DCS cerebral blood flow monitor for extreme low-birth-weight infants

项目概要/摘要 在美国，每年60，000名极早产儿（<30周）中约有30% 胎龄和<1000 g出生体重[ELGA]）发生脑室内出血（IVH）。IVH是 与脑瘫和严重智力残疾的高风险相关，导致终身影响， 受害儿童及其家庭的经济负担相当沉重。IVH是由血管壁破裂引起的。 脑血管基质中脆弱的毛细血管，无法承受脑血流（CBF）的波动。在 >90%的情况下，这些损伤发生在出生后的前三天，在心肺功能恢复期间， 不稳定性对CBF有直接影响，导致大脑低灌注和高灌注期。 目前的管理策略，如通气或正性肌力药物支持的变化，是盲目的， CBF。迫切需要改进的床边技术来连续监测CBF，以使临床医生能够 做出明智的决定，优化现有战略，促进制定新的干预措施， 降低ELGA婴儿IVH的发生率并改善发育结局。在我们的10个基础上 多年来成功地测量婴儿与非侵入性床边光学方法，我们建议设计和建立 一种新型的快速，三波长，五距离扩散相关光谱（DCS）系统，优化为 连续监测ELGA婴儿的CBFi。DCS直接量化脑血流量指数（CBFi） 通过测量由移动的红细胞的动态散射产生的光的时间波动。 为了在ELGA婴儿中使用，该床旁监护仪需要安全、连续、精确、可靠， 定量和轻轻磨损。通过设计光学传感器将满足这些要求，该光学传感器可以 轻轻地涂在ELGA婴儿身上。该装置将采用一种新颖的多距离、多波长方法， 评估组织散射和吸收系数，这需要与自相关相结合 衰减率以正确量化CBFi。新的DCS系统将由马萨诸塞州进行初步测试 总医院（MGH）团队在phanomelet验证性能并证明精密度和准确度 流量估算然后，该系统将在布里格姆医院的更成熟、更稳定的早产儿中进行测试， 妇女医院（BWH）NICU评估长测量的可行性，与NICU的兼容性 环境、长时间监测后的皮肤完整性和体内算法验证。最后，设备 将用于100名ELGA婴儿在出生后的前72小时内，以检验我们的假设，即DCS测量的 CBFi波动和压力被动事件与IVH的发生率和严重程度相关。我们的目标是 提供急需的脑血流监测仪，以指导个体化治疗， ELGA婴儿IVH的风险和改善长期神经发育结果。这项研究在100 ELGA婴儿将为更大规模的试验和商业化奠定基础。

PROJECT SUMMARY/ABSTRACT Every year in the United States about 30% of the 60,000 infants born extremely premature (<30 weeks gestational age and <1000 g birth-weight [ELGA]) develop intraventricular hemorrhage (IVH). IVH is associated with high risk for cerebral palsy and significant intellectual disability, causing lifelong implications for affected children and their families and considerable economic burden. IVH is caused by the rupture of the fragile capillaries in the germinal matrix which cannot withstand fluctuations in cerebral blood flow (CBF). In >90% of cases, these injuries occur during the first three postnatal days during a period of cardiorespiratory instability that has a direct effect on CBF, which results in periods of cerebral hypo- and hyper-perfusion. Current management strategies, such as changes in ventilation or inotrope support, are blind to the impact on CBF. Improved bedside technologies to continuously monitor CBF are urgently needed to allow the clinician to make informed decisions, to optimize current strategies and foster the development of new interventions to reduce the incidence of IVH in ELGA infants and to improve developmental outcomes. Building on our ten years of success measuring infants with non-invasive bedside optical methods, we propose to design and build a novel fast, three-wavelength, five-distances diffuse correlation spectroscopy (DCS) system, optimized for continuous monitoring of CBFi in ELGA infants. DCS directly quantifies an index of cerebral blood flow (CBFi) by measuring the temporal fluctuations of light generated by the dynamic scattering of moving red blood cells. To be of use in the ELGA infant, this bedside monitor needs to be safe, continuous, precise, reliable, quantitative and gently wearable. These pre-requisites will be met by designing an optical sensor which can be gently applied to the ELGA infant. The device will adopt a novel multi-distance, multi-wavelength method to assess tissue scattering and absorption coefficients, which are needed in combination with autocorrelation decay rates to correctly quantify CBFi. The novel DCS system will be initially tested by the Massachusetts General Hospital (MGH) team in phantoms to verify performance and demonstrate precision and accuracy of flow estimates. The system will then be tested in more mature, stable premature infants at the Brigham and Women's Hospital (BWH) NICU to evaluate feasibility of long measurements, compatibility with the NICU environment, skin integrity after long monitoring periods, and in-vivo algorithm validation. Finally, the device will be used in 100 ELGA infants during the first 72 hours of life to test our hypothesis that DCS-measured CBFi fluctuations and pressure-passive events correlate with incidence and severity of IVH. Our goal is to provide a much-needed cerebral blood flow monitor to guide individualized treatment with the goal of reducing the risk of IVH and improving long term neurodevelopmental outcomes among ELGA infants. This study in 100 ELGA infants will set the stage for a larger trial alongside commercialization.