Publications by authors named "Kerem Pekkan"

95 Publications

Computational modeling of vascular growth in patient-specific pulmonary arterial patch reconstructions.

J Biomech 2021 Mar 25;117:110274. Epub 2021 Jan 25.

Mechanical Engineering, Koc University, Turkey. Electronic address:

Recent progress in vascular growth mechanics has involved the use of computational algorithms to address clinical problems with the use of three-dimensional patient specific geometries. The objective of this study is to establish a predictive computational model for the volumetric growth of pulmonary arterial (PA) tissue following complex cardiovascular patch reconstructive surgeries for congenital heart disease patients. For the first time in the literature, the growth mechanics and performance of artificial cardiovascular patches in contact with the growing PA tissue domain is established. An elastic-growing material model was developed in the open source FEBio software suite to first examine the surgical patch reconstruction process for an idealized main PA anatomy as a benchmark model and then for the patient-specific PA of a newborn. Following patch reconstruction, high levels of stress and strain are compensated by growth on the arterial tissue. As this growth progresses, the arterial tissue is predicted to stiffen to limit elastic deformations. We simulated this arterial growth up to the age of 18 years, when somatic growth plateaus. Our research findings show that the non-growing patch material remains in a low strain state throughout the simulation timeline, while experiencing high stress hot-spots. Arterial tissue growth along the surgical stitch lines is triggered mainly due to PA geometry and blood pressure, rather than due to material property differences in the artificial and native tissue. Thus, non-uniform growth patterns are observed along the arterial tissue proximal to the sutured boundaries. This computational approach is effective for the pre-surgical planning of complex patch surgeries to quantify the unbalanced growth of native arteries and artificial non-growing materials to develop optimal patch biomechanics for improved postoperative outcomes.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110274DOI Listing
March 2021

Patient-Specific Hemodynamics of New Coronary Artery Bypass Configurations.

Cardiovasc Eng Technol 2020 Dec 13;11(6):663-678. Epub 2020 Oct 13.

Department of Mechanical Engineering, Koc University, Rumeli Feneri Campus, Sariyer, Istanbul, Turkey.

Purpose: This study aims to quantify the patient-specific hemodynamics of complex conduit routing configurations of coronary artery bypass grafting (CABG) operation which are specifically suitable for off-pump surgeries. Coronary perfusion efficacy and local hemodynamics of multiple left internal mammary artery (LIMA) with sequential and end-to-side anastomosis are investigated. Using a full anatomical model comprised of aortic arch and coronary artery branches the optimum perfusion configuration in multi-vessel coronary artery stenosis is desired.

Methodology: Two clinically relevant CABG configurations are created using a virtual surgical planning tool where for each configuration set, the stenosis level, anastomosis distance and angle were varied. A non-Newtonian computational fluid dynamics solver in OpenFOAM incorporated with resistance boundary conditions representing the coronary perfusion physiology was developed. The numerical accuracy is verified and results agreed well with a validated commercial cardiovascular flow solver and experiments. For segmental performance analysis, new coronary perfusion indices to quantify deviation from the healthy scenario were introduced.

Results: The first simulation configuration set;-a CABG targeting two stenos sites on the left anterior descending artery (LAD), the LIMA graft was capable of 31 mL/min blood supply for all the parametric cases and uphold the healthy LAD perfusion in agreement with the clinical experience. In the second end-to-side anastomosed graft configuration set;-the radial artery graft anastomosed to LIMA, a maximum of 64 mL/min flow rate in LIMA was observed. However, except LAD, the obtuse marginal (OM) and second marginal artery (m2) suffered poor perfusion. In the first set, average wall shear stress (WSS) were in the range of 4 to 35 dyns/cm for in LAD. Nevertheless, for second configuration sets the WSS values were higher as the LIMA could not supply enough blood to OM and m2.

Conclusion: The virtual surgical configurations have the potential to improve the quality of operation by providing quantitative surgical insight. The degree of stenosis is a critical factor in terms of coronary perfusion and WSS. The sequential anastomosis can be done safely if the anastomosis angle is less than 90 degrees regardless of degree of stenosis. The smaller proposed perfusion index value, O(0.04 - 0) × 10, enable us to quantify the post-op hemodynamic performance by comparing with the ideal healthy physiological flow.
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http://dx.doi.org/10.1007/s13239-020-00493-9DOI Listing
December 2020

A novel method for hemodynamic analysis of penile erection.

Int J Impot Res 2020 Oct 10. Epub 2020 Oct 10.

Department of Urology, Biruni University School of Medicine, Istanbul, Turkey.

Measurement of blood flow velocity through the cavernosal arteries via penile color Doppler ultrasound (PDUS) is the most common objective method for the assessment of erectile function. However, in some clinical cases, this method needs to be augmented via the invasive intracavernosal pressure (ICP) measurement, which is arguably a more direct index for erectile function. The aim of this study is to develop a lumped parameter model (LPM) of the penile circulation mechanism integrated to a pulsatile, patient-specific, bi-ventricular circulation system to estimate ICP values non-invasively. PDUS data obtained from four random patients with erectile dysfunction are used to develop patient-specific LPMs. Cardiac output is estimated from the body surface area. Systemic pressure is obtained by a sphygmomanometer. Through the appropriate parameter set determined by optimization, patient-specific ICP values are predicted with only using PDUS data and validated by pre- and post-papaverine injection cavernosometry measurements. The developed model predicts the ICP with an average error value of 3 mmHg for both phases. Penile size change during erection is predicted with a ~15% error, according to the clinical size measurements. The developed mathematical model has the potential to be used as an effective non-invasive tool in erectile function evaluation, expanding the existing clinical decision parameters significantly.
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http://dx.doi.org/10.1038/s41443-020-00362-yDOI Listing
October 2020

Endothelial shear stress and vascular remodeling in bioresorbable scaffold and metallic stent.

Atherosclerosis 2020 11 10;312:79-89. Epub 2020 Sep 10.

Imperial College London, London, United Kingdom; Department of cardiology, National University of Ireland, Galway (NUIG), Galway, Ireland. Electronic address:

Background And Aims: The impact of endothelial shear stress (ESS) on vessel remodeling in vessels implanted with bioresorbable scaffold (BRS) as compared to metallic drug-eluting stent (DES) remains elusive. The aim of this study was to determine whether the relationship between ESS and remodeling patterns differs in BRS from those seen in metallic DES at 3-year follow-up.

Methods: In the ABSORB II randomized trial, lesions were investigated by serial coronary angiography and intravascular ultrasound (IVUS). Three-dimensional reconstructions of coronary arteries post-procedure and at 3 years were performed. ESS was quantified using non-Newtonian steady flow simulation. IVUS cross-sections in device segment were matched using identical landmarks.

