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: 10468687
• 负责人: TERRIE E INDER
• 金额: $ 8.17万
• 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 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468687
• 关键词: Affect; Algorithms; Automobile Driving; Bedside Technology; Bilateral; Birth; Birth Weight; Blood Pressure; Blood Vessels; Blood capillaries; Boston; Brain Injuries; Cardiovascular system; Cerebral Palsy; Cerebral hemisphere; Cerebrovascular Circulation; Cerebrum; Child; Clinical; Development; Devices; Diffuse; Economic Burden; Effectiveness; Elderly; Electrocardiogram; Environment; Erythrocytes; Evaluation; Event; Executive Dysfunction; Family; Fostering; Gestational Age; Goals; Head; Health Care Costs; Hospitals; Hour; Hydrogels; Image; Incidence; Infant; Injury; Intellectual functioning disability; Intervention; Lead; Length; Life; Light; Measurement; Measures; Mechanical ventilation; Medical; Monitor; Morbidity - disease rate; Mothers; Multiple Birth Offspring; Neonatal; Nervous System Trauma; Neurocognitive; Neurodevelopmental Disability; Optical Methods; Optics; Outcome; Outcome Study; Patients; Pattern; Performance; Perfusion; Phase; Physicians; Pilot Projects; Population; Positioning Attribute; Premature Infant; Pulse Oximetry; Reperfusion Injury; Risk; Rubber; Rupture; Severities; Signal Transduction; Skin; Spectrum Analysis; Survival Rate; System; Target Populations; Technology; Testing; Time; United States; Update; Validation; Variant; Woman; Work; aggressive therapy; base; blind; commercialization; design; disability; dosage; flexibility; high risk; improved; in vivo; indexing; individualized medicine; intraventricular hemorrhage; light weight; mortality; non-invasive monitor; novel; opioid epidemic; optical fiber; optical sensor; personalized medicine; postnatal; premature; pressure; sensor; severe intellectual disability; standard of care; success; tool; trend; ventilation

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.

项目概要/摘要 在美国，每年 60,000 名婴儿中约有 30% 是极早产儿（<30 周） 胎龄和<1000克出生体重[ELGA]）与脑室内出血（IVH）有关。 具有脑瘫和严重智力障碍的高风险，对受影响的人造成终生影响 IVH是由脆弱的破裂造成的儿童及其家庭相当大的经济负担。 生发基质中的毛细血管无法承受 90% 以上的脑血流量 (CBF) 波动。 在某些情况下，这些损伤发生在产后头三天心肺不稳定期间 这对 CBF 有直接影响，导致脑电流低灌注和高灌注时期。 管理策略，例如通气或正性肌力支持的改变，对 CBF 的影响视而不见。 迫切需要改进床边技术来持续监测 CBF，以便临床医生能够 明智的决策，优化当前战略并促进制定新的干预措施，以减少 ELGA 婴儿的 IVH 发生率并改善发育结果 基于 149 医学基础。 团队十年来成功使用非侵入性床边光学方法测量婴儿，我们建议设计 并建立了一种新型快速多距离漫相关光谱（DCS）系统，针对连续测量进行了优化 ELGA 婴儿的 CBFi 监测通过测量直接量化脑血流量 (CBFi) 指数。 通过红细胞的动态散射而移动的光的时间波动可用于 对于 ELGA 婴儿，这款床边监护仪需要安全、连续、精确、可靠、定量且轻柔 通过设计一种可以轻柔地应用于可穿戴设备的光学传感器，可以满足这些先决条件。 ELGA 婴儿的新型 DCS 系统将由 149 Medical 团队在体模中进行初步测试以进行验证。 性能并展示流量估计的精度和准确性，然后将对该系统进行更多测试。 布莱根妇女医院 (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、长时间监测后皮肤的完整性，以及 最后，该设备将在 50 名 ELGA 婴儿出生后 72 小时内使用。 检验我们的假设，即 DCS 测量的 CBFi 波动和压力被动事件与发病率相关 我们的目标是提供急需的脑血流监测仪来指导个体化治疗。 治疗的目标是降低 IVH 风险并改善长期神经发育结果 ELGA 婴儿。这项针对 50 名 ELGA 婴儿的研究将为更大规模的试验和商业化奠定基础。