Small-animal repetitive transcranial magnetic stimulation combined with [18F]-FDG microPET to quantify the neuromodulation effect in the rat brain

- This study combines μPET with rTMS using a custom-made small-animal TMS setup.
- Both 1-Hz and 50-Hz rTMS elicited significant [18F]-FDG uptake changes.
- The dentate gyrus and entorhinal cortex were clearly stimulated.
- High-frequency rTMS (50 Hz) had a more intense effect in a larger volume.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique for the treatment of various neurological and psychiatric disorders. To investigate the working mechanism of this treatment approach, we designed a small-animal coil for dedicated use in rats and we combined this neurostimulation method with small-animal positron emission tomography (microPET or μPET) to quantify regional 2-deoxy-2-(18F)fluoro-d-glucose ([18F]-FDG) uptake in the rat brain, elicited by a low- (1 Hz) and a high- (50 Hz) frequency paradigm. Rats (n = 6) were injected with 1 mCi of [18F]-FDG 10 min after the start of 30 min of stimulation (1 Hz, 50 Hz or sham), followed by a 20-min μPET image acquisition. Voxel-based statistical parametric mapping (SPM) image analysis of 1-Hz and 50-Hz versus sham stimulation was performed. For both the 1-Hz and 50-Hz paradigms we found a large [18F]-FDG hypermetabolic cluster (2.208 mm3 and 2.616 mm3, resp.) (analysis of variance (ANOVA), p < 0.05) located in the dentate gyrus complemented with an additional [18F]-FDG hypermetabolic cluster (ANOVA, p < 0.05) located in the entorhinal cortex (2.216 mm3) for the 50-Hz stimulation. The effect on [18F]-FDG metabolism was 2.9 ± 0.8% at 1 Hz and 2.5 ± 0.8% at 50 Hz for the dentate gyrus clusters and 3.3 ± 0.5% for the additional cluster in the entorhinal cortex at 50 Hz. The maximal (4.19 vs. 2.58) and averaged (2.87 vs. 2.21) T-values are higher for 50 Hz versus 1 Hz.This experimental study demonstrates the feasibility to combine μPET imaging in rats stimulated with rTMS using a custom-made small-animal magnetic stimulation setup to quantify changes in the cerebral [18F]-FDG uptake as a measure for neuronal activity.