Multimodal Neuroimaging: Advanced Tracking of Longitudinal Aphasia Recovery

多模态神经影像：纵向失语症恢复的高级跟踪

• 批准号: 10132738
• 负责人: Venkatagiri Krishnamurthy
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10132738
• 关键词: Acute; Address; Aphasia; Area; Auditory; Behavior; Behavioral; Biological Markers; Blood Vessels; Brain; Brain imaging; Brain region; Cerebrovascular Circulation; Cerebrovascular Physiology; Chronic; Cognitive; Comprehension; Data; Development; Early treatment; Etiology; Fatigue; Foundations; Functional Magnetic Resonance Imaging; Goals; Impairment; Ischemic Stroke; Knowledge; Language; Language Disorders; Lead; Maps; Masks; Measures; Methodology; Modeling; Names; Neuronal Plasticity; Outcome; Pathway Analysis; Patient Recruitments; Patients; Perfusion; Phase; Philadelphia; Physiology; Process; Recovery; Research; Residual state; Rest; Scheme; Scientist; Seeds; Signal Transduction; Stroke; System; Techniques; Testing; Time; Training; Treatment outcome; Vascular remodeling; Veterans; aphasia recovery; aphasia rehabilitation; base; behavior change; blood oxygen level dependent; career; career development; cerebrovascular; clinical outcome measures; clinically relevant; clinically translatable; expectation; functional MRI scan; improved; lexical; multimodality; neuroimaging; neurovascular; novel; post stroke; predict clinical outcome; predictive modeling; relating to nervous system; response; stroke recovery; synergism; tool; vascular contributions

The first few months of post-stroke recovery is a critical time period where spontaneous changes in language functions and underlying neural processes are observed. Imaging brain changes during this time may help clinicians identify the recovery of neural processes, but must be done in a way that is not confounded by stroke- induced cerebrovascular changes. This is important, as evidence suggests that cerebrovascular insult will elicit a cascade of changes that leads to vascular remodeling in the first few months of post-stroke recovery. This CDA2 proposal addresses this gap through development of a set of integrated multi-modal neuroimaging methodologies to dissociate neural and vascular changes during recovery of language functions from early sub- acute (2-6 weeks post-stroke) to late sub-acute phase (12-16 weeks post-stroke) in patients with aphasia. In the first aim, we will determine if regressing out the vascular signals (CVR and CBF) from task Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI) activity at each time point (early and late phase) will improve the relationship between change in task-BOLD activity and change in lexical decision behavior. Our approach will be to track task-BOLD fMRI activity from early to late sub-acute phase while the patients participate in an auditory word recognition task (lexical decision) in both phases. We will apply our sensitization scheme for regressing out vascular signals. The change in BOLD amplitude (from sensitized and unsensitized/standard task BOLD fMRI activity) will then be related to changes in the lexical decision behavior. We expect to see that the neuro-sensitized task BOLD fMRI activity will have a stronger correlation with lexical decision measures than the unsensitized/standard BOLD fMRI signal. In the second aim, we will determine if removing the vascular signals from resting state BOLD (rs-BOLD) acquired from residual language network at each time point (early and late phase) will improve the relationship between change in rs-BOLD network measures and change in language (domain specific and domain general) measures. Our approach will be to acquire rs-BOLD fMRI scans during the early and late sub-acute phase in patients with aphasia. We will then carry out a whole brain voxel-wise network analysis (i.e. modularity) choosing apriori seed ROI from the residual language- related brain areas. To sensitize the rs-BOLD fMRI signals to neural connections, we will carry out the same sensitization scheme (as described in Aim 1) at a voxel level. We will then identify changes in language network measures (from sensitized and unsensitized/standard rs-BOLD fMRI) and correlate them with language behavior (domain specific and domain general). After completing Aim 2, it is our expectation that the proposed sensitization scheme enhances the sensitivity of rs-BOLD network measures to brain network reorganization in language specific and language-nonspecific cognitive domains. In the third aim, we will determine if vascular measures (CBF and CVR) from early phase can predict change in language behavior (Western Aphasia Battery measure of comprehension and Philadelphia Naming Test. Our approach will be to recruit patients with aphasia in the early sub-acute phase and measure their vascular and behavioral recovery at both early and late time points. Specifically, we will acquire voxel-wise CBF and CVR measures at the early time point, and using multiple regression approach, we will model the vascular measures to predict change in clinically-relevant language behavior. After completing Aim 3, it is our expectation that we will have a clinically translatable data driven (vascular physiology-based) prediction model that can be used to identify brain regions that must change to support improvements in language behavior. The expected outcome of this CDA2 is an integration of multimodal neuroimaging tools to more accurately predict longitudinal recovery of language functions in sub- acute patients with aphasia. The long-term goal is to determine how neuroimaging tools can best be used to provide accurate individualized language recovery trajectories and predict treatment outcome.

