Benefit of Contrast-Enhanced Ultrasound (CEUS) in the Follow-Up Care of Patients with Colon Cancer: A Prospective Multicenter Study.

PURPOSE: According to the German guidelines on colorectal cancer, unenhanced ultrasound is recommended for follow-up. On the other hand, ultrasound and radiology societies specify the use of contrast-enhanced ultrasound for ruling out liver metastases. Studies focusing on the follow-up of cancer patients are lacking. The goal of this multicenter study initiated by the German Ultrasound Society (DEGUM) was to determine the potential benefit of contrast-enhanced ultrasound in the follow-up of patients with colon cancer. MATERIALS AND METHODS: Follow-up patients with colon cancer (UICC > IIa) were investigated. As scheduled according to the German guidelines, unenhanced ultrasound was performed followed by contrast-enhanced ultrasound. All liver lesions were recorded. In case of additional metastases detected on contrast-enhanced ultrasound, contrast-enhanced CT, MRI or biopsy was performed to confirm additional liver metastases. RESULTS: A total of 45 liver metastases were detected in 26/290 patients (= 9 %) using unenhanced ultrasound. A further 28 metastases were detected on contrast-enhanced ultrasound in these 26 patients. In 18 patients showing no liver metastases, 40 additional metastases were detected on unenhanced ultrasound. This means that 44 patients with a total of 113 liver metastases were detected on contrast-enhanced ultrasound (p = 0.0006). CONCLUSION: Contrast-enhanced ultrasound should be recommended in the follow-up of patients with colon cancer in addition to unenhanced ultrasound - the up-to-date standard.

Incidence of bleeding in 8172 percutaneous ultrasound-guided intraabdominal diagnostic and therapeutic interventions - results of the prospective multicenter DEGUM interventional ultrasound study (PIUS study).

PURPOSE: To analyse the incidence of bleeding after percutaneous ultrasound guided diagnostic and therapeutic intraabdominal interventions in a prospective multicentre study (DEGUM percutaneous interventional ultrasound study). MATERIALS AND METHODS: Within a time period of 2 years diagnostic and therapeutic intraabdominal interventions (with the exclusion of ascites paracentesis) performed percutaneously under continuous ultrasound (US) guidance were prospectively assessed using a pseudonymized standardized web site entry form. Number and type of intervention, operator experience, patient characteristics, medication, lab data as well as technical aspects of the procedure and bleeding complications were analysed according to the interventional radiology standards. RESULTS: 8172 US-guided intraabdominal interventions (liver n = 5903; pancreas n = 501, kidney n = 434, lymph node = 272, biliary system n = 153, spleen n = 63, other abdominal organs and extra-organic targets n = 999) were analysed in 30 hospitals. The majority were diagnostic biopsies including 1780 liver parenchyma, 3400 focal liver lesions and 404 pancreatic lesions. 7525 interventions (92.1 %) were performed in hospitalized patients (mean age 62.6 years). Most operators were highly experienced in US-guided interventions (> 500 interventions prior to the study n = 5729; 70.1 %). Sedation was administered in 1131 patients (13.8 %). Needle diameter was ≥ 1 mm in 7162 punctures (87.9 %) with main focus on core needle biopsies (18 G, n = 4185). Clinically relevant bleeding complications with need of transfusion (0.4 %), surgical bleeding control (0.1 %) and radiological coiling (0.05 %) were very rare. Bleeding complications with fatal outcome occurred in four patients (0.05 %). The frequency of major bleeding complications was significantly higher in patients with an INR > 1.5 (p < 0.001) and patients taking a medication potentially interfering with platelet function or plasmatic coagulation (p < 0.0333). CONCLUSION: This prospective multicentre study confirms the broad spectrum of percutaneous US-guided intraabdominal interventions. However diagnostic liver biopsies dominate with the use of core needle biopsies (18 G). Percutaneous US-guided interventions performed by experienced sonographers are associated with a low bleeding risk. Major bleeding complications are very rare. A pre-interventional INR < 1.5 and individual medication risk assessment are recommended.

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.

Acoustic radiation force impulse (ARFI) and high-frequency ultrasound of the liver surface for the diagnosis of compensated liver cirrhosis.

