SORDINO-fMRI for mouse brain applications

项目总结 基于梯度回波(GRE)的回波平面成像(EPI)已经成为金标准函数 磁共振成像(FMRI)技术已有近三十年的历史，因为它能够快速获取 大脑体积与MR T2*对血液氧合的敏感性--一个众所周知的大脑活动的替代标记物。 然而，这种被广泛使用的技术受到高声学噪声、重影和运动伪影的影响， 与磁场不均匀相关的伪影，与其他神经成像手段相比灵敏度较低，以及 空间特异性差。一种解决这些问题的功能磁共振成像采样技术有可能改变 日常功能核磁共振检查。特别是，这样的发展将对新兴啮齿动物大有裨益。 功能磁共振成像社区的麻醉和压力混淆是可以避免的。此外，大多数啮齿动物功能磁共振研究都是 在高磁场强度(&gt；7T)下进行，其中GRE-EPI中的磁化率伪影是 加剧了。采集延迟为零且梯度增量最小的成像序列是不敏感的 与GRE相比，有可能提供更好的特异性和敏感性 EPI-功能磁共振成像。该项目的总体目标是推进、验证和传播一个新的3D大脑- 宽成像序列：感应衰减信号的稳态过采样斜坡检测 临床前动物功能磁共振成像社区。此外，我们还将调查索迪诺对比 并探索对比度增强的方法，可能会进一步提高索迪诺敏感性。我们的 发展将以小鼠为基准，其中可以使用头部固定方法来对小鼠进行成像 清醒的状态。在目标1中，我们将开发和传播SODERO序列和重建 封装在临床前动物磁共振平台中。在目标2中，我们将告知最稳健的成像参数和 根据建模的SODIO性能和GRE-EPI-fMRI和零回波时间(ZTE)-fMRI对它们进行基准测试 数据。这将促进未来的SODIO-FMRI应用，并使新的能力能够进行大规模研究， 清醒小鼠的功能和行为相关的脑网络。在目标3中，我们将研究索迪诺 使用与MR兼容的侵入性记录的对比机制，这对数据解释至关重要。这个 对比机制，如果被证实是局部组织氧合、脑血流量和脑血容量， 将阐明SODIO是一种空间上特定的脑功能图谱方法。在目标4中，我们将利用 在较短的基线T1值和使用简单的锰增强的情况下，索迪诺的预期灵敏度增益 磁共振成像(MEMRI)策略是许多临床前MRI实验室广泛使用的一种方法，以进一步增强清醒小鼠 Sordo-fMRI灵敏度。总体而言，我们希望这项工作中的知识和可交付成果具有广泛的 并将显著推动功能磁共振成像技术的发展。我们还预计这项工作将产生广泛的影响 需要快速绘制T1变化图的研究，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.