Chan-Vese based method to segment mouse brain MRI images: application to cerebral malformation analysis in trisomy 21

International audienceIn this paper, a semi automatic active contour method based on Chan-Vese model is proposed for the segmentation of mouse brain MR images. First, a 2 ½ D strategy is applied on the axial images to segment the 3D volume of interest. The method takes into account the special shape of the object to segment. Moreover, the user defines the limits where to search these contours and also provides an initial contour. This semi automatic method makes that human intervention is limited and the tedious manual handling is greatly reduced. Results have shown that the brain volumes estimated by the method are identical to expert manually estimated volumes. Last but not least, the new method was used in the analysis of the cerebral malformations linked to Trisomy 21: no significant difference of the brain volumes between Tri-somy 21 mice and the control ones were found

Capteur de champ magnétique : optimisation dans la bande 10kHz – 100MHz pour applications spatiales

Magnetic field measurement is important for the study of space plasmas, where an intensive electromagnetic activity occurs. The full knowledge of electromagnetic waves needs in situ measurements of electric and magnetic components, coupled differently from free space below plasma frequency. The latter approches 20MHz in the vicinity of Earth and 100MHz at one solar radius. In up-today geophysical space missions, magnetic sensors measured fields from DC to 1MHz, with a 1 fT Hz magnetic noise density between 10kHz and 1MHz. Measurement near the Sun necessitates a magnetometer extending these performances to higher frequencies, 100MHz at best. We design a sensor in the 10kHz-100MHz band, with the same noise level, to satisfy the scientific need without increasing mass and power consumption, limited onboard satellites. Magnetometry state-of-the-art shows that a loop antenna is better. Describing sensor’s antenna and preamplifier, we modelled its transfert function and its equivalent magnetic noise, thus obtaining optimisation criteria. We compare this modelling to the prototyp realised by impedance, magnetic field response and noise measurements. Studying winding method, we reduce the toroidal transformer parasitic capacitances. Using a flux feedback, we keep the signal-to-noise ratio of the open loop sensor. The optimisation leads to an instrument working upto 30MHz and satisfying noise specification between 700kHz and 20MHz, extending magnetic field measurement in space.La mesure du champ magnétique est essentielle dans l’étude des plasmas spatiaux, sièges d’une intense activité électromagnétique. La connaissance complète des ondes électromagnétiques suppose la mesure in situ des composantes électrique et magnétique, couplées différemment que dans le vide aux fréquences inférieures à la fréquence plasma locale, qui approche 20MHz près de la Terre et 100MHz à un rayon solaire. Les missions spatiales géophysiques ont embarqué jusqu’à présent des instruments mesurant les champs magnétiques depuis le continu jusqu’au MHz, avec un seuil de sensibilité de 1 fT Hz dans la gamme 10kHz–1MHz. La mesure à proximité du Soleil nécessite un magnétomètre étendant ces performances à plus haute fréquence, 100MHz idéalement. Nous présentons l’étude d’un capteur adapté dans la bande 10kHz-100MHz devant avoir le même seuil de sensibilité, pour satisfaire les besoins scientifiques sans accroître la masse et la consommation électrique, limitées à bord d’un satellite. L’état de l’art de la magnétométrie montre qu’une boucle sans noyau est la mieux adaptée. A partir de la description détaillée des constituants du capteur, l’antenne et le préamplificateur, nous modélisons sa fonction de transfert et sonseuil de sensibilité et définissons des critères d’optimisation. Nous comparons notre modèle au prototype réalisé, mesurant son impédance, sa réponse au champ magnétique et son seuil de sensibilité. L’étude de la méthode de bobinage permet de réduire les capacités parasites du transformateur torique. Nous appliquons une contre-réaction de flux pour conserver le rapport signal à bruit du capteur en boucle ouverte. L’optimisation aboutit à un instrument fonctionnant jusqu’à 30MHz et satisfaisant la spécification de seuil de sensibilité entre 700kHz et 20MHz. Il prolonge d’une décade la gamme des instruments existants

A phosphorylated zinc finger peptide bearing a gadolinium complex for zinc detection by MRI.

International audienceTwo zinc finger peptides, namely ZFQD(Ln) and ZFQE(Ln) (Ln = Tb or Gd), with an appended Ln(3+) chelate and a phosphoserine able to coordinate the Ln(3+) ion are presented. The two peptides differ by the amino acid anchorage of the chelate, either aspartate (D) or glutamate (E). Both peptides are able to bind Zn2+ and adopt the beta beta alpha fold. Interestingly, ZFQE(Tb) shows a decrease in sensitized Tb3+ luminescence upon Zn2+ binding whereas ZFQD(Tb) does not. The luminescence change upon Zn2+ binding is attributed to a change in hydration number (q) of the Tb3+ ion due to the decoordination of the phosphoserine from the Ln(3+) ion upon Zn2+ binding and peptide folding. This process is highly sensitive to the length of the linker between the Ln chelate and the peptidic backbone. The magnetic properties of the gadolinium analogue ZFQE(Gd) were studied. An impressive relaxivity increase of 140% is observed at 60 MHz and 25 degrees C upon Zn2+ binding. These changes can be attributed to a combined increase effect of the hydration number of Gd3+ and of the rigidity of the system upon Zn2+ binding. Phantom MR images at 9.4 T show a clear signal enhancement in the presence of Zn2+. These zinc finger peptides offer a unique platform to design such Zn-responsive probes

Sensitive trimodal MRI-SERRS-fluorescence detection of cancer cells with stable magneto-plasmonic nanoprobes

