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
基本信息
- 批准号:10204279
- 负责人:
- 金额:$ 61.28万
- 依托单位:
- 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:2020-09-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAlgorithmsAnesthesia proceduresAnimal BehaviorAnimal ModelAnimalsBehavioralBiological MarkersBiomedical ResearchBlood VesselsBrainBrain MappingCarbon DioxideCerebrovascular CirculationCerebrovascular DisordersCerebrumComplexConsciousConsumptionCraniotomyData AnalysesData ReportingDerivation procedureDevicesDiffuseElderlyElectric StimulationElectrodesErythrocytesEyeFiberFlowmetryGlucoseGoalsHeadHemoglobinHomeostasisHumanImpaired cognitionInfarctionInhalationInjectionsInterventionInvestigationIschemic StrokeLasersLeadLightMeasurementMeasuresMental DepressionMetabolicMetabolismMethodsModelingMonitorMotionMotorMovementMusNeuronsNeurosciencesNeurosciences ResearchOperative Surgical ProceduresOpticsOutcomeOutputOxygenOxygen ConsumptionOxygen saturation measurementPathologicPerformanceRadiation ToxicityRattusRodentRodent ModelScientistSensorySleepSleep DisordersSourceStimulusStressStrokeSystemTechniquesTechnologyTestingTimeUltrasonographyUnited States National Institutes of HealthValidationVariantabsorptionattenuationawakebasebehavioral healthbehavioral studybrain healthbrain tissuecerebral hemodynamicscerebral oxygenationcerebrovascularclinical applicationcognitive functioncostcost effectivecraniumdesigndetectorflexibilityhuman diseasehuman subjectinnovationlight scatteringmetabolic rateminiaturizemultimodalitynervous system disorderneural circuitneurovascular couplingnew technologynovel therapeuticsoptical sensorpreterm newbornradiotracerrelating to nervous systemresponsesensorstroke modelstroke outcometooltranslational neuroscience
项目摘要
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
脑血流量(CBF)和脑耗氧代谢率(CMRO2)的测量
对大脑活动的反应可以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新疗法的关键。
和老鼠)一个多世纪以来一直在帮助科学家研究人类疾病,并且仍然占 95%
当今使用的动物模型的主要局限性是脑血流动力学是。
主要在麻醉动物中并在有限的时间点进行测量。然而,麻醉会影响大脑。
深刻影响血流动力学,并干扰行为健康、认知功能和睡眠障碍的研究。
一些可用于清醒啮齿动物脑血流动力学监测的方法需要侵入性开颅手术
在大脑上安装各种光电极/超声波探头,限制动物的头部或
在 NIH (R21) 的支持下,我们最近开发了一种创新的、非侵入性的、
低成本、无纤维、近红外漫散斑对比流量计 (DSCF) 探头,固定在头上
该提案的目标是对麻醉啮齿动物和清醒人类进行连续监测 CBF。
扩展、优化和验证这项新技术,以实现双波长、多通道、漫射散斑
对比血流血氧测定 (DSCFO) 系统可同时进行 CBF、脑氧合和脑血流量的局部绘图
CMRO2 在有意识、自由活动的啮齿动物中使用不同的小型近红外激光二极管。
波长作为点源,微型 CMOS 相机作为 2D 探测器阵列来探测空间动态光
红细胞(即 CBF)的固有运动引起的散射以及氧合血红蛋白和脱氧血红蛋白的光衰减
吸收([HbO2] 和 [Hb]) CBF、[HbO2] 和 [Hb] 的组合可以根据
2D 相机阵列能够绘制两个半球的大脑反应的 2D 映射。
重要的是,DSCFO 探头和控制单元之间的连接。
都是电线/电缆(即无纤维),从而为连续脑部监测提供了希望
使用头部模拟模型校准和优化 DSCFO 系统后,可以自由移动主体。
根据已建立的技术在麻醉啮齿动物中进行验证,我们将评估其性能
对有或没有缺血的清醒、自由活动的啮齿类动物进行连续和纵向的脑监测
当我们在这个项目中探索中风引起的脑部后果时,DSCFO 技术正在发挥作用。
与我们的结合适用于研究其他神经系统疾病和脑血管疾病。
正在进行的人类受试者 R21 研究,完成这项在啮齿类动物中的研究将产生一种独特的非侵入性、
用于神经科学研究和临床的快速、低成本、多尺度、多模式脑图绘制工具
最终,CBF、[HbO2]、[Hb] 和 CMRO2 的水平/变化和组合可以作为
用于评估大脑健康以及脑病理状况和干预结果的生物标志物。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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:
- 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:
- 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:
- 影响因子:3.6
- 作者:
- 通讯作者:
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Guoqiang Yu其他文献
Guoqiang Yu的其他文献
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{{ truncateString('Guoqiang Yu', 18)}}的其他基金
Time-resolved laser speckle contrast imaging of resting-state functional connectivity in neonatal brain
新生儿大脑静息态功能连接的时间分辨激光散斑对比成像
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10760193 - 财政年份:2023
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Development of a Wearable Fluorescence Imaging Device for IntraoperativeIdentification of Brain Tumors
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Integrating Astrocytes into Models of Neural Circuits Regulating Behavior
将星形胶质细胞整合到调节行为的神经回路模型中
- 批准号:
10294803 - 财政年份:2021
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10461225 - 财政年份:2021
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Integrating Astrocytes into Models of Neural Circuits Regulating Behavior
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- 批准号:
10693168 - 财政年份:2021
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$ 61.28万 - 项目类别:
High-density optical tomography of cerebral blood flow and metabolism in small animals
小动物脑血流和代谢的高密度光学断层扫描
- 批准号:
10323090 - 财政年份:2021
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$ 61.28万 - 项目类别:
High-density optical tomography of cerebral blood flow and metabolism in small animals
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10461939 - 财政年份:2021
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