fMRI BOLD contrast relationship to cerebrovascular tone

描述（由申请人提供）：功能性磁共振成像（fMRI）依赖于血流变化与神经元活动的耦合。这些血流变化反过来又改变了神经元周围局部血池中的氧气浓度。由于氧合血红蛋白和脱氧血红蛋白的敏感性不同，因此可以使MR信号对氧浓度敏感;这被称为血氧水平依赖（BOLD）信号。BOLD信号从静止状态到激活状态的变化约为1- 3%。BOLD信号的检测需要稳健的范例、信号的预处理和统计建模以生成激活图。所有这些都是必要的，因为血液动力学正常的受试者中存在微弱的BOLD对比。当受试者由于颈动脉狭窄或闭塞而具有受损的脉管系统和受损的血管反应性时，我们已经证明BOLD信号响应不存在或严重改变超过正常检测。这是一个非常重要的问题，因为功能磁共振成像进入临床环境，并用于研究中风恢复或老龄化人群。例如，在中风恢复中，可以检测到激活随时间增加，并假设它们是由于神经元募集或康复;然而，激活可能是发展侧支血流或血管反应性恢复的结果。该提案的目标之一是调查和表征面对血流动力学改变的BOLD反应。功能性MRI领域的一个限制是用于检测激活的BOLD信号的微小差异。我们已经表明，咖啡因的生理相互作用显著增加了BOLD对比度（在1.5T下为~ 40%，在3 T下为80-170%）。在这个建议中，咖啡因的机制将探讨在正常受试者使用功能磁共振成像，磁共振灌注和经颅多普勒超声表征的BOLD信号和脑血流反应。将对单个组件进行研究，以创建一个简单的BOLD对比度交互模型。BOLD对比度的改善可以用于提高时间和空间分辨率，或允许调查更微妙的认知paradigms.The主题的建议是调查的生理机制（反应性，流量，红细胞压积，神经元活动）的BOLD信号的产生，更重要的是BOLD对比度的影响。

DESCRIPTION (provided by applicant): Functional magnetic resonance imaging (fMRI) relies on the coupling of blood flow changes to neuronal activity. These blood flow changes in turn alter the concentration of oxygen in the local blood pool surrounding the neurons. Because the susceptibility of oxyhemoglobin and deoxyhemoglobin are different, it is possible to make the MR signal sensitive to oxygen concentration; this is termed blood oxygenation level dependent (BOLD) signal. The BOLD signal change from the rest condition to the active condition is approximately 1-3%. Detection of the BOLD signal requires a robust paradigm, preprocessing of the signal, and statistical modeling to generate activation maps. All of this is necessary because of the weak BOLD contrast that exists in hemodynamically normal subjects. When a subject has compromised vasculature and impaired vasoreactivity from a carotid stenosis or occlusion, we have demonstrated that the BOLD signal response is absent or severely altered beyond normal detection. This is a very important issue as fMRI moves into the clinical setting and is used to study stroke recovery or aging populations. For example, in stroke recovery one may detect activation increases over time and assume they are due to neuronal recruitment or rehabilitation; however, the activations may be the result of developing collateral flow or recovery of vasoreactivity. One of the goals of this proposal is to investigate and characterize the BOLD response in the face of altered hemodynamics. A limitation to the field of functional MRI is the small difference in BOLD signal used to detect activations. We have shown that the physiologic interaction of caffeine signigicantly increases the BOLD contrast (-40% at 1,5T and 80-170% at 3T). In this proposal, the mechanisms of caffeine will be explored in normal subjects using fMRI, MR based perfusion and transcranial Doppler ultrasound to characterize the BOLD signal and the cerebral blood flow response. Individual components will be invesitgated in order to create a simple model of the interations with BOLD contrast. The improvement in BOLD contrast can be used to improve the temporal and spatial resolution or to allow the investigation of more subtle cognitive paradigms.The theme of this proposal is to investigate the impact of physiologic mechanisms (reactivity, flow, hematocrit, neuronal activity) on the generation of BOLD signal and more importantly BOLD contrast.