SORDINO-fMRI for mouse brain applications

项目摘要 基于梯度回波（GRE）的回波平面成像（EPI）已成为功能性 磁共振成像（fMRI）技术近三十年来，由于其能够快速获得整个 脑体积与MR T2* 对血氧的敏感性-脑活动的一个众所周知的替代标记。 然而，这种被大量利用的技术受到高声学噪声、重影和运动伪影的影响， 磁场不稳定性相关伪影，与其他神经成像方式相比灵敏度低，以及 空间特异性差。一种能解决这些问题的功能磁共振成像采样技术有可能改变 日常的功能磁共振成像练习特别是，这样的发展将是非常有益的新兴啮齿动物 fMRI社区作为麻醉和应激混淆可以避免。此外，大多数啮齿动物fMRI研究都是 在高磁场强度（> 7 T）下进行，其中GRE-EPI中的磁化率伪影是 加剧了。具有“零”采集延迟和最小梯度增量的成像序列不敏感 并且与GRE相比具有提供上级特异性和灵敏度的潜力。 EPI-fMRI该项目的总体目标是推进，验证和传播一种新的3D大脑- 宽成像序列：过采样感应衰减信号的稳态斜坡检测 （SORDINO）为临床前动物fMRI社区。此外，我们还将研究SORDINO对比度 机制，并探索一种对比增强的方法，可以进一步提高SORDINO的敏感性。我们 发展将在小鼠中进行基准测试，其中头部固定方法可以用于对小鼠进行成像， 清醒状态在目标1中，我们将开发和推广SORDINO序列和重建 包装在临床前动物MRI平台中。在目标2中，我们将告知最稳健的成像参数， 将它们与建模的SORDINO性能和GRE-EPI-fMRI和零回波时间（ZTE）-fMRI进行基准测试 数据这将促进未来的SORDINO-fMRI应用，并使新的能力，研究大规模， 功能和行为相关的大脑网络。在目标3中，我们将研究SORDINO 使用MR兼容的侵入性记录的对比机制，这对数据解释至关重要。的 对比机制，如果证明是局部组织氧合、脑血流量和脑血容量， 将阐明SORDINO作为功能性脑映射的空间特异性方法。在目标4中，我们将利用 SORDINO在较短基线T1值下的预期灵敏度增益，并使用简单的锰增强 MRI（MEMRI）策略，一种被许多临床前MRI实验室广泛使用的方法，用于进一步增强清醒小鼠的 SORDINO-fMRI灵敏度。总的来说，我们希望这项工作中的知识和成果能够广泛传播， 这将极大地推动fMRI技术的发展。我们还希望这项工作产生更广泛的影响 需要快速绘制T1变化的研究，如动态对比增强MRI和分子MRI。

PROJECT SUMMARY Gradient-recalled echo (GRE)–based echo planar imaging (EPI) has been the gold standard functional magnetic resonance imaging (fMRI) technique for nearly three decades due to its ability to rapidly acquire whole brain volumes with MR T2* sensitivity to blood oxygenation — a well-known surrogate marker for brain activity. This immensely utilized technique, however, suffers from high acoustic noise, ghosting and motion artifacts, magnetic field inhomogeneity–related artifacts, low sensitivity compared to other neuroimaging modalities, and poor spatial specificity. An fMRI sampling technique that addresses these problems has the potential to change day-to-day fMRI practices. In particular, such a development would be of great benefit to the emerging rodent fMRI community as anesthesia and stress confounds can be avoided. Additionally, most rodent fMRI studies are performed under high magnetic field strengths (> 7T), wherein susceptibility artifacts in GRE-EPI are exacerbated. Imaging sequences with “zero” acquisition delay and minimal increment of gradients are insensitive to problems stated above and have the potential to provide superior specificity and sensitivity compared to GRE- EPI-fMRI. The overarching goal of this project is to advance, validate, and disseminate a novel 3D brain- wide imaging sequence: Steady-state On-the-Ramp Detection of INduction-decay signal with Oversampling (SORDINO) for the preclinical animal fMRI community. In addition, we will investigate SORDINO contrast mechanisms and explore a contrast-enhanced method that may further augment SORDINO sensitivity. Our developments will be benchmarked in mice, wherein a head-fixation approach can be utilized to image mice in an awake condition. In Aim 1, we will develop and disseminate the SORDINO sequence and reconstruction package in a preclinical animal MRI platform. In Aim 2, we will inform the most robust imaging parameters and benchmark them against modeled SORDINO performance and GRE-EPI-fMRI and zero echo time (ZTE)-fMRI data. This will facilitate future SORDINO-fMRI applications and enable new capabilities to study large-scale, functionally and behaviorally relevant brain networks in awake mice. In Aim 3, we will examine the SORDINO contrast mechanisms using MR-compatible invasive recordings, which are crucial for data interpretation. The contrast mechanisms, if proven to be local tissue oxygenation, cerebral blood flow, and cerebral blood volume, will clarify SORDINO as a spatially specific approach for functional brain mapping. In Aim 4, we will leverage the expected sensitivity gain of SORDINO at shorter baseline T1 values and use a simple manganese-enhanced MRI (MEMRI) strategy, a method widely utilized by many preclinical MRI labs, to further augment awake mouse SORDINO-fMRI sensitivity. Overall, we expect the knowledge and deliverables in this work to have widespread implications and will significantly advance fMRI technologies. We also expect this work to have extended impacts on studies requiring rapid mapping of T1 changes such as dynamic-contrast-enhanced MRI and molecular MRI.