Beyond lesion-language mapping in aphasia: A novel imaging-based prediction model

对中风后失语症语言康复的反应是不同的，主要是因为很少有 可帮助确定个体化治疗选择的预测因素。成像技术，如基于体素的 损害症状图(VLSM)在将特定的大脑区域与语言行为联系起来方面很有用； 然而，还需要进一步发展，以便在指导中优化结构和功能信息的使用 为我们患有失语症的退伍军人提供个性化治疗。此CDA1通过开发 一种新的技术，它使用胶质细胞增殖症+的解剖学测量来改进语言行为的预测 生理指标，如脑血流量(CBF)和葡萄糖提取分数(Gef)。 在第一个目标中，我们测试了我们的新的解剖学测量方法--胶质细胞增殖症+在与 名词和动词的对峙命名，从而推进了当前的VLSM技术。我们的测试方法 工作假设是招募失语症患者，我们将在他们身上测试对峙命名 名词和动词，并获得高分辨率的结构磁共振扫描。名词和动词的研究有多个方面 具有临床意义的途径，包括(1)失语是失语症中最普遍的缺陷，(2)名词和动词 失语症患者的命名功能可能受到不同程度的损害；(3)名词和动词往往是基于功能障碍的目标 治疗。我们计划用三种不同的方法(二进制)来确定结构-行为的关联 病变地图、连续T1w信号地图、胶质增生+地图)，并统计比较行为 每种VLSM技术所占的差异。在完成目标1之后，我们期望我们将拥有 确定了哪种VLSM方法可以解释最大的行为差异。 在第二个目标中，我们开发了一种新的方法，称为基于体素的损伤和生理症状 胶质化+VLSM与局部CBF相结合的标测(VLPSM)提高对脑出血的预测能力 结构-行为关联图，并将其扩展为结构-功能-行为关联图。我们会 然后比较VLPSM和VLSM，并确定哪种方法解释了更多的语言差异 行为，期望结合结构和生理信息将占更多 不同受试者的语言行为不同，而不是只考虑结构性信息。之后 完成目标2，我们期望我们将拥有一种健壮且新颖的语言映射方法 利用来自结构和生理的信息将行为转移到大脑区域。 在第三个目标中，我们将制定全球环境基金关于磁共振成像(MRI)系统的区域措施， 可作为VLPSM患者神经元健康状况的较好标志物。我们的方法将是发展理论 对于脉冲序列，通过Bloch方程建模，确保正确的MRI信号形成，模拟不同的脉冲序列 研究了磁共振成像信号的形成条件，并在3T西门子Prisma平台上实现了脉冲序列。 我们将对幻影进行广泛的质量和重复性测试。如果我们的目标敏感度，空间 分辨率和再现性都不能满足，我们将确定限制因素并通过 改进了脉冲序列设计，并潜在地改进了射频硬件。最后，我们将测试这部小说 全球环境基金技术在神经学健康的青年和老年受试者中确定重复性和敏感性 年龄引起的生理变化，并将这些结果与CBF测量进行比较。在完成目标3之后，它是 我们的期望是，我们将拥有一种完全发展的方法学来非侵入性地测量区域血糖 大脑中的萃取物。 这个应用程序的总体目标是创建一张包含解剖学和 语言行为的生理关联，突出关键的目标大脑区域的康复。长的- 这一系列研究的长期目标是确定如何最好地使用VLPSM为临床医生提供 预测失语症治疗结果的个体化MAP，从而辅助治疗选择。

Response to post-stroke aphasia language rehabilitation is variable, mainly because there are few predictors that can help identify individualized treatment options. Imaging techniques, such as Voxel-based Lesion Symptom Mapping (VLSM) have been useful in linking specific brain areas to language behavior; however, further development is required to optimize use of structural and functional information in guiding individualized treatment for our Veterans with aphasia. This CDA1 addresses this gap through development of a novel technique that improves prediction of language behavior using anatomical measure of gliosis+ as well as physiological measures such as Cerebral Blood Flow (CBF) and Glucose Extraction Fraction (GEF). In the first aim, we test the sensitivity of our novel anatomical measure, gliosis+, in relating to confrontation naming of nouns and verbs, thereby advancing current VLSM techniques. Our approach to testing the working hypothesis will be to recruit patients with aphasia on whom we will test confrontation naming of nouns and verbs and acquire high-resolution structural MRI scans. The study of nouns and verbs has multiple avenues of clinical significance, including (1) anomia is the most pervasive deficit in aphasia, (2) noun and verb naming can be differentially impaired in aphasia, and (3) nouns and verbs are often targets in impairment-based treatment. We plan to determine the structure-behavior association with three different methodologies (binary lesion maps, continuous T1w signal maps, gliosis + maps), and statistically compare the amount of behavioral variance that each VLSM technique accounts for. After completing Aim 1, it is our expectation that we will have identified which VLSM methodology accounts for the most behavioral variance. In the second aim, we develop a novel methodology called Voxel-based Lesion and Physiology Symptom Mapping (VLPSM) by combining gliosis+ VLSM with regional CBF to improve the predictive capability of structure-behavior association maps, and expand them to structure-function-behavior association maps. We will then compare VLPSM to VLSM, and determine which methodology accounts for more variance in language behavior, with the expectation that combining structural and physiological information will account for more language behavior variance across subjects than when considering structural information alone. After completing Aim 2, it is our expectation that we will have a robust and novel method of mapping language behavior to brain areas utilizing information from both structure and physiology. In the third aim, we will develop regional GEF measures on a Magnetic Resonance Imaging (MRI) system, which can be used as a better marker of neuronal health in VLPSM. Our approach will be to develop the theory of the pulse sequence, ensure proper MRI signal formation via Bloch equation modeling, simulate different conditions of the MRI signal formation, and implement the pulse sequence on a 3T Siemens Prisma platform. We will perform extensive quality and reproducibility tests on phantoms. If our target sensitivity, spatial resolution, and reproducibility are not met, we will identify the limiting factors and overcome them through improved pulse sequence design and potentially improvements in RF hardware. Finally, we will test the novel GEF technique on neurologically healthy young and old subjects to determine reproducibility and sensitivity to physiological changes due to age, and compare these results with CBF measures. After completing Aim 3, it is our expectation that we will have a fully developed methodology to non-invasively measure regional glucose extraction fraction in the brain. The over-arching objective of this application is to create a map that contains both anatomical and physiological correlates of language behavior, highlighting key target brain areas for rehabilitation. The long- term goal of this line of research is to determine how VLPSM can be best used to provide clinicians with individualized maps to predict aphasia treatment outcome, thereby assisting in treatment choices.