EXTH-21. INTRAINFUSION CATHETER MOVEMENT FACILITATES INCREASED INFUSATE VOLUME DISPERSED IN AGAROSE GEL

Abstract Glioblastoma has a 5 year survival of only 5.5% and a median patient survival of 12 to 15 months even with gold standard treatment. One potential method of improving treatment of glioblastoma is the use of convection-enhanced delivery (CED) which utilizes local delivery of therapeutics to the brain. However, clinical trials have shown an inability of standard catheters to deliver therapeutics to the entire target area. In this study, we explore the potential of controlled catheter movement to increase the volume dispersed (Vd) of indigo carmine dye in agarose gel brain tissue phantoms. We use four catheter control protocols: stationary, continuous retraction, continuous insertion, and intermittent insertion using a single port stepped catheter. The continuous retraction group resulted in consistent catheter clogging caused by the continued insertion of the catheter and therefore was removed from further analysis. Vd and backflow distance was quantified for all other catheter movement protocols using optical images captured throughout the infusion. Catheter retraction resulted in an increase in Vd of 51% while intermittent insertion resulted in a Vd increase of 24% compared to the stationary catheter. Additionally, a 37% reduction in backflow distance was seen with the retracting catheter when compared to the stationary catheter. These results are further supported by a simplified computational model that we have created. The computational model simulates the infusion of indigo carmine dye through an agarose gel brain tissue phantom and shows an increase in Vd of over 100% with catheter retraction. The increased Vd and decreased backflow distance afforded by the retracting catheter, suggests that the use of catheter movement may be a useful technique in increasing drug dispersal in tumorous tissue. Additional work in live and excised tissue should be conducted to confirm these results and an exploration of optimal needle movement protocols is necessary.

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

Pharmaceutics ◽

10.3390/pharmaceutics12080753 ◽

2020 ◽

Vol 12 (8) ◽

pp. 753

Author(s):

Jason N. Mehta ◽

Gabrielle R. McRoberts ◽

Christopher G. Rylander

Keyword(s):

Brain Tissue ◽

Indigo Carmine ◽

Movement Control ◽

Brain Parenchyma ◽

Agarose Gel ◽

Convection Enhanced Delivery ◽

Forward Flow ◽

Needle Tract ◽

Tissue Phantoms ◽

Catheter Design

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.

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Computational Model of a Two Material Object Predicts Non-Symmetric Dispersal Volume Profile

2021 Design of Medical Devices Conference ◽

10.1115/dmd2021-1087 ◽

2020 ◽

Author(s):

Brianna E. Morales ◽

Jason N. Mehta ◽

Christopher G. Rylander

Keyword(s):

Computational Model ◽

Transient State ◽

Material Object ◽

Target Area ◽

Convection Enhanced Delivery ◽

Catheter System ◽

Volume Profile ◽

High Concentrations ◽

Localized Treatment ◽

The Brain

Abstract Convection-enhanced delivery (CED) is an experimental method of localized treatment to release high concentrations of the drug into a target area. An implementation of CED by our lab is the convection-enhanced thermo-therapy catheter system (CETCS). The device is a collection of arborizing microneedles used to affect a broader coverage of a dispersed volume in the regions of interest. We suspect the coverage of the dispersal volume depends on the material properties of the brain the infusate is being administered. In this study, we create a computational model to evaluate how two adjacent materials with varying permeability (4.45 mm4 N-1 s-1 with 13.35 or 35.6 mm4 N-1 s-1) will disperse into a 0.6% (w/w) agarose gel. Transient state analysis was conducted using the FEBio Software Suite. As expected, results show a much larger dispersal volume in the material with the higher permeability and along the border of the two materials.

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