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

拟议的研究计划旨在推进我们对聚焦超声（FU）神经刺激基本机制的理解。为此，我们建议发展一个内部开发和非常成功的软件平台Proteus（NSERC Discovery资助），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）积极参与了其开发。新提出的平台将专门用于超声图像引导神经刺激（IGNEOUS）。** FU可以安全地集中穿透机械超声波深入到活组织中，产生独特的生物效应。低强度FU是指一种曝光类型，其中脉冲FU以低振幅和低占空比发送。使用低强度FU，可以产生基于瞬时超声的神经刺激效应。还有大量的研究要做，以了解FU神经刺激的机制，其对大脑网络连接和神经可塑性的整体影响。该计划将平衡工程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建立可控的，穿透性的，和非破坏性的神经刺激使用FU。IGNEOUS在Proteus平台上的开发，可以与临床前和人类准备的磁共振成像（MRI）引导聚焦超声系统接口，将大大促进未来的转化工作。IGNEOUS将整合来自成像、电生理学和光学源的近实时大脑活动评估。为了更好地了解大脑过程和认知机制以研究大脑疾病，具有非侵入性，高分辨率和受控的方法来诱导神经刺激具有最高的科学相关性。IGNEOUS计划将由四个核心项目指导：* 脑电图（EEG）信号的捕获和调节，包括在动物模型和人类中使用的源 * 直接在IGNEOUS应用程序中处理功能性MRI（fMRI）数据 * 捕获和处理啮齿动物模型中大脑活动钙激活（Ca2+）的光学监测 * 使用大脑活动（EEG，fMRI，Ca2+）数据源开发FU神经刺激的闭环算法 * 该计划将为生物医学工程领域的研究生提供高影响力的机会。IGNEOUS平台将允许进行转化研究，其中可以使用不同的模型和成像方式研究FU诱导的神经刺激的影响。这种翻译能力将是IGNEOUS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.*****