High-amplitude ultrasound waves, generated outside the body, can be focused deep within tissue onto a region about the size of a grain of rice. In that region, conversion of the mechanical energy carried by the ultrasound wave into heat can lead to cell death by thermal necrosis, leaving tissue outside the HIFU focal region unaffected. The potential of this technique to destroy deep-seated tumours non-invasively is currently being explored in the Clinical HIFU Unit at the Churchill Hospital in Oxford.

Contrast MR of a large tumour in the left kidney (left) and 12 days following HIFU treatment (right)
Photo courtesy of the Clinical HIFU Unit, Churchill Hospital,Oxford

Research carried out in the Biomedical Ultrasonics & Biotherapy Laboratory (BUBL) is aimed at further improving the speed, resolution, targeting and real-time monitoring of HIFU treatments, as applied to cancer therapy and to a range of novel HIFU applications. The laboratory is involved in research at all levels, ranging from the basic science of understanding cell death by ultasound-induced heating, to the clinical trials (in collaboration with the clinical HIFU unit) of novel methods for improved treatment delivery and treatment monitoring.

High amplitude acoustic waves propagating through tissue can spontaneously nucleate and excite small, micron-sized bubbles, a phenomenon known as acoustic cavitation. The presence of such bubbles at the HIFU focus has been shown to greatly enhance the local rate of heating. Furthermore, the frequency-domain signature of cavitating microbubbles could provide a way of monitoring HIFU treatment non-invasively in real-time. Nucleating, controlling and monitoring cavitation activity during HIFU exposure constitutes one of the core research activities at BUBL.

  Lesions of different shapes and sizes created by a HIFU transducer in a polyacrylamide-BSA tissue-mimicking material.

A further area of interest pertains to the development of our understanding of heat-induced cell death. In 1984, Sapareto and Dewey proposed the thermal dose cumulative equivalent minutes (CEM) metric as a means of quantifying cell damage induced by mild heating. Even though the model provides a good descriptor at the temperatures and rates of heating encoutered in mild hypethermia (5-10 C above body temperature), its applicability in the context of the very high rates of heating and high temperatures achieved during ultrasound-induced ablation has yet to be demonstrated. Through the development of a broad range of cell-embedding tissue-mimicking materials, research carried out in the BUBL aims at acquiring a basic understanding of the limitations of the the CEM model and at the development of adequate means of quantifying heat-induced damage under conditions relevant to HIFU therapy.

Further reading

1. S. D. Nandlall, M. Arora, H. A. Schiffter and C.-C. Coussios, ‘On the Applicability of the Thermal Dose Cumulative Equivalent Minutes Metric to the Denaturation of Bovine Serum Albumin in a Polyacrylamide Tissue Phantom’, Proceedings 8th International Symposium on Therapeutic Ultrasound 1113: 205-209 (2008).
2. S. A. Sapareto, and W. C. Dewey, International Journal of Radiation Oncology, Biology, Physics 10, 787–800 (1984).
3. P. Kennedy, M. Arora and C.-C. Coussios, ‘Localization and Interpretation of Bubble Activity during HIFU Exposure’, Proceedings 8th International Symposium on Therapeutic Ultrasound 1113: 68-72 (2008).
4. C.-C. Coussios and R.A. Roy, ‘Applications of Acoustics to Non-Invasive Therapy and Drug Delivery’, Annual Review of Fluid Mechanics Vol. 40:395-420 (2008).
5. G. ter Haar and C.-C. Coussios, ‘HIFU: Physical Principles and Devices’, International Journal of Hyperthermia 23(2): 89-104(2007).
6. C.-C. Coussios, C.H. Farny, G. ter Haar and R.A. Roy , ‘Role of Acoustic Cavitation in the Delivery and Monitoring of Cancer Treatment by High Intensity Focussed Ultrasound (HIFU)’, International Journal of Hyperthermia 23(2): 105-120(2007).
7. Kennedy, J.E., “High-Intensity Focused Ultrasound in the Treatment of Solid Tumours”, Nature Reviews Cancer 5: 321-327 (2005).