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Publication Metadata only Characterization of neonatal aortic cannula jet flow regimes for improved cardiopulmonary bypass(Elsevier Sci Ltd, 2013) Menon, Prahlad G.; Teslovich, Nikola; Chen, Chia-Yuan; Undar, Akif; Department of Mechanical Engineering; Pekkan, Kerem; Faculty Member; Department of Mechanical Engineering; College of Engineering; 161845During pediatric and neonatal cardiopulmonary bypass (CPB), tiny aortic outflow cannulae (2-3 mm inner diameter), with micro-scale blood-wetting features transport relatively large blood volumes (0.3 to 1.0 L/min) resulting in high blood flow velocities (2 to 5 m/s). These severe flow conditions are likely to complement platelet activation, release pro-inflammatory cytokines, and further result in vascular and blood damage. Hemodynamically efficient aortic outflow cannulae are required to provide high blood volume flow rates at low exit force. In addition, optimal aortic insertion strategies are necessary in order to alleviate hemolytic risk, post-surgical neurological complications and developmental defects, by improving cerebral perfusion in the young patient. The methodology and results presented in this study serve as a baseline for design of superior aortic outflow cannulae. In this study, direct numerical simulation (DNS) computational fluid dynamics (CFD) was employed to delineate baseline hemodynamic performance of jet wakes emanating from microCT scanned state-of-the-art pediatric cannula tips in a cuboidal test rig operating at physiologically relevant laminar and turbulent Reynolds numbers (Re: 650-2150, steady inflow). Qualitative and quantitative validation of CFD simulated device-specific jet wakes was established using time-resolved flow visualization and particle image velocimetry (PIV). For the standard end-hole cannula tip design, blood damage indices were further numerically assessed in a subject-specific cross-clamped neonatal aorta model for different cannula insertion configurations. Based on these results, a novel diffuser type cannula tip is proposed for improved jet flow-control, decreased blood damage and exit force and increased permissible flow rates. This study also suggests that surgically relevant cannula orientation parameters such as outflow angle and insertion depth may be important for improved hemodynamic performance. The jet flow design paradigm demonstrated in this study represents a philosophical shift towards cannula flow control enabling favorable pressure-drop versus outflow rate characteristics.Publication Metadata only Computational modeling of vascular growth in patient-specific pulmonary arterial patch reconstructions(Elsevier Sci Ltd, 2021) Coban, Gursan; Kose, Banu; Salihoglu, Ece; Department of Mechanical Engineering; Department of Mechanical Engineering; Lashkarinia, Seyedeh Samaneh; Pekkan, Kerem; Researcher; Faculty Member; Department of Mechanical Engineering; College of Engineering; College of EngineeringRecent 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, nonuniform 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.Publication Metadata only Embryonic aortic arch material properties obtained by optical coherence tomography-guided micropipette aspiration(Elsevier Ltd, 2023) Çoban, Gürşan; Yap, Choon Hwai; Department of Mechanical Engineering; N/A; Department of Mechanical Engineering; Lashkarinia, Seyedeh Samaneh; Siddiqui, Hummaira Banu; Pekkan, Kerem; Researcher; PhD Student; Faculty Member; Department of Mechanical Engineering; College of Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 161845It is challenging to determine the in vivo material properties of a very soft, mesoscale arterial vesselsof size ∼ 80 to 120 μm diameter. This information is essential to understand the early embryonic cardiovascular development featuring rapidly evolving dynamic microstructure. Previous research efforts to describe the properties of the embryonic great vessels are very limited. Our objective is to measure the local material properties of pharyngeal aortic arch tissue of the chick-embryo during the early Hamburger-Hamilton (HH) stages, HH18 and HH24. Integrating the micropipette aspiration technique with optical coherence tomography (OCT) imaging, a clear vision of the aspirated arch geometry is achieved for an inner pipette radius of Rp = 25 μm. The aspiration of this region is performed through a calibrated negatively pressurized micro-pipette. A computational finite element model is developed to model the nonlinear behaviour of the arch structure by considering the geometry-dependent constraints. Numerical estimations of the nonlinear material parameters for aortic arch samples are presented. The exponential material nonlinearity parameter (a) of aortic arch tissue increases