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

Nature Biotechnology volume 18, pages 655–660 (2000)Cite this article

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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References

  1. Kennedy, C. et al. Mapping of functional neural pathways by autoradiographic survey of local metabolic rate with [14C]deoxyglucose. Science 187, 850–853 (1975).

    Article  CAS  Google Scholar 

  2. Schwartz, W.J. et al. Metabolic mapping of functional activity in the hypothalamo-neurohypophysial system of the rat. Science 205, 723–725 (1979).

    Article  CAS  Google Scholar 

  3. Greer, C.A., Stewart, W.B., Kauer, J.S. & Shepherd, G.M. Topographical and laminar localization of 2-deoxyglucose uptake in rat olfactory bulb induced by electrical stimulation of olfactory nerves. Brain Res. 217, 279–293 (1981).

    Article  CAS  Google Scholar 

  4. Chugani, H.T., Hovda, D.A., Villablanca, J.R., Phelps, M.E. & Xu, W.F. Metabolic maturation of the brain: a study of local cerebral glucose utilization in the developing cat. J Cereb. Blood Flow Metab. 11, 35–47 (1991).

    Article  CAS  Google Scholar 

  5. Bruehl, C. & Witte, O.W. Cellular activity underlying altered brain metabolism during focal epileptic activity. Ann. Neurol. 38, 414–420 (1995).

    Article  CAS  Google Scholar 

  6. Hovda, D.A., Villablanca, J.R., Chugani, H.T. & Phelps, M.E. Cerebral metabolism following neonatal or adult hemineodecortication in cats: I. Effects on glucose metabolism using [14C]2-deoxy-D-glucose autoradiography. J. Cereb. Blood Flow Metab. 16, 134–146 (1996).

    Article  CAS  Google Scholar 

  7. Collins, R.C., McLean, M. & Olney, J. Cerebral metabolic response to systemic kainic acid: 14C-deoxyglucose studies. Life Sci. 27, 855–862 (1980).

    Article  CAS  Google Scholar 

  8. Ben-Ari, Y., Tremblay, E., Riche, D., Ghilini, G. & Naquet, R. Electrographic, clinical and pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole: metabolic mapping using the deoxyglucose method with special reference to the pathology of epilepsy. Neuroscience 6, 1361–1391 (1981).

    Article  CAS  Google Scholar 

  9. Albala, B.J., Moshe, S.L. & Okada, R. Kainic-acid-induced seizures: a developmental study. Brain Res. 315, 139–148 (1984).

    Article  CAS  Google Scholar 

  10. Chugani, H.T. & Jacobs, B. Metabolic recovery in caudate nucleus of children following cerebral hemispherectomy. Ann. Neurol. 36, 794–797 (1994).

    Article  CAS  Google Scholar 

  11. Iglesias, S. et al. Do changes in oxygen metabolism in the unaffected cerebral hemisphere underlie early neurological recovery after stroke? A positron emission tomography study. Stroke 27, 1192–1199 (1996).

    Article  CAS  Google Scholar 

  12. Bergsneider, M. et al. Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study [see comments]. J Neurosurg 86, 241–251 (1997).

    Article  CAS  Google Scholar 

  13. Muller, R.A., Chugani, H.T., Muzik, O. & Mangner, T.J. Brain organization of motor and language functions following hemispherectomy: a [15O]-water positron emission tomography study. J. Child Neurol. 13, 16–22 (1998).

    Article  CAS  Google Scholar 

  14. Kuhl, D.E., Engel, J. Jr., Phelps, M.E. & Selin, C. Epileptic patterns of local cerebral metabolism and perfusion in humans determined by emission computed tomography of 18FDG and 13NH3 . Ann. Neurol. 8, 348–360 (1980).

    Article  CAS  Google Scholar 

  15. Chugani, H.T., Rintahaka, P.J. & Shewmon, D.A. Ictal patterns of cerebral glucose utilization in children with epilepsy. Epilepsia 35, 813–822 (1994).

