Quantitative and Dynamic MRI Measures of Peripheral Vascular Function

Abstract

The endothelium regulates and mediates vascular homeostasis, allowing for dynamic changes of blood flow in response to mechanical and chemical stimuli. Endothelial dysfunction underlies many diseases and is purported to be the earliest pathologic change in the progression of atherosclerotic disease. Peripheral vascular function can be interrogated by measuring the response kinetics following induced ischemia or exercise. In the presence of endothelial dysfunction, there is a blunting and delay of the hyperemic response, which can be measured non-invasively using a variety of quantitative magnetic resonance imaging (MRI) methods. In this review, we summarize recent developments in non-contrast, proton MRI for dynamic quantification of blood flow and oxygenation. Methodologic description is provided for: blood oxygenation-level dependent (BOLD) signal that reflect combined effect of blood flow and capillary bed oxygen content; arterial spin labeling (ASL) for quantification of regional perfusion; phase contrast (PC) to quantify arterial flow waveforms and macrovascular blood flow velocity and rate; high-resolution MRI for luminal flow-mediated dilation; and dynamic MR oximetry to quantify oxygen saturation. Overall, results suggest that these dynamic and quantitative MRI methods can detect endothelial dysfunction both in the presence of overt cardiovascular disease (such as in patients with peripheral artery disease), as well as in sub-clinical settings (i.e., in chronic smokers, non-smokers exposed to e-cigarette aerosol, and as a function of age). Thus far, these tools have been relegated to the realm of research, used as biomarkers of disease progression and therapeutic response. With proper validation, MRI-measures of vascular function may ultimately be used to complement the standard clinical workup, providing additional insight into the optimal treatment strategy and evaluation of treatment efficacy.

Keywords: MRI; blood flow; endothelial (dys)function; flow mediated dilatation; perfusion; reactive hyperemia.

FIGURE 1

Time course oxygen saturation and blood flow over a reactive hyperemia protocol. (Top) Illustration of hemoglobin oxygen saturation (%HbO₂) measured in the artery, proximal to the cuff (red), capillary (black dotted line), and venous (blue) circulations. During the period of ischemia, arterial and venous %HbO₂ remain constant, but progressively decreases in the stagnant blood in the capillaries. Upon cuff release, the deoxygenated blood from the capillaries serves as an endogenous tracer and can be tracked as it flows into the large draining veins. The capillary bed and venous oxygen saturations surpass the baseline condition during hyperemia. (Bottom) Blood flow velocity and tissue perfusion decrease from the relative low baseline value to approximately zero during induced ischemia. Following cuff release, there is a transient surge in arterial flow velocity, which translates to increased perfusion, albeit at a slight lag. This figure shows the mean arterial velocity averaged over a cardiac cycle (dark red) and the real-time flow waveform (light red). The arterial flow waveform, initially triphasic at rest in healthy subjects, becomes entirely antegrade during the period of hyperemia. Dynamic, temporally resolved MRI methods can quantify various aspects of the illustrated processes. Figure adapted from Englund et al. (2013) and Englund et al. (2016) with permission.