Development and Evaluation of Diffuse Correlation Spectroscopy to Monitor Cerebral Blood Flow and Detect Intraventricular Hemorrhage in Extremely Premature Infants

项目摘要/摘要 在美国，每年6万名极早产(30周)婴儿中约有30%出生 胎龄和1000克出生体重[埃尔加])会导致脑室出血(IVH)。IVH关联 脑性瘫痪和严重智力残疾的高风险，对受影响的人造成终身影响 儿童及其家庭和相当大的经济负担。IVH是由脆性破裂引起的 生发基质中的毛细血管，不能承受脑血流量的波动。在&gt；中的90% 这些损伤发生在出生后头三天的心肺不稳定时期。 这对脑血流有直接影响，从而导致大脑低灌注期和高灌注期。当前 管理策略，如换气或正性肌力支持的改变，对CBF的影响视而不见。 迫切需要改进的床边技术来持续监测CBF，以便临床医生能够 在知情的情况下作出决定，以优化现有战略，并促进制定新的干预措施，以减少 为了提高埃尔加婴儿的IVH发生率并改善发育结果。在149个医疗创始的基础上 团队十年来成功地用非侵入性床边光学方法测量婴儿，我们建议设计 并建立了一种新的快速多距离漫反射相关光谱(DCS)系统，优化了连续 埃尔加新生儿的脑血流显像监测分布式控制系统通过测量脑血流量(CBFI)直接量化一个指数 由运动的红血球的动态散射产生的光的时间波动。对…有用处 埃尔加婴儿，这台床边监护仪需要安全、连续、准确、可靠、定量和温和 可穿戴的。这些先决条件将通过设计一种光学传感器来满足，该传感器可以轻轻地应用于 埃尔加婴儿。新的分布式控制系统将由149医疗团队在幻影中进行初步测试，以验证 性能，并展示流量估计的精确度和准确性。然后，该系统将在更多的 在布里格姆妇女医院(BWH)NICU治疗成熟、稳定的早产儿，以评估 长时间测量，与NICU环境的兼容性，长时间监测后的皮肤完整性，以及 体内算法验证。最后，该设备将在50名埃尔加婴儿生命的前72小时内使用 测试我们的假设，即分布式控制系统测量的CBFI波动和压力被动事件与发病率相关 和IVH的严重程度。我们的目标是提供一种急需的脑血流监测仪来指导个性化 以降低IVH风险和改善长期神经发育结局为目标的治疗 埃尔加婴儿。这项对50名埃尔加婴儿的研究将为在商业化的同时进行更大规模的试验奠定基础。

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 149 Medical founding team’s ten years of success measuring infants with non-invasive bedside optical methods, we propose to design and build a novel fast multi-distance 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 novel DCS system will be initially tested by the 149 Medical’s 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 50 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 50 ELGA infants will set the stage for a larger trial alongside commercialization.