Three-dimensional phase contrast angiography of the mouse aortic arch using spiral MRI

Atherosclerosis is an inflammatory disease of the wall of large arteries resulting in the development of lesions and the narrowing of blood vessels (1,2). The focal development of atherosclerosis correlates to the complex hemodynamic environment at branch points and regions of high curvature. Wall shear stress (WSS), the shear force experienced by the vessel wall due to blood flow within the lumen, is believed to be a primary factor in the development of atherosclerotic plaques. Atherosclerotic plaques predominantly occur in regions with low, oscillatory WSS (3,4). Manipulation of the mouse genome has enabled the detailed investigation of the role of specific genes in complex disease processes. Transgenic mice, specifically apolipoprotein E knockout (ApoE−/−) mice, have proven invaluable in the study of atherosclerosis (5–9). Using transgenic mice and imaging, the potential exists for probing the relationship between WSS and the molecular factors involved in atherosclerosis in vivo. Multiple imaging modalities have been proposed to measure WSS in small animals including ultrasound (10) and magnetic resonance imaging (MRI) (11,12). Flow measurements made with ultrasound and/or MRI can be used as boundary conditions for computational fluid dynamic (CFD) models of blood flow in the mouse vasculature. CFD approaches are advantageous due to their ability to estimate WSS at a high resolution with only a few measurements. However, the models are limited by their assumptions and their ability to model higher order effects such as vessel wall compliance. The use of direct calculation of WSS in regions of curved vasculature has been reported in humans (13); however it has yet to be reported in small animal studies. In theory, phase contrast (PC) MRI can measure every vector component of velocity in any oblique spatial orientation and at any depth in the mouse, potentially making it an ideal method for measuring WSS. However, in practice, the specific flows encountered in the mouse create severe artifacts when traditional rectilinear trajectories are used. Blood velocities in the mouse aortic arch are comparable to blood velocities found in human aortic arch (~100 cm/sec), yet the anatomy is an order of magnitude smaller. These fast flows through small and complex anatomy result in displacement artifacts and signal loss comparable to stenotic jets in humans (14). Movement of blood between excitation and data acquisition causes displacement artifacts, and their severity is proportional to the echo time (TE) and the amount of in-plane motion. Signal loss is a result of phase dispersion across a voxel and its severity is proportional to the gradient moments, the velocity gradient, and pixel size. Spiral k-space trajectories have desirable properties with respect to signal-to-noise ratio (SNR), efficiency, and flow properties (15,16). Since a readout prephaser is not needed, spiral trajectories have a short TE and therefore have reduced displacement artifacts. Spiral MRI has successfully been applied to humans (14,17,18); however special considerations are necessary when applying spiral trajectories at high field strength. Off-resonance effects increase with field strength and lead to increased blurring. Gradient fidelity errors, and therefore k-space trajectory errors, occur when fast slew rates (>500 mT/m/ms) are used and result in image artifacts. In this work, short duration spiral readouts along with k-space trajectory measurements will be investigated to overcome blurring and gradient fidelity errors, respectively. A two-dimensional spiral cine PC sequence and a three-dimensional stack-of-spirals cine PC sequence are presented for measuring the hemodynamic environment of the mouse aorta. The dataset is then automatically segmented and WSS calculated via direct evaluation of the velocity gradient near the vessel wall. The methods are then used to measure and describe the hemodynamic environment in ApoE−/− mice.