A Quantitative Model for the Measurement of Cerebral Vascular Extraction Fraction In vivo following Intravenous Injection: Simulation Studies

Abstract

A mathematical method has been developed by which the cerebral vascular extraction fraction of flow- and diffusion-limited tracers injected intravenously can be measured quantitatively. Successive injections of three tracers are required: a test tracer such as 15O-labeled water; a completely diffusible tracer as a reference tracer and also as a flow tracer; and a tracer for cerebral blood volume (CBV). The arterial tracer concentration curves and total integrated head counts of the test and reference tracers, as well as CBF and CBV values, are required to calculate the extraction fraction. No calibration is required between the head counts and arterial curves. No decay correction of the head and arterial activity is required, because isotopic decay is explicitly included in the equation. The effect of nonextracted test tracer can be corrected. Simulation studies have shown that the calculated extraction fraction values are not sensitive to measurement error in CBF, CBV, partition coefficient, change in measurement time, or time shift effect between the arterial and head data. If there is mixing of two different tissues in the brain, the calculated extraction fraction values are close to the weighted mean values of extraction fraction by relative weight of the tissues. It is concluded that it is possible to apply this method to human studies with a positron emission tomograph scanner and to animal studies with external coincidence detectors.

Water extraction fraction and permeability-surface product after intravenous injection in rats.

“…First, we used a notional value of 0.03 for CBV instead of the actual CBV for each rat because of the difficulty of measuring CBV after introduction of ["C]butanol in the same rat. This value of CBV agrees with CBV reported for rats,' 7 and also with that for normal rats in our laboratory (unpublished data). As discussed in our previous paper, 8 it is important to perform the CBV correction.…”

“…This value of CBV agrees with CBV reported for rats,' 7 and also with that for normal rats in our laboratory (unpublished data). As discussed in our previous paper, 8 it is important to perform the CBV correction. However, the effect of an error in CBV on calculated WEF is not large.…”

Basis and current state of computed tomography perfusion imaging: a review

“…Equation (4) represents the transport and exchange of contrast agent within capillaries, and equation (5) represents the rate of contrast agent concentration in the interstitial compartment. It should be noted that lots of studies have been developed to solve both equation (4) and equation (5) (Johnson and Wilson 1966, Takagi et al 1984, Gambhir et al 1987, Ohta et al 1996, St Lawrence and Lee 1998. Meanwhile these methods are not commonly used in the real scenario applications.…”