A Simplified in vivo Autoradiographic Strategy for the Determination of Regional Cerebral Blood Flow by Positron Emission Tomography: Theoretical Considerations and Validation Studies in the Rat

Abstract
Summary: A simplified mathematical model is described for the measurement of regional cerebral blood flow by positron emission tomography in man, based on a modification of the autoradiographic strategy originally developed for experimental animal studies. A modified ramp intravenous infusion of radiolabeled tracer is used; this results in a monotonically increasing curvilinear arterial activity curve that may be accurately described by a polynomial of low degree (= z). Integrated cranial activity CB is measured in regions of interest during the latter portion of the tracer infusion period (times T1 to T2). It is shown that where each of the terms Ax is a readily evaluated function of the blood flow rate constant k, the brain:blood partition coefficient for the tracer, the cranial activity integration limits 7\ and T2, the coefficients of the polynomial describing the arterial curve, and an iteration factor n that is chosen to yield the desired degree of precision. This relationship permits generation of a table of CB vs. k, thus facilitating on-line computer solution for blood flow. This in vivo autoradiographic paradigm was validated in a series of rats by comparing it to the classical autoradiographic strategy developed by Kety and associates. Excellent agreement was demonstrated between blood flow values obtained by the two methods: CEFin vivo = CBFclassicalx 0.99 - 0.02 (units in ml g-1 min-1; correlation coefficientr = 0.966).