Guy Mareels

Three-dimensional numerical modeling and computational fluid dynamics simulations to analyze and improve oxygen availability in the AMC bioartificial liver

A numerical model to investigate fluid flow and oxygen (O2) transport and consumption in the AMC-Bioartificial Liver (AMC-BAL) was developed and applied to two representative micro models of the AMC-BAL with two different gas capillary patterns, each combined with two proposed hepatocyte distributions. Parameter studies were performed on each configuration to gain insight in fluid flow, shear stress distribution and oxygen availability in the AMC-BAL. We assessed the function of the internal oxygenator, the effect of changes in hepatocyte oxygen consumption parameters in time and the effect of the change from an experimental to a clinical setting. In addition, different methodologies were studied to improve cellular oxygen availability, i.e. external oxygenation of culture medium, culture medium flow rate, culture gas oxygen content (pO2) and the number of oxygenation capillaries. Standard operating conditions did not adequately provide all hepatocytes in the AMC-BAL with sufficient oxygen to maintain O2 consumption at minimally 90% of maximal uptake rate. Cellular oxygen availability was optimized by increasing the number of gas capillaries and pO2 of the oxygenation gas by a factor two. Pressure drop over the AMC-BAL and maximal shear stresses were low and not considered to be harmful. This information can be used to increase cellular efficiency and may ultimately lead to a more productive AMC-BAL.

Particle image velocimetry-validated, computational fluid dynamics-based design to reduce shear stress and residence time in central venous hemodialysis catheters.

As crucial factors in blood clot formation, shear stress distribution and low flow zones are assessed in different central venous catheter tip designs by using a combined numeric and experimental approach. Computational Fluid Dynamics was validated with Particle Image Velocimetry by comparing simulated and measured velocities and shear strains in three designs of the blood withdrawing arterial lumen: cylindrical and with tip (1) cut straight, (2) cut at an angle, or (3) cut straight with a sleeve entrance. After validation, four additional designs were studied: (4) with two side holes and tip cut straight or (5) at an angle, (6) concentric lumens, and (7) Ash Split–based. In these seven designs, shear stress (SS), blood residence time (RT), and Platelet Lysis Index, which combines the influence of shear stress magnitude and exposure time, were simulated. Concentric catheter was discarded due to highly elevated SS. Ash Split–based design had elevated RT values in the distal tip zone as major inflow occurs through the most proximal side holes, but this is compensated by low average SS. A straight-cut tip and possibly two side holes are preferred when aiming at minimal SS and RT. These data may lead to more patent catheters.

Experimental and numerical modelling of the ventriculosinus shunt (El-Shafei shunt)

This study assesses malresorptive hydrocephalus treatment by ventriculosinus shunting with the shunt in the antegrade or retrograde position. First, an experimental model of the cerebral ventricles, the arachnoid villi, the cortical veins, and the superior sagittal sinus was built. For this purpose, the compliance of a human cortical vein was measured and then modelled by means of Penrose tubes. The dimensions of the superior sagittal sinus were determined in vivo by measurements on magnetic resonance imaging scans of 21 patients. Second, a numerical model of the cortical veins and the superior sagittal sinus was built. The numerical results were validated with the results from the experimental model. The experimental and numerical pressure difference between the intracranial pressure and the static sinus pressure was small (0–20 Pa) and corresponded to the theoretically expected values. No overdrainage was found in either the antegrade or the retrograde position of the shunt. Blood reflow was only found while mimicking lumbar puncture or changes in position with the experimental model (lowering the intracranial pressure or increasing the sinus pressure rapidly). Optimal results can be obtained with the shunt positioned in the most downstream half of the superior sagittal sinus. The experimental and numerical results confirm the potential of ventriculosinus shunting as therapy for malresorptive hydrocephalus patients. The ventriculosinus shunt thus proves to be a promising technique.

Experimental and numerical modelling of the ventriculo-sinus shunt to treat malresoptive hydrocephalus

This study assesses malresorptive hydrocephalus treatment by ventriculosinus (VS) shunting with the shunt in antegrade or retrograde position. First, an experimental model of the cerebral ventricles, the arachnoid villi, the cortical veins and the superior sagittal sinus (SSS) was built. For this purpose, the compliance of a human cortical vein was measured ex vivo and then modelled by means of Penrose tubes. The dimensions of the superior sagittal sinus were also determined in vivo by measurements on MRI-scans of 21 patients. Secondly, with the experimental model, a numerical model of the cortical veins and the superior sagittal sinus was validated. The experimental and numerical pressure difference between the intracranial pressure and the static sinus pressure was small (0–20 Pa) and corresponded with the theoretically expected values. No overdrainage was found in either antegrade or retrograde position of the shunt. Blood reflow was only found while mimicking lumbar puncture or changes in position with the experimental model (fast lowering the intracranial pressure respectively fast increasing the sinus pressure). Both model results confirm the potential of ventriculosinus shunting as therapy for malresorptive hydrocephalus patients. The ventriculosinus shunt thus proves to be a promising technique.Copyright

Numerical simulations of fluid flow and oxygen transport on a three-dimensional parametric model of the AMC bioartificial liver

Liver failure is a serious disease with a high mortality rate. The only efficient therapy at present is an orthotopic liver transplantation. Shortage of suitable donor livers, however, has created the need for an artificial liver that can bridge the patient to transplantation or to regeneration of the diseased liver. One possibility is the use of a bioartificial liver (BAL) in which living hepatocytes are used. It is of utmost importance that all cells are adequately perfused with plasma and that sufficient oxygen is available. Oxygen transfer is considered the main limitation in the efficiency of the BAL, particularly due to the low solubility in plasma and the high oxygen uptake rate of hepatocytes. The development of a full-scale computer model of the BAL geometry and subsequent computational fluid dynamics (CFD—Fluent) simulations could provide insight in the local flow field and oxygen availability. This information can be used to further optimize the design of the bio-artificial liver.