Acoustic radiation force impulse (ARFI) elastography of the bowel wall as a possible marker of inflammatory activity in patients with Crohn's disease.

AIM: To evaluate acoustic radiation force impulse (ARFI) shear-wave velocities of the bowel wall in patients with Crohn's disease (CD). MATERIAL AND METHODS: ARFI shear-wave elastography was analysed within the wall of the stomach, terminal ileum, and sigmoid, and correlated with ultrasound signs of activity in CD patients both retrospectively and in a prospective cohort. RESULTS: A total of 77 retrospective and 21 prospective CD patients were included. ARFI elastography in the stomach, the normal ileum, and sigmoid was lower than in ileitis or sigmoiditis. Retrospectively, the ARFI values correlated with the bowel wall thickness and Limberg vascularisation score. Prospectively, there was no correlation between ARFI and bowel wall thickness, Limberg score, clinical activity, or C-reactive protein. A cut-off analysis of 105 ileal ARFI measurements showed a cut-off value of 1.92 m/s for the diagnosis of ileal inflammation with 75.3% sensitivity and 87.5% specificity. CONCLUSION: In patients with CD, ARFI shear-wave velocities show a trend to higher values in inflamed bowel wall thickening on B-mode ultrasound; however, the differences appear small and may not be clinically significant. The factors influencing ARFI measurements of the bowel wall require further investigation.

Diagnostic accuracy and interobserver variability of Dynamic Vascular Pattern (DVP) in primary liver malignancies - A simple semiquantitative tool for the analysis of contrast enhancement patterns.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a valuable tool in the diagnostic approach of focal liver lesions, but occasionally subjective and observer-dependent. Semiquantitative evaluation of dynamic CEUS (DCEUS) with standardised software programmes such as Dynamic Vascular Pattern (DVP) could help to improve diagnostic accuracy and objectivity in liver tumour assessment. OBJECTIVES: The present study aimed at evaluation of diagnostic accuracy of DVP in a clinical setting. MATERIALS AND METHODS: DVP images of 52 focal liver lesions [30 hepatocellular carcinomas (HCCs), 15 intrahepatic cholangiocellular carcinomas (ICCs), 7 focal nodular hyperplasias (FNHs)] were analysed by four blinded observers with different levels of CEUS-experience. Diagnostic accuracies for the assessment of dignity and entity were evaluated. RESULTS: Mean sensitivity, specificity, positive and negative predictive value for detection of malignancy with DVP were 48.4% /67.8% /92.7% and 29.3%, respectively. Total diagnostic accuracies for dignity/entity were 63.9% /38.5% (HCC: 58.3% /25.8%; ICC: 73.3% /50%; FNH: 67.9% /67.9%). Interreader-agreement was moderate (κ= 0.42-0.58). Differential diagnosis between ICC and HCC was most challenging. CONCLUSION: Although developed to improve diagnostic accuracy and objectivity in the assessment of focal liver lesions, DVP alone seems insufficient for differential diagnosis of HCC, ICC and FNH and cannot replace the skills of an experienced observer.

LI-RADS-CEUS - Proposal for a Contrast-Enhanced Ultrasound Algorithm for the Diagnosis of Hepatocellular Carcinoma in High-Risk Populations.

