title: Analysis of a simulation algorithm for direct brain drug delivery.
abstract: Convection enhanced delivery (CED) achieves targeted delivery of drugs with a pressure-driven infusion through a cannula placed stereotactically in the brain. This technique bypasses the blood brain barrier and gives precise distributions of drugs, minimizing off-target effects of compounds such as viral vectors for gene therapy or toxic chemotherapy agents. The exact distribution is affected by the cannula positioning, flow rate and underlying tissue structure. This study presents an analysis of a simulation algorithm for predicting the distribution using baseline MRI images acquired prior to inserting the cannula. The MRI images included diffusion tensor imaging (DTI) to estimate the tissue properties. The algorithm was adapted for the devices and protocols identified for upcoming trials and validated with direct MRI visualization of gadoinium in 20 infusions in non-human primates. We found strong agreement between the size and location of the simulated and gadolinium volumes, demonstrating the clinical utility of this surgical planning algorithm.
authors.affiliation: Department of Neurosurgery, University of California San Francisco (UCSF), San Francisco, CA 94103-0555, USA. Kate.Rosenbluth@ucsf.edu
authors.forename: Kathryn Hammond
authors.initials: KH
authors.lastname: Rosenbluth
authors.forename: Jan Felix
authors.initials: JF
authors.lastname: Eschermann
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mittermeyer
authors.forename: Rowena
authors.initials: R
authors.lastname: Thomson
authors.forename: Stephan
authors.initials: S
authors.lastname: Mittermeyer
authors.forename: Krystof S
authors.initials: KS
authors.lastname: Bankiewicz
mesh_terms: D000465:Algorithms; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology*; D002404:Catheterization; D003198:Computer Simulation; D003287:Contrast Media / Q000008:administration & dosage; D018481:Convection; D056324:Diffusion Tensor Imaging / Q000379:methods*; D016503:Drug Delivery Systems; D005682:Gadolinium / Q000008:administration & dosage; D018014:Gene Transfer Techniques; D007091:Image Processing, Computer-Assisted; D007267:Injections; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D011312:Pressure; D015203:Reproducibility of Results; D013238:Stereotaxic Techniques
chemical_list: D003287:Contrast Media; D005682:Gadolinium