Evaluation of hepatocellular carcinoma transarterial chemoembolization using 3D contrast enhanced ultrasound time-intensity curve analysis

Transarterial chemoembolization (TACE) is standard of care for patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma (HCC). Current guidelines recommend follow-up imaging 4-6 weeks after treatment. An earlier indicator of residual disease would enable clinicians to retreat sooner, potentially improving disease control. In this study, time-intensity curves from 3D contrast-enhanced ultrasound (CEUS) were assessed as an alternative for the identification of TACE patients requiring retreatment. To date, 13 patients undergoing TACE for the treatment of HCC provided informed consent to participate in 3 CEUS exams: prior to TACE, 1-2 weeks post treatment, and approximately one month post treatment. CEUS was performed using a Logiq E9 scanner with an RAB2-5-D probe (GE Healthcare, Wauwatosa, WI, USA). Following baseline imaging, patients received an intravenous bolus injection of 0.2-0.3 ml of Definity (Lantheus Medical Imaging, N Billerica, MA, USA), while 3D data was continuously obtained from the entire tumor and surrounding tissue using coded harmonics at low MI until contrast washout was observed (after 3-4 minutes). Volume data at each time point was extracted offline as 8 equidistant 2D slices across the mass. Time-intensity curves for the HCC and normal tissue were calculated by averaging over the 8 planes and compared to the patient's treatment response. A total of 11 subjects' data (7 subjects with complete and 4 with incomplete treatment response) were included for the time-intensity curve analysis. Peak enhancement intensities of the tumor prior to TACE were similar between the complete and incomplete treatment groups (82.3 ± 37.4 vs. 85.8 ± 52.2 arbitrary unit (AU); p=0.91), while 1-2 weeks and 1 month post treatment they were significantly lower in the complete treatment group than in the incomplete treatment group (24.6 ± 6.4 vs. 68.9 ± 32.7 AU; p=0.01 and 17.2 ± 4.74 vs. 87.2 ± 27.8 AU; p=0.0001, respectively). The contrast wash-in and wash-out did not differentiate responders (p>0.06). In spite of the limited sample size, time-intensity curve analysis from 3D CEUS shows potential to identify TACE patients requiring retreatment as early as 1-2 weeks post treatment.