The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization

Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo [Formula: see text]-weighted images (90 µm isotropic resolution) and in vivo T2-weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.This work is part of the SIGMA project with the reference FCT-ANR/NEU-OSD/0258/2012, co-financed by the French public funding agency ANR (Agence Nationale pour laRecherche, APP Blanc International II 2012), the Portuguese FCT (Fundação para aCiência e Tecnologia) and the Portuguese North Regional Operational Program (ON.2—O Novo Norte) under the National Strategic Reference Framework (QREN), through theEuropean Regional Development Fund (FEDER) as well as the Projecto Estratégico co-funded by FCT (PEst-C/SAU/LA0026-/2013) and the European Regional DevelopmentFund COMPETE (FCOMP-01-0124-FEDER-037298). D.A.B. and A.N. were funded bygrants from FCT-ANR/NEU-OSD/0258/2012. R.M. was supported by the FCT fellow-ship grant with the reference PDE/BDE/113604/2015 from the PhDiHES program. A.C.was supported by a grant from the foundation NRJ. P.M. was funded by FundaçãoCalouste Gulbenkian (Portugal;‘Better mental health during ageing based on temporalprediction of individual brain ageing trajectories TEMPO’) with Grant Number P-139977. France Life Imaging is acknowledged for its support in funding the NeuroSpinplatform of preclinical MRI scanners. The authors also acknowledge and thank EdwardGanz, MD, for proof reading our work

The dynamics of stress: a longitudinal MRI study of rat brain structure and connectome

Stress is a well-established trigger for a number of neuropsychiatric disorders, as it alters both structure and function of several brain regions and its networks. Herein, we conduct a longitudinal neuroimaging study to assess how a chronic unpredictable stress protocol impacts the structure of the rat brain and its functional connectome in both high and low responders to stress. Our results reveal the changes that stress triggers in the brain, with structural atrophy affecting key regions such as the prelimbic, cingulate, insular and retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices, the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed nucleus of the stria terminalis, the thalamus and several brain stem nuclei. These structural changes are associated with increasing functional connectivity within a network composed by these regions. Moreover, using a clustering based on endocrine and behavioural outcomes, animals were classified as high and low responders to stress. We reveal that susceptible animals (high responders) develop local atrophy of the ventral tegmental area and an increase in functional connectivity between this area and the thalamus, further spreading to other areas that link the cognitive system with the fight-or-flight system. Through a longitudinal approach we were able to establish two distinct patterns, with functional changes occurring during the exposure to stress, but with an inflection point after the first week of stress when more prominent changes were seen. Finally, our study revealed differences in functional connectivity in a brainstem-limbic network that distinguishes resistant and susceptible responders before any exposure to stress, providing the first potential imaging-based predictive biomarkers of an individual's resilience/vulnerability to stressful conditions.This work is part of the Sigma project with the reference FCT-ANR/NEU-OSD/ 0258/2012 co-financed by the French public funding agency ANR (Agence National pour la Recherche, APP Blanc International II 2012), the Portuguese FCT (Fundação para a Ciência e Tecnologia) and by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER) as well as the Projecto Estratégico co-funded by FCT (PEst-C/SAU/LA0026-/2013) and the European Regional Development Fund COMPETE (FCOMP-01-0124-FEDER-037298). DAB and AN were funded by grants from FCT-ANR/NEU-OSD/0258/2012. RM is supported by the FCT fellowship grant with the reference PDE/BDE/113604/2015 from the PhDiHES program; AC was supported by a grant from the foundation NRJ. PM was funded by Fundação Calouste Gulbenkian (Portugal; ‘Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)’), Grant Number P-139977. We thank Drs Patrício Costa and Pedro Moreira for support on the various statistical analyses.info:eu-repo/semantics/publishedVersio

Characterization of long-term cerebral alterations in a mouse model of in utero high dose irradiation using anatomical and diffusion MRI

