White matter changes in microstructure associated with a maladaptive response to stress in rats.

In today's society, every individual is subjected to stressful stimuli with different intensities and duration. This exposure can be a key trigger in several mental illnesses greatly affecting one's quality of life. Yet not all subjects respond equally to the same stimulus and some are able to better adapt to them delaying the onset of its negative consequences. The neural specificities of this adaptation can be essential to understand the true dynamics of stress as well as to design new approaches to reduce its consequences. In the current work, we employed ex vivo high field diffusion magnetic resonance imaging (MRI) to uncover the differences in white matter properties in the entire brain between Fisher 344 (F344) and Sprague-Dawley (SD) rats, known to present different responses to stress, and to examine the effects of a 2-week repeated inescapable stress paradigm. We applied a tract-based spatial statistics (TBSS) analysis approach to a total of 25 animals. After exposure to stress, SD rats were found to have lower values of corticosterone when compared with F344 rats. Overall, stress was found to lead to an overall increase in fractional anisotropy (FA), on top of a reduction in mean and radial diffusivity (MD and RD) in several white matter bundles of the brain. No effect of strain on the white matter diffusion properties was observed. The strain-by-stress interaction revealed an effect on SD rats in MD, RD and axial diffusivity (AD), with lower diffusion metric levels on stressed animals. These effects were localized on the left side of the brain on the external capsule, corpus callosum, deep cerebral white matter, anterior commissure, endopiriform nucleus, dorsal hippocampus and amygdala fibers. The results possibly reveal an adaptation of the SD strain to the stressful stimuli through synaptic and structural plasticity processes, possibly reflecting learning processes.

Hyper-responsivity to stress in rats is associated with a large increase in amygdala volume. A 7T MRI study.

Stress is known to precipitate psychiatric disorders in vulnerable people. Individual differences in the stress responsivity can dramatically affect the onset of these illnesses. Animal models of repeated stress represent valuable tools to identify region-specific volumetric changes in the brain. Here, using high resolution 7T MRI, we found that amygdala is the most significant parameter for distinction between F344 and SD rats known to have differential response to stress. A significant substantial increase (45%) was found in the amygdala volume of rats that do not habituate to the repeated stress procedure (F344 rats) compared to SD rats. This strain-specific effect of stress was evidenced by a significant strain-by-stress interaction. There were no significant strain differences in the volumes of hippocampi and prefrontal cortices though stress produces significant reductions of smaller amplitude in the medial prefrontal cortex (mPFC) (9% and 12%) and dorsal hippocampus (5% and 6%) in both strains. Our data further demonstrate the feasibility and relevance of high isotropic resolution structural ex vivo 7T MRI in the study of the brain effects of stress in small animals. Neuroimaging is a valuable tool to follow up brain volumetric reorganization during the stress response and could also be easily used to test pharmacological interventions to prevent the deleterious effects of stress.

Hindered diffusion of MRI contrast agents in rat brain extracellular micro-environment assessed by acquisition of dynamic T1 and T2 maps.

The knowledge of brain tissues characteristics (such as extracellular space and tortuosity) represents valuable information for the design of optimal MR probes for specific biomarkers targeting. This work proposes a methodology based on dynamic acquisition of relaxation time maps to quantify in vivo MRI contrast agent concentration after intra-cerebral injection in rat brain. It was applied to estimate the hindered diffusion in brain tissues of five contrast agents with different hydrodynamic diameters (Dotarem(®) ≈ 1 nm, P846 ≈ 4 nm, P792 ≈ 7 nm, P904 ≈ 22 nm and Gd-based emulsion ≈ 170 nm). In vivo apparent diffusion coefficients were compared with those estimated in an obstacle-free medium to determine brain extracellular space and tortuosity. At a 2 h imaging timescale, all contrast agents except the Gd-based emulsion exhibited significant diffusion through brain tissues, with characteristic times compatible with MR molecular imaging (<70 min to diffuse between two capillaries). In conclusion, our experiments indicate that MRI contrast agents with sizes up to 22 nm can be used to perform molecular imaging on intra-cerebral biomarkers. Our quantification methodology allows a precise estimation of apparent diffusion coefficients, which is helpful to calibrate optimal timing between contrast agent injection and MRI observation for molecular imaging studies.

Implanted, inductively-coupled, radiofrequency coils fabricated on flexible polymeric material: application to in vivo rat brain MRI at 7 T.

Combined with high-field MRI scanners, small implanted coils allow for high resolution imaging with locally improved SNR, as compared to external coils. Small flexible implantable coils dedicated to in vivo MRI of the rat brain at 7 T were developed. Based on the Multi-turn Transmission Line Resonator design, they were fabricated with a Teflon substrate using copper micromolding process and a specific metal-polymer adhesion treatment. The implanted coils were made biocompatible by PolyDimethylSiloxane (PDMS) encapsulation. The use of low loss tangent material achieves low dielectric losses within the substrate and the use of the PDMS layer reduces the parasitic coupling with the surrounding media. An implanted coil was implemented in a 7 T MRI system using inductive coupling and a dedicated external pick-up coil for signal transmission. In vivo images of the rat brain acquired with in plane resolution of (150 µm)(2) thanks to the implanted coil revealed high SNR near the coil, allowing for the visualization of fine cerebral structures.