Bioimpedance-based Intracranial Mapping for Monitoring Evolving TBI

摘要 每年约有300万人遭受创伤性脑损伤（TBI），预计超过50，000人 因受伤而死亡。在这些最严重的病例中，患者通常被送入重症监护室， ICU（重症监护室），以持续监测和治疗他们的伤害。标准监测包括植入 颅内压（ICP）传感器、动脉血压（ABP）监测和偶尔成像 研究（通常使用CT）。这些监测策略的目的是检测在一个特定的年龄段中的演变病理学。 及时的方式，以便在这些患者的损伤升级到 这种治疗变得无效。不幸的是，这些策略的检测能力有限 恶化的条件。ICP峰值代表了恶化状况的全球衡量标准，但它没有提供 定位信息，并且通常比临床期望的晚得多地达到关注水平（>20 mmHg）。 结合ICP的ABP感测代表脑灌注压的替代测量，但很难 准确计量。偶尔的影像学检查提供了精致的颅内细节，但难以管理 在重症监护室患者中，仅偶尔获得，通常在损伤开始后， 中求进工作总我们建议通过开发一个小表格来克服当前监测策略的局限性- 因素，实时连续监测，能够空间映射不断发展的颅内创伤。我们特别 建议为此目的使用电阻抗谱的适应形式。我们的新方法 利用头皮电极和颅内电极， 创伤导致的体液和组织改变我们已经在一项试点动物研究中证明， 这种类型的模态能够检测由于质量效应、血肿和脑死亡引起的颅内变化。 在这个项目中，我们将迈出重要的一步，为商业部署开发这项技术。 并使用术中CT扫描证明在动物模型中的可行性。因为这 系统设计用于最小程度地增强现有临床方案（设计用于与 ICU中的重度器械患者）相对便宜（电阻抗采集<1万美元 系统），并有可能能够在目前临床上接受的颅内损伤之前检测到进展中的颅内损伤。 技术，这项技术有可能被容易地转化为临床接受， TBI后持续监测患者的益处。我们希望在这个节目结束时， 我们将提交第二阶段申请，重点是优化我们的技术， 更大样本量的动物模型试验，以证明我们的颅内阻抗标测技术的有效性。

ABSTRACT Approximately 3 million individuals suffer from traumatic brain injury (TBI) annually, with over 50,000 expected to die as a result of their injury. In these most severe cases, patients are typically admitted to the intensive care unit (ICU) for continuous monitoring and treatment of their injury. Standard monitoring includes implantation of an intracranial pressure (ICP) sensor, arterial blood pressure (ABP) monitoring, and occasional imaging studies (typically with CT). The objective of these monitoring strategies is to detect evolving pathology in a timely manner so that treatment can be provided to these patients prior to their injury escalating to a point at which treatment becomes ineffective. Unfortunately, these strategies are limited in their ability to detect worsening conditions. Spiking ICP represents a global measure of worsening status, however it provides no localizing information and typically reaches levels of concern (>20 mmHg) much later than is clinically desired. ABP sensing coupled with ICP represents a surrogate measure of cerebral perfusion pressure, but is difficult to accurately gauge. Occasional image studies provide exquisite intracranial details, but are difficult to administer in heavily instrumented ICU patients and are only acquired occasionally, often after injury has begun to progress. We propose to overcome the limitations of current monitoring strategies by developing a small form- factor, real-time continuous monitor, able to spatially map evolving intracranial trauma. Specifically, we propose to use an adapted form of electrical impedance spectroscopy for this purpose. Our novel approach leverages both scalp and intracranial electrodes to map dynamic intracranial impedance changes associated with fluid and tissue alterations resulting from trauma. We have demonstrated in a pilot animal study that this type of modality is capable of detecting intracranial changes due to mass effect, hematoma, and brain death. During this program we will take the significant step of developing this technology for commercial deployment and demonstrating proof of feasibility in an animal model using intraoperative CT scanning. Because this system is being designed to minimally augment an already existing clinical protocol (designed to interface with a heavily instrument patient in the ICU), is relatively inexpensive (<$10k for an electrical impedance acquisition system), and is potentially able to detect evolving intracranial injury prior to current clinically-accepted technologies, this technology has the potential of being easily translated to and accepted by the clinic for the benefit of continuously monitoring patients following TBI. We expect that by the end of this program we will be in a position to submit a Phase II application that will focus on optimizing our technology and conducting a larger sample size animal model trial to demonstrate efficacy of our intracranial impedance mapping technique.