CRCNS: Crossbeam Transcranial Ultrasound Technology to Stimulate the Deep Brain

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SUMMARY Numerous neuroscience and clinical applications exist for a noninvasive neuromodulation technology that can reach deep in the brain with high resolution. One compelling clinical application is the treatment of drug addiction, a major public health challenge in the US. In humans, the neural targets for treatment are 1-4 mm3, and thus a critical goal is to stimulate deep in the brain with higher resolutions than currently available with any noninvasive stimulation modality. The goal of this research is the development and experimental validation of computational models for optimization of high resolution deep brain transcranial ultrasound stimulation (TUS) for neuroscience and clinical application. Noninvasive transcranial ultrasound stimulation has been shown to be safe and spatially specific in various animal models. However, current systems are not optimized for high resolution TUS of the deep brain. Computational modeling suggests we can optimize TUS with phased array systems that can be driven in pairs while oriented at 90° to each other and focused to the same point, called “crossbeam.” This improves the stimulation resolution by more than an order of magnitude. In addition, our modeling suggests that we can selectively stimulate neural tissue using a “pinch” or “stretch.” In this project, we will perform a biological validation of crossbeam’s improved effectiveness due to the neural tissue’s sensitivity to “pinch” or “stretch.” Our validated modeling will be used to refine a crossbeam neurostimulation strategy involving optimized array probes. This will allow not only choice of focal depth, but also compensation of phase aberrations resulting from the propagation through the skull bone. The optimized hardware and the developed computational models will be integrated with imaging guidance and validated in skull phantom experiments. RELEVANCE (See instructions): We are developing the technology for improving health through the noninvasive treatment of neurological disorders such as addiction.