This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Purpose: The objectives of our computational fluid dynamics (CFD) studies are i) to optimize the orientation and design of the pediatric canullation techniques during neonatal/pediatric cardiopulmonary bypass (CPB), particularly we like to extent our current work [1] to complex reconstructive surgeries of the hypoplastic aortic arch syndrome ii) to investigate the role of flow-driven hemodynamic loading on the development of the aortic arches (abnormal loading conditions can cause complex heart defects) [2,4] (iii) to advance and enable cyber-enabled pre-surgical cardiovascular planning in complex reconstructive surgeries. Introduction and Research Aims: Coupled with the accurate reconstructions of anatomical data (via MRI, angiograms, echocardiograms and CT) CFD simulation technologies have been increasingly recognized as a surgical planning tool for the cardiovascular systems. Example studies include abdominal aortic aneurism [5-6], arterial stenosis [7], coronary arteries [8] and congenital heart diseases (CHD) [9,10]. The research interest in such patient-specific modeling CFD applications currently move from analysis towards systematic geometric optimization and require high performance computing power. To illustrate the scope of the problem, typical numbers from a standard transient anatomic 3D CFD result (n=1) which require ~125Gb of storage space for the raw data (and ~1week of CPU time in a single-PI 16 node cluster) can be considered. For each anatomy reconstruction 15 of these solutions are needed, typically for three cardiac outputs. The raw data of this CFD modeling effort alone require ~2.4Terabytes of temporary and permanent data storage systems. Referring to our first research aim, pediatric canullation constitutes a key element for the staged palliation of complex congenital heart defects which requires open heart surgeries very early in life. Prolonged cardiopulmonary bypass (CPB) usually required during these surgeries affecting 20,000 children annually. Standard CPB techniques on neonates [11] are known to be very detrimental, including higher inflammation risk, premature Circle of Willis [12], unbalanced, non-physiological organ perfusion [13, 14] resulting in temporary or permanent brain damage up to 25% of patients. Therefore, there is an urgent need to optimize the biomechanical design of pediatric/neonatal CPB circuit components, which is challenged by complex pulsatile and cavitating flows, has to be customized for the patient-specific anatomy and physiology. Our second research aim investigating the flow-driven hemodynamic loading addresses the form-flow relationship on the development of aortic arches. Although the altered (abnormal) venous flow patterns have been confirmed as the major reasons for the CHD by systematic in vivo flow visualization studies [15], engineering fluid dynamic analysis tools are recently advanced to support the quantification of these observations. Essentially, quantification of these flow alterations during the cardiac development is critical for defining the mechanism responsible for clinically prevalent heart defects (1 in 100 children) and in optimizing their in-utero and post-natal management. Recently our group has also embarked upon attempting to cyber-enabled pre-surgical cardiovascular planning by virtually modifying and optimizing anatomical MRI reconstructions at the clinic or at the bed-side using computer aided tools and simulating flow using CFD. The proposed methodology is illustrated in Figure 1. Cutting-edge high performance computing is again essential for all steps of this process namely, pre-processing, solver and post-processing. Since the pre-surgical clinical decision will be based on at least ~10 different candidate parametric anatomies for each patient the total row data of this CFD modeling effort will alone require ~24Terabytes of storage. Although the amount of CFD data generated for a single patient is quite large and at present practically inaccessible on a routine basis, there is a clear benefit for the patients health to undertake this effort. Clinically this corresponds to improved quality of life with higher cardiac outputs and better exercise tolerance. Example Methodology: Pediatric CPB: A virtual CPB is created on the 3D cardiac MRI reconstruction of a pediatric patient (Age: 12.5, BSA: 1.32m2) with a normal aortic arch by clamping the ascending aorta and inserting the computer-aided design model of the 