Optical Functional Neuroimaging of Acute and Chronic Hypoxia

项目摘要/摘要 我是一名内科医生/科学家，专注于光学神经成像技术的发展，以改善 危重儿童神经损伤的床边检测。我的导师职业发展奖的目标是 是在小鼠缺氧模型以及高级统计方法方面获得培训，以分析 静息状态的大脑活动。这项培训将启动独立的研究生涯，目的是将成像 从长凳到床边的生物标志物。 许多曾经普遍致命的儿科疾病(例如复杂的先天性心脏病和极端的 早产儿)现在的存活率相对较高。然而，神经发育结果有所改善。 只是略微有点。有了及时的干预，将缺氧损伤降至最低是可能的，但目前的床边工具 麻木不仁的，不适合这个目的的。此外，临床人群的异质性限制了临床 学习。每个患者都有独特的损伤和治疗方法，并在不同的时间进行神经成像 因此，很难对这些数据进行严格的分析，以确定最好、最具普遍性的 生物标志物。 本工作旨在通过使用小鼠缺氧性神经损伤模型来解决这些问题， 稳健的统计方法、光学功能神经成像技术和静息状态血流动力学 评估(例如，功能连接)。光学方法类似于功能磁共振 但具有更低的成本、更高的便携性和更高的吞吐量。我的提议将检验这一假设 静息状态血流动力学指标可作为急性和慢性损伤后的神经影像生物标志物 缺氧。AIM 1将开发适用于光学神经成像的统计方法，以允许更强的噪声 过滤、脑分割、图谱和图像分析。目标2将使用静息状态血流动力学在 缺血性卒中超急性期鉴别半影区。目标3将研究 小鼠发育过程中的功能连接网络和慢性低氧血症的破坏性影响。 这项研究将在Arjun Yodh博士的指导下进行，Daniel将共同指导 这两个学院都是光学神经监测技术发展领域公认的领导者。在……里面 此外，我还召集了一个跨学科的合作者小组，他们在老鼠模型方面具有专业知识。 低氧血症、神经影像统计和先进的网络分析方法。我将受益于这一极好的 导师和研究环境，以及我独特的光学神经成像方法提供了一条途径 独立。我是一名获得董事会认证的儿科心脏病专家，我的长期职业目标是将 在一家儿科研究医院担任终身教职的神经成像。特殊的研究环境 在CHOP/Penn，将在重症监护病房进行未来的翻译研究，以及进一步的动物模型 疾病的威胁。 第1页

Project Summary/Abstract I am a physician/scientist focusing on the development of optical neuroimaging techniques to improve bedside detection of neurologic injury in critically-ill children. The goal of my mentored career development award is to acquire training in mouse models of hypoxia as well as in advanced statistical methods for the analysis of resting-state brain activity. This training will launch an independent research career with the aim to bring imaging biomarkers from bench to bedside. Many pediatric diseases that were once universally fatal (e.g., complex congenital heart disease and extreme prematurity) now have relatively good survival rates. However, neurodevelopmental outcomes have improved only marginally. With timely intervention, it is possible to minimize hypoxic injury, but current bedside tools are insensitive and inadequate for this purpose. Furthermore, the heterogeneity of clinical populations limits clinical studies. Each patient has a unique injury and treatment, and neuroimaging is performed at varying times after injury; thus, it can be difficult to rigorously analyze such data to determine the best, most generalizable biomarkers. The present work aims to solve these problems by using mouse models of hypoxemic neurologic injury, robust statistical methods, optical functional neuroimaging techniques, and resting-state hemodynamic assessment (e.g., functional connectivity). The optical methods are similar to functional magnetic resonance imaging but have much lower cost, higher portability, and higher through-put. My proposal will test the hypothesis that resting-state hemodynamic metrics can serve as neuroimaging biomarkers of injury after acute and chronic hypoxia. Aim 1 will develop statistical methods adapted to optical neuroimaging to permit more robust noise filtering, brain segmentation, atlasing, and image analysis. Aim 2 will use resting-state hemodynamics in the hyperacute phase of ischemic stroke to identify the penumbra. Aim 3 will study the longitudinal development of functional connectivity networks across mouse development and the disruptive effects of chronic hypoxemia. This research will be conducted under the mentorship of Arjun Yodh, PhD, with co-mentorship by Daniel Licht, MD; both faculty are recognized leaders in the development of optical neuromonitoring techniques. In addition, I have assembled an interdisciplinary group of collaborators with expertise in mouse models of hypoxemia, neuroimaging statistics, and advanced network analysis methods. I will benefit from this excellent mentorship and research environment, and my unique optical neuroimaging methods offer a path to independence. I am a board-certified pediatric cardiologist, and my long-term career goals are to combine neuroimaging with a tenure-track position at a pediatric research hospital. The exceptional research environment at CHOP/Penn will enable future translational studies in the intensive care unit, as well as further animal models of disease. Page 1