An in vivo investigation of dynamic contrast-enhanced ultrasound (DCE-US) imaging for the assessment of tumour response to radiotherapy

Abstract

Imaging biomarkers of early response to cancer therapy can facilitate more effective treatment adaptation and improve cancer management. These biomarkers can detect functional, structural or molecular tumour changes that occur shortly after treatment and inform on response. For radiation therapy, such indicators of response could be obtained from the tumour vasculature; hypofractionated radiation has been shown to lead to tumour vascular damage, which is suggested to be an important determinant of overall tumour response. This thesis investigated the potential of dynamic contrast enhanced ultrasound (DCE-US) imaging to detect vascular changes associated with tumour response to radiotherapy in preclinical models of cervical and head and neck cancer. Longitudinal two-dimensional (2D) DCE-US was used to image xenograft tumours prior to, and shortly following, single-fraction radiation. A decrease in the DCE-US metrics modified transit time (MTT), washout time (WOUT), and area under the curve (AUC) was observed following treatment, indicating radiation-induced disruption. A greater decrease in these 2D DCE-US metrics was observed in tumours with a complete response, compared to tumours with a partial response, supporting the potential of DCE-US imaging as a biomarker of response. The use of three-dimensional (3D) DCE-US imaging revealed a decrease in wash-in time (WIT) is associated with response, which was not detected with 2D imaging. However, 3D imaging did not detect changes in any other metrics. The repeatability of 2D and 3D DCE-US was examined through imaging of the mouse kidney, and it was revealed that the measurement variation associated with both 3D and 2D DCE-US is of the same order of magnitude as the measured significant changes. Hence improving repeatability will be important in the development of DCE-US for longitudinal monitoring of the tumour vasculature. In summary, DCE-US can detect vascular changes associated with response to radiotherapy, and further technical validation could improve its accuracy as a biomarker of response to radiotherapy.