Arterial stiffness has been demonstrated to predict cardiovascular morbidity above and beyond traditional risk factors and can be estimated from measurements such as pulse wave velocity (PWV). Aortic PWV can be estimated from the carotid and femoral sites (CFPWV) by applanation tonometry and ultrasound. However, these methods only estimate a gross global burden, which may mitigate regional stiffness within the vasculature, and can be subjected to errors relating to uncertainties in estimating vessel length. Magnetic resonance imaging (MRI) is an established clinical cardiovascular imaging modality which like ultrasound, has the advantage of being non-invasive and non-ionising. Whilst not typically part of a clinical cardiovascular examination, MRI sequences can be implemented to provide localised aortic PWV measurements directly from aortic sites.
PWV derived by MRI (MR-PWV) is mostly confined to clinical research. It has been determined with high reproducibility and validated against invasive pressure measurements. MRI, as a technique, bears the potential to evaluate vascular anatomy and cardiac function in a single examination. For instance, it can provide aortic stiffness measure with a corresponding left ventricular assessment. Therefore, techniques such as MR-PWV warrants further investigation to see if it may prove beneficial in the detection of subclinical disease or as an imaging biomarker of cardiovascular disease (CVD).
In this research, MR-PWV was estimated using conventional methodology by determining the pulse wave transit time between two aortic sites, derived using MRI velocity encoded imaging of the aorta. When the technique was applied to a complicated diabetic population with and without symptomatic CVD in chapter 5, PWV yielded an important distinction between the groups (CVD with T2DM: 8.7 ± 2.8 ms-1, n =22, T2DM: 7.5 ± 2.3 ms-1, n =28, CVD without T2DM: 8.9 ± 3.6 ms-1, n =19 versus control 6.7 ± 1.8 ms-1, n =19, ANOVA P < 0.05). However, it did not show significant differences in patients with T2DM before onset of symptomatic CVD.
This conventional method of PWV assessment was extended into a multi-site approach sampling several points along the aorta, with the hypothesis that aortic stiffness is a heterogeneous process that varies along the aortic length. This multi-site pulse wave velocity (MS-PWV) technique has been shown to increase the accuracy of PWV measures and was utilised in a subsequent study in chapter 6 and 7, involving healthy volunteers and patients with peripheral vascular disease (PVD) , (healthy volunteers under 40 years: 4.5 ± 0.7 ms-1, n = 22, older healthy volunteers over 40 years: 6.5 ± 1.5 ms-1, n=22 versus PVD patients 8.6 ± 3.1 ms-1, n = 26, P < 0.001).
This thesis provides a novel insight into the process of arterial stiffening and subsequent cardiovascular health throughout different disease cohorts. It differs from current published work by examining MR-PWV in a heterogeneous diabetes and CVD population, while previous studies have solely examined either diabetic or CVD patients. Secondly, the use of MS-PWV has only been implemented in three previous studies to date; involving both a healthy population and cohort with Marfan syndrome. This research is the first to use this technique in PVD and the only study to derive MS-PWV in this population.
In summary, PWV was shown to change with both the extent and severity of atherosclerosis and CVD, which is agreement with previous studies. This demonstrates that MR-PWV may be a useful research tool within the area of cardiovascular MRI and further work is needed to clinically define the potential impact of PWV.
|Date of Award
|Medical Research Council
|Graeme Houston (Supervisor), Stephen Gandy (Supervisor) & Faisel Khan (Supervisor)