Can the microsphere model by applied to cerebral blood flow measurement using N-isopropyl-p-[123I]iodoamphetamine with SPET regardless of washout from brain tissue?

The microsphere model and the continuous withdrawal of arterial blood have commonly been used in clinical studies when measuring regional cerebral blood flow (rCBF) by N-isopropyl-p-[123I]iodoamphetamine (IMP) single photon emission tomography. The method is considered to underestimate rCBF because of the washout of tracer from brain tissue; however, the extent of this underestimation is not known. To assess whether this underestimation can be determined quantitatively, we performed simulation analysis based on the microsphere model and the two-compartment model [influx, K1(rCBF); and outflux, k2(washout)] using the time-activity curves of 123I-IMP in arterial blood [Ca(t)] of 10 subjects. With the microsphere method, rCBF values fell as time post-injection increased. The extent of underestimation of rCBF was 4.7 +/- 0.28% (mean +/- S.D.) at 5 min, 10.2 +/- 0.42% at 10 min and 15.2 +/- 0.55% at 15 min. There was little variation in the extent of underestimation and it was not dependent on the Ca(t) of the subjects. We therefore considered the results to be generally applicable to various studies of the microsphere model. As 4.7% is considered to be negligible in clinical studies, we conclude that the microsphere model can be applied to obtain accurate measurement of rCBF up to 5 min regardless of washout.