We reported numerical simulation results resolving complex blood flow features and particle clearance in aneurysms at resting, mild exercise, and moderate exercise levels using subject-specific aneurysm morphology and volumetric blood flow waveforms measured at two aortic locations, SC and IR, for 10 AAA subjects. We used physiologic exercise flow waveforms acquired with MRI during actual lower-limb cycling exercise (mild exercise), and generated flow waveforms at a higher-intensity exercise level (moderate exercise) by extrapolating the measured flow data for each subject. In contrast to dramatic hemodynamic changes from the resting to mild exercise levels, differences between mild exercise and moderate exercise were not as significant suggesting that rest-to-exercise changes of OSI and PRT may not have a proportional relationship with respect to exercise intensity.
We observed an augmentation of mean flow at both SC and IR locations and a removal of retrograde diastolic flow at the IR location from the resting to the mild exercise level (). The increase of the mean IR flow was approximately 2.5-fold greater than that of mean SC flow. We observed reduction of SRBF from the resting to the mild exercise level, changes that may result from the local vasoconstriction of arterioles of splanchnic organs and kidneys. Resultant redistribution of blood flow supply more blood to the active muscles. Comparison of the simulated IR flow waveforms and the measured IR flow waveforms showed that our simulated IR flow agreed well with the measured IR flow at the resting and mild exercise levels (). When considering the challenges of matching the downstream flow waveform and blood pressure with the measured data, an automated boundary condition tuning algorithm appears to be a useful tool for simulating subject-specific flow patterns in aneurysms.
We computed three-dimensional velocity fields for each AAA model, and observed notable changes in velocity magnitude and more complex flow patterns as the level of activity increased (). Near-zero or stagnant flow patterns in the aneurysm observed during diastole at the resting level were not seen at the higher levels of activity. Instead, jet-like flow during peak systole, and complex flow patterns during diastole were observed at both levels of exercise for both subjects. Although we only presented two subjects in , we consistently observed the augmentation of velocity magnitude and removal of static flow in other subjects. Moreover, high-speed vortices were formed after peak systole at the saccular aneurysms of subjects 6, 7, 8, 9, and 10 during exercise. Due to the increase in exercise-induced mean blood flow and the elimination of retrograde diastolic flow, the resulting flow field became more complex and the mixing of aneurysmal blood appeared to be enhanced. Les et al
. documented a moderate level of turbulence in aneurysms under simulated exercise conditions.16
Such exercise-induced flow patterns with increased flow magnitude and moderate turbulence reduce regions of flow stasis that have been correlated with thrombus development.1,9,17
Comparing flow changes for mild and moderate exercise, we observed similar flow patterns of jet-like flow and eddy formation for both exercise levels, with overall augmentation of velocity magnitudes from mild to moderate exercise.
Computation of MWSS and OSI revealed that the athero-prone shear conditions at the resting level (relatively low MWSS and high OSI), diminished as the level of activity increased (). Changes in MWSS and OSI values during exercise were greater at the IR and MA locations compared to the SC locations. At the IR and MA locations, increases in MWSS from the resting to moderate exercise were greater than the increases from resting to mild exercise due to further augmentation of IR flow. Interestingly, however, changes in OSI were not significantly different between rest to mild exercise vs. rest to moderate exercise transitions. OSI values at the moderate exercise level were barely greater than OSI values at the mild exercise level at the SC, IR, and MA locations. Les et al
. reported that OSI values were not reduced to zero in the aneurysm at a simulated exercise level with 50% elevation of heart rate.16
In the aneurysm, it seems that the diametric expansion and exercise-induced turbulence may introduce oscillatory components to the flow during exercise, hence preventing OSI from reducing to zero at higher exercise intensities. This is supported by the presence of moderate turbulence in the aneurysm during exercise.16
To demonstrate the incidence of particle recirculation in AAAs and their response to exercise, we traced the released particles for 10 s at three levels of activity in two distinctly different aneurysm geometries. The particle residence was longer than 10 s for both aneurysms at the resting level, and there were different degrees of particle clearance enhancement at the mild and moderate exercise levels for the two different aneurysms (). At the resting level, a number of particles were not washed out by 5 s possibly due to slow and stagnant flow (subject 1) or recirculating flow (subject 10). In such regions of flow stagnation and recirculation, platelet activation process may be initiated and completed within 1–5 s.3
At the graded exercise levels, most particles were cleared within 5 s, notably faster than that at the resting level. The enhancement of particle clearance (below 5 s) that occurs with mild intensity exercise may be sufficient to decrease the incidence of platelet activation. For subject 1 with the diffuse aneurysm, no particle recirculation was observed in the aneurysm at all levels of physical activity. The lack of recirculation facilitated the bulk flow of particles through the lumen of the diffuse aneurysm. On the other hand, for subject 10 with the bi-lobed saccular aneurysm, particles seemed to be trapped by a rotating flow field for ≥1 s in the lower lobe, not only at the resting level but also at exercise levels. The recirculation zone of subject 10 may be responsible for the differences in particle clearance when compared to that of subject 1.
