MetaOx, Optical Monitor of Metabolic Rate of Oxygen Consumption

描述(由申请人提供)：ISS Inc.与马萨诸塞州总医院的Franceschini博士和宾夕法尼亚大学的Yodh博士合作，提议开发和构建一种新型仪器的原型，以监测脑氧代谢(CMRO2)，该仪器结合了频域近红外组织血氧计(FDNIRS)和扩散相关光谱(DCS)设备。结合FDNIRS和DCS将使我们能够测量脑血红蛋白氧合(SO2)和脑血流量指数(BFI)来估计CMRO2。我们的临床合作者波士顿儿童医院的Ellen Grant博士和费城儿童医院的Daniel Licht博士将为我们提供针对新生儿ICU临床环境优化设备的建议。快速、准确地评估新生儿床旁脑代谢的能力对于改善新生儿的患者管理至关重要。目前还没有能够准确筛查脑损伤、监测损伤演变或评估治疗反应的床边工具。众所周知，头部超声波是出了名的不敏感和非特异性，EEG起到了补充作用，而MRI过于昂贵和耗时，无法用于筛查或监测，而且还存在不必要的风险，可能会破坏危重婴儿的稳定，这些婴儿必须被送往MRI套间。 传统的近红外血氧仪未能成为新生儿的常规临床工具，因为在创伤后几个小时，当氧输送和消耗重新建立平衡时，二氧化硫在检测脑损伤方面的敏感性较差。我们提出的用这种新型仪器测量大脑氧利用的直接测量方法，将提供更高的灵敏度来检测脑损伤，并能够监测正常和异常的脑发育。如果成功，这种设备将允许实时干预，从而可能改善临床结果。我们的长期计划包括首个FDNIRS/DCS脑代谢监测系统的商业化。在第一阶段，我们将建造第一个商业原型，开始开发统一的采集和数据分析软件，并在幻影和成年人体受试者中测试这一新系统。然后，我们将在新生儿中进行一项初步研究，并将EEG证实的癫痫发作活动的婴儿与健康对照组进行比较，以验证氧气消耗指标比血红蛋白氧合指标更能诊断脑损伤的假设。虽然CMRO2监测以前是在研究环境中进行的，但通过将ISS FDNIRS系统与实验室构建的DCS仪器相结合，这些测量需要训练有素的操作员和光学成像专家的数据分析。我们的目标是将这些繁琐的研究系统转变为更强大的交钥匙设备，使医务人员能够在床边获得临床上和相关的测量结果。在项目第一阶段完成后，我们将继续进行第二阶段，在此期间，我们计划完善系统，并开始在三家医院(波士顿的布里格姆医院和妇女儿童医院，以及费城儿童医院丹尼尔·利希特博士)展示我们的CMRO2测量的临床相关性。如果该计划全部被接受，我们预计将在预计的四年内完成FDNIRS/DCS系统的开发，我们称之为MetaOx。 公共卫生相关性：新生儿脑损伤会导致严重的发病率。缺乏新生儿大脑健康的床边监测仪阻碍了可以改善神经发育结果的护理方面的进展。这项SBIR的总体目标是开发一种仪器，用于量化新生儿重症监护病房床边的脑氧代谢。这种设备将在评估脑组织损伤和疾病以及跟踪治疗反应方面具有重要的临床实用价值。

DESCRIPTION (provided by applicant): ISS Inc., in collaboration with Dr. Franceschini of the Massachusetts General Hospital and Dr. Yodh of the University of Pennsylvania, proposes to develop and construct the prototype of a novel instrument to monitor cerebral oxygen metabolism (CMRO2) that combines a frequency-domain near-infrared tissue oximeter (FDNIRS) and a diffusion correlation spectroscopy (DCS) device. Combining FDNIRS and DCS will enable us to measure cerebral hemoglobin oxygenation (SO2) and an index (BFi) of cerebral blood flow (CBF) to estimate CMRO2. Our clinical collaborators Dr. Ellen Grant of Children's Hospitals in Boston, and Dr. Daniel Licht of Children's Hospital of Philadelphia will advise us on optimizing the device for the neonatal ICU clinical setting. The ability to rapidly an accurately assess cerebral metabolism at bedside in neonates is critical to improving patient management in neonatology. Currently there is no bedside tool that can accurately screen for brain injury, monitor injury evolution or assess response to therapy. Head ultrasounds are notoriously insensitive and nonspecific, EEG serves a complementary role, and MRI is too expensive and time-consuming to be used for screening or monitoring, and involves unnecessary risks of destabilizing critically ill infants who must be transported to the MRI suite. Conventional NIRS oximetry has failed to become a routine clinical tool in neonatology due to the poor sensitivity of SO2 in detecting brain injury hours after the insult, when equilibrium between oxygen delivery and consumption is reestablished. The direct measure of cerebral oxygen utilization we propose to measure with this novel instrument will provide higher sensitivity to detect brain injury and the ability to monitor normal and abnormal brain development. If successful, this device will allow for real-time interventions and thus could improve clinical outcome. Our long-term plans encompass the commercialization of the first FDNIRS/DCS cerebral metabolism monitoring system. In phase I we will build the first commercial prototype, start to develop unified acquisition and data analysis software, and test this new system in phantoms and adult human subjects. We will then perform a pilot study in newborns and compare infants with seizure activity confirmed by EEG with healthy controls, to validate the hypothesis that a measure of oxygen consumption is better able to diagnose brain damage than measure of hemoglobin oxygenation. While CMRO2 monitoring has been performed previously in a research setting, by combining ISS FDNIRS systems with lab-built DCS instrumentation, these measurements have required highly trained operators and data analysis by optical imaging experts. Our goal is to transform these cumbersome research systems into a more robust turnkey device that will enable medical staff to obtain clinically and relevant measurements at the bedside. After completion of the Phase I portion of the project, we will proceed with Phase II, during which we plan to refine the system and start demonstrating the clinical relevance of our CMRO2 measurements in three hospitals (Brigham and Women's and Children's Hospitals in Boston, and Children's Hospital of Philadelphia with Dr. Daniel Licht). If the plan is accepted in its entirety, we expect to complete development of the FDNIRS/DCS system, which we call MetaOx, within the projected four-year period. PUBLIC HEALTH RELEVANCE: Newborn brain injury causes significant morbidity. The lack of a bedside monitor for newborn brain health is hindering progress in care that could improve neurodevelopmental outcomes. The overall goal of this SBIR is to develop an instrument with which to quantify cerebral oxygen metabolism in at the bedside to be used in neonatal intensive care units. Such a device will have significant clinical utility for assessing cerebral tissue injuy and disease, and to follow response to treatment.