Front Cardiovasc Med

IntroductionInterventional cardiac MRI in the context of the treatment of cardiac arrhythmia requires submillimeter image resolution to precisely characterize the cardiac substrate and guide the catheter-based ablation procedure in real-time. Conventional MRI receiver coils positioned on the thorax provide insufficient signal-to-noise ratio (SNR) and spatial selectivity to satisfy these constraints.MethodsA small circular MRI receiver coil was developed and evaluated under different experimental conditions, including high-resolution MRI anatomical and thermometric imaging at 1.5 T. From the perspective of developing a therapeutic MR-compatible catheter equipped with a receiver coil, we also propose alternative remote active detuning techniques of the receiver coil using one or two cables. Theoretical details are presented, as well as simulations and experimental validation.ResultsAnatomical images of the left ventricle at 170 µm in-plane resolution are provided on ex vivo beating heart from swine using a 2 cm circular receiver coil. Taking advantage of the increase of SNR at its vicinity (up to 35 fold compared to conventional receiver coils), real-time MR-temperature imaging can reach an uncertainty below 0.1°C at the submillimetric spatial resolution. Remote active detuning using two cables has similar decoupling efficiency to conventional on-site decoupling, at the cost of an acceptable decrease in the resulting SNR.DiscussionThis study shows the potential of small dimension surface coils for minimally invasive therapy of cardiac arrhythmia intraoperatively guided by MRI. The proposed remote decoupling approaches may simplify the construction process and reduce the cost of such single-use devices.Thermometrie cardiaque haute résolution sur une IRM clinique en utilisant des antennes intracardiaquesL'Institut de Rythmologie et modélisation CardiaqueFrance Life Imagin

Evaluation quantitative par IRM et ¹H SRM de l'exposition à des xénobiotiques chez le petit animal dans un contexte clinique et environnemental

Magnetic Resonance Imaging and Spectroscopy (MRI and ¹H MRS) are new methods in toxicology. These tools allow the assessment of the impact of xenobiotics at structural and metabolic levels respectively. In this perspective, this thesis presents two studies in animal models: (i) repeated administrations of linear gadolinium-based contrast agent (gadodiamide) in rat leading to a deposition of gadolinium in deep cerebellar nuclei (DCN); (ii) gestational and lactational exposure to bisphenol A (BPA) and its chlorinated derivatives at low dose (20 μg/kg/day) which are endocrine disruptors.The study of repeated injections of gadodiamide showed a hypersignal of DCN on T1-weighed images at 6and 11 weeks post-injections. In an unprecedented way, it was demonstrated that the hypersignal of DCN persisted for 1 year post-injections. A prolonged increase of total creatine concentration in DCN was also measured by the quantitation ERETIC digital method. Nevertheless, this variation was not confirmed by other conventional quantitation methods (jMRUI and LCModel). A comparison of quantitation methods in ¹H MRS (ERETIC digital, jMRUI and LCModel) was performed in order to elucidate the influence of baseline correction in the processing of in vivo ¹H spectra.Early disturbances caused by chlorinated derivatives of BPA were quantified in young male and female mice perinatally exposed: (i) modifications of hepatic lipid composition which precedes any structural change; (ii)microstructural and metabolic alterations in the hippocampus. A spectroscopic diffusion method was optimized, leading to in vivo experiments in order to characterize those abnormalities of intracellular integrity in the brain of male mice.L’Imagerie et la Spectroscopie par Résonance Magnétique du proton (IRM et ¹H SRM) sont des méthodes innovantes en toxicologie. Ces outils permettent l’évaluation de l’impact des xénobiotiques in vivo au niveau structural et métabolique respectivement. Dans cette perspective, les travaux de cette thèse ont été réalisés sur deux modèles murins : (i) des injections répétées de gadodiamide chez le rat entrainant une accumulation de gadolinium dans les noyaux profonds cérébelleux (NCP) ; (ii) une exposition à faible dose(20 μg/kg/jour) pendant la gestation et la lactation au bisphénol A (BPA) et à ses dérivés chlorés qui sont des perturbateurs endocriniens.L’étude des effets des injections répétées du gadodiamide a montré un rehaussement du signal des NCP sur des images pondérées T1 à 6 et 11 semaines post-injections. De manière inédite, il a été mis en évidence que le rehaussement du signal des NCP se maintient jusqu’à 1 an post-injections. Il a été également mesuré une augmentation prolongée de la concentration de créatine totale dans les NCP par la méthode de quantification ERETIC digital. Néanmoins, cette variation n’a pas été confirmée par les autres méthodes de quantification conventionnelles (jMRUI et LCModel). Une comparaison des méthodes de quantification en ¹H SRM (ERETIC digital, jMRUI et LCModel) a été réalisée afin de mettre en évidence l’influence de la correction de la ligne de base dans le traitement des spectres ¹H in vivo.Des perturbations précoces des dérivés chlorés du BPA ont été quantifiés chez les jeunes souris mâles et femelles exposées pendant la période périnatale : (i) des modifications de la composition lipidique hépatique, et cela préalablement à tout changement structural ; (ii) des altérations microstructurales et métaboliques au niveau de l’hippocampe. Une méthode de diffusion spectroscopique a été optimisée puisdes expériences in vivo ont été effectuées afin de caractériser ces anomalies de l’intégrité intracellulaire dans le cerveau des souris mâles

