Imaging of brain oxygen extraction fraction in vascular contributions to dementia

脑氧提取分数在血管对痴呆症影响中的成像

• 批准号: 10660865
• 负责人: Audrey Peiwen Fan
• 金额: $ 63.73万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660865
• 关键词: Address; Adopted; Affect; Age; Alzheimer' s Disease; Anterior; Biological; Biological Markers; Blood - brain barrier anatomy; Blood Vessels; Blood flow; Blood specimen; Brain; Brain Diseases; Brain Ischemia; Brain Mapping; Brain imaging; Brain region; Cerebrovascular Disorders; Cerebrum; Clinical; Cognition; Cognitive; Compensation; Complex; Contrast Media; Cyclotrons; Dementia; Early Diagnosis; Endothelium; Episodic memory; Etiology; Evolution; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Future; Heterogeneity; Hypoxia; Image; Imaging Techniques; Imaging technology; Impaired cognition; Impairment; Individual; Infarction; Inferior; Injury; Intervention; Intervention Studies; Ischemia; Knowledge; Lesion; Link; Location; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Maps; Measures; Medial; Memory; Metabolic; Metabolism; Methods; Nerve Degeneration; Neurodegenerative Disorders; Neuronal Injury; Noise; Oxygen; Parietal; Parietal Lobe; Pathologic; Pathology; Patients; Performance; Perfusion; Physiological; Play; Positron-Emission Tomography; Process; Research; Rest; Risk; Role; Scanning; Signal Transduction; Site; Specificity; Stenosis; Techniques; Technology; Temporal Lobe; Testing; Time; Tissues; Translating; Vascular Dementia; Vascular Diseases; White Matter Hyperintensity; biophysical model; blood oxygen level dependent; brain tissue; cerebrovascular health; endothelial dysfunction; executive function; gray matter; improved; innovation; ischemic injury; magnetic resonance imaging biomarker; microvascular pathology; neuroimaging; neurovascular coupling; new therapeutic target; novel; older patient; prevent; radiotracer; success; support network; synergism; tau Proteins; thalamocortical tract; tissue oxygenation; tool; vascular abnormality; vascular cognitive impairment and dementia; vascular contributions; vascular injury; white matter; white matter injury

Imaging of brain oxygen extraction fraction in vascular contributions to dementia Vascular pathology is increasingly recognized as a major contributor to cognitive impairment and dementia, and arises from many pathophysiological mechanisms including endothelial damage of cerebral vessels, hypoxia, and blood-brain barrier breakdown. Vascular abnormalities have been identified as white matter hyperintensities (WMHs) on structural magnetic resonance imaging (MRI) scans, but the heterogeneity of and mechanisms underlying WMH evolution remain unclear. This lack of fundamental understanding of WMHs to predict cognitive impact is in large part due to limited imaging technologies to directly assess brain pathophysiology in clinical settings. In this project, we develop and optimize a new MRI technique to assess a critical parameter of brain vascular health, oxygen extraction fraction (OEF), in elderly patients with WMHs indicating the presence of cerebrovascular disease. In ischemic brain disorders, vulnerable tissue around an infarct compensates for reduced blood flow by increasing OEF, such that pathologically high OEF is an important indicator of a “penumbra” of at-risk tissue. However, MRI tools to measure OEF are limited by low signal-to-noise ratio and biological confounds on the MRI signal, and have not been fully tested in elderly patients at risk of cognitive impairment. We aim to address these limitations by using a novel, clinically feasible MRI method to map OEF in brain tissues. This quantitative BOLD (blood oxygenation level dependent) technique adopts a unique MRI acquisition in synergy with a biophysical model of microvessels in each voxel to quantify OEF. Using quantitative BOLD MRI in patients with vascular contributions to dementia (VCID), we will 1) characterize OEF abnormalities in WMHs and surrounding penumbra for different brain locations and their relationship to cognition; (2) associate longitudinal OEF changes with microvascular MRI markers of white matter injury to establish an ischemic pathophysiological mechanism of WMH evolution; and (3) test the hypothesis that OEF changes in white matter have long-range effects on functional connectivity within brain networks that support episodic memory and executive function. Successful completion of this project will provide critical biological knowledge about oxygenation in WMHs and link multiple vascular biomarkers in a mechanism for WMH progression over time. The novel OEF MRI approach also shifts the paradigm in imaging of VCID toward quantitative, physiologically- specific measures of vascular risk. Ultimately, non-invasive OEF imaging may detect early microvascular changes that drive neuronal injury in cognitive impairment and dementia, and serve future longitudinal studies of interventions to prevent cognitive decline due to vascular disease.

脑氧摄取分数显像在脑血管病变中的作用 痴呆 血管病理学越来越被认为是认知障碍的主要原因， 痴呆，并由许多病理生理机制引起，包括内皮损伤， 脑血管、缺氧和血脑屏障破坏。血管异常一直是 在结构磁共振成像（MRI）上确定为白色高信号（WMH） 扫描，但异质性和机制的WMH演变仍然不清楚。这种缺乏 对WMH预测认知影响的基本理解在很大程度上是由于有限的成像 在临床环境中直接评估大脑病理生理学的技术。 在这个项目中，我们开发和优化了一种新的MRI技术，以评估一个关键参数， 老年WMH患者的脑血管健康、氧摄取分数（OEF）表明， 存在脑血管疾病。在缺血性脑疾病中，梗塞周围的脆弱组织 通过增加OEF来补偿减少的血流量，使得病理性高OEF是一种 这是危险组织“半影”的重要指标。然而，测量OEF的MRI工具有限 由于低信噪比和MRI信号上的生物学混淆， 有认知障碍风险的老年患者。 我们的目标是通过使用一种新的，临床上可行的MRI方法来映射OEF来解决这些限制 在脑组织中。这种定量BOLD（血氧水平依赖）技术采用了独特的 MRI采集与每个体素中微血管的生物物理模型协同作用，以量化OEF。使用 定量BOLD MRI在血管性痴呆（VCID）患者中的应用，我们将1）表征 不同脑区WMH及其周围半暗带的OEF异常及其相互关系 （2）纵向OEF变化与白色物质的微血管MRI标记物相关 损伤以建立WMH演变的缺血性病理生理学机制;以及（3）测试 假设白色物质的OEF变化对内部的功能连接有长期影响， 支持情景记忆和执行功能的大脑网络。 这个项目的成功完成将提供关于氧合的重要生物学知识 并将多种血管生物标志物与WMH随时间进展的机制联系起来。的 新的OEF MRI方法也将VCID成像的范例转向定量的，生理学的， 血管风险的具体措施。最终，非侵入性OEF成像可以检测早期微血管 在认知障碍和痴呆症中驱动神经元损伤的变化， 研究干预措施，以防止由于血管疾病认知能力下降。