Purpose: To develop a contrast-enhanced ultrasound algorithm (LI-RADS-CEUS = liver imaging reporting and data system with contrast-enhanced ultrasound) for the diagnosis of hepatocellular carcinoma (HCC) in patients at risk. Materials and Methods: A CEUS algorithm (LI-RADS-CEUS) was designed analogously to CT- and MRI-based LI-RADS. LI-RADS-CEUS was evaluated retrospectively in 50 patients at risk with confirmed HCC or non-HCC lesions (test group) with subsequent validation in a prospective cohort of 50 patients (validation group). Results were compared to histology, CE-CT and CE-MRI as reference standards. Results: Tumor diagnosis in the test group/validation group (n = 50/50) were 46/41 HCCs, 3/3 intrahepatic cholangiocellular carcinomas (ICCs) and 1/6 benign lesions. The diagnostic accuracy of LI-RADS-CEUS for HCC, ICC and non-HCC-non-ICC-lesions was 89 %. For the diagnosis of HCC, the diagnostic accuracy was 93.5 % (43/46 cases) in the test group and 95.1 % (39/41 cases) in the validation group. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 94.3 %, 66.6 %, 94.3 % and 66.6 %, respectively (mean values from both cohorts). Histological findings of HCC were available in 40 versus 23 cases (in total: G1 / G2/G3: 15/35/13). Arterial hyperenhancement was seen in 68/87 (78.2 %) of HCCs. Arterial hyperenhancement with subsequent portal venous or late phase hypoenhancement was seen in 66 % of HCCs. Conclusion: LI-RADS-CEUS offers a CEUS algorithm for standardized assessment and reporting of focal liver lesions in patients at risk for HCC. Arterial hyperenhancement in CEUS is the key feature for the diagnosis of HCC in patients at risk, whereas washout is not a necessary prerequisite.

Comparison of Acoustic Radiation Force Impulse (ARFI) Elastography Measurements with the 4C1 Transducer to the 6C1HD Transducer: A Phantom and Patient Study.

Purpose: The aim of this study was to evaluate whether acoustic radiation force impulse (ARFI) elastography done with the 4C1 probe yields comparable results to the recently introduced 6C1HD probe. Materials and Methods: Measurements with the 4C1 and 6C1HD probes (Acuson S2000) were performed and compared in four different inclusions of an elasticity phantom model (QA049 CIRS) as well as in the liver of healthy individuals and patients with liver cirrhosis. Results: Measurements with the 6C1HD probe were slightly higher in all phantom inclusions (8, 14, 45, 80kPA) with a mean of 1.48 m/s (95 %-CI; 1.47 - 1.49), 2.18 m/s (95 %-CI; 2.17 - 2.19), 3.61 m/s (95 %-CI; 3.57 - 3.64) and 4.34 m/s (95 %-CI; 4.29 - 4.39) compared to the 4C1 transducer with 1.46 m/s (95 %-CI; 1.45 - 1.47), 2.15 m/s (95 %-CI; 2.14 - 2.16), 3.39 m/s (95 %-CI; 3.37 - 3.41) and 3.98 m/s (95 %-CI; 3.75 - 4.21), respectively (p = 0.04, p < 0.01, p < 0.01, p < 0.01). Cirrhotic patients (n = 40) had a higher mean shear wave speed with 3.00 m/s (95 %-CI; 2.80 - 3.21) with the 6C1HD transducer compared to 2.81 m/s (95 %-CI; 2.64 - 2.99) with the 4C1 transducer (p = 0.03). Healthy individuals (n = 20) had a mean shear wave speed of 1.12 m/s (95 %-CI; 1.06 - 1.17) with the 6C1HD probe and 1.12 m/s (95 %-CI; 1.05 - 1.19) with the 4C1 probe (p = 0.96). Conclusion: ARFI values assessed with a 6C1HD transducer are slightly higher than measurements with a 4C1 transducer in an ARFI phantom and in patients with liver cirrhosis. As the difference is small, current cut-off values keep their usefulness but should be interpreted with caution if measurements are close to the cut-off.

[Contrast-enhanced Ultrasound in Diagnostic Imaging of Muscle Injuries: Perfusion Imaging in the Early Arterial Phase]. / Kontrastmittelsonografie (CEUS) in der bildgebenden Diagnostik von Muskelverletzungen--Perfusionsdarstellung in der früharteriellen Phase.

