QUANTITATIVE BOLD CONTRAST IN HEALTH AND DISEASE

描述（由申请人提供）：近年来，在理解MR BOLD信号的潜在生物物理性质方面取得了实质性进展。大多数研究都是针对大脑活动变化过程中BOLD信号的动态变化进行的。与此同时，很少有人注意到大脑静息状态下BOLD对比的性质。这样的理解对于解释脑疾病（如中风、阿尔茨海默病、亨廷顿病和其他神经系统疾病）造成的基线状态损害的后果至关重要。它对脑和其他器官肿瘤内缺氧的评估也具有重要意义。我们开发了MRI中BOLD对比（qBOLD）的定量生物物理模型，将BOLD MRI信号与血液动力学参数（如脱氧血容量（DBV）和氧提取分数（OEF））分析联系起来。我们在健康人类受试者上获得的初步核磁共振测量的血液动力学参数与先前的测定结果很好地一致。迄今为止，临床神经学研究中最被接受的OEF体内测量方法是使用[15O]示踪剂和PET。为了使我们基于qBOLD的MR技术成为研究和临床应用的有效工具，需要对qBOLD和PET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。这种罕见疾病的特征是脑底部大动脉闭塞性血管病变，导致区域性OEF增加。如果我们发现在健康和病理条件下，我们的OEF MR估计值和OEF PET测量值之间存在高度相关性，我们将在验证qBOLD方法用于神经疾病研究方面迈出重要的一步。在已知视觉激活会降低局部OEF的过程中，正常人也将被招募进行PET和qBOLD MR测量。这些数据将为静息状态下未见的OEF值范围提供补充信息。qBOLD技术在视觉激活期间产生的OEF估计值与PET测量值高度相关，这一确定将为我们在脑血流动力学的神经学研究中使用新的MR方法提供额外的理由。我们希望qBOLD模型能为数据分析提供充分的依据。然而，我们也将对模型的局限性进行定量评估，并将进一步完善模型，以研究改进OEF和DBV量化的可能性。本提案的总体目标是开发一种新的基于核磁共振的方法，用于健康和疾病中脑血流动力学的定量体内评估。一旦全面实施，这将为认知研究和临床诊断提供一种非凡的工具，对于临床医生和研究人员来说，它比基于氧-15的PET更广泛地用于测量脑血流动力学。本提案的总体目标是开发一种新的基于磁共振成像的方法，用于健康和疾病中脑血流动力学的定量体内评估。当全面实施时，这将为认知研究和临床诊断提供一个非凡的工具，一个比基于氧-15的正电子发射断层扫描更广泛地应用于临床医生和研究人员，用于测量脑血流动力学和代谢。

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.