EFSUMB Technical Review - Update 2023: Dynamic Contrast-Enhanced Ultrasound (DCE-CEUS) for the Quantification of Tumor Perfusion.

Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US.

Liver Elastography in Healthy Children Using Three Different Systems - How Many Measurements Are Necessary?

PURPOSE: Liver elastography is increasingly being applied in screening for and follow-up of pediatric liver disease, and has been shown to correlate well with fibrosis staging through liver biopsy. Because time is of the essence when examining children, we wanted to evaluate if a reliable result can be achieved with fewer acquisitions. MATERIALS AND METHODS: 243 healthy children aged 4-17 years were examined after three hours of fasting. Participants were divided into four age groups: 4-7 years; 8-11 years; 12-14 years and 15-17 years. Both two-dimensional shear wave elastography (2D-SWE; GE Logiq E9) and point shear wave elastography (pSWE; Samsung RS80A with Prestige) were performed in all participants, while transient elastography (TE, Fibroscan) was performed in a subset of 87 children aged 8-17 years. Median liver stiffness measurement (LSM) values of 3, 4, 5, 6, 7, and 8 acquisitions were compared with the median value of 10 acquisitions (reference standard). Comparison was performed for all participants together as well as within every specific age group. We investigated both the intraclass correlation coefficient (ICC) with absolute agreement and all outliers more than 10 %, 20 % or ≥ 0.5 or 1.0 kPa from the median of 10 acquisitions. RESULTS: For all three systems there was no significant difference between three and ten acquisitions, with ICCs ≥ 0.97. All systems needed 4 acquisitions to achieve no LSM deviating ≥ 1.0 kPa of a median of ten. To achieve no LSM deviating ≥ 20 % of a median of ten acquisitions, pSWE and TE needed 4 acquisitions, while 2D-SWE required 6 acquisitions. CONCLUSION: Our results contradict recommendations of 10 acquisitions for pSWE and TE and only 3 for 2D-SWE.

Professional Standards in Medical Ultrasound - EFSUMB Position Paper (Long Version) - General Aspects.

This first position paper of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) on professional standards presents a common position across the different medical professions within EFSUMB regarding optimal standards for the performing and reporting of ultrasound examinations by any professional ultrasound operator. It describes general aspects of professionality that ensure procedure quality, effectiveness, efficiency, and sustainability in virtually all application fields of medical ultrasound. Recommendations are given related to safety and indication of ultrasound examinations, requirements for examination rooms, structured examination, systematic reporting of results, and management, communication and archiving of ultrasound data. The print version of this article is a short version. The long version is published online.

Professional Standards in Medical Ultrasound - EFSUMB Position Paper (Short Version) - General Aspects.

This first position paper of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) on professional standards presents a common position across the different medical professions within EFSUMB regarding optimal standards for the performing and reporting of ultrasound examinations by any professional ultrasound operator. It describes general aspects of professionality that ensure procedure quality, effectiveness, efficiency, and sustainability in virtually all application fields of medical ultrasound. Recommendations are given related to safety and indication of ultrasound examinations, requirements for examination rooms, structured examination, systematic reporting of results, and management, communication and archiving of ultrasound data. The print version of this article is a short version. The long version is published online.

Performance of contrast-enhanced ultrasound (CEUS) in assessing thyroid nodules: a systematic review and meta-analysis using histological standard of reference.

BACKGROUND: The present study was undertaken to systematically review the literature on the reliability of using contrast-enhanced ultrasound (CEUS) to assess thyroid nodules. To avoid the potential bias in studies using a cytological standard of reference, here we aimed to meta-analyze data from studies adopting histological diagnosis as the gold standard. METHODS: A comprehensive literature exploration of PubMed and Scopus was conducted. The search was updated until June 2018 and references of the retrieved articles screened. Only original articles reporting the histological follow-up of nodules previously undergone CEUS evaluation were eligible for inclusion. Pooled sensitivity, specificity, PPV, and NPV of CEUS were calculated by DerSimonian and Laird method (random-effects model). RESULTS: The literature search retrieved 1885 articles, and 14 were included for the study. There were Chinese, Italian, German, and Austrian authors. All studies used SonoVue. The overall number of reported nodules was 1515, of which 775 were classified as positive at CEUS and 740 as negative. Pooled sensitivity, specificity, PPV, and NPV of CEUS were 85% (95% CI 83-88), 82% (95% CI 77-87), 83% (95% CI 77-88), and 85% (95% CI 81-88), respectively. Moderate inconsistency was present for specificity and PPV. There was publication bias for sensitivity and NPV. CONCLUSIONS: CEUS reaches good performance in discriminating between malignant and benign thyroid lesions.

