Echo-planar BOLD fMRI of mice on a narrow-bore 9.4 T magnet

Abstract

The feasibility of BOLD fMRI in association with electrical somatosensory stimulation on spontaneously breathing, isoflurane-anesthetized mice was investigated using spin-echo, echo-planar imaging (EPI) on a vertical narrow-bore 9.4 T magnet. Three experiments were performed to derive an optimal fMRI protocol. In Experiment 1 (n = 9), spin-echo BOLD responses to 10% CO2 challenge under graded isoflurane (0.25-1.25%) ranged from 10 +/- 2% to 3.5 +/- 0.9%; the optimal BOLD contrast-to-noise ratio peaked at 0.75% isoflurane. In Experiment 2 (n = 6), hindpaw somatosensory stimulations using 1-7 mA under 0.75% isoflurane revealed the optimal BOLD response was at 6 mA. In Experiment 3 (n = 5), BOLD responses to 4 and 6 mA stimulation under 0.75% and 1% isoflurane were evaluated in detail, confirming the optimal conditions in Experiment 2. These results demonstrated that BOLD fMRI using single-shot, spin-echo EPI in a mouse somatosensory stimulation model could be routinely performed on high-field, vertical, narrow-bore magnets. This protocol might prove useful for fMRI studies of transgenic mice.

FIG. 1

Animal holder with stereotaxic headset, RF probe, and monitoring sensors. a: Rectal probe; b: respiratory belt (sensor underneath the animal); c: shoulder bar (a hollow tube); d: stereotaxic headset; e: RF probe. The tooth bar, not visible, is located below the RF probe platform. Warm water tube and air tube run below the animal's body.

FIG. 2

a: Representative single-shot, spin-echo EPI images. b: BOLD time courses from a spontaneously breathing mouse under graded isoflurane levels. c: Group-average BOLD percent changes and CNR under graded isoflurane levels (mean ± SEM, n = 9, Experiment 1).

FIG. 3

a: Representative activation maps (overlaid on anatomy) obtained with 6 mA stimulation under 0.75% isoflurane. Activations are localized to the contralateral primary hindpaw somatosensory cortex. Scale bar indicates cross-correlation coefficient from 0.4–0.8. b: Representative BOLD time courses at selected graded stimulation currents under 0.75% isoflurane. c: Group-average BOLD percent changes at graded stimulation currents under 0.75% isoflurane (mean ± SEM, n = 6, Experiment 2).