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Am J Physiol Regul Integr Comp Physiol 277: R1218-R1229, 1999;
0363-6119/99 $5.00
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Vol. 277, Issue 4, R1218-R1229, October 1999

Focal delivery during direct infusion to brain: role of flow rate, catheter diameter, and tissue mechanics

Paul F. Morrison1, Michael Y. Chen2, Richard S. Chadwick3, Russell R. Lonser2, and Edward H. Oldfield2

1 Bioengineering and Physical Science Program, Office of Research Services; 2 Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke; and 3 Laboratory of Cell Biology, National Institute of Deafness and Communicative Disorders, National Institutes of Health, Bethesda, Maryland 20892

Direct interstitial infusion is a technique capable of delivering agents over both small and large dimensions of brain tissue. However, at a sufficiently high volumetric inflow rate, backflow along the catheter shaft may occur and compromise delivery. A scaling relationship for the finite backflow distance along this catheter in pure gray matter (xm) has been determined from a mathematical model based on Stokes flow, Darcy flow in porous media, and elastic deformation of the brain tissue: xm = constant Qo3R4rc4G-3µ-1 (Qo = volumetric inflow rate, R = tissue hydraulic resistance, rc = catheter radius, G = shear modulus, and µ = viscosity). This implies that backflow is minimized by the use of small diameter catheters and that a fixed (minimal) backflow distance may be maintained by offsetting an increase in flow rate with a similar decrease in catheter radius. Generally, backflow is avoided in rat gray matter with a 32-gauge catheter operating below 0.5 µl/min. An extension of the scaling relationship to include brain size in the resistance term leads to the finding that absolute backflow distance obtained with a given catheter and inflow rate is weakly affected by the depth of catheter tip placement and, thus, brain size. Finally, an extension of the model to describe catheter passage through a white matter layer before terminating in the gray has been shown to account for observed percentages of albumin in the corpus callosum after a 4-µl infusion of the compound to rat striatum over a range of volumetric inflow rates.

mathematical model; intracerebral drug delivery


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