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

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.

Convection‐enhanced delivery with controlled catheter movement: A parametric finite element analysis

“…This can be accomplished in a similar method presented by Orozco et al 43,44 It should also be noted that the model presented here utilizes material properties based on agarose gel and indigo carmine dye in order to validate the model with experimental results conducted in agarose. However, despite its common use as a surrogate to brain tissue, 23,25,26,[55][56][57][58][59] the homogeneous nature of agarose cannot replicate the true heterogeneous and non-isotropic features of brain tissue including blood vessels and ventricles which are known to distort the dispersal volume shape. 60…”

“…25 We have recently shown that controlled catheter retraction at a rate of 0.25 mm/min can result in an increase in V d by 50% in an agarose gel model. 26 Additionally, we have shown that the use of constant pressure infusions coupled with controlled catheter retraction can result in an increase in V d of 94% and 143% with 0.25 and 0.5 mm/min catheters, respectively. 27 Our objective is to use a computational model to parametrically understand the role of catheter retraction rate on the overall efficacy of controlled catheter movement in CED infusions.…”

Convection Enhanced Delivery in the Setting of High-Grade Gliomas

“…The continuous retraction and intermittent insertion protocols showed significantly higher volumes of distribution than traditional stationary catheters, which were found to have greater backflow and lower forward flow distances. This highlights how tumor coverage can be improved by using dynamic catheters 68 . Apart from infusate reflux, cerebral catheters can also become obstructed during chronic CED.…”

Convection Enhanced Delivery in the Setting of High-Grade Gliomas

“…The continuous retraction and intermittent insertion protocols showed significantly higher volumes of distribution than traditional stationary catheters, which were found to have greater backflow and lower forward flow distances. This highlights how tumor coverage can be improved by using dynamic catheters [ 73 ]. Apart from infusate reflux, cerebral catheters can also become obstructed during chronic CED.…”