Biophysical basis of functional MRI of white matter

摘要 这项拟议的研究旨在测量白质中的血氧水平依赖(BOLD)信号 (WM)使用功能磁共振成像(FMRI)，验证它们与皮质神经活动的关系， 并量化它们的特征和潜在的生物物理来源。大胆的信号此前一直是 在大量的研究中，在灰质(GM)对刺激的反应中被强烈检测到。此外, 分析了静息状态下大脑皮层区域之间的信号波动相关性，以得出 功能连接。然而，这些信号是否可靠地出现在WM中仍然存在争议，而且他们的 目前尚不清楚对此的解释。我们之前已经证明，在WM中可以可靠地检测到粗体信号，如果 使用了适当的检测和分析方法，并且在静止状态下它们表现出各向异性 与WM区域基本一致的时间相关性。多条这样的证据汇聚在一起，表明 WM BOLD信号与固有的、依赖功能的神经活动有关，仅在神经束中明显 从事特定职能的。然而，WM和对应的GM信号之间的精确关系 尚未确定，血流动力学反应功能的特征和起源 (HRF)已被阐明。我们假设，WM区域中的大胆信号变化直接 与它们连接和/或共享的GM体积中神经活动的相应变化有关 具体职能作用，进一步研究将为更充分地结合结构 以及神经组织的功能方面。在建议的研究中，我们将[1]演示和测量 WM波束中的BOLD信号(通过扩散成像识别)与Gm体积之间的关系 对参数刺激的反应，其变化调节特定皮质中神经活动的程度 区域；[2]使用事件相关功能磁共振成像测量和表征特定WM区域的HRF，并修改 传统的大胆反应模型来解释和拟合这些数据；[3]建立了 通过比较来自不同成像序列的数据和脑白质刺激诱发的大胆激活 场强，并通过测量非人类灵长类动物大脑中的大胆信号，有没有 血管内敏感性造影剂用于区分血容量与血液的变化 氧合作用。总体而言，这些研究将验证WM大胆效应的性质，证明它们的相关性 在神经处理方面，并为未来研究广泛范围的西医功能变化提供了基础。 相关疾病以及发育和退化。

Abstract The proposed research aims to measure blood oxygenation level dependent (BOLD) signals in white matter (WM) using functional magnetic resonance imaging (fMRI), validate their relationships to cortical neural activity, and quantify their characteristics and their underlying biophysical origins. BOLD signals have previously been robustly detected in gray matter (GM) in response to stimuli in a very large number of studies. In addition, correlations of signal fluctuations between cortical regions in a resting state have been analyzed to derive functional connectivity. However, whether such signals reliably arise in WM remains controversial, and their interpretation is unclear. We have previously shown that BOLD signals can be reliably detected in WM if appropriate detection and analysis methods are used, and that in a resting state they exhibit anisotropic temporal correlations that largely align with WM tracts. Multiple such lines of evidence converge to suggest that WM BOLD signals are related to intrinsic, function-dependent neural activity and are apparent only in tracts engaged in specific functions. However, the precise relationships between WM and corresponding GM signals have not been established, and neither the characteristics nor origins of the hemodynamic response function (HRF) of WM have been elucidated. We hypothesize that BOLD signal variations in WM tracts are directly related to corresponding variations in neural activity in GM volumes to which they connect and/or which share specific functional roles, and that further studies will provide a new basis for more fully integrating structural and functional aspects of neural organization. In the proposed research we will [1] demonstrate and measure the relationships between BOLD signals in WM tracts (identified using diffusion imaging) and GM volumes in response to parametric stimuli whose variations modulate the degree of neural activity in specific cortical areas; [2] measure and characterize the HRF in specific WM tracts using event-related fMRI, and modify conventional models of BOLD responses to explain and fit those data; [3] establish the biophysical basis of stimulus-evoked BOLD activations in white matter by comparing data from different imaging sequences and field strengths, and by measuring BOLD signals in the brains of non-human primates with and without an intravascular susceptibility contrast agent to separate contributions from changes in blood volume vs blood oxygenation. Overall, these studies will validate the nature of WM BOLD effects, demonstrate their relevance in neural processing, and provide a basis for future studies of functional changes in a broad range of WM- associated disorders as well as development and degeneration.