PURPOSE: To evaluate the diagnostic value of acoustic radiation force impulse (ARFI) and high-frequency ultrasound of the liver surface, using histology as a gold standard for the diagnosis of compensated liver cirrhosis. MATERIALS AND METHODS: 73 patients without ascites undergoing liver biopsy were included in the study. The left and right liver lobes were examined with ARFI and high-frequency ultrasound. Liver surface irregularity was quantified using image analysis software to calculate the difference between the real surface and the approximated physiological surface through a 20 mm standardized line. RESULTS: There is a significant difference between cirrhotic and non-cirrhotic patients for both quantified liver surface (QLS) and ARFI (p < 0.001). The mean values for QLS of the left lobe were 0.71 ± 0.24 mm and 1.17 ±â€Š0.80 mm, of the right lobe 0.56 ±â€Š0.26 mm and 0.87 ±â€Š0.26 mm for non-cirrhotic and cirrhotic patients, respectively. The mean values of ARFI measurements of the left lobe were 2.04 ±â€Š0.76 m/s and 2.85 ±â€Š0.81 m/s, of the right lobe 1.65 ±â€Š0.61 m/s and 3.02 ±â€Š0.77 m/s for non-cirrhotic and cirrhotic patients, respectively. Diagnostic accuracy (AUROC) was 0.78/0.80 for QLS and 0.77/0.91 for ARFI of the left/right lobe, respectively. ARFI of the right lobe is significantly better than ARFI of the left (p = 0.023) or QLS of the left (p = 0.025)/right (p = 0.046) lobe of the liver. CONCLUSION: Assessment of liver surface irregularity by high-frequency ultrasound (QLS) is a useful diagnostic test for the assessment of compensated liver cirrhosis. ARFI of the right liver lobe is significantly better than high-frequency ultrasound (QLS of the left/right lobe of the liver) and ARFI of the left lobe of the liver.

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.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

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.

Mesenteric transit time using contrast-enhanced ultrasound (CEUS) does not correlate with disease activity in Crohn's disease.

PURPOSE: Evaluation of mesenteric transit time (MTT) - measured by contrast-enhanced ultrasound - as a marker for inflammatory activity in Crohn's disease. MATERIALS AND METHODS: The time of maximum enhancement of the contrast agent in the superior mesenteric artery and vein was determined visually and by software analysis. The MTT was calculated as the difference between these two time points. Findings were correlated with the Harvey-Bradshaw Index (HBI) using the Pearson correlation coefficient (r). In addition, a healthy control group was evaluated both in the fasting state and 1, 2, 3 and 4 hours postprandially. RESULTS: In 20 healthy controls the mean visual MTT during fasting was 9.76 ± 2.83 sec and decreased to a minimum 1 hour after the meal (6.6 ± 2.27 sec). 45 patients with Crohn's disease (9 males, 36 females, mean age 35 years) had a mean HBI of 5.9 ± 4.7 points. The mean software-based MTT of 9.76 ± 3.7 sec was significantly higher (p = 0.034) than the mean visual MTT of 8.22 ± 3.05 sec. The two figures correlated well (r = 0.72, p < 0.001). The HBI correlated neither with the visual (r = 0.14, p = 0.371) nor with the software-based (r = 0.16, p = 0.293) MTT. CONCLUSION: The MTT decreases in the first two hours after eating. The visually assessed and the software-based MTT correlate well, however MTT does not correlate with disease activity in patients with Crohn's disease.

Frequency of tumor entities among liver tumors of unclear etiology initially detected by sonography in the noncirrhotic or cirrhotic livers of 1349 patients. Results of the DEGUM multicenter study.

AIM: Investigation of the frequency of various solid focal liver lesions (SFLL) in noncirrhotic and cirrhotic livers with focus on the frequency of metastasis in cirrhotic livers. MATERIAL AND METHODS: The patient collective in the DEGUM multicenter study (n = 1349) was reevaluated and divided in subcollective A without (n = 1067) and B with cirrhosis (n = 282). 74.6 % of the various tumor entities were confirmed histologically (n = 1006). RESULTS: In subcollective A there were 385 patients with metastases (36.4 %) and 65 with HCC (6.1 %), whereas the most common benign lesions were hemangioma, with 237 cases (22.4 %) and FNH, with 170 cases (16.1 %). In subcollective B there were 216 cases of HCC (76.6 %) and 12 metastases (4.3 %), as well as 42 benign lesions (14.9 %). CCC was rare in both subcollective A (3.3 %) and subcollective B (2.5 %). A positive oncological history increased the probability of a malignant SFLL in subcollective A by 1.8 times, but did not do so in subcollective B. CONCLUSION: The frequency of various tumor entities is different in patients with and without cirrhosis of the liver. In noncirrhotic livers, malignant and benign SFLL are equally common. The most common forms are metastases, hemangiomas and FNH, CCC is rare. A positive history of extrahepatic malignancy increases the probability of a malignant SFLL. In cirrhosis, HCC dominates, HCC is 18 times as common as metastases. Benign SFLL and CCC are rare.

