IGNEOUS : A characterization platform for Image-Guided NEurOstimulation with UltraSound

拟议的研究计划旨在促进我们对聚焦超声(FUS)刺激神经的基本机制的理解。为此，我们建议开发一个内部开发的非常成功的软件平台Proteus(NSERC Discovery-Funding)，用于聚焦超声的图像引导干预，14名研究生和本科生高素质人员(HQP)积极参与了该平台的开发。新提出的平台将专门用于图像引导的超声波神经刺激(火成岩)。*FUS可以安全地将穿透性机械超声波集中到活组织深处，产生独特的生物效果。低强度FUS是指以低幅度和低占空比发送脉冲FUS的曝光类型。使用低强度FUS，可以产生基于瞬时超声波的神经刺激效应。要了解FUS神经刺激的机制，以及它对大脑网络连通性和神经可塑性的整体影响，还需要做大量的研究。*这个项目将平衡工程学和神经科学的研究活动。我们将开发近实时高级图像处理、多通道信号处理、闭环控制算法和人机界面的新方法。我们将应用这些工程方法来利用FUS建立可控的、穿透性的和非破坏性的神经刺激。在Proteus平台上开发的Fireneous可以与临床前和人类准备好的磁共振成像(MRI)引导的聚焦超声系统对接，这将大大促进未来的翻译工作。火星号将从成像、电生理学和光学来源整合对大脑活动的近实时评估。为了更好地了解大脑过程和认知机制以研究大脑疾病，拥有一种非侵入性、高分辨率和可控的方法来诱导神经刺激具有最高的科学意义。*火成岩计划将由四个核心项目指导：*脑电信号的捕获和调节，包括动物模型和人类使用的来源*在火成岩应用中直接处理功能磁共振(FMRI)数据*捕捉和处理啮齿动物模型中大脑活动的钙激活(Ca2+)光学监测*使用大脑活动的数据来源(EEG、fMRI、Ca2+)开发FUS神经刺激闭环算法*该项目将为生物医学工程领域的研究生提供高影响力的机会。火成岩平台将允许进行翻译研究，其中FUS诱导的神经刺激的影响可以使用不同的模型和成像方式进行研究。这种翻译能力将是火成岩平台最具创新性和影响力的功能。*

The proposed research program aims to advance our understanding of the fundamental mechanisms of neurostimulation with focused ultrasound (FUs). For this purpose, we propose to evolve an in-house developed and highly successful software platform Proteus (NSERC Discovery-funded) for image-guided interventions with focused ultrasound, on which fourteen graduate and undergraduate High Qualified Personnel (HQP) have actively contributed to its development. The newly proposed platform will be specific for Image-Guided NEurOstimulation with UltraSound (IGNEOUS).******FUs can safely concentrate penetrating mechanical ultrasound waves deep into living tissue to produce distinctive biological effects. Low-intensity FUs refers to a type of exposure where pulsed FUs is sent with both low amplitude and low duty cycle. With low-intensity FUs, a transient ultrasound-based neurostimulation effect can be produced. A substantial amount of research remains to be done to understand the mechanisms of FUs neurostimulation, its overall effects in brain network connectivity and neuroplasticity.******This program will balance research activities in engineering and neuroscience. We will develop new methods for near real-time advanced image processing, multi-channel signal processing, closed-loop control algorithms, and human-machine interfaces. We will apply these engineering methods to establish controllable, penetrating, and non-destructive neurostimulation using FUs. The development of IGNEOUS on top of the Proteus platform, which can interface with pre-clinical and human-ready Magnetic Resonance Image (MRI)-guided focused ultrasound systems, will significantly facilitate translational efforts in the future. IGNEOUS will integrate near real-time assessment of brain activity from imaging, electrophysiology, and optical sources. For a better understanding of brain processes and cognitive mechanisms to study brain disorders, having a non-invasive, high-resolution and controlled method to induce neurostimulation is of the highest scientific relevance.******The IGNEOUS program will be guided by four core projects:*** Capture and conditioning of electroencephalography (EEG) signals, including sources utilized in animal models and humans*** Processing of functional MRI (fMRI) data directly in the IGNEOUS application*** Capture and processing of optical monitoring of calcium activation (Ca2+) of brain activity in rodent models *** Development of closed-loop algorithms for neurostimulation with FUs using data sources of brain activity (EEG, fMRI, Ca2+)******This program will provide high-impact opportunities for graduate students in the areas of Biomedical Engineering. The IGNEOUS platform will allow translational studies where the effects of FUs-induced neurostimulation can be studied using different models and imaging modalities. This translational capability will be the most innovative and impactful feature of the IGNEOUS platform.*****