Medical and Biological Imaging with High Frequency Ultrasound
Ultrasound is a well established imaging modality that currently accounts for about 1/3 of all diagnostic imaging procedures and is a cornerstone in medical disciplines such as cardiology and radiology. Conventional medical diagnostic imaging methods provide resolution on the order of 0.5 - 1 mm and penetration greater than 100 mm. My lab has extended the powerful B-mode backscatter methods developed for clinical imaging in the 3 - 10 MHz frequency range to much higher frequencies (20 – 200 MHz) thereby enabling tissue microimaging. This technique, called ultrasound microimaging, enables biological structures to be imaged with resolutions ranging from 30 to 100 micrometres over fields of view ranging from 4 – 20 mm[1].
There are numerous clinical and basic biological research applications for ultrasound microimaging at elevated frequencies. Clinical applications include imaging of the eye, vasculature, skin and cartilage. In the eye, ultrasound microimaging provides images with fascinating detail not visible using any other means. Commercial instrumentation for ocular imaging has proliferated and found wide clinical acceptance as a means of assessing glaucoma and anterior segment tumors. Probes for invasive applications such as catheter based intravascular imaging or needle based ultrasound imaging pose an interesting engineering challenge because the imaging transducer and scanning actuation must fit within a sub-millimeter cavity. Intravascular scanners are designed to provide clinicians with quantitative information regarding the distribution and structure of atherosclerotic plaque in arterial vessels such as the coronary arteries that feed the heart. Ultrasound technology is rapidly infiltrating the field of preclinical imaging. Together with other U of T colleagues we have founded the Mouse Imaging Centre (MICe) at the Toronto Centre for Phenogenomics and the Toronto Angiogenesis Research Centre (TARC) at Sunnybrook. These facilities are focused on the applications of microimaging technologies to the fields of genomics and angiogenesis respectively. The biological applications of ultrasound microimaging are being investigated in combination with micro-MR, micro-CT and optical microscopies. These techniques greatly facilitate in vivo assessment of developmental and pathophysiological processes under highly controlled conditions. Disease models ranging from glaucoma to breast cancer are under investigation. In the field of cardiovascular research we have created high speed (> 1000 frames per second) tools for the visualization of the mouse heart[2]. The development of high frequency flow sensitive imaging offers a new dimension of information on blood flow at the arteriolar and capillary level to facilitate a deeper understanding of angiogenesis and antiangiogenic therapies[3, 4].
The field of contrast agents is central to future developments in microultrasound. In particular, we are studying the use of microbubble (< 3 micron dia.) and sub-micron particle contrast agents at high frequencies and applying these to models of cardiovascular disease and cancer[5]. We have recently demonstrated Molecular Imaging approaches based on targeted microbubble contrast agents and believe these approaches will also make an important contribution to bioresearch[6].
Specific research opportunities exist in:
- Transducer array and imaging systems development
- Studies of vascular morphology and hemodynamics in the microcirculation
- Ultrasonic propagation and fundamental interactions in tissues
- Microbubble and nanoparticle contrast agents
- Imaging for genomics and disease models
- Molecular Imaging
Graduate Students:
- Robin Castelino
- Janet Denbeigh
- Michael Sprague
- Amandeep Thind
Selected References:
Link to Pubmed Publications-
Foster, F.S., et al., A New Ultrasound Instrument for In Vivo Micro-Imaging of Mice. Ultrasound in Medicine and Biology, 2002. 20: p. 1165-1172.
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Cherin, E., et al., Ultrahigh Frame Rate Ultrasound in Micro- Imaging and Blood Flow Visualization in Mice in Vivo. Submitted to Ultrasound in Medicine and Biology,, 2006. 32: p. 683-691.
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Franco, M., et al., Targeted anti-vascular endothelial growth factor
receptor-2 therapy leads to short-term and long-term impairment of vascular function and increase in tumor hypoxia. Cancer Research, 2006. 66: p. 3639-3648. -
Shaked, Y., et al., Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science, 2006. 313(5794): p. 1785-1787.
- Couture, O., et al., Investigating perfluorohexane particles with
high-frequency ultrasound. Ultrasound Med Biol, 2006. 32(1): p.
73-82.
- Rychak, J.J., et al., Micro-ultrasound molecular imaging of VEGFR-2 in a mouse model of tumor angiogenesis. Molecular Imaging, 2007 6: p. 289-296.
