Predicting 1-year in-stent restenosis in superficial femoral arteries through multiscale computational modelling

Abstract

In-stent restenosis in superficial femoral arteries (SFAs) is a complex, multi-factorial and multiscale vascular adaptation process whose thorough understanding is still lacking. Multiscale computational agent-based modelling has recently emerged as a promising approach to decipher mechanobiological mechanisms driving the arterial response to the endovascular intervention. However, the long-term arterial response has never been investigated with this approach, although being of fundamental relevance. In this context, this study investigates the 1-year post-operative arterial wall remodelling in three patient-specific stented SFA lesions through a fully coupled multiscale agent-based modelling framework. The framework integrates the effects of local haemodynamics and monocyte gene expression data on cellular dynamics through a bi-directional coupling of computational fluid dynamics simulations with an agent-based model of cellular activities. The framework was calibrated on the follow-up data at 1 month and 6 months of one stented SFA lesion and then applied to the other two lesions. The calibrated framework successfully captured (i) the high lumen area reduction occurring within the first post-operative month and (ii) the stabilization of the median lumen area from 1-month to 1-year follow-ups in all the stented lesions, demonstrating the potentialities of the proposed approach for investigating patient-specific short- and long-term responses to endovascular interventions.

Impact of Tissue Damage and Hemodynamics on Restenosis Following Percutaneous Transluminal Angioplasty: A Patient-Specific Multiscale Model

“…Notably, plane 2 showed the greatest lumen area reduction, reaching 75% at day 30 and 66% at day 60. The distinctive behavior of this plane, which underwent a slight recovery during the second month, has been previously observed in the patient-specific framework of in-stent restenosis developed by our group [ 18 ]. This behavior is attributed to the assumed constraint on the ratio between ECM and cells, according to which the initial ECM/SMC ratio should be preserved throughout the restenosis process, with admissible oscillations of the ECM/SMC ratio normalized to the initial value in the range [0.5 1.5].…”

“…While the overall underlying hypotheses were built on our previous works [ 17 , 18 , 28 ], the primary innovation lies in the integration of a sophisticated finite element model of the PTA procedure within the framework. This model incorporates anisotropic hyperelastic arterial tissues embedding a damage model, utilizing material properties derived from human SFA data.…”

“…However, these prior frameworks were (i) mainly focused on either the effects of the intervention-induced damage [ 16 , 24 – 27 ] or the hemodynamic alteration [ 14 , 15 , 20 – 23 ] on the arterial wall response and (ii) applied to idealized case scenarios. To the best of the authors’ knowledge, the sole application of a multiscale agent-based modeling of vascular adaptation to patient-specific cases is the in-stent restenosis model recently developed by Corti et al, [ 17 , 18 ]. Nevertheless, in that application, only the arterial lumen geometry was derived from patient-specific images, with the outer wall assumed to be circular, and uniform tissue composition without plaque components considered.…”

An agent-based model of cardiac allograft vasculopathy: toward a better understanding of chronic rejection dynamics

“…The ABM was able to effectively replicate a 4-week CAV initiation and progression, characterized by lumen area decrease due to progressive intimal thickening in regions exposed to high inflammation and low WSS. While hemodynamic-based vascular remodeling processes were already simulated in previous ABMs by our research group ( Garbey et al, 2017 ; Corti et al, 2019 ; Corti et al, 2020 ; Corti et al, 2022a ; Corti et al, 2022b ; Corti et al, 2023b ; Corti et al, 2023a ), the explicit modeling of inflammatory processes is the key novelty of the present work, being crucial to capture CAV-related phenomena. In particular, the simulated inflammatory cascade encompassed macrophage infiltration in the arterial wall and subsequent mitosis/apoptosis and chemoattractant release, in turn affecting SMC activity.…”

“…Accordingly, the current work presents the development of an ABM of CAV initiation and progression along 4 weeks of follow-up in a mouse left coronary artery (LCA) cross-section to provide further understanding in the immunologic and non-immunologic events involved in the pathology initiation and development. We leveraged the versatility of a previously developed ABM, which has demonstrated successful applications in various maladaptive phenomena ( Garbey et al, 2017 ; Corti et al, 2019 ; Corti et al, 2020 ; Corti et al, 2022a ; Corti et al, 2022b ; Corti et al, 2023a ; Corti et al, 2023b ). By adapting this ABM to investigate the specific pathology of CAV, we efficiently explored unique dynamics and mechanisms of this disease while capitalizing on the proven effectiveness of the computational framework.…”