A method is suggested to ensure independence between the estimated glo
bal flow and changes in local flow in PET activation studies. Global f
low is estimated as the average of all intracerebral voxels, except th
ose that exhibit a consistent change in flow as a consequence of the e
xperimental design. This is achieved by performing an initial analysis
, using all intracerebral voxels for estimation of global flow, in whi
ch an F-map depicting task related changes is produced. A second analy
sis is performed, now excluding all voxels with a P < 0.05 in the F-ma
p when evaluating global flow, thereby ensuring independence from area
s changing in a task-dependent manner. The feasibility of the method i
s demonstrated on phantom data, showing that the distribution is skewe
d in nonactivated areas when including the activated areas in the calc
ulation of global flow. By excluding these areas the distribution is t
ranslated toward zero and becomes consistent with the null-hypothesis.
Furthermore, the usefulness of the suggested scheme is demonstrated o
n human data. Scans performed while subjects watched a movie featuring
snakes were contrasted to scans performed while watching white noise,
producing highly significant activations of the visual system. When u
sing the traditional way of estimating global flow, deactivations were
observed in very large portions of the frontal, parietal, and tempora
l lobes. When using the method suggested in the present paper these di
sappeared, which would be more consistent with the expected effects of
the stimulation. The method was used in conjunction with both ratio a
nd ANCOVA adjustment with very similar results. (C) 1997 Academic Pres
s.