BACKGROUND: Ultrasound is a standard procedure widely used in the diagnostic investigation of muscle injuries and widely described in the literature. Its advantages include rapid availability, cost effectiveness and the possibility to perform a real-time dynamic examination with the highest possible spatial resolution. In the diagnostic work-up of minor lesions (muscle stiffness, muscle strain), plain ultrasound has so far been inferior to MRI. The case presented by us is an example of the possibilities offered by contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries compared with plain B-mode image ultrasound and MRI imaging of the affected region. MATERIAL/METHODS: This case report is about a high-performance football player who sustained a muscle injury. He underwent an ultrasound examination (S 2000, 9L4 Probe, Siemens, Germany), which was performed simultaneously in the conventional and contrast-enhanced mode at the level of the lesion. An intravenous bolus injection of 4.8 ml of intravascular contrast agent (SonoVue(®), Bracco, Italy) was given via a cubital intravenous line. After that, the distribution of contrast agent was visualised in the early arterial phase. In addition, a plain magnetic resonance imaging scan of both thighs was performed for reference. RESULTS: On conventional ultrasound, the lesion was not clearly distinguishable from neighbouring tissue, whereas contrast-enhanced ultrasound demonstrated a well delineated, circumscribed area of impaired perfusion with hypoenhancement compared with the surrounding muscles at the clinical level of the lesion in the arterial wash-in phase (0-30 sec, after intravenous administration). The MRI scan revealed an edema signal with perifascial fluid accumulation in the corresponding site. CONCLUSION: The use of intravascular contrast agent enabled the sensitive detection of a minor injury by ultrasound for the first time. An intramuscular edema seen in the MRI scan showed a functional arterial perfusion impairment on ultrasound, which was sensitively detected in the early phase. Further examinations must be performed on muscle injuries of various degrees of severity in order to validate the application of this procedure and to standardise the examination process.

Prospective Evaluation of Acoustic Radiation Force Impulse (ARFI) Elastography and High-Frequency B-Mode Ultrasound in Compensated Patients for the Diagnosis of Liver Fibrosis/Cirrhosis in Comparison to Mini-Laparoscopic Biopsy.

PURPOSE: Ultrasound is a well-established noninvasive test for assessing patients with liver disease. This study aims to prospectively compare ultrasound to the new technique elastography (ARFI) for the assessment of liver fibrosis/cirrhosis. MATERIALS AND METHODS: High-frequency B-mode ultrasound (liver surface/vein irregularity, liver homogeneity, spleen size), ARFI quantification, mini-laparoscopic liver evaluation including biopsy were prospectively obtained in compensated patients scheduled for liver biopsy. For the diagnosis of cirrhosis, a combined gold standard (cirrhosis at histology and/or at macroscopic liver evaluation) was used. RESULTS: Out of 157 patients, 35 patients were diagnosed cirrhotic. Ultrasound (combination of liver vein and/or surface irregularity) showed no significant difference compared to ARFI quantification for the diagnosis of significant liver fibrosis (Ishak> = 3) and cirrhosis. Diagnosis of cirrhosis had a sensitivity/specificity/PPV/NPV of 83 %(±â€Š12) / 82 %(±â€Š7) / 57 %(±â€Š14) / 94 %(±â€Š4), respectively, with ultrasound and 86 %(±â€Š12) / 81 %(±â€Š7) / 57 %(±â€Š13) / 95 %(±â€Š4), respectively, with ARFI quantification. The sensitivity/specificity/PPV/NPV for the detection of significant fibrosis were 68 %(±â€Š13) / 86 %(±â€Š7) / 71 %(±â€Š13) / 84 %(±â€Š7), respectively, for ultrasound and 70 %(±â€Š12) / 84 %(±â€Š7) / 69 %(±â€Š12) / 84 %(±â€Š7), respectively, for ARFI quantification. CONCLUSION: ARFI elastography and high-frequency B-mode ultrasound show similar and good results for the diagnosis of compensated liver cirrhosis and high-grade fibrosis. A key benefit of both methods is the high NPV suggesting them as noninvasive exclusion tests.

Quantitative perfusion analysis in pancreatic contrast enhanced ultrasound (DCE-US): a promising tool for the differentiation between autoimmune pancreatitis and pancreatic cancer.

