Functional MRI of the rodent somatosensory pathway using multislice echo planar imaging

Abstract

A multislice EPI sequence was used to obtain functional MR images of the entire rat brain with BOLD contrast at 11.7 T. Ten to 11 slices covering the rat brain, with an in-plane resolution of 300 m, provided enough sensitivity to detect activation in brain regions known to be involved in the somatosensory pathway during stimulation of the forelimbs. These regions were identified by warping a digitized rat brain atlas to each set of images. Data analysis was constrained to four major areas of the somatosensory pathway: primary and secondary somatosensory cortices, thalamus, and cerebellum. Incidence maps were generated. Electrical stimulation at 3 Hz led to significant activation in the primary sensory cortex in all rats. Activation in the secondary sensory cortex and cerebellum was observed in 70% of the studies, while thalamic activation was observed in 40%. The amplitude of activation was measured for each area, and average response time courses were calculated. Finally, the frequency dependence of the response to forepaw stimulation was measured in each of the activated areas. Optimal activation occurred in all areas at 3 Hz. These results demonstrate that whole-brain fMRI can be performed on rodents at 11.7 T to probe a well-defined neural network.

Stimulus frequency dependence of blood oxygenation level-dependent functional magnetic resonance imaging signals in the somatosensory cortex of rats

“…On the other hand, studies conducted by using the spin-echo EPI sequence (Huttunen et al, 2008;Keilholz et al, 2004) showed that the BOLD signal measured at 4.7 and 11.7 T peaked at 3 Hz during the forepaw stimulation (30 to 45-s duration). These results and ours using the spin-echo sequence contradict those using the gradient-echo sequence (Gyngell et al, 1996;Brinker et al, 1999).…”

“…A large number of studies have been conducted by using electrical stimulations on the rat somatosensory model by using the blood oxygenation level-dependent (BOLD) fMRI (Brinker et al, 1999;Gyngell et al, 1996;Huttunen et al, 2008;Keilholz et al, 2004;Kida et al, 2001;Ogawa et al, 2000;Van Camp et al, 2006), laser Doppler flowmetry (LDF) (Ances et al, 1999;Detre et al, 1998;Matsuura and Kanno, 2001;Ngai et al, 1999;Ureshi et al, 2004), and optical imaging (Sheth et al, 2004;. Since BOLD signals correlate with the deoxygenated hemoglobin content (Ogawa et al, 1990), the stimulus frequency dependence of BOLD signals should correspond to the deoxygenated hemoglobin content assessed by optical imaging, and a similar dependence is expected with regard to changes in the cerebral blood flow (CBF) (Hoge et al, 1999;Kida et al, 2000;Silva et al, 2000).…”

“…This discrepancy in the results of stimulation is probably because of the difference in the stimulus durations. In the studies that employed rat somatosensory models, the stimulus duration in LDF techniques was relatively short (2-5 s) (Ances et al, 1999;Detre et al, 1998;Matsuura and Kanno, 2001;Ureshi et al, 2004), whereas that in BOLD fMRI techniques was relatively long (several tens of seconds) (Brinker et al, 1999;Gyngell et al, 1996;Huttunen et al, 2008;Keilholz et al, 2004;Kida et al, 2001;Van Camp et al, 2006). However, no fMRI studies have investigated the stimulus frequency dependence for short stimulus durations in order to compare the results obtained using the fMRI and LDF techniques in the rat somatosensory model.…”

BOLD fMRI and somatosensory evoked potentials are well correlated over a broad range of frequency content of somatosensory stimulation of the rat forepaw

“…For example, a number of studies have optimized stimulation protocols for the model of electrical somatosensory stimulation of a rat paw. Typically, the amplitude, repetition rate of short current pulses and the duration of the train of pulses have been varied (Leniger-Follert and Hossman, 1979;Gyndell et al, 1996;Brinker et al, 1999;Silva et al, 1999;Ogawa et al, 2000;Keilholz et al, 2004). Using this paradigm, short pulses of a few hundred microseconds of a few mAmp current and repetition rates of 3-5 Hz elicit the maximum evoked SEP and fMRI responses.…”

“…Using this paradigm, short pulses of a few hundred microseconds of a few mAmp current and repetition rates of 3-5 Hz elicit the maximum evoked SEP and fMRI responses. The low repetition rates that maximize the response of the paw somatosensory cortex are assumed to be due to refractory phenomena, when a stimulus reduces the response to the subsequent stimulus, and a train of activations occurring at too high a repetition rate cannot sustain maximum effects (Brinker et al, 1999;Ogawa et al, 2000;Keilholz et al, 2004).…”