Collaborators: Dr. Ann F. Chambers (London Regional Cancer Program), Dr. Aaron Fenster (Robarts Imaging Laboratories), and Dr. Jim W. Xuan (UWO Department of Surgery)
Background: Mouse cancer models reproduce genetic, molecular, and physiological factors that control tumour initiation, growth, and metastasis, and so are important experimental systems for investigating causes and treatment of cancer in humans. In conventional experimental protocols, mice must be sacrificed to obtain histology specimens for evaluating responses to treatment. The conventional methods require large numbers of mice to produce statistically significant results and are unable to directly observe dynamic processes such as tumour growth and formation of new blood vessels. The limitations of these techniques are a suspected cause of the inconsistent ability of "preclinical" experiments to select the most promising treatments for further study in human patients. The cancer care implications of this shortcoming include inflated drug development costs and slow progress toward the discovery of more effective anticancer therapies.
Objectives: We are developing three-dimensional (3-D) ultrasound micro-imaging techniques to noninvasively measure tumour growth and changes in tumour blood flow in live mouse cancer models. The ultrasound techniques must be validated by comparison to conventional measurements and must be implemented in a manner that enables them to be used efficiently by cancer biologists. We are also investigating the application of mathematical models of tumour growth and treatment response to maximize the biological information provided by the ultrasound data.
Approach: Ultrasound imaging techniques are being developed for liver metastasis models used by Dr. Chambers' laboratory and for a transgenic prostate cancer model created by Dr. Xuan's laboratory. Tumour volumes are measured in 3-D ultrasound images using software developed by Dr. Fenster's laboratory. We have shown that longitudinal imaging performed at two- to three-day intervals enables measurement of tumour growth parameters such as volume doubling times, and that these measurements quantify changes in tumour growth produced by chemotherapy. We have also demonstrated 3-D power Doppler ultrasound imaging of tumour vasculature in mice (see the power Doppler image in the Image Gallery). Ongoing research will develop and validate quantitative methods for analyzing power Doppler blood flow images, investigate image acquisition strategies to improve the performance of automated tumour volume measurement software, and assess the feasibility of using mathematical models in combination with ultrasound micro-imaging to optimize chemotherapy regimens in mouse models of specific cancers.
Recent Journal Papers:
L.A. Wirtzfeld, G. Wu, M. Bygrave, Y. Yamasaki, H. Sakai, M. Moussa, J.I. Izawa, D.B. Downey, N.M. Greenberg, A. Fenster, J.W. Xuan, and J.C. Lacefield, "A new three-dimensional ultrasound micro-imaging technology for preclinical studies using a transgenic prostate cancer mouse model," Cancer Res., vol. 65, pp. 6337-6345, 2005.
K.C. Graham, L.A. Wirtzfeld, L.T. MacKenzie, C.O. Postenka, A.C. Groom, I.C. MacDonald, A. Fenster, J.C. Lacefield, and A.F. Chambers, "Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models," Cancer Res., vol. 65, pp. 5231-5237, 2005.