    Article  CAS  Google Scholar 

  16. Melega, W.P. et al. Recovery of striatal dopamine function after acute amphetamine- and methamphetamine-induced neurotoxicity in the vervet monkey. Brain Res. 766, 113–120 (1997).

    Article  CAS  Google Scholar 

  17. Brownell, A.L. et al. PET and MR studies of experimental focal stroke. J. Comput. Assist. Tomogr. 15, 376–380 (1991).

    Article  CAS  Google Scholar 

  18. Magata, Y. et al. Noninvasive measurement of cerebral blood flow and glucose metabolic rate in the rat with high-resolution animal positron emission tomography (PET): a novel in vivo approach for assessing drug action in the brains of small animals. Biol. Pharm. Bull. 18, 753–756 (1995).

    Article  CAS  Google Scholar 

  19. Ouchi, Y. et al. Cholinergic projection from the basal forebrain and cerebral glucose metabolism in rats: a dynamic PET study [see comments]. J. Cereb. Blood Flow Metab. 16, 34–41 (1996).

    Article  CAS  Google Scholar 

  20. Kuge, Y. et al. Positron emission tomography for quantitative determination of glucose metabolism in normal and ischemic brains in rats: an insoluble problem by the Harderian glands. J. Cereb. Blood Flow Metab. 17, 116–120 (1997).

    Article  CAS  Google Scholar 

  21. Cherry, S. et al. MicroPET: a high resolution PET scanner for imaging small animals. IEEE Trans. Nucl. Sci. 44, 1161–1166 (1997).

    Article  CAS  Google Scholar 

  22. Chatziioannou, A.F. et al. Performance evaluation of microPET: a high-resolution LSO PET scanner for animal imaging. J. Nucl. Med. 40, 1164–1175 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Chugani, H.T. et al. Surgical treatment of intractable neonatal-onset seizures: the role of positron emission tomography. Neurology 38, 1178–1188 (1988).

    Article  CAS  Google Scholar 

  24. Chugani, H.T. & Phelps, M.E. Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography. Science 231, 840–843 (1986).

    Article  CAS  Google Scholar 

  25. Cutler, P.D., Cherry, S.R., Hoffman, E.J., Digby, W.M. & Phelps, M.E. Design features and performance of a PET system for animal research. J. Nucl. Med. 33, 595–604 (1992).

    CAS  PubMed  Google Scholar 

  26. Kinahan, P. & Rogers, J. Analytic 3D imager reconstruction using all detected events. IEEE Trans. Nucl. Sci. 36, 964–968 (1989).

    Article  CAS  Google Scholar 

  27. Qi, J., Leahy, R.M., Cherry, S.R., Chatziioannou, A. & Farquhar, T.H. High-resolution 3D Bayesian image reconstruction using the microPET small-animal scanner. Phys. Med. Biol. 43, 1001–1013 (1998).

    Article  CAS  Google Scholar 

  28. Dietrich, W.D., Ginsberg, M.D., Busto, R. & Smith, D.W. Metabolic alterations in rat somatosensory cortex following unilateral vibrissal removal. J. Neurosci. 5, 874–880 (1985).

    Article  CAS  Google Scholar 

  29. Kossut, M. Effects of sensory denervation and deprivation on a single cortical vibrissal column studied with 2-deoxyglucose. Physiol. Bohemoslov. 34, 79–83 (1985).

    PubMed  Google Scholar 

  30. Miller, M.W. & Dow-Edwards, D.L. Vibrissal stimulation affects glucose utilization in the trigeminal/somatosensory system of normal rats and rats prenatally exposed to ethanol. J. Comp. Neurol. 335, 283–284 (1993).

    Article  CAS  Google Scholar 

  31. Dunn-Meynell, A.A. & Levin, B.E. Lateralized effect of unilateral somatosensory cortex contusion on behavior and cortical reorganization. Brain Res. 675, 143–156 (1995).

    Article  CAS  Google Scholar 

  32. Krynaw, R. Infantile hemiplegia treated by removing one cerebral hemisphere. J. Neurol. Neurosurg. Psychiatry 13, 243–267 (1950).

