fMRI Technologies for Imaging at the Limit of Biological Spatiotemporal Resolution: Administrative Supplement

项目总结/摘要 功能磁共振成像（fMRI）是最广泛使用的工具，以非侵入性地测量大脑功能，并已产生 我们目前对人脑功能组织的大部分认识。然而，所有的功能磁共振成像方法， 通过跟踪血流和氧合的相关局部变化来间接测量神经元活动。 虽然这通常被视为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的活动反应迅速，因此， 这表明功能磁共振成像可以提供一个更真实的神经元活动的图片 比以前认为的要多--如果人们能够专门从微血管系统测量功能磁共振成像信号，如BOLD。 在上一个资助周期中，我们成功地验证了我们的假设，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BOLD响应的最早阶段， 在反应扩散到更大的血管并在空间上变得更小之前， 本地化。可靠地提取BOLD响应的最早阶段的能力是通过快速 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。我们的研究结果 与我们的假设一致-BOLD响应的最快分量提供了最高的 微血管特异性在这里，我们测试匡威的假设：BOLD信号来自微血管系统， 是最快的，并表现出最高的时间特异性，而来自大血管系统的信号是时间特异性的。 延迟和涂抹。为了测试这一点，我们将开发自旋回波BOLD技术，它专门测量 从微血管系统中提取，并进行快速时间采样。在这个循环中，我们的中心假设是， BOLD仅对微血管敏感，将产生比梯度回波更高的时间特异性 BOLD，包含来自大血管系统的较慢信号。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，我们的目标是开发和验证功能磁共振成像技术， 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的几种新颖的MRI技术来实现 介绍核心技术是回波平面时间分辨成像（EPTI），是回波平面的扩展 成像（EPI），它可以提供纯T2加权BOLD-同时与T2* 加权BOLD， 直接比较。我们将联合收割机与我们的新方法相结合，以提高时间采样效率 通过和运动鲁棒性，以及在使用快速采样率时最大化信号。最后，所有实验 将在7特斯拉下进行，其中BOLD表现出更强的微血管加权和更高的灵敏度 与标准场强相比，使用并行发射RF脉冲设计来减少功率沉积， 提高fMRI灵敏度的空间均匀性。

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.