In the work-up of focal pancreatic lesions autoimmune pancreatitis (AIP) is a rare differential diagnosis to pancreatic cancer (PC) with similar clinical constellations. The aim of our study was to compare differences between proven AIP and PC using transabdominal dynamic contrast enhanced ultrasound (DCE-US). Therefore we recorded 3-minute-clips of CEUS examinations and analyzed perfusion parameters with VueBox®-quantification software. To obtain DCE-US Parameters, Regions-of-Interest were selected within the lesions and the surrounding pancreas parenchyma, serving as reference tissue. We compared 3 patients with AIP (mean age: 58 years; lesion mean size: 40 mm) to 17 patients with PC (mean age: 68 years; lesion mean size: 35.9 mm). Significant differences between PC and parenchyma could be found in the following parameters: Peak-Enhancement (PE), Wash-in-and-Wash-out-AUC, Wash-in Perfusion-Index. PE of AIP was comparable to normal parenchyma. The relation of PE between parenchyma and lesion (ΔPE) AIP and PC was significantly different [AIP: 0.21 (±0.06); PC: 0.81 (±0.1); p<0.01]. PE of neoplastic lesions was significantly lower as AIP and normal parenchyma (p<0.01). Therefore perfusion analysis in DCE-US can help to differentiate hypovascular PC from AIP presenting nearly isovascular time intensity curves. Diagnostic accuracy of DCE-US in this setting has to be validated in future prospective studies in comparison to CT and MRI.

CEUS in hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma in 320 patients - early or late washout matters: a subanalysis of the DEGUM multicenter trial.

PURPOSE: The aim of the study was the comparison of tumor vascularization and contrast enhancement in contrast-enhanced ultrasound (CEUS) for the characterization of hepatocellular carcinoma (HCC) and intrahepatic cholangiocellular carcinoma (ICC). We present data of the subpopulations HCC and ICC examined in the DEGUM multicenter trial for the characterization of focal liver lesions in clinical practice. MATERIALS AND METHODS: Based on the data of the DEGUM multicenter trial (1349 patients), all patients with histologically proven HCC (n = 278) and ICC (n = 42) were analyzed. The vascularity pattern and contrast enhancement pattern during the arterial, portal-venous and late phase were compared. RESULTS: An underlying liver cirrhosis was found in 214/278 patients with HCC (76.9 %) and 7/42 patients with ICC (16.7 %). In CEUS, HCC showed a global arterial hyperenhancement compared to ICC (HCC: tumor center: 60.3 %; tumor periphery: 75 %; ICC: tumor center: 16.7 %; tumor periphery: 40.5 %). ICC showed an initial contrast enhancement primarily at the tumor periphery (ICC: 85.7 % vs. HCC: 61 %) followed by an early portal-venous contrast washout in the tumor center (ICC: 85.8 % vs. HCC: 49.8 %) and tumor periphery (ICC: 66.7 % vs. HCC: 32.6 %). HCC showed a delayed contrast washout (late phase hypoenhancement: HCC: 75 % vs. ICC: 92.9 %). CONCLUSION: ICCs are rare in cirrhotic livers. CEUS can demonstrate differences in the vascularization patterns between HCC and ICC. HCC showed an arterial global hyperenhancement and delayed contrast washout in the late phase. ICCs are characterized by an arterial contrast enhancement at the tumor periphery with early contrast washout of the vascularized parts of the lesions in the portal-venous and late phase.

Dynamic contrast-enhanced ultrasound (DCE-US) for the characterization of hepatocellular carcinoma and cholangiocellular carcinoma.

