Transcatheter aortic valve (TAV) implantation has become an established alternative to open-hearth surgical valve replacement. Current research aims to improve the treatment safety and extend the ...range of eligible patients. In this regard, computational modeling is a valuable tool to address these challenges, supporting the design phase by evaluating and optimizing the mechanical performance of the implanted device. In this study, a computational framework is presented for the shape and cross-sectional size optimization of TAV frames. Finite element analyses of TAV implantation were performed in idealized aortic root models with and without calcifications, implementing a mesh-morphing procedure to parametrize the TAV frame. The pullout force magnitude, peak maximum principal stress within the aortic wall, and contact pressure in the left ventricular outflow tract were defined as objectives of the optimization problem to evaluate the device mechanical performance. Design of experiment coupled with surrogate modeling was used to define an approximate relationship between the objectives and the TAV frame parameters. Surrogate models were interrogated within a fixed design space and multi-objective design optimization was conducted. The investigation of the parameter combinations within the design space allowed the successful identification of optimized TAV frame geometries, suited to either a single or groups of aortic root anatomies. The optimization framework was efficient, resulting in TAV frame designs with improved mechanical performance, ultimately leading to enhanced procedural outcomes and reduced costs associated with the device iterative development cycle.
In-stent restenosis (ISR) is the major drawback of superficial femoral artery (SFA) stenting. Abnormal hemodynamics after stent implantation seems to promote the development of ISR. Accordingly, this ...study aims to investigate the impact of local hemodynamics on lumen remodeling in human stented SFA lesions. Ten SFA models were reconstructed at 1-week and 1-year follow-up from computed tomography images. Patient-specific computational fluid dynamics simulations were performed to relate the local hemodynamics at 1-week, expressed in terms of time-averaged wall shear stress (TAWSS), oscillatory shear index and relative residence time, with the lumen remodeling at 1-year, quantified as the change of lumen area between 1-week and 1-year. The TAWSS was negatively associated with the lumen area change (ρ = - 0.75, p = 0.013). The surface area exposed to low TAWSS was positively correlated with the lumen area change (ρ = 0.69, p = 0.026). No significant correlations were present between the other hemodynamic descriptors and lumen area change. The low TAWSS was the best predictive marker of lumen remodeling (positive predictive value of 44.8%). Moreover, stent length and overlapping were predictor of ISR at follow-up. Despite the limited number of analyzed lesions, the overall findings suggest an association between abnormal patterns of WSS after stenting and lumen remodeling.
Drug-coated balloon therapy for diseased superficial femoral arteries remains controversial. Despite its clinical relevance, only a few computational studies based on simplistic two-dimensional ...models have been proposed to investigate this endovascular therapy to date. This work addresses the aforementioned limitation by analyzing the drug transport and kinetics occurring during drug-coated balloon deployment in a three-dimensional geometry. An idealized three-dimensional model of a superficial femoral artery presenting with a calcific plaque and treated with a drug-coated balloon was created to perform transient mass transport simulations. To account for the transport of drug (i.e. paclitaxel) released by the device, a diffusion-reaction equation was implemented by describing the drug bound to specific intracellular receptors through a non-linear, reversible reaction. The following features concerning procedural aspects, pathologies and modelling assumptions were investigated: (i) balloon application time (60-180 seconds); (ii) vessel wall composition (healthy vs. calcified wall); (iii) sequential balloon application; and (iv) drug wash-out by the blood stream vs. coating retention, modeled as exponential decay. The balloon inflation time impacted both the free and specifically-bound drug concentrations in the vessel wall. The vessel wall composition highly affected the drug concentrations. In particular, the specifically-bound drug concentration was four orders of magnitude lower in the calcific compared with healthy vessel wall portions, primarily as a result of reduced drug diffusion. The sequential application of two drug-coated balloons led to modest differences (~15%) in drug concentration immediately after inflation, which became negligible within 10 minutes. The retention of the balloon coating increased the drug concentration in the vessel wall fourfold. The overall findings suggest that paclitaxel kinetics may be affected not only by the geometrical and compositional features of the vessel treated with the drug-coated balloon, but also by balloon design characteristics and procedural aspects that should be carefully considered.
Abstract
Aims
Atherosclerotic plaque development has been associated with wall shear stress (WSS). However, the multidirectionality of blood flow, and thus of WSS, is rarely taken into account. The ...purpose of this study was to comprehensively compare five metrics that describe (multidirectional) WSS behaviour and assess how WSS multidirectionality affects coronary plaque initiation and progression.