10Fr tapered generic cannula. Cannula and aortic arch are oriented with respect to each other to simulate a typical standard pediatric CPB configuration. Pulsatile 3D blood flow velocities and pressures are computed using the commercial computational fluid dynamics (CFD) software (Fluent, ANSYS Inc.) using the 2nd order accurate experimentally validated solver [3]. Simulations are performed on a parallel Linux cluster by invoking twenty nodes each with 3.2 GHz 32 bit Intel Pentium4 processors simultaneously. Computations took approximately 72 hours to simulate three converged cycles with a period of 0.635 seconds. Cannula inlet flow waveform is measured from in vivo PC-MRI and piglet animal model physiological experiments (with DLP75010 cannula), distributed equally between the head-neck vessels and the descending aorta. This methodology will be extended to the hypoplastic heart surgeries where the cannulation has to be performed through ductus arterious due to the underdeveloped aorta anatomy, Figure 2. We also like to compute entire operating characteristics of these configurations (close to 30 individual CFD runs at different operating configurations for each patient-specific model). Embryonic Aortic Arch Development: Casts of the embryonic aortic arches are dissected from White Leghorn Eggs (at different developmental Hamburger-Hamilton stage) under fluorescent microscope and scanned with Micro-CT in order to reconstruct the 3D aortic arch anatomy. The flow domain inside the aortic arches is discretized with 500,000 tetrahedral elements using Gambit (Ansys Inc.). As an ongoing study [16], the aforementioned pulsatile 2nd Order CFD solver is employed to calculate mesh independent solution for each model representing a different developmental stage (close to 10 different development stages). Flow split boundary conditions are used at the outlets distributing the total cardiac output to dorsal aorta and cranial vessels with a ratio of 90/10. Pulsatile flow waveforms from the literature are used for each stage as plug-flow inflow boundary conditions [17]. Cyber-enabled Pre-Surgical Cardiovascular Planning: Current attempt towards the cyber-enaled pre-surgical cardiovascular planning is to translate the complex patient-specific, time-critical three-dimensional (3D) actions of the surgeon to the subsequent CFD analysis. The state-of-art human-shape sketching beacon developed by our group will enable the generation of the complex, experience driven inventions of the surgeon and evaluating their quantitative effect on flow dynamics. The current emphasis is given towards the coronary artery bypass grafts (CARBG) with 10 different surgical configurations. Preliminary Results Pediatric Cannulation: Hemodynamic parameters describing the pulsatile energetics, pressure drop, perfusion, wall shear stress and blood damage index are calculated for the CPB model. The high-speed canulla jet flow and its stagnation on the aortic wall contributed to the reduced flow pulsaility in the head neck vessels which relates to the poor cerebral perfusion observed during CBP [18]. Wall shear and hemolysis index values appear above the physiological limits which prominently demands extensive design optimization on pediatric cannulation. Concluding Remarks and Future Directions: Pediatric Cannulation: As identified in our previous study [1] drastic hemodynamic differences and intense biophysical loading of the pathological CPB configuration necessitates urgent bioengineering improvements in cannula design, perfusion flow waveform and configuration. Hence, the validated CFD model will serve as a valuable tool to document the baseline condition for different congenital disease states and a key tool for CPB cannula design and optimization. Coupled to a lumped parameter model the 3D hemodynamic characteristics will aid the surgical decision making process of the perfusion strategies in complex congenital heart surgeries. Embryonic Chick Aortic Arch: As an initial attempt to investigate and quantify the hemodynamic and anatomical changes in the aortic arch over the course of entire developmental timeline this study can be correlated with morphodynamic studies and existing gene/protein expression patterns. The proposed simulations will be used to characterize alterations in fluid dynamics, associated with cardiac development which is critical for defining the mechanism responsible for clinically prevalent heart defects. Cyber-enabled Pre-Surgical Cardiovascular Planning: The proposed