Full length articleTowards the characterisation of carotid plaque tissue toughness: Linking mechanical properties to plaque composition
Graphical abstract
Introduction
Atherosclerotic plaque localised at the carotid artery bifurcation remains one of the most challenging regions of the human vasculature to treat using endovascular device based intervention. The unique geometrical configuration and physiological flow properties of the carotid bifurcation predispose this vessel as a high risk target for the development of focal atherosclerotic plaque [1], [2]. Carotid artery stenosis is conventionally treated by endarterectomy [3], [4]. However, the SAPHIRE Trial (the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) has determined the safety and efficacy of the angioplasty followed by carotid artery stenting (CAS) for the subset of patients with high grade stenosis that are deemed unsuitable for surgical endarterectomy [5]. Consequently, the use of endovascular CAS has been advocated as a non-inferior alternative treatment strategy for this patient cohort [3]. Despite this, there is still a large subset of patients that are excluded from this group [6]. Of these, patients who present with heavily calcified plaque lesions are generally deemed unsuitable for CAS [7]. Heavily calcified plaques are associated with stent under-expansion and stent strut malapposition [8], [9] as a result of the rigid inclusions mechanically restraining the forceful circumferential inflation [10]. This can lead to peri-procedural complications including severe arterial injury triggering a restenotic response [11].
The use of Cutting Balloon Angioplasty (CBA) has been advocated as a potential superior treatment strategy to conventional balloon angioplasty (BA) for the pre-dilation phase in calcified lesions [12], [13]. The CBA protocol involves dissecting the plaque tissue through the use of force-focused fractures which are controlled by surgical blades oriented along the length of a non-compliant angioplasty balloon. Numerous studies have demonstrated that CBA can achieve a significantly larger acute lumen gain in vessels with calcified plaque in comparison with BA [13]. The incisions created by CBA dilatation relieve the hoop stress of the artery vessel wall by disrupting and fragmenting the calcific deposits [14]. Subsequently, lumen patency is restored through widening the incisions at lower inflation pressures. This induces lower vessel wall trauma and reduces the incidence of restenosis [15]. The potential of CBA has been demonstrated in the pre-dilation phase of CAS in highly calcified carotid plaque lesions indicating that it is a safe technique to prepare this lesion subset for stenting [16], [17]. Notwithstanding, a number of procedural complications have been reported including failure of the CBA device to overcome the calcific resistance in the calcified lesions. Furthermore, arterial rupture and vessel perforation can also occur due to the use of excessive forces [18]. Finally, a number of adverse clinical events have been related to CBA device failure in treating heavily calcified lesions including fracture of cutting blades, blade withdrawal resistance, balloon rupture and catheter fracture [19], [20], [21].
The CBA treatment strategy is largely limited by the paucity of information regarding the toughness properties of the carotid plaque tissue resisting the cutting blade penetration and how this varies with plaque composition across the length of the target vessel. The toughness properties of human femoral artery plaques have been recently characterised demonstrating a strong relationship between the mechanical toughness properties and the degree of calcification [22]. However, histological evidence has demonstrated distinctions in the calcification within the femoral and carotid arterial beds with femoral plaques containing significantly higher degrees of calcification and a high prevalence of osteoid metaplasia that is not associated with the carotid vasculature [23]. Furthermore, the morphological characteristics of the carotid artery plaques are diverse and the vascular calcification varies in both its origin and morphological manifestation within the carotid artery vessel [24], [25].
The importance of tissue appropriate properties are highlighted in a study by [26] who demonstrate the difference in using aortic plaque properties to represent femoral plaque mechanical response. It is now becoming clear that territory specific mechanical properties are required to accurately represent plaque mechanics [27]. Classifying the experimental toughness properties of carotid plaque tissue under controlled cutting conditions is a prerequisite to distinguishing the upper and lower scale toughness properties associated with this complex tissue. Such mechanical information is a crucial starting point for simulations of carotid plaque treatment by CBA that can be employed to improve device design and information can be leveraged to correlate pre-operative imaging of the plaque to support patient stratification into groups where the patient plaque types can be classified for CBA applicability.
In this regard, this study characterises the toughness properties of carotid artery plaques by determining the plaques resistance to blade penetration and quantifying the necessary cutting forces required to propagate a controlled cut in the calcified plaque tissue in order to achieve successful plaque dissection. This mechanical toughness parameter is correlated to specific regions within the carotid vessel distinguishing the unique dissection properties of the common, bifurcation and internal carotid artery regions. Additionally, toughness properties are related to plaque composition in order to understand the biomechanical influence of distinct pathological components of the carotid vasculature. This correlation is made using structural examination under electron microscopy and spectroscopic Fourier transform infrared characterisation.
Section snippets
Carotid plaque acquisition
Human carotid plaque samples were obtained from twenty-one endarterectomy patients in the University Hospital Limerick in a manner that conformed to the declaration of Helsinki and was approved by the hospital’s Ethical Research Committee. Patient sample characteristics included gender [Male (13/21); Female (8/21)], side [Left (10/21); Right (11/21)] and the cohort had an average age range of 70.38 ± 8.83 years. The symptomatic high-grade stenosed carotid plaque samples were removed by standard
Region specific toughness
Fig. 3 illustrates the distribution of region specific toughness properties within the carotid vessel. In these box plots, the boxes encompass the middle 50% range of toughness values, the lines in the boxes represent the median values and the protruding bars encompass the remainder of the data for both the maximum and minimum toughness values with the exception of outliers (1.5 times the interquartile range) represented by hollow circles and extreme outliers (3 times the interquartile range)
Discussion
Atherosclerotic plaque localised at the carotid artery bifurcation remains one of the most challenging regions of the human vasculature to treat using endovascular device based intervention. Currently, conventional endarterectomy is the gold standard method of intervention for patients who are eligible for surgery that present with a significant stenosis [3], [4]. Therefore, this study focuses on characterising all plaque types distinguishing the upper and lower scale toughness properties
Limitations
There are a number of inherent limitations within this study. A limitation regarding the sample size is that the development of a grouping classification of the plaques into respective types is relatively small. However, in a global sense the regional difference reflects the importance of region specific characterisation and this study warrants further investigation to define a CBA classification based on plaque region and calcification configuration type. The harvested carotid plaque samples
Conclusions
This study identifies the toughness of carotid artery plaques, a mechanical parameter which determines the plaques resistance to blade penetration. This parameter can assist in better understanding the mechanism of plaque dissection which is compounded by specific plaque components during CBA. Moreover, distinguishing between the plaque specific toughness profiles, with respect to the three anatomical regions of the carotid artery, identifies a classification of plaque toughness that are
Disclosures
There are no actual or perceived conflicts of interest relating to this work.
Acknowledgements
This research work was funded by the Irish Research Council, Ireland Grant No. (GOIPG/2013/1309) and the framework of the Irish Governments Programme for Research in Third Level Institutions Cycle 5, with the assistance of the European Regional Development Fund.
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