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 mm 3 with spoiled gradient-recalled sequences. We obtained images of E ⅐ F (where E is the extraction fraction, and F is perfusion) by subjecting DCE-MR images to Kety analysis. We obtained highly reproducible E ⅐ 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 ⅐ F should be a well-suited parameter for describing tumor blood perfusion. Observations consistent with this hypothesis were made by comparison of E ⅐ F-images with immunostained histological preparations from the imaged sections. The E ⅐ F images mirrored the histological appearance of the tumor tissue perfectly. Quantitative studies showed that E ⅐ 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 ⅐ F was almost identical to that in the blood supply, as assessed by the use of Na 99m TcO 4 as a perfusion tracer. Taken together, our observations show that highresolution images reflecting tumor blood perfusion can be obtained by DCE-MRI. Magn Reson Med 52:269 -276, 2004.

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MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region.

Purpose: To evaluate the potential of Gd-DTPA-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for providing high-resolution tumor blood perfusion images. Materials and Methods:Xenografted tumors from two amelanotic human melanoma lines (A-07 and R-18) were used as preclinical models of human cancer. DCE-MRI was performed at a voxel size of 0.5 ϫ 0.2 ϫ 2.0 mm 3 with the use of spoiled gradient recalled sequences. We produced tumor images of E ⅐ F (where E is the initial extraction fraction, and F is perfusion) by subjecting the DCE-MRI data to Kety analysis, and then compared those images with images of tumor blood supply. We obtained high-resolution tumor blood supply images using the Bioscope silicon strip detector system to measure the uptake of Na 99m TcO 4 in histological preparations. We assessed the global blood supply by measuring the tumor uptake of three freely diffusible blood flow tracers: 86 RbCl, [ 14 C]IAP, and Na 99m TcO 4 .Results: E ⅐ F was found to mirror the blood supply well in A-07 and R-18 tumors. The mean E ⅐ F differed between the A-07 and R-18 tumors by a factor of ϳ1.6, and this difference was similar to the difference in the global blood supply. The intratumor heterogeneity in E ⅐ F was significant for tumors of both lines, and this heterogeneity was similar to the intratumor heterogeneity in the blood supply. The intratumor heterogeneity in the blood supply differed slightly between the A-07 and R-18 tumors, and even this difference was mirrored by the E ⅐ F images.Conclusion: E ⅐ F images of xenografted tumors reflect blood perfusion. This implies that E ⅐ F may be a useful parameter for improving cancer diagnostics and individualizing cancer treatment. This possibility deserves to be investigated thoroughly in clinical studies.