Diagnostic accuracy of CEUS in the differential diagnosis of small (≤ 20  mm) and subcentimetric (≤ 10  mm) focal liver lesions in comparison with histology. Results of the DEGUM multicenter trial.

PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of small and subcentimetric liver tumors in clinical practice. MATERIALS AND METHODS: 1349 patients with a hepatic tumor lacking a definite diagnosis based on B-mode ultrasound and power Doppler ultrasound were examined at 14 hospitals by CEUS using a standardized protocol (pulse/phase inversion imaging, mechanical index < 0.4). Differential diagnosis was based on the vascularity pattern and contrast enhancement pattern during the arterial, portal, and late phase according to the EFSUMB guidelines. 335 patients with focal liver lesions (FLL) ≤ 20  mm were analyzed. The tumor status established after CEUS was compared to histology (73.2 %) or in some cases to CT or MRI. RESULTS: A definitive diagnosis based on the gold standard was possible in 329 FLLs, while 6 FLLs remained unclear even in the combined gold standard (histology and/or CT and/or MRI). The final diagnoses of ≤ 20  mm FLL with histological confirmation (n = 241) included 87 benign and 154 malignant entities. The overall diagnostic accuracy of CEUS in FLL ≤ 20  mm with histological confirmation was 83.8 %. CEUS correctly identified 144 /154 malignant FLLs (sensitivity 93.5 %) and 58 /87 benign FLLs (specificity 66.7 %). 24 /241 FLLs remained unclear after CEUS (9.9 %). CEUS misclassified 15 /241 FLLs (6.2 %; 12 benign and 3 malignant FLLs). The positive predictive value of CEUS for a malignant FLL was 92.3 % and the negative predictive value was 95.1 %. Out of 241 small FLLs with histological confirmation, 62  FLLs were ≤ 10  mm (diagnostic accuracy of CEUS 80.6 %) and 179 FLLs were > 10  mm and ≤ 20  mm (diagnostic accuracy of CEUS 84.9 %). CONCLUSION: CEUS has a high diagnostic accuracy for the differential diagnosis of small and subcentimetric FLLs in clinical practice.

Efficacy of contrast-enhanced US versus CT or MRI for the therapeutic control of percutaneous radiofrequency ablation in the case of hepatic malignancies.

PURPOSE: The goal of this study was to assess the informative value of contrast-enhanced ultrasound after radiofrequency ablation (RFA). Patients who had undergone RFA of malignant liver tumors were followed up with contrast-enhanced sonography (CEUS), computed tomography (CT) and/or magnetic resonance tomography (MRI), and the outcomes were compared. MATERIALS AND METHODS: 76 patients undergoing 194 RFAs for 118 hepatic neoplasms (n = 55 HCC, n = 63 metastases) in the course of a 7-year period were examined post-interventionally using CEUS and CT or MRI. During follow-up (gold standard of evaluation), contrast agent rim accumulations with a diameter greater than 5 mm and a growth rate of at least 25 % were counted as a recurrence. RESULTS: CEUS-CT comparison group: A total of 65 scan pairs were compared. In 54 cases (83.1 %) the findings were the same with either method. In 7 cases (10.8 %) CEUS confirmed the correct diagnosis, and in 2 cases (3.1 %) only CT was correct. In 2 cases (3.1 %) both methods yielded incorrect results. Diagnostic accuracy (DA): CEUS 93.8 %, CT 86.2 %. CEUS-MRI comparison group: In 23 cases (88.5 %) of a total of 26 scan pairs, the findings were the same for both CEUS and MRI. In 3 discordant cases only CEUS confirmed the correct diagnosis (3 cases, 11.5 %). Diagnostic accuracy DA (n = 26): CEUS 100 %, MRI 88.4 %. CONCLUSION: CEUS performs equally to CT and MRI in the follow-up of patients treated for liver tumors by RFA.

