1 Imaging Tumour Blood Flow using Radial Modulation Imaging, A New Ultrasound Contrast Imaging Technique Hamid H. Shariff, Peter D. Bevan, Raffi Karshafian, John Hudson and Peter N. Burns Department of Medical Biophysics, University of Toronto, Toronto, Canada Imaging Research, Sunnybrook and Women’s Collage Health Sciences Centre, Toronto, Canada Ontario Centre of Excellence for Breast Cancer Imaging Research Introduction: Angiogenesis is a key element in the progression of solid cancer. It describes the formation of new blood vessels, which provide the blood containing oxygen and nutrients to the tumor [1][2][3]. Without such a supply, a breast cancer in situ, for example, will grow to a few millimeters and remain harmless [4]. Detecting ultrasound contrast agents (UCA) where there is low blood flow such as in angiogenesis remains challenging. Pulse inversion [5] and other current contrast imaging techniques for ultrasound rely on same frequency to induce bubble resonance and to form the image, because these resonant frequencies lie between 2 and 4MHz, the resulting images lack the spatial resolution needed to detect microbubbles in small blood vessels typically associated with angiogenesis in a superficial cancer. Experimental Methods: The principles on which the “Radial Modulation Imaging” [6][8] is based is that, a bubble driven by ultrasound below its resonance frequency will oscillate out of phase with one driven above its resonant frequency [7][8]. This property is exploited for bubble detection by continuously driving the bubble below its disruption threshold at a frequency near resonance with a ‘modulating’ source (500kHz). A second source of ultrasound is then used for conventional pulse-echo imaging at a higher frequency (10MHz), with the pulses synchronized to insonate the bubble at the points of peak expansion and peak compression due to the modulating wave. The two resulting echoes are then subtracted. Echoes from linear scatterers, which are unaffected by the modulating wave, cancel. Those from the modulated bubble combine additively over the entire bandwidth of the imaging pulse. Results: As shown in Figure [1], the bubble echo from the peak of the compression phase of modulation (sinusoidal trace), where bubbles reached their minimum radius, was very strong. In contrast, the echo from the peak of the rarefaction phase of modulation, where bubbles reached their maximum radius, gave a much weaker response. Imaging signals originating from these two phases of modulation where different in amplitude and also phase shifted. These signals were approximately 120 0 out of phase with each other at modulating pressure of 200kPa. In these experiments, the contrast-to-clutter ratio (CTR) increased with peak pressure of the modulating signal, reaching a peak of 35dB. Conclusions: Radial modulation imaging offers a means of decoupling the imaging and excitation frequencies in microbubble contrast imaging for ultrasound, and hence a potential method for high frequency, high- resolution contrast imaging using currently available contrast agents. This may aid in the detection and diagnosis of breast cancers using ultrasound, which does not involve the use of any ionizing radiation. References: [1] Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible or angiogenesis. J Exp Med 1971;133:275-88. [2] Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996; 86:353-64. [3] Folkman J. Incipient angiogenesis. Journal of the National Cancer Institute 2000;92:94-5. [4] Peter N.Burns, Imaging Angiogenesis, Eleventh European Symposium on Ultrasound Contrast Imaging. Book of Abstracts P19-21 Rotterdam: Erasmus Univ, 2006 [5] Hope Simpson D, Chin CT, Burns PN. Pulse Inversion Doppler: A new method for detecting nonlinear echoes from microbubble contrast agents. IEEE Transactions, UFFC 1999; 46:372-382 [6] Shariff H, Bevan P, Karshafian R, Karakolis M, Banerjee M and Burns P, “Radial Modulation Imaging: A dual frequency ultrasound imaging technique for microbubble contrast”. Eleventh European Symposium on Ultrasound Contrast Imaging. Book of Abstracts P64-66 Rotterdam: Erasmus Univ, 2006 [7] Hansen R, Johansen TF, Burns PN, Angelsen BAJ. Contrast Agent Detection through Low Frequency Manipulation of High Frequency Scattering Properties. IEEE UFFC Ultrasonics Symposium. Montreal, 2004 [8] Hansen R, Angelsen B, Burns PN,Bouakaz A, Borsboom J, Versluis M, deJong N,. “Radial modulation imaging”. In: tenCate F, deJong N, eds. Tenth European Symposium on Ultrasound Contrast Imaging. Book of Abstracts. P90-92 Rotterdam: Erasmus Univ, 2005. Acknowledgement: This work is supported by, the Terry Fox Programme of National Cancer Institute of Canada, Canadian Institute of Health Research and ORDCF