Cerebral serotonin transporter measurements with [11C]DASB: A review on acquisition and preprocessing across 21 PET centres

Abstract

Positron Emission Tomography (PET) imaging has become a prominent tool to capture the spatiotemporal distribution of neurotransmitters and receptors in the brain. The outcome of a PET study can, however, potentially be obscured by suboptimal and/or inconsistent choices made in complex processing pipelines required to reach a quantitative estimate of radioligand binding. Variations in subject selection, experimental design, data acquisition, preprocessing, and statistical analysis may lead to different outcomes and neurobiological interpretations. We here review the approaches used in 105 original research articles published by 21 different PET centres, using the tracer [¹¹C]DASB for quantification of cerebral serotonin transporter binding, as an exemplary case. We highlight and quantify the impact of the remarkable variety of ways in which researchers are currently conducting their studies, while implicitly expecting generalizable results across research groups. Our review provides evidence that the foundation for a given choice of a preprocessing pipeline seems to be an overlooked aspect in modern PET neuroscience. Furthermore, we believe that a thorough testing of pipeline performance is necessary to produce reproducible research outcomes, avoiding biased results and allowing for better understanding of human brain function.

Keywords: Positron Emission Tomography; [C]DASB; data sharing; kinetic modeling; preprocessing.

Figure 1.

Timeline of number of patient and healthy controls in the 105 published [¹¹C]DASB studies. The colors indicate either healthy controls, or a specific disorder as a function of time and sample size. ADHD: attention-deficit/hyperactive disorder; MDD: major depressive disorder; MDMA: ecstasy; HIV: human immunodeficiency virus; OCD: obsessive compulsive disorder; SAD: seasonal affective disorder; PTSD: post-traumatic stress syndrome; PD: Parkinson's disease.

Figure 2.

Schematic overview of the different data acquisition workflows used to acquire dynamic [¹¹C]DASB data. The workflow consists of scanners providing anatomical information, i.e. MRI scanners at various field strengths (Tesla), various PET scanners, duration of the dynamic PET acquisition, frame sequence used to temporally acquire 4D [¹¹C]DASB data, injected dose (ranging from approximately 100-740 MBq), and finally the reconstruction methods used to reconstruct the 4D PET sequence. The colors indicate the frequency per step that has been applied in a [¹¹C]DASB PET study out of the total 105 studies. Injected dose is filled as white, because it spans a continuous range and is highly subject-specific. The 4D imaging data are the output of the data acquisition workflow and input to the preprocessing workflow.

Figure 3.

Schematic overview of the various preprocessing steps used in analyzing dynamic [¹¹C]DASB data. This ranges from different motion correction techniques, co-registration, volume-of-interest definitions, partial volume correction, and kinetic modeling. The colors indicate the percentage, in which a given step has been applied in the 105 [¹¹C]DASB PET studies.