Modeling of transient oxygen delivery in the brain

大脑瞬时氧输送的建模

• 批准号: 8094052
• 负责人: DAVID B RESS
• 金额: $ 18.97万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8094052
• 关键词: Affect; Behavior; Blood; Blood Vessels; Blood capillaries; Blood flow; Brain; Brain imaging; Brain region; Cerebral cortex; Cerebrovascular Disorders; Cerebrum; Complex; Consumption; Convection; Coupling; Data Set; Development; Diagnosis; Diagnostic; Diffusion; Dissociation; Elements; Equilibrium; Erythrocytes; Event; Felis catus; Forelimb; Fractals; Functional Imaging; Functional Magnetic Resonance Imaging; Hemoglobin; Image; Imaging Techniques; Individual; Investigation; Lateral Geniculate Body; Mainstreaming; Measurement; Measures; Mediating; Metabolism; Modeling; Neurons; Non-linear Models; Oxygen; Oxygen Consumption; Pathology; Photic Stimulation; Physics; Physiology; Research; Rest; Rodent; Scanning; Somatosensory Cortex; Spatial Distribution; Speed; Testing; Time; Tissues; Variant; Visual Cortex; Work; arteriole; base; brain tissue; capillary; cerebrovascular; density; hemodynamics; imaging modality; improved; neglect; neural stimulation; novel; novel strategies; operation; optical imaging; oxygen transport; relating to nervous system; research study; response; two-photon

DESCRIPTION (provided by applicant): Summary Brief periods of neural activity trigger a vascular response with a complex but stable form. This hemodynamic response function (HRF) is extensively exploited in popular imaging methods such as functional magnetic resonance imaging (fMRI) and reflectance based optical imaging. Proper interpretation and utilization of these imaging techniques requires a detailed understanding the HRF. Moreover, because the brain is continually active, transient responses are likely to be important in normal function of the healthy brain. Better understanding of the HRF will enable research efforts that rely on "resting-state" or "default-mode" activity that is clearly evident in the brain. Finally, cerebrovascular pathology is likely to affect such transient responses, so a more complete understanding of their normal character should enable their investigation as diagnostics of incipient or extant pathology. The physiology and physics of the HRF are not well understood. A standard model has been developed that incorporates a non-linear compliant element (balloon) to explain flow and volume changes. However, some specific predictions of the balloon model have not been confirmed experimentally, and there is now great controversy on the subject. We have developed a new model that combines a linear flow description with one-dimensional convection-diffusion oxygen transport. The flow model includes the inertial dynamics of moving blood, which should not be neglected in the larger arterioles that mechanically mediate the flow response. Our full model has provided remarkably accurate fits to tissue oxygen measurements performed with polarographic probes consequent to brief (few second) neural stimulation events. This model also provides an explanation for the neurovascular coupling utilized in resting-state fMRI. We propose further development and testing of our model. Specifically, we want to improve the quality of its intravascular oxygen concentration predictions, and to enable examination of oxygen mass-balance issues. Aim 1 is to expand the model in several ways: by adding the dynamics of oxygen dissociation from hemoglobin, and by adding terms to deal with alternative oxygen transport mechanisms such as oxygen consumption by endothelial tissue. Aim 2 is to further test our model by fitting additional tissue oxygen measurements obtained using polarographic probes. Aim 3 is to use two-photon optical imaging to measure flow speeds in small arterioles and capillaries, and how they change consequent to brief neural stimulation. We will test how well these measurements are fit by our linear flow model as well as previous non-linear models. The proposed work will further vet our model, bringing it into the mainstream as a simple but powerful analytic description for cerebrovascular hemodynamics. PUBLIC HEALTH RELEVANCE: We need a better understanding of oxygen transfer from blood to brain tissue, both during steady-state metabolism and as a consequence of brief neural stimulation. Such understanding is critical to the proper use and interpretation of brain imaging techniques that rely on neurovascular coupling, as well as the diagnosis and treatment of cerebrovascular diseases. We propose further development of a novel model for the transient delivery of oxygen to brain tissue, together with efforts that test the model's predictions against precise local measurements of tissue oxygen and blood flow changes induced by brief neural stimulation.

描述（由申请人提供）：总结短暂的神经活动会触发复杂但稳定形式的血管反应。这种血流动力学响应函数 (HRF) 广泛应用于流行的成像方法，例如功能磁共振成像 (fMRI) 和基于反射的光学成像。正确解释和利用这些成像技术需要详细了解 HRF。此外，由于大脑持续活跃，瞬态反应可能对健康大脑的正常功能很重要。更好地理解 HRF 将使依赖于大脑中明显明显的“静息状态”或“默认模式”活动的研究工作成为可能。最后，脑血管病理学可能会影响这种短暂的反应，因此对其正常特征的更全面的了解应该能够使它们的研究成为早期或现有病理学的诊断。 HRF 的生理学和物理学尚不清楚。已经开发出一个标准模型，其中包含非线性顺应元件（气球）来解释流量和体积变化。然而，气球模型的一些具体预测尚未得到实验证实，目前该问题存在很大争议。 我们开发了一种新模型，将线性流动描述与一维对流扩散氧传输相结合。血流模型包括移动血液的惯性动力学，在机械介导血流响应的较大小动脉中不应忽视这一点。我们的完整模型为短暂（几秒）神经刺激事件后使用极谱探针进行的组织氧测量提供了非常准确的拟合。该模型还为静息态功能磁共振成像中使用的神经血管耦合提供了解释。 我们建议进一步开发和测试我们的模型。具体来说，我们希望提高其血管内氧浓度预测的质量，并能够检查氧质量平衡问题。目标 1 是以多种方式扩展模型：添加氧从血红蛋白解离的动力学，以及添加术语来处理替代氧运输机制，例如内皮组织的氧消耗。目标 2 是通过拟合使用极谱探针获得的额外组织氧测量值来进一步测试我们的模型。目标 3 是使用双光子光学成像来测量小动脉和毛细血管中的流速，以及它们在短暂的神经刺激后如何变化。我们将测试这些测量结果与我们的线性流量模型以及之前的非线性模型的拟合程度。拟议的工作将进一步审查我们的模型，使其成为主流，作为脑血管血流动力学的简单但强大的分析描述。 公共健康相关性：我们需要更好地了解氧气从血液到脑组织的转移，无论是在稳态代谢过程中还是短暂神经刺激的结果。这种理解对于正确使用和解释依赖于神经血管耦合的脑成像技术以及脑血管疾病的诊断和治疗至关重要。我们建议进一步开发一种向脑组织瞬时输送氧气的新模型，并根据短暂神经刺激引起的组织氧和血流变化的精确局部测量来测试模型的预测。