Contrast-enhanced ultrasound for examining tumor biology

Abstract

This paper reviews the potential of ultrasound for assessing the viability and biological behavior of tumors. Unlike color Doppler sonography, modern techniques for contrast-enhanced ultrasound permit the measurement of tissue perfusion irrespective of vessel size or flow velocity. Perfusion can also be assessed quantitatively, using replenishment kinetics or derivates thereof. The perfusion of tumors is a surrogate parameter of their viability and may mirror their response to therapy. Furthermore, the degree of vascularity in a tumor may express its aggressiveness and help to predict its response to treatment. In animal models, a decrease in blood flow has been shown to precede a shrinkage of tumors treated with anti-angiogenic compounds. In liver metastases, arterial and portal blood supply can be assessed separately, and a response to stereotactic radiotherapy was found to go along with a decrease in arterial perfusion. Moreover, a relatively high arterial perfusion of liver metastases may predict a response to chemotherapy. Contrast-enhanced ultrasound may be a potent tool for assessing the effects of anti-angiogenic treatment in patients.

Figure 1

Subcutaneous heterotransplant of human squamous cell carcinoma cells in nude mice treated with a blocking antibody to vascular endothelial growth factor receptor 2 (DC101), which were repeatedly examined at weekly intervals. At contrast-enhanced intermittent ultrasound the small tumor is highly vascularized at the offset. After 1 week, the tumor has grown, but shows almost no blood flow inside. The final scan, after 2 weeks, shows that the tumor has shrunk and the blood flow is still absent. From , with permission.

Figure 2

The arterial perfusion of the liver and a metastasis of colon carcinoma before stereotactic radiotherapy (a, c) and 5 months later (b, d), visualized by low-MI sonography after injection of 2.4 ml SonoVue i.v. (a, b) and by contrast-enhanced computed tomography (CT) (b, d). In contrast to CT (130 ml Ultravist 300 i.v.), contrast-enhanced ultrasound (CEUS) clearly shows a high arterial enhancement of the untreated liver metastasis, its reduction after therapy and an arterially hypervascularized perifocal liver reaction after therapy. From , with permission.