Normalization in PET group comparison studies-The importance of a valid reference region

Ratio normalization to the global mean readily elevates CBF in unchanged regions when a systematic between-group difference exists in gCBF, also when this difference is below the detection threshold. We suggest that the routine normalization to the global mean in earlier studies resulted in spurious interpretations of perturbed CBF. Normalization to central WM yields less biased results in aging and HE and could potentially serve as a normalization reference region in other disorders as well.