancement in combination with internal enhancement patterns, and slow wash-in and wash-out curve lower than in normal thyroid tissue. In contrast, homogeneous, intense enhancement with smooth rim enhancement and “fast-in and slow-out” are indicative of the benignity of the thyroid nodule. Even though overlapping features require standardization, with further research, CEUS may achieve reliable performance in detecting or excluding thyroid cancer. It can also play an operative role in guiding ablation procedures of benign and malignant thyroid nodules and metastatic lymph nodes, and providing accurate follow-up imaging to assess treatment efficacy.

Computer vision, biomedical image processing and deep learning are related fields with a tremendous impact on the interpretation of medical images today. Among biomedical image sensing modalities, ultrasound (US) is one of the most widely used in practice, since it is noninvasive, accessible, and cheap. Its main drawback, compared to other imaging modalities, like computed tomography (CT) or magnetic resonance imaging (MRI), consists of the increased dependence on the human operator. One important step toward reducing this dependence is the implementation of a computer-aided diagnosis (CAD) system for US imaging. The aim of the paper is to examine the application of contrast enhanced ultrasound imaging (CEUS) to the problem of automated focal liver lesion (FLL) diagnosis using deep neural networks (DNN). Custom DNN designs are compared with state-of-the-art architectures, either pre-trained or trained from scratch. Our work improves on and broadens previous work in the field in several aspects, e.g., a novel leave-one-patient-out evaluation procedure, which further enabled us to formulate a hard-voting classification scheme. We show the effectiveness of our models, i.e., 88% accuracy reported against a higher number of liver lesion types: hepatocellular carcinomas (HCC), hypervascular metastases (HYPERM), hypovascular metastases (HYPOM), hemangiomas (HEM), and focal nodular hyperplasia (FNH).