International audienceNovel magneto-plasmonic nanoprobes were designed for multimodal diagnosis of cancer bycombination of Magnetic Resonance Imaging (MRI), Surface-Enhanced Resonance RamanScattering (SERRS) and fluorescence emission in the very near infrared (VNIR). A controlledelectrostatic assembly of silver nanoparticles (Ag NPs), superparamagnetic iron oxidenanoparticles (SPIONs), VNIR dye Nile blue (NB) and biopolymer chitosan (Chi) was used toformulate the AgIONs-Chi nanoprobes. The formulation protocol did not involve organicsolvents, was rapid and efficient as confirmed by magnetic sorting. The SERRS response of thenanoprobes was very intense and constant for days. It decreased linearly upon 1000-fold dilutionand was still recognizable at 0.1 nM NB concentration. After 30 days storage, the SERRS losswas less than 30% and the hydrodynamic size of the AgIONs-Chi in PBS remained below200nm. The gradual decrease of the ratio SERRS/fluorescence allowed monitoring the release ofthe fluorescent molecule upon long-term nanoprobe dissociation. The AgIONs-Chi exhibitedtwo-fold higher MRI contrast than that of commercially available SPION suspensions. Finally,the nanoprobes were actively uptaken by HeLa cancer cells and ensured trimodal MRI-SERRSfluorescencedetection of 10μL cell inclusions in cm-sized agarose gels used here as phantommodels of microtumors. The above results show that the magneto-plasmonic AgIONs-Chi arepromising substrates for SERRS analysis in solution and for multimodal imaging of cancer cells

MRI and luminescence detection of Zn{2+}with a lanthanide complex-zinc finger peptide conjugate.

International audienceA bioinspired probe based on a zinc finger peptide functionalized by a lanthanide(iii)-DOTA monoamide complex turns out to be active for both luminescence and MRI detection of $Zn^{2+}$, depending on the lanthanide cation. A mechanism for MRI-based detection is proposed

Brain orchestration of pregnancy and maternal behavior in mice: A longitudinal morphometric study

International audienceReproduction induces changes within the brain to prepare for gestation and motherhood. However, the dynamic of these central changes and their relationships with the development of maternal behavior remain poorly understood. Here, we describe a longitudinal morphometric neuroimaging study in female mice between pre-gestation and weaning, using new magnetic resonance imaging (MRI) resources comprising a high-resolution brain template, its associated tissue priors (60-mu m isotropic resolution) and a corresponding mouse brain atlas (1320 regions of interest). Using these tools, we observed transient hypertrophies not only within key regions controlling gestation and maternal behavior (medial preoptic area, bed nucleus of the stria terminalis), but also in the amygdala, caudate nucleus and hippocampus. Additionally, unlike females exhibiting lower levels of maternal care, highly maternal females developed transient hypertrophies in somatosensory, entorhinal and retrosplenial cortices among other regions. Therefore, coordinated and transient brain modifications associated with maternal performance occurred during gestation and lactation

In vivo magnetic resonance microscopy of Drosophilae at 9.4 T.

International audienceIn preclinical research, genetic studies have made considerable progress as a result of the development of transgenic animal models of human diseases. Consequently, there is now a need for higher resolution MRI to provide finer details for studies of small animals (rats, mice) or very small animals (insects). One way to address this issue is to work with high-magnetic-field spectrometers (dedicated to small animal imaging) with strong magnetic field gradients. It is also necessary to develop a complete methodology (transmit/receive coil, pulse sequence, fixing system, air supply, anesthesia capabilities, etc.). In this study, we developed noninvasive protocols, both in vitro and in vivo (from coil construction to image generation), for drosophila MRI at 9.4 T. The 10 10 80-μm resolution makes it possible to visualize whole drosophila (head, thorax, abdomen) and internal organs (ovaries, longitudinal and transverse muscles, bowel, proboscis, antennae and optical lobes). We also provide some results obtained with a Drosophila model of muscle degeneration. This opens the way for new applications of structural genetic modification studies using MRI of drosophila

1H-NMR metabolomics of TIEG1 KO muscle mice

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An adult Drosophila glioma model to highlight metabolic dysfunctions and evaluate the role of the serotonin 5‐HT 7 receptor as a potential therapeutic target

International audienceAbstract Gliomas account for 50% of brain cancers and are therefore the most common brain tumors. Molecular alterations involved in adult gliomas have been identified and mainly affect tyrosine kinase receptors with amplification and/or mutation of the epidermal growth factor receptor (EGFR) and its associated signaling pathways. Several targeted therapies have been developed, but current treatments remain ineffective for glioblastomas, the most severe forms. Thus, it is a priority to identify new pharmacological targets. Drosophila glioma models established in larvae and adults are useful to identify new genes and signaling pathways involved in glioma progression. Here, we used a Drosophila glioma model in adults, to characterize metabolic disturbances associated with glioma and assess the consequences of 5‐HT 7 R expression on glioma development. First, by using in vivo magnetic resonance imaging, we have shown that expression of the constitutively active forms of EGFR and PI3K in adult glial cells induces brain enlargement. Then, we explored altered cellular metabolism by using high‐resolution magic angle spinning NMR and 1 H‐ 13 C heteronuclear single quantum coherence solution states. Discriminant metabolites identified highlight the rewiring of metabolic pathways in glioma and associated cachexia phenotypes. Finally, the expression of 5‐HT 7 R in this adult model attenuates phenotypes associated with glioma development. Collectively, this whole‐animal approach in Drosophila allowed us to provide several rapid and robust phenotype readouts, such as enlarged brain volume and glioma‐associated cachexia, as well as to determine the metabolic pathways involved in glioma genesis and finally to confirm the interest of the 5‐HT 7 R in the treatment of glioma

Direct Monitoring of Doxorubicin Release via sensitization of NIR-emitting Ytterbium Liposomes

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