Cluster versus ROI analysis to assess combined antiangiogenic therapy and radiotherapy in the F98 rat-glioma model.

For glioblastoma (GBM), current therapeutic approaches focus on the combination of several therapies, each of them individually approved for GBM or other tumor types. Many efforts are made to decipher the best sequence of treatments that would ultimately promote the most efficient tumor response. There is therefore a strong interest in developing new clinical in vivo imaging procedures that can rapidly detect treatment efficacy and allow individual modulation of the treatment.

Evaluation of Parametric Response Mapping to Assess Therapeutic Response to Human Mesenchymal Stem Cells after Experimental Stroke.

Stroke is the leading cause of disability in adults. After the very narrow time frame during which treatment by thrombolysis and mechanical thrombectomy is possible, cell therapy has huge potential for enhancing stroke recovery. Accurate analysis of the response to new therapy using imaging biomarkers is needed to assess therapeutic efficacy.

Intermittent hypoxia-induced insulin resistance is associated with alterations in white fat distribution.

Sleep apnea syndrome is characterized by repetitive upper airway collapses during night leading to intermittent hypoxia (IH). The latter is responsible for metabolic disturbances that rely, at least in part, on abdominal white fat inflammation. Besides qualitative alterations, we hypothesized that IH could also modify body fat distribution, a key factor for metabolic complications.

Permeability of Brain Tumor Vessels Induced by Uniform or Spatially Microfractionated Synchrotron Radiation Therapies.

Purpose: To compare the blood-brain barrier permeability changes induced by synchrotron microbeam radiation therapy (MRT, which relies on spatial fractionation of the incident x-ray beam into parallel micron-wide beams) with changes induced by a spatially uniform synchrotron x-ray radiation therapy.

Methods And Materials: Male rats bearing malignant intracranial F98 gliomas were randomized into 3 groups: untreated, exposed to MRT (peak and valley dose: 241 and 10.5 Gy, respectively), or exposed to broad beam irradiation (BB) delivered at comparable doses (ie, equivalent to MRT valley dose); both applied by 2 arrays, intersecting orthogonally the tumor region.

Multiparametric magnetic resonance imaging including oxygenation mapping of experimental ischaemic stroke.

Recent advances in MRI methodology, such as microvascular and brain oxygenation (StO) imaging, may prove useful in obtaining information about the severity of the acute stroke. We assessed the potential of StO to detect the ischaemic core in the acute phase compared to apparent diffusion coefficient and to predict the final necrosis. Sprague-Dawley rats (n = 38) were imaged during acute stroke (D0) and 21 days after (D21).

Vascular permeability in the RG2 glioma model can be mediated by macropinocytosis and be independent of the opening of the tight junction.

This study evaluates the extravasation pathways of circulating macromolecules in a rat glioma model (RG2) which was observed by both magnetic resonance imaging using ultrasmall superparamagnetic iron oxide and electron microscopy. Although magnetic resonance imaging signal enhancement was observed as soon as 10 min after injection (9.4% 2 h after injection), electron microscopy showed that endothelial cells were still tightly sealed.

Intravenous Injection of Clinical Grade Human MSCs After Experimental Stroke: Functional Benefit and Microvascular Effect.

Stroke is the leading cause of disability in adults. Many current clinical trials use intravenous (IV) administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs). This autologous graft requires a delay for ex vivo expansion of cells.

Multiparametric MRI as an early biomarker of individual therapy effects during concomitant treatment of brain tumours.

The aim of this study was to determine the ability of multiparametric MRI to identify the early effects of individual treatment, during combined chemo-radiotherapy on brain tumours. Eighty male rats bearing 9L gliosarcomas were randomized into four groups: untreated, anti-angiogenic therapy (SORA group), microbeam radiation therapy (MRT group) and both treatments (MRT+SORA group). Multiparametric MRI (tumour volume, diffusion-weighted MR imaging (ADC), blood volume fraction (BVf), microvessel index (VSI), vessel wall integrity (AUC(P846)) and tissue oxygen saturation (StO2)) was performed 1 day before and 2, 5 and 8 days after treatment initiation.

Spatial profiles of markers of glycolysis, mitochondria, and proton pumps in a rat glioma suggest coordinated programming for proliferation.

Background: In cancer cells in vitro, the glycolytic pathway and the mitochondrial tricarboxylic acid (TCA) cycle are programmed to produce more precursor molecules, and relatively less ATP, than in differentiated cells. We address the questions of whether and where these changes occur in vivo in glioblastomas grown from C6 cells in rat brain. These gliomas show some spatial organization, notably in the upregulation of membrane proton transporters near the rim.

