Minimally Invasive Cerebral Blood Flow and Oxygenation Monitoring for Intracranial Hypertension

摘要/项目摘要 外伤性脑损伤、急性缺血性中风和脑出血经常并发 颅内高压导致进行性缺血和继发性脑损伤。最近的努力重点 因此，改善结果的重点是改善脑氧合和 开发监测设备来指导治疗。当前设计用于测量组织氧合的设备 然而，其监视范围和准确性受到严重限制。表面血氧监测仪 仅询问浅层脑组织，并受到皮肤和头骨的污染。实质内 脑组织氧探针调查代谢相对较不活跃的白质（与灰质相比）， 体积小于 3 mm3，并且位于单个位置。最后，实质内组织氧监测仪是 体积庞大，与磁共振成像不相容，并且尚未证明临床疗效。 为了满足这一需求，我们将完成大脑特异性、微创、光血流的开发 和氧合监测系统（FLOXBR），然后将该设备应用到人类身上。 FLOXBR，采用 通过脑表面探针进行的漫射光学和相关光谱可以提供更高的灵敏度和 与非侵入式探头相比具有特异性，并且比目前可用的侵入式探头探测更大的体积 探针，例如 LicoxTM 组织 pO2 探针。与实质内探针不同，该装置可以位于上方或上方 位于硬脑膜下方，对代谢高度活跃的灰质更加敏感。其体积小且灵活性强 将允许多个探头通过单个钻孔放置，从而允许监测区域 流量和氧合的差异。与表面血氧测定法不同，FLOXBR 不受表面创伤的影响 或水肿，提高可靠性和灵敏度。连续、易于解释且可靠的微创 监测脑氧输送可以改善患有以下疾病的患者的管理和结果 颅内高压。 我们的目标简要总结如下。 目标 1) 完成 FLOXBR 脑流和血氧监测装置的开发和制造。 目标 2) FLOXBR 的临床前器械评估、测量验证和安全性测试。 目标 3) 完成监管和安全要求，以支持 FLOXBR 首次人体可行性测试。 目标 4) 进行首次人体可行性测试。

ABSTRACT/PROJECT SUMMARY Traumatic brain injury, acute ischemic stroke, and intracerebral hemorrhage are frequently complicated by intracranial hypertension leading to progressive ischemia and secondary brain injury. Recent efforts focused on improving outcomes have therefore been focused upon improving cerebral oxygenation and the development of monitoring devices to guide therapy. Current devices designed to measure tissue oxygenation are, however, severely limited in their scope of surveillance and accuracy. Surface oximetry monitors interrogate only superficial brain tissue, with contamination from intervening skin and skull. Intraparenchymal brain tissue oxygen probes survey relatively metabolically less active white matter (compared to gray matter), a volume of less than 3 mm3, and at a single location. Lastly, intraparenchymal tissue oxygen monitors are bulky, incompatible with magnetic resonance imaging, and have yet to demonstrate clinical efficacy. To fill this need, we will finalize the development of a brain-specific, minimally invasive, optical blood flow and oxygenation monitoring system (FLOXBR), then translate this device to humans. The FLOXBR, employing diffuse optical and correlation spectroscopies via a brain surface probe, may offer improved sensitivity and specificity compared to non-invasive probes and will probe larger volumes than currently available invasive probes, such as the LicoxTM tissue pO2 probe. Unlike intraparenchymal probes, this device can lie above or below the dura and will be more sensitive to highly metabolically active gray matter. Its small size and flexibility will permit multiple probes to be placed through a single burr hole, thus allowing for the monitoring of regional differences in flow and oxygenation. Unlike surface oximetry, the FLOXBR is not impacted by superficial trauma or edema, improving reliability and sensitivity. Continuous, easily interpreted, and reliable minimally invasive monitoring of cerebral oxygen delivery may enhance management and outcomes in patients suffering from intracranial hypertension. Our aims are succinctly summarized below. Aim 1) Finalize development & manufacture the FLOXBR brain flow and oximetry monitoring device. Aim 2) Pre-clinical device evaluation, measurement validation, and safety testing of FLOXBR. Aim 3) Complete regulatory and safety requirements to support FLOXBR first-in-humans feasibility testing. Aim 4) Conduct first-in-humans feasibility testing.