Longitudinal multi-modality imaging in progressive apraxia of speech (Diversity Supplement)

进行性言语失用的纵向多模态成像（多样性补充）

• 批准号: 10590477
• 负责人: Jennifer Louise Whitwell
• 金额: $ 1.15万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10590477
• 关键词: Affect; Apraxias; Articulation; Biological; Brain; Brain region; Clinical; Clinical Treatment; Development; Diagnostic Specificity; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Knowledge; Language; Lead; Ligands; MRI Scans; Measures; Modality; Motor; Motor Cortex; Multimodal Imaging; Nerve Degeneration; Neurologic; Pathologic Processes; Patients; Positron-Emission Tomography; Production; Rest; Speech; Techniques; Time; Treatment Efficacy; base; functional MRI scan; gray matter; improved; interest; multimodality; neurobiological mechanism; neuroimaging; novel imaging technique; patient subsets; protein distribution; recruit; tau Proteins; tractography; treatment trial; uptake; white matter

PROJECT SUMMARY Progressive apraxia of speech is a neurodegenerative speech motor planning disorder that affects the production of speech. In the 1st cycle of the R01 we demonstrated that progressive apraxia of speech is associated with progressive degeneration of both the grey and white matter of the brain, with degeneration spreading throughout the brain from a relatively focal starting point, and we showed that regional changes correlated to clinical decline. However, the neurobiological mechanisms underlying these structural changes and disease progression remain elusive and represent a gap in knowledge. Understanding disease mechanisms will be critical for the development of appropriate therapies and for assessing the efficacy of treatments. The primary goal of our 2nd cycle is, therefore, to utilize advanced neuroimaging techniques to assess the neurobiological mechanisms underlying disease progression in progressive apraxia of speech. The first objective of the study is to determine the regional distribution and progressive spread of tau uptake using tau PET imaging. The second objective is then to using resting-state and task-based functional MRI and diffusion tensor tractography to characterize how disruptions in functional and structural connectivity within and across brain networks progress over time, and how these changes are related to regional tau uptake. Our last objective is then to investigate correlations between these neuroimaging measures and clinical disease progression. To accomplish these aims we will recruit 50 patients with progressive apraxia of speech, and each patient will undergo two serial assessments one year apart. At each assessment, patients will have a neurological and speech-language assessment, tau-PET scan using the [18F]AV-1451 ligand and a 3T magnetic resonance imaging scan that will include resting-state functional MRI and diffusion tensor imaging sequences. A subset of patients will also undergo a short task-based fMRI scan to allow us to assess brain activity related to speech articulation. Our analysis will assess abnormalities in these modalities within the motor speech network of regions, particularly premotor and motor cortex, and determine how dysfunction within this network changes over time and whether the disease spreads to involve other networks. We will calculate tau-PET uptake in a standard set of regions-of-interest and then measure both structural and functional connectivity between these regions-of-interest. This approach will allow us to assess multi-modal correlations and determine how these different disease mechanisms are related to each other as well as clinical decline. This mechanistic approach will increase our understanding of disease progression and the relationship between pathological processes and brain connectivity in progressive apraxia of speech; knowledge that may help improve diagnostic specificity and will be critical for the future development of mechanistically based therapies.

项目摘要 进行性言语失用症是一种神经退行性言语运动规划障碍， 演讲的制作。在R 01的第一个周期中，我们证明了进行性言语失用症是 与大脑灰质和白色物质的进行性变性相关， 从一个相对集中的起点开始扩散到整个大脑，我们发现， 与临床衰退相关。然而，这些结构变化背后的神经生物学机制 和疾病进展仍然难以捉摸，代表着知识的空白。理解疾病 这些机制对于开发适当的治疗方法和评估 治疗。因此，我们第二个周期的主要目标是利用先进的神经成像技术， 评估进行性言语失用症的神经生物学机制。的 研究的第一个目标是确定tau摄取的区域分布和逐步扩散， tau PET成像。第二个目标是使用静息状态和基于任务的功能性MRI， 弥散张量纤维束成像，以表征内部和内部的功能和结构连接的中断， 随着时间的推移，大脑网络的进展，以及这些变化如何与区域tau摄取有关。我们最后 目的是研究这些神经影像学指标与临床疾病之间的相关性 进展为了实现这些目标，我们将招募50名进行性言语失用症患者， 每名病人将接受两次连续评估，每次相隔一年。在每次评估中，患者将有一个 神经学和言语语言评估，使用[18 F]AV-1451配体和3 T 磁共振成像扫描，包括静息态功能性MRI和弥散张量成像 序列的一部分患者还将接受简短的基于任务的功能磁共振成像扫描，以使我们能够评估大脑 与言语清晰度有关的活动。我们的分析将评估这些模式中的异常， 运动言语网络的区域，特别是前运动和运动皮层，并确定如何功能障碍 随着时间的推移，疾病是否会蔓延到其他网络。我们将 计算标准组感兴趣区域中的tau-PET摄取，然后测量结构和 这些感兴趣区域之间的功能连接。这种方法将使我们能够评估多模式 相关性，并确定这些不同的疾病机制是如何相互关联的， 临床衰退这种机制的方法将增加我们对疾病进展的理解， 进行性言语失用症的病理过程与脑连接的关系; 这些知识可能有助于提高诊断特异性，并对未来的发展至关重要。 基于机械的疗法