Quantitative assessment by MRI and ¹H MRS of xenobiotics exposure in small animal within a clinical and environmental context

L’Imagerie et la Spectroscopie par Résonance Magnétique du proton (IRM et ¹H SRM) sont des méthodes innovantes en toxicologie. Ces outils permettent l’évaluation de l’impact des xénobiotiques in vivo au niveau structural et métabolique respectivement. Dans cette perspective, les travaux de cette thèse ont été réalisés sur deux modèles murins : (i) des injections répétées de gadodiamide chez le rat entrainant une accumulation de gadolinium dans les noyaux profonds cérébelleux (NCP) ; (ii) une exposition à faible dose(20 μg/kg/jour) pendant la gestation et la lactation au bisphénol A (BPA) et à ses dérivés chlorés qui sont des perturbateurs endocriniens.L’étude des effets des injections répétées du gadodiamide a montré un rehaussement du signal des NCP sur des images pondérées T1 à 6 et 11 semaines post-injections. De manière inédite, il a été mis en évidence que le rehaussement du signal des NCP se maintient jusqu’à 1 an post-injections. Il a été également mesuré une augmentation prolongée de la concentration de créatine totale dans les NCP par la méthode de quantification ERETIC digital. Néanmoins, cette variation n’a pas été confirmée par les autres méthodes de quantification conventionnelles (jMRUI et LCModel). Une comparaison des méthodes de quantification en ¹H SRM (ERETIC digital, jMRUI et LCModel) a été réalisée afin de mettre en évidence l’influence de la correction de la ligne de base dans le traitement des spectres ¹H in vivo.Des perturbations précoces des dérivés chlorés du BPA ont été quantifiés chez les jeunes souris mâles et femelles exposées pendant la période périnatale : (i) des modifications de la composition lipidique hépatique, et cela préalablement à tout changement structural ; (ii) des altérations microstructurales et métaboliques au niveau de l’hippocampe. Une méthode de diffusion spectroscopique a été optimisée puisdes expériences in vivo ont été effectuées afin de caractériser ces anomalies de l’intégrité intracellulaire dans le cerveau des souris mâles.Magnetic Resonance Imaging and Spectroscopy (MRI and ¹H MRS) are new methods in toxicology. These tools allow the assessment of the impact of xenobiotics at structural and metabolic levels respectively. In this perspective, this thesis presents two studies in animal models: (i) repeated administrations of linear gadolinium-based contrast agent (gadodiamide) in rat leading to a deposition of gadolinium in deep cerebellar nuclei (DCN); (ii) gestational and lactational exposure to bisphenol A (BPA) and its chlorinated derivatives at low dose (20 μg/kg/day) which are endocrine disruptors.The study of repeated injections of gadodiamide showed a hypersignal of DCN on T1-weighed images at 6and 11 weeks post-injections. In an unprecedented way, it was demonstrated that the hypersignal of DCN persisted for 1 year post-injections. A prolonged increase of total creatine concentration in DCN was also measured by the quantitation ERETIC digital method. Nevertheless, this variation was not confirmed by other conventional quantitation methods (jMRUI and LCModel). A comparison of quantitation methods in ¹H MRS (ERETIC digital, jMRUI and LCModel) was performed in order to elucidate the influence of baseline correction in the processing of in vivo ¹H spectra.Early disturbances caused by chlorinated derivatives of BPA were quantified in young male and female mice perinatally exposed: (i) modifications of hepatic lipid composition which precedes any structural change; (ii)microstructural and metabolic alterations in the hippocampus. A spectroscopic diffusion method was optimized, leading to in vivo experiments in order to characterize those abnormalities of intracellular integrity in the brain of male mice

Combination of MRI‐Guided High‐Intensity Focused Ultrasound and Bioluminescent Biological Systems to Assess Thermal Therapies for Tumor and Tumor Microenvironment

