Max Planck Institute of Psychiatry, Munich, Germany.
NMR Biomed. 2013 May;26(5):542-56. doi: 10.1002/nbm.2891. Epub 2012 Nov 20.
Manganese-enhanced MRI has recently become a valuable tool for the assessment of in vivo functional cerebral activity in animal models. As a result of the toxicity of manganese at higher dosages, fractionated application schemes have been proposed to reduce the toxic side effects by using lower concentrations per injection. Here, we present data on regional-specific manganese accumulation during a fractionated application scheme over 8 days of 30 mg/kg MnCl2 , as well as on the clearance of manganese chloride over the course of several weeks after the termination of the whole application protocol supplying an accumulative dose of 240 mg/kg MnCl2 . Our data show most rapid accumulation in the superior and inferior colliculi, amygdala, bed nucleus of the stria terminalis, cornu ammonis of the hippocampus and globus pallidus. The data suggest that no ceiling effects occur in any region using the proposed application protocol. Therefore, a comparison of basal neuronal activity differences in different animal groups based on locally specific manganese accumulation is possible using fractionated application. Half-life times of manganese clearance varied between 5 and 7 days, and were longest in the periaqueductal gray, amygdala and entorhinal cortex. As the hippocampal formation shows one of the highest T1 -weighted signal intensities after manganese application, and manganese-induced memory impairment has been suggested, we assessed hippocampus-dependent learning as well as possible manganese-induced atrophy of the hippocampal volume. No interference of manganese application on learning was detected after 4 days of Mn(2+) application or 2 weeks after the application protocol. In addition, no volumetric changes induced by manganese application were found for the hippocampus at any of the measured time points. For longitudinal measurements (i.e. repeated manganese applications), a minimum of at least 8 weeks should be considered using the proposed protocol to allow for sufficient clearance of the paramagnetic ion from cerebral tissue.
锰增强磁共振成像最近已成为评估动物模型体内功能脑活动的一种有价值的工具。由于较高剂量的锰具有毒性，因此提出了分段应用方案，通过每次注射使用较低的浓度来减少毒副作用。在这里，我们提供了在 30mg/kg MnCl2 8 天的分段应用方案中区域特异性锰积累的数据，以及在整个应用方案结束后数周内清除氯化锰的数据，该方案提供了 240mg/kg MnCl2 的累积剂量。我们的数据显示，在上丘和下丘、杏仁核、终纹床核、海马角回和苍白球中积累最快。数据表明，在任何区域使用所提出的应用方案都不会出现上限效应。因此，使用分段应用可以根据局部特定的锰积累来比较不同动物组之间的基础神经元活动差异。锰清除的半衰期在 5 到 7 天之间变化，在中脑导水管周围灰质、杏仁核和内嗅皮层最长。由于海马结构在锰应用后显示出最高的 T1 加权信号强度之一，并且已经提出了锰诱导的记忆障碍，因此我们评估了海马依赖性学习以及可能的锰诱导的海马体积萎缩。在 Mn(2+)应用后 4 天或应用方案后 2 周，未发现锰应用对学习有干扰。此外，在任何测量时间点，均未发现锰应用引起的海马体积变化。对于纵向测量（即重复锰应用），建议使用所提出的方案至少考虑 8 周，以便从脑组织中充分清除顺磁性离子。