An abdominal and thyroid status with Acoustic Radiation Force Impulse Elastometry--a feasibility study: Acoustic Radiation Force Impulse Elastometry of human organs.

PURPOSE: Acoustic Radiation Force Impulse (ARFI) is a new method for the quantification of tissue elasticity. To date, ARFI technology has not been applied systematically to establish an abdominal and thyroid status. The aim of this prospective feasibility study was to evaluate ARFI elastometry performed on various healthy abdominal organs and the thyroid gland. MATERIAL AND METHODS: 94 patients (43 females, 51 males) with a mean age of 54 years and 20 healthy controls were enrolled in the study. A routine ultrasound examination of the abdomen was scheduled in 72, and of the thyroid in 25. ARFI elastometry was performed in liver, spleen, pancreas, prostate, kidneys and thyroid gland with the ultrasound system Acuson S2000. ARFI values are proportional to tissue elasticity. Patients with ultrasonic or anamnestic evidence of diseased organs were excluded from the analysis. ARFI measurements were compared with the aid of the t-test and correlated using Spearman's correlation coefficient. RESULTS: ARFI elastometry proved feasible and the measurements obtained in the various organs differed significantly. Among healthy organs the spleen showed the highest mean ARFI velocities, followed by the kidney, thyroid, pancreas and the prostate. The lowest ARFI values were regularly found in healthy liver. Measurements in the kidneys and the spleen showed high standard deviation. CONCLUSIONS: ARFI elastometry may describe parenchymal stiffness of various abdominal organs and the thyroid gland. Further investigations are needed to compare these baseline findings in healthy organs with those of various tumours or diseases affecting the individual organs.

Unclear focal liver lesions in contrast-enhanced ultrasonography--lessons to be learned from the DEGUM multicenter study for the characterization of liver tumors.

PURPOSE: To discuss the difficulties of contrast-enhanced ultrasound (CEUS) in a large multi-center trial. MATERIALS AND METHODS: CEUS was performed on 1349 liver lesions with an unclear diagnosis after native ultrasound using a standardized protocol (phase inversion; low MI < 0.4; Sonovue Bolus 1.2 - 4.8 ml). The early arterial, arterial, portal venous and late phase > 2 min. were documented. The diagnosis based on CEUS results was compared to the final diagnosis (histology: n = 1006; MRI: n = 269; CT: n = 269 - multiple examinations possible). RESULTS: Of the 1349 enclosed liver lesions, 20 could not be definitively diagnosed even using all diagnostic steps including histology (the others were proven to be benign n = 573 or malignant n = 756). Of the 1349 unclear liver lesions, 1257 could be differentiated with an accuracy of 90.3% using CEUS. The sensitivity, specificity, and positive and negative predictive value for malignant liver lesions was 95.8%, 83.1%, 88.2% and 93.7% respectively. 92 liver lesions (6.8%) could not be definitively diagnosed using CEUS. Most of them were benign (n = 67) on final diagnosis. The CEUS diagnosis was wrong for 39 lesions. However, only 8 lesions classified as benign by CEUS turned out to be malignant. In 3 cases HCC proven by histology was incorrectly diagnosed by CEUS as adenoma and 2 lesions incorrectly diagnosed by CEUS as FNH turned out to be an HCC and a metastasis. Two lesions diagnosed by CEUS as hemangiomas turned out to be an HCC and a metastasis. One lesion classified as benign by CEUS was ultimately diagnosed as a lymphoma. CONCLUSION: Even in this multi-center trial, CEUS proved to be an excellent method for clarifying liver lesions remaining unclear after native ultrasound. The CEUS diagnosis of benign was only incorrect in a few cases.

Contrast-enhanced ultrasound (CEUS) for the characterization of focal liver lesions in clinical practice (DEGUM Multicenter Trial): CEUS vs. MRI--a prospective comparison in 269 patients.

