NMR imaging of changes in vascular morphology due to tumor angiogenesis

Tumor-sprouted vessels are greater in both number and diameter in comparison to their healthy counterparts, A novel technique based on magnetic susceptibility contrast mechanisms that are sensitive to varying sizes of blood vessels is presented to measure differences between the relaxation rates (1/T-2 and 1/T-2*) in a rat glioma model and normal cerebral cortex. Delta R2 and Delta R2*, the differences between relaxation rates precontrast and postcontrast agent injection, were measured for an intravascular equilibrium contrast agent (MION) at various echo times. Since Delta R2*/Delta R2 increases as vessel size increases, this ratio can be used as a measure of the average vessel size within an ROI or a voxel, The stability and longevity of the contrast agent within the vasculature were verified (n = 2 trials), and the ratio of Delta R2*/Delta R2 between the tumor and normal cortex was measured to be 1.9 +/- 0.2 (n = 4, echo time = 20 ms, and susceptibility difference (Delta chi) approximate to 10(-6)). This ratio compared favorably to a predicted ratio determined using histologically determined vessel sizes and theoretical Monte Carlo modeling results (1.9 +/- 0.1). Maps of the ratio of Delta R2*/Delta R2 were also made on a pixel-by-pixel basis. These techniques support the hypothesis that susceptibility contrast MRI can provide useful quantitative metrics of in vivo tumor vascular morphology.