A computer-based decision support system to assist radiologists in diagnosing and grading brain tumours has been developed by the multi-centre INTERPRET project. Spectra from a database of 1 H single-voxel spectra of different types of brain tumours, acquired in vivo from 334 patients at four different centres, are clustered according to their pathology, using automated pattern recognition techniques and the results are presented as a two-dimensional scatterplot using an intuitive graphical user interface (GUI). Formal quality control procedures were performed to standardize the performance of the instruments and check each spectrum, and teams of expert neuroradiologists, neurosurgeons, neurologists and neuropathologists clinically validated each case. The prototype decision support system (DSS) successfully classified 89% of the cases in an independent test set of 91 cases of the most frequent tumour types (meningiomas, low-grade gliomas and high-grade malignant tumours-glioblastomas and metastases). It also helps to resolve diagnostic difficulty in borderline cases. When the prototype was tested by radiologists and other clinicians it was favourably received. Results of the preliminary clinical analysis of the added value of using the DSS for brain tumour diagnosis with MRS showed a small but significant improvement over MRI used alone. In the comparison of individual pathologies, PNETs were significantly better diagnosed with the DSS than with MRI alone.

We show for the first time that preferential damage of MRT to tumor vessels versus preservation of radioresistant normal brain vessels contributes to the efficient palliation of 9L gliosarcomas in rats. Molecular pathways of repair mechanisms in normal and tumoral vascular networks after MRT may be essential for the improvement of such differential effects on the vasculature.

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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 ...

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Assessment of angiogenesis may help to determine tumor grade and therapy follow-up. In vivo imaging methods for non-invasively monitoring microvasculature evolution are therefore of major interest for tumor management. MRI evaluation of blood volume fraction (BVf) and vessel size index (VSI) was applied to assess the evolution of tumor microvasculature in two rat models of glioma (C6 and RG2). The results show that repeated MRI of BVf and VSI -which involves repeated injection of an iron-based MR contrast agent -does not affect either the physiological status of the animals or the accuracy of the MR estimates of the microvascular parameters. The MR measurements were found to correlate well with those obtained from histology. They indicate that microvascular evolution differs significantly between the two glioma models, in good agreement with expression of angiogenic factors (vascular endothelial growth factor, angiopoietin-2) and with activities of matrix metalloproteinases, also assessed in this study. These MRI methods thus provide considerable potential for assessing the response of gliomas to anti-angiogenic and anti-vascular agents, in preclinical studies as well as in the clinic. Furthermore, as differences between the fate of tumor microvasculature may underlie differences in therapeutic response, there is a need for preclinical study of several tumor models.

Blood oxygen saturation (SO(2)) is a promising parameter for the assessment of brain tissue viability in numerous pathologies. Quantitative blood oxygenation level-dependent (qBOLD)-like approaches allow the estimation of SO(2) by modelling the contribution of deoxyhaemoglobin to the MR signal decay. These methods require a high signal-to-noise ratio to obtain accurate maps through fitting procedures. In this article, we present a version of the qBOLD method at long TE taking into account separate estimates of T(2), total blood volume fraction (BV(f)) and magnetic field inhomogeneities. Our approach was applied to the brains of 13 healthy rats under normoxia, hyperoxia and hypoxia. MR estimates of local SO(2) (MR_LSO(2)) were compared with measurements obtained from blood gas analysis. A very good correlation (R(2) = 0.89) was found between brain MR_LSO(2) and sagittal sinus SO(2).

Human mesenchymal stem cells (hMSC) are a promising source for cell therapy after stroke. To deliver these cells, an IV injection appears safer than a local graft. We aimed to assess the whole-body biodistribution of IV-injected (99m)Tc-HMPAO-labeled hMSC in normal rats (n = 9) and following a right middle cerebral artery occlusion (MCAo, n = 9). Whole-body nuclear imaging, isolated organ counting (at 2 and 20 h after injection) and histology were performed. A higher activity was observed in the right damaged hemisphere of the MCAo group [6.5 +/- 0.9 x 10(-3) % of injected dose (ID)/g] than in the control group (3.6 +/- 1.2 x 10(-3) %ID/g), 20 h after injection. In MCAo rats, right hemisphere activity was higher than that observed in the contralateral hemisphere at 2 h after injection (11.6 +/- 2.8 vs. 9.8 +/- 1.7 x 10(-3) %ID/g). Following an initial hMSC lung accumulation, there was a decrease in pulmonary activity from 2 to 20 h after injection in both groups. The spleen was the only organ in which activity increased between 2 and 20 h. The presence of hMSC was documented in the spleen, liver, lung, and brain following histology. IV-injected hMSC are transiently trapped in the lungs, can be sequestered in the spleen, and are predominantly eliminated by kidneys. After 20 h, more hMSC are found in the ischemic lesion than into the undamaged cerebral tissue. IV delivery of hMSC could be the initial route for a clinical trial of tolerance.