Positron Emission Tomography (PET) imaging has become an important tool to investigate brain function, such as the serotonin neurotransmitter system. The outcome of a PET study can, however, potentially be obscured by suboptimal and/or inconsistent choices made in very complex processing pipelines required to reach a quantitative estimate of radioligand binding. Variations in subject selection, experimental design, data acquisition, preprocessing, and data analysis may therefore lead to different neurobiological interpretations. In this article, we investigate the various approaches made by 21 different PET centres published in 105 original research articles in quantifying the cerebral serotonin transporter binding with [11C]DASB PET. Combinatorially, there are a total of 21 million different workflow possibilities.
We highlight the remarkable variety of ways in which researchers are currently conducting their studies, while implicitly expecting generalizable results across research groups. This study provides powerful evidence that the importance of preprocessing pipelines and their experimental interactions seem to be an overlooked aspect in modern PET neuroscience, and we believe that such testing is necessary in order to reliably provide new insights into human brain function. The key findings provide insight into acquisition- and preprocessing differences in published [11C]DASB studies, thereby enforcing the need for transparency, reproducibility and standardization for future data sharing opportunities in the PET neuroimaging community.