Small-animal Repetitive Transcranial Magnetic Stimulation Combined with [¹⁸F]-FDG MicroPET to Quantify the Neuromodulation Effect in the Rat Brain

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-((18)F)fluoro-d-glucose ([(18)F]-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 [(18)F]-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 [(18)F]-FDG hypermetabolic cluster (2.208 mm(3) and 2.616 mm(3), resp.) (analysis of variance (ANOVA), p<0.05) located in the dentate gyrus complemented with an additional [(18)F]-FDG hypermetabolic cluster (ANOVA, p<0.05) located in the entorhinal cortex (2.216 mm(3)) for the 50-Hz stimulation. The effect on [(18)F]-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 [(18)F]-FDG uptake as a measure for neuronal activity.