Methods and results
Adult familial hypercholesterolaemic pigs (n = 10) that were fed a high-fat diet, underwent imaging of the three main coronary arteries at three-time points 3 (T1), 9 (T2), and 10–12 (T3) months. Three-dimensional geometry of the arterial lumen, in combination with local flow velocity measurements, was used to calculate WSS at T1 and T2. For analysis, arteries were divided into 3 mm/45° sectors (n = 3648). Changes in wall thickness and final plaque composition were assessed with near-infrared spectroscopy–intravascular ultrasound, optical coherence tomography imaging, and histology. Both in pigs with advanced and mild disease, the highest plaque progression rate was exclusively found at low time-averaged WSS (TAWSS) or high multidirectional WSS regions at both T1 and T2. However, the eventually largest plaque growth was located in regions with initial low TAWSS or high multidirectional WSS that, over time, became exposed to high TAWSS or low multidirectional WSS at T2. Besides plaque size, also the presence of vulnerable plaque components at the last time point was related to low and multidirectional WSS. Almost all WSS metrics had good predictive values for the development of plaque (47–50%) and advanced fibrous cap atheroma (FCA) development (59–61%).
Conclusion
This study demonstrates that low and multidirectional WSS promote both initiation and progression of coronary atherosclerotic plaques. The high-predictive values of the multidirectional WSS metrics for FCA development indicate their potential as an additional clinical marker for the vulnerable disease.
Graphical Abstract
Graphical Abstract
Although unphysiological wall shear stress (WSS) has become the consensus hemodynamic mechanism for coronary atherosclerosis, the complex biomechanical stimulus affecting atherosclerosis evolution is ...still undetermined. This has motivated the interest on the contraction/expansion action exerted by WSS on the endothelium, obtained through the WSS topological skeleton analysis. This study tests the ability of this WSS feature, alone or combined with WSS magnitude, to predict coronary wall thickness (WT) longitudinal changes. Nine coronary arteries of hypercholesterolemic minipigs underwent imaging with local WT measurement at three time points: baseline (T1), after 5.6 ± 0.9 (T2), and 7.6 ± 2.5 (T3) months. Individualized computational hemodynamic simulations were performed at T1 and T2. The variability of the WSS contraction/expansion action along the cardiac cycle was quantified using the WSS topological shear variation index (
TSVI
). Alone or combined, high
TSVI
and low WSS significantly co-localized with high WT at the same time points and were significant predictors of thickening at later time points.
TSVI
and WSS magnitude values in a physiological range appeared to play an atheroprotective role. Both the variability of the WSS contraction/expansion action and WSS magnitude, accounting for different hemodynamic effects on the endothelium, (1) are linked to WT changes and (2) concur to identify WSS features leading to coronary atherosclerosis.
In-stent restenosis (ISR) represents a major drawback of stented superficial femoral arteries (SFAs). Motivated by the high incidence and limited knowledge of ISR onset and development in human SFAs, ...this study aims to (i) analyze the lumen remodeling trajectory over 1-year follow-up period in human stented SFAs and (ii) investigate the impact of altered hemodynamics on ISR initiation and progression. Ten SFA lesions were reconstructed at four follow-ups from computed tomography to quantify the lumen area change occurring within 1-year post-intervention. Patient-specific computational fluid dynamics simulations were performed at each follow-up to relate wall shear stress (WSS) based descriptors with lumen remodeling. The largest lumen remodeling was found in the first post-operative month, with slight regional-specific differences (larger inward remodeling in the fringe segments,
p
< 0.05). Focal re-narrowing frequently occurred after 6 months. Slight differences in the lumen area change emerged between long and short stents, and between segments upstream and downstream from stent overlapping portions, at specific time intervals. Abnormal patterns of multidirectional WSS were associated with lumen remodeling within 1-year post-intervention. This longitudinal study gave important insights into the dynamics of ISR and the impact of hemodynamics on ISR progression in human SFAs.
One of the relevant phenomenon associated with in-stent restenosis in coronary arteries is an altered haemodynamics in the stented region. Computational fluid dynamics (CFD) offers the possibility to ...investigate the haemodynamics at a level of detail not always accessible within experimental techniques. CFD can quantify and correlate the local haemodynamics structures which might lead to in-stent restenosis. The aim of this work is to study the fluid dynamics of realistic stented coronary artery models which replicate the complete clinical procedure of stent implantation. Two cases of pathologic left anterior descending coronary arteries with their bifurcations are reconstructed from computed tomography angiography and conventional coronary angiography images. Results of wall shear stress and relative residence time show that the wall regions more prone to the risk of restenosis are located next to stent struts, to the bifurcations and to the stent overlapping zone for both investigated cases. Considering a bulk flow analysis, helical flow structures are generated by the curvature of the zone upstream from the stent and by the bifurcation regions. Helical recirculating microstructures are also visible downstream from the stent struts. This study demonstrates the feasibility to virtually investigate the haemodynamics of patient-specific coronary bifurcation geometries.
