title: Convection-enhanced drug delivery: increased efficacy and magnetic resonance image monitoring.
abstract: Convection-enhanced drug delivery (CED) is a novel approach to directly deliver drugs into brain tissue and brain tumors. It is based on delivering a continuous infusion of drugs via intracranial catheters, enabling convective distribution of high drug concentrations over large volumes of the target tissue while avoiding systemic toxicity. Efficient formation of convection depends on various physical and physiologic variables. Previous convection-based clinical trials showed significant diversity in the extent of convection among patients and drugs. Monitoring convection has proven to be an essential, yet difficult task. The current study describes the application of magnetic resonance imaging for immediate assessment of convection efficiency and early assessment of cytotoxic tissue response in a rat brain model. Immediate assessment of infusate distribution was obtained by mixing Gd-diethylenetriaminepentaacetic acid in the infusate prior to infusion. Early assessment of cytotoxic tissue response was obtained by subsequent diffusion-weighted magnetic resonance imaging. In addition, the latter imaging methodologies were used to establish the correlation between CED extent and infusate's viscosity. It was found that low-viscosity infusates tend to backflow along the catheter track, whereas high-viscosity infusates tend to form efficient convection. These results suggest that CED formation and extent may be significantly improved by increasing the infusate's viscosities, thus increasing treatment effects.
authors.affiliation: Advanced Technology Center, Neurosurgery Department, Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Ramat Gan. yaer.mardor@sheba.health.gov.il
authors.forename: Yael
authors.initials: Y
authors.lastname: Mardor
authors.forename: Ofer
authors.initials: O
authors.lastname: Rahav
authors.forename: Yacov
authors.initials: Y
authors.lastname: Zauberman
authors.forename: Zvi
authors.initials: Z
authors.lastname: Lidar
authors.forename: Aharon
authors.initials: A
authors.lastname: Ocherashvilli
authors.forename: Dianne
authors.initials: D
authors.lastname: Daniels
authors.forename: Yiftach
authors.initials: Y
authors.lastname: Roth
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Maier
authors.forename: Arie
authors.initials: A
authors.lastname: Orenstein
authors.forename: Zvi
authors.initials: Z
authors.lastname: Ram
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D016190:Carboplatin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002408:Catheters, Indwelling; D018481:Convection; D016503:Drug Delivery Systems / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000008:administration & dosage; D014783:Viscosity
chemical_list: D012709:Serum Albumin; D016190:Carboplatin; D019786:Gadolinium DTPA; D017239:Paclitaxel