In vivo imaging of dopaminergic and noradrenergic neurons using neuromelanin-sensitive MRI

我们试图用一种新发展的神经黑色素敏感的MRI技术显示黑质致密部(SNC)内的多巴胺能神经元和蓝斑(LC)内的去甲肾上腺素能神经元，并定量评估帕金森病、抑郁症和精神分裂症中SNC和LC的信号变化。通过使用神经黑色素敏感的MRI(高分辨率T1加权快速自旋回波技术)，我们可以成功地将SNC和LC描绘为高信号区，与宏观标本中与神经黑素相关的黑色区域很好地对应。在帕金森病患者中，黑质和蓝斑的对比度(CRS)明显低于年龄匹配的对照组，提示这些核团存在神经元耗竭，这一点已被病理证实。在抑郁症患者中，与年龄匹配的对照组相比，LC吻端三分之二的CRS显著降低，提示去甲肾上腺素能系统功能障碍，这被认为是抑郁症的发病机制之一。在精神分裂症患者中，与年龄匹配的抑郁症患者和对照组相比，黑质核团的CRS显著增加；这表明多巴胺能系统过度活跃，这支持经典的多巴胺假说。我们开发的神经黑色素敏感核磁共振技术使体内可视化神经黑素含量的核团，如黑素核和LC。此外，它还可以用于测量影响这些核团的退行性疾病和精神疾病的病理或功能变化。

We attempted to visualize dopaminergic neurons within the substantia nigra pars compacts (SNc) and noradrenergic neurons within the locus ceruleus (LC) using a newly developed neuromelanin-sensitive MRI technique, and to quantitatively evaluate the signal alterations of the SNc and LC in Parkinson's disease, depression, and schizophrenia.By using the neuromelanin-sensitive MRI.(a high-resolution T1-weighted fast spin-echo technique at 3 Thsla), we can successfully depict the SNc and LC as high signal intensity areas that correspond well to the neuromelanin-related black areas in macroscopic specimens. In patients with Parkinson's disease, the contrast ratios (CRs) of the SNc and LC decreased significantly as compared with those in the age-matched controls, suggesting the existence of neuronal depletion in these nuclei, which has been proven pathologically. In patients with depression, the CRs of the rostral two-thirds of the LC diminished significantly as compared with those in the age-matched controls, suggesting a dysfunction in the ascending noradrenergic system, which is believed to be one of the pathogeneses of depression. In patients with schizophrenia, the CRs of the SNc increased significantly as compared with those in the age-matched depressive patients and controls; this suggests the hyperactivity of the dopaminergic system, which supports the classical dopamine hypothesis.The neuromelanin-sensitive MRI, which we have developed, enabled the in vivo visualization of neuromelanin-contsirting nuclei, such as the SNc and LC. Further, it can also be useful for measuring the pathological or functional alterations in the degenerative and psychiatric disorders affecting these nuclei.