Results: Paired ESS calculations post-procedure and at 3 years were feasible in 57 lesions in 56 patients. Post-procedure, median ESS at frame level was higher in BRS than in DES, with marginal statistical significance (0.97 ± 0.48 vs. 0.75 ± 0.39 Pa, p = 0.063). In the BRS arm, vessel area and lumen area showed larger increases in the highest tercile of median ESS post-procedure as compared to the lowest tercile. In contrast, in DES, no significant relationship between median ESS post-procedure and remodeling was observed. In multivariate analysis, smaller vessel area, larger lumen area, higher plaque burden post-procedure, and higher median ESS post-procedure were independently associated with expansive remodeling in matched frames. Only in BRS, younger age was an additional significant predictor of expansive remodeling.

Conclusions: In a subset of lesions with large plaque burden, shear stress could be associated with expansive remodeling and late lumen enlargement in BRS, while ESS had no impact on vessel dimension in metallic DES.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.08.031DOI Listing
November 2020

Microstructure of early embryonic aortic arch and its reversibility following mechanically altered hemodynamic load release.

Am J Physiol Heart Circ Physiol 2020 05 3;318(5):H1208-H1218. Epub 2020 Apr 3.

Department of Mechanical Engineering, Koç University, Istanbul, Turkey.

In the embryonic heart, blood flow is distributed through a bilaterally paired artery system composed of the aortic arches (AAs). The purpose of this study is to establish an understanding of the governing mechanism of microstructural maturation of the AA matrix and its reversibility, toward the desired macroscopic vessel lumen diameter and thickness for healthy, abnormal, and in ovo repaired abnormal mechanical loading. While matrix-remodeling mechanisms were significantly different for normal versus conotruncal banding (CTB), both led to an increase in vessel lumen. Correlated with right-sided flow increase at Hamburger & Hamilton stages 21, intermittent load switching between collagen I and III with elastin and collagen-IV defines the normal process. However, decreases in collagen I, elastin, vascular endothelial growth factor-A, and fibrillin-1 in CTB were recovered almost fully following the CTB-release model, primarily because of the pressure load changes. The complex temporal changes in matrix proteins are illustrated through a predictive finite-element model based on elastin and collagen load-sharing mechanism to achieve lumen area increase and thickness increase resulting from wall shear stress and tissue strain, respectively. The effect of embryonic timing in cardiac interventions on AA microstructure was established where abnormal mechanical loading was selectively restored at the key stage of development. Recovery of the normal mechanical loading via early fetal intervention resulted in delayed microstructural maturation. Temporal elastin increase, correlated with wall shear stress, is required for continuous lumen area growth. The present study undertakes comparative analyses of the mechanistic differences of the arterial matrix microstructure and dynamics in the three fundamental processes of control, conotruncal banded, and released conotruncal band in avian embryo. Among other findings, this study provides specific evidence on the restorative role of elastin during the early lumen growth process. During vascular development, a novel intermittent load-switching mechanism between elastin and collagen, triggered by a step increase in wall shear stress, governs the chronic vessel lumen cross-sectional area increase. Mimicking the fetal cardiovascular interventions currently performed in humans, the early release of the abnormal mechanical load rescues the arterial microstructure with time lag.
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http://dx.doi.org/10.1152/ajpheart.00495.2019DOI Listing
May 2020

Spatiotemporal remodeling of embryonic aortic arch: stress distribution, microstructure, and vascular growth in silico.

Biomech Model Mechanobiol 2020 Oct 4;19(5):1897-1915. Epub 2020 Mar 4.

Department of Mechanical Engineering, Koc University, Rumeli Feneri Kampüsü, Sariyer, Istanbul, Turkey.

The microstructure for mature vessels has been investigated in detail, while there is limited information about the embryonic stages, in spite of their importance in the prognosis of congenital heart defects. It is hypothesized that the embryonic vasculature represents a disorganized but dynamic soft tissue, which rapidly evolves toward a specialized multi-cellular vascular structure under mechanical loading. Here the microstructural evolution process of the embryonic pharyngeal aortic arch structure was simulated using an in ovo validated long-term growth and remodeling computational model, implemented as an in-house FEBio plug-in. Optical coherence tomography-guided servo-null pressure measurements are assigned as boundary conditions through the critical embryonic stages. The accumulation of key microstructural constituents was recorded through zoom confocal microscopy for all six embryonic arch arteries simultaneously. The total amount and the radial variation slope of the collagen along the arch wall thickness in different arch types and for different embryonic times, with different dimension scales, were normalized and compared statistically. The arch growth model shows that the stress levels around the lumen boundary increase from [Formula: see text] (Stage 18) to a level higher than [Formula: see text] (Stage 24), depending on matrix constituent production rates, while the homeostatic strain level is kept constant. The statistical tests show that although the total collagen levels differentiate among bilateral positions of the same arch, the shape coefficient of the matrix microstructural gradient changes with embryonic time, proving radial localization, in accordance with numerical model results. In vivo cell number (DAPI) and vascular endothelial growth factor distributions followed similar trends.
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http://dx.doi.org/10.1007/s10237-020-01315-6DOI Listing
October 2020

Hemodynamics of neonatal double lumen cannula malposition.

Perfusion 2020 05 3;35(4):306-315. Epub 2019 Oct 3.

Department of Pediatric Cardiovascular Surgery, Faculty of Medicine, Demiroğlu Bilim Üniversitesi, Istanbul, Turkey.

Objective: Malposition of dual lumen cannula is a frequent and challenging complication in neonates and plays a significant role in shaping the in vitro device hemodynamics. This study aims to analyze the effect of the dual lumen cannula malposition on right-atrial hemodynamics in neonatal patients using an experimentally validated computational fluid dynamics model.

Methods: A computer model was developed for clinically approved dual lumen cannula (13Fr Origen Biomedical, Austin, Texas, USA) oriented inside the atrium of a 3-kg neonate with normal venous return. Atrial hemodynamics and dual lumen cannula malposition were systematically simulated for two rotations (antero-atrial and atrio-septal) and four translations (two intravascular movements along inferior vena cava and two dislodged configurations in the atrium). A multi-domain compartmentalized mesh was prepared to allow the site-specific evaluation of important hemodynamic parameters. Transport of each blood stream, blood damage levels, and recirculation times are quantified and compared to dual lumen cannula in proper position.

Results: High recirculation levels (39 ± 4%) in malpositioned cases resulted in poor oxygen saturation where maximum recirculation of up to 42% was observed. Apparently, Origen dual lumen cannula showed poor inferior vena cava blood-capturing efficiency (48 ± 8%) but high superior vena cava blood-capturing efficiency (86 ± 10%). Dual lumen cannula malposition resulted in corresponding changes in residence time (1.7 ± 0.5 seconds through the tricuspid). No significant differences in blood damage were observed among the simulated cases compared to normal orientation. Compared to the correct dual lumen cannula position, both rotational and translational displacements of the dual lumen cannula resulted in significant hemodynamic differences.

Conclusion: Rotational or translational movement of dual lumen cannula is the determining factor for atrial hemodynamics, venous capturing efficiency, blood residence time, and oxygenated blood delivery. Results obtained through computational fluid dynamics methodology can provide valuable foresight in assessing the performance of the dual lumen cannula in patient-specific configurations.
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http://dx.doi.org/10.1177/0267659119874697DOI Listing
May 2020

Infusion Jet Flow Control in Neonatal Double Lumen Cannulae.

