Assessing arterial stiffness and cardiac pulsations in the brain at sub-millimetre resolution using MRI

人类的大脑需要持续顺畅的血液流动来维持良好的神经系统健康。当心脏跳动时，血液在大动脉中“搏动”，当心脏收缩时加速，当心脏放松时减慢。正是大动脉壁的弹性结构改变了这种脉动流，它很重要，因为它保护大脑微循环免受过度的脉动能量。然而，随着年龄的增长，动脉壁的结构发生了变化，导致它们变硬。由于大脑是一个高血流器官，因此动脉僵硬度增加与脑血管疾病有关就不足为奇了。由于这个原因，评估动脉的僵硬度和搏动性在临床上是非常必要的，然而目前在大脑中进行这项工作的方法很少。在这个项目中，我们建议开发一种新的超高场磁共振成像（MRI）方法来评估大脑动脉的刚度和脉搏。现有的核磁共振成像方法将血流速度“编码”到核磁共振成像信号中，但这需要扫描仪产生额外的磁场，这需要时间。我们的新方法是基于利用MRI信号在特定条件下固有的对血流速度的强敏感性，从而使我们能够以高时间分辨率测量脑动脉的脉动血流。提出的项目包括一个MRI序列开发主题和一个应用主题。对于序列发展主题，我们将开发一种通过测量心脏压力波的速度（即脉搏波速度）来评估脑大动脉硬度的新方法。这种测量技术将提供一个定量测量刚度在颈内动脉和大脑中动脉段。然后我们将重点测量从大脑中动脉直接分支出来的小荚状纹状动脉的脉搏。这些新开发的技术将使我们能够探索大脑大动脉的硬度与下游小动脉的相关搏动之间的关系。在应用主题中，我们将在广泛年龄范围的健康个体队列和脑血管疾病患者队列中应用这些新的测量技术。这个实验计划将使我们能够描述大脑大动脉僵硬度和下游脉搏是如何随着年龄的增长而变化的，以及这个过程在小血管病变患者中是如何改变的。

The human brain requires a constant smooth flow of blood to maintain good neurological health. As the heart beats it causes blood to ‘pulsate’ through the large arteries, speeding up when the heart contracts, and slowing down when it relaxes. It is the elastic structure of the walls of large arteries that modify this pulsatile flow, and it is important as it protects the cerebral microcirculation from excessive pulsatile energy. However, as we age, changes occur in the structure of the artery wall that cause them to stiffen. As the brain is a high-flow organ, it is unsurprising that increased arterial stiffness is associated with cerebrovascular disease. For this reason, assessing the stiffness and pulsatility of arteries is highly clinically desirable, however there are currently very few methods to do this in the brain. In this project we propose to develop a novel ultra-high field magnetic resonance imaging (MRI) method for assessing both stiffness and pulsatility of cerebral arteries. Existing MRI methods ‘encode’ blood flow velocity into the MRI signal, but this requires additional magnetic fields to be generated by the scanner, which takes time. Our new approach is based on exploiting the strong sensitivity to blood flow velocity inherent in the MRI signal under certain conditions, and thus allows us to measure pulsatile flow in cerebral arteries with high temporal resolution.The proposed project includes an MRI sequence development theme and an applications theme. For the sequence development theme, we will develop a new method for assessing cerebral large arterial stiffness by measuring the speed of the cardiac pressure wave (i.e. pulse wave velocity). This measurement technique will provide a quantitative measure of stiffness in the internal carotid and middle cerebral artery segments. Then we will focus on measuring the pulsatility in the small lenticulostriate arteries that branch directly from the middle cerebral artery. These newly developed techniques will allow us to explore the relationship between the stiffness of large cerebral arteries and the associated pulsatility downstream in the small arteries. In the applications theme we will apply these new measurement techniques in a cohort of healthy individuals across a broad age range and in a cohort of patients with cerebral small vessel disease. This programme of experiments will allow us to characterise how cerebral large artery stiffness and downstream pulsatility evolve with age, and how this process is altered in patients with small vessel pathology.