Author + information
- Xuan Pei, MSc,
- Baijian Wu, PhD,
- Tjun Y. Tang, MD,
- Jonathan H. Gillard, MD and
- Zhi-Yong Li, PhD∗ ()
- ↵∗Dr. Zhi-Yong Li, Biomedical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
Identification of vulnerable plaque pre-rupture is extremely important for patient risk stratification. The mechanism of plaque rupture is still not entirely clear, but it is thought to be a process involving multiple factors. From a biomechanical viewpoint, plaque rupture is usually seen as a structural failure when the plaque cannot resist the hemodynamic blood pressure and shear stress exerted on it. However, the cardiovascular system is naturally a cyclical hemodynamic environment, and myocardial infarction can be a symptomatically quiescent but potentially progressive process when plaque ruptures at stresses much lower than its strength. Therefore, fatigue accumulation is a possible mechanism for plaque rupture. In this study, a crack growth model was developed, and the previously-mentioned hypothesis was tested by conducting a comparative study between 18 symptomatic and 16 asymptomatic patients with carotid stenosis.
All symptomatic patients had recently experienced either a retinal or cortical transient ischemic attack and received imaging within 6 months of the event. Asymptomatic patients had not experienced any symptoms within 6 months prior to imaging. Multicontrast magnetic resonance imaging (MRI) studies were conducted on a 1.5-T whole-body system (SignalHDx, GE Diagnostic Imaging, Cambridge, United Kingdom). The MRI protocol has been published previously (1). Plaque cross sections were reconstructed from high-resolution MRI. Segmentation of the individual plaque components was on the basis of analysis of all magnetic resonance sequences according to signal intensity and morphological criteria, as described in previous studies (2).
Here plaque rupture was seen as the result of crack growth driven by the periodical pressure. Stress intensity factor K (3) was used to drive the crack growth. Figure 1A gives a schematic flowchart of the numerical simulation of the rupture process. For ruptured plaques, the total number of heartbeats (Nr) together with crack growth path and rupture locations was outputted. Then plaque life could be estimated as:
After all cases were done, a rupture risk index could be defined by normalizing the plaque life over a baseline life. The rupture risk index (RRI) for a given crack initial location was defined as:
For each patient, the overall rupture risk index (ORRI) was defined as the maximum of RRI among all cracks initializations, that is:and the acute rupture risk index (ARRI) was defined as maximum of the rupture risk index among all cracks ruptured at the pool, that is:
The Young's modulus of the arterial wall, the fibrous cap, and the lipid pool was chosen as 0.3, 0.6, and 0.02 Mpa, respectively. Poisson's ratio for all components was set equally as 0.48. The fatigue parameters c and m were chosen as 1 and 2.6. Figure 1B shows the finite element modeling process for 1 case.
The ARRI values in plaques of symptomatic patients were significantly higher than those of asymptomatic patients (44.2 ± 62.6 vs. 10.6 ± 17.7, p = 0.003). No difference was found for the ORRI value (p = 0.61). It is interesting to find an obvious difference of the ORRI rupture path between the symptomatic and asymptomatic patients. In the symptomatic group, 78% (14 of 18) of the ORRI rupture path was toward the lipid pool; in contrast, there were only 12% (2 of 16) for the asymptomatic group. It seems that the cross-sectional geometry of an asymptomatic patient may successfully avoid an acute pool-rupture event. Figure 1C shows RRI results for 1 symptomatic patient and 1 asymptomatic patient.
The risk index defined here is a composite factor, which comprises vessel cross-sectional geometry, material property, blood pressure, heart rate, and so on. It is also an overall value on the whole rupture path, so that local high stress may not significantly affect it. This finding may indicate that fatigue crack growth under pulsatile pressure is a mechanism for atheromatous plaque rupture. Thus, the fatigue model may be a useful tool to predict and assess plaque vulnerability, if further validated by large-scale longitudinal studies.
Please note: This work was supported by the National 973 Basic Research Program of China [No. 2013CB733803] and the National Natural Science Foundation of China (NSFC)http://dx.doi.org/10.13039/501100001809 (No. 11272091).
- American College of Cardiology Foundation