J Biomech Eng 2019 Aug 1. Epub 2019 Aug 1.

Department of Mechanical Engineering, Koç University, Sarıyer, Istanbul, Turkey.

Clinical success of extracorporeal membrane oxygenation (ECMO) depends on the proper venous cannulation. Venovenous (VV) ECMO is the preferred clinical intervention as it provides a single-site access by utilizing a VV double lumen cannula (VVDLC) with a higher level of mobilization and physical rehabilitation. Concurrent venous blood drainage and oxygenated blood infusion in the right atrium at the presence of the cannula makes the flow dynamics complex where potential mixing of venous and oxygenated blood can drastically decreases the overall performance of ECMO. There are no studies focusing the neonatal and pediatric populations, in which the flow related effects are of paramount importance due to the small atrium size. In this study, fluid dynamics of infusion outflow jet for two commercially available neonatal VVDLC is analyzed using particle image velocimetry. Moreover, six new designs are proposed for the infusion channel geometry and compared. Important flow parameters such as flow turning angle (FTA), velocity decay, potential core and turbulent intensity are investigated for the proposed models. The experiments showed that the outflow parameters of commercial cannulae such as FTA are strongly dependent on the operating Re number. This may result in a drastic efficiency reduction for cannula operating at off-design flow conditions. Moreover, the infusion outlet tip structure and jet internal guiding pathway (JIGP) was observed to greatly affect the outflow flow features. This is of paramount importance since the anatomical positioning of the cannula and the infusion outlet is strongly dependent on the outflow properties such as FTA.
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http://dx.doi.org/10.1115/1.4044548DOI Listing
August 2019

Thrust and Hydrodynamic Efficiency of the Bundled Flagella.

Micromachines (Basel) 2019 Jul 4;10(7). Epub 2019 Jul 4.

Department of Mechanical Engineering, Koc University, Istanbul 34450, Turkey.

The motility mechanism of prokaryotic organisms has inspired many untethered microswimmers that could potentially perform minimally invasive medical procedures in stagnant fluid regions inside the human body. Some of these microswimmers are inspired by bacteria with single or multiple helical flagella to propel efficiently and fast. For multiple flagella configurations, the direct measurement of thrust and hydrodynamic propulsion efficiency has been challenging due to the ambiguous mechanical coupling between the flow field and mechanical power input. To address this challenge and to compare alternative micropropulsion designs, a methodology based on volumetric velocity field acquisition is developed to acquire the key propulsive performance parameters from scaled-up swimmer prototypes. A digital particle image velocimetry (PIV) analysis protocol was implemented and experiments were conducted with the aid of computational fluid dynamics (CFD). First, this methodology was validated using a rotating single-flagellum similitude model. In addition to the standard PIV error assessment, validation studies included 2D vs. 3D PIV, axial vs. lateral PIV and simultaneously acquired direct thrust force measurement comparisons. Compatible with typical micropropulsion flow regimes, experiments were conducted both for very low and higher Reynolds (Re) number regimes (up to a Re number = 0.01) than that are reported in the literature. Finally, multiple flagella bundling configurations at 0°, 90° and 180° helical phase-shift angles were studied using scaled-up multiple concentric flagella thrust elements. Thrust generation was found to be maximal for the in-phase (0°) bundling configuration but with ~50% lower hydrodynamic efficiency than the single flagellum. The proposed measurement protocol and static thrust test-bench can be used for bio-inspired microscale propulsion methods, where direct thrust and efficiency measurement are required.
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http://dx.doi.org/10.3390/mi10070449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680724PMC
July 2019

The impact of plaque type on strut embedment/protrusion and shear stress distribution in bioresorbable scaffold.

Eur Heart J Cardiovasc Imaging 2020 04;21(4):454-462

Department of Interventional Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands.

Aims: Scaffold design and plaque characteristics influence implantation outcomes and local flow dynamics in treated coronary segments. Our aim is to assess the impact of strut embedment/protrusion of bioresorbable scaffold on local shear stress distribution in different atherosclerotic plaque types.

Methods And Results: Fifteen Absorb everolimus-eluting Bioresorbable Vascular Scaffolds were implanted in human epicardial coronary arteries. Optical coherence tomography (OCT) was performed post-scaffold implantation and strut embedment/protrusion were analysed using a dedicated software. OCT data were fused with angiography to reconstruct 3D coronary anatomy. Blood flow simulation was performed and wall shear stress (WSS) was estimated in each scaffolded surface and the relationship between strut embedment/protrusion and WSS was evaluated. There were 9083 struts analysed. Ninety-seven percent of the struts (n = 8840) were well-apposed and 243 (3%) were malapposed. At cross-section level (n = 1289), strut embedment was significantly increased in fibroatheromatous plaques (76 ± 48 µm) and decreased in fibrocalcific plaques (35 ± 52 µm). Compatible with strut embedment, WSS was significantly higher in lipid-rich fibroatheromatous plaques (1.50 ± 0.81 Pa), whereas significantly decreased in fibrocalcified plaques (1.05 ± 0.91 Pa). After categorization of WSS as low (<1.0 Pa) and normal/high WSS (≥1.0 Pa), the percent of low WSS in the plaque subgroups were 30.1%, 31.1%, 25.4%, and 36.2% for non-diseased vessel wall, fibrous plaque, fibroatheromatous plaque, and fibrocalcific plaque, respectively (P-overall < 0.001).

Conclusion: The composition of the underlying plaque influences strut embedment which seems to have effect on WSS. The struts deeply embedded in lipid-rich fibroatheromas plaques resulted in higher WSS compared with the other plaque types.
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http://dx.doi.org/10.1093/ehjci/jez155DOI Listing
April 2020

Transitional fetal hemodynamics and gas exchange in premature postpartum adaptation: immediate vs. delayed cord clamping.

Matern Health Neonatol Perinatol 2019 12;5. Epub 2019 Apr 12.

5Department of Mechanical Engineering, Koç Univeresity, Istanbul, Turkey.

Background: Recent studies suggest that delayed cord clamping (DCC) is advantageous for achieving hemodynamic stability and improving oxygenation compared to the immediate cord clamping (ICC) during fetal-to-neonatal transition yet there is no quantitative information on hemodynamics and respiration, particularly for pre-term babies and fetal disease states. Therefore, the objective of this study is to investigate the effects of ICC and DCC on hemodynamics and respiration of the newborn preterm infants in the presence of common vascular pathologies.

Methods: A computational lumped parameter model (LPM) of the placental and respiratory system of a fetus is developed to predict blood pressure, flow rates and oxygen saturation. Cardiovascular system at different gestational ages (GA) are modeled using scaling relations governing fetal growth with the LPM. Intrauterine growth restriction (GR), patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS) were modeled for a newborn at 30 weeks GA. We also formulated a "severity index ()" which is a weighted measure of ICC vs. DCC based on the functional parameters derived from our model and existing neonatal disease scoring systems.

