Contrast-Enhanced Ultrasound for Monitoring Treatment Response in Different Stages of Hepatocellular Carcinoma

Abstract

The capacity of contrast-enhanced ultrasound (CEUS) to detect microvessel perfusion has received much attention in cancer imaging since it can be used to evaluate the enhancement patterns of the lesions during all vascular phases in real time, with higher temporal resolution as compared other imaging modalities. A rich body of literature has demonstrated the potential usefulness of CEUS in the assessment of HCC in response to both locoregional and systemic therapies. It is useful to evaluate the efficacy of ablation immediately after treatment to provide guidance for the retreatment of residual unablated tumors. In patients treated with transarterial chemoembolization (TACE), CEUS showed a high degree of concordance with computed tomography and magnetic resonance for the differentiation of responders from non-responders. Dynamic CEUS (D-CEUS) has emerged as a promising tool for the depicting changes in tumor perfusion during anti-angiogenetic treatment that can be associated with tumor response and clinical outcome. This article provides a general review of the current literature regarding the usefulness of CEUS in monitoring HCC response to therapy, highlighting the role of the procedure in different stages of the disease.

Keywords: contrast-enhanced ultrasound; dynamic contrast-enhanced ultrasound; hepatocellular carcinoma; tumor response.

Figure 1

An example of a time–intensity curve after CEUS examination and an explanation of the most important parameters. Microbubble signal strength is usually measured using absolute intensity units and time in seconds. Abbreviations: time to peak, TP; wash-in time, WIT; wash-out time, WOT; peak intensity, PI; mean transit time, MTT; area under the curve, AUC.

Figure 2

A 2.2 cm solitary HCC in segment IV with complete response after RFA. (a) Arterial phase CEUS (8 s after SonoVue injection) shows an avascular pattern with peripheral rim enhancement. (b) Late-phase CEUS (141 s after SonoVue injection) confirms an avascular pattern with persistent peripheral rim enhancement, suggesting reactive hyperemia. (c) Arterial phase CECT 1 month after RFA confirms complete necrosis.

Figure 3

A 5 cm HCC of the segment VIII with discordant behavior after combined therapy (RFA + TACE). (a) Arterial phase imaging (22 s after SonoVue injection) shows no enhancement within the lesion. (b) Arterial phase CECT scan 1 month after treatment shows the persistence of viable tumor (red arrow) in the upper posterior part of the lesion not detected by CEUS.

Figure 4

Two examples of HCC patients undergoing systemic therapy. (a) Contrast-enhanced ultrasound with the corresponding time–intensity curve at baseline (T0). At 15 (T1) and 30 days (T2) after the onset of sorafenib therapy, CEUS revealed an increase in tumor necrosis with a drastic reduction in tumor perfusion parameters, as shown by the contrast enhancement pattern and the corresponding time-intensity curve. Time–intensity curves of tumor enhancement are shown at baseline (green curve), on day 15 (blue curve), and on day 30 (yellow curve). It is possible to observe a reduced maximum enhancement and lower area under the enhancement curve early after treatment. Intensity is measured in absolute intensity units (AIU) on the ordinate, while time is measured on the abscissa (in seconds). (b) Contrast-enhanced ultrasound images and the corresponding time intensity curves of HCC lesion before and after treatment with sorafenib are shown in a non-responder patient. The CEUS and the corresponding time–intensity curves of tumor enhancement show no significant difference in perfusion parameters at baseline (T0, green curve), on day 15 (T1, blue curve), or on day 30 (T 2, yellow curve). Intensity is measured in absolute intensity units (AIU) on the ordinate, while time is measured on the abscissa (in seconds).