2D Projection Maps of WSS and OSI Reveal Distinct Spatiotemporal Changes in Hemodynamics in the Murine Aorta during Ageing and Atherosclerosis

Figures

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  Figure 1. Study design. WT mice were fed a chow and Apoe−/− mice a Western diet starting at the age of 4 weeks. At 12, 18 and 24 weeks, flow and WSS were measured with 4D-PC MRI. After 24 weeks, aortas were analyzed histologically for collagen, SMC and MAC content, necrotic core size and calcification. Obtained data were correlated with spatially resolved WSS and OSI values.

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  Figure 2. Lumen surface grid and 2D projection map generation. (A) Schematic zoom of an aortic segment from (B). For each node, WSS components (l^—longitudinal; c^—circumferential; r^—radial) were determined. (B) Lumen surface grid of the aorta with centerline (red). (C) Aortic arch of an Apoe−/− mouse with streamlines and WSS components. Blue arrows: Longitudinal WSS. Green arrows: Circumferential WSS. Red arrows: Radial strain. (D) Anterior (top) and frontal (bottom) view of the aorta with mean WSS values and a schematic ring segment. (E) Branches are cut off, aorta was opened on the posterior side at 0° and the WSS was projected to the coordinates (z, θ). Convention: θ = 0°: Posterior side (P). (F) 2D projection map of WSS values of the arch. WSS and OSI values of the exact plaque position in the inner radius were used for histological correlation (G). AAo: Ascending aorta; BA: brachiocephalic artery; LCCA: left common carotid artery; LSA: left subclavian artery; DAo: descending aorta.

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  Figure 3. Aortic volumes are decreased and aortic flow and PWV are increased in atherosclerotic Apoe−/− mice. (A) Mean aortic volumes were significantly larger in WT compared with Apoe−/− mice at 24 weeks. (B) Scheme of the analyzed planes. Plane 1: Inflow into the ascending part of the aortic arch. Plane 2: Residual flow after the BA. Plane 3: Residual flow after the LCCA. Plane 4: Residual flow after the LSA. (C) Net flow in the 4 analysis planes. WT mice showed a decrease, whereas Apoe−/− mice showed an increase in net flow over the course of the study. (D) PWV values. In contrast to WT mice, Apoe−/− mice displayed an increase in PWV over time. * vs. WT 12 weeks, p < 0.05; ** vs. WT 12 weeks, p < 0.01; + vs. WT 18 weeks, p < 0.05; x vs. Apoe−/− 12 weeks, p < 0.05; xx vs. Apoe−/− 12 weeks, p < 0.01; xxx vs. Apoe−/− 12 weeks, p < 0.001; xxxx vs. Apoe−/− 12 weeks, p < 0.0001; ♦ vs. Apoe−/− 18 weeks, p < 0.05; # vs. WT, p < 0.05; ## vs. WT, p < 0.01; ### vs. WT, p < 0.001.

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  Figure 4. LongWSS increases in Apoe−/− mice during atherosclerosis progression but decreases in WT mice over time. (A) Three-dimensional longWSS map of a 24-week-old WT (left) and Apoe−/− mouse (right) from anterior and posterior view. A stronger WSS gradient was observed in Apoe−/− compared with WT mice and in the IR, lowered WSS is observable (dark blue spots). (B) Mean longWSS was decreasing in WT and increasing in Apoe−/− mice over time. * vs. WT 12 weeks, p < 0.05; **** vs. WT 12 weeks, p < 0.0001; ++ vs. WT 18 weeks, p < 0.01; x vs. Apoe−/− 12 weeks, p < 0.05; xx vs. Apoe−/− 12 weeks; # vs. WT, p < 0.05; ## vs. WT, p < 0.01. (C) LongWSS maps of WT mice (group average) for all measurement time points and statistical intragroup comparison of longWSS values (12 vs. 24 weeks), showing the difference maps of longWSS values and significance maps. (D) LongWSS Maps of Apoe−/− mice.

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  Figure 5. CircWSS shows inverse changes in Apoe−/− and WT mice. (A) Three-dimensional circWSS map of a 24-week-old WT mouse (left) and an Apoe−/− mouse (right) from anterior and posterior view. In comparison with the WT, high circWSS is visible in the posterior side of the AAo in the Apoe−/− mouse (red area in bottom right image). (B) Mean circWSS. WT mice showed significantly higher values at 12 compared to 24 weeks and compared with age-matched Apoe−/− mice. * vs. WT 12 weeks, p < 0.05; # vs. WT, p < 0.05. (C) CircWSS maps of WT mice (group average) for all measurement time points and statistical intragroup comparison of circWSS values (12 vs. 24 weeks), showing the difference maps of circWSS values and significance maps. (D) CircWSS maps of Apoe−/− mice.

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  Figure 6. OSI decreases in Apoe−/− mice during atherosclerosis progression but increases in WT mice during ageing. (A) Three-dimensional OSI map of a 24-week-old WT mouse (left) and Apoe−/− mouse (right) from anterior and posterior view. The WT mouse showed high OSI values throughout the IR of the complete aorta, whereas in the Apoe−/− mouse, values were only elevated in the IR of the AAo (see red spot). (B) Mean OSI: Values significantly increased in WT and decreased in Apoe−/− mice. *** vs. WT 12 weeks, p < 0.001; ++ vs. WT 18 weeks, p < 0.01; x vs. Apoe−/− 12 weeks, p < 0.05; ### vs. WT, p < 0.001. (C) OSI maps of WT mice (group average) for all measurement time points and statistical intragroup comparison of OSI values (12 vs. 24 weeks), showing the difference maps of OSI values and significance maps. (D) OSI maps of Apoe−/− mice.

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  Figure 7. Plaque characteristics correlate with WSS values. (A) Plaque size was significantly smaller in the DAo compared with the AAo (p < 0.05, *). A correlation was found with longWSS and circWSS. (B) Relative MAC area. A correlation with circWSS was observed. (C) SMC area in atherosclerotic plaques. In the top region, a significantly higher SMC content was observed compared with the DAo (p < 0.05, *), but no correlation with WSS was found. (D) Necrotic core area showed no regional differences but positively correlated with circWSS. (E) Collagen analysis in atherosclerotic plaques. A correlation with longWSS was found. (F) Media thickness was significantly increased in Apoe−/− mice (p < 0.01, **), but no significant correlation with WSS was found. (G) Calcification: Larger areas were found in the AAo. A negative correlation was found with circWSS and a positive correlation with OSI.

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  Figure 8. PWV correlates with WSS and vessel wall characteristics. (A) Correlation with longWSS. (B) Correlation with circWSS. (C) Correlation with maximum radStrain. (D) Correlation with OSI. (E) Media thickness: Significantly higher values were found in the AAo and top region of Apoe−/− compared with WT mice. (F) Correlation with media thickness. Media thickening increases PWV. (G) Collagen content of the vessel wall. No differences were observed. (H) Correlation with collagen content in the vessel wall. # vs. WT, p < 0.05; vs. WT, ## p < 0.01.