Results: Our results show that transitional hemodynamics is smoother in DCC compared to ICC for all GAs. Blood volume of the neonate increases by 10% for moderately preterm and term infants (32-40 wks) and by 15% for very and extremely preterm infants (22-30 wks) with DCC compared to ICC. DCC also improves the cardiac output and the arterial blood pressure by 17% in term (36-40 wks), by 18% in moderately preterm (32-36 wks), by 21% in very preterm (28-32 wks) and by 24% in extremely preterm (20-28 wks) births compared to the ICC. A decline in oxygen saturation is observed in ICC received infants by 20% compared to the DCC received ones. At 30 weeks GA, SI were calculated for healthy newborns (1.18), and newborns with GR (1.38), PDA (1.22) and RDS (1.2) templates.

Conclusion: Our results suggest that DCC provides superior hemodynamics and respiration at birth compared to ICC. This information will help preventing the complications associated with poor oxygenation arising in premature births and pre-screening the more critical babies in terms of their cardiovascular severity.
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http://dx.doi.org/10.1186/s40748-019-0100-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460527PMC
April 2019

Heart valve inspired and multi-stream aortic cannula: Novel designs for cardiopulmonary bypass improvement in neonates.

Artif Organs 2019 Oct 29;43(10):E233-E248. Epub 2019 Apr 29.

Department of Mechanical Engineering, Koç University, Sarıyer, Istanbul, Turkey.

In a typical open-heart surgery, the blood flow through the aortic cannula is a critical element of the cardiopulmonary bypass (CPB) procedure. Especially for the neonatal and pediatric CPB flow conditions, the need for small hydraulic diameter and large blood flow results confined turbulent jet flow regimes that exacerbate blood damage and platelet activation. Simultaneously, the confined jet wake leads to complex stagnation and recirculating flows that cause considerable thrombosis, blood, and endothelial cell damage through the aorta. Thus, an ideal neonatal CPB cannula should be able to generate optimal jet expansion so that sufficient cerebral perfusion is achieved through the head-neck vessels to avoid postoperative neurological complications and developmental defects in children. To address these challenges, a formal bio-inspired design framework is conducted to reach the desired cannula function through novel analogous biological components, first-time in literature. Among the biological jet flow regimes studied, the ventricle filling-jet generated through the atrio-ventricle (AV) valves are found to be the most promising. Inspired from human AV valve shapes, 8 different novel cannula designs, considering the size constrains of neonatal and pediatric patients are built via high-accurate micro stereo-lithography. Using 2-dimensional time-resolved particle image velocimetry the turbulent jet wake characteristics are measured and compared. The proposed designs have exhibited a significant improvement as compared to standard circular cannula by around 30% reduction in maximum outflow velocity and more than 80% reduction in potential core length and spatial energy dissipation which results in a lower risk of cardiovascular and blood damage.
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http://dx.doi.org/10.1111/aor.13462DOI Listing
October 2019

Asymmetry in Mechanosensitive Gene Expression during Aortic Arch Morphogenesis.

Sci Rep 2018 11 16;8(1):16948. Epub 2018 Nov 16.

Mechanical Engineering Department, Koç University, Istanbul, Turkey.

Embryonic aortic arches (AA) are initially bilaterally paired, transitional vessels and failures in remodeling based on hemodynamic and growth-related adaptations cause a spectrum of congenital heart disease (CHD) anatomies. Identifying regulatory mechanisms and cross-talk between the genetic elements of these vessels are critical to understand the ethiology of CHD and refine predictive computational models. This study aims to screen expression profiles of fundamental biological pathways in AA at early stages of chick embryo morphogenesis and correlate them with our current understanding of growth and mechanical loading. Reverse transcription-quantitative PCR (RT-qPCR) was followed by correlation and novel peak expression analyses to compare the behaviour and activation period of the genes. Available protein networks were also integrated to investigate the interactions between molecules and highlight major hierarchies. Only wall shear stress (WSS) and growth-correlated expression patterns were investigated. Effect of WSS was seen directly on angiogenesis as well on structural and apoptosis-related genes. Our time-resolved network suggested that WSS-correlated genes coordinate the activity of critical growth factors. Moreover, differential gene expression of left and right AA might be an indicator of subsequent asymmetric morphogenesis. These findings may further our understanding of the complex processes of cardiac morphogenesis and errors resulting in CHD.
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http://dx.doi.org/10.1038/s41598-018-35127-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240117PMC
November 2018

Post-implantation shear stress assessment: an emerging tool for differentiation of bioresorbable scaffolds.

Int J Cardiovasc Imaging 2019 Mar 13;35(3):409-418. Epub 2018 Nov 13.

Department of Interventional Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands.

Optical coherence tomography based computational flow dynamic (CFD) modeling provides detailed information about the local flow behavior in stented/scaffolded vessel segments. Our aim is to investigate the in-vivo effect of strut thickness and strut protrusion on endothelial wall shear stress (ESS) distribution in ArterioSorb Absorbable Drug-Eluting Scaffold (ArterioSorb) and Absorb everolimus-eluting Bioresorbable Vascular Scaffold (Absorb) devices that struts with similar morphology (quadratic structure) but different thickness. In three animals, six coronary arteries were treated with ArterioSorb. At different six animals, six coronary arteries were treated with Absorb. Following three-dimensional(3D) reconstruction of the coronary arteries, Newtonian steady flow simulation was performed and the ESS were estimated. Mixed effects models were used to compare ESS distribution in the two devices. There were 4591 struts in the analyzed 477 cross-sections in Absorb (strut thickness = 157 µm) and 3105 struts in 429 cross-sections in ArterioSorb (strut thickness = 95 µm) for the protrusion analysis. In cross-section level analysis, there was significant difference between the scaffolds in the protrusion distances. The protrusion was higher in Absorb (97% of the strut thickness) than in ArterioSorb (88% of the strut thickness). ESS was significantly higher in ArterioSorb (1.52 ± 0.34 Pa) than in Absorb (0.73 ± 2.19 Pa) (p = 0.001). Low- and very-low ESS data were seen more often in Absorb than in ArterioSorb. ArterioSorb is associated with a more favorable ESS distribution compared to the Absorb. These differences should be attributed to different strut thickness/strut protrusion that has significant effect on shear stress distribution.
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http://dx.doi.org/10.1007/s10554-018-1481-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453863PMC
March 2019

Real-World Variability in the Prediction of Intracranial Aneurysm Wall Shear Stress: The 2015 International Aneurysm CFD Challenge.

Cardiovasc Eng Technol 2018 12 10;9(4):544-564. Epub 2018 Sep 10.

University of Toronto, Toronto, ON, Canada.

Purpose: Image-based computational fluid dynamics (CFD) is widely used to predict intracranial aneurysm wall shear stress (WSS), particularly with the goal of improving rupture risk assessment. Nevertheless, concern has been expressed over the variability of predicted WSS and inconsistent associations with rupture. Previous challenges, and studies from individual groups, have focused on individual aspects of the image-based CFD pipeline. The aim of this Challenge was to quantify the total variability of the whole pipeline.

Methods: 3D rotational angiography image volumes of five middle cerebral artery aneurysms were provided to participants, who were free to choose their segmentation methods, boundary conditions, and CFD solver and settings. Participants were asked to fill out a questionnaire about their solution strategies and experience with aneurysm CFD, and provide surface distributions of WSS magnitude, from which we objectively derived a variety of hemodynamic parameters.

