(D-129) Coupled Fluid Flow and Vessel Wall Analysis in Patients with Sickle Cell Disease and Pulmonary Hypertension

Sickle cell disease is a genetic disease which is caused by a single amino acid substitution in the beta globin subunit. Under hypoxic conditions, polymerization of HbS leads to sickling and stiffening of red blood cells. [1, 2] Sickle cell disease involves recurrent events of hemolysis and vaso-occlusion. Hemolysis promotes development of pulmonary hypertension (PH). Pulmonary hypertension because of sickle cell disease is characterized by a mean pulmonary arterial pressure >20 mm Hg. [3] Pulmonary hypertension has a prevalence of 10% to 33% in sickle cell disease (SCD) patients based on data from right heart catheterization or echocardiography. [4] Mortality risk increases in SCD patients who develop diastolic heart failure and pulmonary hypertension. [5] In a study by Nebor et al. [6] whole blood viscosity of subjects with mild and severe sickle cell anemia and control subjects was measured at moderate (46 s^-1) and high (230 s^-1) shear rates. Based on their results whole blood viscosity is lower in SCD groups. Also subjects with severe sickle cell disease revealed higher blood viscosity than mild SCD subjects. The blood viscosity at high shear rate was 3.18±0.76 mPa/s for control subjects, 1.87±0.75 mPa/s for mild SCD subjects and 2.38±0.41 mPa/s for severe SCD subjects. [6] The aim of this study is to obtain time averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) as the hemodynamic markers from the fluid -structure interaction simulations of SCD subjects with and without PH and compare the results of normal and disease specific blood viscosities.

This study was approved by the institutional review board of East Carolina University, UMCIRB 11-0275. Two subjects were considered for this study. Subject 1 has sickle cell disease, subject 2 has sickle cell disease and pulmonary hypertension. Two different sets of images were used for each subject to create the geometry and the inlet velocity waveforms. The image acquisition was carried out on a Siemens Espree 1.5 T for subject 1 and Siemens Aera 1.5 T model MR scanner for subjects 2. The patient specific pulmonary artery geometries were reconstructed using the segmentation techniques in Mimics 20.0 (Materialise, Inc., Plymouth, MI). The solid models were then imported into ANSYS Workbench (ANSYS, Inc., Canonsburg, PA) where the arterial wall thickness was added in Spaceclaim and the computational mesh was generated. The coupled fluid structure interaction simulations were set up using Fluent and transient structural modules of Ansys Workbench. Both the fluid and solid domains were examined for mesh convergence. The blood was taken to be a non-Newtonian fluid with a normal viscosity of 3.5 mPa/s and a SCD viscosity of 1.87 mPa/s based on Nebor et al. [6] and a density of 1060kg/m³. The solid domain was modeled as a linear elastic material with modulus of elasticity of 2 MPa and Poisson’s ratio of 0.48. [7] The transient velocity waveform was implemented at the inlet boundary and the outlets were taken to be zero pressure gradient outlets. In the structural model the inlet and outlets were assumed to be fixed. 

Time averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) were obtained from the fluid-structure interaction simulations of two subjects. The effect of normal and disease specific values of blood viscosity on the results were examined. The solution data over three cardiac cycles were averaged to calculate TAWSS and OSI. Oscillatory shear index is a measure of change of direction of wall shear stress vector relative to the blood flow. The range of OSI is between 0 and 0.5 where a value of 0 shows that wall shear stress vector does not change direction over time and value of 0.5 represents an oscillatory flow.[8] TAWSS contours with normal and SCD viscosities are shown in figure (1) for subject 1 and OSI contours are shown in figure (2). For subject 1, maximum TAWSS was observed to be 36.25 Pa for normal viscosity and 25.47 Pa for SCD viscosity. For subject 2, the maximum TAWSS was 3.77 Pa for normal viscosity and 2.85 Pa for SCD viscosity. Therefore, using SCD viscosity in FSI simulations resulted in about 30% decrease in maximum TAWSS values for both subjects. For OSI, maximum values of 0.41 and 0.49 were observed when normal and SCD viscosities were used in FSI simulations of subject 1 and 0.44 and 0.47 for subject 2. Larger values of TAWSS and lower values of OSI were observed for both subjects when normal viscosity is used compared to SCD viscosity. Also for subject 2, which has pulmonary hypertension with larger pulmonary artery and lower values of inlet velocity, lower TAWSS and higher values of OSI were observed. The subjects in this study were assumed to have mild sickle cell disease, data about the severity of SCD could be helpful to use the appropriate blood viscosity and improve the results. Comparing results from these FSI simulations with previously obtained results from CFD simulations of subjects 1 and 2 shows negligible difference in maximum TAWSS values. Future work could incorporate a hyperplastic material model for the vessel wall which may be advantageous as the model is more physiologically representative.

The authors would like to thank Constantin B. Marcu, MD for image acquisition. This work was supported in part by the Division of Research, Economic Development, and Engagement, East Carolina University.

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