Neuroimaging Biomarkers in Parkinsonism: Differentiating Subtypes and Tracking Disease Progression

项目总结 这个应用程序的目标有两个。首先，我们将跨两个成像站点测试和验证一组 我们最近发布的用于区分和跟踪疾病的诊断和进展生物标记物 帕金森病(PD)、帕金森变异型多系统萎缩(MSAp)和 进行性核上麻痹(PSP)。第二，我们将使用一套新的成像生物标志物来进一步 了解这三种疾病的神经生物学差异及其随时间的发展。怀着敬意 对于目标1，在过去的5年里，我们的团队领导了 帕金森氏病生物标记物计划(PDBP)，并开发了两个用于区分的创新生物标记物 Pd、MSAp和PSP。自由水扩散成像和任务功能磁共振成像都揭示了明确的模式 基底节和小脑的退行性变和功能异常激活 区分PD、MSAp和PSP。在纵向研究中，我们发现自由水扩散成像和任务- FMRI跟踪PD、MSAp和PSP在一年内的进展，年龄和性别没有匹配的变化 控制。基于MRI的可重复性、可靠性、客观性和有效性的进展标记具有重要的意义 意义和将改变PD、MSAp和PSP的临床试验。关于目标2，除了 使用我们的标准化方案跨两个成像站点评估免费水和基于任务的fMRI，我们将 同时使用多切片技术测试利用先进成像脉冲序列的新生物标志物 成像，以更快的速度和更高的空间分辨率获取数据。这样的技术进步提供了更丰富的 黑质纹状体、皮质纹状体和小脑-丘脑-皮质解剖束的疾病检查 为了了解疾病是如何随着时间的推移沿着疾病特有的途径传播的。 利用同步多层成像将促进用于检查的多层扩散成像模型 游离水，轴突密度和定向分散，以及任务-功能磁共振连通性，以检查 整个网络中的正常连接。在我们的两个成像站点，我们将获得100PD，50MSAp， PSP组50例，年龄、性别相匹配的健康对照组50例。我们将与PDBP及时提供数据共享 社区。我们在神经学和神经成像方面拥有一支非常有经验的专家团队，并拥有悠久的 一起在高影响力的期刊上发表文章。

PROJECT SUMMARY The goal of this application is two-fold. First, we will test and validate across two imaging sites a set of diagnostic and progression biomarkers we have recently published that differentiate and track disease progression in Parkinson's disease (PD), parkinsonian variant of multiple system atrophy (MSAp) and progressive supranuclear palsy (PSP). Second, we will use a set of novel imaging biomarkers to further understand the neurobiology of how each of these three diseases differ and progress over time. With respect to goal 1, over the past 5 years our group has led the efforts in magnetic resonance imaging (MRI) for the Parkinson's Disease Biomarker Program (PDBP) and has developed 2 innovative biomarkers for differentiating PD, MSAp, and PSP. Both free-water diffusion imaging and task-fMRI have uncovered clear patterns of degeneration and abnormal functional activation in the basal ganglia and cerebellum that can reliably differentiate PD, MSAp, and PSP. In longitudinal studies we found that free-water diffusion imaging and task- fMRI track progression of PD, MSAp, and PSP over one year with no changes in age and sex matched controls. Reproducible, reliable, objective and validated MRI-based progression markers are of great significance and would transform clinical trials in PD, MSAp, and PSP. With respect to goal 2, in addition to evaluating free-water and task-based fMRI using our standardized protocol across two imaging sites, we will also test new biomarkers that leverage advanced imaging pulse sequences using simultaneous multi-slice imaging for acquiring data faster and at a higher spatial resolution. Such technical advances provide a richer examination of the nigrostriatal, cortico-striatal, and cerebellar-thalamo-cortical anatomical tracts for disease differentiation, and for understanding how the disease spreads along disease-specific tracts over time. Leveraging simultaneous multi-slice imaging will facilitate multi-shell diffusion imaging models for examining free-water, neurite density and orientation dispersion, as well as task-fMRI connectivity for examining the functional connections across a network. At our two imaging sites, we will acquire data on 100 PD, 50 MSAp, 50 PSP, and 50 healthy age and sex matched controls. We will provide timely data sharing with the PDBP community. We have a very experienced team of experts in neurology and neuroimaging, and a long history of publishing together in high impact journals.