A New Approach for Quantitative fMRI

定量功能磁共振成像的新方法

• 批准号: 8428250
• 负责人: RICHARD BRUCE BUXTON
• 金额: $ 22.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8428250
• 关键词: Address; Automobile Driving; Beds; Behavior; Behavioral; Brain; Calibration; Cerebrovascular Circulation; Cerebrum; Complex; Coupling; Data; Data Analyses; Detection; Development; Disease; Frequencies; Functional Magnetic Resonance Imaging; Goals; Image; Maps; Measurement; Measures; Metabolic; Methodology; Methods; Modality; Modeling; Morphologic artifacts; Noise; Non-linear Models; Oxygen; Pattern; Performance; Pharmaceutical Preparations; Physiological; Research; Rest; Series; Signal Transduction; Sleep; Spin Labels; Stimulus; Techniques; Testing; Time; Work; base; blood flow measurement; blood oxygen level dependent; blood oxygenation level dependent response; deoxyhemoglobin; design; high reward; high risk; human subject; improved; independent component analysis; novel; novel strategies; relating to nervous system; research study; response; tool; visual stimulus

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. PUBLIC HEALTH RELEVANCE: Functional magnetic resonance imaging (fMRI) studies of the brain using blood oxygenation level dependent (BOLD) methods are currently limited by the difficulty of interpreting these signals in a meaningful physiologic way. The goal of this proposal is to develop a new methodology for measuring fluctuations in cerebral blood flow in a quantitative way. This methodology will open new directions for research in disease and evaluating the effects of drugs, as well as explorations of brain dynamics during complex behavior.

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）的新实验范例建立基础，该实验范例使得在执行复杂任务期间、在休息时或在对药物作出反应时以绝对脑血流量（CBF）的定量单位确定波动的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信号是潜在的生理变化的敏感指标，但BOLD-fMRI应用目前受到限制，因为BOLD信号的幅度不提供可靠的定量测量的生理意义的量。动脉自旋标记（ASL）方法提供了CBF的定量测量，CBF是一个定义明确的生理变量。然而，由于ASL测量的低信噪比，CBF动态的灵敏测量仍然具有挑战性。该建议的关键思想是一种新的方法，同时测量ASL和BOLD的时间序列，并与适当的模型的BOLD响应，处理这些信号都是从相同的基础CBF波动的时间序列。合并后的数据用于估计CBF波动，而不知道这些波动的潜在驱动因素。所提出的新方法基于两个假设：1）局部区域的CBF/CMRO 2耦合比在测量期间保持恒定;以及2）不存在与CBF波动无关的BOLD信号的系统波动。这两个假设都不是严格正确的，因此这一提议的“高风险”hal是一个悬而未决的问题，即这些影响是否足够小，或者是否可以得到适当的纠正，以使该方法具有鲁棒性。我们建议测试这种方法的可行性，通过：测量同时ASL和BOLD反应的视觉刺激，在健康的人类受试者的实验范式，旨在挑战的基本假设的方法，包括变量CBF/CMRO 2耦合，动态转换和BOLD瞬变（目标1）;并开发了两种新的分析技术来提高方法的准确性，一种是采用最近的独立分量分析（伊卡）方法来使用我们的多回波采集来识别和去除测量的BOLD信号中的伪影分量，第二种方法用于改进模型参数的估计并使用贝叶斯方法处理时变的CBF/CMRO 2耦合比。对系统误差的评估以及为最大限度地减少其影响而开发的稳健分析工具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，以及定量评估发育、疾病或药物给药对基线生理状态和刺激诱发反应的影响。 公共卫生相关性：功能磁共振成像（fMRI）研究的大脑使用血氧水平依赖（BOLD）的方法目前受到限制的困难，解释这些信号在一个有意义的生理方式。这项提案的目的是 是发展一种新的定量测量脑血流波动的方法。这种方法将为疾病研究和药物效果评估以及复杂行为期间大脑动力学的探索开辟新的方向。