University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
Beckman Institute, California Institute of Technology, Pasadena, California, USA.
NMR Biomed. 2022 Jun;35(6):e4675. doi: 10.1002/nbm.4675. Epub 2022 Mar 6.
Manganese-enhanced magnetic resonance imaging (MEMRI) holds exceptional promise for preclinical studies of brain-wide physiology in awake-behaving animals. The objectives of this review are to update the current information regarding MEMRI and to inform new investigators as to its potential. Mn(II) is a powerful contrast agent for two main reasons: (1) high signal intensity at low doses; and (2) biological interactions, such as projection tracing and neural activity mapping via entry into electrically active neurons in the living brain. High-spin Mn(II) reduces the relaxation time of water protons: at Mn(II) concentrations typically encountered in MEMRI, robust hyperintensity is obtained without adverse effects. By selectively entering neurons through voltage-gated calcium channels, Mn(II) highlights active neurons. Safe doses may be repeated over weeks to allow for longitudinal imaging of brain-wide dynamics in the same individual across time. When delivered by stereotactic intracerebral injection, Mn(II) enters active neurons at the injection site and then travels inside axons for long distances, tracing neuronal projection anatomy. Rates of axonal transport within the brain were measured for the first time in "time-lapse" MEMRI. When delivered systemically, Mn(II) enters active neurons throughout the brain via voltage-sensitive calcium channels and clears slowly. Thus behavior can be monitored during Mn(II) uptake and hyperintense signals due to Mn(II) uptake captured retrospectively, allowing pairing of behavior with neural activity maps for the first time. Here we review critical information gained from MEMRI projection mapping about human neuropsychological disorders. We then discuss results from neural activity mapping from systemic Mn(II) imaged longitudinally that have illuminated development of the tonotopic map in the inferior colliculus as well as brain-wide responses to acute threat and how it evolves over time. MEMRI posed specific challenges for image data analysis that have recently been transcended. We predict a bright future for longitudinal MEMRI in pursuit of solutions to the brain-behavior mystery.
锰增强磁共振成像（MEMRI）在清醒动物的全脑生理学的临床前研究中具有特殊的应用前景。本文综述的目的是更新有关 MEMRI 的最新信息，并向新的研究人员介绍其潜力。Mn（II）是一种强大的对比剂，原因有二：（1）在低剂量下具有高信号强度；（2）生物学相互作用，例如通过进入活脑中的电活性神经元进行投射示踪和神经活动映射。高自旋 Mn（II）会缩短水质子的弛豫时间：在 MEMRI 中通常遇到的 Mn（II）浓度下，会获得强烈的超强度而不会产生不良反应。Mn（II）通过电压门控钙通道选择性进入神经元，突出活跃的神经元。安全剂量可重复数周，以便在同一个体中进行跨时间的全脑动力学的纵向成像。当通过立体定向脑内注射给药时，Mn（II）进入注射部位的活跃神经元，然后在轴突内长距离迁移，追踪神经元投射解剖结构。首次在“时移”MEMRI 中测量了脑内轴突内的运输速度。当全身给药时，Mn（II）通过电压敏感钙通道进入整个大脑中的活跃神经元，并缓慢清除。因此，在 Mn（II）摄取期间可以监测行为，并且可以回顾性捕获由于 Mn（II）摄取而导致的超强度信号，从而首次将行为与神经活动图谱配对。在这里，我们回顾了从 MEMRI 投射映射中获得的有关人类神经心理障碍的关键信息。然后，我们讨论了从系统给予的 Mn（II）进行的纵向成像中获得的神经活动映射的结果，这些结果阐明了下丘脑中音调图谱的发育以及对急性威胁的全脑反应及其随时间的演变。MEMRI 对图像数据分析提出了特定的挑战，这些挑战最近已经得到了克服。我们预测，在寻求解决大脑-行为之谜的过程中，纵向 MEMRI 将有一个光明的未来。
