QUANTITATIVE BOLD CONTRAST IN HEALTH AND DISEASE

健康与疾病的定量大胆对比

• 批准号: 7560322
• 负责人: DMITRIY A YABLONSKIY
• 金额: $ 33.25万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7560322
• 关键词: Agreement; Alzheimer' s Disease; Applications Grants; Arteries; Attention; Base of the Brain; Blood; Blood Vessels; Blood Volume; Blood capillaries; Blood flow; Brain; Brain Diseases; Brain Neoplasms; Brain region; Cerebrovascular Circulation; Cerebrum; Clinical; Clinical Research; Clinical Trials; Cognitive; Data; Data Analyses; Data Set; Day Care; Dependency; Diffusion; Disease; Doctor of Medicine; Enrollment; Ensure; Evaluation; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Health; Heterogeneity; Human; Huntington Disease; Hypoxia; Image; Impairment; Individual; Investigation; Ionizing radiation; Label; Lead; Literature; Magnetic Resonance Imaging; Measurement; Measures; Metabolism; Methods; Modality; Modeling; Molecular; Moyamoya Disease; Mus; National Institute of Neurological Disorders and Stroke; Nature; Neurologic; Neurosciences; Noise; Organ; Oxygen; Parkinson Disease; Pathologic; Patients; Play; Positron-Emission Tomography; Procedures; Quantitative Evaluations; Rare Diseases; Rattus; Recruitment Activity; Research; Research Personnel; Resolution; Rest; Role; Signal Transduction; Stroke; Structure; TNFRSF5 gene; Techniques; Testing; Time; Tissues; Tracer; Validation; Variant; Vascular Diseases; Visual; Water; Work; base; brain tissue; capillary; clinical Diagnosis; clinical application; clinical practice; hemodynamics; human subject; in vivo; mathematical model; nervous system disorder; research study; response; simulation; tool; water diffusion

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.

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。大多数的努力都是针对在大脑活动的变化过程中BOLD信号的动态变化的研究。与此同时，很少有人注意到BOLD对比在大脑静息状态下的性质。这样的理解对于破译脑疾病如中风、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。它也可以是非常重要的脑和其他器官的肿瘤内的缺氧评估。我们已经开发了一个定量生物物理模型的BOLD对比度（qBOLD）在MRI分析连接BOLD MRI信号的血液动力学参数，如脱氧血容量（DBV）和氧提取分数（OEF）。我们的初步MR测量的血液动力学参数获得的健康人类受试者与以前的确定是在一个很好的协议。迄今为止，临床神经学研究中最被接受的OEF体内测量使用[15 O]示踪剂和PET。为了使我们的基于qBOLD的MR技术成为研究和临床应用的有效工具，需要qBOLD和PET之间的直接比较。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闭塞性血管病变的大动脉在基地的大脑，导致区域性增加的OEF。如果我们在健康和病理条件下发现我们的MR估计OEF和PET测量OEF之间的高度相关性，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。还将招募正常人类受试者在视觉激活期间进行PET和qBOLD MR测量，已知视觉激活会降低局部OEF。这些数据将为静息状态下未观察到的OEF值范围提供补充信息。qBOLD技术在视觉激活期间产生与PET测量高度相关的OEF估计值的确定将是使用我们的新MR方法进行脑血流动力学神经学研究的额外理由。我们希望我们的qBOLD模型将为数据分析提供足够的基础。然而，我们还将对模型的局限性进行定量评估，并将进一步完善模型，以研究改善OEF和DBV定量的可能性。该提案的总体目标是开发一种新的基于MR的方法，用于定量评价健康和疾病中的脑血流动力学。当完全实施时，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PET更广泛地提供给临床医生和研究人员用于测量脑血流动力学的工具。该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价。当完全实施时，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提供给临床医生和研究人员用于测量脑血流动力学和代谢的工具。