Imaging the microvessel caliber and density: Principles and applications of microvascular MRI.

Twenty years ago, theoretical developments were initiated to model the behavior of the NMR transverse relaxation rates in presence of vessels. These developments enabled the MRI-based mapping of mean vessel diameter, microvascular density, and vessel size index with comparable results to those obtained by a pathologist. The transfer of these techniques to routine clinical use has been hindered by the unavailability of the required sequences, namely fast gradient-echo spin-echo sequences.

Tissue oxygen saturation mapping with magnetic resonance imaging.

A quantitative estimate of cerebral blood oxygen saturation is of critical importance in the investigation of cerebrovascular disease. While positron emission tomography can map in vivo the oxygen level in blood, it has limited availability and requires ionizing radiation. Magnetic resonance imaging (MRI) offers an alternative through the blood oxygen level-dependent contrast.

Microvascular MRI and unsupervised clustering yields histology-resembling images in two rat models of glioma.

Imaging heterogeneous cancer lesions is a real challenge. For diagnosis, histology often remains the reference, but it is widely acknowledged that biopsies are not reliable. There is thus a strong interest in establishing a link between clinical in vivo imaging and the biologic properties of tissues.

Differential hippocampal and retrosplenial involvement in egocentric-updating, rotation, and allocentric processing during online spatial encoding: an fMRI study.

The way new spatial information is encoded seems to be crucial in disentangling the role of decisive regions within the spatial memory network (i.e., hippocampus, parahippocampal, parietal, retrosplenial,…).

Magnetic resonance imaging and fluorescence labeling of clinical-grade mesenchymal stem cells without impacting their phenotype: study in a rat model of stroke.

Human mesenchymal stem cells (hMSCs) have strong potential for cell therapy after stroke. Tracking stem cells in vivo following a graft can provide insight into many issues regarding optimal route and/or dosing. hMSCs were labeled for magnetic resonance imaging (MRI) and histology with micrometer-sized superparamagnetic iron oxides (M-SPIOs) that contained a fluorophore.

Evaluation of the relationship between MR estimates of blood oxygen saturation and hypoxia: effect of an antiangiogenic treatment on a gliosarcoma model.

Purpose: To assess the reproducibility of the magnetic resonance (MR) estimate of blood oxygen saturation (sO(2)) in the rat brain, to evaluate the relationship between low MR estimate of sO(2) values and tissue hypoxia in a hypoxic and necrotic glioscarcoma model (9L gliosarcoma cells), and to evaluate the capability of the MR estimate of sO(2) parameter to help identify modifications induced by an antiangiogenic treatment (sorafenib) in 9L gliosarcoma tumors.

Materials And Methods: Experiments were performed with permits from the French Ministry of Agriculture. Forty-eight male rats bearing a 9L gliosarcoma were randomized in untreated and treated (sorafenib) groups.

Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of glioblastoma.

Background: Glioma is the most aggressive tumor of the brain and the most efficient treatments are based on radiotherapy. However, tumors are often resistant to radiotherapy due to an enhanced DNA repair activity. Short and stabilized DNA molecules (Dbait) have recently been proposed as an efficient strategy to inhibit DNA repair in tumor.

In vivo imaging of vessel diameter, size, and density: a comparative study between MRI and histology.

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.

Monochromatic minibeams radiotherapy: from healthy tissue-sparing effect studies toward first experimental glioma bearing rats therapy.

Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats.

Methods And Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm(3) volume centered in the right hemisphere), respectively.

Quantitative MR estimates of blood oxygenation based on T2*: a numerical study of the impact of model assumptions.

Several MR methods have been proposed over the last decade to obtain quantitative estimates of the tissue blood oxygen saturation (StO2) using a quantification of the blood oxygen level dependent effect. These approaches are all based on mathematical models describing the time evolution of the MR signal in biological tissues in the presence of magnetic field inhomogeneities. Although the experimental results are very encouraging, possible biases induced by the model assumptions have not been extensively studied.

Is T2* enough to assess oxygenation? Quantitative blood oxygen level-dependent analysis in brain tumor.

Purpose: To analyze the contribution of the transverse relaxation parameter (T2), macroscopic field inhomogeneities (B0), and blood volume fraction (BVf) to blood oxygen level-dependent (BOLD)-based magnetic resonance (MR) measurements of blood oxygen saturation (SO2) obtained in a brain tumor model.

Materials And Methods: This study was approved by the local committee for animal care and use. Experiments were performed in accordance with permit 380 820 from the French Ministry of Agriculture.

Vessel size index measurements in a rat model of glioma: comparison of the dynamic (Gd) and steady-state (iron-oxide) susceptibility contrast MRI approaches.

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.