The best magazine
Leakage of Infusates during CED
In the ideal scenario, agents delivered through CED should be contained within the targeted area of the CNS. Studies both in humans and experimental animals have shown widespread distribution of the infusate, such as labeled liposomes into various regions of the brain. Infused agents may leave targeted areas, such as tumors, and leak into either the ventricles or sulci. This is undesirable because it results in waste in terms of the therapeutic agent and an inadvertent opportunity for more intense, direct and potentially adverse interactions of drugs with the normal the CNS. The frequency of the leakage is substantial, since it may affect more than 20% of CED attempts. It becomes critical to eventually understand and measure what happens to the efficiency of the targeted CED in the presence of the leakage. Varenika et al. made one of the first attempts in this direction generating volume-distributed versus volume-infused graphs during CED in dogs and monkeys using real-time MRI. Quite predictably, the presence of leakage prevented further increase in the concentration of the infused agent in the targeted area of CNS; instead, the concentration of infusate in the target actually diminished once leakage begins to occur. It remains to be seen if the phenomenon of inadvertent leakage is irreversible, that is, whether stopping and subsequent restarting of the infusion would potentially eliminate leakage routes. It would also be interesting to analyze how repositioning of catheters might avoid unwanted leakage in the same study or treatment subject. This would provide an argument for not abandoning CED in a patient in whom leakage takes place and who could still be offered effective CED following changes in stereotactic placement of catheters. One important conclusion that can be derived from the type of studies conducted by Veranika et al. is that CED must be supported by effective imaging of the fate of the infusates, which has already been investigated extensively. This is compatible with the need for personalized targeted therapy approaches and personalized medicine.
Source: ...