Utilizing multimodal MRI to detect somatosensory stimulation in the rabbit
Magnetic resonance imaging (MRI) is a powerful tool to investigate neural processing. Utilizing animal models enables research that is difficult to perform in humans. However, some animal models require anesthesia or sedation when undergoing MRI which negatively impacts the cognitive state of the animal and the physiology underlying hemodynamic correlates of neural activity.
Activity-induced manganese-dependent MRI (AIM-MRI) is a powerful tool to track system-wide neural activity using high resolution, quantitative T1-weighted MRI in animal models. Because manganese (Mn2+) acts as a calcium analogue, AIM-MRI is more directly attributable to neuronal activation than the blood-oxygen-level dependent (BOLD) response. With AIM-MRI, Mn2+ ions enter neurons via preferentially active voltage-gated calcium channels. The more active a neuron is, the more Mn2+ will accumulate and the more the MR signal intensity will change. Once inside a neuron, Mn2+ becomes temporarily sequestered by binding to proteins and nucleic acids. Studies utilizing AIM-MRI can either be performed inside or outside of the MRI environment using still or free-moving animals since Mn2+ accumulation can be assessed via MRI at a later time representing a “snapshot” of the regions that were activated by the experimental manipulation.
Few studies have provided a systematic evaluation of the factors influencing the detection of Mn2+ such as dosage and the temporal characteristics of Mn2+ uptake. In our study, we identified an optimal dose of Mn2+ that minimized the toxic effects of Mn2+ but enabled the detection of Mn2+ accumulation in active neural regions of the rabbit. T1-weighted MRI and functional MRI were collected 0-3, 6-9, and 24-27h post-Mn2+ injection while the whiskers on the right side were vibrated. Significant BOLD activation in the left somatosensory (SS) cortex and left ventral posteromedial (VPM) thalamic nucleus was detected during whisker vibration. T1-weighted signal intensities were extracted from these regions, their corresponding contralateral regions and the visual cortex (to serve as controls). A significant elevation in T1-weighted signal intensity in the left SS cortex (relative to right) was evident 6-9 and 24-27h post-Mn2+ injection while the left VPM thalamus showed a significant enhancement (relative to the right) only during the 24-27h session. Visual cortex showed no hemispheric difference at any timepoint. Our results suggest that studies employing AIM-MRI would benefit by conducting experimental manipulations 6-24h after subcutaneous MnCl2 injections to optimize the concentration of contrast agent in the regions active during the exposure.
Activity-induced manganese-dependent MRI (AIM-MRI) and functional MRI in awake rabbits during somatosensory stimulation.
Schroeder MP, Weiss C, Procissi D, Wang L, Disterhoft JF.
Neuroimage. 2016 Feb 1