Noninvasive MR imaging of cerebral arterial blood volume in humans

描述(申请人提供)：局部脑血容量(CBV)及其由神经活动引起的动态变化是评估组织活性和功能的关键指标。目前，人类CBV的常规磁共振成像(MRI)需要注射基于Gd的血液造影剂，这阻碍了重复测量，并可能导致肾源性系统性纤维化。因此，在人类中进行CBV标测需要替代的非侵入性技术。重要的是，特定于脑室的CBV测量对于深入了解生理反应中的血流调节至关重要，因为动脉血管扩张和收缩以主动控制脑血流量(CBF)，而静脉血管则被动反应。在这一应用中，我们建议在3特斯拉的人体中评估和实施无创、无造影剂的动脉CBV测量技术，执行基线动脉CBV的定量标测，并确定其在刺激过程中的相对变化。要测试的假设是确定是否可以通过非侵入性MRI技术可靠地在人类体内绘制定量的动脉CBV，并确定在人类神经活动期间动脉CBV的变化是否显著。我们最新的动脉自旋标记技术可以测量基线动脉CBV，该技术已成功地应用于定量绘制动物的动脉CBV和CBF。翻译到3-T清醒人体研究需要考虑物种、生理条件和磁场强度的差异。因此，我们将仔细评估和优化人类动脉CBV测量技术，并检查动脉CBV定量的一致性。在刺激过程中，人们通常认为动脉的CBV变化很小，因此在功能磁共振成像(FMRI)研究中可以忽略不计。然而，最近我们的动物研究表明，动脉CBV增加是总CBV反应的主要贡献，这一观点受到了挑战。因此，我们建议将这种基于动脉CBV的功能磁共振技术应用于人类，以确定在神经刺激过程中动脉CBV的动态变化和空间特异性以及“真实”BOLD信号。这些研究的目标是在不注射造影剂的情况下，为常规人体成像实施无创血容量成像技术，这将使未来对血管疾病的诊断和研究成为可能。 公共卫生相关性：开发新的无创磁共振血容量成像技术，并测量人体基线脑血容量及其在刺激过程中的变化。

DESCRIPTION (provided by applicant): Regional cerebral blood volume (CBV) and its dynamic change induced by neural activity are critical indices for evaluating tissue viability and function. Routine magnetic resonance imaging (MRI) of CBV in humans currently requires injection of gadolinium-based blood contrast agents, hampering repeated measurements and potentially causing nephrogenic systemic fibrosis. Therefore, alternative non-invasive techniques are required for CBV mapping in humans. Importantly, compartment-specific CBV measurements will be crucial to obtain insight into blood flow regulation during physiological responses, because arterial vessels dilate and constrict to actively control cerebral blood flow (CBF), while venous vessels respond passively. In this application, we propose in humans at 3 Tesla to evaluate and implement non-invasive, arterial CBV measurement techniques without contrast agents, to perform quantitative mapping of baseline arterial CBV, and to determine its relative change during stimulation. The hypotheses to be tested are to determine whether quantitative arterial CBV can be reliably mapped in humans by non-invasive MRI techniques and to determine whether the arterial CBV change is significant during neural activity in humans. Baseline arterial CBV can be measured by our recent arterial spin-labeling techniques, which have been successfully applied to quantitatively map arterial CBV and CBF in animals. Translation to 3-T awake human studies necessitates consideration of differences in species, physiological conditions, and magnetic field strengths. Therefore we will carefully evaluate and optimize human techniques for arterial CBV measurement, and examine the consistency of arterial CBV quantification. During stimulation, it is often assumed that the arterial CBV change is minimal and therefore can be ignored in functional MRI (fMRI) studies. However, this notion has recently been challenged by our animal studies showing that the arterial CBV increase is the dominant contribution to the total CBV response. Thus, we propose to apply this arterial CBV-based fMRI technique to humans to determine dynamic changes and spatial specificity of arterial CBV and 'true' BOLD signals during neural stimulation. The goal of these investigations is to implement non-invasive blood volume mapping techniques for routine human imaging without the injection of contrast agents, which will enable future diagnosis and study of vascular disease. PUBLIC HEALTH RELEVANCE: Develop noval non-invasive MR blood volume imaging techniques and to measure baseline cerebral blood volume and its changes during stimulation in humans.