    Article  Google Scholar 

  33. Napieralski, J.A., Butler, A.K. & Chesselet, M.F. Anatomical and functional evidence for lesion-specific sprouting of corticostriatal input in the adult rat. J. Comp. Neurol. 373, 484–497 (1996).

    Article  CAS  Google Scholar 

  34. Chatziioannou, A. et al. Comparison of 3D maximum a posteriori and filtered backprojection algorithms for high resolution animal imaging with microPET. IEEE Trans. Med. Imag. in press (2000).

  35. Moore, A., Cherry, S., Annala, A. & Hovda, D. Quantitative assessment of FDG-PET studies in rat brain using microPET. J. Cereb. Blood Flow Metab. 19(Suppl 1), S764 (1999).

    Google Scholar 

  36. Hoffman, E.J., Huang, S.C. & Phelps, M.E. Quantitation in positron emission computed tomography: 1. Effect of object size. J. Comput. Assist. Tomogr. 3, 299–308 (1979).

    Article  CAS  Google Scholar 

  37. Coyle, J.T. Neurotoxic action of kainic acid. J. Neurochem. 41, 1–11 (1983).

    Article  CAS  Google Scholar 

  38. Sokoloff, L. et al. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28, 897–916 (1977).

    Article  CAS  Google Scholar 

  39. Kolb, B., Gibb, R. & van der Kooy, D. Cortical and striatal structure and connectivity are altered by neonatal hemidecortication in rats. J. Comp. Neurol. 322, 311–324 (1992).

    Article  CAS  Google Scholar 

  40. Tatsukawa, K., Shields, S. & Kornblum, H. Limited corticostriatal plasticity following hemidecortication in the rat. Soc. Neurosci. Abstr. 23, 1447 (1997).

    Google Scholar 

  41. Kolb, B. Recovery from early cortical damage in rats. I. Differential behavioral and anatomical effects of frontal lesions at different ages of neural maturation. Behav. Brain Res. 25, 205–220 (1987).

    Article  CAS  Google Scholar 

  42. Fowler, J. & Wolf, A. Positron emitter-labeled compounds. in Positron emission tomography and autoradiography. (eds Phelps, M.E., Mazziotta, J. & Schelbert, H.R.) 391–450 (Raven Press, New York; 1986).

    Google Scholar 

  43. Phelps, M.E. et al. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann. Neurol. 6, 371–388 (1979).

    Article  CAS  Google Scholar 

  44. Ackermann, R.F. & Lear, J.L. Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose. J. Cereb. Blood Flow Metab. 9, 774–785 (1989).

    Article  CAS  Google Scholar 

  45. Kornblum, H.I., Chugani, H.T., Tatsukawa, K. & Gall, C.M. Cerebral hemidecortication alters expression of transforming growth factor alpha mRNA in the neostriatum of developing rats. Brain Res. Mol. Brain Res. 21, 107–114 (1994).

    Article  CAS  Google Scholar 

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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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Authors and Affiliations

  1. Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, 90095, CA

    Harley I. Kornblum, Dalia M. Araujo, Alexander J. Annala, Keith J. Tatsukawa, Michael E. Phelps & Simon R. Cherry

  2. Department of Pediatrics, UCLA School of Medicine, Los Angeles, 90095, CA

    Harley I. Kornblum

  3. Department of Crump Institute for Biological Imaging, UCLA School of Medicine, Los Angeles, 90095, CA

    Harley I. Kornblum, Dalia M. Araujo, Alexander J. Annala, Keith J. Tatsukawa, Michael E. Phelps & Simon R. Cherry

  4. Department of Energy–UCLA Laboratory of Structural Biology and Molecular Medicine, UCLA School of Medicine, Los Angeles, 90095, CA

    Harley I. Kornblum, Michael E. Phelps & Simon R. Cherry

  5. Department of Brain Research Institute, UCLA School of Medicine, Los Angeles, 90095, CA

    Harley I. Kornblum

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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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