PhD, University of Toronto
Ultrasound in Cancer Treatment: New Therapies and Methods of Therapy Evaluation
Our research is centered on understanding how radiation affects blood vessels and how this contributes to tumour death. We have developed a number of small animal micro-ultrasound methods in our laboratory to detect vascular changes and separately apoptotic cell death in vivo. A number of different research projects are underway to study the basic science behind vascular responses to radiation and to therapeutically exploit this in order to radiosensitize tumours. In that regard our research interests include the novel use of pharmacologic anti-angiogenic agents and new ultrasound-activated anti-angiogenic agents.
Other projects include
(A) Cell and Molecular Biology
Despite the use of medical ultrasound for decades the features inside cells that contribute to ultrasound backscatter at conventional- and high-frequencies remain unknown. We are systematically probing how subcellular constituents such as DNA, RNA, protein and lipids contribute to backscatter. In particular we are interested in how nuclear and chromatin structure affects ultrasound signals since we have found it to be a dominant structure in the formation of backscatter signals.
(B) Image and Spectroscopic Analysis
We are collaboratively investigating a number of spectroscopic parameters for characterizing tumours and tumour responses to chemotherapy and radiation therapy at conventional and high-frequencies. We are developing these methods to generate colour-coded ultrasound parameteric maps to aid in assessing tumour responses to therapy. Since these spectroscopic signals are potentially linked to nuclear structure and chromatin structure which differs between normal and neoplastic tissue there is potential to develop our spectroscopic methods not only into a method to track tumour responses but a potentially important diagnostic tool.
(C) Clinical Evaluation of Ultrasound Imaging & Spectroscopy
We are instituting a number of clinical evaluations of our spectroscopic detection of cell death. Our main investigational site is breast cancer patients with large "locally-advanced" breast cancers who receive neoadjuvant combined chemotherapy and radiation therapy. We hope to be able to rapidly ascertain responding tumours from those that are non-responding so that the latter may be treated with different chemotherapy regimens or with radiation sensitizers in order to hopefully improve outcomes.
- Czarnota GJ, Kolios M, Vaziri H, Benchimol S, Ottensmeyer FP, Hunt JW: Ultrasound Biomicroscopy of Living, Dead, and Apoptotic Cells. Ultrasound in Medicine and Biology 23: 961-5, 1997.
- Czarnota GJ, Kolios M, Abraham J, Portnoy M, Sherar MD, Ottensmeyer FP, Hunt JW: Ultrasound Imaging of Apoptosis: High resolution Non-invasive Monitoring of Programmed Cell Death in vitro, in situ, and in vivo. British Journal of Cancer 81:520-7, 1999.
- Tunis AS, Czarnota GJ, Giles A, Sherar MD, Hunt JW, Kolios MC: Monitoring structural changes in cells with high frequency ultrasound signal statistics. Ultrasound in Medicine and Biology 31, 1041-9, 2005.
- Czarnota GJ: Role of ultrasound in the detection of apoptosis. Eur. J. Nucl. Med. Mol. Imaging 32:622, 2005.
Kai Xuan Leong