Development and evaluation of diffuse correlation spectroscopy to monitor cerebral blood flow and detect intraventricular hemorrhage in extremely premature infants

漫相关光谱监测脑血流和检测极早产儿脑室内出血的开发和评估

• 批准号: 10403869
• 负责人: TERRIE E INDER
• 金额: $ 54.22万
• 依托单位: 149 MEDICAL INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10403869
• 关键词: Development; evaluation; diffuse; correlation; spectroscopy

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.

项目总结/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与 脑瘫和严重智力残疾的高风险，对受影响的人造成终身影响， 儿童及其家庭的经济负担相当大。IVH是由脆弱的 脑血管基质中的毛细血管不能承受脑血流（CBF）的波动。在>90%的 例，这些损伤发生在出生后的头三天，在一个时期的心肺不稳定 这对CBF有直接影响，导致脑灌注不足和过度灌注的时期。电流 管理策略，如通气或正性肌力药物支持的变化，对CBF的影响是盲目的。 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 知情决策，优化现有战略，促进制定新的干预措施， ELGA婴儿IVH的发病率，并改善发育结果。149医学基础 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 并建立了一个新的快速多距离扩散相关光谱（DCS）系统，优化了连续 在ELGA婴儿中监测CBFi。DCS通过测量脑血流量（CBFi）的指数， 由移动的红细胞的动态散射产生的光的时间波动。对…有用 ELGA婴儿床旁监护仪需要安全、连续、精确、可靠、定量和轻柔 可穿的这些预处理将通过设计一种光学传感器来满足，该光学传感器可以轻轻地应用于 爱尔佳婴儿。新型DCS系统将由149医疗团队在幻影中进行初步测试，以验证 性能，并证明流量估计的精度和准确性。该系统随后将在更多的 在布里格姆妇女医院（BWH）NICU的成熟，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，该设备将用于50个ELGA婴儿在生命的前72小时内， 测试我们的假设，即DCS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个急需的脑血流监测仪，以指导个性化的 治疗的目的是降低IVH的风险，改善长期的神经发育结果， ELGA婴儿这项在50名ELGA婴儿中进行的研究将为更大规模的商业化试验奠定基础。