Keren Noam I, Taheri Saeid, Vazey Elena M, Morgan Paul S, Granholm Ann-Charlotte E, Aston-Jones Gary S, Eckert Mark A
Department of Neurosciences, Medical University of SC, Charleston, SC, USA.
Medical Physics, Nottingham University Hospitals, NHS Trust, Nottingham, UK.
Neuroimage. 2015 Jun;113:235-45. doi: 10.1016/j.neuroimage.2015.03.020. Epub 2015 Mar 17.
The locus coeruleus (LC) noradrenergic system regulates arousal and modulates attention through its extensive projections across the brain. LC dysfunction has been implicated in a broad range of neurodevelopmental, neurodegenerative and psychiatric disorders, as well as in the cognitive changes observed during normal aging. Magnetic resonance imaging (MRI) has been used to characterize the human LC (elevated contrast relative to surrounding structures), but there is limited understanding of the factors underlying putative LC contrast that are critical to successful biomarker development and confidence in localizing nucleus LC. We used ultra-high-field 7 T magnetic resonance imaging (MRI) to acquire T1-weighted microscopy resolution images (78 μm in-plane resolution) of the LC from post-mortem tissue samples. Histological analyses were performed to characterize the distribution of tyrosine hydroxylase (TH) and neuromelanin in the scanned tissue, which allowed for direct comparison with MR microscopy images. Our results indicate that LC-MRI contrast corresponds to the location of neuromelanin cells in LC; these also correspond to norepinephrine neurons. Thus, neuromelanin appears to serve as a natural contrast agent for nucleus LC that can be used to localize nucleus LC and may have the potential to characterize neurodegenerative disease.
蓝斑（LC）去甲肾上腺素能系统通过其在大脑中的广泛投射来调节觉醒并调控注意力。LC功能障碍与多种神经发育、神经退行性和精神疾病有关，也与正常衰老过程中观察到的认知变化有关。磁共振成像（MRI）已被用于表征人类LC（相对于周围结构对比度升高），但对于假定的LC对比度背后的因素了解有限，而这些因素对于成功开发生物标志物以及确定LC核的位置至关重要。我们使用超高场7T磁共振成像（MRI）从死后组织样本中获取LC的T1加权显微镜分辨率图像（平面分辨率为78μm）。进行了组织学分析以表征扫描组织中酪氨酸羟化酶（TH）和神经黑色素的分布，从而能够与MR显微镜图像进行直接比较。我们的结果表明，LC-MRI对比度对应于LC中神经黑色素细胞的位置；这些细胞也对应于去甲肾上腺素能神经元。因此，神经黑色素似乎可作为LC核的天然对比剂，可用于定位LC核，并且可能具有表征神经退行性疾病的潜力。