Results: A total of 28 datasets were submitted, from 26 teams with varying levels of self-assessed experience. Wide variability of segmentations, CFD model extents, and inflow rates resulted in interquartile ranges of sac average WSS up to 56%, which reduced to < 30% after normalizing by parent artery WSS. Sac-maximum WSS and low shear area were more variable, while rank-ordering of cases by low or high shear showed only modest consensus among teams. Experience was not a significant predictor of variability.

Conclusions: Wide variability exists in the prediction of intracranial aneurysm WSS. While segmentation and CFD solver techniques may be difficult to standardize across groups, our findings suggest that some of the variability in image-based CFD could be reduced by establishing guidelines for model extents, inflow rates, and blood properties, and by encouraging the reporting of normalized hemodynamic parameters.
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http://dx.doi.org/10.1007/s13239-018-00374-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290689PMC
December 2018

Effect of modified Blalock-Taussig shunt anastomosis angle and pulmonary artery diameter on pulmonary flow.

Anatol J Cardiol 2018 Jul;20(1):2-8

Department of Cardiovascular Surgery, Faculty of Medicine, Acıbadem Mehmet Ali Aydınlar University; İstanbul-Turkey.

Objective: This study aimed to identify the best graft-to-pulmonary artery (PA) anastomosis angle measuring pulmonary blood flow, wall shear stress (WSS), and shunt flow.

Methods: A tetralogy of Fallot with pulmonary atresia computer model was used to study three different modified Blalock-Taussig shunt (mBTS) anastomosis angle configurations with three different PA diameter configurations. Velocity and WSS were analyzed, and the flow rates at the right PA (RPA) and left PA (LPA) were calculated.

Results: A 4-mm and 8-mm diameter of RPA and LPA, respectively with vertical shunt angle produces the highest total flow. In the RPA larger diameter than the LPA configutations, the left-leaning shunt produces the lowest total PA flow whereas in the LPA larger diameter than the RPA configuratios, the right-leaning shunt produces the lowest total PA flow. Therefore, the shunt anastomosis should not be leaned through the narrow side of PA to reach best flow. As the flow inside the shunt increased, WSS also increased due to enhanced velocity gradients.

Conclusion: The anastomosis angle between the conduit and PA affects the flow to PA. Vertical anastomosis configurations increase the total PA flow; thus, these configurations are preferable than the leaned configurations.
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http://dx.doi.org/10.14744/AnatolJCardiol.2018.54810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237788PMC
July 2018

Computational Pre-surgical Planning of Arterial Patch Reconstruction: Parametric Limits and In Vitro Validation.

Ann Biomed Eng 2018 Sep 14;46(9):1292-1308. Epub 2018 May 14.

Department of Mechanical Engineering, Koc University, Rumeli Feneri Kampüsü, Sarıyer, Istanbul, Turkey.

Surgical treatment of congenital heart disease (CHD) involves complex vascular reconstructions utilizing artificial and native surgical materials. A successful surgical reconstruction achieves an optimal hemodynamic profile through the graft in spite of the complex post-operative vessel growth pattern and the altered pressure loading. This paper proposes a new in silico patient-specific pre-surgical planning framework for patch reconstruction and investigates its computational feasibility. The proposed protocol is applied to the patch repair of main pulmonary artery (MPA) stenosis in the Tetralogy of Fallot CHD template. The effects of stenosis grade, the three-dimensional (3D) shape of the surgical incision and material properties of the artificial patch are investigated. The release of residual stresses due to the surgical incision and the extra opening of the incision gap for patch implantation are simulated through a quasi-static finite-element vascular model with shell elements. Implantation of different unloaded patch shapes is simulated. The patched PA configuration is pressurized to the physiological post-operative blood pressure levels of 25 and 45 mmHg and the consequent post-operative stress distributions and patched artery shapes are computed. Stress-strain data obtained in-house, through the biaxial tensile tests for the mechanical properties of common surgical patch materials, Dacron, Polytetrafluoroethylene, human pericardium and porcine xenopericardium, are employed to represent the mechanical behavior of the patch material. Finite-element model is experimentally validated through the actual patch surgery reconstructions performed on the 3D printed anatomical stenosis replicas. The post-operative recovery of the initially narrowed lumen area and post-op tortuosity are quantified for all modeled cases. A computational fluid dynamics solver is used to evaluate post-operative pressure drop through the patch-reconstructed outflow tract. According to our findings, the shorter incisions made at the throat result in relatively low local peak stress values compared to other patch design alternatives. Longer cut and double patch cases are the most effective in repairing the initial stenosis level. After the patch insertion, the pressure drop in the artery due to blood flow decreases from 9.8 to 1.35 mmHg in the conventional surgical configuration. These results are in line with the clinical experience where a pressure gradient at or above 50 mmHg through the MPA can be an indication to intervene. The main strength of the proposed pre-surgical planning framework is its capability to predict the intra-operative and post-operative 3D vascular shape changes due to intramural pressure, cut length and configuration, for both artificial and native patch materials.
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http://dx.doi.org/10.1007/s10439-018-2043-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097742PMC
September 2018

In vitro validation of a self-driving aortic-turbine venous-assist device for Fontan patients.

J Thorac Cardiovasc Surg 2018 07 11;156(1):292-301.e7. Epub 2018 Mar 11.

Department of Cardiovascular Surgery, School of Medicine, Acıbadem University, Istanbul, Turkey.

Background: Palliative repair of single ventricle defects involve a series of open-heart surgeries where a single-ventricle (Fontan) circulation is established. As the patient ages, this paradoxical circulation gradually fails, because of its high venous pressure levels. Reversal of the Fontan paradox requires an extra subpulmonic energy that can be provided through mechanical assist devices. The objective of this study was to evaluate the hemodynamic performance of a totally implantable integrated aortic-turbine venous-assist (iATVA) system, which does not need an external drive power and maintains low venous pressure chronically, for the Fontan circulation.

Methods: Blade designs of the co-rotating turbine and pump impellers were developed and 3 prototypes were manufactured. After verifying the single-ventricle physiology at a pulsatile in vitro circuit, the hemodynamic performance of the iATVA system was measured for pediatric and adult physiology, varying the aortic steal percentage and circuit configurations. The iATVA system was also tested at clinical off-design scenarios.

Results: The prototype iATVA devices operate at approximately 800 revolutions per minute and extract up to 10% systemic blood from the aorta to use this hydrodynamic energy to drive a blood turbine, which in turn drives a mixed-flow venous pump passively. By transferring part of the available energy from the single-ventricle outlet to the venous side, the iATVA system is able to generate up to approximately 5 mm Hg venous recovery while supplying the entire caval flow.

Conclusions: Our experiments show that a totally implantable iATVA system is feasible, which will eliminate the need for external power for Fontan mechanical venous assist and combat gradual postoperative venous remodeling and Fontan failure.
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http://dx.doi.org/10.1016/j.jtcvs.2018.02.088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021195PMC
July 2018

Patient-Specific Atrial Hemodynamics of a Double Lumen Neonatal Cannula in Correct Caval Position.