Good Agreement Between Transabdominal and Endoscopic Ultrasound of the Pancreas in Chronic Pancreatitis.

PURPOSE: We aimed to evaluate the agreement of single criteria and dedicated scores from transabdominal ultrasound of the pancreas (US) compared to standards by endoscopic ultrasound (EUS) and computed tomography (CT). MATERIALS AND METHODS: In this observational cohort study performed in a tertiary care center, US and EUS were performed in 110 patients referred for suspected CP. Based on the Mayo score, 52 patients were diagnosed with CP. The sonographic findings obtained by both methods were registered. The number of criteria was counted and scored according to the Rosemont score. RESULTS: Agreement between the number of detected US and EUS criteria was substantial (ICC = 0.74 [0.61-0.83]. Adding Rosemont weighting improved the agreement (ICC = 0.88 [0.81-0.92]). Regarding individual criteria, the agreement was substantial for the detection of calcifications (κ = 0.86) and moderate for cysts and irregular or dilated pancreatic duct (κ = 0.42-0.58). Agreement for the other criteria was poorer (κ≤ 0.40). The diagnostic performance indices [95 % CI] of US for diagnosing CP (using Mayo score as reference standard) were for the unweighted score: Sensitivity: 0.65 [0.51-0.78], specificity: 0.97 [0.87-1.00]; and for Rosemont score: Sensitivity: 0.75 [0.61-0.86], specificity: 0.95 [0.83-0.99]. CONCLUSION: The agreement between US and EUS for the unweighted and weighted scores was substantial. For the features calcifications, cysts and main pancreatic duct (MPD) changes, agreement was moderate to substantial. For the other detected US criteria, the agreement with EUS was too poor to be clinically relevant.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Elastography in Non-Hepatic Applications: Update 2018.

This manuscript describes the use of ultrasound elastography, with the exception of liver applications, and represents an update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography.

EUS Needle Identification Comparison and Evaluation study (with videos).

BACKGROUND AND AIMS: EUS-guided FNA or biopsy sampling is widely practiced. Optimal sonographic visualization of the needle is critical for image-guided interventions. Of the several commercially available needles, bench-top testing and direct comparison of these needles have not been done to reveal their inherent echogenicity. The aims are to provide bench-top data that can be used to guide clinical applications and to promote future device research and development. METHODS: Descriptive bench-top testing and comparison of 8 commonly used EUS-FNA needles (all size 22 gauge): SonoTip Pro Control (Medi-Globe); Expect Slimline (Boston Scientific); EchoTip, EchoTip Ultra, EchoTip ProCore High Definition (Cook Medical); ClearView (Conmed); EZ Shot 2 (Olympus); and BNX (Beacon Endoscopic), and 2 new prototype needles, SonoCoat (Medi-Globe), coated by echogenic polymers made by Encapson. Blinded evaluation of standardized and unedited videos by 43 EUS endoscopists and 17 radiologists specialized in GI US examination who were unfamiliar with EUS needle devices. RESULTS: There was no significant difference in the ratings and rankings of these needles between endosonographers and radiologists. Overall, 1 prototype needle was rated as the best, ranking 10% to 40% higher than all other needles (P < .01). Among the commercially available needles, the EchoTip Ultra needle and the ClearView needle were top choices. The EZ Shot 2 needle was ranked statistically lower than other needles (30%-75% worse, P < .001). CONCLUSIONS: All FNA needles have their inherent and different echogenicities, and these differences are similarly recognized by EUS endoscopists and radiologists. Needles with polymeric coating from the entire shaft to the needle tip may offer better echogenicity.

Characterization of solid focal pancreatic lesions using endoscopic ultrasonography with real-time elastography.

