BIOPHYSICAL BASIS OF FUNCTIONAL BRAIN FMRI

所提出的工作的总体目的是更好地理解 影响BOLD（血氧）的物理和生理因素 水平依赖的）信号 （fMRI）。功能磁共振成像是一个非常重要的补充方法， 非侵入性的人类大脑映射，并被广泛用于临床 医学以及认知的基础研究。虽然有一般 关于BOLD信号如何产生的协议，仍然有许多功能， BOLD效应是不确定的，有几个因素的影响， 未知，尤其是所谓的事件相关功能磁共振成像。这些赤字在 我们的理解限制了我们定量解释fMRI数据的能力。 此外，我们还不清楚是什么限制了功能磁共振成像的灵敏度， 实践，也没有什么收益可能是可能的，因为更高的磁场强度磁铁 变得更加广泛。在下一阶段，我们将量化 改变形状的几个技术和物理因素的影响， 瞬时事件相关fMRI反应的幅度。在两种大鼠模型中， 躯体感觉激活和人类皮层，我们将量化的影响， 场强、脉冲序列、刺激参数和固有血液 易感性，对事件相关的潜伏期，幅度和持续时间 响应，并验证这些可能会增加非线性时，紧密间隔。我们将 还量化了几种生理和药理因素的影响 在人类受试者中，事件相关反应通常会有所不同，包括 基础血流量改变、轻度低血糖、血细胞比容降低 血液中一氧化碳、尼古丁、咖啡因和雌激素的水平， 与事件相关的BOLD信号的特征。为了弄清 用于将BOLD信号与基础信号相关联的当前模型的有效性 代谢和生理变化，我们将测量 在分级高碳酸血症和 神经刺激，最后，我们将量化和表征的来源， 影响fMRI信号的噪声。我们将测量信号的贡献 可能由心脏、呼吸、运动和血管扩张引起的变化 影响，并评估这些如何影响fMRI信号/噪声比，对于不同的 技术因素的选择，包括场强、脉冲序列、回波 时间和空间分辨率。这些研究将促进我们的努力， 更好地理解和解释fMRI提供的数据，并提供重要的 深入了解如何提高fMRI可获得的信息质量， 在不同场强下的不同应用。

The overall purpose of the work proposed is to better understand the physical and physiological factors that affect the BOLD (blood oxygenation level dependent) signals detected in functional magnetic resonance imaging (fMRI). FMRI is a very important addition to the methods available for non-invasive mapping of the human brain, and is being widely used in clinical medicine as well as in basic studies of cognition. Although there is general agreement about how BOLD signals originate, there are still many features of the BOLD effect that are uncertain, and the influence of several factors is unknown, especially for so-called event-related fMRI. These deficits in understanding limit our ability to interpret fMRI data quantitatively. Furthermore, we do not understand well what limits the sensitivity of fMRI in practice, nor what gains may be possible as higher field strength magnets become more widely available. In the next phase of this grant we will quantify the effects of several technical and physical factors that modify the shape and amplitude of transient event-related fMRI responses. In both a rat model of somatosensory activation and human cortex, we will quantify the effects of field strength, pulse sequence, stimulation parameters, and intrinsic blood susceptibility, on the latency, magnitude and duration of event related responses, and verify these may add non-linearly when closely spaced. We will also quantify the effects of several physiological and pharmacological factors that commonly vary in humans subjects on the event-related responses, including the effects of altered basal flow, mild hypoglycemia, reduced hematocrit, levels of blood carbon monoxide, nicotine and caffeine, and estrogen, on the characteristics of the event-related BOLD signal. In order to clarify the validity of current models that are used to relate BOLD signals to underlying metabolic and physiological changes, we will measure the relationship between cerebral blood volume and flow in a rat model with graded hypercapnia and with neural stimulation, Finally, we will quantify and characterize the sources of noise that affect the fMRI signal. We will measure the contributions to signal variance that may arise from cardiac, respiratory, movements and vasomotor effects, and assess how these affect the fMRI signal/noise ratio, for different choices of technical factors including field strength, pulse sequence, echo time, and spatial resolution. These studies will further our efforts to understand and interpret data provided from fMRI better, and provide important insights into how to improve the quality of information obtainable by fMRI in diverse applications at different field strengths.