Vascular Stiffening and the Brain: Direct Measures of Cerebrovascular Stiffness in Aging and Vasodilation

Christopher S. Balestrini, The University of Western Ontario

Abstract

Dampening of pulsatile pressure waves within blood vessels is an essential feature of the arterial system. Vascular stiffening increases the speed and the pulsatile energy of the pressure wave, leaving low resistance organs like the brain vulnerable to microvascular mechanical damage. Due to access limitations, the effect of cerebrovascular stiffening on brain structure and neurological outcomes remains unknown. The purpose of this thesis was to assess the influence of vascular stiffening in peripheral arteries on white matter integrity (WMLv) (Chapter 2), obtain direct measures of cerebrovascular stiffness via phase contrast magnetic resonance imaging (PCMRI) (Chapter 3), and examine the impact of acute vasodilation on cerebrovascular stiffness (Chapter 4). We found that ischemic heart disease patients (IHD) had greater vascular stiffness compared with controls. However, IHD status did not influence WMLv. Regardless of vascular pathology, common carotid stiffness and ultrasound-based carotid-cerebral pulse wave transit times were associated with WMLv independently. Therefore, we applied PCMRI to the cerebral vessels to acquire direct measures of cerebrovascular stiffness in the internal carotid (ICA) and middle cerebral (MCA) arteries. Using cardiac-gated PCRMI, we collected blood flow velocity data at multiple segments of the ICA (icaPWV) and M1-M2 segment of the MCA (mcaPWV) to construct time–intensity curves and calculate PWV at temporal resolutions up to 25ms. We demonstrated that mcaPWV can detect vascular stiffening in a cross-section of young and older healthy individuals. Additionally, PWV increases from extracranial to intracranial segments, and this acceleration is amplified with age. We then measured peripheral and intracranial vascular stiffness in response to vasodilation using hypercapnia (HC; 6% CO₂, 21% O₂, balanced N₂) and nitroglycerin (NTG; 0.4mg, sublingual) in healthy young adults. Vasodilation in the MCA increased PWV and characteristic impedance. Additionally, the preferential effect of HC on conduit and downstream vascular properties of cerebral vessels versus non-specific conduit vasodilation of NTG suggests that multiple mechanisms may contribute to cerebrovascular stiffening. This thesis provides a method to obtain direct measures of intracranial PWV and demonstrates the capacity for acute modification of cerebrovasculature stiffness. This work may advance future understanding of cerebrovascular changes, damage, and therapeutics in vulnerable populations.