OBJECTIVES. The aim of this study was to evaluate the diagnostic potential of strain assessment in solid focal pancreatic lesions using real-time elastography in combination with endoscopic ultrasonography (EUS). MATERIAL AND METHODS. Forty-eight solid focal pancreatic lesions in 39 patients were included prospectively over a 3-year period and studied by EUS with real-time elastography (EUS-RTE). Lesions previously described as cystic by CT were not included. Distribution patterns of tissue strain were assessed using strain ratio (SR) measurements, continuous visual analog scale (VAS), and a visual categorical score (VCS), based on color coding of relative strain. Final diagnosis was based on histopathology, fine-needle aspiration cytology, and/or follow-up for ≥6 months. RESULTS. The 48 lesions included 11 adenocarcinomas, 7 malignant neuroendocrine tumors (NETs), 11 benign or indeterminate NETs, 8 focal pancreatic lesions, 2 microcystic adenomas, and 9 other benign lesions. Malignant lesions had significantly higher median SR (7.05 vs. 1.56) and VAS scores (93.0 vs. 63.5) than benign lesions. A receiver operation characteristic curve analysis showed sensitivity of 67% and specificity of 71%, when using SR = 4.4 as a cut-off for malignancy. The highest SR values were found in two benign microcystic adenomas. CONCLUSIONS. EUS-RTE with SR measurements and VAS evaluation demonstrated a significant strain difference between benign and malignant lesions. However, the variation within the entities was substantial and some benign lesions presented with low strain. Benign lesions were generally characterized by a strain similar to reference tissue, whereas malignant lesions were harder. The recorded strain pattern in individual lesions must be interpreted with caution.

The outcome of primary per oral endoscopic myotomy (POEM) for treatment of achalasia: Norwegian single-center experience with long-term follow-up.

BACKGROUND AND AIMS: Per oral endoscopic myotomy (POEM) has become an established treatment for achalasia, but no Scandinavian studies with long-term follow-up exist. This study from a tertiary referral center in Norway investigates the short-, mid-, and long-term feasibility, safety, efficacy, and complications of POEM. METHODS: Prospective data from the first 84 patients who underwent POEM from 2014 to 2019 were analyzed. The median follow-up time was 44 months. Clinical success was defined as the Eckardt score (ES) ⩽3, and reflux as pathological if the acid exposure time (pH < 4) was more than 6%. ES was used for symptom evaluation before, and at 6, 12, and up to 64 months after POEM. RESULTS: A total of 50 males and 34 females were included. A total of 43 (51%) were treatment naïve, 24 (28.6%) had been previously treated with botulinum toxin, pneumatic balloon dilatation, or both, and 17 (20.2%) were previously treated with Heller's myotomy. The median post-POEM ES at 12 months was 1 (0-9), compared to pre-POEM 7 (4-12) (p < 0.01). At 12 months after POEM, clinical success persisted in 74 patients (88.1%). Clinical success was the highest for patients who were naïve to treatment, 41/43 (95%), and lower for those previously treated with Heller's myotomy 12/17 (70.6%). Long-term follow-up at 5-6 years of 42 patients showed a clinical success rate of 94%. We experienced adverse events in five patients (6%). Post-POEM pathological reflux was found in 46% (28/61). After 3-4 years, the median ES was 1, and after 5-6 years, it was 2. CONCLUSION: POEM was safe and relieved the symptoms of achalasia significantly and persistently. The procedure had a better outcome in treatment naïve than previously treated patients. However, POEM is associated with significantly increased esophageal acid exposure. TWITTER SUMMARY: Norwegian single-center study: POEM had a clinical success rate of 94% after 5-6 years since its introduction at the center in 2014, providing a safe and effective treatment for achalasia.

Diagnostic Accuracy of Transabdominal Ultrasound and Computed Tomography in Chronic Pancreatitis: A Head-to-Head Comparison.

Purpose Computed tomography (CT) is the most used imaging modality for diagnosing chronic pancreatitis (CP), but advances in transabdominal ultrasound (US) technology have given US a position as a viable alternative. We aimed to evaluate the diagnostic accuracy of abdominal CT and pancreatic US compared to the reference standard, a modified Mayo score. Materials and Methods CT, US, and endoscopic ultrasound (EUS) were performed in patients referred due to suspected CP. The modified Mayo score included EUS results, clinical presentation, and results from exocrine and endocrine pancreatic function tests. We scored CT findings according to the modified Cambridge classification and US findings according to the Rosemont classification. Results In total, 73 patients were included. 53 patients (73%) were categorized as CP and 20 (27%) as non-CP. CT and US yielded similar sensitivities (68% and 64%, respectively) and specificities (75 and 85%, respectively) and similar areas under the receiver operating characteristic curves for diagnosing CP. We found no significant differences between the areas under the receiver operating characteristic curves (AUROCs) for CT (AUROC 0.75, 95% CI 0.63-0.87) and US (AUROC 0.81, 95% CI 0.71-0.91). Conclusion We conclude that CT and US had comparable, moderate accuracy in diagnosing CP. Neither modality had high enough sensitivity to exclude the diagnosis as a standalone method.

