Controlled Catheter Movement Affects Dye Dispersal Volume in Agarose Gel Brain Phantoms.

Christopher G Rylander,Jason N Mehta,Gabrielle R Mcroberts

doi:10.3390/pharmaceutics12080753

Christopher G Rylander, Jason N Mehta + Show 1 more

Open Access

https://doi.org/10.3390/pharmaceutics12080753

Copy DOI

Abstract

The standard of care for treatment of glioblastoma results in a mean survival of only 12 to 15 months. Convection-enhanced delivery (CED) is an investigational therapy to treat glioblastoma that utilizes locoregional drug delivery via a small-caliber catheter placed into the brain parenchyma. Clinical trials have failed to reach their endpoints due to an inability of standard catheters to fully saturate the entire brain tumor and its margins. In this study, we examine the effects of controlled catheter movement on dye dispersal volume in agarose gel brain tissue phantoms. Four different catheter movement control protocols (stationary, continuous retraction, continuous insertion, and intermittent insertion) were applied for a single-port stepped catheter capable of intrainfusion movement. Infusions of indigo carmine dye into agarose gel brain tissue phantoms were conducted during the controlled catheter movement. The dispersal volume (Vd), forward dispersal volume (Vdf), infusion radius, backflow distance, and forward flow distance were quantified for each catheter movement protocol using optical images recorded throughout the experiment. Vd and Vdf for the retraction and intermittent insertion groups were significantly higher than the stationary group. The stationary group had a small but significantly larger infusion radius than either the retracting or the intermittent insertion groups. The stationary group had a greater backflow distance and lower forward flow distance than either the retraction or the intermittent insertion groups. Continuous retraction of catheters during CED treatments can result in larger Vd than traditional stationary catheters, which may be useful for improving the outcomes of CED treatment of glioblastoma. However, catheter design will be crucial in preventing backflow of infusate up the needle tract, which could significantly alter both the Vd and shape of the infusion.

Highlights

Glioblastoma is a highly infiltrative brain tumor with margins that typically extend centimeters beyond the visible tumor [1]
In order to bypass the blood–brain barrier (BBB) and overcome the limitations of diffusive delivery of drugs, Bobo et al proposed the use of convection-enhanced delivery (CED) [10]
Unlike the previous work mentioned, in this study we examine the effects of continuous remote retraction and insertion, intermittent insertion, and stationary catheter infusions on volume dispersed (Vd) in agarose gel brain tissue phantoms

Summary

Introduction

Glioblastoma is a highly infiltrative brain tumor with margins that typically extend centimeters beyond the visible tumor [1]. Even combinatory therapy, which uses multiple standard-of-care treatments, has resulted in only moderate improvement in overall patient survival [7], and the tumor generally recurs at or near the site of the original tumor location [8,9]. CED uses locoregional delivery of therapeutics to bypass the BBB by inserting a small caliber catheter though a burr hole in the skull and directly into the brain parenchyma. This technique utilizes pressure-driven flow to deliver large amounts of therapeutics directly to the region of interest [10,11]. Drug infusion times can range from a few hours to several days [12]

Methods

Results

Discussion

Conclusion