Continuous and Longitudinal Monitoring of Cerebral Blood Flow and Metabolism in Freely Moving Rodents

自由移动啮齿动物脑血流和代谢的连续和纵向监测

• 批准号: 10204279
• 负责人: Guoqiang Yu
• 金额: $ 61.28万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204279
• 关键词: Adult; Algorithms; Anesthesia procedures; Animal Behavior; Animal Model; Animals; Behavioral; Biological Markers; Biomedical Research; Blood Vessels; Brain; Brain Mapping; Carbon Dioxide; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Complex; Conscious; Consumption; Craniotomy; Data Analyses; Data Reporting; Derivation procedure; Devices; Diffuse; Elderly; Electric Stimulation; Electrodes; Erythrocytes; Eye; Fiber; Flowmetry; Glucose; Goals; Head; Hemoglobin; Homeostasis; Human; Impaired cognition; Infarction; Inhalation; Injections; Intervention; Investigation; Ischemic Stroke; Lasers; Lead; Light; Measurement; Measures; Mental Depression; Metabolic; Metabolism; Methods; Modeling; Monitor; Motion; Motor; Movement; Mus; Neurons; Neurosciences; Neurosciences Research; Operative Surgical Procedures; Optics; Outcome; Output; Oxygen; Oxygen Consumption; Oxygen saturation measurement; Pathologic; Performance; Radiation Toxicity; Rattus; Rodent; Rodent Model; Scientist; Sensory; Sleep; Sleep Disorders; Source; Stimulus; Stress; Stroke; System; Techniques; Technology; Testing; Time; Ultrasonography; United States National Institutes of Health; Validation; Variant; absorption; attenuation; awake; base; behavioral health; behavioral study; brain health; brain tissue; cerebral hemodynamics; cerebral oxygenation; cerebrovascular; clinical application; cognitive function; cost; cost effective; cranium; design; detector; flexibility; human disease; human subject; innovation; light scattering; metabolic rate; miniaturize; multimodality; nervous system disorder; neural circuit; neurovascular coupling; new technology; novel therapeutics; optical sensor; preterm newborn; radiotracer; relating to nervous system; response; sensor; stroke model; stroke outcome; tool; translational neuroscience

ABSTRACT Measurements of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO2) in response to brain activity allows investigation of underlying excitatory and inhibitory neural responses and holds the key to optimizing novel therapies for neurological disorders and cerebrovascular diseases. Rodents (mice and rats) have been helping scientists investigate human diseases for well over a century and still make up 95% of the animal models used today. Major limitations with these rodent models are that cerebral hemodynamics is measured mostly in anesthetized animals and at limited time points. However, anesthesia impacts cerebral hemodynamics profoundly and interferes with studies of behavioral health, cognitive function, and sleep disorder. A few methods available for cerebral hemodynamic monitoring in conscious rodents require invasive craniotomy with installation of various opto-electrode/ultrasound probes onto the brain, which restrains animal’s head or body during measurements. Supported by NIH (R21), we have recently developed an innovative, noninvasive, low-cost, fiber-free, near-infrared diffuse speckle contrast flowmetry (DSCF) probe, which affixes on the heads of anesthetized rodents and awake humans for continuous monitoring of CBF. The goal of this proposal is to extend, optimize, and validate this novel technology toward a dual-wavelength, multi-channel, diffuse speckle contrast flow-oximetry (DSCFO) system for simultaneous regional mapping of CBF, cerebral oxygenation, and CMRO2 in conscious, freely moving rodents. DSCFO uses small near-infrared laser diodes at different wavelengths as point sources and a tiny CMOS camera as a 2D detector array to detect spatial dynamic light scattering by intrinsic motions of red blood cells (i.e., CBF) and light attenuations by oxy- and deoxy- hemoglobin absorptions ([HbO2] and [Hb]). Combination of CBF, [HbO2], and [Hb] enables derivation of CMRO2 based on established models. The 2D camera array enables 2D mapping of cerebral responses over two hemispheres and at different depths of the rodent head. Importantly, connections between the DSCFO probe and control unit are all electrical wires/cables (i.e., fiber-free), thereby offering the promise for continuous cerebral monitoring in freely moving subjects. After calibrating and optimizing the DSCFO system using head-simulating phantoms and validation in anesthetized rodents against established techniques, we will evaluate its performance for continuous and longitudinal cerebral monitoring in conscious, freely moving rodents with or without ischemic stroke insult. While we explore stroke-induced cerebral outcomes in this project, the DSCFO technology is applicable for studying other neurological disorders and cerebrovascular diseases. In combination with our ongoing R21 studies in human subjects, completion of this study in rodents will generate a unique noninvasive, fast, low-cost, multiscale, and multimodal brain mapping tool for both neuroscience research and clinical applications. Ultimately, the levels/variations and combination of CBF, [HbO2], [Hb], and CMRO2 may serve as biomarkers for assessing brain health and outcomes of cerebral pathological conditions and interventions.

