Continuous Photoacoustic Monitoring of Neonatal Stroke in Intensive Care Unit

项目摘要/摘要 新生儿脑病可由分娩过程中胎儿缺氧缺血、慢性子宫胎盘 炎症和主要由胎盘血栓移位引起的大脑大动脉栓塞术。 由于重叠的临床表现，鉴别诊断通常被推迟到癫痫发作和 核磁共振可以安全地进行，在这个时候大多数神经保护剂都是无效的。而体温过低则是 被批准在出生后6小时内用于缺氧缺血，还没有被批准用于围产期的治疗 动脉缺血性卒中，因为临床试验分层所需的确诊诊断困难。 出生。据估计，每10万名活产儿中有17-93人发生中风，围产期中风的发生率 与成年人的中风发病率(每10万人中有17-23人)不相上下。因此，一种可以快速而可靠地 在出生后不久识别局灶性脑缺血区域将产生重大影响，因为它能够测试 在早期治疗时间窗使用神经保护剂，以最大限度地提高疗效。樱草花技术 该公司与约翰·霍普金斯大学合作，提出了一种光声头盔(PAH)设备，它可以 安全地部署在新生儿重症监护病房的床边，以1)持续快速地进行监测 在出生后不久识别高危新生儿，迅速对他们进行分诊治疗；2)监测进展情况 以及3)向面临终身脑损伤风险的新生儿的父母提供预后信息。这个 PA成像机制是一种纯粹的混合机制，提供了组织氧的丰富的光吸收对比度。 和脱氧血红蛋白穿过完整的头皮和头骨。一种检测组织减少的概念验证 用实验室标准PA激光证实了1厘米诱发的实验性中风中的氧合血红蛋白。 光源和临床超声探测仪。我们的目标是整合更安全的发光二极管(LED)和 配置在新生儿头盔中的更灵敏的超声探测器，以定位低血压的皮质区域 新生儿的氧合作用。在拟议的第一阶段技术转让计划中，我们将开发基本的硬件和软件 有效集成的组件。目标1-用于高对比度分辨率的安全PAH成像的软件，包括 深度神经网络和最佳光谱分解技术实现基于LED的安全高速PAH 系统。AIM 2-模块化多环芳烃系统的硬件，包括光纤耦合的BrimRose超灵敏多通道 弹跳激光传声器与高时空光谱PAH成像模块的优化设计 通过完整的头皮和头骨进行分解。AIM 3-模块化PAH系统集成框架，支持 PAH系统中的模块单元与使用光学跟踪的刚体标签配准的强健集成 可以适应不同的新生儿头部形状和不同成像规格的需求。这个 第一阶段的里程碑是检测全血氧饱和度范围在&lt；10 mm全宽-半最大值在 经体外新生仔猪头皮标本横断平面和5 mm传感深度的整合 一套硬件和软件包，允许在第二阶段进行临床前验证研究。

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.