statistically significantly from a = 0.068 ± 0.013 at HH18 to a = 0.260 ± 0.014 at HH24 (p = 0.0286). As such, the aspirated tissue length decreases from 53 μm at HH18 to 34 μm at HH24. The calculated NeoHookean shear modulus increases from 51 Pa at HH18 to 93 Pa at HH24 which indicates a statistically significant stiffness increase. These changes are due to the dynamic changes of collagen and elastin content in the media layer of the vessel during development.Publication Metadata only Hemodynamic performance limits of the neonatal double-lumen cannula(Elsevier, 2021) Yıldız, Yahya; Salihoğlu, Ece; Department of Mechanical Engineering; Department of Mechanical Engineering; Department of Mechanical Engineering; Department of Mechanical Engineering; Rasooli, Reza; Jamil, Muhammad; Rezaeimoghaddam, Mohammad; Pekkan, Kerem; Researcher; Researcher; Researcher; Faculty Member; Department of Mechanical Engineering; College of Engineering; College of Engineering; College of Engineering; College of Engineering; N/A; N/A; N/A; 161845Venovenous extracorporeal membrane oxygenation (VV-ECMO) is the preferred surgical intervention for patients suffering from severe cardiorespiratory failure, also encountered in SARS-Cov-2 management. The key component of VV-ECMO is the double-lumen cannula (DLC) that enables single-site access. The biofluid dynamics of this compact device is particularly challenging for neonatal patients due to high Reynolds numbers, tricuspid valve location and right-atrium hemodynamics. In this paper we present detailed findings of our comparative analysis of the right-atrial hemodynamics and salient design features of the 13Fr Avalon Elite DLC (as the clinically preferred neonatal cannula) with the alternate Origen DLC design, using experimentally validated computational fluid dynamics. Highly accurate 3D reconstructions of both devices were obtained through an integrated optical coherence tomography and micro-CT imaging approach. Both cannula configurations displayed complex flow structures inside the atrium, superimposed over predominant recirculation regimes. We found that the Avalon DLC performed significantly better than the Origen alternative, by capturing 80% and 94% of venous blood from the inferior and superior vena cavae, respectively and infusing the oxygenated blood with an efficiency of more than 85%. The micro-scale geometric design features of the Avalon DLC that are associated with superior hemodynamics were investigated through 14 parametric cannula configurations. These simulations showed that the strategic placement of drainage holes, the smooth infusion blood stream diverter and efficient distribution of the venous blood capturing area between the vena cavae are associated with robust blood flow performance. Nevertheless, our parametric results indicate that there is still room for further device optimization beyond the performance measurements for both Avalon and Origen DLC in this study. In particular, the performance envelope of malpositioned cannula and off-design conditions require additional blood flow simulations for analysis.Publication Metadata only In vitro measurement of hepatic flow distribution in Fontan vascular conduits: towards rapid validation techniques(Elsevier, 2022) Köse, Banu; Şaşmazel, Ahmet; Department of Mechanical Engineering; Department of Mechanical Engineering; Department of Mechanical Engineering; Rasooli, Reza; Lashkarinia, Seyedeh Samaneh; Pekkan, Kerem; Researcher; Researcher; Faculty Member; Department of Mechanical Engineering; College of Engineering; College of Engineering; College of Engineering; N/A; N/A; 161845Fontan operation is the last stage of single-ventricle surgical reconstructions that connects superior and inferior vena cava (SVC, IVC) to the pulmonary arteries. The key design objectives in total cavopulmonary connections (TCPC) are to achieve low power loss (PL) and balanced hepatic flow distribution (HFD). Computational fluid dynamics (CFD) played a pivotal role in pre-surgical design of single-ventricle patients. However, the clinical application of current CFD techniques is limited due to their complexity, high computational time and untested accuracy for HFD prediction. This study provides a performance assessment of computationally low-cost steady Reynolds-Averaged Navier-Stokes (RANS) k-epsilon turbulent models for simulation of Fontan hemodynamics. The performance is evaluated based on prediction accuracy for three clinically important Fontan hemodynamic indices: HFD, PL and total pulmonary flow split (TPFS). For this purpose, a low-cost experimental technique is developed for rapid quantification of Fontan performance indices. Experiments and simulations are performed for both an idealized and a complex 3D reconstructed patient-specific TCPC. Time-averaged