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至关重要。新生儿脑室内出血（IVH）是一种常见的早产后果，大约30%的体重小于1500克的婴儿有一定程度的出血。虽然一些新生儿表现出与IVH相关的明显的外部体征，如呼吸暂停、脸色苍白、癫痫发作和代谢性酸中毒，但高达50%的IVH可能在临床上没有症状。较大的ivh与不良的神经系统预后相关。不良的神经发育后遗症包括脑瘫、癫痫、出血性脑积水（可能需要脑室-腹膜分流术）、失明、耳聋和认知障碍（Hintz and O’shea 2008; Goldenberg and Jobe 2001）。尽管超声几乎普遍被用作生命7天的回顾性筛查，但50%的ivh发生在生命的第一天（75%发生在生命的前3天）。此外，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人员，可用时间有限。临床表现的变化和早期干预的需要强调需要一种简单的解释设备，可以实时监测和检测发展中的IVHs，允许给予支持性治疗（血液制品）或治疗（活化因子VII）。虽然IVH的临床后果很严重，但对其确切的病因知之甚少。通过回顾性研究，许多生理障碍（如脑血流自动调节丧失、中心静脉压升高、低血压）与IVHs有关，但这些参数之间不存在确切的因果关系（Ballabh 2010）。此外，IVH发病率与IVH中观察到的神经电异常之间的因果关系，如阳性罗兰发作和癫痫发作尚未确定。在这个项目中，我们建议开发一种设备，可用于未来对IVH背景下循环和神经电异常之间联系的全面调查。如果试验成功，该装置不仅可以帮助了解导致IVH的潜在机制，还可以用于早期识别出血，并结合适当的治疗，限制出血和其他脑损伤的程度。监测早产儿提出了独特的挑战，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成像设备，该设备使用类似脑电图的电极阵列来连续监测和量化新生儿脑室中的少量（< 0.5 ml）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图和出血状态数据，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. PUBLIC HEALTH RELEVANCE: Premature birth accounts for roughly 12 percent of all live births annually in the United States. Despite advances in technologies and treatments in the past decade, the incidence of severe acute complications for very premature infants accompanied by risks for chronic medical conditions, such as cerebral palsy, have not markedly diminished since the mid-1990s. A majority of these neurodevelomental problems are associated with damage to the subventricular zone and subsequent intraventricular hemorrhage. Currently, detection of intraventricular hemorrhage is retrospective. The overall goal of this project is to develop a novel brain-monitoring device that will allow the bedside clinician to improve the delivery of care to these neonates in real time, thereby decreasing the extent of intraventricular hemorrhages and decreasing the severity of neurodevelopmental deficits.