AJP - Heart and Circulatory Physiology, Vol 266, Issue 3 987-H999, Copyright © 1994 by American Physiological Society
Blood-brain barrier permeability measurements by double-indicator method using intravenous injection
G. M. Knudsen, K. D. Pettigrew, C. S. Patlak and O. B. Paulson
Department of Neurology, University Clinic Rigshospitalet, Copenhagen, Denmark.
The double-indicator technique with intracarotid bolus injection is useful
for the estimation of transfer rates across the human blood-brain barrier.
A method using intravenous tracer injection is developed whereby the input
is measured at a peripheral artery and the output is measured at the
jugular vein. To correct for differences in the brain input of test and
reference substances, a five-parameter Dirac impulse response for passage
through the cerebrovascular bed is computed from the input and output of
the reference substance. This response is then combined with a capillary
model of the brain. This is then convoluted with the arterial input curve
of the test substance to yield a theoretical test output curve, which is
compared with the actual test output curve. On the basis of these two
curves and an appropriate mathematical model for the brain, estimates of
blood-brain barrier permeability are obtained. In the present study, the
techniques are compared in 13 patients in whom alternating intracarotid and
intravenous bolus injections were given. For D-glucose, the two techniques
yielded similar results. This was also the case for L-phenylalanine,
provided that the erythrocyte compartment was taken into account. Data
obtained after intravenous injection of leucine and water yielded similar
results compared with previous intracarotid data.
