Imaging of brain oxygen extraction fraction in vascular contributions to dementia

脑氧摄取分数在脑血管成像中的贡献 痴呆症 血管病变日益被认为是认知障碍和 痴呆，由许多病理生理机制引起，包括血管内皮细胞损伤。 脑血管、缺氧和血脑屏障破裂。血管的异常已经被 结构磁共振成像诊断为脑白质高信号(WMH) 扫描，但WMH进化的异质性和机制仍不清楚。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成像能力有限 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技术来评估 老年WMHs患者的脑血管健康，氧摄取分数(OEF)，表明 脑血管疾病的存在。在缺血性脑疾病中，梗塞周围的脆弱组织 通过增加OEF来补偿血流减少，从而使病理上较高的OEF是一种 高危组织“半暗带”的重要指标。然而，用于测量OEF的MRI工具是有限的 由于低信噪比和生物混杂对MRI信号的影响，并且还没有在 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方法来绘制OEF图来解决这些局限性 在脑组织中。这种定量的BOLD(血氧水平依赖)技术采用了一种独特的 磁共振成像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。vbl.使用 血管性痴呆(VCID)患者的定量BOLD MRI，我们将1)表征 不同脑区WMH和周围半暗带的OEF异常及其关系 (2)纵向OEF变化与脑白质微血管MRI标志物的关系 损伤以建立WMH演变的缺血病理生理机制；以及(3)测试 假设脑白质中OEF的变化对脑内的功能连接有长期影响 支持情节记忆和执行功能的大脑网络。 该项目的成功完成将提供有关氧合作用的关键生物学知识。 在WMH中，并在WMH随时间进展的机制中连接多个血管生物标记物。这个 新的OEF MRI方法也将VCID的成像范式转向定量的、生理学的- 血管风险的具体衡量标准。最终，无创OEF成像可能会检测到早期的微血管 在认知障碍和痴呆症中驱动神经元损伤的变化，并服务于未来的纵向 预防因血管疾病导致的认知功能衰退的干预研究。

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.