A constitutive modelling framework for applications to in vivo longitudinal data: Evaluation in a 60‐day head‐down bed rest study on arterial function

The Journal of Physiology, vol. 604, pp. 8028–8049

Abstract

Abstract Vascular cells continuously remodel the arterial wall (micro)structure in response to changes in their biomechanical/biochemical environment. Although the functional effects of arterial remodelling can be easily measured, assessing the underlying microstructural mechanisms is complex in vivo . Constitutive modelling is a computational technique that allows for linking whole‐organ function to tissue constituent‐level mechanics. However, the need for comprehensive biomechanical data for model parametrisation hampers its clinical applicability. In the present study, we propose a novel constitutive modelling framework that addresses this limitation by leveraging longitudinal acquisitions of pressure–diameter relationships at different arterial beds to aid model parametrisation. We applied our constitutive framework to data from a study on the effect of 60 days head‐down bed rest (HDBR) on arterial function, where pressure–diameter relationships of three arteries (carotid, femoral and popliteal) were measured at baseline, during HDBR (two time points) and during a 30‐day recovery (two time points). We modelled the arterial wall as a constrained mixture of elastin, collagen and vascular smooth muscle cells (VSMCs). The dimensionality of the parameterisation problem was reduced through assumptions on (i) the time evolution of the behaviour of individual constituents and (ii) consistency in intrinsic constituent mechanical properties across different arterial beds. Overall, the proposed framework captured well the in vivo data ( R 2 = 0.89 ± 0.05). We identified increased VSMC contraction and microstructural re‐arrangement of collagen fibres as key adaptations to haemodynamic changes during HDBR, also resulting in reversible de‐stiffening of peripheral arteries. The proposed approach appears promising for disentangling microstructural mechanisms of arterial remodelling in clinical settings. image Key points Constitutive modelling is a computational technique that links the macroscopic behaviour of arteries to the microstructure and mechanics of the constituents of their wall. Although constitutive modelling is used extensively on ex vivo data, the sparsity of biomechanical data that can be acquired in vivo hinders its applicability in clinical settings, where it could be instrumental in disentangling remodelling processes in ageing and disease. We propose a novel framework that leverages longitudinal acquisition of arterial waveforms at different arterial sites to aid in the parametrisation of comprehensive constitutive models. We exemplify the utility of our approach by teasing out the pivotal adaptation roles of vascular smooth muscle cell contraction and collagen microstructural remodelling in response to haemodynamic alterations resulting from prolonged head‐down bed rest. Our approach shows promise for the quantitative characterisation of arterial remodelling from non‐invasive in vivo data that can be easily measured in clinical settings.

Authors 10

1. Alessandro Giudici corresponding

   Maastricht University

   Affiliation as printed

   Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Maastricht The Netherlands

   GROW Institute of Oncology and Reproduction Maastricht University Maastricht The Netherlands

2. Karen Barchetti

   Inserm · Université Paris Cité · Paris Cardiovascular Research Center

   Affiliation as printed

   Université Paris Cité, INSERM U970, Paris Cardiovascular Research Centre – PARCC Paris France

3. Umit Gencer

   Inserm · Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Hôpital Européen Georges-Pompidou · Paris Cardiovascular Research Center

   Affiliation as printed

   Hôpital Européen Georges Pompidou, Assistance Publique‐Hopitaux de Paris Pharmacology and Hypertension and Radiology Units Paris France

   Université Paris Cité, INSERM U970, Paris Cardiovascular Research Centre – PARCC Paris France

4. Hakim Khettab

   Inserm · Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Hôpital Européen Georges-Pompidou · Paris Cardiovascular Research Center

   Affiliation as printed

   Hôpital Européen Georges Pompidou, Assistance Publique‐Hopitaux de Paris Pharmacology and Hypertension and Radiology Units Paris France

   Université Paris Cité, INSERM U970, Paris Cardiovascular Research Centre – PARCC Paris France

5. Élie Mousseaux

   Inserm · Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Hôpital Européen Georges-Pompidou · Paris Cardiovascular Research Center

   Affiliation as printed

   Hôpital Européen Georges Pompidou, Assistance Publique‐Hopitaux de Paris Pharmacology and Hypertension and Radiology Units Paris France

   Université Paris Cité, INSERM U970, Paris Cardiovascular Research Centre – PARCC Paris France

6. Carole Leguy Aachen Department of Cardiovascular Engineering Medical Faculty

   Ruhr West University of Applied Sciences · RWTH Aachen University

   Affiliation as printed

   Department of Cardiovascular Engineering, Institute of Applied Medical Engineering Helmholtz Institute, Medical Faculty RWTH Aachen University Aachen Germany

   Institute of Measurement Engineering and Sensor Technology University of Applied Sciences Ruhr West Mülheim an der Ruhr Germany

7. Tammo Delhaas

   Maastricht University

   Affiliation as printed

   Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Maastricht The Netherlands

8. Rosa María Bruno

   Inserm · Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Hôpital Européen Georges-Pompidou · Paris Cardiovascular Research Center

   Affiliation as printed

   Hôpital Européen Georges Pompidou, Assistance Publique‐Hopitaux de Paris Pharmacology and Hypertension and Radiology Units Paris France

   Université Paris Cité, INSERM U970, Paris Cardiovascular Research Centre – PARCC Paris France

9. Bart Spronck

   Maastricht University · Macquarie University

   Affiliation as printed

   Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Maastricht The Netherlands

   Macquarie Medical School Faculty of Medicine, Health and Human Sciences Macquarie University, Macquarie Park Sydney NSW Australia

10. Pierre Boutouyrie

    Inserm · Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Hôpital Européen Georges-Pompidou · Paris Cardiovascular Research Center

    Affiliation as printed

    Hôpital Européen Georges Pompidou, Assistance Publique‐Hopitaux de Paris Pharmacology and Hypertension and Radiology Units Paris France

    Université Paris Cité, INSERM U970, Paris Cardiovascular Research Centre – PARCC Paris France