Translation of Preclinical PET Imaging Findings: Challenges and Motion Correction to Overcome the Confounding Effect of Anesthetics

Abstract

Preclinical brain positron emission tomography (PET) in animals is performed using anesthesia to avoid movement during the PET scan. In contrast, brain PET scans in humans are typically performed in the awake subject. Anesthesia is therefore one of the principal limitations in the translation of preclinical brain PET to the clinic. This review summarizes the available literature supporting the confounding effect of anesthesia on several PET tracers for neuroscience in preclinical small animal scans. In a second part, we present the state-of-the-art methodologies to circumvent this limitation to increase the translational significance of preclinical research, with an emphasis on motion correction methods. Several motion tracking systems compatible with preclinical scanners have been developed, each one with its advantages and limitations. These systems and the novel experimental setups they can bring to preclinical brain PET research are reviewed here. While technical advances have been made in this field, and practical implementations have been demonstrated, the technique should become more readily available to research centers to allow for a wider adoption of the motion correction technique for brain research.

[18F]FDG brain uptake of C57Bl/6 male mice is affected by locomotor activity after cocaine use: A small animal positron emission tomography study

“…Different from clinical neuroimaging acquisitions that are performed in awake subjects, small animal in vivo imaging is generally conducted under anesthesia, as restriction of movements is necessary to avoid undesirable artifacts. Anesthesia is therefore one limitation for translational data, as studies in anesthetized animals have reported alterations in brain functioning and connectivity, cerebral blood, and inhibitory GABAergic neurotransmission (Gutierrez‐Barragan et al, 2022; Miranda et al, 2021; Ogawa et al, 2011; Prando et al, 2019). To avoid these limitations, some methodologies have been developed for evaluations in awake‐animals, such as performing scans using devices that restrict movement (Gutierrez‐Barragan et al, 2022; Mizuma et al, 2010; Suzuki et al, 2021) or using motion tracking and motion correction during image reconstruction (Miranda et al, 2019; Spangler‐Bickell et al, 2016).…”

PET imaging of animal models with depressive-like phenotypes

“…Furthermore, there are also methodological constrains that might affect the translatability of findings from animal models to patients. For example, the use of anaesthetics in animal studies has been already identified as a confounding factor that can hamper the translatability of imaging studies [130][131][132]. Additionally, differences in the processing and quantification of the images can also debilitate the translatability of PET methods.…”

Isoflurane and ketamine-xylazine modify pharmacokinetics of [18F]SynVesT-1 in the mouse brain

“…7 Translation of results from preclinical PET studies to human subjects can be compromised due to the additional use of anesthesia to perform preclinical PET scans. 8,9 For example, anesthesia has been shown to change the uptake of the glucose analog [ 18 F]FDG, as well as the binding of tracers targeting neurotransmitter receptors. 9 To circumvent the use of anesthesia in brain PET, motion correction methods have been developed to scan awake rodents.…”

“…9 To circumvent the use of anesthesia in brain PET, motion correction methods have been developed to scan awake rodents. 9 Particularly for mouse brain PET scans in freely moving animals, point source tracking with motion correction can be performed. 10…”