Open-field PET: Simultaneous brain functional imaging and behavioural response measurements in freely moving small animals

Abstract

A comprehensive understanding of how the brain responds to a changing environment requires techniques capable of recording functional outputs at the whole-brain level in response to external stimuli. Positron emission tomography (PET) is an exquisitely sensitive technique for imaging brain function but the need for anaesthesia to avoid motion artefacts precludes concurrent behavioural response studies. Here, we report a technique that combines motion-compensated PET with a robotically-controlled animal enclosure to enable simultaneous brain imaging and behavioural recordings in unrestrained small animals. The technique was used to measure in vivo displacement of [ 11 C]raclopride from dopamine D2 receptors (D2R) concurrently with changes in the behaviour of awake, freely moving rats following administration of unlabelled raclopride or amphetamine. The timing and magnitude of [ 11 C]raclopride displacement from D2R were reliably estimated and, in the case of amphetamine, these changes coincided with a marked increase in stereotyped behaviours and hyper-locomotion. The technique, therefore, allows simultaneous measurement of changes in brain function and behavioural responses to external stimuli in conscious unrestrained animals, giving rise to important applications in behavioural neuroscience.

Motion Dependent and Spatially Variant Resolution Modeling for PET Rigid Motion Correction

“…Radial, axial and tangential coordinates in (12) are defined with respect to the radial, axial and tangential directions, which in turn are calculated from the Cartesian coordinates (x c , y c , z c ) of the PSF center. The radial direction has unit vector cos(θ c ) sin(θ c ) 0 , and the tangential direction −sin(θ c ) cos(θ c ) 0 , where θ c = atan(y c /x c ).…”

“…Recently, research has been carried out to perform brain PET scans of awake small animals to circumvent the confounding effect of anesthesia [10]. In addition, in scans of freely moving animals the behavior of the animal can be measured during the PET scan [11], [12]. These methods require to perform rigid motion correction on the PET data to obtain brain reconstructions unaffected by motion.…”

“…Despite of the fact that there is a great amount of research in PET motion correction [12]- [15], the vast majority of the spatial resolution correction methods have been developed to be implemented in motion-free PET image reconstruction. Given the advancement in the field to perform PET scans of freely moving animals, and its promise to change the paradigm of preclinical research [16], improvement of spatial resolution in motion corrected PET reconstructions is becoming more relevant.…”

“…In PET scans of freely moving animals, the image PSF of the reconstructed image is both spatially variant and motion dependent since the animal head can traverse the whole scanner FOV during the scan [11], [12], [14]. For example, This work is licensed under a Creative Commons Attribution 4.0 License.…”

Quantitative Rodent Brain Receptor Imaging

“…The approach was further validated using mice, where the authors found that mementine led to a 2.6 larger [ 18 F]FDG uptake on awake animals in comparison to anesthetized animals [245]. Kyme et al [246] further investigated the field of awake-animal imaging by using an automated motion-tracking robot in combination with motion correction approaches and placing a visual marker on the animal's head. The robot performed accurate and responsive movements in order to real-time correct the animal's alignment to the center of the FOV.…”