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 18F-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 18F-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 18F-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.
Highlights
Small-animal PET is performed under anesthesia to ensure immobilization of the animal and to avoid motion artifacts in the images
Our group developed this method further, replacing optical motion tracking with point-source tracking (PST) in which radioactive markers are fixed to the head of the rat to measure its movement [9]
The PST method does not require any hardware other than the PET scanner, and it allows tracking to be performed throughout the entire field of view (FOV), regardless of animal pose or scanner-bore size
Summary
Small-animal PET is performed under anesthesia to ensure immobilization of the animal and to avoid motion artifacts in the images. Immobilization stress affects the uptake of such radiotracers as 18F-FDG [5] and 11C-raclopride [6] Given these confounding factors, it is desirable to perform PET acquisitions on freely moving animals, to ensure an unaffected brain response. An approach by Kyme et al [8] used a commercially available PET scanner to perform PET acquisitions with minimal restraint In the latter method, an optical device tracked the motion of the rat head during the acquisition, and motion correction was subsequently applied to the images. Earlier studies have been based only on PET imaging performed on awake rats, transgenic models commonly used in neuroscience are more widely available for mice [10] For this reason, we report on the adaptation of the PST method to track head motion in freely moving mice during PET acquisitions. It allowed us to assess the ability of the awake-mouse imaging to detect memantine-induced alterations in brain uptake and in behavior
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