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Modeling of transient oxygen delivery in the brain

大脑瞬时氧输送的建模

基本信息

批准号：
8280343
负责人：
DAVID B RESS
金额：
$ 18.98万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-15 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8280343
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

项目摘要

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.

描述（由申请人提供）：概述短暂的神经活动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）在流行的成像方法中被广泛利用，例如功能性磁共振成像（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，由于大脑是持续活跃的，瞬态反应在健康大脑的正常功能中可能是重要的。对HRF的更好理解将使研究工作能够依赖于大脑中明显存在的“静息状态”或“默认模式”活动。最后，脑血管病理可能会影响这种短暂的反应，所以更全面地了解他们的正常性格，应使他们的调查作为诊断的初期或现存的病理。 HRF的生理学和物理学还没有得到很好的理解。已经开发了一个标准模型，该模型包含一个非线性顺应性元件（球囊）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，现在对这个问题有很大的争议。我们已经开发了一个新的模型，结合了一维对流扩散氧气输送的线性流动描述。流动模型包括移动血液的惯性动力学，这在机械介导流动响应的较大小动脉中不应被忽略。我们的完整模型提供了非常准确的适合组织氧测量与极谱探针随之而来的简短（几秒钟）的神经刺激事件。这个模型也提供了一个解释的神经血管耦合利用静息态功能磁共振成像。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。目的1是扩展模型在几个方面：通过添加从血红蛋白的氧解离的动力学，并通过添加条款来处理替代氧运输机制，如内皮组织的氧消耗。目的2是进一步测试我们的模型，通过拟合使用极谱探针获得的额外的组织氧测量。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，以及它们如何随着短暂的神经刺激而变化。我们将测试这些测量值与我们的线性流量模型以及以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，作为一个简单但强大的分析描述脑血管血流动力学。