PURPOSE: In a prospective study, we compared the different perfusion kinetics of HCC and ICC using dynamic contrast-enhanced ultrasound (DCE-US). MATERIALS AND METHODS: Patients with proven HCC and ICC were included. Three-minute video clips of CEUS examinations (CPS - low MI mode) after a bolus injection of 1.2 ml SonoVue were recorded and analyzed with quantification software (VueBox). Parameters for the arterial contrast enhancement [rise time (RT), time-to-peak (TTP)] towards portal venous contrast enhancement [mean transit time (local) (mTTl) and fall time (FT)] were quantified. Furthermore, contrast wash-out after peak enhancement (PE) (40 s, 80 s, 100 s and 120 s after PE) was compared between HCC and ICC. RESULTS: 43 patients with proven HCC (n = 23 HCC; cirrhosis n = 16) and ICC (n = 20 ICC; Cirrhosis n = 6) were examined. No statistical difference of the arterial DCEUS parameters was found between HCC and ICC. Contrast enhancement of the portal venous and late phases showed significantly lower values in the ICC group indicating early wash-out of the contrast agent: mTTl (p = 0.0209): HCC 118.4 s (SD±â€Š88.4); ICC 64.8 s (SD±â€Š49.7). FT (p = 0.0433): HCC 42.5 s (SD±â€Š27.7); ICC 27.7 s (SD±â€Š16.2). The percental loss of intensity at a definite time point after PE was significantly higher in ICC than in HCC lesions. CONCLUSION: DCE-US is able to detect and quantify differences in perfusion kinetics between HCC and ICC. Whereas arterial contrast enhancement patterns may overlap between HCC and ICC, a timed characterization of wash-out kinetics may offer an additional tool to characterize HCC and ICC. The presence of a rapid loss of signal intensity in the early portal venous phase is significantly higher in ICC than in HCC lesions.

Liver stiffness assessed by acoustic radiation force impulse (ARFI) technology is considerably increased in patients with cholestasis.

PURPOSE: To explore the impact of cholestasis on liver stiffness assessed by acoustic radiation force impulse (ARFI) technology. MATERIALS AND METHODS: Over a period of four months, patients with sonographic cholestasis and increased cholestatic blood values (Bilirubin, γGT, AP > 2 times ULN) scheduled for endoscopic therapy were recruited. Exclusion criteria were: known liver disease; signs of cirrhosis at ultrasound (irregular liver veins and/or surface); heart insufficiency (NYHA III-VI). ARFI (Siemens S2000), ultrasound and blood examinations were performed before and in a subgroup after successful biliary drainage. RESULTS: In total, 21 patients with cholestasis were included in the study. ARFI measurements were above the cut-off for cirrhosis (1.8  m/s) in all patients with a mean of 2.91  m/s ±â€Š0.89  m/s without a history or signs of cirrhosis. Bilirubin, γGT and AP were elevated on average to 9.7 ±â€Š5.3  mg/dl, 1192 ±â€Š960  U/l and 730 ±â€Š389  U/l. A subgroup of 10 patients was measured after successful drainage. ARFI measurements declined in all patients of that subgroup on average by 0.76  m/s at a mean time interval of 4.5 days (p < 0.001). CONCLUSION: Cholestasis significantly increases liver stiffness assessed by ARFI. Therefore, it is important to exclude profound cholestasis when using ARFI for evaluating patients for liver fibrosis.

Postinterventional pain and complications of sonographically guided interventions in the liver and pancreas.