Diagnostic Accuracy of Computed Tomography Scores in Chronic Pancreatitis.

OBJECTIVES: Computed tomography (CT) is the most commonly used imaging modality when diagnosing chronic pancreatitis (CP). We aimed to evaluate the diagnostic accuracy of CT scores for diagnosing CP. METHODS: One hundred eighteen patients were retrospectively included from an observational cohort study that comprised patients referred because of suspected CP. Patients were categorized as CP or non-CP using a modified Mayo score based on biochemistry, clinical presentation, and findings on endoscopic ultrasound and/or transabdominal ultrasound. The CT scans were scored according to the modified Cambridge classification and the unweighted CT score. Diagnostic performance indices were calculated using the modified Mayo score as reference standard. RESULTS: Seventy-six of the 118 patients fulfilled the CP diagnostic criteria (Mayo score ≥4). The modified Cambridge classification and the unweighted CT score yielded sensitivities of 63% and 67% and specificities of 91% and 91%, respectively, and similar areas under the receiver operating characteristic curves (95% confidence interval) of 0.79 (0.71-0.88)/0.81 (0.73-0.89), respectively (P, not significant). CONCLUSIONS: Both CT scores had similar, moderate accuracies for diagnosing CP. The limitation in diagnostic accuracy makes CT ineligible as a single method to diagnose CP, supporting that the diagnostic process for CP needs to incorporate other imaging methods and/or markers for better diagnostics.

Liver elasticity in healthy individuals by two novel shear-wave elastography systems-Comparison by age, gender, BMI and number of measurements.

OBJECTIVE: Establishing normal liver stiffness (LS) values in healthy livers is a prerequisite to differentiate normal from pathological LS values. Our aim was to define normal LS using two novel elastography methods head-to-head and to assess the number of measurements, variability and reproducibility. MATERIALS AND METHODS: We evaluated shear wave elastography (SWE) methods integrated in Samsung RS80A and GE S8 by obtaining LS measurements (LSM) in 100 healthy subjects (20-70 years). Transient Elastography (TE) was used as reference method. Data were analyzed according to age, sex, BMI and 5 vs. 10 measurements. All subjects underwent B-mode ultrasound examination and lab tests to exclude liver pathology. Interobserver variation was evaluated in a subset (n = 24). RESULTS: Both methods showed excellent feasibility, measuring LS in all subjects. LSM-mean for GE S8 2D-SWE was higher compared to TE (4.5±0.8 kPa vs. 4.2±1.1, p<0.001) and Samsung RS80A (4.1±0.8 kPa, p<0.001). Both methods showed low intra- and interobserver variation. LSM-mean was significantly higher in males than females using 2D-SWE, while a similar trend for Samsung SWE did not reach significance. No method demonstrated statistical significant difference in LSM across age and BMI groups nor between LSM-mean based on 5 vs. 10 measurements. CONCLUSION: LSM was performed with high reproducibility in healthy adult livers. LSM-mean was significantly higher for GE S8 2D-SWE compared to Samsung RS80A and TE in healthy livers. Males had higher LSM than females. No method demonstrated statistical significant difference in LSM-mean across age- and non-obese BMI groups. Our results indicate that five LSM may be sufficient for reliable results.

Repeatability of shear wave elastography in liver fibrosis phantoms-Evaluation of five different systems.

