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Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph

Abstract

Positron emission tomography (PET) neuroimaging and behavioral assays in rodents are widely used in neuroscience. PET gives insights into the molecular processes of neuronal communication, and behavioral methods analyze the actions that are associated with such processes. These methods have not been directly integrated, because PET studies in animals have until now required general anesthesia to immobilize the subject, which precludes behavioral studies. We present a method for imaging awake, behaving rats with PET that allows the simultaneous study of behavior. Key components include the 'rat conscious animal PET' or RatCAP, a miniature portable PET scanner that is mounted on the rat's head, a mobility system that allows considerable freedom of movement, radiotracer administration techniques and methods for quantifying behavior and correlating the two data sets. The simultaneity of the PET and behavioral data provides a multidimensional tool for studying the functions of different brain regions and their molecular constituents.

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Figure 1: RatCAP tomograph and validation.
Figure 2: Animal mobility system.
Figure 3: D2 receptor neuroimaging using bolus injections of [11C]raclopride in the behaving and anesthetized rat.
Figure 4: Transient changes in BPND in relation to behavioral activity during the PET scan.
Figure 5: Transient changes in BPND and behavior after D2 receptor blockade.

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Acknowledgements

We thank W. Lenz for mechanical design and fabrication; D. Alexoff for assistance with rat handling; S. Park for coincidence-processing methods; W. Schiffer for assistance with data analysis; C. Reiszel for expertise in catheter design; V. Radeka, R. Lecomte and R. Fontaine for contributions to the electronics; J. Logan for advice on kinetic modeling; J. Fowler and the personnel of the Brookhaven National Laboratory PET center and cyclotron for making the radiotracers available for our studies and N. Volkow for proposing the idea of a conscious-animal PET scanner. The research was carried out at Brookhaven National Laboratory under contract number DE-AC02-98CH10886 with the US Department of Energy and funded by the Department of Energy's Office of Biological and Environmental Research.

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Authors and Affiliations

Authors

Contributions

D.S. proposed and carried out most of the rat work, acquired and analyzed behavioral data and wrote the paper. S.S. developed quantitative PET data processing and reconstruction software and acquired and analyzed PET data. S.S.J. developed front-end and data acquisition electronics, software and firmware. J.-F.P. developed the front-end microchip. M.L.P. developed data processing and image reconstruction software. S.P.S. assembled and debugged scanner and mechanics. B.R. and S.H.M. acquired rat data and performed data analysis. S.K. constructed scanner components. F.A.H. contributed to the behavioral neuroimaging experiments. P.O. oversaw and conceived key aspects of the electronics. C.L.W. oversaw development of the scanner, especially the front-end detectors and electronics. D.J.S. oversaw development of the scanner and performed rat studies and data analysis. P.V. oversaw development of the scanner, software and mechanics, performed rat studies and wrote the paper.

Corresponding author

Correspondence to Paul Vaska.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Note (PDF 162 kb)

Supplementary Software

Raw code and input files necessary to process data from the RatCAP scanner into images, including coincidence processing and image reconstruction. (ZIP 199379 kb)

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Schulz, D., Southekal, S., Junnarkar, S. et al. Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph. Nat Methods 8, 347–352 (2011). https://doi.org/10.1038/nmeth.1582

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