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. 2019 Aug;2(3):0310021-310029.
doi: 10.1115/1.4042874. Epub 2019 Apr 1.

Parametric Study of the Design Variables of an Arborizing Catheter on Dispersal Volume Using a Biphasic Computational Model

Egleide Y Elenes  1 , Manuel K Rausch  2 , Christopher G Rylander  3
Affiliations
Free PMC article

Parametric Study of the Design Variables of an Arborizing Catheter on Dispersal Volume Using a Biphasic Computational Model

Egleide Y Elenes et al. J Eng Sci Med Diagn Ther. 2019 Aug.
Free PMC article

Abstract

Convection-enhanced delivery (CED) is an investigational therapy developed to circumvent the limitations of drug delivery to the brain. Catheters are used in CED to locally infuse therapeutic agents into brain tissue. CED has demonstrated clinical utility for treatment of malignant brain tumors; however, CED has been limited by lack of CED-specific catheters. Therefore, we developed a multiport, arborizing catheter to maximize drug distribution for CED. Using a multiphasic finite element (FE) framework, we parametrically determined the influence of design variables of the catheter on the dispersal volume of the infusion. We predicted dispersal volume of a solute infused in a permeable hyperelastic solid matrix, as a function of separation distance (ranging from 0.5 to 2.0 cm) of imbedded infusion cavities that represented individual ports in a multiport catheter. To validate the model, we compared FE solutions of pressure-controlled infusions to experimental data of indigo carmine dye infused in agarose tissue phantoms. The Tc50, defined as the infusion time required for the normalized solute concentration between two sources to equal 50% of the prescribed concentration, was determined for simulations with infusion pressures ranging from 1 to 4 kPa. In our validated model, we demonstrate that multiple ports increase dispersal volume with increasing port distance but are associated with a significant increase in infusion time. Tc50 increases approximately tenfold when doubling the port distance. Increasing the infusion flow rate (from 0.7 μL/min to 8.48 μL/min) can mitigate the increased infusion time. In conclusion, a compromise of port distance and flow rate could improve infusion duration and dispersal volume.

Keywords: agarose gel; biphasic finite element analysis; convection-enhanced delivery; infusion; multiport catheter; solute transport.

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Figures

Fig. 1
Fig. 1
Schematic of the arborizing catheter, showing multiple ports or microneedles deflected from the primary cannula
Fig. 2
Fig. 2
(a) FE model geometry of the biphasic solid with two embedded infusion cavities (i.e., source ports) and (b) constant infusion pressure applied at a rapid ramp time of t0 and constant effective solute concentration were applied at the inner surface boundary of the infusion cavities. Zero interstitial pressure and traction free surface boundary conditions were applied at the outer boundaries of the solid.
Fig. 3
Fig. 3
(a) Indigo carmine stock solution (5% w/w) was serially diluted from 1:100 in an agarose solution and plotted as percentages versus their corresponding grayscale intensity threshold values from postprocessed images and (b) volume dispersed, Vd (milliliter), plotted versus time (minutes) for FE simulations compared to infusion experiments (Exp) for two flow rates (1 μL/min and 7 μL/min)
Fig. 4
Fig. 4
Prescribed infusion pressure versus resultant average infusion flow rates. Flow rates were calculated after the pressure was applied at a rapid ramp to the boundary of the infusion cavity.
Fig. 5
Fig. 5
Representative color maps for simulation with source ports (infusion cavities) spaced 1.5 cm apart for infusion pressures ranging from 1 kPa to 4 kPa. The color map shows the normalized effective solute concentration at time = 300 min.
Fig. 6
Fig. 6
Time (hours) required for the normalized effective concentration between sources to reach 50% of the prescribed concentration at the sources (Tc50) versus the port separation distance, d (centimeter)
Fig. 7
Fig. 7
Time to reach a concentration overlap (ranging from 0.1 to 0.5 of the normalized effective solute concentration) midway between two sources for port separation distance ranging from 0.5 to 2.0 cm
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