A New Approach for Quantitative fMRI

描述（由申请人提供）：我们的总体目标是为功能性磁共振成像（fMRI）的新实验范式建立基础，使以绝对脑血流量（CBF）为定量单位，在执行复杂任务、休息或对药物作出反应时确定波动的大脑活动模式成为可能。传统的功能磁共振成像（fMRI）是基于检测血氧水平依赖（BOLD）信号调制。BOLD信号是潜在生理变化的敏感指标，但BOLD- fmri的应用目前受到限制，因为BOLD信号的大小不能提供可靠的定量测量生理上有意义的量。动脉自旋标记（ASL）方法提供了CBF的定量测量，这是一个定义良好的生理变量。然而，由于ASL测量的低信噪比，CBF动力学的敏感测量仍然具有挑战性。本提案的关键思想是一种同时测量ASL和BOLD时间序列的新方法，并使用适当的BOLD响应模型，将这些信号视为来自相同的CBF波动的潜在时间序列。合并后的数据用于估计CBF波动，但对这些波动的潜在驱动因素一无所知。提出的新方法基于两个假设：1)在测量期间，局部区域的CBF/ cmor2耦合比保持不变；2) BOLD信号不存在与CBF波动无关的系统波动。这两种假设都不是严格正确的，因此，这个提议的“高风险”部分是一个悬而未决的问题，即这些影响是否足够小，或者是否可以充分纠正，以使该方法可靠。为了验证该方法的可行性，我们提出了以下方法：测量健康受试者对视觉刺激的同时ASL和BOLD反应，并设计了一个实验范式来挑战该方法的基本假设，包括可变CBF/ cmr2耦合、动态转换和BOLD瞬态（目的1）；并开发了两种新的分析技术来提高方法的准确性，一种是采用最新的独立分量分析（ICA）方法，利用我们的多回波采集来识别和去除实测BOLD信号中的伪成分，另一种是改进模型参数的估计，并使用贝叶斯方法处理时变的CBF/ cmor2耦合比。对系统误差的评估，以及对其影响最小化的稳健分析工具的开发，将为新方法的广泛应用奠定基础。这将大大拓宽功能磁共振成像的可能应用，包括测量复杂行为过程中的大脑活动，定量评估发育、疾病或药物管理对基线生理状态和刺激诱发反应的影响。

DESCRIPTION (provided by applicant): Our overall goal is to establish the basis for a new experimental paradigm for functional magnetic resonance imaging (fMRI) that makes possible the determination of fluctuating brain activity patterns during performance of complex tasks, at rest, or in response to a drug, in quantitative units of absolute cerebral blood flow (CBF). Conventional functional magnetic resonance imaging (fMRI) is based on detection of blood oxygenation level dependent (BOLD) signal modulations. The BOLD signal is a sensitive indicator of underlying physiological changes, but BOLD-fMRI applications are currently limited because the magnitude of the BOLD signal does not provide a reliable quantitative measure of a physiologically meaningful quantity. Arterial spin labeling (ASL) methods provide quantitative measurements of CBF, a well-defined physiological variable. However, sensitive measurement of CBF dynamics remains challenging because of the low signal to noise ratio of the ASL measurement. The key idea of this proposal is a new method to take simultaneous measurements of ASL and BOLD time series, and with an appropriate model of the BOLD response, treat these signals as both being generated from the same underlying time series of CBF fluctuations. The combined data are used to estimate the CBF fluctuations without knowing anything about the underlying drivers of those fluctuations. The proposed new methodology rests on two assumptions: 1) the CBF/CMRO2 coupling ratio for a local region remains constant during the measurement period; and 2) there are no systematic fluctuations of the BOLD signal that are unrelated to CBF fluctuations. Neither assumption is strictly true, so the "high risk" hal of this proposal is the open question of whether these effects are sufficiently small or can be adequately corrected for the methodology to be robust. We propose to test the feasibility of this method by: Measuring simultaneous ASL and BOLD responses to visual stimuli in healthy human subjects with an experimental paradigm designed to challenge the basic assumptions of the methodology, including variable CBF/CMRO2 coupling, dynamic transitions and BOLD transients (Aim 1); and developing two new analysis techniques to improve the accuracy of the method, one to adapt a recent independent components analysis (ICA) method to use our multi-echo acquisition to identify and remove artifact components in the measured BOLD signals, and the second to improve estimation of the model parameters and deal with a time varying CBF/CMRO2 coupling ratio with a Bayesian approach. The assessment of systematic errors, and the development of robust analysis tools for minimizing their effect, will establish a basis fo widespread application of the new method. This will substantially broaden the possible applications of fMRI, including measurement of brain activity during complex behavior, and quantitative assessments of the effects of development, disease, or drug administration on both the baseline physiological state and stimulus-evoked responses.