PURPOSE: The aim of this prospective multicenter study was to assess the diagnostic role of CEUS in the diagnosis of newly discovered focal liver lesions in clinical practice. One important aspect is the comparison of CEUS with magnetic resonance imaging (MRI). MATERIALS AND METHODS: From 05 / 2004 to 12 / 2006, standardized CEUS was performed prospectively on 1349 patients with focal liver lesions that had been newly detected by fundamental ultrasound in order to determine tumor differentiation and tumor entity. 269 patients had a standardized MRI after CEUS. In typical liver hemangioma and focal nodular hyperplasia (FNH), the definitive diagnosis was based on the MRI as the "diagnostic gold standard" and on clinical evidence and additional follow-up (subgroup A) or on histology (subgroup B). 262 patients met the diagnostic standard that had been set. RESULTS: In the subcollective (n = 262), the tumor differentiation (malignant or benign) of CEUS and MRI was concordant in 225 cases (85.9%), and the assessment of tumor entity in 204 cases (77.9%). In subgroup A (n = 180), concordant results for tumor differentiation were obtained in 169 (93.2%) and for tumor entity in 160 (88.9%) cases. Liver hemangiomas (n = 122) and FNH (n = 43) were most frequent. Subgroup B (n = 82) comprised mainly malignant liver lesions (n = 55), with only a few of hemangiomas (n = 8) or FNH (n = 5). Tumor differentiation was concordant in 56 (68.3%) and tumor entity in 44 cases (53.7%). There were no statistically proven differences between CEUS and MRI. CONCLUSION: CEUS and MRI are of equal value for the differentiation and specification of newly discovered liver tumors in clinical practice. CEUS and MRI are extremely reliable for the differentiation of benign and malignant lesions, the diagnosis of liver hemangiomas and FNH. The characterization of metastases and HCC is also very reliable.

Characterization of focal liver lesions (FLL) with acoustic radiation force impulse (ARFI) elastometry.

PURPOSE: The technology of acoustic radiation force impulse (ARFI) represents an innovative method for the quantification of tissue elasticity. The aim of this prospective pilot study was to evaluate the role of ARFI elastometry of focal liver lesions (FLL) and the surrounding liver parenchyma. MATERIALS AND METHODS: All patients with unclear FLL in B-mode ultrasound were assigned to ARFI elastometry (m/sec). Measurement sites were located within the FLL, in the peritumoral tissue and in hepatic segment VIII (intercostal approach). Histology and CEUS served as the reference for the characterization of the lesions. RESULTS: A total of 81 patients were enrolled, of whom 62 patients (39 females, 23 males; mean age 54 years) had FLL measurable by means of ARFI. The lesions were: 38 benign (61 %) and 24 malignant FLL (39 %). The ARFI elastometric values of the FLL differed significantly from those of the liver parenchyma (p < 0.001). Elastometry of benign lesions and of malignant tumors showed statistically comparable results (p = 0.28). The lowest ARFI values were observed in focal fatty sparing and the highest in CCC. Only focal fatty sparing and HCC showed negative differences between FLL and peritumoral tissue or liver parenchyma. In 23 % of the hepatic lesions, no reliable quantitative ARFI results were obtainable due to false, inconsistent or technically failed measurements. CONCLUSION: FLL vary in ARFI elastometry. However, high ARFI values occur in benign as well as in malignant lesions and do not permit differentiation between them.

Measurement of liver elasticity with acoustic radiation force impulse (ARFI) technology: an alternative noninvasive method for staging liver fibrosis in viral hepatitis.

PURPOSE: The acoustic radiation force impulse (ARFI) technology is a novel ultrasound method that provides information about the local elasticity of tissue in real-time. ARFI is integrated in a conventional ultrasound system. The aim of this exploratory study was to evaluate this new technique in the assessment of liver fibrosis in a cohort with chronic viral hepatitis B and C and to ascertain the most reliable hepatic segment for measurements. MATERIALS AND METHODS: 57 patients (27 female, 30 male, mean age 54 years) with chronic viral hepatitis B and C underwent ARFI imaging and consecutively liver biopsy. The results were compared to the histological fibrosis degree (F), which served as the reference. 20 healthy volunteers received ARFI quantification of different segments of the liver. RESULTS: The best ARFI assessments with the lowest rate of invalid measurements were carried out by an intercostal approach to segment VII/VIII of the liver. The ARFI velocities of the healthy group had a mean of 1.09 m/s (range 0.79 - 1.32 m/s), the means of the patient group ranged from 0.83 to 4.19 m/s. ARFI quantification correlated significantly with the histological fibrosis stage (p < 0.001). The area under the receiver operating characteristic (ROC) curves for the accuracy of ARFI imaging was 85 %, 92 % and 87 % for the diagnosis of moderate fibrosis (>or= F2), severe fibrosis (>or= F3) and cirrhosis ( = F 4), respectively. CONCLUSION: This study underscores the usefulness of ARFI as a quick method for assessing liver fibrosis or cirrhosis in patients with HBV or HCV. ARFI measurements of the liver should be performed via an intercostal access. Increasing ARFI velocities correlate with higher degree of hepatic fibrosis.

