MetaOx, Optical Monitor of Metabolic Rate of Oxygen Consumption

描述（由申请人提供）：ISS公司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，提出开发和构建一种新型仪器的原型，该仪器结合了频域近红外组织血氧仪（FDNIRS）和扩散相关光谱（DCS）装置，用于监测脑氧代谢（cmo 2）。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（CBF）指数（BFi）来估计cmor2。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博士将建议我们优化新生儿ICU临床设置的设备。快速准确地评估新生儿床边脑代谢的能力对于改善新生儿患者管理至关重要。目前还没有床边工具可以准确地筛查脑损伤，监测损伤演变或评估对治疗的反应。头部超声波是出了名的不敏感和非特异性，脑电图是一种补充作用，而核磁共振成像（MRI）用于筛查或监测过于昂贵和耗时，并且涉及不必要的危险，危及危重婴儿的稳定，他们必须被送到核磁共振套件。

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.