QUANTITATIVE BOLD CONTRAST IN HEALTH AND DISEASE

描述(由申请人提供)：近年来，在理解MR BOLD信号潜在的生物物理性质方面取得了实质性进展。大部分的努力都被用于研究大脑活动变化过程中大胆信号的动态变化。与此同时，很少有人注意到大脑休息状态下的大胆对比的性质。这样的理解对于破译中风、阿尔茨海默病、亨廷顿病和其他神经疾病等大脑疾病造成的基线状态损害的后果至关重要。它对评估脑肿瘤和其他器官内的缺氧也非常重要。我们建立了一个MRI BOLD的定量生物物理模型，该模型将BOLD信号与血流动力学参数，如脱氧血容量(DBV)和氧摄取分数(OEF)解析地联系起来。我们在健康人身上获得的初步MR测量的血流动力学参数与以前的测定结果非常一致。到目前为止，临床神经学研究中最被接受的OEF活体测量使用[150]示踪剂和PET。为了使我们的基于qBOLD的磁共振技术成为研究和临床应用的工作工具，需要在qBOLD和PET之间进行直接比较。我们建议在正常健康受试者和烟雾综合征受试者中进行这些比较。这种罕见的疾病的特点是大脑底部的大动脉闭塞性血管病变，导致局部OEF增加。如果我们发现，在健康和病理条件下，我们对OEF的MR估计与OEF的PET测量之间存在高度相关性，我们将完成验证我们用于神经系统疾病研究的qBOLD方法的重要一步。正常人也将被招募接受PET和qBOLD磁共振测量，在视觉激活期间，已知会降低局部OEF。这些数据将提供休眠状态下看不到的一系列OEF值的补充信息。在视觉激活过程中，qBOLD技术产生的OEF估计值与PET测量高度相关，这将是我们在脑部血流动力学的神经学研究中使用新的MR方法的另一个理由。我们期望我们的qBOLD模型将为数据分析提供足够的基础。然而，我们也将对模型的局限性进行定量评估，并将进一步改进模型，以研究在OEF和DBV量化方面改进的可能性。这项建议的总体目标是开发一种新的基于磁共振的方法，用于在健康和疾病中对脑血流动力学进行定量体内评估。全面实施后，这将为认知研究和临床诊断提供一种非凡的工具，临床医生和研究人员可以比氧气-15 PET更广泛地使用该工具来测量大脑血流动力学。这项建议的首要目标是开发一种新的基于磁共振成像的方法，用于在健康和疾病中对脑血流动力学进行定量体内评估。全面实施后，这将为认知研究和临床诊断提供一个非凡的工具，临床医生和研究人员比基于氧-15的正电子发射断层扫描更广泛地可用于测量大脑血流动力学和新陈代谢。

DESCRIPTION (provided by applicant): Substantial progress has been achieved in recent years in understanding the underlying biophysical nature of the MR BOLD signal. Most efforts have been directed toward study of dynamic changes in the BOLD signal during changes in brain activity. At the same time, very little attention has been paid to the nature of BOLD contrast in the resting state of the brain. Such an understanding is crucial to deciphering the consequences of baseline state impairment by diseases of the brain such as stroke, Alzheimer's disease, Huntington's disease, and other neurological disorders. It can also be of great importance for evaluation of hypoxia within tumors of the brain and other organs. We have developed a quantitative biophysical model of BOLD contrast (qBOLD) in MRI that analytically connects BOLD MRI signal to hemodynamic parameters, such as deoxygenated blood volume (DBV) and oxygen extraction fraction (OEF). Our preliminary MR-measured hemodynamic parameters obtained on healthy human subjects are in a good agreement with previous determinations. To date, the most accepted in vivo measurement of OEF in clinical neurological research uses [15O] tracers and PET. To make our qBOLD- based MR technique a working tool for research and clinical applications, direct comparisons between qBOLD and PET are required. We propose to conduct these comparisons in normal healthy subjects and in subjects with a Moyamoya syndrome. This rare disorder is characterized by an obliterative vasculopathy of the large arteries at the base of the brain leading to regionally increased OEF. If we find high correlation between our MR estimates of OEF and PET measures of OEF in both healthy and pathologic conditions, we will have completed an important step in validating our qBOLD approach for neurological disease research. Normal human subjects will also be recruited to undergo both PET and qBOLD MR measurements during visual activation is known to decrease regional OEF. These data will provide complementary information with a range of OEF values not seen in the resting state. The determination that the qBOLD technique yields estimates of OEF during visual activation that are highly correlated to PET measures will be additional justification for use of our new MR method in neurological investigation of brain hemodynamics. We expect our qBOLD model will provide adequate basis for data analysis. However, we will also perform quantitative evaluation of the model limitations and will further refine the model to investigate possibility of improvements in OEF and DBV quantification. The overarching goal of this proposal is to develop a new MR-based method for the quantitative in vivo evaluation of brain hemodynamics in health and disease. When fully implemented, this will provide an extraordinary tool for cognitive studies and clinical diagnosis, one that is much more widely available to clinicians and researchers than is oxygen-15 based PET for the measurement of brain hemodynamics. The overarching goal of this proposal is to develop a new Magnetic Resonance Imaging -based method for the quantitative in vivo evaluation of brain hemodynamics in health and disease. When fully implemented, this will provide an extraordinary tool for cognitive studies and clinical diagnosis, one that is much more widely available to clinicians and researchers than is oxygen-15 based Positron Emission Tomography for the measurement of brain hemodynamics and metabolism.