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）的新实验范例奠定基础，该范例能够以绝对脑血流量（CBF）的定量单位确定执行复杂任务期间、休息时或对药物的反应期间波动的大脑活动模式。传统的功能磁共振成像 (fMRI) 基于血氧水平依赖性 (BOLD) 信号调制的检测。 BOLD 信号是潜在生理变化的敏感指标，但 BOLD-fMRI 应用目前受到限制，因为 BOLD 信号的幅度不能提供对生理有意义的量的可靠定量测量。动脉自旋标记 (ASL) 方法提供 CBF 的定量测量，CBF 是一个明确的生理变量。然而，由于 ASL 测量的信噪比较低，CBF 动态的灵敏测量仍然具有挑战性。该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，并通过适当的 BOLD 响应模型，将这些信号视为由 CBF 波动的相同基础时间序列生成。组合数据用于估计 CBF 波动，而无需了解这些波动的根本驱动因素。所提出的新方法基于两个假设：1）局部区域的 CBF/CMRO2 耦合比在测量期间保持恒定； 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，因此该提案的“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，或者是否可以得到充分纠正以使方法稳健。我们建议通过以下方式测试该方法的可行性：使用旨在挑战该方法的基本假设的实验范式，测量健康人类受试者对视觉刺激的同时 ASL 和 BOLD 反应，包括可变 CBF/CMRO2 耦合、动态过渡和 BOLD 瞬态（目标 1）；并开发两种新的分析技术来提高该方法的准确性，一种是采用最近的独立分量分析（ICA）方法，以使用我们的多回波采集来识别和消除测量的 BOLD 信号中的伪影分量，第二种是改进模型参数的估计并使用贝叶斯方法处理随时间变化的 CBF/CMRO2 耦合比。系统误差的评估以及开发稳健的分析工具以尽量减少其影响，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，包括测量复杂行为期间的大脑活动，以及定量评估发育、疾病或药物管理对基线生理状态和刺激诱发反应的影响。 公共健康相关性：使用血氧水平依赖（BOLD）方法对大脑进行功能性磁共振成像（fMRI）研究目前由于难以以有意义的生理方式解释这些信号而受到限制。本提案的目标 旨在开发一种定量测量脑血流量波动的新方法。这种方法将为疾病研究和评估药物效果以及复杂行为期间大脑动力学的探索开辟新的方向。