Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations

Abstract

Summary:The method of graphical analysis for the eval uation of sequential data (e.g., tissue and blood concen trations over time) in which the test substance is irre versibly trapped in the system has been expanded. A sim pler derivation of the original analysis is presented.General equations are derived that can be used to analyze tissue uptake data when the blood-plasma concentration of the test substance cannot be easily measured. In ad dition, general equations are derived for situations when trapping of the test substance is incomplete and for a combination of these two conditions. These derivationsThe study of the movement of solute molecules across tissue capillaries and their localization within selected tissues of both animal and human subjects has been greatly facilitated by the use of tomo graphic machines. These instruments can provide sequential measurements over time of regional tissue concentrations. The general experimental protocol usually involves the injection of the test substance into the blood of the subject and then measuring the concentration of the substance in both the blood and various tissue regions over a period of time. These data may then be analyzed by a number of methods to ascertain the desired parameters of the system.One method of analysis that has been proposed for those substances that are irreversibly trapped in the system is a graphical analysis of multiple time data points . For this method, an equation has been developed for a very general model. When certain measurable quantities are This approach is also shown to result in equations with at least one less nonlinear term than those derived from direct compartmental analysis. Specific applications of these equations are illustrated for a compartmental system with one reversible region (with or without re versible binding) and one irreversible region.

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