Continuous Photoacoustic Monitoring of Neonatal Stroke in Intensive Care Unit

重症监护病房新生儿中风的连续光声监测

• 批准号: 10548689
• 负责人: Emad M Boctor
• 金额: $ 34.45万
• 依托单位: BRIMROSE TECHNOLOGY CORPORATION
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-02 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10548689
• 关键词: Accounting; Acoustics; Acute; Address; Adult; Affect; Algorithms; Area; Birth; Blood; Brain; Brain Hypoxia-Ischemia; Brain Injuries; Brain region; Cerebral Ischemia; Cerebral Palsy; Cerebral cortex; Child; Chronic; Clinical; Clinical Trials; Computer software; Coupled; Detection; Development; Developmental Disabilities; Devices; Diagnosis; Differential Diagnosis; Early Diagnosis; Encephalopathies; Fiber; Frequencies; Goals; Head; Helmet; Hemiplegia; Hour; Human; Hybrids; Image; Incidence; Infant; Inflammation; Intensive Care Units; Ischemic Stroke; Laboratories; Lasers; Life; Light; Lighting; Live Birth; Machine Learning; Magnetic Resonance Imaging; Measurement; Modeling; Monitor; Monte Carlo Method; Muscle hypotonia; Neonatal; Neonatal Brain Injury; Neonatal Intensive Care Units; Nervous System Trauma; Neurologic; Neurologic Symptoms; Neuroprotective Agents; Newborn Infant; Optics; Oxyhemoglobin; Parents; Pathway interactions; Performance; Phase; Physiologic pulse; Pre-Clinical Model; Preclinical Testing; Preparation; Prognosis; Research; Resolution; Risk; Robot; Safety; Sagittal Sinus; Sampling; Scalp structure; Seizures; Shapes; Signal Transduction; Small Business Technology Transfer Research; Source; Stratification; Stroke; System; Systems Integration; Techniques; Technology; Term Birth; Testing; Therapeutic; Therapeutic Embolization; Thick; Thrombus; Time; Tissues; Triage; Universities; Width; acoustic imaging; base; brain tissue; cerebral artery; commercialization; contrast imaging; cranium; deep neural network; deoxyhemoglobin; design; detector; effective therapy; fetus hypoxia; in silico; innovation; lightspeed; magnetic field; microphone; monitoring device; natural hypothermia; neonatal brain; neonatal encephalopathy; neonatal hypoxic-ischemic brain injury; neonatal stroke; neonate; neuroprotection; novel therapeutics; perinatal ischemic stroke; perinatal period; perinatal stroke; personalized management; photoacoustic imaging; pre-clinical; prognostic; prototype; signal processing; stroke incidence; stroke trials; success; tool; treatment planning; ultrasound; validation studies

