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.
Highlights
Positron emission tomography (PET) is a molecular imaging technique that allows to quantify the distribution of radiolabeled biomolecules in the living body
It is assumed that the effect of anesthesia is small and, if this is true, this scan reflects the awake state uptake. This approach does not allow to study the kinetics of the tracer from the onset of radiotracer administration, but pseudo-dynamic data can be obtained. (iii) The animal can be restrained during the scan and the tracer can be administered in the awake state. This method allows to perform the PET scan from the radiotracer administration onset in the awake state, but the stress caused by restraining can affect the radiotracer uptake. (iv) Using advanced methods, such as the specialized PET scanners or motion correction, the animal can be scanned in the awake state without physical restraining
Since studies investigating the mechanisms of action of anesthetics demonstrate that they modify physiological parameters and interact with neurotransmitter systems, it is expected that anesthetics will modify the brain response to PET tracers
Summary
Positron emission tomography (PET) is a molecular imaging technique that allows to quantify the distribution of radiolabeled biomolecules in the living body. Ketamine, and isoflurane are some of the most common anesthetics used for animal immobilization in preclinical PET [5] These compounds can have a pharmacological effect, affecting physiological parameters such as body temperature and cerebral blood flow, which in turn can Motion Correction in Unanesthetized Animals affect the pharmacokinetics of a radiotracer [6]. These anesthetics have been proven to work principally by interaction with neurotransmitter systems [7], which, for many neurological studies, are the object of study. The use of anesthesia in preclinical brain PET studies can be considered a confounding factor, and one of the principal limitations for translation of preclinical results to the clinic [8]
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