Detection and Quantification of Neonatal Intraventricular Hemorrhage

描述(由申请人提供)：临床新生儿监测对急性病理的诊断和预后也是至关重要的。其中一种病理是新生儿脑室出血(IVH)，这是早产的常见后果，大约30%的体重低于1500克的婴儿有不同程度的出血。虽然一些新生儿表现出明显的与IVH相关的外在体征，如呼吸暂停、苍白、癫痫发作和代谢性酸中毒，但高达50%的IVHS可能在临床上是沉默的。大的IVHS与不良的神经结局相关。不利的神经发育后遗症包括脑性瘫痪、癫痫发作、出血后脑积水(可能需要脑室-腹膜分流术)、失明、耳聋和认知障碍(Hintz和O‘Shea 2008，Goldenberg和Jobe 2001)。虽然超声波几乎被普遍用作出生7天的回顾性筛查，但50%的IVHS发生在生命的第一天(75%发生在前3天)。进一步的超声对II级IVHS的敏感性较低(Babcock等人1982年，Mack等人1981年)，其作为诊断工具的可用性取决于操作员，可用时间有限。临床表现的多样性和早期干预的需要强调了需要一种简单易懂的设备，能够实时监测和检测正在发生的IVHS，从而允许实施支持性治疗(血液制品)或治疗(激活的因子VII)。虽然IVH的临床后果很严重，但对其确切病因知之甚少。通过回顾性研究，许多生理障碍(例如，脑血流自动调节丧失、中心静脉压升高、低血压)与IVHS相关，但这些参数之间尚不存在确切的因果关系(Ballabh 2010)。此外，IVH的发生率与IVH中观察到的神经电异常(如阳性罗兰氏尖波和癫痫发作)之间的因果联系尚未确定。在这个项目中，我们建议开发一种设备，用于未来在IVH背景下全面调查循环和神经电异常之间的联系。如果成功，这种装置不仅有助于了解导致IVH的潜在机制，而且还可以用于早期识别发展中的出血，并结合适当的治疗，限制出血和其他脑损伤的程度。对早产儿的监测提出了独特的挑战，其中之一是理想的非侵入性床边监测。我们之前已经开发了一种电子成像设备，它使用类似EEG的电极阵列来连续监测和量化新生儿脑室中的小(0.5毫升)血液积聚。我们建议开发一种监测设备，可以使用相同的电极阵列同时收集脑电和出血状态数据，而对临床管理的影响最小。来自该设备的数据将以一种也允许与其他生理监测系统进行比较的方式提供。

DESCRIPTION (provided by applicant): Clinical neonatal monitoring is also vital for diagnosis and prognosis of acute pathologies. One such pathology, neonatal intraventricular hemorrhage (IVH), is a common consequence of premature birth, with approximately 30 percent of infants weighing less than 1500 g having some degree of bleeding. While some neonates exhibit clear outward signs related to IVH such as apnea, pallor, seizures and metabolic acidosis, up to 50 percent of IVHs may be clinically silent. Large IVHs are associated with unfavorable neurologic outcomes. Adverse neurodevelopmental sequelae include cerebral palsy, seizures, posthemorrhagic hydrocephalus (which may require a ventriculoperitoneal shunt), blindness, deafness, and cognitive impairment (Hintz and O'Shea 2008, Goldenberg and Jobe 2001). Although ultrasound is almost universally employed as a retrospective screen at 7 days of life, 50 percent of IVHs occur during the first day of life (and 75 percent in the first 3 days). Further ultrasound is less sensitive to Grade II IVHs (Babcock et al 1982, Mack et al 1981), and its availability as a diagnostic tool is operator dependent, with limited hours of availability. The variation in clinical presentation and need to intervene early stresses the need for a simple to interpret device that can monitor and detect developing IVHs in real time, allowing administration of supportive therapies (blood products) or treatments (activated factor VII). While the clinical consequences of IVH are severe, little is known about its exact etiology. Many physiologic disturbances (e.g., loss of cerebral blood flow autoregulation, increased central venous pressure, hypotension) have been associated with IVHs through retrospective studies, but exact cause-effect relationships between these parameters do not exist (Ballabh 2010). Further, causal connections between the incidence of IVH and neuroelectric abnormalities observed in IVH such as positive rolandic sharps and seizures have not been established. In this project we propose developing a device that can be used in a future comprehensive investigation of the connections between circulatory and neuroelectric abnormalities in the context of IVH. If it is successful, this device may not only aid understanding of the underlying mechanisms leading to IVH, but also be of use in early identification of developing bleeds, and combined with appropriate therapies, limiting the extent of bleeding and other brain damage. Monitoring of premature infants poses unique challenges, one of these being the ideal of non-invasive bedside monitoring. We have previously developed an electrical imaging device that uses an EEG- like electrode array to continuously monitor and quantify small (< 0.5 ml) blood accumulations in the neonatal ventricles. We propose developing a monitoring device that can simultaneously gather EEG and bleeding status data using the same electrode array, with minimal impact on clinical management. Data from the device will be made available in a manner that also allows comparison with other physiological monitoring systems.