Noninvasive scalp detection of cortical spreading depression for brain injury

 描述（由申请人提供）：急性脑损伤（包括中风、蛛网膜下腔出血和严重创伤性脑损伤）中的皮质扩散性抑制（CSD）具有显著的临床意义（320万患者/年）和经济意义（> 340亿美元/年）。目前CSD评估的一个主要限制是，它只能用需要侵入性开颅手术的皮质电极观察。因此，只有一小部分最严重的受伤患者受到监测。我们建议开发一个系统，可靠地检测CSD与非侵入性，头皮安装传感器阵列，使用直流脑电图（DC-EEG）。传统的交流耦合脑电在临床上得到了广泛的应用，但它并不适合于检测CSD缓慢移动的直流电位波。相比之下，DC耦合EEG的未充分使用的技术非常适合CSD检测。我们的目标是设计，构建和验证一个头皮安装，CSD检测系统，首先优化传感器阵列使用计算机模拟和创建软件来处理信号和检测CSD。我们初步的数值模拟CSD检测头皮同意与有限的公布的数据，并表明CSD的传播是检测到一个足够密集的阵列。具体目标1涉及不同形状和传播模式的CSD产生的头皮电位的计算机模拟，这将允许传感器阵列的虚拟设计和检测软件的开发。具体目标2涉及原型开发，包括传感器阵列和用户界面。具体目标3需要在正常对照受试者中进行器械试验， 使用神经重症监护病房（Neuro-ICU）中已知表现出CSD的急性脑损伤患者对其进行验证。在实现这三个具体目标的过程中，我们将达到五个里程碑：1）传感器系统的虚拟设计; 2）用于检测和分析CSD的软件包; 3）功能原型阵列; 4）图形用户界面;以及5）原型的人工验证。在第二阶段，我们的主要目标将是开发一种用于神经ICU急性脑损伤的可销售设备。第二阶段还将测试是否可以扩展使用范围，以包括假设会发生CSD的其他情况，但目前在没有我们的设备的情况下无法检测到（例如，脑震荡，紧急情况下的急性脑损伤患者）。从我们的设备在神经ICU中的使用（约为开颅手术数量的20倍）来看，我们估计潜在的美国市场有6万客户，每年可以产生700万美元的收入，市场份额为5%。我们的团队结合了在电气硬件和软件设计，EEG电极开发和实施，数值建模和虚拟设计，以及脑损伤中CSD的临床和实验研究方面的专业知识。这种专业知识将使我们能够通过坚实的工程原理生产这种设备。CSD作为一种主要的神经病理学机制，其直接和非侵入性评估将允许治疗靶向改善患有CSD的急性脑损伤患者的结局，并可能在SBIR II期后提供对脑震荡的客观评估。

 DESCRIPTION (provided by applicant): Cortical spreading depression (CSD) in acute brain injury, including stroke, subarachnoid hemorrhage, and severe traumatic brain injury has significant clinical (3.2M patients/year) and economic importance (>$34B/year). A major limitation to current assessment of CSD is that it can only be observed with cortical electrodes requiring an invasive craniotomy. Thus only a small fraction of the most critically injured patient are monitored. We propose to develop a system that reliably detects CSDs with a non-invasive, scalp-mounted sensor array using direct-current electroencephalography (DC-EEG). Whereas conventional AC-coupled EEG is widely used clinically, it is not optimal for detecting the slowly moving DC-potential wave of CSD. In contrast, the underused technology of DC-coupled EEG is ideally suited for CSD detection. We aim to design, build, and validate a scalp-mounted, CSD-detection system by first optimizing the sensor array using computer simulation and creating software to process the signals and detect the CSDs. Our preliminary numerical simulations of CSD detection from the scalp agree well with the limited published data and indicate that propagation of the CSD is detectable with a sufficiently dense array. Specific Aim 1 involves the computer simulation of scalp potentials generated by CSDs of varying shapes and propagation patterns which will allow for the virtual design of the sensor array and the development of detection software. Specific Aim 2 involves prototype development, including the sensor array and user interface. Specific Aim 3 entails the testing of the device in normal control subjects and validating it using patients with acute brain injury in the Neuro-Intensive Care Unit (Neuro-ICU) who is known to exhibit CSD. In achieving these three Specific Aims we will reach five milestones: 1) the virtual design of the sensor system; 2) a software package for detection and analysis of CSDs; 3) a functioning prototype array; 4) a graphical user interface; and 5) human validation of the prototype. In Phase II, our primary goal will be to develop a marketable device for acute brain injury in the Neuro-ICU. Phase II will also test whether use could be expanded to include other conditions where CSD is hypothesized to occur, but which cannot currently be detected without our device (e.g. concussion, acute brain injury patients in emergency situations). From the use of our device in the Neuro-ICU (~20 times the number of those with a craniotomy), we estimate a potential market of 60K US customers that could generate $7M/year in revenue with a 5% market share. Our team combines individuals with expertise in electrical hardware and software design, EEG electrode development and implementation, numerical modeling and virtual design, and clinical and experimental investigation of CSD in brain injury. This expertise will allow us to produce this device through solid engineering principals. The direct and non-invasive assessment of CSD, as a primary neuropathological mechanism, would allow therapeutic targeting to improve outcomes in acute brain injury patients with CSDs, and possibly, after SBIR Phase II, provide an objective assessment of concussion.