Biophysical basis of functional MRI of white matter

摘要 该研究旨在测量白色物质中的血氧水平依赖（BOLD）信号 (WM)使用功能性磁共振成像（fMRI），验证它们与皮质神经活动的关系， 并量化其特征及其潜在的生物物理起源。此前，BOLD信号 在大量的研究中，在灰质（GM）中对刺激的反应中被稳健地检测到。此外，本发明还提供了一种方法， 已经分析了静息状态下皮质区域之间的信号波动的相关性， 功能性连接。然而，这些信号是否可靠地出现在WM中仍然存在争议， 解释不清楚。我们以前已经表明，BOLD信号可以在WM中可靠地检测到，如果 使用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 时间相关性与WM束基本一致。多条这样的证据表明， WM BOLD信号与内在的、功能依赖的神经活动相关，并且仅在神经束中明显 从事特定职能。然而，WM和相应GM信号之间的精确关系 尚未建立，血流动力学反应函数的特征和起源 (HRF)的WM已经被阐明。我们假设WM束中BOLD信号的变化是直接的， 与它们连接和/或共享的GM体积中的神经活动的相应变化有关 进一步的研究将为更充分地整合结构性和可持续性的工作提供新的基础， 和神经组织的功能方面。在拟议的研究中，我们将[1]演示和测量 WM束中的BOLD信号（使用扩散成像识别）和GM体积之间的关系， 对参数刺激的反应，其变化调节特定皮层神经活动的程度 区域; [2]使用事件相关fMRI测量和表征特定WM束中的HRF，并修改 传统的BOLD响应模型来解释和拟合这些数据; [3]建立生物物理基础， 通过比较来自不同成像序列的数据， 场强度，并通过测量非人类灵长类动物的大脑中的BOLD信号， 血管内敏感性对比剂分离血容量与血液变化的贡献 氧合总之，这些研究将验证WM BOLD效应的性质，证明其相关性， 在神经加工，并提供了一个基础，为未来的研究功能的变化，在广泛的WM- 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.