MRI Techniques and New Animal Models for Imaging the Brain

Chapitre 10absen

Toward a better understanding of the effects of endocrine disrupting compounds on health : Human-relevant case studies from sheep models

The 3 case studies reviewed in this article were supported by funders including: SRF Academic Scholarship Award 2013, the Wellcome Trust (080388), the European Community’s Seventh Framework Programme under grant agreement no 212885 and French Region Midi-Pyrénées [31000642] the French National Research Program for Environmental and Occupational Health of Anses [grant number 2015/1/112, 2015] and the French National Research Agency [ANR-13-CESA0007-1].Peer reviewedPostprin

Optimization of sample preparation for MRI of formaldehyde-fixed brains

International audienceMagnetic resonance imaging of post-mortem brains allows long acquisition times up to several days and can be used to obtain high-resolution images at high field (7 T) which can be readily correlated with histological examination of the tissue. However, death and formaldehyde fixation are known to modify severely the relaxivity and diffusion properties of brain tissue. In particular, formaldehyde is known to shorten T2, which drastically reduces SNR.In order to counteract this effect and recover better SNR, free fixative can be washed out by soaking the sample in isotonic saline solution. This has been demonstrated in small biopsy-sized tissue samples, but little data is available concerning whole brain specimens.This study was designed to describe the kinetics of the change of relaxivity and diffusion properties of whole brain specimen at 7 T, during fixation, and during soaking in saline solution, in order to determine optimal soaking times.In the ewe brain, the fixation was found to stabilize after approximately 8 weeks, and the optimal duration of saline soaking is found to be around 3 weeks. These durations can be expected to be longer for larger specimen, such as human brains, which require longer penetration times

2.5D Representations Combining in vivo 3D MRI and ex vivo 2D MSI Approaches to Study the Lipid Distribution in the Whole Sheep Brain

National audienceMass Spectrometry Imaging (MSI) provides easily high spatially resolved masses allowing characterization of endogenous lipids. These latter constitute about 70% of the composition of the white matter of the brain which can be implicated in developmental and/or cognitive troubles. In order to examine the molecular distribution of lipids in whole sheep brain, and especially in white/grey matter, we combined in vivo and ex vivo images, obtained in the same animals, using Magnetic Resonance Imaging (MRI) and MSI, respectively. In order to view the topology of the molecular species within the organ, we propose the construction of a 2.5 D representation where a single section imaged with 2D MSI is localized within the tissue volume obtained by 3D MRI. 3D T1-weighted MPRAGE images were acquired on two anesthetized sheep with a 3 Tesla MRI (Siemens, Verio ®). The parameters of acquisition for the MPRAGE were: TR 2500ms, TE 3.2ms, FA 12, NEX 1, matrix 384×384, FOV 192mm, 288 slices with a thickness of 0.5mm. In order to improve data quality, the 3D MRI volumes have been pre-processed using in-house algorithms using volume fitting and Markov random field methods. T1 3D planes corresponding to MSI planes were reconstructed using Osirix imaging software.Brains were collected after sacrifice and frozen at -80°C. Frontal and sagittal 14 µm brain sections were performed with a cryostat adapted to large sections (CM3050 S, Leica) and mounted onto conductive ITO-coated slides. The spray of α-cyano-4-hydroxycinnamic acid matrix was performed using an Image Prep device (Bruker). Spectra were acquired using an UltrafleXtrem MALDI-TOF instrument (Bruker) in the 200–1200 m/z range with a spatial resolution set at 125 µm. Raw spectra were analyzed with SCiLS Lab software to generate 2D ion density maps and segmentation maps (data partitioning). The tissue sections analyzed by MSI were stained with cresyl violet to manually delimitate neuronal nuclei and areas. This histological map was used to delineate the MRI and MSI 2D views and overlay them regardless the same brain areas used as fiducials. After, a 2.5 D representation was proposed to visualize the lipid distribution within the entire organ.In conclusion, in this study, frontal and sagittal whole sheep brain sections analyzed by MSI showed a clear difference in lipid distribution between different compartments of brain tissues, especially between grey and white matter, until the cerebral envelopment presenting circumvolution. Furthermore, the alignment of 2D MALDI-imaging with T1-weighted images showed that MSI can provide finer details on the structural connectivity of myelinated fiber tracts. Here, the 2.5 D representation combining MRI and MSI was presented as an alternative approach to 3D anatomical and molecular atlas providing a perfect topology of the molecular species within an organ. For the moment, 3D MSI of whole sheep brain is a challenge, while the 2.5 D construction demonstrated to be a capable tool for exploring molecular distributions throughout sample volumes.Nowadays, the reported results may serve as a starting point for further experiments associating MSI and dynamic and functional MRI, especially for the characterization of brain

Impact of early experience on brain development and cognition in lambs

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From emotion to affective state. Is there a theoretical framework for studying animal mental health?

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Comment parler d'expérimentation animale au grand public?

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Sheep brain atlases project

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