Validation in Baboon Model of Broadband NIR Monitoring for Neonate Gut Perfusion

描述（由申请方提供）：极早产新生儿的床旁管理依赖于传统的监测方法，如动脉血压、心率、脉搏血氧测定、尿量和代谢性酸中毒的证据。然而，这些参数可能会延迟或误导不良组织灌注的检测。即使组织灌注可能不足，动脉血压也可能由于代偿性血管收缩而在正常范围内。尽管这些措施被广泛使用，但没有研究表明使用这些措施可以改善结局，单独依赖这些措施可能导致不适当的心血管干预。组织光谱学可以通过测量局部静脉加权血氧饱和度来提供对向组织输送氧气的充分性的更直接的测量，并且对局部缺血敏感。Spectros于2006年推出了第一台可见光光谱血氧仪T-Stat。T-Stat通过使用可见光而不是近红外（更常用于组织血氧测定），并通过结合宽带光谱（数百个波长）来进一步提高测量精度，从而实现了更高的性能。Spectross现在正在通过宽带可见光/红外血氧仪将这种方法扩展到红外线，从而可以可靠地测量许多物质。肠功能受损是新生儿重症监护中发病率和死亡率的主要来源。肠功能障碍表现为喂养不耐受、生长不良、吸收不良，在最严重的情况下，还表现为坏死性小肠结肠炎（NEC）。虽然NIRS血氧测定装置已在新生儿中体细胞（肾脏、肠道）应用，但其无法补偿组织中不同水平的脂肪、水和粪便，严重限制了其作为体细胞灌注监测器的实用性。因此，期望开发一种使用光谱的可见/近红外部分的非侵入性躯体监测器，其实现非侵入性躯体监测所需的穿透深度，但是其还结合了补偿可能存在的水、脂肪和粪便所需的宽带分析技术。这项研究的影响可能真的很大。该项目旨在研究组织灌注作为早期识别循环系统受损的标志物，从而早期识别有躯体器官损伤风险的患者。通过这些患者的早期识别，我们预计可以开发灌注目标，以更好地管理喂养，输血和使用正性肌力药物，以显着改善这些患者的结局并降低住院费用。目的1 -减少制造宽带维斯/NIR组织血氧仪，用于监测肠道的氧合，在刚刚完成的NIH可行性研究中原型化，具有针对粪便、脂肪和水校正的值。目的2 -在早产狒狒极低出生体重儿模型中，确定宽带血氧仪检测组织灌注和肠血流量诱导变化的有效性。 目的3 -确定与T-Stat灌注监测仪配合使用的探头的安全性。 公共卫生相关性：在新生儿重症监护室对极早产儿的临床管理具有挑战性。我们将在狒狒模型中测试一种新设备的性能，该设备用于非侵入性地监测早产新生儿重要器官的血流充足性。由于未成熟的心脏和肺可能还没有达到允许它们在没有干预的情况下发挥功能的发育阶段（例如呼吸支持、输血和血管活性药物的给药），因此许多用于成人评估心肺功能的常用工具要么不能使用，要么不足以用于这些较小的患者。该设备最终设计用于早产儿，使NICU医生能够更及时和准确地调整影响心脏和血管功能的护理。

DESCRIPTION (provided by applicant): The bedside management of extremely pre-term neonates relies on the traditional methods of monitoring such as arterial blood pressure, heart rate, pulse oximetry, urine output and evidence of metabolic acidosis. However, these parameters may be delayed or misleading in the detection of poor tissue perfusion. Very frequently even though tissue perfusion may be inadequate, the arterial blood pressure may be in a normal range due to compensatory vasoconstriction. Despite their widespread use, no study has shown that use of these measures improves outcome, and reliance on these measures alone, may result in inappropriate cardiovascular intervention. Tissue spectroscopy can provide a more direct measure of the adequacy of oxygen delivery to tissue, by measuring local, venous-weighted, blood oxygen saturation, and is sensitive to local ischemia. Spectros introduced the first visible light spectroscopy oximeter, T-Stat, in 2006. The T-Stat achieves improved performance by using visible light as opposed to near-infrared (more commonly used in tissue oximetry), and by incorporating broadband spectroscopy (hundreds of wavelengths) to further improve accuracy of the measurement. Spectros is now extending this approach into the infrared with broadband visible/infrared oximetry, allowing for a number of substances to be reliably measured. Impaired intestinal function is a major source of morbidity and mortality in neonatal intensive care. Intestinal dysfunction is manifested by feeding intolerance, poor growth, malabsorbtion, and, in the severest cases, necrotizing enterocolitis (NEC). While NIRS oximetry devices have been applied somatically (renal, gut) in neonates, their inability to compensate for varying levels of fat, water and stool in the tissue has severely limited their utility as monitors of somatic perfusion. It is therefore desirable to develop a non-invasive somatic monitor using the visible/near-infrared portion of the spectrum that achieves the depth of penetration necessary for non-invasive somatic monitoring, but which also incorporates the broadband analysis techniques required to compensate for water, fat and stool that may be present. The impact of this study could be truly significant. This project is designed to study tissue perfusion as a marker for the early identification of circulatory compromise, providing early identification of patients at risk of somatic organ damage. Through the early identification of these patients, we anticipate perfusion targets can be developed to better manage feeding, transfusion, and use of inotropes to significantly improve outcome and reduce hospital costs for these patients. Aim 1 - To reduce to manufacturing a broadband Vis/NIR tissue oximeter for monitoring the oxygenation of the gut, prototyped in a just-completed NIH feasibility study, with values corrected for stool, fat, and water. Aim 2 - To determine the efficacy of the broadband oximeter to detect induced changes in tissue perfusion and intestinal blood flow in a premature baboon model for very low birth weight infants. Aim 3 - To determine the safety of probes used with the T-Stat Perfusion Monitor. PUBLIC HEALTH RELEVANCE: The clinical management of extremely pre-term neonates in the neonatal intensive care unit is challenging. We will test, in a baboon model, the performance of a new device to non-invasively monitor the sufficiency of blood flow to important organs in the premature neonate. As immature hearts and lungs may not have reached the developmental stage that allows them to function without interventions (such as ventilatory support, blood transfusions, and administration of vaso-active drugs), many of the common tools used in adults to assess heart and lung function either cannot be used, or are inadequate for use in these smaller patients. Designed ultimately for use on premature neonates, this device would enable NICU physicians to make more timely and accurate adjustments to care affecting the function of the heart and blood vessels.