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价组织活力和功能的关键指标。目前，人体CBV的常规磁共振成像（MRI）需要注射钆基血液造影剂，这妨碍了重复测量，并可能导致肾源性系统性纤维化。因此，需要替代的非侵入性技术用于人体CBV标测。重要的是，隔室特异性CBV测量对于了解生理反应期间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），而静脉血管则被动响应。在本申请中，我们提出在人体中以3特斯拉评价和实施无造影剂的非侵入性动脉CBV测量技术，以执行基线动脉CBV的定量标测，并确定其在刺激期间的相对变化。待检验的假设是确定定量动脉CBV是否可以通过非侵入性MRI技术可靠地映射在人体中，并确定在人体神经活动期间动脉CBV变化是否显著。我们最近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动脉CBV和CBF。转化为3-T清醒人类研究需要考虑物种，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技术的动脉CBV测量，并检查动脉CBV定量的一致性。在刺激过程中，通常假设动脉CBV变化很小，因此在功能性MRI（fMRI）研究中可以忽略。然而，这一概念最近受到了我们的动物研究的挑战，表明动脉CBV增加是总CBV反应的主要贡献。因此，我们建议将这种基于动脉CBV的功能磁共振成像技术应用于人类，以确定在神经刺激过程中动脉CBV和“真实”BOLD信号的动态变化和空间特异性。这些研究的目标是实现非侵入性的血容量映射技术，用于常规人体成像，而无需注射造影剂，这将使未来的诊断和血管疾病的研究。 公共卫生相关性：发展新型无创MR血容量成像技术，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.