title: The influence of composition and location on the toughness of human atherosclerotic femoral plaque tissue.
abstract: The toughness of femoral atherosclerotic tissue is of pivotal importance to understanding the mechanism of luminal expansion during cutting balloon angioplasty (CBA) in the peripheral vessels. Furthermore, the ability to relate this parameter to plaque composition, pathological inclusions and location within the femoral vessels would allow for the improvement of existing CBA technology and for the stratification of patient treatment based on the predicted fracture response of the plaque tissue to CBA. Such information may lead to a reduction in clinically observed complications, an improvement in trial results and an increased adoption of the CBA technique to reduce vessel trauma and further endovascular treatment uptake. This study characterises the toughness of atherosclerotic plaque extracted from the femoral arteries of ten patients using a lubricated guillotine cutting test to determine the critical energy release rate. This information is related to the location that the plaque section was removed from within the femoral vessels and the composition of the plaque tissue, determined using Fourier Transform InfraRed spectroscopy, to establish the influence of location and composition on the toughness of the plaque tissue. Scanning electron microscopy (SEM) is employed to examine the fracture surfaces of the sections to determine the contribution of tissue morphology to toughness. Toughness results exhibit large inter and intra patient and location variance with values ranging far above and below the toughness of healthy porcine arterial tissue (Range: 1330-3035 for location and 140-4560J/m(2) for patients). No significant difference in mean toughness is observed between patients or location. However, the composition parameter representing the calcified tissue content of the plaque correlates significantly with sample toughness (r=0.949, p<0.001). SEM reveals the presence of large calcified regions in the toughest sections that are absent from the least tough sections. Regression analysis highlights the potential of employing the calcified tissue content of the plaque as a preoperative tool for predicting the fracture response of a target lesion to CBA (R(2)=0.885, p<0.001).
  
  
  CONCLUSIONS
  This study addresses a gap in current knowledge regarding the influence of plaque location, composition and morphology on the toughness of human femoral plaque tissue. Such information is of great importance to the continued improvement of endovascular treatments, particularly cutting balloon angioplasty (CBA), which require experimentally derived data as a framework for assessing clinical cases and advancing medical devices. This study identifies that femoral plaque tissue exhibits large inter and intra patient and location variance regarding tissue toughness. Increasing calcified plaque content is demonstrated to correlate significantly with increasing toughness. This highlights the potential for predicting target lesion toughness which may lead to an increased adoption of the CBA technique and also further the uptake of endovascular treatment.
authors.affiliation: Centre for Applied Biomedical Engineering Research, Department of Mechanical, Aeronautical and Biomedical Engineering, Materials and Surface Science Institute and the Health Research Institute, University of Limerick, Limerick, Ireland.
authors.forename: E M
authors.initials: EM
authors.lastname: Cunnane
authors.affiliation: Centre for Applied Biomedical Engineering Research, Department of Mechanical, Aeronautical and Biomedical Engineering, Materials and Surface Science Institute and the Health Research Institute, University of Limerick, Limerick, Ireland.
authors.forename: H E
authors.initials: HE
authors.lastname: Barrett
authors.affiliation: Department of Vascular Surgery, University Hospital Limerick, Limerick, Ireland.
authors.forename: E G
authors.initials: EG
authors.lastname: Kavanagh
authors.affiliation: Department of Mechanical Engineering, McGill University, Montreal, Quebec, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Mongrain
authors.affiliation: Centre for Applied Biomedical Engineering Research, Department of Mechanical, Aeronautical and Biomedical Engineering, Materials and Surface Science Institute and the Health Research Institute, University of Limerick, Limerick, Ireland. Electronic address: michael.walsh@ul.ie.
authors.forename: M T
authors.initials: MT
authors.lastname: Walsh
mesh_terms: D000368:Aged; D000800:Angioplasty, Balloon / Q000379:methods; D000818:Animals; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000503:physiopathology*; D012044:Regression Analysis; D017550:Spectroscopy, Fourier Transform Infrared; D013314:Stress, Mechanical; D013552:Swine
keywords: Atherosclerotic plaque; Calcification; FTIR; Femoral artery; Fracture; Tissue characterisation; Toughness