Evaluation of pressure-driven brain infusions in nonhuman primates by intra-operative 7 Tesla MRI.
OBJECTIVE
To characterize the effects of pressure-driven brain infusions using high field intra-operative MRI. Understanding these effects is critical for upcoming neurodegeneration and oncology trials using convection-enhanced delivery (CED) to achieve large drug distributions with minimal off-target exposure.


METHODS
High-resolution T2-weighted and diffusion-tensor images were acquired serially on a 7 Tesla MRI scanner during six CED infusions in nonhuman primates. The images were used to evaluate the size, distribution, diffusivity, and temporal dynamics of the infusions.


RESULTS
The infusion distribution had high contrast in the T2-weighted images. Diffusion tensor images showed the infusion increased diffusivity, reduced tortuosity, and reduced anisotropy. These results suggested CED caused an increase in the extracellular space.


CONCLUSIONS
High-field intra-operative MRI can be used to monitor the distribution of infusate and changes in the geometry of the brain's porous matrix. These techniques could be used to optimize the effectiveness of pressure-driven drug delivery to the brain.
Department of Neurosurgery, University of California San Francisco, San Francisco, California, USA. khrosenbluth@gmail.com
Kathryn H
KH
Rosenbluth
Alastair J
AJ
Martin
John
J
Bringas
Krystof S
KS
Bankiewicz
D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism*; D057967:Infusions, Intraventricular; D008253:Macaca mulatta; D053783:Magnetic Resonance Imaging, Interventional / Q000379:methods*; D011312:Pressure; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D012965:Sodium Chloride