Research Project: Full name of the project
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Contributors
Funders
ID
EC.00050
Authors
Pekkan, Kerem
Faculty Member
Publications
Computational modeling of vascular growth in patient-specific pulmonary arterial patch reconstructions
(Elsevier, 2021) Lashkarinia, Seyedeh Samaneh; Pekkan, Kerem; Coban, Gursan; Kose, Banu; Salihoglu, Ece; Department of Mechanical Engineering; Yes; College of Engineering
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.
Asymmetry in mechanosensitive gene expression during aortic arch morphogenesis
(Nature Publishing Group (NPG), 2018) Çelik, Merve; Göktaş, Selda; Karakaya, Cansu; Pekkan, Kerem; Kowalski, William J.; Keller, Bradley B.; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Yes; College of Engineering; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
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.
A novel Fontan Y-graft for interrupted inferior vena cava and azygos continuation
(Oxford University Press (OUP), 2022) Lashkarinia, Seyedeh Samaneh; Pekkan, Kerem; Rasooli, Reza; Rezaeimoghaddam, Mohammad; Çicek, Murat; Köse, Banu; Yılmaz, Emine Hekim; Aydemir, Numan Ali; Özkök, Serçin; Yurtseven, Nurgül; Erdem, Hasan; Sasmazel, Ahmet; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Yes; College of Engineering; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
Objectives: to evaluate the hemodynamicdynamic advantage of a new Fontan surgical template that is intended for complex single-ventricle patients with interrupted inferior vena cava-azygos and hemi-azygos continuation. The new technique has emerged from a comprehensive pre-surgical simulation campaign conducted to facilitate a balanced hepatic flow and somatic Fontan pathway growth after Kawashima procedure. Methods: for 9 patients, aged 2 to 18 years, majority having poor preoperative oxygen saturation, a pre-surgical computational fluid dynamics customization is conducted. Both the traditional Fontan pathways and the proposed novel Y-graft templates are considered. Numerical model was validated against in vivo phase-contrast magnetic resonance imaging data and in vitro experiments. Results: the proposed template is selected and executed for 6 out of the 9 patients based on its predicted superior hemodynamic performance. Pre-surgical simulations performed for this cohort indicated that flow from the hepatic veins (HEP) do not reach to the desired lung. The novel Y-graft template, customized via a right- or left-sided displacement of the total cavopulmonary connection anastomosis location resulted a drastic increase in HEP flow to the desired lung. Orientation of HEP to azygos direct shunt is found to be important as it can alter the flow pattern from 38% in the caudally located direct shunt to 3% in the cranial configuration with significantly reversed flow. The postoperative measurements prove that oxygen saturation increased significantly (P-value = 0.00009) to normal levels in 1 year follow-up. Conclusions: the new Y-graft template, if customized for the individual patient, is a viable alternative to the traditional surgical pathways. This template addresses the competing hemodynamic design factors of low physiological venous pressure, high postoperative oxygen saturation, low energy loss and balanced hepatic growth factor distribution possibly assuring adequate lung development.
Motile-cilia-mediated flow improves sensitivity and temporal resolution of olfactory computations
(Cell Press, 2017) Pekkan, Kerem; Uslu, Fazıl Emre; Reiten, Ingrid; Fore, Stephanie; Pelgrims, Robbrecht; Ringers, Christa; Verdugo, Carmen Diaz; Hoffman, Maximillian; Lal, Pradeep; Kawakami, Koichi; Yaksi, Emre; Jurisch-Yaksi, Nathalie; Department of Mechanical Engineering; Yes; College of Engineering
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.
Computer modeling for the prediction of thoracic aortic stent graft collapse
(Elsevier, 2013) Pekkan, Kerem; Pasta, Salvatore; Cho, Jae-Sung; Dur, Onur; Vorp, David A.; Department of Mechanical Engineering; Yes; College of Engineering
Objective: To assess the biomechanical implications of excessive stent protrusion into the aortic arch in relation to thoracic aortic stent graft (TASG) collapse by simulating the structural load and quantifying the fluid dynamics on the TASG wall protrusion extended into a model arch. Methods: One-way coupled fluid-solid interaction analyses were performed to investigate the flow-induced hemodynamic and structural loads exerted on the proximal protrusion of the TASG and aortic wall reconstructed from a patient who underwent traumatic thoracic aortic injury repair. Mechanical properties of a Gore TAG thoracic endoprosthesis (W. L. Gore and Assoc, Flagstaff, Ariz) were assessed via experimental radial compression testing and incorporated into the computational modeling. The TASG wall protrusion geometry was characterized by the protrusion extension (PE) and by the angle (q) between the TASG and the lesser curvature of the aorta. The effect of q was explored with the following four models with PE fixed at 1.1 cm: q [ 10 degrees, 20 degrees, 30 degrees, and 40 degrees. The effect of PE was evaluated with the following four models with q fixed at 10 degrees: PE [ 1.1 cm, 1.4 cm, 1.7 cm and 2.0 cm. Results: The presence of TASG wall protrusion into the aortic arch resulted in the formation of swirling, complex flow regions in the proximal luminal surface of the endograft. High PE values (PE [ 2.0 cm) led to a markedly reduced left subclavian flow rate (0.27 L/min), low systolic perfusion pressure (98 mm Hg), and peak systolic TASG diameter reduction (2 mm). The transmural pressure load across the TASG was maximum for the model with the highest PE and q, 15.2 mm Hg for the model with PE [ 2.0 cm and q [ 10 degrees, and 11.6 mm Hg for PE [ 1.1 cm and q [ 40 degrees. Conclusions: The findings of this study suggest that increased PE imparts an apparent risk of distal end-organ malperfusion and proximal hypertension and that both increased PE and q lead to a markedly increased transmural pressure across the TASG wall, a load that would portend TASG collapse. Patient-specific computational modeling may allow for identification of patients with high risk of TASG collapse and guide preventive intervention.
