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The aim of this study was to compare magnetic resonance imaging (MRI) and histological estimates of the mean vessel diameter (mVD), the vessel density (Density), and the vessel size index (VSI) obtained in the same tumor-bearing animals. Twenty-seven rats bearing intracranial glioma (C6 or RG2) were imaged by MRI. Changes in transverse relaxations (ΔR 2* and R(2)) were induced by the injection of an iron-based contrast agent and were mapped using a multi gradient-echo spin-echo sequence. Then, brain vascular network was studied ex vivo by histology. Three regions of interest were drawn in apparently normal tissue (neocortex and striatum) and in the tumor. In vivo mVD(MRI), Density(MRI), and VSI(MRI) were measured; ex vivo, mVD(histo), Density(histo), and VSI(histo) were quantified on the same animals. MRI and histology measurements differed by -15 to 26%. A positive correlation was found between MRI and histology for mVD, Density, and VSI counterparts (R(2) = 0.62, 0.50, 0.73, respectively; P < 0.001 in all cases). This study indicates that MRI and histology yields well correlated the estimates of mVD, Density, and VSI. VSI is the closest MRI estimate to histology. As Density and mVD or VSI provide complementary information, it is worth computing them to characterize angiogenesis beyond blood volume fraction., (Copyright © 2012 Wiley Periodicals, Inc.)

Vessel size index (VSI), a parameter related to the distribution of vessel diameters, may be estimated using two MRI approaches: (i) dynamic susceptibility contrast (DSC) MRI following the injection of a bolus of Gd-chelate. This technique is routinely applied in the clinic to assess intracranial tissue perfusion in patients; (ii) steady-state susceptibility contrast with USPIO contrast agents, which is considered here as the standard method. Such agents are not available for human yet and the steady-state approach is currently limited to animal studies. The aim is to compare VSI estimates obtained with these two approaches on rats bearing C6 glioma (n = 7). In a first session, VSI was estimated from two consecutive injections of Gd-Chelate (Gd(1) and Gd(2)). In a second session (4 hours later), VSI was estimated using USPIO. Our findings indicate that both approaches yield comparable VSI estimates both in contralateral (VSI{USPIO} = 7.5 ± 2.0 µm, VSI{Gd(1)} = 6.5 ± 0.7 µm) and in brain tumour tissues (VSI{USPIO} = 19.4 ± 7.1 µm, VSI{Gd(1)} = 16.6 ± 4.5 µm). We also observed that, in the presence of BBB leakage (as it occurs typically in brain tumours), applying a preload of Gd-chelate improves the VSI estimate with the DSC approach both in contralateral (VSI{Gd(2)} = 7.1 ± 0.4 µm) and in brain tumour tissues (VSI{Gd(2)} = 18.5 ± 4.3 µm) but is not mandatory. VSI estimates do not appear to be sensitive to T(1) changes related to Gd extravasation. These results suggest that robust VSI estimates may be obtained in patients at 3 T or higher magnetic fields with the DSC approach., (Copyright © 2011 John Wiley & Sons, Ltd.)

Diffusion tensor imaging (DTI) was used to study traumatic brain injury. The impact-acceleration trauma model was used in rats. Here, in addition to diffusivities (mean, axial and radial), fractional anisotropy (FA) was used, in particular, as a parameter to characterize the cerebral tissue early after trauma. DTI was implemented at 7 T using fast spiral k-space sampling and the twice-refocused spin echo radiofrequency sequence for eddy current minimization. The method was carefully validated on different phantom measurements. DTI of a trauma group (n = 5), as well as a sham group (n = 5), was performed at different time points during 6 h following traumatic brain injury. Two cerebral regions, the cortex and corpus callosum, were analyzed carefully. A significant decrease in diffusivity in the trauma group versus the sham group was observed, suggesting the predominance of cellular edema in both cerebral regions. No significant FA change was detected in the cortex. In the corpus callosum of the trauma group, the FA indices were significantly lower. A net discontinuity in fiber reconstructions in the corpus callosum was observed by fiber tracking using DTI. Histological analysis using Hoechst, myelin basic protein and Bielschowsky staining showed fiber disorganization in the corpus callosum in the brains of the trauma group. On the basis of our histology results and the characteristics of the impact-acceleration model responsible for the presence of diffuse axonal injury, the detection of low FA caused by a drastic reduction in axial diffusivity and the presence of fiber disconnections of the DTI track in the corpus callosum were considered to be related to the presence of diffuse axonal injury., (Copyright © 2011 John Wiley & Sons, Ltd.)

Early imaging or blood biomarkers of tumor response is needed to customize anti-tumor therapy on an individual basis. This study evaluates the sensitivity and relevance of five potential MRI biomarkers. Sixty nude rats were implanted with human glioma cells (U-87 MG) and randomized into three groups: one group received an anti-angiogenic treatment (Sorafenib), a second a cytotoxic drug [1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU (Carmustine)] and a third no treatment. The tumor volume, apparent diffusion coefficient (ADC) of water, blood volume fraction (BVf), microvessel diameter (vessel size index, VSI) and vessel wall integrity (contrast enhancement, CE) were monitored before and during treatment. Sorafenib reduced tumor CE as early as 1 day after treatment onset. By 4 days after treatment onset, tumor BVf was reduced and tumor VSI was increased. By 14 days after treatment onset, ADC was increased and the tumor growth rate was reduced. With BCNU, ADC was increased and the tumor growth rate was reduced 14 days after treatment onset. Thus, the estimated MRI parameters were sensitive to treatment at different times after treatment onset and in a treatment-dependent manner. This study suggests that multiparametric MR monitoring could allow the assessment of new anti-tumor drugs and the optimization of combined therapies., (Copyright © 2010 John Wiley & Sons, Ltd.)

