Correlation of brain magnetic resonance imaging changes with pallidal manganese concentrations in rhesus monkeys following subchronic manganese inhalation
Correlation of brain magnetic resonance imaging changes with pallidal manganese concentrations in rhesus monkeys following subchronic manganese inhalation
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DOI：
10.1093/toxsci/kfj209
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发表时间：
2006-07-01
影响因子：
3.8
通讯作者：
Robertson, Ian D.
中科院分区：
文献类型：
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作者：
Dorman, David C.;Struve, Melanie F.;Robertson, Ian D.
高剂量锰暴露与帕金森综合征有关。由于锰是顺磁性的，它在大脑中的相对分布可以使用磁共振成像（MRI）检查。在此，我们提出了第一个全面的研究，使用MRI，苍白球指数（PI），T-1弛豫率（R1）与化学分析相结合，以建立一个直接关联的MRI变化和苍白球锰浓度在恒河猴亚慢性吸入硫酸锰（MnSO 4）。暴露于MnSO 4浓度>= 0.06 mg Mn/m3的猴子，苍白球、壳核、嗅上皮、嗅球和小脑中的锰浓度增加。锰浓度的MnSO 4暴露的猴子的嗅觉系统内表现出下降的rostralcaudal浓度梯度，发现与嗅觉运输吸入锰一致。在嗅球和苍白球内观察到明显的MRI信号高信号;然而，在介入组织中无法辨别出类似的变化。R1和PI与苍白球锰浓度相关。然而，在白色物质锰浓度的MnSO 4暴露的猴子混淆PI测量，并可能导致低估苍白球锰的积累。我们的研究结果表明，R1可以用来估计区域脑锰浓度，并可能是一个可靠的职业锰暴露的生物标志物。据我们所知，这项研究是第一个提供证据的直接嗅觉运输的吸入金属在非人类灵长类动物。然而，锰的Pallidal交付可能主要来自全身交付，而不是直接从嗅觉运输。
High-dose manganese exposure is associated with parkinsonism. Because manganese is paramagnetic, its relative distribution within the brain can be examined using magnetic resonance imaging (MRI). Herein, we present the first comprehensive study to use MRI, pallidal index (PI), and T-1 relaxation rate (R1) in concert with chemical analysis to establish a direct association between MRI changes and pallidal manganese concentration in rhesus monkeys following subchronic inhalation of manganese sulfate (MnSO4). Monkeys exposed to MnSO4 at >= 0.06 mg Mn/m(3) developed increased manganese concentrations in the globus pallidus, putamen, olfactory epithelium, olfactory bulb, and cerebellum. Manganese concentrations within the olfactory system of the MnSO4-exposed monkeys demonstrated a decreasing rostralcaudal concentration gradient, a finding consistent with olfactory transport of inhaled manganese. Marked MRI signal hyperintensities were seen within the olfactory bulb and the globus pallidus; however, comparable changes could not be discerned in the intervening tissue. The R1 and PI were correlated with the pallidal manganese concentration. However, increases in white matter manganese concentrations in MnSO4-exposed monkeys confounded the PI measurement and may lead to underestimation of pallidal manganese accumulation. Our results indicate that the R1 can be used to estimate regional brain manganese concentrations and may be a reliable biomarker of occupational manganese exposure. To our knowledge, this study is the first to provide evidence of direct olfactory transport of an inhaled metal in a non-human primate. Pallidal delivery of manganese, however, likely arises primarily from systemic delivery and not directly from olfactory transport.