flow data from phase contrast MRI was used as the boundary conditions for the patient-specific model. For the idealized model, different SVC/IVC flow ratios corresponding to different cardiac outputs and Reynolds' numbers were examined. This study revealed that steady RANS k-epsilon models are able to estimate the Fontan hemodynamic indices with acceptable accuracy within minutes. Among these, standard k-epsilon two-layer was found to deliver the best agreement with the in vitro data with an average error percentage of 1.7, 2.0 and, 3.9 for HFD, TPFS and, PL, respectively for all cases.Publication Metadata only Novel fenestration designs for controlled venous flow shunting in failing fontans with systemic venous hypertension(Wiley, 2013) Albal, Priti G.; Menon, Prahlad G.; Kowalski, William; Undar, Akif; Turkoz, Riza; Department of Mechanical Engineering; Pekkan, Kerem; Faculty Member; Department of Mechanical Engineering; College of Engineering; 161845The Fontan procedure is employed as the final-stage palliation in single-ventricle congenital heart patients and results in diversion of venous blood directly to the pulmonary arteries. Fontan patients have been known to suffer from postoperative systemic venous hypertension, which in turn is associated with pleural effusions and protein losing enteropathy, leading to a decreased duration and quality of life. Despite the ongoing debate on its benefits, a circular fenestration hole (typically 4?mm) establishing a venous shunt to the common atrium is traditionally employed to relieve venous pressure in the Fontan conduit and improve early postoperative Fontan hemodynamics. However, these improvements come at the cost of reduced oxygen saturation due to excessive right-to-left shunting if the fenestration is permanent. The ideal selective fenestration would therefore limit or eliminate shunt flow at tolerable systemic venous pressures and allow increased flow at high pressures. The objective of this study is to introduce new fenestration designs that exhibit these desirable pressure-flow characteristics. Novel plus-shaped and S-shaped fenestration designs with leaflets are introduced as alternatives to the traditional circular fenestration, each having identical effective orifice areas at the fully open states. In vitro steady leakage flow tests were performed for physiological flow-driving pressures in order to obtain pressure-drop versus flow-rate characteristics. In addition, the leaflet opening kinematics of the plus-shaped fenestration was investigated computationally using finite element simulation. Fluid-structure interaction analysis was performed to determine leaflet displacements and pressure-flow characteristics at low pressures. Further, a lumped parameter model of the single-ventricle circuit was created to simulate pulsatile flow conditions For the plus-shaped fenestration, the flow rate was found to increase nonlinearly with increased driving systemic venous pressures at high physiological-pressure drops which did not cause the leaflets to fully open, and linearly for low driving pressures. These results indicate that leaflets of the plus-shaped fenestration design activated passively after a critical systemic venous pressure threshold. This feature is ideal for minimizing undesirable excessive venous shunting. A large variability in shunting flow rate may be obtained by changing the shape, thickness, size, and material of the fenestration to suit requirements of the patient, which can further limit shunt flow in a controlled manner.Publication Metadata only Polycaprolactone/silk fibroin electrospun nanofibers-based lateral flow test strip for quick and facile determination of bisphenol A in breast milk(Wiley, 2021) Gurel-Gokmen, Begum; Taslak, Hava Dudu; Ozcan, Ozan; Tunali-Akbay, Tuğba; N/A; İpar, Necla; Doctor; N/A; Koç University Hospital; N/AThis study aimed to develop a sensitive lateral flow test strip for the detection of bisphenol A (BPA) in breast milk. Conventional nitrocellulose test membrane was coated with the coaxial nanofiber, consisting of the inner polycaprolactone (PCL) and the outer PCL/silk fibroin (SF) mixture, to decrease the flow rate of the breast milk in the lateral flow assay (LFA). The nanofiber was prepared by using coaxial electrospinning, and BPA antibody was immobilized physically to the nanofiber. This nanofiber was used as a test membrane in the LFA. Color changes on the test membrane were evaluated as the signal intensity of the BPA. Breast milk creates a background on surfaces due to its structural properties. This background was detected by comparing the signal intensity with the signal intensity of water. The higher signal intensity was found in water samples when compared to breast milk samples. Although the detection limit