On-demand Transcranial Focused Ultrasound Neuromodulation in Awake Animals

University Of Minnesota, Minneapolis MN

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Abstract

Abstract: The long-term goal of this research is to develop wearable ultrasound neuromodulation devices capable of de- livering and real-time monitoring of transcranial focused ultrasound (tFUS) to speci?ed brain circuits on demand. Compared to well established neuromodulation methods such as TMS and tCDS, tFUS offers the advantage of producing spatially precise neural inhibition/stimulation while being noninvasive. Furthermore, it appears to be non disease speci?c, which means it has the potential for being used in a wide range of treatments. Recently, we have demonstrated several potential advantages of dual-mode ultrasound array (DMUA) technology in the guidance, monitoring and delivery of tFUS in vivo rodent models. DMUAs utilize the same array elements for delivering the tFUS neuromodulation and imaging the mechanical and/or thermal tissue response with high spatial and temporal resolutions. In particular, we have shown that low-intensity tFUS reversibly inhibits neural activity and robustly suppresses somatosensory evoked potential (SSEP) when ventral posterolateral nucleus of the tha- lamus (VPL) is targeted. Furthermore, results have shown the SSEP suppression and recovery correlate directly with the application and cessation of tFUS for repeated exposures of approximately 2 minutes at a time. These results motivated us to investigate the effects of long-duration application of the low-intensity tFUS with spatial speci?city in awake animals. We seek to develop lightweight ultrasound transducer arrays for tFUS neuromodu- lation devices that maintain the advantages of the DMUA approach; real-time monitoring and closed-loop control while minimizing the number of elements and designing for low-power operation. This is especially important to advance tFUS neuromodulation research on awake animals, but could also apply to clinical applications. We propose to investigate a new, image-based design approach to conformal wearable patch transducers for targeting of speci?c brain circuits (SA1 ). We will use 3D imaging for pro?ling the scalp/skull surfaces and characterize tFUS transmission in vivo. Aperture synthesis methods will be used to optimize the array geometry with mini- mum number of elements to meet focusing speci?cations within the target region. We will also investigate the performance of on-demand tFUS application using the lightweight, conformal transducers in vivo (SA2 ). In vivo experiments to demonstrate on-demand targeting of the VPL to suppress the SSEP will be performed under dif- ferent conditions, including sham treatments. If successful, this research will lead to the development of wearable conformal arrays for on-demand tFUS neuromodulation in human subjects.