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Functional CT Imaging of Tumor Microenvironment
Ivan Yeung
Tumor microenvironment is a critical factor of the survival and propagation of tumors. Specially,
tumor vasculature is structurally and functionally abnormal, and the vessels are hyperpermeable,
tortuous, dilated and of tangled architecture. The resulting hemodynamics is thought to play an important role in tumor hypoxia that partly explains tumor resistance to anti-cancer therapies. There are active research efforts to alter microvasculature with anti-angiogenesis or anti-vascular therapy in an attempt to "starve off" tumor cells. Therefore, it is invaluable to have an in-vivo functional imaging method for the design, application and monitoring for anti-cancer treatment in solid
tumors.
The research direction of our lab is to develop and validate functional imaging techniques of tumor microenvironment. We are especially interested in functional CT (fCT) imaging as an imaging modality for treatment monitoring. In the Hypoxia program, we are to develop and validate our recently proposed tracer kinetics model (fCT-DCATH) for quantification of tumor microenvironment in terms of blood flow, blood volume, mean transit time, and transit time spread. We are particularly interested in the last parameter as it qualifies the width of transit time as contrast agent traverses through the microvasculature and we believe it is a measure of complexity of tissue vasculature. We are conducting fCT experiments using the rabbit VX2 tumor model under anti-angiogenesis and anti-vascular treatment. The fCT parameters are compared with PO2 and IFP in-vivo, as well as morphometric measurement on excised tumor samples. Figure
1 is a CT cine image (0.5 sec interval) of a fCT study in which a rabbit with VX2 tumor was injected with contrast agent.
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Figure 1: CT Cine-Image
of Rabbit VX2 Tumour Injected with Contrast Agent |
We are also extending the methodology to cone beam CT technology (i.e. fCBCT) on mice models using a GE eXplore Ultra Locus preclinical CT system, in collaboration with Dr. T.Y. Lee in London, Ontario. Figure 2
is a surface rendering image of a mouse obtained with the GE preclinical system.
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Figure 2: Surface
Rendering of a Mouse using a GE eXplore Ultra Locus CT
System |
 Figure 3
shows blood flow and blood volume maps of a syngeneic C3H mouse with the KHT-C tumor before and 1 hr after treatment with anti-vascular agent, ZD6126 (AstraZeneca). These functional maps show marked decrease in blood flow and blood volume 1 hr post treatment.
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Figure 3: Blood Flow
& Blood Volume Maps of C3H Mouse with a KHT-C Tumour |
Different degree of geometry based on-line adaptive radiation treatment has become a clinical reality. We are also interested in the research of on-line functional CBCT and fluoroscopy for on-line function based adaptive treatment. Such functional information is potentially a useful tool for measurement of changes in the tumor microenvironment altered by biologically targeted agents in combination with radiation therapy.
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