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&#95;LSO(2)) were compared with measurements obtained from blood gas analysis. A very good correlation (R(2) = 0.89) was found between brain MR&#95;LSO(2) and sagittal sinus SO(2)., (Copyright © 2010 John Wiley & Sons, Ltd.)

Degeneration of the dopaminergic neurons of the substantia nigra pars compacta in Parkinson's disease induces an abnormal activation of the glutamatergic neurotransmission system within the basal ganglia network and related structures. The aim of this study was to use proton MRS to show metabolic changes in the striatum of 6-hydroxydopamine-lesioned rats, a rodent animal model of Parkinson's disease. Animals were examined before and after extensive lesioning of the nigral dopaminergic neurons and after acute administration of L-3,4-dihydroxyphenylalanine. No significant alterations in glutamate concentrations, assessed by the MR signal dominated by glutamate with minor contributions from glutamine and gamma-aminobutyric acid, could be measured. The total choline/total creatine ratio was found to be reduced in the striatum of the ipsilateral hemisphere., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

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., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Lactate (Lac) and mobile lipids (Lip), which are present in rat gliomas, are difficult to map because their 1H resonances overlap in the 1.3 ppm region. 2D J-resolved spectroscopy enables proper separation of the two resonance lines. To obtain high-spatial-resolution mapping of Lac and Lip resonances within a reasonable experiment time, we coupled 2D J-resolved spectroscopy with a fast spectroscopic imaging (SI) method, based on an out-and-in spiral k-space description. The method was applied to a rat glioma at 7 T, and Lac and Lip maps were reconstructed. The duration of SI (2D spatial, 2D spectral) was 64 min for a theoretical in-plane resolution of 1 x 1 mm, and a slice thickness of 2 mm (voxel size 8.2 microl, taking into account the point-spread function (PSF))., (Copyright 2004 Wiley-Liss, Inc.)

Vessel size imaging (VSI) for brain tumor characterization was evaluated and the vessel size index measured by MRI (VSIMRI) was correlated with VSI obtained by histology (VSIhisto). Blood volume (BV) and VSI maps were obtained on 12 rats by simultaneous measurements of R2* and R2, 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 (VSIhisto). 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. The quantitative analysis showed a good correlation (Spearman rank's rho = 0.74) between VSIhisto and VSIMRI with a linear regression coefficient of 1.17. The good correlation coefficient supports VSI imaging as a quantitative method for tumor vasculature characterization., (Copyright 2004 Wiley-Liss, Inc.)

The aim of this study was to investigate the possible correlation between the 1H MRS mobile lipid signal, necrosis and lipid droplets in C6 rat glioma. First, the occurrence of necrosis and lipid droplets was determined during tumor development, by a histological analysis performed on 34 rats. Neither necrosis nor lipid droplets were observed before 18 days post-implantation. At later stages of development, both necrosis and lipid droplets were apparent, the lipid droplets being mainly located within the necrotic areas. Using a second group of eight rats, a temporal correlation was evidenced between mobile lipid signal detected by in vivo single-voxel one- (136 ms echo time) and two-dimensional J-resolved 1H MR spectroscopy, and the presence of necrosis and lipid droplets on the histological sections obtained from the brains of the same rats. Finally, spatial distribution of the mobile lipid signal was analyzed by chemical-shift imaging performed on a third group of eight animals, at the end of the tumor growth. The spectroscopic image corresponding to the resonance of mobile lipids had its maximum intensity in the center of the tumor where necrotic regions were observed on the histological sections. These necrotic areas contained large amounts of lipid droplets. All these results suggest that mobile lipids detected in vivo by 1H MRS (136 ms echo time) in C6 rat brain glioma arise mainly from lipid droplets located in necrosis., (Copyright 2003 John Wiley & Sons, Ltd.)

Pulsed field gradient NMR was used to measure the root mean square displacement lambda of the NMR visible lipid molecules in C6 brain tumors in the rat at different diffusion times. For a distribution of spherical droplets of diameter with volume fraction xi(Phi(i)), the mean characteristic droplet diameter Phi(c) = square root of Sigma(i)xi(Phi(i)Phi(i)(2) was shown to be related to the root mean square displacement at long diffusion times by the simple relationship Phi(c)(2) = 10 lambda(2). In the range of diffusion times 100--530 msec, lambda was found to be independent of the diffusion time and equal to 1.35 +/- 0.22 microm and Phi(c) to 4.27 +/- 0.71 microm. The data reinforce the notion that the presence of lipid resonances in NMR spectra of tumors is due to lipid droplets. Light microscopy of histologic slices showed the presence of lipid droplets mainly in the necrotic region and in a layer of tumor cells surrounding the necrosis. Magn Reson Med 45:409-414, 2001., (Copyright 2001 Wiley-Liss, Inc.)