A FINITE-ELEMENT MODEL FOR PREDICTING THE DISTRIBUTION OF DRUGS DELIVERED INTRACRANIALLY TO THE BRAIN

Drug therapy to the central nervous system is complicated by the prese nce of the blood-brain barrier. The development of new drug delivery t echniques to overcome this obstacle will be aided by a clear understan ding of the transport processes in the brain. A rigorous theoretical f ramework of the transport of drugs delivered locally to the parenchyma has been developed using the finite element method. Magnetic resonanc e imaging has been used to track the transport of paramagnetic contras t markers in the brain. The information obtained by postprocessing spi n-echo, T1-weighted, and proton density images has been used to refine the mathematical model that includes realistic brain geometry and sal ient anatomic features and allows for two-dimensional transport of che mical species, including both diffusive and convective contributions. In addition, the effects of regional differences in tissue properties, ventricular boundary, and edema on the transport have been considered The model has been used to predict transport of interleukin-2 in the brain and study the major determinants of transport, at both early and late times after drug delivery.