PROJECT SUMMARY/ABSTRACT Neonatal encephalopathy can arise from fetal hypoxia-ischemia during labor, chronic uteroplacental inflammation, and large cerebral artery embolization primarily arising from dislodgement of a placental thrombus. Because of overlapping clinical presentation, differential diagnosis is often delayed until seizures develop and MRI can be safely performed, a time at which most neuroprotectants are ineffective. Whereas hypothermia is approved for use within 6 hours of birth for hypoxia-ischemia, no treatments have been approved for perinatal arterial ischemic stroke because of the difficulty of definitive diagnosis required for clinical trial stratification at birth. With an estimated incidence of 17-93 per 100,000 live births, the incidence of stroke in the perinatal period rivals the incidence of stroke in adults (17-23 per 100,000). Therefore, a device that could rapidly and reliably identify an area of focal cerebral ischemia soon after birth would have a major impact by enabling the testing of neuroprotectants at an early therapeutic time window that would maximize efficacy. The Brimrose Technology Corporation, partnering with Johns Hopkins University, propose a photoacoustic helmet (PAH) device that can be safely deployed at the bedside in the neonatal intensive care unit to 1) continuously monitor and rapidly identify at-risk neonates, shortly after birth, rapidly allowing them to be triaged to therapy; 2) monitor the progress of therapy; and 3) provide prognostic information to the parents of newborns at risk for life-long brain injury. The PA imaging mechanism is a purely hybrid mechanism, providing rich optical absorbance contrast of tissue oxy- and deoxyhemoglobin through intact scalp and skull. A proof-of-concept of detecting decreased tissue oxyhemoglobin in a 1 cm-induced experimental stroke has been demonstrated with standard laboratory PA laser light source and clinical ultrasound detector. Our goal is to incorporate safer light-emitting diodes (LEDs) and more sensitive ultrasound detectors configured in a neonatal helmet to localize cortical regions of low oxygenation in the newborn. In the proposed Phase-I STTR, we will develop fundamental hardware and software components for effective integration. Aim 1 - Software for safe PAH imaging at high contrast resolution, including deep neural network and optimal spectral unmixing techniques to enable a safe and high-speed LED-based PAH system. Aim 2 - Hardware for modular PAH system, including a fiber-coupled Brimrose ultra-sensitive multi- bounce laser microphone and optimal modular unit design for a PAH imaging at high spatial-temporal-spectral resolution through intact scalp and skull. Aim 3 - Framework for modular PAH system integration, enabling a robust integration of modular units in a PAH system with rigid-body tag registration using optical tracking, in which different neonatal head shapes and need for different imaging specifications can be accommodated. The Phase-I milestone is detection of the full blood O2 saturation range at <10 mm full-width-half-maximum in the transverse plane and 5 mm sensing depth through ex vivo neonatal piglet skull + scalp sample with an integrated set of hardware and software packages, allowing preclinical validation studies to proceed in Phase II.

项目总结/摘要 新生儿脑病可由分娩时胎儿缺氧缺血、慢性子宫胎盘炎、 炎症和主要由胎盘血栓移位引起的大脑动脉栓塞。 由于重叠的临床表现，鉴别诊断往往被推迟，直到癫痫发作的发展， MRI可以安全地进行，此时大多数神经保护剂无效。而体温过低 批准在出生后6小时内用于缺氧缺血，尚未批准用于围产期 动脉缺血性卒中，因为临床试验分层需要明确诊断， 出生估计发病率为每100，000例活产17-93例，围产期中风发病率 与成人中风发病率（17-23/100，000）相当。因此，一种可以快速可靠地 在出生后不久确定一个局灶性脑缺血区域将产生重大影响， 在早期的治疗时间窗口，神经保护剂将最大限度地提高疗效。Brimrose技术 公司与约翰霍普金斯大学合作，提出了一种光声头盔（PAH）设备， 安全地部署在新生儿重症监护病房的床边，以1）连续监测和快速监测 在新生儿出生后不久就识别出高危新生儿，迅速将其分类治疗; 2）监测进展情况 3）为有终身脑损伤风险的新生儿父母提供预后信息。的 PA成像机制是一种纯混合机制，提供了组织氧合物的丰富的光吸收对比度。 和脱氧血红蛋白的混合物检测组织减少的概念验证 用标准实验室PA激光已经证明了在1cm诱导的实验性中风中的氧合血红蛋白 光源和临床超声探测器。我们的目标是采用更安全的发光二极管（LED）， 新生儿头盔中配置更灵敏的超声探测器，以定位低皮质区域 新生儿的氧合。在拟议的第一阶段STTR中，我们将开发基本硬件和软件 有效整合的组成部分。目标1 -用于高对比度分辨率下安全PAH成像的软件，包括 深度神经网络和最佳光谱分解技术，以实现安全和高速的LED PAH 系统目标2 -模块化PAH系统的硬件，包括光纤耦合Brimrose超灵敏多功能 用于高时空谱下PAH成像的反射激光麦克风和最佳模块化单元设计 通过完整的头皮和头骨的分辨率。目标3 -模块化PAH系统集成框架， PAH系统中的模块化单元与使用光学跟踪的刚体标签配准的鲁棒集成， 其可以适应不同的新生儿头部形状和对不同成像规格的需要。的 第一阶段的里程碑是在<10 mm的半高全宽处检测到全血氧饱和度范围， 横向平面和5 mm传感深度通过离体新生仔猪颅骨+头皮样品， 一套硬件和软件包，允许在第二阶段进行临床前验证研究。