Local versus global aortic pulse wave velocity in early atherosclerosis: An animal study in ApoE-/--mice using ultrahigh field MRI

Abstract

Increased aortic stiffness is known to be associated with atherosclerosis and has a predictive value for cardiovascular events. This study aims to investigate the local distribution of early arterial stiffening due to initial atherosclerotic lesions. Therefore, global and local pulse wave velocity (PWV) were measured in ApoE-/- and wild type (WT) mice using ultrahigh field MRI. For quantification of global aortic stiffness, a new multi-point transit-time (TT) method was implemented and validated to determine the global PWV in the murine aorta. Local aortic stiffness was measured by assessing the local PWV in the upper abdominal aorta, using the flow/area (QA) method. Significant differences between age matched ApoE-/- and WT mice were determined for global and local PWV measurements (global PWV: ApoE-/-: 2.7±0.2m/s vs WT: 2.1±0.2m/s, P<0.03; local PWV: ApoE-/-: 2.9±0.2m/s vs WT: 2.2±0.2m/s, P<0.03). Within the WT mouse group, the global PWV correlated well with the local PWV in the upper abdominal aorta (R2 = 0.75, P<0.01), implying a widely uniform arterial elasticity. In ApoE-/- animals, however, no significant correlation between individual local and global PWV was present (R2 = 0.07, P = 0.53), implying a heterogeneous distribution of vascular stiffening in early atherosclerosis. The assessment of global PWV using the new multi-point TT measurement technique was validated against a pressure wire measurement in a vessel phantom and showed excellent agreement. The experimental results demonstrate that vascular stiffening caused by early atherosclerosis is unequally distributed over the length of large vessels. This finding implies that assessing heterogeneity of arterial stiffness by multiple local measurements of PWV might be more sensitive than global PWV to identify early atherosclerotic lesions.

Fig 1. Phase-Contrast-Cine pulse sequence.

Phase-Contrast-Cine pulse sequence to measure global and local pulse wave velocities (PWV). The sequence was repeated five times (segment loop) starting with a variable delay Δt = (0ms, 1ms, 2ms, 3ms, 4ms) thus yielding to an effective temporal resolution of 1000 frames per second. Further abbreviations: RF: radio frequency transmission; G_P: phase encoding gradient; G_R: frequency encoding gradient; G_S: slice encoding gradient; FE_QA: axial flow encoding for the local PWV measurement; FE_TT: 1D in-plane flow encoding for the global PWV measurement.

Fig 2. Phantom experimental setup.

Panel (A) shows a schematic depiction of the PVA-C phantom with electrical pulse generator and pressure sensor. The pulse wave velocity phantom actually mounted is shown in (B). The sites for the transit-time pressure measurements and the transit-time MR measurements as well as the measurement slices for the QA-measurement are marked.

Fig 3. Slice positioning in-vivo.

In the abdominal aorta, local PWV was measured in a slice perpendicular to the direction of the vessel. The global PWV was obtained from a slice parallel to the descending aorta.

Fig 4. Determination of global PWV.

In vivo determination of global pulse wave velocity (PWV) with the multi-point transit-time method in the descending aorta of a wild type mouse (A-C). Ten evenly spaced segments for the global PWV measurements (red) and the derived flow curves are shown in a magnitude image of a PC-Cine-FLASH scan (A). In each segment (B), the arrival time of the pulse wave is determined in the flow curve as the intersection point of the pre-systolic baseline (A, green) and the systolic upslope (B, red). The slope of the linear fit (C) of distance over the according pulse wave arrival times represents the global PWV.

Fig 5. Validation of MR multi-point TT-measurement for global PWV.

Direct comparison of the transit time measurements using a pressure sensor (A) and the corresponding MR multi-point TT-measurements (B) in the PVA-C phantom.

Fig 6. Determination of local PWV.

Local PWV is assessed by simultaneously recording flow (A) and cross-sectional area (B) through an imaging slice perpendicular to the upper abdominal. The slope of the flow/area plot (C) represents the local PWV at the examined location (exemplarily dataset shown for a WT mouse).

Fig 7. Correlation and agreement between global and local PWV in ApoE^-/- and WT mice.

Linear regression between global PWV values obtained with the multi-point TT-method and the local PWV, assessed with the QA-method for the WT group (A) and the ApoE^-/- group (B, blue: regression line, red: identity line). The Bland-Altman plots show that there is a higher agreement between local and global PWV in WT mice (C) as compared to ApoE^-/- mice (D).