No abstract

Vessel size imaging (VSI) for brain tumor characterization was evaluated and the vessel size index measured by MRI (VSI MRI ) was correlated with VSI obtained by histology (VSI histo ). Blood volume (BV) and VSI maps were obtained on 12 rats by simultaneous measurements of R 2 * and R 2 , before and after the injection of a macromolecular contrast agent, AMI-227. Immunostaining of collagen IV in vessels was performed. An expression was derived for evaluating VSI from stereologic measurements on histology data (VSI histo ). On BV and VSI images obtained from large-size tumors (n ‫؍‬ 9), three regions could be distinguished and correlated well with histological sections: a high BV region surrounding the tumor, a necrotic area where BV is very low, and a viable tumor tissue region showing lower BV but higher VSI than the normal rat cortex, with the presence of larger vessels. Angiogenesis is an important stage in tumor development. Neovascularization, which is associated with rapid tumor growth, is characterized by a higher vessel density in some areas of the tumor and by vessels of larger lumen than in normal tissues (1). Microvessel density was found to be a major factor in predicting the aggressiveness of the disease (2) and patient survival in different tumor types (2-5). This is currently determined by immunohistochemistry on biopsies. Nevertheless, regional tumor heterogeneity limits the use of this technique for routine examinations since biopsy samples are small and might not be sampled in the most aggressive or representative part of the tumor. In addition, its invasiveness prevents the use of this technique for therapy follow-up.Among the possible imaging methods for vascularization characterization, perfusion MR techniques allow brain microvascularization assessment, are noninvasive, and provide a high spatial resolution. Blood volume (BV) imaging could be a noninvasive alternative to histology since an increase in the mean vessel density and/or vessel lumen can be detected through an increase in BV. For example, in rat mammary adenocarcinoma models, statistically significant differences were observed by Okuhata et al. (6) in MRI-estimated tumor BV between tumor subtypes and between the tumor periphery and tumor center. More recently, Dennie et al. (7) suggested that the ratio of gradient-echo and spin-echo relaxation rate changes (⌬R 2 */⌬R 2 ) induced by a high molecular weight contrast agent provides an indication of the average vessel size in a voxel, under certain conditions related to the echo time, the contrast agent concentration, and the main magnetic field (8). A good correspondence between MRI and histology results was shown in a rat glioma model (7). More recently, the ⌬R 2 */⌬R 2 ratio obtained after Gd-DTPA injection was found to correlate strongly with tumor grade (9) in patients with brain tumors. However, access to the morphology of the vessels is not straightforward, since correlation with histology necessitates Monte-Carlo simulations (7). ⌬R 2 */ ⌬R 2 is a dimensionless ratio and its ...