PURPOSE: Sonographically guided interventions in abdominal organs are routine procedures with rare severe complications. However, potential patient discomfort or pain is frequently not addressed in the literature. MATERIALS AND METHODS: In a prospective 1-year study, the peri- and postinterventional pain of patients undergoing sonographically guided punctures of the liver and pancreas was analyzed. Data acquisition was done with a standardized questionnaire. This included three numeric rating scales (NRS) ranging from "0" to "10" to be answered at puncture and 1 hour and 4 hours later. Data concerning complications and administered analgesic medication was acquired from the patients' charts. RESULTS: 223/274 patients could be analyzed (83 %). 91 women (40.8 %) and 132 men (59.2 %) were included. The mean age was 56.0 yrs. Overall the average level of pain was 2.98  at puncture, 1.21 after 1 hour and 0.71 after 4 hours. In patients with diagnostic biopsies, the pain levels were 3.37(0  h)/1.33(1  h)/0.71(4  h) for liver parenchyma, 2.64(0  h)/0.95(1  h)/0.65(4  h) for focal liver lesions and 3.1(0  h)/1.9(1  h)/1.1(4  h) for pancreatic punctures. The pain levels at therapeutic interventions were 3.00(0  h)/2.00(1  h)/0.50(4  h). Female and younger (< 50 yrs) patients had statistically significantly more pain at puncture and 1 hour postintervention. Only minor complications occurred (0.9 %). CONCLUSION: Severe pain after sonographically guided interventions is rare. Most patients suffer only from mild pain postinterventionally.

Outcome analysis of liver stiffness by ARFI (acoustic radiation force impulse) elastometry in patients with chronic viral hepatitis B and C.

AIM: To evaluate the association between liver stiffness measured by acoustic radiation force impulse (ARFI) elastometry and the outcome of antiviral treatment in patients with chronic viral hepatitis B and C. MATERIALS AND METHODS: Thirty-eight patients with chronic viral hepatitis B (n = 16) or hepatitis C (n = 22) underwent liver biopsy and ARFI elastometry of the right hepatic lobe. A follow-up assessment using ARFI was performed a mean of 2.3 years after the baseline evaluation. The patients with favourable outcome were classified in group S and those receiving no treatment, showing no response to treatment, or experiencing a relapse were classified in group N. RESULTS: The 38 patients had an initial mean ARFI value of 1.56 ± 0.62 m/s as compared with 1.54 ± 0.64 m/s in the follow-up evaluation. Group S showed a significant decline in ARFI values (1.55 ± 0.60 m/s versus 1.34 ± 0.47 m/s; p < 0.05) and included 16 (64%) patients with lower shear wave velocities at follow-up. In group N, liver stiffness values showed a slight but not significant increase (1.57 ± 0.70 m/s versus 1.93 ± 0.77 m/s). CONCLUSION: Changes in liver stiffness during antiviral therapy can be assessed by ARFI reflecting response or no response. ARFI elastometry is an additional, useful tool for the follow-up assessment of treatment outcome in patients with chronic viral hepatitis B or C infection.

Early response to anti-tumoral treatment in hepatocellular carcinoma--can quantitative contrast-enhanced ultrasound predict outcome?

PURPOSE: In order to detect an early response to anti-angiogenic therapy, this study aims at analyzing specific effects of a sorafenib-based regime on intra-tumoral D-CEUS flow parameters of patients with HCC. MATERIALS AND METHODS: Videos of the arterial phase were captured before initiation of a therapy with sorafenib and 1 and 3 months after (n = 9). Patients receiving a non-anti-angiogenic therapy (TACE, n = 10) served as a comparison group. Cross-sectional imaging was performed at the same time points and patients were followed up for 1 year. RESULTS: In the responder group (RE), the absolute (percentage) TTP was 11.28 s ± 2.03 s (1.00) before treatment, 13.60 s ± 1.52 s (1.53 ± 0.08) after one month (p = 0.0405), and 16.17 s ± 2.35 s (1.46 ± 0.07) after three months of treatment (p = 0.0071). The TTP increased significantly in the RE group as early as 1 month after initiation of sorafenib compared to the non-responder group. There were no significant differences in the non-responder group or between the NR and the TACE group at any time point. D-CEUS values from all sorafenib-treated patients showed good accordance with RECICL (response evaluation criteria in cancer of the liver) criteria (R2 = 0.7154, p = 0.0001). CONCLUSIONS: Quantitative CEUS reveals variations of dynamic parameters of blood flow during anti-tumoral therapy in liver cancer patients. Further investigations and clinical trails have to confirm that the TTP is a promising parameter in the prediction of early response to sorafenib-based therapy.