Focused ultrasound for vagus nerve stimulation

 

Other than electrical stimulation, focused ultrasound stimulation (FUS) has also shown potential in targeting specific neural tissue within a larger neural mass, including tissue deeper in the nerve structure. FUS thanks its spatial selectivity to the short wavelength of ultrasound in biological tissue. In ideal circumstances, FUS can achieve a spatial resolution in the order of cubic millimetres in tissue. The inherent focusing ability of ultrasound also simplifies the stimulator design compared to electrical stimulation. Ultrasound has the potential to stimulate the vagus nerve distally and non-invasively while maintaining focality (e.g., transcutaneously through the neck, Fig. 1 left).

 

The goal of this PhD research is to design a FUS system for spatially selective activation of the vagus nerve. The focus is on two usage scenarios: non-invasive transcutaneous FUS (Fig. 1 left) and minimally invasive FUS that places the transducer directly on the vagus nerve (Fig. 1 right). FUS has been rediscovered in the past 15 years and has enjoyed much attention from researchers. Despite this, the mechanisms of action of FUS are still not well-understood. For this reason, this PhD focuses on fundamental research including simulations of FUS biophysics and validation in experimental in-vitro/in-vivo setups. The first subobjective is to build extensive validated knowledge of the biophysics of FUS for VNS. The second subobjective is to formulate the requirements of a prototype FUS system for VNS, focusing on steerability of the stimulation target and low complexity of implementation.

 

In the first phase of the project, the PhD candidate performs numerical simulations of the acoustic pressure and particle velocity fields induced in the vagus nerve by a FUS transducer or transducer array. Both non-invasive (transcutaneous) and minimally invasive (transducer(s) on the vagus nerve) usage scenarios are considered. The goal is to design a transducer system of which the pressure focal point is aligned with the stimulation target. In the second phase, the field simulations are combined with simulations of the electro-mechanical neuron coupling and vagus nerve fibre response. In-silico optimization of the FUS focal spot and stimulation waveform is performed to maximize fibre recruitment. Of note is that the optimal FUS focal spot is not necessarily located on the cervical vagus nerve in the neck as in Fig. 1, left. There are indications that the vagus nerve branches in the abdominal cavity may be more sensitive to FUS than the cervical branch, explained by the larger presence of mechanosensitive ion channels in the former. In the third phase, the optimized design is experimentally validated in phantom models, living tissue and optionally animals. The project end result is a comprehensive set of requirements for a (pre)clinical FUS system for VNS. The end result should pave the way for a future prototype hardware realization of vagus nerve FUS.

 

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