Influence of the pressure field distribution in Transcranial ultrasonic neurostimulation
Résumé
In this study, 37 ultrasonic neurostimulation sessions were achieved in rats (N=8) using a 320 kHz transducer. The corresponding beam profile in the entire head was simulated in order to investigate the in situ pressure and intensity level as well as the spatial pressure distribution, thanks to a rat micro-computed tomography scan (CT)-based 3D finite differences time domain solver. Results: Ultrasound pulse evoked a motor response in more than 60% of the experimental sessions. In those sessions, the stimulation was always present, repeatable with a pressure threshold under which no motor response occurred. This average acoustic pressure threshold was found to be 0.68 ± 0.1 MPa (corresponding mechanical index, MI =1.2 and spatial peak, pulse averaged intensity, Isppa = 7.5 W.cm -2 ), as calibrated in free water. A slight variation was observed between deep anesthesia stage (0.77 ± 0.04 MPa) and light anesthesia stage (0.61 ± 0.03 MPa), assessed from the pedal reflex. Several kinds of motor responses were observed: movements of the tail, the hind legs, the forelimbs, the eye and even a single whisker were induced separately. Numerical simulations of an equivalent experiment with identical acoustic parameters showed that the acoustic field was spread over the whole rat brain with the presence of several secondary pressure peaks. Due to reverberations, a 1.8-fold increase of the spatial peak, temporal peak acoustic pressure (Psptp) (± .4 standard deviation), a 3.6-fold increase (± 1.8) for the spatial peak, temporal peak acoustic intensity (Isptp), and 2.3 for the spatial peak, pulse averaged acoustic intensity (Isppa), were found compared to simulations of the beam in free water. Applying such corrections due to reverberations on the experimental results would yield a higher estimation for the average acoustic pressure threshold for motor neurostimulation at 320 KHz at 1.2± 0.3 MPa (MI=2.2±0.5 and Isppa=17.5 ± 7.5 W.cm -2 ). Conclusions: Transcranial ultrasonic stimulation is pressure-and anesthesia-dependent in the rat model. Numerical simulations have shown that the acoustic pattern can be complex inside the rat head and that special care must be taken for small animal studies relating acoustic parameters to neurostimulation effects, especially at a low frequency.
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