Assessment of brain responses to innocuous and noxious electrical forepaw stimulation in mice using BOLD fMRI

Functional magnetic resonance imaging (fMRI) using the blood oxygen level-dependent (BOLD) contrast was used to study sensory processing in the brain of isoflurane-anesthetized mice. The use of a cryogenic surface coil in a small animal 9.4T system provided the sensitivity required for detection and quantitative analysis of hemodynamic changes caused by neural activity in the mouse brain in response to electrical forepaw stimulation at different amplitudes. A gradient echo-echo planar imaging (GE-EPI) sequence was used to acquire five coronal brain slices of 0.5 mm thickness. BOLD signal changes were observed in primary and secondary somatosensory cortices, the thalamus and the insular cortex, important regions involved in sensory and nociceptive processing. Activation was observed consistently bilateral despite unilateral stimulation of the forepaw. The temporal BOLD profile was segregated into two signal components with different temporal characteristics. The maximum BOLD amplitude of both signal components correlated strongly with the stimulation amplitude. Analysis of the dynamic behavior of the somatosensory ‘fast’ BOLD component revealed a decreasing signal decay rate constant koff with increasing maximum BOLD amplitude (and stimulation amplitude). This study demonstrates the feasibility of a robust BOLD fMRI protocol to study nociceptive processing in isoflurane-anesthetized mice. The reliability of the method allows for detailed analysis of the temporal BOLD profile and for investigation of somatosensory and noxious signal processing in the brain, which is attractive for characterizing genetically engineered mouse models.