virtual surgical prediction/optimization study will aid the surgical decision making process and once clinically implemented will reduce the cardiopulmonary by-pass time, improve hemodynamic outcome and eliminate trial-error during complex cardiac surgeries. In conclusion based on the growing needs of our cutting-edge research we are looking for high computing power which is beyond the limits of that is currently eligible through our university. References: 1. Pekkan K, Dur O, Kanter K, Sundareswaran K, Fogel M, Yoganathan A, Undar A, Neonatal Aortic Arch Hemodynamics and Perfusion during Cardiopulmonary Bypass, Journal of Biomechanical Engineering, in 2nd revision, 2008 2. Pekkan K., Dasi LP, Nourparvar P, Yerneni S, Tobita K, Fogel MA, Keller B, Yoganathan A, In Vitro Hemodynamic Investigation of the Embryonic Aortic Arch at Late Gestation, Journal of Biomechanics, accepted, 2008. 3. Wang C, Pekkan K, de Zlicourt D, Parihar A, Kulkarni A, Horner M, Yoganathan AP, Progress in the CFD Modeling of Flow Instability in Anatomical Total Cavopulmonary Connections, accepted, Annals of Biomedical Engineering, Nov;35(11):1840-56, 2007. (Results featured on the cover illustration) 4. Groenendijk BC, Van der Heiden K, Hierck BP, Poelmann RE. The role of shear stress on ET-1, KLF2, and NOS-3 expression in the developing cardiovascular system of chicken embryos in a venous ligation model. Physiology. 2007 Dec;22:380-9. 5. Raghavan M.L., Kratzberg, J., Castro de Tolosa, E.M., Hanaoka, M.M., Walker, P. and da Silva, E.S., Regional distribution of wall thickness and failure properties of human abdominal aortic aneurysm. J Biomech, 2005. 6. Li Z. and Kleinstreuer, C., Fluid-structure interaction effects on sac-blood pressure and wall stress in a stented aneurysm. J Biomech Eng, 2005. 127(4): p. 662-71. 7. Vsrghese, S., and Frankel, S., 2003, Numerical Modeling of Pulsatile Turbulent Flow in a Stenosed Tube, ASME J. Biomech. Eng,. 126, pp. 625-635. 8. Toriia, R., Wooda, N. B., Hughesb, A. D., Thomb, S. A., Aguado-Sierrac, J., Daviesb, J. E., Francisb, D. P., Parkerc, K. H., and Xua, X. Y., 2007, 'A computational study on the influence of catheter-delivered intravascular probes on blood flow in a coronary artery model,' Journal of Biomechanics, in press. 9. de Zelicourt D.A., Pekkan, K.,Parks, J.,Kanter, K.,Fogel, M.,Yoganathan, A. P., Flow study of an extracardiac connection with persistent left superior vena cava. J Thorac Cardiovasc Surg, 2006. 131(4): p. 785-91. 10. Pekkan K., Kitajima, H.D., de Zelicourt, D., Forbess, J.M., Parks, W.J., Fogel, M.A., Sharma, S., Kanter, K.R., Frakes, D. and Yoganathan, A.P., Total cavopulmonary connection flow with functional left pulmonary artery steno angioplasty and fenestration in vitro. Circulation, 2005. 112(21): p. 3264-71. 11. Ungerleider, R. M., 2005, 'Practice Patterns in Neonatal Cardiopulmonary Bypass,' Asaio J, 51(6), pp. 813-815. 12. Papantchev V, H. S., Todorova D, Naydenov E, Paloff A, Nikolov D,, and Tschirkov A, O. W., 2007, 'Some variations of the circle of Willis, important for cerebral protection in aortic surgery - a study in Eastern Europeans,' Eur J Cardiothorac Surg., 31(6), pp. 982-989. 13. Schumacher, J., Eichler, W., Heringlake, M., Sievers, H. H., and Klotz, K. F., 2004, 'Intercompartmental fluid volume shifts during cardiopulmonary bypass measured by A-mode ultrasonography,' Perfusion, 19(5), pp. 277-281. 14. Undar, A., Vaughn, W. K., and Calhoon, J. H., 2000, 'The effects of cardiopulmonary bypass and deep hypothermic circulatory arrest on blood viscoelasticity and cerebral blood flow in a neonatal piglet model,' 15, pp. 121-128. 15. Hogers, B., DeRuiter, M. C., Baasten, A. M., Gittenberger-de Groot, A. C., and Poelmann, R. E., 1995, 'Intracardiac blood flow patterns related to the yolk sac circulation of the chick embryo,' Circulation research, 76(5), pp. 871-877. 16. Yajuan Wang, Onur Dur, Michael J. Patrick, Joseph P. Tinney, Kimimasa Tobita, Kerem Pekkan, Bradley B. Keller.Hemodynamic Investigation of Normal Developing Aortic Arch in the Chick Aortic Arch in the Chick Embryo, Bypass. ASME Summer Conference 2008 17. Hu N, Clark EB. Hemodynamics of the stage 12 to stage 29 chick embryo. Circ Res. 1989 Dec;65(6):1665-70. 18. Undar, A., Vaughn, W. K., and Calhoon, J. H. The effects of cardiopulmonary bypass and deep hypothermic circulatory arrest on blood viscoelasticity and cerebral blood flow in a neonatal piglet model, 2000, 15, pp. 121-128.
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