This study aimed to assess and validate the repeatability and agreement of quantitative elastography of novel shear wave methods on four individual tissue-mimicking liver fibrosis phantoms with different known Young's modulus. We used GE Logiq E9 2D-SWE, Philips iU22 ARFI (pSWE), Samsung TS80A SWE (pSWE), Hitachi Ascendus (SWM) and Transient Elastography (TE). Two individual investigators performed all measurements non-continued and in parallel. The methods were evaluated for inter- and intraobserver variability by intraclass correlation, coefficient of variation and limits of agreement using the median elastography value. All systems used in this study provided high repeatability in quantitative measurements in a liver fibrosis phantom and excellent inter- and intraclass correlations. All four elastography platforms showed excellent intra-and interobserver agreement (interclass correlation 0.981-1.000 and intraclass correlation 0.987-1.000) and no significant difference in mean elasticity measurements for all systems, except for TE on phantom 4. All four liver fibrosis phantoms could be differentiated by quantitative elastography, by all platforms (p<0.001). In the Bland-Altman analysis the differences in measurements were larger for the phantoms with higher Young's modulus. All platforms had a coefficient of variation in the range 0.00-0.21 for all four phantoms, equivalent to low variance and high repeatability.

Assessing Liver Stiffness by 2-D Shear Wave Elastography in a Healthy Cohort.

The aim of this study was to assess the normal ranges of liver stiffness measurements (LSMs) in participants with healthy livers, using General Electric 2-D shear wave elastography (2-D-SWE-GE) compared with transient elastography (TE). We included 80 participants with healthy livers and without known liver disease, in whom liver stiffness was evaluated in the same session using two elastographic methods, TE and 2-D-SWE-GE. Reliable LSMs were defined for TE as the median of 10 measurements with a success rate of ≥60% and an interquartile range (IQR) < 30%, and for 2-D-SWE-GE, as the median of 10 measurements acquired in a homogenous area and an IQR < 30%. Participants with LSMs > 6.5 kPa by TE were excluded. Reliable LSMs were obtained in 79 participants (98.7%) by means of 2-D-SWE-GE and in 80 participants (100%) by means of TE (p = 0.9). The mean LSM obtained by 2-D-SWE-GE in our cohort of participants with healthy livers was 5.1 ± 1.3 kPa, which was significantly higher than the LSM assessed by TE (4.3 ± 0.9 kPa, p < 0.0001). In 2-D SWE-GE, mean LSMs were significantly higher for men than for women, 5.9 ± 1.2 kPa versus 4.7 ± 1.2 kPa (p = 0.0005). In conclusion, 2-D-SWE-GE has very good feasibility (98.7%) in healthy persons. The mean LSM determined by 2-D-SWE-GE in healthy participants was 5.1 ± 1.3 kPa. LSMs obtained by means of 2-D-SWE-GE were higher than those obtained by TE in participants with healthy livers.

Initial experience with EUS-guided microbiopsy forceps in diagnosing pancreatic cystic lesions: A multicenter feasibility study (with video).

BACKGROUND AND OBJECTIVES: Cystic lesions of the pancreas represent a diagnostic dilemma. Recently, a through-the-needle microbiopsy forceps has become available, enabling procurement of EUS-guided histological specimens from the pancreatic cyst wall. The aim of this study was to evaluate the use of this novel instrument in a multicenter clinical setting. PATIENTS AND METHODS: Patients referred for EUS evaluation of pancreatic cysts and attempted EUS-guided microbiopsy was included retrospectively from six international tertiary centers. Patient's demographics, EUS findings, technical and clinical success, and histopathological results were recorded. RESULTS: : A total of 28 patients were identified. We report a technical success rate of 85.7% (n = 24). Biopsies were generally of good quality and contributed to the diagnosis in 20 patients (clinical success of 71.4%). Three adverse events were recorded (10.7%). CONCLUSIONS: The use of the microbiopsy forceps is feasible with acceptable rates of technical and clinical success. Prospective studies are warranted to determine the diagnostic potential compared to the other modalities. However, the results from this preliminary study are promising.

Strain Elastography - How To Do It?

Tissue stiffness assessed by palpation for diagnosing pathology has been used for thousands of years. Ultrasound elastography has been developed more recently to display similar information on tissue stiffness as an image. There are two main types of ultrasound elastography, strain and shear wave. Strain elastography is a qualitative technique and provides information on the relative stiffness between one tissue and another. Shear wave elastography is a quantitative method and provides an estimated value of the tissue stiffness that can be expressed in either the shear wave speed through the tissues in meters/second, or converted to the Young's modulus making some assumptions and expressed in kPa. Each technique has its advantages and disadvantages and they are often complimentary to each other in clinical practice. This article reviews the principles, technique, and interpretation of strain elastography in various organs. It describes how to optimize technique, while pitfalls and artifacts are also discussed.