CERVOXY COLLInternational audienc

MRI characterization of long-term brain damage induced by low dose

CERVOXYInternational audienc

Noninvasive Assessment of Neurodevelopmental Disorders after In Utero Irradiation in Mice: An In Vivo Anatomical and Diffusion MRI Study

CERVOXYInternational audienceIn utero exposure to ionizing radiation can lead to cerebral alterations during adulthood. Using anatomical magnetic resonance imaging (MRI), it is possible to assess radiation-induced structural brain damage noninvasively. However, little is currently known about microstructure alterations in brain tissue. Therefore, the goal of this study was to establish, based on an original and robust pipeline of MRI image analysis, whether the long-term effects of in utero radiation exposure on brain tissue microstructure could be detected noninvasively. Pregnant C57BL/6N mice received a single dose of 1 Gy on gestation day 14.5, which led to behavioral impairments in adults. At 3 months old, in vivo MRI data were acquired from in utero irradiated and nonirradiated male mice. An MRI protocol was designed to assess the effects of radiation on the parameters of brain volume, non-Gaussian diffusion (ADC0, kurtosis and signature index) and anisotropic diffusion (fractional anisotropy and mean, axial, radial diffusivities and anisotropic signature index) in 10 key cerebral structures defined using an in-house atlas of the mouse brain. Based on the relative amplitude of these anatomical and microstructural changes, maps of the radiosensitivity of the brain to in utero irradiation were created. We observed microcephaly in irradiated mice with noticeably larger volume changes in the cortex and the corpus callosum. We also observed significantly lower ADC0, anisotropy fraction (sFA), radial diffusivity (sRD), as well as signature index (S-index and SI3) values, which are original markers sensitive to tissue microstructure alterations. All these changes together are in favor of a decreased cellular "imprint" and in some regions a reduced density in myelinated axons. A reduction in the number and complexity of myelinated axons was further revealed by myelin basic protein immunostaining. Combining anatomical and diffusion MRI is a promising approach to noninvasively investigate the radiosensitivity of local brain areas in adult mice after in utero irradiation in terms of microstructure

MRI characterization of long-term cerebral alterations in a NHEJ deficient mouse model following low dose irradiation at the juvenile stage

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Multimodal neuroimaging provides a highly consistent picture of energy metabolism, validating 31P MRS for measuring brain ATP synthesis

International audienceNeuroimaging methods have considerably developed over the last decades and offer various noninvasive approaches for measuring cerebral metabolic fluxes connected to energy metabolism, including PET and magnetic resonance spectroscopy (MRS). Among these methods, 31 P MRS has the particularity and advantage to directly measure cerebral ATP synthesis without injection of labeled precursor. However, this approach is methodologically challenging, and further validation studies are required to establish 31 P MRS as a robust method to measure brain energy synthesis. In the present study, we performed a multimodal imaging study based on the combination of 3 neuroimaging techniques, which allowed us to obtain an integrated picture of brain energy metabolism and, at the same time, to validate the saturation transfer 31 P MRS method as a quantitative measurement of brain ATP synthesis. A total of 29 imaging sessions were conducted to measure glucose consumption (CMRglc), TCA cycle flux (VTCA), and the rate of ATP synthesis (VATP) in primate monkeys by using 18 F-FDG PET scan, indirect 13 C MRS, and saturation transfer 31 P MRS, respectively. These 3 complementary measurements were performed within the exact same area of the brain under identical physiological conditions, leading to: CMRglc ‫؍‬ 0.27 ؎ 0.07 mol⅐g ؊1 ⅐min ؊1 , VTCA ‫؍‬ 0.63 ؎ 0.12 mol⅐g ؊1 ⅐min ؊1 , and VATP ‫؍‬ 7.8 ؎ 2.3 mol⅐g ؊1 ⅐min ؊1. The consistency of these 3 fluxes with literature and, more interestingly, one with each other, demonstrates the robustness of saturation transfer 31 P MRS for directly evaluating ATP synthesis in the living brain