The objective of this proposed R21 work is to develop and demonstrate a novel high-speed (10Hz) multi-slice dynamic MRI acquisition and model-based analysis technique to quantify the biomechanical properties of cerebral blood vessels. This novel approach measures T1-weighted inflow fluctuations (related to blood flow/velocity) in large arterial and venous blood vessels. Fluid mechanics model-based analysis is then applied to examine the frequency-dependent dampening and phase between velocity waveforms measured from proximal and distal ends of blood vessel segments allows the characterization of the biophysical properties of these segments including vascular resistance, inductance, and compliance. These high temporal signals are combined with structural MRI angiography to provide a spatial map of the blood vessel properties and topology. We believe that these quantifiable biomechanical and mathematical parameters can be linked to cerebral vascular diseases, since these directly reflect properties such as the rigidity and flow resistance of the vessels. The development of these methods has significant clinical implications toward quantitative assessment of cerebral vascular physiology in the context of vascular disorders such as hypertension, stenosis, and risk of stroke. As a proof-of-concept of this approach, and to initially investigate the sensitivity of this method, this technique will be applied to characterize the cerebral vascular properties of two groups of patients with chronic hypertension and isolated systolic hypertension in comparison to age-matched normotensive controls.
The specific aims of this project are:
Aim 1. Optimize methods for high-speed MR arterial compliance mapping.
Aim 2. Demonstrate proof-of-concept for high-speed MR arterial compliance mapping in chronic hypertensive (HT) and isolated systolic hypertension (ISH) patients and compared to age-matched normotensive (NT) healthy controls. We hypothesize that: Hypothesis 1. Measurements of vascular resistance and compliance is sensitive to hypertrophic changes in HT and ISH patients and can be reliably measured using our proposed high-speed MR arterial compliance mapping approach. Hypothesis 2. HT and ISH patients will show increased resistance (stiffness) and decreased capacitance (compliance) compared to NT controls. These changes will be larger in the ISH group. The dynamic cerebral auto-regulation index (dCAI) will be impaired in both HT and ISH.
The dynamic and biomechanical properties of cerebral blood vessels, such as their elasticity and ability to expand transiently under changes in inter-vascular pressure, are markers of vascular health and predictive of future risks of blockages or ruptures. While transcranial Doppler ultrasound (TCD) methods have been established to quantify these properties, this technique is limited to only a few large arterial vessels in the head and neck through accessible skull regions. The goal of this R21 proposed project is to evaluate and demonstrate the utility of a novel dynamic magnetic resonance imaging (MRI) approach that uses high speed (10Hz) dynamic measurements of blood (inflow; T1) fluctuations in large central cerebral arteries and veins combined with mathematical models of vascular compliance to quantify changes in vascular elasticity, resistance, and compliance in chronic hyper-tension.
