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; 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.

项目摘要/摘要 每年在美国，每年的60,000名婴儿中约有30％非常早（<30周） 胎龄和<1000 g的出生体重[ELGA]）发生脑室内出血（IVH）。 IVH是关联的 具有脑瘫和重大智力障碍的高风险，对受影响的人产生了终生影响 儿童及其家人和巨大的经济负担。 IVH是由脆弱的破裂引起的 生发基质中的毛细血管无法承受脑血流（CBF）的波动。在> 90％中 案例，这些伤害发生在心脏呼吸不稳时的前三天的前三天 这对CBF具有直接影响，这导致脑部低血症和过度灌注时期。当前的 管理策略，例如通风或肌电支持的变化，对CBF的影响视而不见。 迫切需要改进的床头技术以连续监测CBF，以使临床制作 明智的决定，优化当前策略并促进新干预措施的发展，以减少 ELGA婴儿IVH的发病率并改善发育效果。建立在149个医疗创业 团队通过非侵入性床旁光学方法进行了十年的成功测量婴儿，我们建议设计 并建立一个新颖的快速多距离弥散相关光谱（DCS）系统，可用于连续 在ELGA婴儿中监测CBFI。 DC通过测量直接量化脑血流（CBFI）的指数 动态红细胞动态散射产生的光的暂时波动。用 Elga婴儿，此床旁监视器需要安全，连续，精确，可靠，定量且轻轻地 可穿戴。这些先决条件将通过设计一个可以轻轻地应用于的光学传感器来满足 ELGA婴儿。新颖的DCS系统最初将由149个医疗团队在Phantoms进行测试以验证 性能并证明流量估计的精度和准确性。然后将对系统进行更多测试 Brigham and妇女医院（BWH）NICU成熟，稳定的早产婴儿，以评估可行性 长期测量，与NICU环境的兼容性，长期监测后的皮肤完整性以及 体内算法验证。最后，该设备将在生命的最初72小时内使用50位ELGA婴儿 测试我们的假设，即DCS测量CBFI波动和压力事件与入射相关 和IVH的严重性。我们的目标是提供急需的脑血流监测仪，以指导个性化的 以降低IVH的风险并改善长期神经发育结果的目的 ELGA婴儿。在50名ELGA婴儿中进行的这项研究将为更大的试验和商业化奠定基础。