Abstract
Radioligand positron emission tomography (PET) with dual scan paradigms can provide valuable insight into changes in synaptic neurotransmitter concentration due to experimental manipulation. The residual t-test has been utilized to improve the sensitivity of the t-test in PET studies. However, no further development of statistical tests using residuals has been proposed so far to be applied in cases when there are more than two conditions. Here, we propose the residual f-test, a one-way analysis of variance (ANOVA), and examine its feasibility using simulated [11C]raclopride PET data. We also re-visit data from our previously published [11C]raclopride PET study, in which 10 individuals underwent three PET scans under different conditions. We found that the residual f-test is superior in terms of sensitivity than the conventional f-test while still controlling for type 1 error. The test will therefore allow us to reliably test hypotheses in the smaller sample sizes often used in explorative PET studies.
Highlights
Positron emission tomography (PET) is a widely used research tool to assess the neurochemical changes induced by pharmacological, behavioral or physiological intervention
Theory Under the same assumption stated in Aston et al [2], i.e., 1) the residuals are not correlated in time; 2) the basis function fitting method [3] is equivalent to a nonlinear least squares fit; 3) The only sources of differences in parameter estimates among the scans are the noise of the PET measurement and the biological effect of different condition used in the PET scans; 4) The noise in the reference tissue is negligible, if subjects underwent multiple numbers of scans in different conditions, we can test the effect of condition using: F
With 6 randomly selected subjects, the residual f-test successfully identified the significant effect of condition in the left caudate, while the conventional f-test did not, especially when there were less prominent changes in binding potentials (BP) (i.e., 5%–10% change)
Summary
Positron emission tomography (PET) is a widely used research tool to assess the neurochemical changes induced by pharmacological, behavioral or physiological intervention. By utilizing the residuals of the fitting in the simplified reference tissue model [3], this method greatly increases the degree of freedom that determines the size of the t-statistic considered significant. This is important because low sample sizes, and small degrees of freedom (and as a result, low statistical power) are one of the major obstacles in costly PET imaging studies. Aston et al.’s method has been widely used in many radio-ligand PET studies with repeated measures designs [4,5,6,7,8,9,10,11,12]
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