Activity-induced manganese-dependent MRI (AIM-MRI) and functional MRI in awake rabbits during somatosensory stimulation

- First study of Mn2 +-related efficacy, toxicology, and T1W enhancement in rabbits
- Right whisker vibration induces BOLD activation in left somatosensory pathway.
- These regions preferentially accumulate Mn2 + compared to contralateral counterparts.
- Without BBB disruption, Mn2 + accumulation depends on spatial location of regions.

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 and has significant advantages for investigating neural activity over other modalities including BOLD fMRI. With AIM-MRI, Mn2+ ions enter neurons via voltage-gated calcium channels preferentially active during the time of experimental exposure. A broad range of AIM-MRI studies using different species studying different phenomena have been performed, but few of these studies provide a systematic evaluation of the factors influencing the detection of Mn2+ such as dosage and the temporal characteristics of Mn2 + uptake.We identified an optimal dose of Mn2+ (25 mg/kg, s.c.) in order to characterize the time-course of Mn2+ accumulation in active neural regions in the rabbit. T1-weighted MRI and functional MRI were collected 0-3, 6-9, and 24-27 h post-Mn2+ injection while the vibrissae 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 24-27 h post-Mn2+ injection while the left VPM thalamus showed a significant enhancement (relative to the right) only during the 24-27 h session. Visual cortex showed no hemispheric difference at any timepoint. Our results suggest that studies employing AIM-MRI would benefit by conducting experimental manipulations 6-24 h after subcutaneous MnCl2 injections to optimize the concentration of contrast agent in the regions active during the exposure.