J. Skrok

Characterisation of focal liver lesions with unenhanced and contrast enhanced low MI real time ultrasound: on-site unblinded versus off-site blinded reading.

OBJECTIVE To compare on-site and blinded off-site reading of baseline ultrasound (US) and contrast enhanced ultrasound (CEUS) for classification and characterisation of focal liver lesions. MATERIALS AND METHODS 99 patients (57 women and 42 men, age range 18-89 years, mean age: 59 years) with 53 malignant and 46 benign liver lesions were studied with unenhanced US followed by contrast enhanced US after injection of 2.4 ml SonoVue® (Bracco, Milano, Italy). Image interpretation was performed on-site with clinical information available by consensus of two readers and off-site by two independent blinded readers at two different centers. Comparison of pre and post contrast scans and of the different readers was performed. Reference examinations were histology, intraoperative US, MRI or CT. RESULTS Sensitivity for malignancy improved from 81/89/66% (on-site/off-site reader 1/2) before to 100/96/96% post contrast administration (p<0.05, except for reader 1). Specificity improved from 48/48/54% on baseline US to 89/80/76% on CEUS (p<0.05). Accuracy for specific lesion diagnosis was 62/59/50% pre and 90/77/72% post contrast (p<0.05). Classification and characterisation post contrast were mildly inferior for off-site reading. Agreement between on-site and off-site readers of unenhanced scans was fair (κ=0.29-0.39) while it was good for CEUS (κ=0.63-0.79). CONCLUSIONS CEUS improves classification and characterisation of focal liver lesions and interobserver agreement compared to conventional US. Classification and characterisation post contrast were mildly but statistically significantly better for on-site than for off-site reading.

Hepatic transit time analysis using contrast-enhanced ultrasound with BR1: A prospective study comparing patients with liver metastases from colorectal cancer with healthy volunteers.

We prospectively compared hepatic transit time (HTT) measurements in subjects with liver metastases from colorectal cancer (group a) and healthy volunteers (group b) using contrast-enhanced ultrasound with BR1. The purpose of this study was to verify our hypothesis that the hemodynamic changes of the liver, which occur during metastasis seeding, would shorten the HTT, and we expect that such changes could be used for the detection of occult liver metastases from colorectal cancer in the future. The study had institutional review board approval and all subjects gave informed written consent. Group a and group b consisted of 22 subjects each. Baseline and post contrast images were acquired starting 10 s before and ending 40 s after administration of BR1, using nonlinear imaging at a frame rate of 5/s. The baseline images were used to determine the signal intensity without contrast enhancement as the reference signal. Arrival times (AT) of the contrast agent for the hepatic artery, the portal vein and one hepatic vein were determined using (i) quantitative analysis and (ii) subjective analysis by two blinded readers. HTT was calculated based on arrival time measurements. Quantitative and subjective analysis showed significantly shorter arterial to venous and portal to venous HTT in group a compared with group b (p < 0.001). Arterial to venous HTT (quantitative analysis) was < or = 9 s in 19 of 22 subjects of group a and >9 s in 18 of 22 subjects of group b (sensitivity 86%, specificity 82%, positive predictive value 83%, negative predictive value 86%, area under the curve [AUC] 0.87). Portal to venous HTT (quantitative analysis) was < 7 s in 21 of 22 subjects of group a and > 7s in 15 of 22 subjects of group b (sensitivity 95%, specificity 68%, PPV 75%, NPV 94%, AUC 0.85). There was an inverse relation with number of liver segments involved for arterial to venous and portal to venous HTT in group a (p < 0.05), but no correlation between HTT and overall volume of metastases (group a) or subject age (group b). From the results of our study, we conclude that HTT measurements using contrast-enhanced ultrasound with BR1 can detect hemodynamic changes caused by metastatic liver disease from colorectal cancer. However, comparison with the literature suggests that the use of other contrast agents might provide better results. Comparison of different contrast agents for the purpose of transit time analysis would therefore be useful before embarking on a prospective trial looking at the detection of occult liver metastases in patients with colorectal cancer. (E-mail: jhohmann@uhbs.ch).

Detection of hepatocellular carcinoma and liver metastases with BR14: a multicenter phase IIA study.

The study was designed primarily to find the optimal dosage range of BR14 contrast-enhanced ultrasonography (CEUS) to detect malignant focal liver lesions. Secondary objectives were the evaluation of the safety profile and comparison with contrast-enhanced MRI (CE MRI). We studied 25 patients (9 females, 16 males, mean age, 66 years) with known hepatocellular carcinoma or liver metastases at 3 centers over a 3-month period. Each patient underwent a baseline examination and at least 3 CEUS examinations with ascending dose levels (0.25 mL; 1.0 mL; 4.0 mL) of BR14. CE MRI was performed 4 weeks before or after the CEUS examination. Dedicated liver maps were used to record the location, size, and type of detected lesions. Examination quality was documented and safety parameters were assessed. The number of lesions detected by BR14 CEUS increased with dosage, whereas the number of missed lesions and the lesion sizes decreased. Despite the increasing contrast enhancement, substantial differences among dosages were not seen for other image quality parameters. No significant changes were noted in safety parameters and no serious adverse events were reported. We conclude that the recommended dose level of BR14 is between 1 mL and 4 mL; at this dosage, lesion detection is comparable to that of CE MRI.