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神经刺激(火成岩)。 FUS可以安全地将穿透机械超声波深入活体组织，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，还需要进行大量的研究。 该计划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来研究大脑疾病，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(EEG)信号的捕获和调节，包括用于动物模型和人类的信号源 火成岩应用中功能磁共振(FMRI)数据的直接处理 光学监测啮齿动物模型脑活动钙激活的捕获和处理 利用脑活动数据源(EEG、fMRI、Ca~(2+))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特点。

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.