抽象的 大脑血流（CBF）和脑消耗的大脑代谢率（CMRO2）的测量值（CMRO2） 对大脑活动的反应允许研究潜在的兴奋性和抑制性神经反应并保持 优化神经系统疾病和脑血管疾病的新疗法的关键。啮齿动物（小鼠） 大鼠）一直在帮助科学家调查一个多世纪以来的人类疾病，但仍然占95％ 当今使用的动物模型。这些啮齿动物模型的主要局限性是脑血液动力学是 主要在麻醉动物和有限的时间点测量。但是，麻醉会影响大脑 血液动力学深刻地干扰了行为健康，认知功能和睡眠障碍的研究。 有意识的啮齿动物中可用于脑血液动力学监测的几种方法需要浸润性颅骨切开术 随着在大脑上安装各种选择性电极/超声问题，这限制了动物的头部或 测量过程中的身体。在NIH（R21）的支持下，我们最近开发了一种创新的无创，无创的 低成本，无纤维，近红外弥漫性斑点对比度（DSCF）探针，该探针粘在头上 麻醉啮齿动物和清醒的人，用于连续监测CBF。该提议的目的是 扩展，优化和验证这项新技术朝着双波长，多通道，弥漫范围 与CBF同时区域映射，脑氧合和对比度流动型（DSCFO）系统 CMRO2在有意识的自由移动啮齿动物中。 DSCFO使用不同的近红外激光二极管 波长作为点源和微小的CMOS摄像机作为2D检测器阵列，以检测空间动态光 红细胞（即CBF）的内在运动和氧气和脱氧血红蛋白的光衰减散射 抽象（[HBO2]和[HB]）。 CBF，[HBO2]和[HB]的组合可以基于CMRO2的推导 建立的模型。 2D摄像头阵列可以在两个半球上的大脑反应的2D映射 并在啮齿动物头的不同深度处。重要的是，DSCFO探针与控制单元之间的连接 都是所有电线/电缆（即无光纤），从而提供了连续脑监测的承诺 自由移动的主题。在使用头部构图幻象和 麻醉啮齿动物对既定技术的验证，我们将评估其性能 有或没有缺血的有意识的自由移动啮齿动物中的连续和纵向大脑监测 中风侮辱。当我们探索该项目中引起中风引起的大脑结果时，DSCFO技术是 适用于研究其他神经系统疾病和脑血管疾病。与我们的联合 正在进行的R21在人类受试者中的研究，啮齿动物的这项研究的完成将产生独特的无创，， 用于神经科学研究和临床的快速，低成本，多尺度和多模式脑图工具 申请。最终，CBF，[HBO2]，[HB]和CMRO2的水平/变化和组合可以用作 评估大脑健康以及脑病理状况和干预措施的生物标志物。

项目成果

Noncontact optical imaging of brain hemodynamics in preterm infants: a preliminary study.

• DOI: 10.1088/1361-6560/abc5a7
• 发表时间: 2020-12-22
• 期刊: Physics in medicine and biology
• 影响因子: 3.5
• 作者: Abu Jawdeh EG;Huang C;Mazdeyasna S;Chen L;Chen L;Bada HS;Yu G
• 通讯作者: Yu G

Noncontact Speckle Contrast Diffuse Correlation Tomography of Blood Flow Distributions in Burn Wounds: A Preliminary Study.

烧伤创面血流分布的非接触散斑对比漫射相关断层扫描：初步研究。

• DOI: 10.1093/milmed/usz233
• 发表时间: 2020
• 期刊: Military medicine
• 影响因子: 1.2
• 作者: Zhao,Mingjun;Mazdeyasna,Siavash;Huang,Chong;Agochukwu-Nwubah,Nneamaka;Bonaroti,Alisha;Wong,Lesley;Yu,Guoqiang
• 通讯作者: Yu,Guoqiang

Intraoperative Optical and Fluorescence Imaging of Blood Flow Distributions in Mastectomy Skin Flaps for Identifying Ischemic Tissues.

• DOI: 10.1097/prs.0000000000009333
• 发表时间: 2022-08-01
• 期刊: Plastic and reconstructive surgery
• 影响因子: 3.6