In vivo imaging of neuronal activation and plasticity in the rat brain by high resolution positron emission tomography (microPET)

Abstract

The study of neural repair and neuroplasticity in rodents would be enhanced by the ability to assess neuronal function in vivo. Positron emission tomography (PET) is used to study brain plasticity in humans, but the limited resolution and sensitivity of conventional scanners have generally precluded the use of PET to study neuroplasticity in rodents. We now demonstrate that microPET, a PET scanner developed for use with small animals, can be used to assess metabolic activity in different regions of the conscious rodent brain using [18F]fluorodeoxyglucose (FDG) as the tracer, and to monitor changes in neuronal activity. Limbic seizures result in dramatically elevated metabolic activity in the hippocampus, whereas vibrissal stimulation results in more modest increases in FDG uptake in the contralateral neocortex. We also show that microPET can be used to study lesion-induced plasticity of the brain. Cerebral hemidecortication resulted in diminished relative glucose metabolism in the neostriatum and thalamus ipsilateral to the lesion, with subsequent, significant recovery of metabolic function. These studies demonstrate that microPET can be used for serial assessment of metabolic function of individual, awake rats with a minimal degree of invasiveness, and therefore, has the potential for use in the study of brain disorders and repair.

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Figure 1: MicroPET images of representative transaxial (coronal) sections through the rat brain following intravenous injection of 2.5 mCi of FDG and reconstructed using the MAP algorithm.
Figure 2: FDG-PET images of a rat that had previously undergone decortication of the left hemisphere (asterisk).
Figure 3: (A–F) Stimulation of cerebral metabolism by KA.
Figure 4: Induction of metabolic activity by vibrissal stimulation.
Figure 5: Effects of hemidecortication on metabolic activity in the neostriatum and thalamus.

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Acknowledgements

The authors thank Drs. Kim Seroogy and Roger Woods for helpful review of the manuscript, Dr. Arion Chatziioannou for technical assistance with microPET and helpful discussions regarding quantitation, Dr. Amy Moore for aid in the performance of kinetic studies, and Drs. Richard Leahy and Jinyi Qi for providing the MAP reconstruction algorithm. We also thank Ron Sumida, Judy Edwards, Der-Jenn Liu, Victor Dominguez, and Waldimar Ladno for outstanding assistance with microPET scanning, and Ms. Cheri Sneed for some initial data analysis. This work was supported by the Department of Energy, contract DE-FC03-ER60615 (S.R.C., M.E.P., D.M.J., H.I.K.), NIH grants CA69370-03 (S.R.C.), and NS01837-01A1 (H.I.K.).

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Correspondence to Harley I. Kornblum.

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Kornblum, H., Araujo, D., Annala, A. et al. In vivo imaging of neuronal activation and plasticity in the rat brain by high resolution positron emission tomography (microPET). Nat Biotechnol 18, 655–660 (2000). https://doi.org/10.1038/76509

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