PHYSIOLOGY & PATHOPHYSIOLOGY OF ACTIVATION FLOW COUPLING

生理

• 批准号: 6392500
• 负责人: JOHN A DETRE
• 金额: $ 21.3万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6392500
• 关键词: bioimaging /biomedical imaging; biological models; biological signal transduction; brain circulation; brain electrical activity; carotid artery; evoked potentials; hemodynamics; laboratory rat; lasers; nitric oxide synthase; oscillatory blood flow; oxidoreductase inhibitor; oxygen consumption; pathologic process; phosphorescence; respiratory oxygenation; somesthetic sensory cortex; stimulus interval; ultrasound blood flow measurement; vasomotion

DESCRIPTION: (Adapted from the Investigator's Abstract) A fundamental aspect of brain physiology is the coupling between regional neuronal activation and changes in regional cerebral blood flow (CBF), herein referred to as activation-flow coupling (AFC). This coupling is the basis of many functional neuroimaging techniques that detect regional brain activation in response to specific sensorimotor or cognitive tasks by utilizing changes in regional CBF as a surrogate marker for neuronal activation. However, neither the specific mechanisms underlying AFC nor the effects of pathophysiological changes or the influences of vasoactive drugs on AFC have been well characterized. Neuroimaging techniques such as functional MRI (fMRI) can monitor changes in regional hemodynamics with high spatial and temporal resolution. Activation paradigms may be administered singly, periodically, or in blocks, yet the hemodynamic consequences of these differing experimental designs are largely unknown. Further, as neuroimaging studies are extended to patient populations for diagnostic purposes, the effects of pathophysiological changes on AFC responses must be better understood to allow results of such studies to be correctly interpreted. The proposed research is motivated by the goal of better understanding factors influencing AFC responses and neuroimaging techniques which rely on AFC as a surrogate marker of neural activity. Signal averaged laser Doppler monitoring will be used to measure AFC responses in a rat model of AFC, with CBF changes recorded from somatosensory cortex in response to electrical forepaw stimulation. The applicant will also monitor tissue oxygenation changes by in vivo phosphorescence quenching to characterize changes in oxygen utilization in relation to blood flow and will monitor somatosensory evoked responses elicited by stimulation as a measure of neural activity. A laser Doppler-imaging system will also be implemented to investigate spatial aspects of AFC. These studies will provide further insight into the parameters affecting the AFC. A computerized 'virtual instrument' allows stimulus and recording parameters to be flexibly controlled. Specific aims of the proposed research include characterization of the stimulus timing effects on the AFC response, characterizing oxygenation changes; characterizing the interactions between AFC and vasomotion oscillations; and the effects of hemodynamic impairment on the AFC response. These studies will provide further insight into the parameters affecting the AFC response, and will suggest approaches for optimizing and interpreting functional imaging data.

描述：（根据调查员的摘要进行了改编） 大脑生理学的一个基本方面是区域之间的耦合 神经元激活和区域脑血流（CBF）的变化，此处 称为激活流耦合（AFC）。这种耦合是 许多检测区域大脑激活的功能性神经影像学技术 通过利用更改的变化来应对特定的感觉运动或认知任务 区域CBF作为神经元激活的替代标记。但是，都不是 AFC背后的特定机制或病理生理的影响 血管活性药对AFC的变化或影响一直很好 特征。神经影像学技术，例如功能MRI（fMRI）可以 监测具有高空间和时间的区域血流动力学的变化 解决。激活范例可以单独，定期进行或 在块中，但是这些不同的实验的血液动力学后果 设计在很大程度上未知。此外，随着神经影像学研究扩大到 出于诊断目的的患者人群，病理生理的影响 必须更好地理解AFC响应的变化，以允许这样的结果 可以正确解释的研究。拟议的研究是由 更好地理解影响AFC反应和神经影像的因素的目标 依靠AFC作为神经活动的替代标志的技术。信号 平均激光多普勒监测将用于测量AFC响应 AFC的大鼠模型，CBF变化从体感皮质中记录 对电前科刺激的反应。申请人还将监视 组织氧合通过体内磷光淬火而变化以表征 与血流相关的氧气利用情况的变化，并将监测 体感诱发的反应是通过刺激作为神经的量度引起的 活动。激光多普勒成像系统也将实施 研究AFC的空间方面。这些研究将提供进一步的见识 进入影响AFC的参数。计算机化的“虚拟仪器” 允许灵活控制刺激和记录参数。具体的 拟议研究的目的包括刺激时间的表征 对AFC反应的影响，表征氧合变化；特征 AFC和血管症之间的相互作用；以及 AFC反应上的血液动力学障碍。这些研究将进一步提供 深入了解影响AFC响应的参数，并建议 优化和解释功能成像数据的方法。