Interstitial transport and transvascular fluid exchange during infusion into brain and tumor tissue.
A model of convection-enhanced delivery in brain and neoplastic tissue is presented that includes transvascular fluid exchange in addition to interstitial fluid transport. Measured values for the relevant material parameters are compiled from published literature. The transient distributions of interstitial fluid pressure and fluid velocity resulting from infusion into brain tissue and into a tissue-isolated tumor are derived, in addition to the steady-state distribution of interstitial fluid pressure and fluid velocity resulting from infusion into a tumor with a necrotic core. The analytic solutions suggest that (1) the distributions of both pressure and fluid velocity are very sensitive to the ratio of vascular conductivity and hydraulic conductivity; (2) in brain tissue, the convective fluid velocity is significant (within three orders of magnitude of the peak value, for example) for a large number of infusion catheter diameters away from the infusion site, whereas in neoplastic tissue the convective velocity is significant for a small number of infusion catheter diameters away from the infusion site; (3) the presence of a necrotic core substantially increases the convective fluid velocity in its vicinity; and (4) infusion proximal to a tumor is greatly impeded by the outward flow at the tumor's periphery. These and related findings are discussed in terms of their relevance to the treatment of tumors.
Smith
Joshua H
JH
Department of Mechanical and Aerospace Engineering, University of Virginia, P.O. Box 400746, Charlottesville, VA 22904-4746, USA. josh@virginia.edu
Humphrey
Joseph A C
JA
D000465:Algorithms; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology; D045604:Extracellular Fluid / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D006874:Hydrostatic Pressure; D007263:Infusions, Parenteral; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D012212:Rheology