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

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 277; no. 4; pp. 1218 - R1229
• Main Authors: Morrison, Paul F, Chen, Michael Y, Chadwick, Richard S, Lonser, Russell R, Oldfield, Edward H
• Format: Journal Article
• Language: English
• Published: United States 01.10.1999
• Subjects: Animals; Autoradiography; Brain - physiology; Catheterization; Caudate Nucleus - metabolism; Drug Delivery Systems - instrumentation; Models, Neurological; Rats; Serum Albumin - administration & dosage; Serum Albumin - pharmacokinetics
• ISSN: 0363-6119; 0002-9513; 1522-1490; 2163-5773
• DOI: 10.1152/ajpregu.1999.277.4.r1218

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 ( x m ) has been determined from a mathematical model based on Stokes flow, Darcy flow in porous media, and elastic deformation of the brain tissue: x m  = constant Q o 3 R 4 r c 4 G 3 µ 1 ( Q o  = volumetric inflow rate, R  = tissue hydraulic resistance, r c  = 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