Monitoring of Cardiovascular Function in Infants By Transcutaneous Dye Dilution

描述(由申请人提供)：心输出量(CO)和心脏前负荷(中心血容量，CBV)和全身血管阻力(SVR)的测量是循环功能的关键临床参数。热稀释技术是目前公认的测量CO的标准。然而，这种测量所需的肺动脉导管的放置和维护在新生儿和婴儿中具有技术挑战性，并与导管相关的并发症有关。血容量测量可以定量进行，然而，这些测量通常涉及注射放射性标记示踪剂和/或广泛的连续采血，而且很少进行。事实上，这些患者的低灌注状态(休克)的治疗目前主要是根据血压和其他间接的、相当不可靠的组织灌注迹象做出的临床决定。这些局限性促使人们研究更新、侵入性更小的技术。我们最近描述了一种新的指示剂稀释方法和仪器，用于评估CO、循环血容量(BV)、CBV和SVR，该方法基于FDA批准的药物吲哚青绿(ICG)的静脉推注和循环血ICG荧光的光学测量。我们现在建议开发和验证一种皮肤探头，它可以用于经皮测量心血管参数。挑战在于皮肤的血流是动态的，这会影响荧光信号的强度。我们建议通过设计一种探测器来解释这种可变性，该探测器将循环ICG的光学荧光测量与使用公认的激光多普勒技术的皮肤部位的局部血液灌流测量相结合。这将使我们能够调整我们的荧光染料稀释信号，以准确地得出CO、CBV和SVR，而不考虑局部皮肤灌注的变化。目标1是在兔模型中开发和验证这种皮肤探头。目的2是在南加州大学/达维塔肾脏中心接受门诊血液透析的成人受试者中验证临床级别的皮肤探头。目的3是在洛杉矶儿童医院新生儿和婴儿重症监护病房的新生儿和婴儿中测试该探头，并与功能超声心动图获得的CO值进行比较。目前，临床上存在对微创技术的强烈需求，这种技术可以快速、连续地测量新生儿和婴儿的心功能。这项拟议的技术将导致开发一种实用的设备，用于在重症监护、手术和手术后环境中使用最少器械的新生儿，以及那些病情不适合使用中央监测的患者。这项申请是为了响应NHLBI关于改善心脏成像技术的研究重点(2002年儿科心血管疾病研究特别工作组报告)，以及NCRR的战略重点(2009-2013年)将生物医学技术创新纳入临床研究，以及NIBIB的战略计划(2006)促进跨学科研究，以加速将有前景的技术转化为改善人类健康的技术。 与公共卫生相关：目前，临床上迫切需要一种微创技术，它可以为危重新生儿和婴儿提供快速、连续的心功能和循环血量测量，这些新生儿和婴儿的身体较小，使得更具侵入性的方法(肺动脉热稀释导管)在技术上具有挑战性，并与重大风险相关。事实上，目前有关治疗低血流灌注状态(休克)的临床决定主要是根据血压和其他间接的、相当不可靠的组织灌注迹象做出的。我们的建议通过开发和验证光学探头来满足这一需求，该探头可用于通过皮肤测量心脏功能，用于新生儿重症监护和病情不足以证明使用更具侵入性监测的患者。

DESCRIPTION (provided by applicant): Cardiac output (CO) and measures of cardiac preload (central blood volume, CBV) and systemic vascular resistance (SVR) are critical clinical parameters of circulatory function. The thermodilution technique is the accepted standard for measurement of CO. However, placement and maintenance of a pulmonary artery catheter required for such a measurement is technically challenging in neonates and infants and is associated with catheter-associated complications. Blood volume measurements can be performed quantitatively, however, these typically involve injection of radiolabelled tracers and/or extensive serial blood sampling and are infrequently performed. In fact, clinical decisions about the treatment of low perfusion states (shock) in these patients are currently being made based primarily on blood pressure and other indirect, fairly unreliable signs of tissue perfusion. These limitations have motivated studies of newer, less invasive techniques. We recently described a new indicator dilution method and instrumentation for assessing CO, circulating blood volume (BV), CBV, and SVR that is based on an intravenous bolus injection of the FDA-approved drug indocyanine green (ICG) and optical measurement of circulating blood ICG fluorescence. We now propose to develop and validate a skin probe, which can be used to measure cardiovascular parameters transcutaneously. The challenge is that skin perfusion is dynamic, which can affect the intensity of the fluorescence signal. We propose to account for this variability by designing a probe that combines the optical fluorescence measurements of circulating ICG with the measurement of local blood perfusion at the skin site using the well-established laser Doppler technique. This would allow us to adjust our fluorescence dye dilution signals to accurately derive CO, CBV, and SVR, irrespective of changes in local skin perfusion. Aim 1 is to develop and validate such a skin probe in a rabbit model. Aim 2 is to validate a clinical grade skin probe in adult subjects undergoing outpatient hemodialysis at the USC/DaVita Kidney Center. Aim 3 is to test the probe in neonates and infants in the Newborn and Infant Critical Care Unit at Children's Hospital Los Angeles and compare CO values with those obtained by functional echocardiography. Currently, a strong clinical need exists for a minimally invasive technique, which can provide rapid, serial measurements of cardiac function in neonates and infants. The proposed technique will lead to the development of a practical device for monitoring CO in minimally instrumented neonates in intensive care, operative and postsurgical settings, and in patients whose condition does not justify the use of central monitoring. This application is responsive to the NHLBI's research priority for improved technologies to image the heart (Task Force Report on Research in Pediatric Cardiovascular Disease, 2002), as well as the strategic priority (2009-2013) of the NCRR to incorporate innovations in biomedical technology into clinical research, and the NIBIB's Strategic Plan (2006) to foster interdisciplinary research for the accelerated translation of promising technologies to improve human health. PUBLIC HEALTH RELEVANCE: Currently, a strong clinical need exists for a minimally invasive technique, which can provide rapid, serial measurements of cardiac function and circulating blood volume in critically ill neonates and infants whose small body size renders more invasive methods (pulmonary artery thermodilution catheter) technically challenging and associated with significant risk. In fact, clinical decisions about the treatment of low perfusion states (shock) are currently being made based primarily on blood pressure and other indirect, fairly unreliable signs of tissue perfusion. Our proposal addresses this need with the development and validation of an optical probe, which can be used to measure cardiac function through the skin for applications in neonatal critical care and in patients whose condition does not justify the use of more invasive monitoring.