CED was originally investigated predominantly for treatment of diseases such as glioblastoma because it offers several advantages, including of delivery of high concentration of molecules, robust distribution, targeted treatment, and lower system effects [5]. Since distribution is affected by hydrostatic pressure rather than diffusion, the molecular weight of the molecule is not usually the limiting factor controlling distribution. This supported the investigation of viral delivery into the CNS with the CED method.

CED was initially examined in gene therapy studies as a way to increase the distribution of rAAV2 vectors in the brain . Bankiewicz et al. revealed that CED can significantly increase gene transfer and distribution of rAAV expressing AADC in the striatum of MPTP-treated monkeys [8]. Similar results have been replicated by Cunningham et al. in the rat brain with rAAV2 expressing thymidine kinase (TK) [9]. The CED method showed robust gene transfer and increased distribution within the putamen, with immunoreactive cells found outside the striatum, including the globus pallidus, subthalamic nucleus, thalamus, and substantia nigra [9, 10]. Carty et al. examined the use of CED in mouse models [11]. They demonstrate that CED can be successfully used for different serotypes of rAAV for increased transduction of the mouse CNS .

Most recently a new method of real time convection delivery (RCD) has been established in order to make the method safer and more efficacious. This currently utilizes magnetic resonance imaging (MRI ) [12–14]. Viral samples can be co-administered with an MRI tracer such as gadoteridol or gadopentetic acid (Gd-DTPA) to monitor optimal placement of the injection. This also has the advantages of identifying if any reflux is occurring (especially at higher flow rates), or if the injected sample is leaking into the ventricles and to allow for corrections of flow rate or needle placement if necessary. In nonhuman primates, it has been shown that there is a direct correlation between gadoteridol distribution and AAV2 transduction [15].

Back flow failure using needles and catheters is a significant concern with injections into the CNS and this is one of the theoretical mechanistic limitations of the CED method as well. To limit this problem, Krauze et al. developed a step cannula design [6]. This can effectively reduce reflux by placing a silica tubing within the needle creating a horizontal step that reduces the back flow of fluid. The optimization of more efficient cannula designs coupled with the encouraging results from studies showing enhanced gene transfer and distribution emphasize the therapeutic potential of the CED method in helping overcome some of the mechanical disadvantages of gene delivery for gene therapy [6]. However, further refinements are required before CED becomes a standard clinical practice. CED is, however, an excellent method to achieve significant transduction of virus in research animals. This chapter continues to describe in detail the method used for CED delivery into a rodent brain .