Artif Organs 2018 Apr 23;42(4):401-409. Epub 2018 Mar 23.

Department of Mechanical Engineering, Koç University, Sarıyer, Turkey.

Clinical success of pediatric veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is associated with the double lumen cannula cardiovascular device design as well as its anatomic orientation in the atrium. The positions of cannula ports with respect to the vena cavae and the tricuspid valve are believed to play a significant role on device hemodynamics. Despite various improvements in ECMO catheters, especially for the neonatal and congenital heart patients, it is still challenging to select a catalogue size that would fit to most patients optimally. In effect, the local unfavorable blood flow characteristics of the cannula would translate to an overall loss of efficiency of the ECMO circuit. In this study, the complex flow regime of a neonatal double lumen cannula, positioned in a patient-specific right atrium, is presented for the first time in literature. A pulsatile computational fluid dynamics (CFD) solver that is validated for cardiovascular device flow regimes was used to perform the detailed flow, oxygenated blood transport, and site-specific blood damage analysis using an integrated cannula and right atrium model. A standard 13Fr double lumen cannula was scanned using micro-CT, reconstructed and simulated under physiologic flow conditions. User defined scalar transport equations allowed the quantification of the mixing and convection of oxygenated and deoxygenated blood as well as blood residence times and hemolysis build-up. Site-specific CFD analysis provided key insight into the hemodynamic challenges encountered in cannula design and the associated intra-atrial flow patterns. Due to neonatal flow conditions, an ultra high velocity infusion jet emanated from the infusion port and created a zone of major recirculation in the atrium. This flow regime influenced the delivery of the oxygenated blood to the tricuspid valve. Elevated velocities and complex gradients resulted in higher wall shear stresses (WSS) particularly at the infusion port having the highest value followed by the aspiration hole closest to the drainage port. Our results show that, in a cannula that is perfectly oriented in the atrium, almost 38% of the oxygenated blood is lost to the atrial circulation while only half of the blood from inferior vena cava (IVC) can reach to the tricuspid valve. As such, approximately 6% of venous blood from superior vena cava (SVC) can be delivered to tricuspid. High values of hemolysis index were observed with blood damage encountered around infusion hole (0.025%). These results warrant further improvements in the cannula design to achieve optimal performance of ECMO and better patient outcomes.
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http://dx.doi.org/10.1111/aor.13127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947122PMC
April 2018

Haemodynamic Recovery Properties of the Torsioned Testicular Artery Lumen.

Sci Rep 2017 Nov 14;7(1):15570. Epub 2017 Nov 14.

Koc University, Mechanical Engineering Department, Istanbul, 34450, Turkey.

Testicular artery torsion (twisting) is one such severe vascular condition that leads spermatic cord injury. In this study, we investigate the recovery response of a torsioned ram testicular artery in an isolated organ-culture flow loop with clinically relevant twisting modes (90°, 180°, 270° and 360° angles). Quantitative optical coherence tomography technique was employed to track changes in the lumen diameter, wall thickness and the three-dimensional shape of the vessel in the physiological pressure range (10-50 mmHg). As a control, pressure-flow characteristics of the untwisted arteries were studied when subjected to augmented blood flow conditions with physiological flow rates up to 36 ml/min. Both twist and C-shaped buckling modes were observed. Acute increase in pressure levels opened the narrowed lumen of the twisted arteries noninvasively at all twist angles (at ∼22 mmHg and ∼35 mmHg for 360°-twisted vessels during static and dynamic flow experiments, respectively). The association between the twist-opening flow rate and the vessel diameter was greatly influenced by the initial twist angle. The biomechanical characteristics of the normal (untwisted) and torsioned testicular arteries supported the utilization of blood flow augmentation as an effective therapeutic approach to modulate the vessel lumen and recover organ reperfusion.
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http://dx.doi.org/10.1038/s41598-017-15680-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686114PMC
November 2017

Tetralogy of Fallot Surgical Repair: Shunt Configurations, Ductus Arteriosus and the Circle of Willis.

Cardiovasc Eng Technol 2017 06 5;8(2):107-119. Epub 2017 Apr 5.

Department of Mechanical Engineering, Koç University, Rumeli Feneri Kampüsü, Sarıyer, Istanbul, Turkey.

In this study, hemodynamic performance of three novel shunt configurations that are considered for the surgical repair of tetralogy of Fallot (TOF) disease are investigated in detail. Clinical experience suggests that the shunt location, connecting angle, and its diameter can influence the post-operative physiology and the neurodevelopment of the neonatal patient. An experimentally validated second order computational fluid dynamics (CFD) solver and a parametric neonatal diseased great artery model that incorporates the ductus arteriosus (DA) and the full patient-specific circle of Willis (CoW) are employed. Standard truncated resistance CFD boundary conditions are compared with the full cerebral arterial system, which resulted 21, -13, and 37% difference in flow rate at the brachiocephalic, left carotid, and subclavian arteries, respectively. Flow splits at the aortic arch and cerebral arteries are calculated and found to change with shunt configuration significantly for TOF disease. The central direct shunt (direct shunt) has pulmonary flow 5% higher than central oblique shunt (oblique shunt) and 23% higher than modified Blalock Taussig shunt (RPA shunt) while the DA is closed. Maximum wall shear stress (WSS) in the direct shunt configuration is 9 and 60% higher than that of the oblique and RPA shunts, respectively. Patent DA, significantly eliminated the pulmonary flow control function of the shunt repair. These results suggests that, due to the higher flow rates at the pulmonary arteries, the direct shunt, rather than the central oblique, or right pulmonary artery shunts could be preferred by the surgeon. This extended model introduced new hemodynamic performance indices for the cerebral circulation that can correlate with the post-operative neurodevelopment quality of the patient.
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http://dx.doi.org/10.1007/s13239-017-0302-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446850PMC
June 2017

Motile-Cilia-Mediated Flow Improves Sensitivity and Temporal Resolution of Olfactory Computations.

Curr Biol 2017 Jan 29;27(2):166-174. Epub 2016 Dec 29.

Kavli Institute for Systems Neuroscience, Center for Neural Computation, The Faculty of Medicine, NTNU, Olav Kyrres Gate 9, 7030 Trondheim, Norway. Electronic address:

Motile cilia are actively beating hair-like structures that cover the surface of multiple epithelia. The flow that ciliary beating generates is utilized for diverse functions and depends on the spatial location and biophysical properties of cilia. Here we show that the motile cilia in the nose of aquatic vertebrates are spatially organized and stably beat with an asymmetric pattern, resulting in a robust and stereotypical flow around the nose. Our results demonstrate that these flow fields attract odors to the nose pit and facilitate detection of odors by the olfactory system in stagnant environments. Moreover, we show that ciliary beating quickly exchanges the content of the nose, thereby improving the temporal resolution of the olfactory system for detecting dynamic changes of odor plumes in turbulent environments. Altogether, our work unravels a central function of ciliary beating for generating flow fields that increase the sensitivity and the temporal resolution of olfactory computations in the vertebrate brain.
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http://dx.doi.org/10.1016/j.cub.2016.11.036DOI Listing
January 2017

Hemodynamics of patient-specific aorta-pulmonary shunt configurations.

