Factors are examined in this report which govern the uniqueness and sensitivity of regional cerebral blood flow (rCBF), as determined by an in vivo autoradiographic strategy and positron emission tomography (PET), and a series of theorems is derived which specify conditions under which a unique relationship between cumulative cranial activity of the tracer (C) and regional blood flow (f) may be assured. It is demonstrated that, independent of the specific form of the arterial tracer input function, flow is a unique function of C whenever the start time (T1) of the PET scan is coincident with the start of tracer infusion. Other theorems state that, even for nonzero T1S, a unique solution for flow may be expected, as long as the duration of the scan is sufficiently short. The implementation of this theory is illustrated using arterial tracer activity curves obtained in three normal subjects by a multiple arterial sampling procedure following the bolus i.v. infusion of 20-30 microCi of [15O]water. Based on these arterial curves, it is confirmed that the C vs. f relationship resulting from scan parameters T1 = 0 and T2 = 1.5 min (i.e., a PET scan of 90 s commencing with tracer infusion) has an excellent separation of flow values within the range of physiological interest, whereas a 90-s scan beginning at time T1 = 1.7 min results in poorer separation of flow values and loss of the monotonic relationship between C and f at higher flows. The results of this study serve to clarify the in vivo autoradiographic method for measuring rCBF in humans and help to define favorable study parameters for assuring uniqueness and sensitivity of the flow measurement.

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An in vivo autoradiographic strategy is described for the measurement of local cerebral blood flow in humans by positron emission tomography, based on an application of the single-compartment model originally proposed by Kety. A variety of factors are considered upon which the successful quantitation of local blood flow depends. These factors include the mode of tracer administration and the definition of the arterial input function; the choice of scan parameters to assure unique and sensitive values of flow throughout the physiological range of interest; the influence of these parameters on the stability and signal/noise characteristics of the computed flow; the error introduced by the presence of heterogeneity of flow within a volume element; and factors related to the choice of the radiotracer itself. The in vivo autoradiographic method is compared to an alternative local cerebral blood flow method employing continuous inhalation of oxygen-15-labeled carbon dioxide. The general relevance of these issues to all local blood flow methods intended for emission tomographic application is emphasized.

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