Blood-brain barrier permeability to manganese and to Gd-DOTA in a rat model of transient cerebral ischaemia.: BBB permeability after transient cerebral ischemia

International audienceLoss of integrity of the blood-brain barrier (BBB) and brain swelling is a potentially lethal complication of reperfusion in human stroke. To assess the time course of BBB modifications, we performed angiography, diffusion-weighted imaging, T1-weighted (T1 W) imaging and T1 mapping, and monitored acute changes after middle cerebral artery occlusion and recanalization in rats (n = 27). The animals were grouped according to the duration of occlusion: 30 min (group A, n = 8), 1 h 30 min (group B, n = 9), and 2 h 30 min (group C, n = 10). For 17 animals (four in group A, six in group B, and seven in group C), MnCl2 and dimeglumine gadoterate (Gd-DOTA) were injected at 13 min and 34 min after recanalization, respectively. The 10 remaining animals (control groups) underwent the same acquisition protocols, but no contrast agents were injected. Cell damage was determined 1 h after recanalization on haematoxylin and eosin-stained sections. Our results indicate that in the middle cerebral artery occlusion model in the rat, changes in BBB permeability assessed by contrast agent extravasation occur within the first hour of reperfusion, even after an occlusion period not exceeding 30 min. No differences between BBB permeability to Gd-DOTA and Mn2+ were detected in our experimental conditions. The reduction in apparent diffusion coefficient during occlusion appears to be a good predictor of BBB modifications after reperfusion in this model

Hyperosmolar treatment of soman-induced brain lesions in mice: evaluation of the effects through diffusion-weighted magnetic resonance imaging and through histology.

International audiencePURPOSE: A convulsive dose of soman induces seizure-related brain damage (SRBD), including cerebral edema (CE) and neuronal loss. In the present study on soman-intoxicated mice, we applied diffusion-weighted magnetic resonance imaging (DW-MRI) and quantitative histology, and we measured brain water content to investigate the antiedematous and neuroprotective efficacies of two hyperosmolar treatments: mannitol (Mann) and hypertonic saline (HTS). METHODS: Mice intoxicated with soman (172 microg/kg after a protective pretreatment) were administered 1 min and 5-h post-challenge an i.v. bolus of saline, of Mann or of HTS. 1 day later, mice were examined with DW-MRI and then sacrificed for brain histology. Additional animals were intoxicated and treated similarly for the measurement of the brain water content (dry/wet weight method). RESULTS: In intoxicated controls, a significant decrease of the apparent diffusion coefficient (ADC), numerous damaged (eosinophilic) cells, high edema scores, and a significant increase in brain water content were detected 24-h post-challenge in sensitive brain structures. These soman-induced changes were not significantly modified by treatment with Mann or HTS. CONCLUSIONS: Treatment with hyperosmolar solutions did not reduce the effects of soman on ADC, on cell damage and on CE. Therefore, despite similar treatment protocols, the prominent protection by Mann that was previously demonstrated by others in poisoned rats, was not reproduced in our murine model

MP3: Medical software for Processing multi-Parametric images Pipelines

International audienceThis article presents an open source software able to convert, display and process medical images. It differentiates itself from the existing software by its ability to design complex processing pipelines and to wisely execute them on a large database. An MP3 pipeline can contain unlimited homemade or ready-made processes and can be carried out with a parallel execution system. As a viewer, MP3 allows to display up to 4 images together and to draw Regions Of Interest (ROI). Two applications showing the strengths of the software are here exposed: a preclinical study involving Magnetic Resonance Imaging (MRI) data and a clinical one involving Computed Tomography (CT) images. MP3 is downloadable at https://github.com/nifm-gin/MP3

MRI-guided clinical 6-MV radiosensitization of glioma using a unique gadolinium-based nanoparticles injection

International audienceAim: This study reports the use of gadolinium-based AGuIX nanoparticles (NPs) as a theranostic tool for both image-guided radiation therapy and radiosensitization of brain tumors. Materials & methods: Pharmacokinetics and regulatory toxicology investigations were performed on rodents. The AGuIX NPs’ tumor accumulation was studied by MRI before 6-MV irradiation. Results: AGuIX NPs exhibited a great safety profile. A single intravenous administration enabled the tumor delineation by MRI with a T1 tumor contrast enhancement up to 24 h, and the tumor volume reduction when combined with a clinical 6-MV radiotherapy. Conclusion: This study demonstrates the efficacy and the potential of AGuIX NPs for image-guided radiation therapy, promising properties that will be assessed in the upcoming Phase I clinical trial

Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology.

International audiencePURPOSE: In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. METHODS: Three hours and 24 h after the intoxication with soman (172 microg/kg), the mice were anesthetized with an isoflurane/N(2)O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. RESULTS: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication and was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. CONCLUSIONS: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into the brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures

MRI Assessment of Oxygen Metabolism and Hemodynamic Status in Symptomatic Intracranial Atherosclerotic Stenosis: A Pilot Study

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An MRI-based classification scheme to predict passive access of 5 to 50-nm large nanoparticles to tumors OPEN

Nanoparticles are useful tools in oncology because of their capacity to passively accumulate in tumors in particular via the enhanced permeability and retention (EPR) effect. However, the importance and reliability of this effect remains controversial and quite often unpredictable. In this preclinical study, we used optical imaging to detect the accumulation of three types of fluorescent nanoparticles in eight different subcutaneous and orthotopic tumor models, and dynamic contrast-enhanced and vessel size index Magnetic Resonance Imaging (MRI) to measure the functional parameters of these tumors. The results demonstrate that the permeability and blood volume fraction determined by MRI are useful parameters for predicting the capacity of a tumor to accumulate nanoparticles. Translated to a clinical situation, this strategy could help anticipate the EPR effect of a particular tumor and thus its accessibility to nanomedicines. Low-molecular-weight targeted anticancer drugs administered intravenously are usually homogeneously distributed in most tissues but are expected to eventually perform their (specific) function in cancer cells only. Depending on the importance and quality of this specific therapeutic activity, these drugs often provide insufficient therapeutic benefits and cause severe systemic toxicity. In such cases, it is expected that their entrapment in a nanoparticle (NP) will reduce their accumulation in healthy tissues while improving it in tumors via the so-called "enhanced permeability and retention (EPR) effect 1,2 ". Indeed, molecules less than 40-45 kDa can leak out of the tumor vascular bed by diffusion, depending on the difference in concentration between the therapeutic solution and tumor. They are also rapidly cleared as they are evacuated by the lymph and blood circulation. By contrast, larger molecules and NPs (up to 500 nm in size) have greater difficulties extravasating from the vascular bed. They benefit from the augmented permeability of tumor blood vessels to leak out of the vascular bed more efficiently than in normal tissues under a convection flow, which can be represented by the difference in pressure between the therapeutic solution and tumor. Large molecules are then captured in the tumor's interstitial space. The quantitative importance of the EPR effect is thus related to the tumor biology (i.e., systolic blood pressure that pushes blood into the tumor tissue, blood and lymphatic vessel architecture and functions, interstitial fluid and extracellular matrix composition and pressur