Assessment of tumor blood perfusion by high‐resolution dynamic contrast‐enhanced MRI: A preclinical study of human melanoma xenografts

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Abstract
A noninvasive method to obtain high‐resolution images of tumor blood perfusion is needed for individualized cancer treatments. In this study we investigated the potential usefulness of dynamic contrast‐enhanced MRI (DCE‐MRI), using human melanoma xenografts as models of human cancer. Gadopentetate dimeglumine (Gd‐DTPA) was used as the contrast agent, and DCE‐MRI was performed at a voxel size of 0.5 × 0.2 × 2.0 mm3 with spoiled gradient‐recalled sequences. We obtained images of E · F (where E is the extraction fraction, and F is perfusion) by subjecting DCE‐MR images to Kety analysis. We obtained highly reproducible E · F images, which we verified by imaging heterogeneous tumors twice. We hypothesized that the extraction fraction of Gd‐DTPA would be high and would not vary significantly in tumor tissue, implying that E · F should be a well‐suited parameter for describing tumor blood perfusion. Observations consistent with this hypothesis were made by comparison of E · F‐images with immunostained histological preparations from the imaged sections. The E · F images mirrored the histological appearance of the tumor tissue perfectly. Quantitative studies showed that E · F was highest in nonhypoxic tissue with high microvascular density, second highest in nonhypoxic tissue with low microvascular density, third highest in hypoxic tissue, and lowest in necrotic tissue. Moreover, the radial heterogeneity in E · F was almost identical to that in the blood supply, as assessed by the use of Na99mTcO4 as a perfusion tracer. Taken together, our observations show that high‐resolution images reflecting tumor blood perfusion can be obtained by DCE‐MRI. Magn Reson Med 52:269–276, 2004.