title: Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery.
abstract: OBJECTIVE
  The authors have shown that convection-enhanced delivery (CED) of gadoteridol-loaded liposomes (GDLs) into different regions of normal monkey brain results in predictable, widespread distribution of this tracking agent as detected by real-time MR imaging. They also have found that this tracking technique allows monitoring of the distribution of similar nanosized agents such as therapeutic liposomes and viral vectors. A limitation of this procedure is the unexpected leakage of liposomes out of targeted parenchyma or malignancies into sulci and ventricles. The aim of the present study was to evaluate the efficacy of CED after the onset of these types of leakage.
  
  
  METHODS
  The authors documented this phenomenon in a study of 5 nonhuman primates and 7 canines, comprising 54 CED infusion sessions. Approximately 20% of these infusions resulted in leakage into cerebral ventricles or sulci. All of the infusions and leakage events were monitored with real-time MR imaging. The authors created volume-distributed versus volume-infused graphs for each infusion session. These graphs revealed the rate of distribution of GDL over the course of each infusion and allowed the authors to evaluate the progress of CED before and after leakage.
  
  
  RESULTS
  The distribution of therapeutics within the target structure ceased to increase or resulted in significant attenuation after the onset of leakage.
  
  
  CONCLUSIONS
  An analysis of the cases in this study revealed that leakage undermines the efficacy of CED. These findings reiterate the importance of real-time MR imaging visualization during CED to ensure an accurate, robust distribution of therapeutic agents.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA, USA.
authors.forename: Vanja
authors.initials: V
authors.lastname: Varenika
authors.forename: Peter
authors.initials: P
authors.lastname: Dickinson
authors.forename: John
authors.initials: J
authors.lastname: Bringas
authors.forename: Richard
authors.initials: R
authors.lastname: LeCouteur
authors.forename: Robert
authors.initials: R
authors.lastname: Higgins
authors.forename: John
authors.initials: J
authors.lastname: Park
authors.forename: Massimo
authors.initials: M
authors.lastname: Fiandaca
authors.forename: Mitchel
authors.initials: M
authors.lastname: Berger
authors.forename: John
authors.initials: J
authors.lastname: Sampson
authors.forename: Krystof
authors.initials: K
authors.lastname: Bankiewicz
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018481:Convection; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes / Q000493:pharmacokinetics; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D023421:Models, Animal; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium