现代功能神经成像技术给临床提供了将整个大脑活动可视化的机会,是癫痫诊断中一项不可或缺的工具。多种形式的无创性功能神经成像技术现在也作为研究工具应用于动物癫痫模型的研究中,可以进行动物/人类的平行研究,探究癫痫根本机制,发现癫痫生物标志物。文章综述了近期应用正电子发射断层扫描术、纤维示踪成像技术和功能磁共振成像技术进行动物癫痫研究的文献。癫痫由突发的神经网络特性的异常紊乱导致,即使是局灶性癫痫发作,也累及到广泛分布的多个系统,通常涉及双侧大脑半球。动物癫痫模型的功能神经成像检查为临床提供了检查全脑神经紊乱的机会,这可能是全面性和局灶性痫性发作以及多种类型癫痫发生的基础。利用当前的功能神经成像方法取得了诸多进展,进一步理解了广泛神经网络的特性对于正常以及异常人类行为的贡献。全脑功能神经成像技术在动物实验中的成功应用允许其研究癫痫的产生过程,并与深部脑电活动相关联。随着成像技术以及分析方法的持续发展,未来癫痫影像的转化研究领域有无限发展前景。
Citation: StefanieDedeurwaerdere, SandyR Shultz, PaoloFederico, JeromeEngel Jr, 任洁钏, 王群. 癫痫动物模型中的神经系统影像学新方法——癫痫神经生物工作组报告. Journal of Epilepsy, 2016, 2(6): 535-543. doi: 10.7507/2096-0247.20160094 Copy
1. | Virdee K, Cumming P, Caprioli D, et al. Applications of positronemission tomography in animal models of neurological andneuropsychiatric disorders. Neurosci Biobehav Rev, 2012, 36(7):1188-1216. |
2. | Dedeurwaerdere S, Jupp B, O'Brien TJ. Positron emission tomographyin basic epilepsy research:a view of the epileptic brain. Epilepsia, 2007, 48(Suppl. 4):56-64. |
3. | Goffin K, Dedeurwaerdere S, Van Laere K, et al. Neuronuclear assessment of patients with epilepsy. Semin Nucl Med, 2008, 38(10):227-239. |
4. | O'Brien TJ, Jupp B. In-vivo imaging with small animal FDG-PET:atool to unlock the secrets of epileptogenesis?. Exp Neurol, 2009, 220(11):1-4. |
5. | Kornblum HI, Araujo DM, Annala AJ, et al. In vivo imaging of neuronal activation and plasticity in the rat brain by high resolution positron emission tomography (microPET). Nat Biotechnol, 2000, 18(8):655-660. |
6. | Mirrione MM, Schiffer WK, Siddiq M, et al. PET imaging of glucose metabolism in a mouse model of temporal lobe epilepsy. Synapse, 2006, 59(7):119-121. |
7. | Mirrione MM, Schiffer WK, Fowler JS, et al. A novel approach for imaging brain-behavior relationships in mice reveals unexpected metabolic patterns during seizures in the absence of tissue plasminogen activator. Neuroimage, 2007, 38(11):34-42. |
8. | Wang D, Pascual JM, Yang H, et al. A mouse model for Glut-1haploinsufficiency. Hum Mol Genet, 2006, 15(10):1169-1179. |
9. | Goffin K, Van Paesschen W, Dupont P, et al. Longitudinal microPET imaging of brain glucose metabolism in rat lithium-pilocarpine modelof epilepsy. Exp Neurol, 2009, 217(6):205-209. |
10. | Guo Y, Gao F, Wang S, et al. In vivo mapping of temporos patial changes in glucose utilization in rat brain during epileptogenesis:an 18F-fluorodeoxyglucose-small animal positron emission tomographystudy. Neuroscience, 2009, 162(21):972-979. |
11. | Lee EM, Park GY, Im KC, et al. Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium-pilocarpine model of epilepsy. Epilepsia, 2012, 53(11):860-869. |
12. | Jupp B, Williams J, Binns D, et al. Hypometabolism precedes limbicatrophy and spontaneous recurrent seizures in a rat model of TLE.Epilepsia, 2012, 53(2):1233-1244. |
13. | Shultz SR, Cardamone L, Liu YR, et al. Can structural or functional changes following traumatic brain injury in the rat predict epileptic outcome?. Epilepsia, 2013, 54(10):1240-1250. |
14. | Vivash L, Gregoire MC, Lau EW, et al. 18F-flumazenil:a gamma aminobutyric acid A-specific PET radiotracer for the localization ofdrug-resistant temporal lobe epilepsy. J Nucl Med, 2013, 54(3):1270-1277. |
15. | Van Paesschen W. Qualitative and quantitative imaging of the hippocampus in mesial temporal lobe epilepsy with hippocampal sclerosis. Neuroimaging Clin N Am, 2004, 14(s2):373-400, vii. |
16. | Liefaard LC, Ploeger BA, Molthoff CF, et al. Changes in GAB A Areceptor properties in amygdala kindled animals:in vivo studies using[11C]flumazenil and positron emission tomography. Epilepsia, 2009, 50(12):88-98. |
17. | Syvanen S, Labots M, Tagawa Y, et al. Altered GABA A receptor density and unaltered blood-brain barrier transport in a kainate modelof epilepsy:an in vivo study using 11C-flumazenil and PET. J NuclMed, 2012, 53(7):1974-1983. |
