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.

对血管贡献的脑氧提取分数的成像 失智 血管病理越来越被认为是认知障碍和 痴呆症，源自许多病理生理机制，包括 脑血管，缺氧和血脑屏障分解。血管异常已经 在结构磁共振成像（MRI）上被鉴定为白质超强度（WMHS） 扫描，但是WMH进化的基础机制的异质性和机制尚不清楚。这种缺乏 对WMHS预测认知影响的基本理解在很大程度上是由于想象力有限 在临床环境中直接评估脑病理生理的技术。 在这个项目中，我们开发并优化了一种新的MRI技术，以评估 脑血管健康，氧气提取部分（OEF），老患者的患者表明 存在脑血管疾病。在缺血性脑部疾病中，保险公司周围脆弱的组织 通过增加OEF来补偿血液流量减少，因此病理上高的OEF是一种 处于风险组织的“半月”的重要指标。但是，测量OEF的MRI工具有限 通过MRI信号上的低信噪比和生物混淆，尚未完全测试 老年患者有认知障碍的风险。 我们旨在通过使用新颖的临床可行MRI方法来解决这些限制来绘制OEF 在脑组织中。这种定量粗体（血液氧合水平）技术采用了独特的 与每个体素中微血管生物物理模型的协同作用中的MRI获取以量化OEF。使用 对痴呆症血管贡献（VCID）患者的定量BOLD MRI，我们将1）表征 WMHS和周围的Penumbra的OEF异常用于不同的大脑位置及其关系 认知； （2）与白质微血管MRI标记的纵向OEF变化 损伤以建立WMH进化的缺血性病理生理机制； （3）测试 假设白质的OEF变化对内部功能连通性具有长期影响 支持情节记忆和执行功能的大脑网络。 成功完成该项目将提供有关氧合的重要生物学知识 在WMHS中，并在WMH进展的机制中链接多个血管生物标志物。这 新型OEF MRI方法还将VCID成像成像的范式转移到定量，物理上 - 血管风险的特定措施。最终，非侵入性OEF成像可能检测到早期微血管 导致认知障碍和痴呆症中神经元损伤的变化，并为未来的纵向服务 研究因血管疾病而导致认知能力下降的干预措施的研究。