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Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson’s disease
npj Parkinson's Disease ( IF 9.304 ) Pub Date : 2018-04-10 , DOI: 10.1038/s41531-018-0047-3
David Sulzer , Clifford Cassidy , Guillermo Horga , Un Jung Kang , Stanley Fahn , Luigi Casella , Gianni Pezzoli , Jason Langley , Xiaoping P. Hu , Fabio A. Zucca , Ioannis U. Isaias , Luigi Zecca

The diagnosis of Parkinson’s disease (PD) occurs after pathogenesis is advanced and many substantia nigra (SN) dopamine neurons have already died. Now that therapies to block this neuronal loss are under development, it is imperative that the disease be diagnosed at earlier stages and that the response to therapies is monitored. Recent studies suggest this can be accomplished by magnetic resonance imaging (MRI) detection of neuromelanin (NM), the characteristic pigment of SN dopaminergic, and locus coeruleus (LC) noradrenergic neurons. NM is an autophagic product synthesized via oxidation of catecholamines and subsequent reactions, and in the SN and LC it increases linearly during normal aging. In PD, however, the pigment is lost when SN and LC neurons die. As shown nearly 25 years ago by Zecca and colleagues, NM’s avid binding of iron provides a paramagnetic source to enable electron and nuclear magnetic resonance detection, and thus a means for safe and noninvasive measure in living human brain. Recent technical improvements now provide a means for MRI to differentiate between PD patients and age-matched healthy controls, and should be able to identify changes in SN NM with age in individuals. We discuss how MRI detects NM and how this approach might be improved. We suggest that MRI of NM can be used to confirm PD diagnosis and monitor disease progression. We recommend that for subjects at risk for PD, and perhaps generally for older people, that MRI sequences performed at regular intervals can provide a pre-clinical means to detect presymptomatic PD.



中文翻译:

磁共振成像(MRI)检测神经黑色素及其作为帕金森氏病生物标志物的前景

帕金森氏病(PD)的诊断发生在发病机理进展并且许多黑质(SN)多巴胺神经元已经死亡之后。现在,正在开发阻止这种神经元丢失的疗法,因此必须尽早诊断出该疾病,并监测对疗法的反应。最近的研究表明,可以通过磁共振成像(MRI)检测神经性黑色素(NM),SN多巴胺能的特征性色素和蓝斑能量(LC)的去甲肾上腺素能神经元来实现。NM是通过儿茶酚胺氧化和后续反应合成的自噬产物,在SN和LC中,它在正常衰老过程中呈线性增加。然而,在PD中,当SN和LC神经元死亡时,色素会丢失。正如25年前Zecca及其同事所展示的那样,NM对铁的狂热结合提供了顺磁性源,可以进行电子和核磁共振检测,因此是在人的活脑中进行安全且无创测量的一种手段。现在,最近的技术改进为MRI提供了一种区分PD患者和与年龄匹配的健康对照的方法,并且应该能够识别SN NM随着年龄的变化。我们讨论了MRI如何检测NM以及如何改进这种方法。我们建议NM的MRI可用于确认PD诊断和监测疾病进展。我们建议,对于有PD风险的受试者,也许对于一般老年人而言,定期进行的MRI序列检查可提供临床前检测症状前PD的方法。因此,这是一种在人脑中进行安全无创测量的方法。现在,最近的技术改进为MRI提供了一种区分PD患者和与年龄匹配的健康对照的方法,并且应该能够识别SN NM随着年龄的变化。我们讨论了MRI如何检测NM以及如何改进这种方法。我们建议NM的MRI可用于确认PD诊断和监测疾病进展。我们建议,对于有PD风险的受试者,也许对于一般老年人而言,定期进行的MRI序列检查可提供临床前检测症状前PD的方法。因此,这是一种在人脑中进行安全无创测量的方法。现在,最近的技术改进为MRI提供了一种区分PD患者和与年龄匹配的健康对照的方法,并且应该能够识别SN NM随着年龄的变化。我们讨论了MRI如何检测NM以及如何改进这种方法。我们建议NM的MRI可用于确认PD诊断和监测疾病进展。我们建议,对于有PD风险的受试者,也许对于一般老年人而言,定期进行的MRI序列检查可提供临床前检测症状前PD的方法。并且应该能够识别个体中SN NM随年龄的变化。我们讨论了MRI如何检测NM以及如何改进这种方法。我们建议NM的MRI可用于确认PD诊断和监测疾病进展。我们建议,对于有PD风险的受试者,也许对于一般老年人而言,定期进行的MRI序列检查可提供临床前检测症状前PD的方法。并且应该能够识别个体中SN NM随年龄的变化。我们讨论了MRI如何检测NM以及如何改进这种方法。我们建议NM的MRI可用于确认PD诊断和监测疾病进展。我们建议,对于有PD风险的受试者,也许对于一般老年人而言,定期进行的MRI序列检查可提供临床前检测症状前PD的方法。

更新日期:2019-11-18
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