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1 Bioengineering and Physical
Science Program,
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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