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 ≤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).