Automatic algorithms for stent struts segmentation in optical coherence tomography (OCT) images of coronary arteries have been developed over the years, particularly with application on metallic ...stents. The aim of this study is three-fold: (1) to develop and to validate a segmentation algorithm for the detection of both lumen contours and polymeric bioresorbable scaffold struts from 8-bit OCT images, (2) to develop a method for automatic OCT pullback quality assessment, and (3) to demonstrate the applicability of the segmentation algorithm for the creation of patient-specific stented coronary artery for local hemodynamics analysis.
The proposed OCT segmentation algorithm comprises four steps: (1) image pre-processing, (2) lumen segmentation, (3) stent struts segmentation, (4) strut-based lumen correction. This segmentation process is then followed by an automatic OCT pullback image quality assessment. This method classifies the OCT pullback image quality as 'good' or 'poor' based on the number of regions detected by the stent segmentation. The segmentation algorithm was validated against manual segmentation of 1150 images obtained from 23 in vivo OCT pullbacks.
When considering the entire set of OCT pullbacks, lumen segmentation showed results comparable with manual segmentation and with previous studies (sensitivity ~97%, specificity ~99%), while stent segmentation showed poorer results compared to manual segmentation (sensitivity ~63%, precision ~83%). The OCT pullback quality assessment algorithm classified 7 pullbacks as 'poor' quality cases. When considering only the 'good' classified cases, the performance indexes of the scaffold segmentation were higher (sensitivity >76%, precision >86%).
This study proposes a segmentation algorithm for the detection of lumen contours and stent struts in low quality OCT images of patients treated with polymeric bioresorbable scaffolds. The segmentation results were successfully used for the reconstruction of one coronary artery model that included a bioresorbable scaffold geometry for computational fluid dynamics analysis.
Although coronary tortuosity can influence the hemodynamics of coronary arteries, the relationship between tortuosity and flow has not been thoroughly investigated partly due to the absence of a ...widely accepted definition of tortuosity and the lack of patient-specific studies that analyze complete coronary trees. Using a computational approach we investigated the effects of tortuosity on coronary flow parameters including pressure drop, wall shear stress, and helical flow strength as measured by helicity intensity. Our analysis considered idealized and patient-specific geometries. Overall results indicate that perfusion pressure decreases with increased tortuosity, but the patient-specific results show that more tortuous vessels have higher physiological wall shear stress values. Differences between the idealized and patient-specific results reveal that an accurate representation of coronary tortuosity must account for all relevant geometric aspects, including curvature imposed by the heart shape. The patient-specific results exhibit a strong correlation between tortuosity and helicity intensity, and the corresponding helical flow contributes directly to the observed increase in wall shear stress. Therefore, helicity intensity may prove helpful in developing a universal parameter to describe tortuosity and assess its impact on patient health. Our data suggest that increased tortuosity could have a deleterious impact
via
a reduction in coronary perfusion pressure, but the attendant increase in wall shear stress could afford protection against atherosclerosis.
Optical coherence tomography (OCT) is an established catheter-based imaging modality for the assessment of coronary artery disease and the guidance of stent placement during percutaneous coronary ...intervention. Manual analysis of large OCT datasets for vessel contours or stent struts detection is time-consuming and unsuitable for real-time applications. In this study, a fully automatic method was developed for detection of both vessel contours and stent struts. The method was applied to in vitro OCT scans of eight stented silicone bifurcation phantoms for validation purposes. The proposed algorithm comprised four main steps, namely pre-processing, lumen border detection, stent strut detection, and three-dimensional point cloud creation. The algorithm was validated against manual segmentation performed by two independent image readers. Linear regression showed good agreement between automatic and manual segmentations in terms of lumen area (r>0.99). No statistically significant differences in the number of detected struts were found between the segmentations. Mean values of similarity indexes were >95% and >85% for the lumen and stent detection, respectively. Stent point clouds of two selected cases, obtained after OCT image processing, were compared to the centerline points of the corresponding stent reconstructions from micro computed tomography, used as ground-truth. Quantitative comparison between the corresponding stent points resulted in median values of ~150 μm and ~40 μm for the total and radial distances of both cases, respectively. The repeatability of the detection method was investigated by calculating the lumen volume and the mean number of detected struts per frame for seven repeated OCT scans of one selected case. Results showed low deviation of values from the median for both analyzed quantities. In conclusion, this study presents a robust automatic method for detection of lumen contours and stent struts from OCT as supported by focused validation against both manual segmentation and micro computed tomography and by good repeatability.
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