J Biomech 2017 01 11;50:166-171. Epub 2016 Nov 11.

Department of Biomedical Engineering, Koc University, Istanbul, Turkey; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, USA. Electronic address:

Optimal hemodynamics in aorta-pulmonary shunt reconstruction is essential for improved post-operative recovery of the newborn congenital heart disease patient. However, prior to in vivo execution, the prediction of post-operative hemodynamics is extremely challenging due to the interplay of multiple confounding physiological factors. It is hypothesized that the post-operative performance of the surgical shunt can be predicted through computational blood flow simulations that consider patient size, shunt configuration, cardiac output and the complex three-dimensional disease anatomy. Utilizing only the routine patient-specific pre-surgery clinical data sets, we demonstrated an intelligent decision-making process for a real patient having pulmonary artery atresia and ventricular septal defect. For this patient, a total of 12 customized candidate shunt configurations are contemplated and reconstructed virtually using a sketch-based computer-aided anatomical editing tool. Candidate shunt configurations are evaluated based on the parameters that are computed from the flow simulations, which include 3D flow complexity, outlet flow splits, shunt patency, coronary perfusion and energy loss. Our results showed that the modified Blalock-Taussig (mBT) shunt has 12% higher right pulmonary artery (RPA) and 40% lower left pulmonary artery (LPA) flow compared to the central shunt configuration. Also, the RPA flow regime is distinct from the LPA, creating an uneven flow split at the pulmonary arteries. For all three shunt sizes, right mBT innominate and central configurations cause higher pulmonary artery (PA) flow and lower coronary artery pressure than right and left mBT subclavian configurations. While there is a trade-off between energy loss, flow split and coronary artery pressure, overall, the mBT shunts provide sufficient PA perfusion with higher coronary artery pressures and could be preferred for similar patients having PA overflow risk. Central shunts would be preferred otherwise particularly for cases with very low PA overflow risk.
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http://dx.doi.org/10.1016/j.jbiomech.2016.11.014DOI Listing
January 2017

Mytilus galloprovincialis as a smart micro-pump.

Biol Open 2016 Oct 15;5(10):1493-1499. Epub 2016 Oct 15.

Mechanical Engineering Department, Koc University, Istanbul 34450, Turkey

Hydrodynamic performance of the marine mussel, Mytilus galloprovincialis, is studied with time-resolved particle image velocimetry. We evaluated inhalant flow, exhalant jet flow, suction performance and flow control capabilities of the mussels quantitatively. Inhalant flow structures of mussels are measured at the coronal plane for the first time in literature. Nutrient fluid is convected into the mussel by three-dimensional sink flow. Inhalant velocity reaches its highest magnitude inside the mussel mantle while it is accelerating outward from the mussels. We calculated pressure gradient at the coronal plane. As inhalant flow approaches the mussel shell tip, suction force generated by the inhalant flow increases and becomes significant at the shell tip. Likewise, exhalant jet flow regimes were studied for 17 mussels. Mussels can control their exhalant jet flow structure from a single potential core region to double potential core region or vice versa. Peak exhalant jet velocity generated by the mussels changes between 2.77 cm s and 11.1 cm s as a function of mussel cavity volume. Measurements of hydrodynamic dissipation at the sagittal plane revealed no interaction between the inhalant and exhalant jet flow, indicating energy-efficient synchronized pumping mechanism. This efficient pumping mechanism is associated with the flow-turning angle between inhalant and exhalant jet flows, ∼90° (s.d. 12°).
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http://dx.doi.org/10.1242/bio.021048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087679PMC
October 2016

Time-Series Interactions of Gene Expression, Vascular Growth and Hemodynamics during Early Embryonic Arterial Development.

PLoS One 2016 23;11(8):e0161611. Epub 2016 Aug 23.

Mechanical Engineering Department, Koc University, Istanbul, Turkey.

The role of hemodynamic forces within the embryo as biomechanical regulators for cardiovascular morphogenesis, growth, and remodeling is well supported through the experimental studies. Furthermore, clinical experience suggests that perturbed flow disrupts the normal vascular growth process as one etiology for congenital heart diseases (CHD) and for fetal adaptation to CHD. However, the relationships between hemodynamics, gene expression and embryonic vascular growth are poorly defined due to the lack of concurrent, sequential in vivo data. In this study, a long-term, time-lapse optical coherence tomography (OCT) imaging campaign was conducted to acquire simultaneous blood velocity, pulsatile micro-pressure and morphometric data for 3 consecutive early embryonic stages in the chick embryo. In conjunction with the in vivo growth and hemodynamics data, in vitro reverse transcription polymerase chain reaction (RT-PCR) analysis was performed to track changes in transcript expression relevant to histogenesis and remodeling of the embryonic arterial wall. Our non-invasive extended OCT imaging technique for the microstructural data showed continuous vessel growth. OCT data coupled with the PIV technique revealed significant but intermitted increases in wall shear stress (WSS) between first and second assigned stages and a noticeable decrease afterwards. Growth rate, however, did not vary significantly throughout the embryonic period. Among all the genes studied, only the MMP-2 and CASP-3 expression levels remained unchanged during the time course. Concurrent relationships were obtained among the transcriptional modulation of the genes, vascular growth and hemodynamics-related changes. Further studies are indicated to determine cause and effect relationships and reversibility between mechanical and molecular regulation of vasculogenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161611PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994943PMC
July 2017

Non-dimensional physics of pulsatile cardiovascular networks and energy efficiency.

J R Soc Interface 2016 Jan;13(114):20151019

Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA Department of Mechanical Engineering, Koç University, Istanbul, Turkey

In Nature, there exist a variety of cardiovascular circulation networks in which the energetic ventricular load has both steady and pulsatile components. Steady load is related to the mean cardiac output (CO) and the haemodynamic resistance of the peripheral vascular system. On the other hand, the pulsatile load is determined by the simultaneous pressure and flow waveforms at the ventricular outlet, which in turn are governed through arterial wave dynamics (transmission) and pulse decay characteristics (windkessel effect). Both the steady and pulsatile contributions of the haemodynamic power load are critical for characterizing/comparing disease states and for predicting the performance of cardiovascular devices. However, haemodynamic performance parameters vary significantly from subject to subject because of body size, heart rate and subject-specific CO. Therefore, a 'normalized' energy dissipation index, as a function of the 'non-dimensional' physical parameters that govern the circulation networks, is needed for comparative/integrative biological studies and clinical decision-making. In this paper, a complete network-independent non-dimensional formulation that incorporates pulsatile flow regimes is developed. Mechanical design variables of cardiovascular flow systems are identified and the Buckingham Pi theorem is formally applied to obtain the corresponding non-dimensional scaling parameter sets. Two scaling approaches are considered to address both the lumped parameter networks and the distributed circulation components. The validity of these non-dimensional number sets is tested extensively through the existing empirical allometric scaling laws of circulation systems. Additional validation studies are performed using a parametric numerical arterial model that represents the transmission and windkessel characteristics, which are adjusted to represent different body sizes and non-dimensional haemodynamic states. Simulations demonstrate that the proposed non-dimensional indices are independent of body size for healthy conditions, but are sensitive to deviations caused by off-design disease states that alter the energetic load. Sensitivity simulations are used to identify the relationship between pulsatile power loss and non-dimensional characteristics, and optimal operational states are computed.
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http://dx.doi.org/10.1098/rsif.2015.1019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759807PMC
January 2016

The Computational Fluid Dynamics Rupture Challenge 2013--Phase II: Variability of Hemodynamic Simulations in Two Intracranial Aneurysms.