中风后恢复的头几个月是语言自发变化的关键时期 观察功能和潜在的神经过程。对这段时间内的大脑变化进行成像可能会有所帮助 临床医生确定神经过程的恢复，但必须以一种不受中风困扰的方式进行- 诱发脑血管改变。这一点很重要，因为有证据表明，脑血管损伤会导致 在中风后恢复的最初几个月，导致血管重塑的一连串变化。这 CDA2提案通过开发一套集成的多模式神经成像来解决这一差距 亚临床期语言功能恢复过程中神经和血管变化的分离方法 失语症患者的急性期(卒中后2-6周)到亚急性期晚期(卒中后12-16周)。 在第一个目标中，我们将确定是否从任务血氧中回归出血管信号(CVR和CBF 每个时间点(早期和晚期)的水平依赖(BOLD)功能磁共振(FMRI)活动将得到改善 大胆任务活动的变化与词汇决策行为的变化之间的关系。我们的方法 将跟踪任务-大胆的fMRI活动从早期到晚期亚急性阶段，同时患者参与 两个阶段的听觉单词再认任务(词汇判断)。我们将把我们的敏化计划应用于 使血管信号退化。粗体幅度变化(从敏感化和非敏感化/标准 任务大胆的fMRI活动)随后将与词汇决定行为的变化相关。我们希望看到这一点 神经敏感型任务BOLD fmri的活动将与词汇判断措施有更强的相关性。 而不是未敏感/标准的BOLD fMRI信号。在第二个目标中，我们将确定是否删除 从残差语言网络中每次获取的静息状态BOLD(RS-BOLD)的血管信号 点(早期和后期)将改善网络措施的变化与 语言(特定领域和一般领域)衡量标准的变化。我们的方法将是收购RS-BOLD 失语症患者亚急性期早期和晚期的fMRI扫描。然后我们将进行一个完整的 从残差语言中选择先验种子ROI的脑体素网络分析(即模块化) 相关的大脑区域。为了使RS-BOLD fmri信号对神经连接敏感，我们将执行同样的操作。 体素级别的敏化方案(如目标1中所述)。然后我们将确定语言网络的变化 测量(来自敏感化和非敏感化/标准RS-BOLD功能磁共振)，并将它们与语言相关联 行为(特定于域和一般域)。在完成目标2后，我们期望拟议的 敏化方案增强RS-BOLD网络措施对脑网络重组的敏感度 语言特定和语言非特定的认知域。在第三个目标中，我们将确定血管 早期的测量(CBF和CVR)可以预测语言行为的变化(西方失语症成套测验 理解力测验和费城命名测验。我们的方法将是招募具有以下特点的患者 早期亚急性期的失语症，并在早期和晚期测量他们的血管和行为恢复 时间点。具体地说，我们将在早期时间点获取体素CBF和CVR测量，并使用 多元回归方法，我们将模型的血管测量，以预测变化的临床相关性 语言行为。在完成目标3之后，我们期望我们将拥有临床可翻译的数据 驱动的(基于血管生理学的)预测模型，可用于识别必须 更改以支持语言行为的改进。这个CDA2的预期结果是集成 多模式神经成像工具更准确地预测亚语言障碍患者语言功能的纵向恢复 急性失语症患者。长期目标是确定如何最好地使用神经成像工具来 提供准确的个性化语言恢复轨迹并预测治疗结果。