Location-Specific Comparison Between a 3D In-Stent Restenosis Model and Micro-CT and Histology Data from Porcine In Vivo Experiments

Abstract

BackgroundCoronary artery restenosis is an important side effect of percutaneous coronary intervention. Computational models can be used to better understand this process. We report on an approach for validation of an in silico 3D model of in-stent restenosis in porcine coronary arteries and illustrate this approach by comparing the modelling results to in vivo data for 14 and 28 days post-stenting.MethodsThis multiscale model includes single-scale models for stent deployment, blood flow and tissue growth in the stented vessel, including smooth muscle cell (SMC) proliferation and extracellular matrix (ECM) production. The validation procedure uses data from porcine in vivo experiments, by simulating stent deployment using stent geometry obtained from micro computed tomography (micro-CT) of the stented vessel and directly comparing the simulation results of neointimal growth to histological sections taken at the same locations.ResultsMetrics for comparison are per-strut neointimal thickness and per-section neointimal area. The neointimal area predicted by the model demonstrates a good agreement with the detailed experimental data. For 14 days post-stenting the relative neointimal area, averaged over all vessel sections considered, was 20 ± 3% in vivo and 22 ± 4% in silico. For 28 days, the area was 42 ± 3% in vivo and 41 ± 3% in silico.ConclusionsThe approach presented here provides a very detailed, location-specific, validation methodology for in silico restenosis models. The model was able to closely match both histology datasets with a single set of parameters. Good agreement was obtained for both the overall amount of neointima produced and the local distribution. It should be noted that including vessel curvature and ECM production in the model was paramount to obtain a good agreement with the experimental data.Electronic supplementary materialThe online version of this article (10.1007/s13239-019-00431-4) contains supplementary material, which is available to authorized users.

In-Stent Restenosis Progression in Human Superficial Femoral Arteries: Dynamics of Lumen Remodeling and Impact of Local Hemodynamics

“…In animal studies on coronary stents, significant differences in lumen area were found between the fringes and mid segments at 1M, 31 or along the stented region at 14 days post-intervention. 35 The present work proves the importance of observing the entire remodeling trajectory of ISR in human arteries, by focusing on human stented SFAs. No longitudinal data on ISR in human stented SFAs are currently available to be directly compared with the findings of the present study.…”

“…Similar considerations are valid for animal studies related to ISR in coronary arteries, characterized by a short follow-up period (2 weeks or 1M). 6,25,35 A similar approach to morphological analysis was applied in a previous longitudinal study quantifying the lumen remodeling trajectory over 1Y follow-up period in patients treated with infra-inguinal veingraft. 15 A direct comparison between the lumen remodeling trajectories is not possible because the biological processes leading to ISR in stented SFAs and restenosis in vein grafts are different.…”

A particle-based model for endothelial cell migration under flow conditions

“…On the other hand, the model gives a reasonable prediction for the behaviour of untreated ECs and should provide a reasonable scenario of endothelium regeneration for a bare metal stent (BMS). This allows it to be used as a part of multiscale models of restenosis in BMS, such as the one described in Zun et al (2017Zun et al ( , 2019.…”

Mechanistic evaluation of long-term in-stent restenosis based on models of tissue damage and growth

“…Coupled with FE analysis, the ABM was adopted by Keshavarzian et al ( 2018 ) to model the response of vessels to the levels of growth factors, proteases, signalling molecules and blood pressure. The ABM was also applied for multiscale modelling of stent deployment, and subsequent blood flow and tissue growth in a stented vessel (Tahir et al 2013 , 2015 ; Zun et al 2019 , 2017 ), in agreement with in vivo post-stenting data. On the other hand, Holzapfel et al ( 2000 , 2002 ) developed a three-dimensional model for simulation of balloon angioplasty and stent deployment in a stenotic artery to gain a mechanistic understanding of the PCI procedure.…”