[A comparative study of the hepatic transit time (HTT) of different ultrasound contrast agents in patients with liver metastases and healthy controls]. / Vergleich der hepatischen Transitzeit (HTT) verschiedener Ultraschallkontrastmittel (USKM) bei Patienten mit Lebermetastasen und gesunden Probanden.

PURPOSE: Liver metastases lead to a shortening of the HTT of an echo enhancer. Studies using SonoVue™ also showed a shortening of the HTT in healthy controls. Hence the HTT depends on the applied contrast agent. We examined whether the HTT of SonoVue™, Luminity™ und Levovist™ is useful to discriminate between patients with and without liver metastases. MATERIALS AND METHODS: We compared the arteriovenous HTT of Levovist™, Sonovue™ und Luminity™ in 20 patients with liver metastases and in 15 controls. An Acuson Sequoia™ ultrasound system was used. The HTT results from the difference of the arrival time of the microbubbles in the hepatic artery and a hepatic vein. RESULTS: Using Levovist™ six patients and three controls had to be excluded from further analysis. The arrival time was undetectable. The mean HTT values in healthy controls were: Levovsit™ 14.75 sec (SD ± 2.53 sec), SonoVue™ 9.27 sec (SD ± 2.41 sec) and Luminity™ 9.2 sec (SD ± 2.34 sec). In patients the mean HTT values were: Levovist™ 9.89 sec (SD ± 1.04 sec), SonoVue™ 6.28 sec (SD ± 2.41 sec) and Luminity™ 6.33 sec (SD ± 1.37 sec). Using a cut off of 8 sec for SonoVue™ and Luminity™, the sensitivity to exclude liver metastases was 75% and 80%. CONCLUSION: The mean HTT values of all contrast agents were shorter in patients. Levovist™ showed a longer HTT in patients and controls than Luminity™ and SonoVue™. Levovist™ showed the best separation between patients and controls but some patients and controls had to be excluded. The HTT could still be a useful tool to exclude liver metastases but the HTT depends on the contrast agent and the applied contrast technique.

Tumor-specific vascularization pattern of liver metastasis, hepatocellular carcinoma, hemangioma and focal nodular hyperplasia in the differential diagnosis of 1,349 liver lesions in contrast-enhanced ultrasound (CEUS).

AIM: To evaluate the incidence and diagnostic accuracy of tumor-specific vascularization pattern in contrast-enhanced ultrasound (CEUS) in the differential diagnosis of liver tumors in clinical practice. MATERIALS AND METHODS: From May 2004 to December 2006 1349 patients (male 677, female 672) with a hepatic tumor lacking a definite diagnosis based on B-mode ultrasound and power Doppler ultrasound were examined at 14 hospitals by CEUS using a standardized protocol (pulse/phase inversion imaging, mechanical index < 0.4). Vascularity pattern and contrast enhancement pattern were analyzed in focal lesions during the arterial, portal, and late phase. The tumor-specific diagnosis established after CEUS was compared to histology (> 75 % cases) or in some cases to CT or MRI. RESULTS: The final diagnosis of 573 benign hepatic tumors included hemangiomas (n = 242) and focal nodular hyperplasia (n = 170), other benign lesions (n = 161). Tumor-specific vascularization pattern such as a wheel-spoke pattern and arterial hyperenhancement followed by isoenhancement in the late phase in FNH or a nodular peripheral enhancement and partial or complete fill-in pattern in hemangiomas could be assessed in the majority, but not all lesions. The diagnostic accuracy of CEUS was 83.1 % for all benign lesions and 82.2 % for hemangioma and 87.1 % for FNH. The final diagnosis of 755 malignant hepatic tumors included metastases n = 383, hepatocellular carcinoma n = 279 and other malignant lesions n = 93. Late phase hypoenhancement was seen in almost all liver metastases (94.7 %) The diagnostic accuracy of CEUS was 95.8 % for all malignant lesions and 91.4 % for liver metastases and 84.9 % for hepatocellular carcinomas. CONCLUSION: Tumor-specific vascularization pattern in CEUS have a high diagnostic impact on the overall high diagnostic accuracy of CEUS for the differential diagnosis of hepatic tumors in clinical practice.