Awake ¹⁸F-FDG PET Imaging of Memantine-Induced Brain Activation and Test–Retest in Freely Running Mice

Abstract

PET scans of the mouse brain are usually performed with anesthesia to immobilize the animal. However, it is desirable to avoid the confounding factor of anesthesia in mouse-brain response. Methods: We developed and validated brain PET imaging of awake, freely moving mice. Head-motion tracking was performed using radioactive point-source markers, and we used the tracking information for PET-image motion correction. Regional 18 F-FDG brain uptake in a test, retest, and memantine-challenge study was measured in awake ( n = 8) and anesthetized ( n = 8) C57BL/6 mice. An awake uptake period was considered for the anesthesia scans. Results: Awake (motion-corrected) PET images showed an 18 F-FDG uptake pattern comparable to the pattern of anesthetized mice. The test–retest variability (represented by the intraclass correlation coefficient) of the regional SUV quantification in the awake animals (0.424–0.555) was marginally lower than that in the anesthetized animals (intraclass correlation coefficient, 0.491–0.629) over the different regions. The increased memantine-induced 18 F-FDG uptake was more pronounced in awake (+63.6%) than in anesthetized (+24.2%) animals. Additional behavioral information, acquired for awake animals, showed increased motor activity on a memantine challenge (total distance traveled, 18.2 ± 5.28 m) compared with test–retest (6.49 ± 2.21 m). Conclusion: The present method enables brain PET imaging on awake mice, thereby avoiding the confounding effects of anesthesia on the PET reading. It allows the simultaneous measurement of behavioral information during PET acquisitions. The method does not require any additional hardware, and it can be deployed in typical high-throughput scan protocols.

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

“…The parameters in (11) where calculated from a non-linear least-square fit to 20 point sources distributed along the radial direction. The fit was performed in Matlab (The MathWorks, Inc., Massachusetts, USA) using the Levenberg-Marquardt algorithm.…”

“…The average eigenvalues ratio for every group of rods is reported for the centered and off-center motion corrected phantom using the 6 resolution models. 4) Freely Moving Mice Brain Scans: For this experiment data from a previous [ 18 F]FDG brain PET study in freely moving mice by our group [11] was used. The experiments followed the European Ethics Committee recommendations (Decree 86/609/CEE) and were approved by the Animal Experimental Ethical Committee of the University of Antwerp, Antwerp, Belgium (ECD 2016-89).…”

“…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.…”

“…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 animal was placed on a cylindrical transparent tube and allowed move freely in the container during the scan. 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.…”