SMALL-ANIMAL REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION COMBINED WITH [~(18)F]-FDG MICROPET TO QUANTIFY THE NEUROMODULATION EFFECT IN THE RAT BRAIN

摘要

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 uPET) 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 (xPET 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 mm3 and 2.616 mm3, 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 mm3) 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 muPET 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.