A realistic brain tissue phantom for intraparenchymal infusion studies.
OBJECTIVE
The goal of this study was to validate a simple, inexpensive, and robust model system to be used as an in vitro surrogate for in vivo brain tissues in preclinical and exploratory studies of infusion-based intraparenchymal drug and cell delivery.


METHODS
Agarose gels of varying concentrations and porcine brain were tested to determine the infusion characteristics of several different catheters at flow rates of 0.5 and 1 microl per minute by using bromophenol blue (BPB) dye (molecular weight [MW] approximately 690) and gadodiamide (MW approximately 573). Magnetic resonance (MR) imaging and videomicroscopy were used to measure the distribution of these infusates, with a simultaneous measurement of infusion pressures. In addition, the forces of catheter penetration and movement through gel and brain were measured. Agarose gel at a 0.6% concentration closely resembles in vivo brain with respect to several critical physical characteristics. The ratio of distribution volume to infusion volume of agarose was 10 compared with 7.1 for brain. The infusion pressure of the gel demonstrated profiles similar in configuration and magnitude to those of the brain (plateau pressures 10-20 mm Hg). Gadodiamide infusion in agarose closely resembled that in the brain, as documented using T1-weighted MR imaging. Gadodiamide distribution in agarose gel was virtually identical to that of BPB dye, as documented by MR imaging and videomicroscopy. The force profile for insertion of a silastic catheter into agarose gel was similar in magnitude and configuration to the force profile for insertion into the brain. Careful insertion of the cannula using a stereotactic guide is critical to minimize irregularity and backflow of infusate distribution.


CONCLUSIONS
Agarose gel (0.6%) is a useful surrogate for in vivo brain in exploratory studies of convection-enhanced delivery.
Chen
Zhi-Jian
ZJ
Department of Neurosurgery, Harold F. Young Neurosurgical Center, Division of Radiation Physics and Biology, Medical College of Virginia Hospitals, Virginia Commonwealth University, Richmond, Virginia 23298-0631, USA.
Gillies
George T
GT
Broaddus
William C
WC
Prabhu
Sujit S
SS
Fillmore
Helen
H
Mitchell
Ryan M
RM
Corwin
Frank D
FD
Fatouros
Panos P
PP
D000818:Animals; D001978:Bromphenol Blue / Q000008:administration & dosage / Q000493:pharmacokinetics; D002493:Central Nervous System Diseases / Q000188:drug therapy; D002540:Cerebral Cortex / Q000378:metabolism*; D004396:Coloring Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D005782:Gels / Q000008:administration & dosage / Q000493:pharmacokinetics; D036502:Infusions, Intralesional; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D019047:Phantoms, Imaging; D011312:Pressure; D012685:Sepharose / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013552:Swine
D004396:Coloring Agents; D005782:Gels; D001978:Bromphenol Blue; D012685:Sepharose