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. 2021 Feb 1;4(1):011003.
doi: 10.1115/1.4048935. Epub 2020 Dec 2.

Convection-Enhanced Arborizing Catheter System Improves Local/Regional Delivery of Infusates Versus a Single-Port Catheter in Ex Vivo Porcine Brain Tissue

Egleide Y Elenes  1 , Jason N Mehta  2 , Fang-Chi Hsu  3 , Christopher T Whitlow  4 , Waldermar Debinski  5 , John Rossmeisl  6 , Stephen Tatter  7 , Christopher G Rylander  2
Affiliations
Free PMC article

Convection-Enhanced Arborizing Catheter System Improves Local/Regional Delivery of Infusates Versus a Single-Port Catheter in Ex Vivo Porcine Brain Tissue

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

Abstract

Standard treatment for glioblastoma is noncurative and only partially effective. Convection-enhanced delivery (CED) was developed as an alternative approach for effective loco-regional delivery of drugs via a small catheter inserted into the diseased brain. However, previous CED clinical trials revealed the need for improved catheters for controlled and satisfactory distribution of therapeutics. In this study, the arborizing catheter, consisting of six infusion ports, was compared to a reflux-preventing single-port catheter. Infusions of iohexol at a flow rate of 1 μL/min/microneedle were performed, using the arborizing catheter on one hemisphere and a single-port catheter on the contralateral hemisphere of excised pig brains. The volume dispersed (Vd) of the contrast agent was quantified for each catheter. Vd for the arborizing catheter was significantly higher than for the single-port catheter, 2235.8 ± 569.7 mm3 and 382.2 ± 243.0 mm3, respectively (n = 7). Minimal reflux was observed; however, high Vd values were achieved with the arborizing catheter. With simultaneous infusion using multiple ports of the arborizing catheter, high Vd was achieved at a low infusion rate. Thus, the arborizing catheter promises a highly desirable large volume of distribution of drugs delivered to the brain for the purpose of treating brain tumors.

Keywords: convection-enhanced delivery; drug delivery; glioblastoma; intracranial infusion; volume dispersed.

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Figures

(a) Drawing of the two components of the fixture for manufacturing the cannula of the arborizing catheter. (b) View of assembled fixture holding and bending the PEEK tubing in place for bonding.
Fig. 1
(a) Drawing of the two components of the fixture for manufacturing the cannula of the arborizing catheter. (b) View of assembled fixture holding and bending the PEEK tubing in place for bonding.
(a) Image shows an arborizing catheter and single-port catheter. (b) Magnified image of distal ends of the catheters showing microneedle deflection in the arborizing catheter and the reflux-arresting step change for the respective catheters. (c) Measured angles for the arborizing catheter. Phi (φ) was defined as the angle along the axes of two adjacent needles. Theta (θ) was defined as the angle of deflection of each microneedle in reference to the axis of the cannula.
Fig. 2
(a) Image shows an arborizing catheter and single-port catheter. (b) Magnified image of distal ends of the catheters showing microneedle deflection in the arborizing catheter and the reflux-arresting step change for the respective catheters. (c) Measured angles for the arborizing catheter. Phi (φ) was defined as the angle along the axes of two adjacent needles. Theta (θ) was defined as the angle of deflection of each microneedle in reference to the axis of the cannula.
(a) Diagram of fixture used to secure arborizing catheter and single-port catheter. The backplate and frontplate support and guide the microneedles (b) axial view of specimen demonstrating the arrangement of pressure sensors within each catheter. For the arborizing catheter, each dot represents the distal end of the microneedles fully deployed. Illustration not to scale.
Fig. 3
(a) Diagram of fixture used to secure arborizing catheter and single-port catheter. The backplate and frontplate support and guide the microneedles (b) axial view of specimen demonstrating the arrangement of pressure sensors within each catheter. For the arborizing catheter, each dot represents the distal end of the microneedles fully deployed. Illustration not to scale.
Grayscale intensity values versus concentration. A concentration of 10% was selected for the lower bound grayscale threshold for selecting voxels of interest.
Fig. 4
Grayscale intensity values versus concentration. A concentration of 10% was selected for the lower bound grayscale threshold for selecting voxels of interest.
Volumetric segmentation with avizo. (a) Voxels with grayscale value corresponding to ≥ 10% of iohexol concentration were selected to derive Vd for the single-port catheter (blue) and arborizing catheter (red). The volume of solution that leaked into the ventricles was segmented into a separate mask (green). (b) Volumetric rendering of the brain and Vd for each group. (c) Volumetric rendering showing infusion volumes for the single-port catheter and the arborizing catheter after removing ventricular leakage from image.
Fig. 5
Volumetric segmentation with avizo. (a) Voxels with grayscale value corresponding to ≥ 10% of iohexol concentration were selected to derive Vd for the single-port catheter (blue) and arborizing catheter (red). The volume of solution that leaked into the ventricles was segmented into a separate mask (green). (b) Volumetric rendering of the brain and Vd for each group. (c) Volumetric rendering showing infusion volumes for the single-port catheter and the arborizing catheter after removing ventricular leakage from image.
(a) Box plot demonstrating dispersed volume (Vd) for the arborizing catheter, single-port catheter, and leakage of the contrast agent into the ventricles. The outlier corresponds to the specimen, which had two microneedles of the arborizing catheter outside of the brain tissue. (b) Box plot of mean distribution ratio (Vd:Vi) for the arborizing catheter and the single-port catheter.
Fig. 6
(a) Box plot demonstrating dispersed volume (Vd) for the arborizing catheter, single-port catheter, and leakage of the contrast agent into the ventricles. The outlier corresponds to the specimen, which had two microneedles of the arborizing catheter outside of the brain tissue. (b) Box plot of mean distribution ratio (Vd:Vi) for the arborizing catheter and the single-port catheter.
Histogram of the voxel percent (ratio) against concentration percent where the blue section represents a larger average percent of voxels with the single-port catheter, the red represents the arborizing catheter having a larger average percent of voxels, and the purple is the overlap between the single-port catheter and the arborizing catheter
Fig. 7
Histogram of the voxel percent (ratio) against concentration percent where the blue section represents a larger average percent of voxels with the single-port catheter, the red represents the arborizing catheter having a larger average percent of voxels, and the purple is the overlap between the single-port catheter and the arborizing catheter
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