Detection and Quantification of Neonatal Intraventricular Hemorrhage

描述（由申请人提供）：临床新生儿监测对于急性病理的诊断和预后也至关重要。新生儿脑室内出血（IVH）是早产的常见后果，体重小于1500 g的婴儿中约有30%有一定程度的出血。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IVH可能在临床上无症状。大IVH与不利的神经系统结局相关。不良神经发育后遗症包括脑瘫、癫痫、出血后脑积水（可能需要脑室腹膜分流）、失明、耳聋和认知障碍（Hintz and O'Shea 2008，Goldenberg and Jobe 2001）。尽管超声几乎普遍用作出生后7天的回顾性筛查，但50%的IVH发生在出生后第一天（75%发生在出生后前3天）。此外，超声对II级IVH的敏感性较低（Babcock等1982，Mack等1981），其作为诊断工具的可用性取决于操作员，可用时间有限。临床表现的变化和早期干预的需要强调了对简单解释的设备的需要，该设备可以真实的实时监测和检测发展中的IVH，允许给予支持疗法（血液制品）或治疗（活化因子VII）。虽然IVH的临床后果很严重，但对其确切病因知之甚少。许多生理障碍（例如，通过回顾性研究发现，脑血流自动调节丧失、中心静脉压升高、低血压）与IVH相关，但这些参数之间不存在确切的因果关系（Ballabh 2010）。此外，尚未建立IVH发生率与IVH中观察到的神经电异常（如阳性罗兰尖和癫痫发作）之间的因果关系。在这个项目中，我们建议开发一种设备，可用于在IVH的背景下，循环和神经电异常之间的连接在未来的全面调查。如果成功的话，这种装置不仅可以帮助理解导致IVH的潜在机制，而且可以用于早期识别出血，并与适当的治疗相结合，限制出血和其他脑损伤的程度。早产儿的监护带来了独特的挑战，其中之一是理想的无创床边监护。我们先前已经开发了一种电成像设备，其使用类似EEG的电极阵列来连续监测和量化新生儿脑室中的少量（<0.5ml）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EEG和出血状态数据，对临床管理的影响最小。将以允许与其他生理监测系统进行比较的方式提供器械数据。 公共卫生相关性：早产约占美国每年所有活产婴儿的12%。尽管在过去十年中技术和治疗取得了进步，但极早产儿严重急性并发症的发生率以及患慢性疾病（如脑瘫）的风险自1990年代中期以来并没有明显减少。大多数神经发育问题与脑室下区损伤和随后的脑室内出血有关。目前，脑室内出血的检测是回顾性的。该项目的总体目标是开发一种新型的脑监测设备，使床旁临床医生能够改善对这些新生儿的真实的护理，从而减少脑室内血肿的程度，降低神经发育缺陷的严重程度。

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.