Quantitative characterization of human subcortical hemodynamic response

项目摘要 人类大脑皮层下区域在从稳态到认知的功能中起着关键作用。但 一直缺乏对人类皮层下健康状况进行全面评估的研究。定量表征 皮层下反应的研究具有很大的潜力，可以揭示各种神经退行性疾病的机制， 包括阿尔茨海默病、亨廷顿病和帕金森病的疾病和脑血管病理学， 创伤性脑损伤（TBI）。 在这里，我们使用功能磁共振成像（fMRI）来测量血氧水平依赖于 （BOLD）皮层下区域的反应。我们将创建简单的多感官整合任务， 由这种短暂的大脑激活引起的BOLD反应-所谓的BOLD血流动力学反应功能（HRF）。 我们还将使用各种MRI方法，如质子密度加权成像（PDWI）和扩散张量 DTI技术用于结构评估。BOLD HRF结合PDWI和DTI可显著提高 皮质下神经血管健康的完整评估，包括核体积的定量，白色 重要的连接性，以及这些指标之间的相关性。在拟议的研究中，我们将获得 健康控制数据库。 我们将开发一种新的生物力学运输模型来预测潜在的脑血流量， 对应于BOLD HRF的氧代谢。我们还将开发一个简单但有效的线性流 基于电路模拟的模型，以显示局部神经元驱动的血流反应机制 活动该流动网络模型将通过动脉自旋标记灌注的流量测量进行验证 磁共振成像。所提出的模型将解决一个关键的差距，我们的知识皮层下脑血管 physiology. 我们将测试我们的测量和建模方案的特点，皮层下的HRF在轻度 创伤性脑损伤（TBI）人群。这将证明我们的指标作为临床诊断的可行性 工具.所提出的实验和建模方案可以更广泛地应用于其他大脑区域， 例如大脑皮层。它将是一种非常有效和可靠的诊断工具，特别是对神经系统疾病。 引起功能缺陷而无结构异常的疾病和脑血管病变，例如 蛛网膜下腔出血、早期阿尔茨海默病和轻度认知障碍。

Project summary Subcortical human brain regions play critical roles in functions from homeostasis to cognition. However, there has been a dearth of research on full assessments of human subcortical health. Quantitative characterization of subcortical responses has a great potential to unveil the mechanisms of various neurodegenerative disorders including Alzheimer's, Huntington's, and Parkinson's Disease and cerebrovascular pathology such as traumatic brain injury (TBI). Here, we use functional magnetic resonance imaging (fMRI) to measure the blood oxygen level dependent (BOLD) response in subcortical regions. We will create simple multisensory integration tasks that produce BOLD response evoked by this brief brain activation – so called BOLD hemodynamic response function (HRF). We will also use various MRI methods such as proton-density weighted imaging (PDWI), and diffusion tensor imaging (DTI) for structural assessments. BOLD HRF combined with PDWI and DTI will enable remarkably complete assessments of subcortical neurovascular health, including quantification of nuclear volumes, white matter connectivity, and correlations among these metrics. In the proposed research study, we will obtain health control database for this novel metrics. We will develop a novel biomechanical transport model to predict underlying cerebral blood flow and oxygen metabolism corresponding to BOLD HRFs. We will also develop a simple but effective linear flow model based on an electrical circuit analogy to show mechanisms of blood flow response driven by local neural activity. This flow network model will be validated with flow measurement from arterial spin labelling perfusion MR imaging. The proposed model will address a critical gap in our knowledge of subcortical cerebrovascular physiology. We will test our measurement and modeling schemes for characterization of subcortical HRFs in the mild traumatic brain injury (TBI) population. This will demonstrate the feasibility of our metrics as clinical diagnostic tools. The proposed experimental and modeling schemes can be applied more broadly to other brain regions, such as cerebral cortex. It will be a very effective and reliable diagnostic tools, especially for neurological disorders and cerebrovascular pathology that cause functional deficits without structural abnormality, such as subarachnoid hemorrhage, early stage Alzheimer's disease, and mild cognitive impairment.