Anatomic compression caused by high-volume convection-enhanced delivery to the brain.
OBJECTIVE
Our group has pioneered the use of gadoteridol-loaded liposomes (GDLs) in convection-enhanced delivery (CED) using real-time magnetic resonance imaging (MRI) to visualize the distribution of therapeutic agents in nonhuman primate and canine brains. We have shown that this procedure is highly predictable and safe. In the course of recent studies, however, we noted that infusion of large volumes caused local anatomic alterations, such as ventricular compression, to occur. This article reports our analysis of CED infusions into normal brains and those compromised by tumors and how monitoring the CED infusion with MRI may be helpful in preventing some complications.


METHODS
A total of 54 CED infusions using GDLs were performed in 7 canines and 10 nonhuman primates and monitored using real-time MRI. The canines, having brain tumors, received infusions of GDLs as well as a chemotherapeutic agent via CED. The nonhuman primates were normal and received GDL infusions alone. Real-time analysis of the CED infusion was performed, looking for correct catheter position and infusion reflux, leakage, and mass effect. Retrospective analysis allowed assessment of CED volume of distribution versus volume of infusion.


RESULTS
Approximately 10% of these infusions caused anatomic compression of the ventricles, especially in the canines with tumors. Reflux along the cannula and leakage of infusate into the ventricular cerebrospinal fluid or subarachnoid space were seen. Animal behavior, however, did not appear to be affected acutely or during the course of the study, and no ventricular compression was noted 2 weeks after the CED infusion on further brain imaging studies.


CONCLUSIONS
These findings illustrate the value of being able to monitor infusions with real-time MRI to identify phenomena such as reflux along the cannula, leakage of infusate, and ventricular compression. Especially in tumor patients, the latter could be associated with morbidity.
Valles
Francisco
F
Movement Disorder Research Program, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94103, USA.
Fiandaca
Massimo S
MS
Bringas
John
J
Dickinson
Peter
P
LeCouteur
Richard
R
Higgins
Robert
R
Berger
Mitchel
M
Forsayeth
John
J
Bankiewicz
Krystof S
KS
D000818:Animals; D001921:Brain / Q000378:metabolism*; D019245:Compressive Strength / Q000502:physiology; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods*; D005682:Gadolinium; D006571:Heterocyclic Compounds; D008081:Liposomes / Q000008:administration & dosage*; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D023421:Models, Animal; D009942:Organometallic Compounds; D013997:Time Factors; D014018:Tissue Distribution
D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium
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