fMRI Technologies for Imaging at the Limit of Biological Spatiotemporal Resolution

项目摘要/摘要 功能磁共振成像(FMRI)是目前应用最广泛的非侵入性脑功能测量工具 我们目前关于人脑功能组织的大部分知识。然而，所有的fMRI方法， 通过跟踪血流量和氧合的相关局部变化，间接测量神经元的活动。 虽然这通常被认为是功能磁共振成像的局限性，但最近在动物模型中的光学成像研究表明 令人惊讶的是，大脑中最小的血管对局部神经元活动迅速做出反应，因此 与神经元紧密相连，这表明功能磁共振成像可以提供更真实的神经元活动图像 比之前认为的-如果一个人可以测量功能磁共振信号，如BOLD专门从微血管系统。 在之前的资金周期中，我们成功地测试了我们的假设，即功能磁共振成像的神经元特异性可以 通过将分析限制在标准梯度回波大胆响应的早期阶段来进行改进，思想 发生在微血管系统中，在反应扩散到更大的血管并变得空间更小之前 本地化。可靠地提取大胆响应的最早阶段的能力是通过FAST实现的 通过我们开发的功能磁共振成像采集技术，时间采样成为可能。我们的发现是 与我们的假设一致--大胆反应中最快的部分提供了最高的 微血管特异性。在这里，我们检验了相反的假设：来自微血管系统的大胆信号 是最快的，并且表现出最高的时间特异性，而来自大血管的信号在时间上 延迟并被抹黑了。为了测试这一点，我们将开发自旋回声粗体技术，它只测量 通过快速的时间采样从微血管中提取。在这个循环中，我们的中心假设是自旋回波 BOLD对微血管系统具有独有的敏感性，将产生比梯度回波更高的时间特异性 粗体，它包含来自大血管系统的较慢的信号。挑战在于，自旋回波收购 理论上提供T2加权，赋予自旋回波BOLD微血管特异性，然而在实践中 很难实现纯T2加权。因此，我们的目标是为Robust开发和验证fMRI技术 纯T2加权BOLD，并测试纯T2加权BOLD是否提供更高的时间特异性。 这些目标只能通过结合我们最近拥有的几种新的核磁共振技术来实现 介绍。核心技术是Echo-Planar时间分辨成像(EPTI)，它是Echo-Planar的扩展 成像(EPI)，它可以同时提供纯T2加权粗体和T2*加权粗体，支持 直接比较。我们将把这一点与我们提高时间采样效率的新方法结合起来 直通性和运动稳健性，并在使用快速采样率时最大化信号。最后，所有的实验 将在7特斯拉下进行，BOLD显示出更强的微血管权重和更高的灵敏度 与标准场强相比，使用并行发射RF脉冲设计可减少功率沉积和 提高fMRI敏感度的空间均匀性。

PROJECT SUMMARY / ABSTRACT Functional MRI (fMRI) is the most widely-used tool to noninvasively measure brain function and has produced much of our current knowledge about the functional organization of the human brain. All fMRI methods, however, measure neuronal activity indirectly by tracking the associated local changes in blood flow and oxygenation. While this is often viewed as a limitation of fMRI, recent optical imaging studies in animal models have shown that, surprisingly, the smallest blood vessels in the brain respond rapidly to local neuronal activity, and are thus tightly coupled to neurons, suggesting that fMRI could provide a far more veridical picture of neuronal activity than previously believed—if one can measure fMRI signals such as BOLD exclusively from the microvasculature. In the previous funding cycle, we successfully tested our hypothesis that the neuronal specificity of fMRI can be improved by restricting analyses to the earliest phases of the standard gradient-echo BOLD response, thought to occur in the microvasculature, before the responses spread to larger blood vessels and become less spatially localized. The ability to reliably extract the earliest phases of the BOLD response was achieved through the fast temporal sampling made possible through the fMRI acquisition technologies we developed. Our findings were consistent with our hypothesis—the fastest component of the BOLD response provides the highest microvascular specificity. Here we test the converse hypothesis: that BOLD signals from the microvasculature are fastest and exhibit the highest temporal specificity, while signals from the macrovasculature are temporally delayed and smeared. To test this we will develop technologies for spin-echo BOLD, which exclusively measures from the microvasculature, with fast temporal sampling. In this cycle our central hypothesis is that spin-echo BOLD with exclusive sensitivity to the microvasculature, will yield higher temporal specificity than gradient-echo BOLD, which contains slower signals from the macrovasculature. The challenge is that spin-echo acquisitions in theory provide T2 weighting, endowing spin-echo BOLD with microvascular specificity, however in practice it is difficult to achieve pure T2 weighting. Thus, our goals are to develop and validate fMRI technologies for robust pure T2-weighted BOLD, and to test whether pure T2-weighted BOLD provides higher temporal specificity. These goals can only be achieved by combining several novel MRI technologies we have recently introduced. The core technology is Echo-Planar Time-Resolved Imaging (EPTI), an extension to Echo-Planar Imaging (EPI), which can provide pure T2-weighted BOLD—concurrently with T2*-weighted BOLD, enabling direct comparisons. We will combine this with our new methods for increasing temporal sampling efficiency through and motion-robustness, and maximizing signal when using fast sampling rates. Finally, all experiments will be performed at 7 Tesla, where BOLD exhibits stronger microvascular weighting and higher sensitivity compared to standard field strengths, using parallel transmit RF pulse designs to reduce power deposition and improve the spatial uniformity of fMRI sensitivity.