Monitoring Brain Health in Neonatal Congenital Heart Disease with Bedside CMR02

描述(申请人提供)：严重先天性心脏病(CHD)仍然是婴儿发病率的常见原因，每年每1000名活产中有6-8名发生。高达50%的患有CHD的新生儿在出生后的头几周需要进行心脏直视手术。尽管由于手术修复的进步，存活率有所提高，但高达50%的患者损害了神经发育结果。持续较高的神经发育结局损害率可能是由于先前存在的宫内脑发育障碍和/或因血流动力学不稳定而在术后早期发生的脑损伤。事实上，CHD受试者的术前新生儿和胎儿核磁共振成像(MRI)研究提供了证据，表明在宫内大脑发育受到影响，特别是当CHD导致脑血流灌注不良时。在手术中，由于低温降低了神经元的活性，从而减少了氧气需求，因此在心内直视手术修复所需的低血流状态下，低温被用来保护大脑。然而，手术后，随着复温和心脏的恢复，大脑仍然特别脆弱。目前，通过床边连续波近红外光谱(CWNIRS)测量额部脑组织相对氧饱和度(RStO2)来评估手术前的脑健康状况，并对急性缺氧缺血性脑损伤进行术后监测。这些rStO2指标用于指导治疗决策，但我们已经表明，StO2对正常早产儿和足月儿的脑发育不敏感，对新生儿急性缺氧缺血性脑损伤不敏感。虽然氧是神经元的主要燃料，但rStO2并不能反映神经元的耗氧量，而且受到血流量、红细胞压积等多种非神经元因素的影响。相比之下，床边频域近红外光谱(FDNIRS)与弥散相关光谱(DCS)相结合，通过提供神经元相对脑耗氧量(RCMRO2)的绝对测量，提供了神经元健康的直接测量。我们已经证明FDNIRS-DCSRCMRO2对脑发育和急性缺氧缺血性脑损伤是敏感的。我们建议使用CMRO2i的床边FDNIRS-DCS测量来评估术前脑健康和监测术后缺氧缺血性脑损伤。我们的目标是建立床边FDNIRS-DCS作为一种信息丰富的床边工具，用于评估和监测接受先天性心脏病心内直视手术的新生儿的脑健康。如果成功，这个项目可能会产生直接和立竿见影的临床影响。

DESCRIPTION (provided by applicant): Severe congenital heart disease (CHD) remains a common cause of infant morbidity, occurring in 6-8 per 1,000 live births per year. Up to 50% of neonates presenting with CHD will require open-heart surgery in the first few weeks of life. Although survival has increased due to progress in surgical repair, up to 50% have impaired neurodevelopmental outcomes. The persistently high rates of impaired neurodevelopmental outcomes may be due to pre-existing impairments in intrauterine cerebral development and/or brain injury that occurs in the early postoperative time period due to hemodynamic instability. In fact, preoperative neonatal and fetal magnetic resonance imaging (MRI) studies of subjects with CHD provide evidence that in utero brain development is compromised, particularly when the CHD results in poor brain perfusion. Intra-operatively, hypothermia is used to protect the brain during the low flow state required for open-heart surgical repair as hypothermia decreases neuronal activity, and therefore oxygen demand. However, post-operatively, as rewarming occurs and the heart recovers, the brain remains particularly vulnerable. Currently, preoperative brain health is assessed and post-surgical monitoring for acute hypoxic ischemic brain injury is performed with bedside continuous wave near infrared spectroscopy (CWNIRS) measures of frontal brain relative tissue oxygen saturation (rStO2). These rStO2 measures are used to guide treatment decisions, but we have shown that StO2 is insensitive to brain growth in normal preterm and term children, and is insensitive to acute hypoxic ischemic brain injury in neonates. Although oxygen is the primary fuel for neurons, rStO2 does not reflect the amount of oxygen consumed by neurons, and is affected by multiple non-neuronal factors such as blood flow and hematocrit. In contrast, bedside frequency domain NIRS (FDNIRS) combined with diffuse correlation spectroscopy (DCS) provide direct measures of neuronal health by providing absolute measures of neuronal relative cerebral oxygen consumption (rCMRO2). We have shown that FDNIRS-DCS rCMRO2 is sensitive to brain development and to acute hypoxic ischemic brain injury. We propose to use bedside FDNIRS-DCS measures of CMRO2i to assess preoperative brain health and monitor for postoperative hypoxic ischemic brain injury. Our goal is to establish bedside FDNIRS-DCS as an informative bedside tool for assessing and monitoring brain health in neonates undergoing open-heart surgery for CHD. If successful, this project may have a direct and immediate clinical impact.