Hike David, Liu Xiaochen, Xie Zeping, Zhang Bei, Choi Sangcheon, Zhou Xiaoqing Alice, Liu Andy, Murstein Alyssa, Jiang Yuanyuan, Devor Anna, Yu Xin
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Charlestown, United States.
Graduate Program in Neuroscience, Boston University, Boston, United States.
Elife. 2025 Jan 9;13:RP95528. doi: 10.7554/eLife.95528.
High-resolution awake mouse functional magnetic resonance imaging (fMRI) remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radio frequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Furthermore, this study provides a thorough acclimation method used to accustom animals to the MRI environment minimizing motion-induced artifacts. Using a 14 T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100 µm×100 µm×200 µm resolution with a 2 s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust blood oxygen level-dependent (BOLD) responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 s prior to the air-puff in awake mice with repetitive stimulation, which was not detected using a randomized stimulation paradigm. This early BC activation indicated a learned anticipation through the vibrissa system and association cortices in awake mice under continuous exposure of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas.
尽管人们为解决运动诱导伪影和应激问题付出了巨大努力，但高分辨率清醒小鼠功能磁共振成像（fMRI）仍然具有挑战性。本研究介绍了一种可植入射频（RF）表面线圈设计，该设计可将小鼠大脑空气/组织界面引起的图像失真降至最低，同时在扫描过程中作为固定的头架。此外，本研究提供了一种全面的适应方法，用于使动物适应MRI环境，从而最大限度地减少运动诱导伪影。使用14 T扫描仪，高分辨率fMRI能够以100 µm×100 µm×200 µm的分辨率和每秒2帧的采样率对视觉和触须刺激进行全脑功能映射。除了激活的视觉和触须上行通路外，在视觉刺激时，在前扣带回皮质检测到了强烈的血氧水平依赖（BOLD）反应，并在触须吹气刺激时通过腹侧 retrosplenial 区域（VRA）扩散，这表明清醒小鼠联合皮质中存在高阶感觉处理。特别是，触须刺激时VRA中的快速血液动力学反应与海马体、丘脑和前额叶皮质区域有很强的相关性。与指定的VRA反应进行的互相关分析显示，在重复刺激的清醒小鼠中，对侧桶状皮质（BC）在吹气前2秒出现早期阳性BOLD信号，而在随机刺激范式中未检测到。这种早期BC激活表明，在持续暴露于重复吹气刺激的情况下，清醒小鼠通过触须系统和联合皮质进行了学习预期。这项工作建立了一个高分辨率清醒小鼠fMRI平台，能够对高级联合皮质区域的感觉信号处理进行全脑功能映射。