J Biomech Eng 2015 Dec;137(12):121008

With the increased availability of computational resources, the past decade has seen a rise in the use of computational fluid dynamics (CFD) for medical applications. There has been an increase in the application of CFD to attempt to predict the rupture of intracranial aneurysms, however, while many hemodynamic parameters can be obtained from these computations, to date, no consistent methodology for the prediction of the rupture has been identified. One particular challenge to CFD is that many factors contribute to its accuracy; the mesh resolution and spatial/temporal discretization can alone contribute to a variation in accuracy. This failure to identify the importance of these factors and identify a methodology for the prediction of ruptures has limited the acceptance of CFD among physicians for rupture prediction. The International CFD Rupture Challenge 2013 seeks to comment on the sensitivity of these various CFD assumptions to predict the rupture by undertaking a comparison of the rupture and blood-flow predictions from a wide range of independent participants utilizing a range of CFD approaches. Twenty-six groups from 15 countries took part in the challenge. Participants were provided with surface models of two intracranial aneurysms and asked to carry out the corresponding hemodynamics simulations, free to choose their own mesh, solver, and temporal discretization. They were requested to submit velocity and pressure predictions along the centerline and on specified planes. The first phase of the challenge, described in a separate paper, was aimed at predicting which of the two aneurysms had previously ruptured and where the rupture site was located. The second phase, described in this paper, aims to assess the variability of the solutions and the sensitivity to the modeling assumptions. Participants were free to choose boundary conditions in the first phase, whereas they were prescribed in the second phase but all other CFD modeling parameters were not prescribed. In order to compare the computational results of one representative group with experimental results, steady-flow measurements using particle image velocimetry (PIV) were carried out in a silicone model of one of the provided aneurysms. Approximately 80% of the participating groups generated similar results. Both velocity and pressure computations were in good agreement with each other for cycle-averaged and peak-systolic predictions. Most apparent "outliers" (results that stand out of the collective) were observed to have underestimated velocity levels compared to the majority of solutions, but nevertheless identified comparable flow structures. In only two cases, the results deviate by over 35% from the mean solution of all the participants. Results of steady CFD simulations of the representative group and PIV experiments were in good agreement. The study demonstrated that while a range of numerical schemes, mesh resolution, and solvers was used, similar flow predictions were observed in the majority of cases. To further validate the computational results, it is suggested that time-dependent measurements should be conducted in the future. However, it is recognized that this study does not include the biological aspects of the aneurysm, which needs to be considered to be able to more precisely identify the specific rupture risk of an intracranial aneurysm.
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http://dx.doi.org/10.1115/1.4031794DOI Listing
December 2015

Computational Modeling of Neonatal Cardiopulmonary Bypass Hemodynamics With Full Circle of Willis Anatomy.

Artif Organs 2015 Oct 1;39(10):E164-75. Epub 2015 May 1.

Department of Mechanical Engineering, Koc University, Istanbul, Turkey.

Cardiopulmonary bypass (CPB) procedure is employed to repair most congenital heart defects (CHD). Cannulation is a critical component of this procedure where the location and diameter of cannula controls the hemodynamic performance. State-of-the-art computational studies of neonatal CPB employed an isolated aortic arch region by truncating the three-dimensional (3D) patient-specific cerebral system. The present work expanded these studies where the 3D patient-specific MRI reconstruction of the cerebral system, including the Circle of Willis (CoW), is integrated with a hypoplastic neonatal aortic arch. The inlet of the arterial cannula is assigned a steady velocity boundary condition of the CPB pump, while all outlets are modeled as resistance boundary conditions, thus allowing acute comparisons between different cannula configurations. Three-dimensional (3D) flow simulations in the aortic arch model are performed at a Reynolds number of 2150 using an experimentally validated commercial solver. Results demonstrate that the inclusion of 3D CoW is essential to predict the accurate head-neck blood perfusion and therefore critical in deciding the neonatal aortic cannulation strategy preoperatively. Using this integrated model two CPB configurations are studied, where the cannulas were placed at innominate artery (IA) (IA-cannula configuration) and ductus arteriosus (DA) (DA-cannula configuration). Configuration change produced significant differences in flow splits and local hemodynamics of blood flow throughout the whole aortic arch, neck and cerebral arteries. Percent flow rate differences between the IA- and DA-cannula configurations are computed to be: 19%, for descending aorta, 198% for ascending aorta (perfusing coronary arteries), 91% for right anterior cerebral artery, and 68% for left anterior cerebral artery. Another important finding is the retrograde flow at vertebral arteries for IA-cannula configuration, but not for DA-cannula. These results may help to translate better neonatal arterial cannulae design for minimizing cerebral complications during CPB procedures.
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http://dx.doi.org/10.1111/aor.12468DOI Listing
October 2015

Noninvasive in vivo determination of residual strains and stresses.

J Biomech Eng 2015 Jun 15;137(6):061011. Epub 2015 Apr 15.

Vascular growth and remodeling during embryonic development are associated with blood flow and pressure induced stress distribution, in which residual strains and stresses play a central role. Residual strains are typically measured by performing in vitro tests on the excised vascular tissue. In this paper, we investigated the possibility of estimating residual strains and stresses using physiological pressure-radius data obtained through in vivo noninvasive measurement techniques, such as optical coherence tomography or ultrasound modalities. This analytical approach first tested with in vitro results using experimental data sets for three different arteries such as rabbit carotid artery, rabbit thoracic artery, and human carotid artery based on Fung's pseudostrain energy function and Delfino's exponential strain energy function (SEF). We also examined residual strains and stresses in the human swine iliac artery using the in vivo experimental ultrasound data sets corresponding to the systolic-to-diastolic region only. This allowed computation of the in vivo residual stress information for loading and unloading states separately. Residual strain parameters as well as the material parameters were successfully computed with high accuracy, where the relative errors are introduced in the range of 0-7.5%. Corresponding residual stress distributions demonstrated global errors all in acceptable ranges. A slight discrepancy was observed in the computed reduced axial force. Results of computations performed based on in vivo experimental data obtained from loading and unloading states of the artery exhibited alterations in material properties and residual strain parameters as well. Emerging noninvasive measurement techniques combined with the present analytical approach can be used to estimate residual strains and stresses in vascular tissues as a precursor for growth estimates. This approach is also validated with a finite element model of a general two-layered artery, where the material remodeling states and residual strain generation are investigated.
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http://dx.doi.org/10.1115/1.4030071DOI Listing
June 2015