Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery: Laboratory investigation

Vanja Varenika, Peter J Dickinson, John Bringas, Richard A Lecouteur, Robert Higgins, John Park, Massimo Fiandaca, Mitchel Berger, John Sampson, Krystof Bankiewicz

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Object. 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.

Original languageEnglish (US)
Pages (from-to)874-880
Number of pages7
JournalJournal of Neurosurgery
Volume109
Issue number5
DOIs
StatePublished - Nov 2008

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Convection
Liposomes
Brain
Cerebral Ventricles
Primates
Haplorhini
Canidae
Therapeutics
Neoplasms

Keywords

  • Brain
  • Convection-enhanced delivery
  • Leakage
  • Liposome
  • Magnetic resonance imaging
  • Real-time imaging

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery : Laboratory investigation. / Varenika, Vanja; Dickinson, Peter J; Bringas, John; Lecouteur, Richard A; Higgins, Robert; Park, John; Fiandaca, Massimo; Berger, Mitchel; Sampson, John; Bankiewicz, Krystof.

In: Journal of Neurosurgery, Vol. 109, No. 5, 11.2008, p. 874-880.

Research output: Contribution to journalArticle

Varenika, Vanja ; Dickinson, Peter J ; Bringas, John ; Lecouteur, Richard A ; Higgins, Robert ; Park, John ; Fiandaca, Massimo ; Berger, Mitchel ; Sampson, John ; Bankiewicz, Krystof. / Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery : Laboratory investigation. In: Journal of Neurosurgery. 2008 ; Vol. 109, No. 5. pp. 874-880.
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AB - Object. 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.

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