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Three-dimensional nonlinear finite element model to estimate backflow during flow-controlled infusions into the
Gustavo A Orozco1, Joshua H Smith2, José J García3
1Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
Summary
Convection-enhanced delivery can be improved by considering brain anatomy. Optimizing infusion placement and accounting for ventricular pressure can reduce drug backflow and enhance delivery efficiency.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Medical Physics
Background:
- Convection-enhanced delivery (CED) aims to bypass the blood-brain barrier for drug delivery.
- Clinical trials show reduced efficacy due to fluid backflow, where infused drugs move away from the target tissue.
- Backflow is primarily caused by an annular gap around the catheter, redirecting flow towards the brain surface.
Purpose of the Study:
- To develop a 3D finite element model of the human brain to investigate backflow during CED.
- To analyze the influence of anatomical structures on fluid flow and drug distribution.
- To evaluate the impact of ventricular pressure and cannula-ventricle distance on backflow length.
Main Methods:
- Development of a three-dimensional finite element model of the human brain.
- Simulation of flow-controlled infusions under varying conditions.
- Comparison of predicted backflow lengths with different ventricular pressures and cannula-ventricle distances.
Main Results:
- Zero relative ventricular pressure resulted in similar backflow lengths for larger cannula-ventricle distances.
- Infusions near ventricles showed reduced backflow, with fluid escaping into fissures and cavities.
- Increased cannula-ventricle distance and non-zero ventricular pressure enhanced fluid flow through brain tissue.
Conclusions:
- Subject-specific anatomical details are crucial for accurate CED modeling.
- Non-linear effects, such as ventricular pressure, significantly influence drug distribution.
- Optimizing infusion parameters based on individual anatomy and pressure dynamics is vital for future CED clinical trials.
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