Image-guided Convection-enhanced Delivery into Agarose Gel Models of the Brain

Abstract

Convection-enhanced delivery (CED) has been proposed as a treatment option for a wide range of neurological diseases. Neuroinfusion catheter CED allows for positive pressure bulk flow to deliver greater quantities of therapeutics to an intracranial target than traditional drug delivery methods. The clinical utility of real time MRI guided CED (rCED) lies in the ability to accurately target, monitor therapy, and identify complications. With training, rCED is efficient and complications may be minimized. The agarose gel model of the brain provides an accessible tool for CED testing, research, and training. Simulated brain rCED allows practice of the mock surgery while also providing visual feedback of the infusion. Analysis of infusion allows for calculation of the distribution fraction (Vd/Vi) allowing the trainee to verify the similarity of the model as compared to human brain tissue. This article describes our agarose gel brain phantom and outlines important metrics during a CED infusion and analysis protocols while addressing common pitfalls faced during CED infusion for the treatment of neurological disease. Video LinkThe video component of this article can be found at

Convection-Enhanced Delivery

“…The shear forces in the tissue balance the pressure field and retrograde axial flow stops. Both types of backflow can be issues in that they allow infusate to exit the target, causing spreading of the agent into unintended areas of the brain [39,40]. This can lead to a decrease in the dose, and can be especially detrimental during cortical infusions, as it may lead to spread into the subarachnoid space with subsequent widespread distribution through the CSF [16].…”

“…The causes of backflow are myriad, but it has been associated with the presence of air bubbles, pressure spikes during the infusion, the catheter insertion technique, and the catheter design. Soft catheters are less likely to cause mechanical disruption and thus backflow [40]. Also, the use of a thin catheter has been shown to be beneficial in overcoming backflow [14], and new Bstep-design^catheters have been developed to overcome the issues associated with a thin catheter (i.e., floppiness) [41].…”

“…Also, the use of a thin catheter has been shown to be beneficial in overcoming backflow [14], and new Bstep-design^catheters have been developed to overcome the issues associated with a thin catheter (i.e., floppiness) [41]. In addition, porousmembrane catheters and valve-tip catheter designs have been thought to alleviate occlusions at the end port, thus decreasing pressure spikes and resultant backflow [40].…”

“…Air bubbles are not inherently a health hazard, but they can disrupt the flow of the infused agent causing unpredictable flow patterns, and can also contribute to backflow [40]. Additionally, air presents an obstacle when attempting to use image guidance for real time monitoring, which is an important step in the effective deployment of CED.…”

“…Air in the infusion line can alter the local measurement of the infusion pressure as well as the volume of the dye being used. In addition, it may cause local tissue disruption, thus affecting distribution of the infusate [40]. Priming the cannula before insertion into the brain prevents air bubbles from occurring at the end of the catheter tip [42].…”