Optical Functional Neuroimaging of Acute and Chronic Hypoxia

急性和慢性缺氧的光学功能神经影像

基本信息

批准号：
10646274
负责人：
BRIAN Richard WHITE
金额：
$ 16.86万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10646274
关键词：
Acute Adult Affect Algorithms Animal Disease Models Anxiety Architecture Area Biological Markers Board Certification Brain Brain Mapping Childhood Chronic Clinical Clinical Research Communities Complex Critical Care Critical Illness Critically ill children Data Detection Development Diagnosis Diffusion Disease Doctor of Philosophy Environment Faculty Frequencies Functional Magnetic Resonance Imaging Funding Future Goals Histologic Histology Hospitals Hour Human Hypoxemia Hypoxia Hypoxic Brain Damage Image Image Analysis Impairment Infarction Injury Intensive Care Units Intervention Ischemia Ischemic Stroke K-Series Research Career Programs Knowledge Learning Life Link Location Longitudinal Studies Magnetic Resonance Imaging Managed Care Measures Medical Mentors Mentorship Methods Modeling Molecular Monitor Mus Neonatal Nervous System Trauma Neurologic Neurons Noise Onset of illness Operative Surgical Procedures Optical Methods Optics Outcome Pathway Analysis Patients Pediatric Research Perfusion Phase Physicians Population Positioning Attribute Reperfusion Therapy Reproducibility Research Rest Role Sampling Scientist Severities Severity of illness Signal Transduction Source Statistical Data Interpretation Statistical Methods Stroke Survival Rate System Techniques Testing Therapeutic Intervention Tissue Viability Tissues Training Translating Translations Variant Work acute stroke behavior test bench to bedside biomarker development career clinical care clinical examination clinical heterogeneity congenital heart disorder cost effective intervention extreme prematurity fetal hemodynamics image registration imaging biomarker improved improved outcome middle cerebral artery mouse development mouse genetics mouse model neonatal hypoxic-ischemic brain injury neonatal injury neonate nervous system disorder neuroimaging neuroimaging marker normoxia novel novel therapeutics optical imaging pediatric cardiologist pediatric patients portability post stroke preclinical development serial imaging skills statistics success tenure track tool translational study trend ultrasound white matter

项目摘要

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

项目摘要/摘要我是一名医生/科学家，致力于发展光学神经影像学技术以改进严重的儿童神经损伤的床边检测。我指导职业发展奖的目标是在低氧小鼠模型以及高级统计方法中获得培训，以分析静止状态的大脑活动。这项培训将启动独立的研究职业，旨在带来成像从长凳到床边的生物标志物。许多曾经普遍致命的小儿疾病（例如，复杂的先天性心脏病和极端早产）现在的生存率相对较好。但是，神经发育结果有所改善只有边缘。通过及时干预，可以最大程度地减少低氧损伤，但是当前的床边工具是不敏感，为此目的不足。此外，临床人群的异质性限制了临床研究。每个患者都有独特的伤害和治疗，并且在不同的时间进行神经影像学受伤;因此，很难严格分析此类数据以确定最佳，最可推广的数据生物标志物。目前的工作旨在通过使用低氧神经损伤的小鼠模型来解决这些问题，强大的统计方法，光学功能性神经影像学技术和静止状态血液动力学评估（例如功能连接）。光学方法类似于功能磁共振成像，但成本较低，便携性较高和较高的贯穿。我的建议将检验假设静止状态血液动力学指标可以用作急性和慢性后损伤的神经影像标志物缺氧。 AIM 1将开发适合光学神经成像的统计方法，以允许更强大的噪声过滤，脑部分割，atlasing和图像分析。 AIM 2将在缺血性中风的超急性相，以鉴定半月。 AIM 3将研究跨小鼠发育的功能连通性网络和慢性低氧血症的破坏性作用。这项研究将在Daniel的Arjun Yodh博士的指导下进行 Licht，医学博士；两位教师都是光学神经监控技术发展的公认领导者。在此外，我已经组建了一个跨学科的合作者，在鼠标模型中具有专业知识低氧血症，神经影像统计和高级网络分析方法。我会从这个优秀的指导和研究环境以及我独特的光学神经影像学方法为通往独立。我是一名经过董事会认证的儿科心脏病专家，我的长期职业目标是结合神经影像学在儿科研究医院具有终身轨道位置。杰出的研究环境在Chop/Penn将在重症监护室和进一步的动物模型中实现未来的翻译研究疾病。第1页

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Venous Flow Variation Predicts Preoperative Pulmonary Venous Obstruction in Children with Total Anomalous Pulmonary Venous Connection.

DOI：
10.1016/j.echo.2021.02.007
发表时间：
2021-07
期刊：
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
影响因子：
0
作者：
White BR;Faerber JA;Katcoff H;Glatz AC;Mascio CE;Cohen MS
通讯作者：
Cohen MS

Variability in atlas registration of optical intrinsic signal imaging and its effect on functional connectivity analysis.

DOI：
10.1364/josaa.410447
发表时间：
2021-02-01
期刊：
Journal of the Optical Society of America. A, Optics, image science, and vision
影响因子：
0
作者：
Padawer-Curry JA;Jahnavi J;Breimann JS;Licht DJ;Yodh AG;Cohen AS;White BR
通讯作者：
White BR

Fetal Doppler Echocardiographic Assessment Predicts Severe Postnatal Obstruction in Total Anomalous Pulmonary Venous Connection.

DOI：
10.1016/j.echo.2022.07.007
发表时间：
2022-11
期刊：
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
影响因子：
0
作者：
通讯作者：

Wavelength censoring for spectroscopy in optical functional neuroimaging.

DOI：
10.1088/1361-6560/abd418
发表时间：
2021-03-12
期刊：
Physics in medicine and biology
影响因子：
3.5
作者：
White BR;Padawer-Curry JA;Ko T;Baker W;Breimann J;Cohen AS;Licht DJ;Yodh AG
通讯作者：
Yodh AG

Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability.

DOI：
10.3390/metabo13111153
发表时间：
2023-11-16
期刊：
Metabolites
影响因子：
4.1
作者：
Benson EJ;Aronowitz DI;Forti RM;Lafontant A;Ranieri NR;Starr JP;Melchior RW;Lewis A;Jahnavi J;Breimann J;Yun B;Laurent GH;Lynch JM;White BR;Gaynor JW;Licht DJ;Yodh AG;Kilbaugh TJ;Mavroudis CD;Baker WB;Ko TS
通讯作者：
Ko TS