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

Pharmaceutics. 2020 Aug 11;12(8):753. doi: 10.3390/pharmaceutics12080753.

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.

Keywords: catheter movement; convection-enhanced delivery; dispersal volume; glioblastoma.