How Does Juxtaluminal Calcium Affect Critical Mechanical Conditions in Carotid Atherosclerotic Plaque? An Exploratory Study

Abstract

The impact of calcification on the carotid atherosclerotic plaque vulnerability remains controversial and unclear. This study assesses the critical mechanical conditions induced by the calcium at the lumen surface, i.e., juxtaluminal calcification (JLCa), within human carotid atherosclerotic plaque. Eleven patients with evidence of JLCa were included for the analysis. The plaque geometry was reconstructed based on computed tomography and magnetic resonance images and 3-D fluid-structure interaction simulation was used for mechanical analysis. The presence of JLCa increased local stresses compared to when calcification was artificially covered with a 0.2-mm-thick fibrous cap (107.87 kPa [76.99, 129.14] versus 63.17 kPa [34.55, 75.13]; Median, [interquartile range]; ). Stretch ratio decreased from 1.18 [1.07, 1.27] to 1.13 [1.10, 1.18] (p = 0.03). The presence of JLCa significantly elevates local stress and stretch level. Further exploration of this plaque feature is warranted as a possible risk factor causing plaque vulnerability.

Calcification in Atherosclerotic Plaque Vulnerability: Friend or Foe?

“…Stiff calcium causes adverse stress within the plaque. The thinner the plaque cap is, the higher the stress concentrations it produces (Zhongzhao et al, 2014). A previous ex vivo study on biomechanical stability came to a different conclusion, suggesting that calcification does not increase fibrous cap stress in typical ruptured or stable human coronary atherosclerotic plaques (Huang et al, 2001).…”

“…Moreover, spotty calcifications were more frequently found in ruptured plaques (Sakaguchi et al, 2016). Most spotty calcifications in ruptured plaques tended to be found in more shallow locations (Sakaguchi et al, 2016), which is more likely to contribute to rupture (Li et al, 2007;Zhongzhao et al, 2014).…”

“…Small calcifications may provoke additional proinflammatory responses (Bostrom, 2005;Nadra et al, 2005), thereby stimulating plaque calcification and disease progression. Small calcifications, especially those located near the lumen or lipid core, could intensify circumferential stress and cause plaque rupture (Li et al, 2007;Hoshino et al, 2009;Zhongzhao et al, 2014). This may provide a possible explanation for why spotty calcifications are positively related to plaque rupture (Figure 2; Kataoka et al, 2014;Sakaguchi et al, 2016).…”

“…Although the definition of superficial calcification varies, the association between superficial calcification and plaque vulnerability has been demonstrated (Xu et al, 2010;Lin et al, 2017;Zhan et al, 2017;Yang et al, 2018). During the complex physiological and biomechanical processes of IPH and plaque rupture, superficial calcifications could increase the local stress and stretch concentration (Zhongzhao et al, 2014). Structural analysis on idealized plaque models showed that calcification within thin fibrous caps may result in high stress concentrations and lead to plaque rupture (Li et al, 2007).…”

The influence of constitutive law choice used to characterise atherosclerotic tissue material properties on computing stress values in human carotid plaques

“…The behavior of material properties is determined from experimental measurements, but also influenced by constitutive laws. Several potential strain energy density functions (SEDFs) can be used to characterize the material, such as neo-Hookean ( Akyildiz et al, 2011 , Caille et al, 2002 , Lee et al, 1996 , Ohayon and Tracqui, 2005 ), one-term Ogden ( Barrett et al, 2009 ), two-term Ogden ( Li et al, 2006 , Li et al, 2007 , Tang et al, 2008 , Versluis et al, 2006 ), Yeoh ( Cunnane et al, 2015 , Lawlor et al, 2011 ), five-parameter Mooney–Rivlin ( Gao and Long, 2008 , Maher et al, 2009 ), Demiray ( Chau et al, 2004 , Delfino et al, 1997 , Kaazempur-Mofrad et al, 2003a ), and modified Mooney–Rivlin SEDF ( Tang et al, 2009a , Tang et al, 2013 , Teng et al, 2014b ). These seven SEDFs have been used in numerous studies to model the mechanical behavior of carotid atherosclerotic plaques.…”