Uncertainty quantification and sensitivity analysis of an arterial wall mechanics model for evaluation of vascular drug therapies

Biomech Model Mechanobiol. 2018 Feb;17(1):55-69. doi: 10.1007/s10237-017-0944-0. Epub 2017 Jul 28.

Abstract

Quantification of the uncertainty in constitutive model predictions describing arterial wall mechanics is vital towards non-invasive assessment of vascular drug therapies. Therefore, we perform uncertainty quantification to determine uncertainty in mechanical characteristics describing the vessel wall response upon loading. Furthermore, a global variance-based sensitivity analysis is performed to pinpoint measurements that are most rewarding to be measured more precisely. We used previously published carotid diameter-pressure and intima-media thickness (IMT) data (measured in triplicate), and Holzapfel-Gasser-Ogden models. A virtual data set containing 5000 diastolic and systolic diameter-pressure points, and IMT values was generated by adding measurement error to the average of the measured data. The model was fitted to single-exponential curves calculated from the data, obtaining distributions of constitutive parameters and constituent load bearing parameters. Additionally, we (1) simulated vascular drug treatment to assess the relevance of model uncertainty and (2) evaluated how increasing the number of measurement repetitions influences model uncertainty. We found substantial uncertainty in constitutive parameters. Simulating vascular drug treatment predicted a 6% point reduction in collagen load bearing ([Formula: see text]), approximately 50% of its uncertainty. Sensitivity analysis indicated that the uncertainty in [Formula: see text] was primarily caused by noise in distension and IMT measurements. Spread in [Formula: see text] could be decreased by 50% when increasing the number of measurement repetitions from 3 to 10. Model uncertainty, notably that in [Formula: see text], could conceal effects of vascular drug therapy. However, this uncertainty could be reduced by increasing the number of measurement repetitions of distension and wall thickness measurements used for model parameterisation.

Keywords: Arterial wall mechanics; Constitutive modelling; Sensitivity analysis; Uncertainty quantification; Vascular ultrasound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteries / drug effects
  • Arteries / physiology*
  • Biomechanical Phenomena
  • Blood Pressure / drug effects
  • Cardiovascular Agents / pharmacology*
  • Diastole / drug effects
  • Diastole / physiology
  • Female
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Male
  • Models, Cardiovascular*
  • Stress, Mechanical
  • Systole / physiology
  • Uncertainty*
  • Young Adult

Substances

  • Cardiovascular Agents
  • Glycation End Products, Advanced