Longitudinal multi-modality imaging in progressive apraxia of speech

进行性言语失用症的纵向多模态成像

• 批准号: 10436959
• 负责人: Jennifer Louise Whitwell
• 金额: $ 56.09万
• 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/10436959
• 关键词: Address; Affect; Aphasia; Apraxias; Area; Articulation; Autopsy; Basal Ganglia; Biological; Brain; Brain Stem; Brain region; Brain scan; Broca' s area; Clinical; Clinical Treatment; Clinical Trials; Data; Deposition; Development; Diagnostic Specificity; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Insula of Reil; Intervention; Knowledge; Language; Lead; Ligands; MRI Scans; Magnetic Resonance Imaging; Measures; Modality; Motor; Motor Cortex; Multimodal Imaging; Nerve Degeneration; Neurologic; Parietal Lobe; Pathologic Processes; Pathology; Patients; Pattern; Positron-Emission Tomography; Prefrontal Cortex; Production; Research; Rest; Severities; Speech; Speech Disorders; Tauopathies; Techniques; Thalamic structure; Time; Treatment Efficacy; Work; base; brain metabolism; brain volume; cingulate gyrus; fluorodeoxyglucose positron emission tomography; functional MRI scan; gray matter; imaging biomarker; improved; interest; multimodality; network dysfunction; neurobiological mechanism; neuroimaging; novel; novel imaging technique; patient subsets; programs; protein distribution; recruit; relating to nervous system; research study; 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 言语的渐进性失用是一种神经退行性的语音运动计划障碍，影响了 言语的产生。在R01的第一个周期中，我们证明了语音的渐进性语言是 与大脑的灰色和白色物质的进行性变性有关，变性 从相对焦点的起点散布在整个大脑中，我们表明了区域变化 与临床下降相关。但是，这些结构变化的基础神经生物学机制 疾病的进展仍然难以捉摸，代表了知识的差距。了解疾病 机制对于开发适当的疗法至关重要，并评估的功效 治疗。因此，我们第二个周期的主要目标是利用高级神经影像学技术 评估言语进行性疾病的疾病进展的神经生物学机制。这 该研究的第一个目的是确定使用的区域分布和使用 tau宠物成像。第二个目标是使用静止状态和基于任务的功能MRI和 扩散张量拖拉术以表征功能和结构连通性内部和结构连通性的破坏和 整个大脑网络随着时间的推移以及这些变化与区域tau的吸收如何相关。我们的最后一个 然后，目的是研究这些神经影像措施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名言语逐步失用的患者， 每个患者将相距一年进行两次连续评估。在每个评估中，患者将有一个 神经和语言评估，使用[18F] AV-1451配体和3T的Tau-pet扫描 磁共振成像扫描将包括静止状态功能MRI和扩散张量成像 序列。一部分患者还将接受简短的基于任务的fMRI扫描，以使我们能够评估大脑 与语音发音有关的活动。我们的分析将评估这些模式中的异常 区域的运动语音网络，尤其是前运动皮层，并确定功能障碍 在这个网络中，随着时间的流逝，疾病是否扩散到其他网络。我们将 计算一套标准区域中的tau-pet吸收，然后测量结构和 这些区域之间的功能连通性。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如何相互关联以及 临床下降。这种机械方法将提高我们对疾病进展的理解和 病理过程与大脑连通性之间的关系，言语的渐进性失用； 可能有助于提高诊断特异性的知识，对于未来的发展至关重要 基于机械的疗法。