We observed long PRT (longer than 3 s) regions at the resting level for most of our subjects, and the reduction or absence of those long PRT regions as the level of activity increased to the mild exercise and moderate exercise levels (). A long PRT region localized along the concaved lumen boundaries of the aneurysm demonstrates that particles released from this region stayed in the aneurysm for longer than 3 s. At the mild exercise level, the PRT decreased notably for all subjects. At the moderate exercise level, PRT decreased further, and most of the particles seemed to be cleared out within a second. Further quantitative analysis using PRI and half-life time revealed that the half-life time difference was <0.2 s between the mild and the moderate exercise levels, and the time difference to clear out all of the particles was approximately 1 s or less (, ). Compared to the dramatic enhancement of particle clearance from the resting to the mild exercise level, additional increases in exercise intensity above mild exercise may not enhance the particle clearance significantly.
From these results, both levels of exercise appear to enhance the clearance of particles and reduce flow stasis. Moreover, changes in blood flow at the mild exercise level induced notable reduction of PRT, whereas the further reduction of PRT from mild to moderate exercise was not pronounced. Assuming that reduction in flow stasis is the primary benefit of exercise in AAA, our findings suggest that the therapeutic effect of exercise may not necessarily be proportional to exercise intensity; mild exercise may yield as much benefit for AAA patient as that of moderate exercise. Elderly patients often cannot increase their heart rate up to the usual suggested target exercise level. We demonstrated that major hemodynamic changes occur at the mild exercise level, therefore, patients who are not capable of moderate exercise may also experience attenuated aneurysmal growth by performing mild exercise.
For our flow simulations, we assumed rigid walls and that blood was a Newtonian fluid. The vessel walls of thrombus-burdened AAAs in elderly subjects are reported to be rigid compared to that of abdominal aortas in healthy young subjects. However, the abdominal aorta may play an important role in the Windkessel effect of the vasculature, and outflow phase shifts and attenuation may occur due to abdominal aortic wall compliance, which we were not able to replicate in this study. Moreover, the assumption of a Newtonian fluid may underestimate shear stress values in AAAs. Although non-Newtonian behavior is generally not significant in large arteries, the sudden geometric expansion of an aneurysm may induce complex flow features that may affect local cell aggregation and hence blood viscosity.13
Our extrapolated flow waveforms to simulate the AAA hemodynamics during moderate exercise may not precisely represent real moderate exercise flow waveforms. We compared the estimated vs. measured moderate exercise flow waveforms of one subject who was able to perform moderate exercise in the magnet. We overestimated both SC and IR flow waveforms by about 17%, suggesting that we were simulating a more strenuous exercise condition than reality. However, if the real moderate exercise condition is in between our mild exercise and estimated moderate exercise conditions, we expect similar or lower reductions of OSI and PRT. Also note that the observations of dramatic enhancement of particle clearance and reduction of oscillatory shear during mild exercise are unequivocal.
In addition, our mesh element size may not be sufficiently refined for computation of particle trajectories and wall shear stress. Les et al
. demonstrated that MWSS values at resting level for three meshes, 2.2-, 8.3- and 31.8-million elements differed by 4–6 dyne/ cm2
at IR and MA locations, and OSI values for the three meshes differed by 0.1–0.2 at IR and MA locations. Also, the discrepancy of velocity magnitudes at the MA location was observed from the three meshes, suggesting that our mesh should be refined further in order to represent the complex flow features in AAAs, especially during exercise conditions.16
Although our results were based on 2.1-million element mesh due to computational cost and storage issues, finer mesh resolutions may be needed for future work.