A finite element model for predicting the distribution of drugs delivered intracranially to the brain

Abstract

Drug therapy to the central nervous system is complicated by the presence of the blood-brain barrier. The development of new drug delivery techniques to overcome this obstacle will be aided by a clear understanding of the transport processes in the brain. A rigorous theoretical framework of the transport of drugs delivered locally to the parenchyma has been developed using the finite element method. Magnetic resonance imaging has been used to track the transport of paramagnetic contrast markers in the brain. The information obtained by postprocessing spin-echo, T1-weighted, and proton density images has been used to refine the mathematical model that includes realistic brain geometry and salient anatomic features and allows for two-dimensional transport of chemical 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.

Imaging‐guided convection‐enhanced delivery and gene therapy of glioblastoma

“…As theoretically expected, 33 reuptake of molecules around leaky blood vessels from brain tissue into the blood circulation was high as indicated by the inverse relationship of BBB permeability and size of tissue volume stained with intracerebrally infused Gd-DTPA. In accordance with mathematical modeling, 34 intracerebrally infused Gd-DTPA was preferentially distributed within white matter, and the presence of brain edema appeared to promote the propagation of the infusate. Most interestingly, an excellent colocalization of the distribution volume of intracerebrally infused Gd-DTPA (equivalent to the assumed vector-distribution volume) and the local antitumor efficacy of suicide gene therapy was found.…”

Modeling Mass Transfer from Carmustine-Loaded Polymeric Implants for Malignant Gliomas

“…This method divides a predetermined domain into simple shapes defined as finite elements. 28 The differential equations of interest are then integrated over each element and the solutions at the boundaries of adjacent elements are matched to generate approximate solutions to the equations over the whole domain.…”

Application of finite element analysis in neurosurgery

“…A finite element model for predicting the distribution of drugs delivered intracranial to the brain [4] Presentation The transport of a drug released from the carrier into the brain is a complicated procedure, because the therapeutic drugs need to bypass the blood-brain barrier. The blood-brain barrier is a complex and unique organ, which is recognized as a highly selective anatomical and physiological barrier regulating the entry and exit of important substances necessary for the maintenance of cerebral metabolism and neuronal activity.…”