Modo Michel, Crum William R, Gerwig Madeline, Vernon Anthony C, Patel Priya, Jackson Michael J, Rose Sarah, Jenner Peter, Iravani Mahmoud M
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2017 Jul 24;12(7):e0180733. doi: 10.1371/journal.pone.0180733. eCollection 2017.
Parkinson's disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics.
帕金森病（PD）是第二常见的神经退行性疾病，会导致多种运动和认知缺陷，其病因在很大程度上仍不清楚。目前认为黑质纹状体通路的逐渐丧失是关键的病理事件。为了更好地理解帕金森病的进展并改善治疗管理，在结构基础上定义该疾病并将脑分析扩展到黑质以外的结构是必不可少的。解剖结构的复杂性和神经黑色素的存在，使得使用非人类灵长类动物成为开发帕金森病假定成像生物标志物的关键要素。为此，从对照和1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的狨猴身上获取了离体T2加权磁共振图像。尾状核、壳核和黑质的体积测量表明存在明显萎缩和皮质变薄。基于张量的形态计量学对毒素对大脑造成的广泛变化提供了更广泛且无假设的评估，尤其突出了区域皮质萎缩。结果强调了在非人类灵长类动物模型中开发帕金森病成像生物标志物的重要性，考虑到它们独特的神经解剖结构。进一步在体内开发这些生物标志物以提供非侵入性工具来检测症状前帕金森病并监测潜在的疾病改变疗法至关重要。