is 2 ng/ml in both coaxial PCL/SF nanofiber and nitrocellulose (NC) test membranes, the color intensity increased with the increasing BPA concentration in the coaxial PCL/SF nanofiber. As a new dimension, the coaxial PCL/SF nanofiber provided higher color intensity than the NC membrane. In conclusion, a sensitive onsite method was developed for the detection of BPA in breast milk by using new coaxial PCL/SF nanofiber as a test membrane in LFA.Publication Metadata only Presurgical evaluation of fontan connection options for patients with apicocaval juxtaposition using computational fluid dynamics(Wiley-Blackwell, 2013) Menon, Prahlad G.; Yoshida, Masahiro; Department of Mechanical Engineering; Pekkan, Kerem; Faculty Member; Department of Mechanical Engineering; College of Engineering; 161845Apicocaval juxtaposition (ACJ) is a rare congenital heart defect associated with single ventricle physiology where optimal positioning of the Fontan conduit for completion of total cavopulmonary connection (TCPC) is still controversial. In ACJ, the cardiac apex is ipsilateral with the inferior vena cava (IVC), risking kinking and collapse of the Fontan conduit at the apex of the heart. The purpose of this study is to evaluate two viable routes for Fontan conduit connection in patients with ACJ, using computational fluid dynamics. Internal energy loss evaluations were used to determine contribution of conduit curvature to the energy efficiency of each cavopulmonary anastomosis configuration. This percentage of energy loss contribution was found to be greater in the case of a curved extracardiac conduit connection (44%, 4.1?mW) traveling behind the ventricular apex, connecting the IVC to the left pulmonary artery, than the straighter lateral tunnel conduit (6%, 1.4?mW) installed through the ventricular apex. In contrast, net energy loss across the anastomosis was significantly lower with extracardiac TCPC (9.3?mW) in comparison with lateral tunnel TCPC (23.2?mW), highlighting that a curved Fontan conduit is favorable provided that it is traded off for a superior cavopulmonary connection efficiency. Therefore, a relatively longer and curved Fontan conduit has been demonstrated to be a suitable connection option independent of anatomical situations.Publication Metadata only Tetralogy of fallot surgical repair: shunt configurations, ductus arteriosus and the circle of willis(Springer, 2017) Unal, Gozde; Arnaz, Ahmet; Sarioglu, Tayyar; Department of Mechanical Engineering; Department of Mechanical Engineering; Pişkin, Şenol; Pekkan, Kerem; Researcher; Faculty Member; Department of Mechanical Engineering; College of Engineering; College of Engineering; 148702; 161845In 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.Publication Open Access Transition from the fetal to neonatal circulation: Modeling the effects of umbilical cord clamping(Elsevier, 2015) Yiğit, Mehmet B.; Kowalski, William J.; Hutchon, David J.R.; Department of Mechanical Engineering; Pekkan, Kerem; Faculty Member; Department of Mechanical Engineering; College of Engineering; 161845Hemodynamics of the fetal to neonatal transition are orchestrated through complex physiological changes and results in cardiovascular adaptation to the adult biventricular circulation. Clinical practice during this critical period can influence vital organ physiology for normal newborns, premature babies and congenital heart defect patients. Particularly, the timing of the cord clamping procedure, immediate (ICC) vs. delayed cord clamping (DCC), is hypothesized to be an important factor for the transitory fetal hemodynamics. The clinical need for a quantitative understanding of this physiology motivated the development of a lumped parameter model (LPM) of the fetal cardio-respiratory system covering the late-gestation to neonatal period. The LPM was validated with in vivo clinical data and then used to predict the effects of cord clamping procedures on hemodynamics and vital gases. Clinical time-dependent resistance functions to simulate the vascular changes were introduced. For DCC, placental transfusion (31.3ml) increased neonatal blood volume by 11.7%. This increased blood volume is reflected in an increase in preload pressures by ~20% compared to ICC, which in turn increased the cardiac output (CO) by 20% (CO.sub.ICC =993ml/min; CO.sub.DCC =1197ml/min). Our model accurately predicted dynamic flow patterns in vivo. DCC was shown to maintain oxygenation if the onset of pulmonary respiration was delayed or impaired. On the other hand, a significant 25% decrease in oxygen saturations was observed when applying ICC under the same physiological conditions. We conclude that DCC has a significant impact on newborn hemodynamics, mainly because of the improved blood volume and the sustained placental respiration.