Evaluation of tumor angiogenesis by dynamic MRI and compartment analysis

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Angiogenesis correlates with tumor growth, invasion and metastasis. Although tumor blood flow increased by angiogensis, it has not been established to noninvasively measure tumor blood flow in vivo. In this research project, we have developed a new method for quantitative measurement of tumor blood flow (TBF) in vivo by using dynamic GdDTPA enhanced magnetic resonance imaging (MRI) and compartment analysis. By fundamental phantom studies, we confirmed good linear relationships between MRI signal intensities and Gd-DTPA concentrations. Preliminarily, we measured normal muscle blood flow in volunteers and confirmed that muscle blood flow could be measured with a good reproducibily by deconvolution analysis and compartment analysis using arterial input function after a bolus injection of Gd-DTPA. We applied our methods in patients with bone and soft-tissue tumors and successfully generated a functional map of TBF with high temporal (scan time = 3.2 sec) and spatial resolution (pixel-by-pixel). TBF map clearly demonstrated heterogeneity of TBF, i.e. increased TBF in tumor periphery due to angiogenesis and low TBF in center of tumor. TBF map showed substantially decreased TBF after chemotherapy. Thus, TBF map would be a promising tool for evaluating tumor blood flow and may be useful to evaluate treatment response. It is necessary to evaluate if our methods could be applied to tumor of other regions where dynamic data analysis would be hindered by motion artifact to date. In future studies, it is also warranted to compare the TBF maps with the results of other imaging modalities and histopathologic findings.