In vivo diffusion tensor mapping of the brain of squirrel monkey, rat, and mouse using single-shot STEAM MRI.

The purpose was to assess the potential of half Fourier diffusion-weighted single-shot STEAM MRI for diffusion tensor mapping of animal brain in vivo. A STEAM sequence with image acquisition times of about 500 ms was implemented at 2.35 T using six gradient orientations and b values of 200, 700, and 1200 s mm(-2). The use of half Fourier phase-encoding increased the signal-to-noise ratio by 45% relative to full Fourier acquisitions. Moreover, STEAM-derived maps of the relative anisotropy and main diffusion direction were completely free of susceptibility-induced signal losses and geometric distortions. Within measuring times of 3 h, the achieved resolution varied from 600x700x1000 microm3 for squirrel monkeys to 140x280x720 microm3 for mice. While in monkeys the accessible white matter fiber connections were comparable to those reported for humans, detectable fiber structures in mice focused on the corpus callosum, anterior commissure, and hippocampal fimbria. In conclusion diffusion-weighted single-shot STEAM MRI allows for in vivo diffusion tensor mapping of the brain of squirrel monkeys, rats, and mice without motion artifacts and susceptibility distortions.

Magnetization transfer MRI of mouse brain reveals areas of high neural density.

Extending applications of magnetization transfer contrast (MTC) in magnetic resonance imaging (MRI) of the human central nervous system, this work quantitatively describes MTC of the murine brain. As a novel finding, complementing T(1)- and T(2)-weighted MRI, MTC allows for the distinction of densely packed gray matter from normal gray and white matter. Examples include the Purkinje cell layer and the granular cell layer in the mouse cerebellum as well as the delineation of the CA3 subfield of the hippocampus relative to surrounding hippocampal gray matter and white matter tracts such as the hippocampal fimbria. Using a kainate lesion model, the CA3 hyperintensities in MTC and T(1)-weighted MRI are assigned to the densely packed somata of pyramidal cells.

Substance P receptor antagonist and clomipramine prevent stress-induced alterations in cerebral metabolites, cytogenesis in the dentate gyrus and hippocampal volume.

The neuropeptide substance P and its receptor, the neurokinin 1 receptor (NK(1)R) have been proposed as possible targets for new antidepressant therapies. The present study investigated the effect of the NK(1)R antagonist L-760,735 and the tricyclic antidepressant clomipramine in the chronic psychosocial stress paradigm of adult male tree shrews. Animals were subjected to a 7-day period of psychosocial stress before the onset of daily oral administration of L-760,735 (10 mg kg(-1) day(-1)) or clomipramine (50 mg kg(-1) day(-1)). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy. Cell proliferation in the dentate gyrus and hippocampal volume were measured post mortem. Stress significantly decreased in vivo concentrations of N-acetyl-aspartate (-14%), creatine and phosphocreatine (-15%) and choline-containing compounds (-15%). The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (-45%), and hippocampal volume was decreased (-14%). The stress-induced changes of brain metabolites, hippocampal volume and dentate cytogenesis rate were prevented by concomitant drug administration. Elevated myo-inositol concentrations after both treatments hint to an astrocytic enhancement. These results suggest that-despite a different pharmacological profile-the NK(1)R antagonist L-760,735, a member of a novel class of antidepressant drugs, has comparable neurobiological efficacy to tricyclic antidepressants such as clomipramine.

High-resolution 3D MRI of mouse brain reveals small cerebral structures in vivo.

This work demonstrates technical approaches to high-quality magnetic resonance imaging (MRI) of small structures of the mouse brain in vivo. It turns out that excellent soft-tissue contrast requires the reduction of partial volume effects by using 3D MRI at high (isotropic) resolution with linear voxel dimensions of about 100-150 microm. The long T(2)* relaxation times at relatively low magnetic fields (2.35 T) offer the benefit of a small receiver bandwidth (increased signal-to-noise) at a moderate echo time which together with the small voxel size avoids visual susceptibility artifacts. For measuring times of 1-1.5 h both T(1)-weighted (FLASH) and T(2)-weighted (Fast Spin-Echo) 3D MRI acquisitions exhibit detailed anatomical insights in accordance with histological sections from a mouse brain atlas. Preliminary applications address the identification of neuroanatomical variations in different mouse strains and the use of Mn(2+) as a T(1) contrast agent for neuroaxonal tracing of fiber tracts within the mouse visual pathway.