International audienceThis work presents an integrated technology for assessing in vivo anti-cancer treatments in mice, based on various heating conditions. Bioluminescence imaging (BLI) was used to assess the physiological response of tumor and tumor microenvironment (TME) to heat treatment induced by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU). Transgenic tumor cells and mouse models with either constitutive or thermoinduced luciferase expressions were combined to monitor cell viability and heat-induced processes in the tumor and TME. BLI performed after MRgHIFU heating shows that a moderate increase in temperature (45°C) over 5 min can be exploited to promote heat-activable treatments in the tumor and its TME, without inducing direct cell death. A higher temperature rise over a shorter exposure time can induce cell death in the tumor, as revealed by a reduction in the BLI signal after treatment. Under these conditions, BLI also revealed that the TME can be stimulated by heat without inducing necrosis. These integrated technologies and models are useful to assess, in vivo in mice, the efficacy of various anticancer strategies exploiting local heat deposition by noninvasive MRgHIFU, including those combining tumor ablation with local drug administration using thermosensitive nanovehicles

Connexin43 amplifies cerebral metabolits alteration due to Bisphenol A exposition

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Étude in vivo de l'exposition à de faibles doses de Bisphénol A. Implication de la Cx43

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Perinatal exposure to dichloro-bisphenol A alters lipid composition of mouse liver

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Gestational and lactational exposure to dichlorinated bisphenol A induces early alterations of hepatic lipid composition in mice

International audienceObjectiveUsing non-invasive magnetic resonance (MR) techniques and a histological approach, we assessed the outcomes of perinatal exposure at a low dose of 3,3′-DCBPA (2-chloro-4-[1-(3-chloro-4-hydroxyphenyl)-1-methylethyl]phenol) and/or 3,5-DCBPA (2,6-dichloro-4-[1-(4-hydroxyphenyl)-1-methylethyl]phenol) on mice livers.Materials and methodsFertilized female Swiss mice were injected intraperitoneally during gestation and lactation with either vehicle control, 20 μg/kg/day of BPA, 3,5-DCBPA, 3,3′-DCBPA or a mixture (mix-DCBPA). Complementary methods were used to evaluate, in male and female pups, (1) liver structure by texture analysis of images obtained through MR imaging (MRI) and histology, (2) hepatic lipid composition through in vivo 1H MR spectroscopy (1H MRS).ResultsPrincipal component analysis of texture parameters showed no structural modification of the liver with BPA and DCBPA treatments. Accordingly, no hepatic microvesicular steatosis was observed through hematoxylin–eosin staining. Compared to control, MRS revealed no difference in lipid composition for BPA, 3,5-DCBPA or 3,3′-DCBPA groups. However, MRS detected a significant increase in the mix-DCBPA groups for the saturated component of fatty acids (FA), total unsaturated FA bond index and polyunsaturated FA bond index.ConclusionPrior to any structural changes, polyunsaturated fatty acids significantly increased in young male and female mice exposed perinatally at a low dose to a mixture of dichlorinated BPA

Perinatal exposure to dichloro-bisphenol A alters hepatic lipid composition in mouse: a study by MRI and 1H MRS

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Effect of Long-Term Retention of Gadolinium on Metabolism of Deep Cerebellar Nuclei After Repeated Injections of Gadodiamide in Rats

International audienceOBJECTIVES:The aim of this study was to determine potential metabolism and histological modifications due to gadolinium retention within deep cerebellar nuclei (DCN) after linear gadolinium-based contrast agent injection (gadodiamide) in rats at 1 year after the last injection.MATERIALS AND METHODS:Twenty female rats received 20 doses of gadodiamide (0.6 mmol of gadolinium per kilogram each) over 5 weeks. They were followed at 1 week (M0), 6 weeks (M1), and 54 to 55 weeks (M13) postinjections to evaluate hypersignal on unenhanced T1-weighted magnetic resonance imaging and metabolic alterations by H magnetic resonance spectroscopy (H-MRS). At 1 year postinjections, brains were sampled to determine the localization of gadolinium within cerebellum by laser ablation inductively coupled mass spectroscopy and to evaluate morphological changes by semiquantitative immunofluorescence analysis.RESULTS:There is a significant increase of the ratio DCN/brainstem for the gadodiamide group at M0 (+7.2% vs control group = 0.989 ± 0.01), M1 (+7.6% vs control group = 1.002 ± 0.018), and it lasted up to M13 (+4.7% vs control group = 0.9862 ± 0.008). No variation among metabolic markers (cellular homeostasis [creatine, choline, taurine], excitatory neurotransmitter [glutamate], and metabolites specific to a cellular compartment [N-acetyl aspartate for neurons and myo-inositol for glial cells]) were detected by H-MRS between gadodiamide and saline groups at M0, M1, and M13. At M13, laser ablation inductively coupled mass spectroscopy demonstrated that long-term gadolinium retention occurred preferentially in DCN. No histological abnormalities (including analysis of astrocytes, neurons, and microglial cells) were found in the rostral part of DCN.CONCLUSIONS:Repeated administration of gadodiamide lead to a retention of gadolinium preferentially within DCN at 1 year postinjections. This retention did not lead to any detectable changes of the measured metabolic biomarkers nor histological alterations