18. | Vivash L, Tostevin A, Liu DS, et al. Changes in hippocampal GABA A/cBZR density during limbic epileptogenesis:relationship tocell loss and mossy fibre sprouting. Neurobiol Dis, 2011, 41(12):227-236. |
19. | Dedeurwaerdere S, Gregoire MC, Vivash L, et al. In-vivo imaging characteristics of two fluorinated flumazenil radiotracers in the rat. EurJ Nucl Med Mol Imaging, 2009, 36(3):958-965. |
20. | Vivash L, Gregoire MC, Bouilleret V, et al. In vivo measurement of hippocampal GABAA/cBZR density with[(18)F]-flumazenil PET forthe study of disease progression in an animal model of temporal lobeepilepsy. PLoS ONE, 2014, 9(1):e86722. |
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25. | Syvanen S, Russmann V, Verbeek J, et al.[(11)C]quinidine and[(11)C]laniquidar PET imaging in a chronic rodent epilepsy model:impactof epilepsy and drug-responsiveness. Nucl Med Biol, 2013, 40(7):764-775. |
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30. | Dedeurwaerdere S, Callaghan PD, Pham T, et al. PET imaging of brain inflammation during early epileptogenesis in a rat model oftemporal lobe epilepsy. EJNMMI Res, 2012, 2(1):60. |
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33. | Bernhardt BC, Hong S, Bernasconi A, et al. Imaging structural and functional brain networks in temporal lobe epilepsy. Front Hum Neurosci, 2013, 7(3):624. |
34. | Engelhorn T, Hufnagel A, Weise J, et al. Monitoring of acute generalized status epilepticus using multilocal diffusion MR imaging:early prediction of regional neuronal damage. AJNR Am J Neuroradiol, 2008, 28(6):321-327. |
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- 1. Virdee K, Cumming P, Caprioli D, et al. Applications of positronemission tomography in animal models of neurological andneuropsychiatric disorders. Neurosci Biobehav Rev, 2012, 36(7):1188-1216.
- 2. Dedeurwaerdere S, Jupp B, O'Brien TJ. Positron emission tomographyin basic epilepsy research:a view of the epileptic brain. Epilepsia, 2007, 48(Suppl. 4):56-64.
- 3. Goffin K, Dedeurwaerdere S, Van Laere K, et al. Neuronuclear assessment of patients with epilepsy. Semin Nucl Med, 2008, 38(10):227-239.
- 4. O'Brien TJ, Jupp B. In-vivo imaging with small animal FDG-PET:atool to unlock the secrets of epileptogenesis?. Exp Neurol, 2009, 220(11):1-4.
- 5. Kornblum HI, Araujo DM, Annala AJ, et al. In vivo imaging of neuronal activation and plasticity in the rat brain by high resolution positron emission tomography (microPET). Nat Biotechnol, 2000, 18(8):655-660.
- 6. Mirrione MM, Schiffer WK, Siddiq M, et al. PET imaging of glucose metabolism in a mouse model of temporal lobe epilepsy. Synapse, 2006, 59(7):119-121.
- 7. Mirrione MM, Schiffer WK, Fowler JS, et al. A novel approach for imaging brain-behavior relationships in mice reveals unexpected metabolic patterns during seizures in the absence of tissue plasminogen activator. Neuroimage, 2007, 38(11):34-42.
- 8. Wang D, Pascual JM, Yang H, et al. A mouse model for Glut-1haploinsufficiency. Hum Mol Genet, 2006, 15(10):1169-1179.
- 9. Goffin K, Van Paesschen W, Dupont P, et al. Longitudinal microPET imaging of brain glucose metabolism in rat lithium-pilocarpine modelof epilepsy. Exp Neurol, 2009, 217(6):205-209.
- 10. Guo Y, Gao F, Wang S, et al. In vivo mapping of temporos patial changes in glucose utilization in rat brain during epileptogenesis:an 18F-fluorodeoxyglucose-small animal positron emission tomographystudy. Neuroscience, 2009, 162(21):972-979.
- 11. Lee EM, Park GY, Im KC, et al. Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium-pilocarpine model of epilepsy. Epilepsia, 2012, 53(11):860-869.
- 12. Jupp B, Williams J, Binns D, et al. Hypometabolism precedes limbicatrophy and spontaneous recurrent seizures in a rat model of TLE.Epilepsia, 2012, 53(2):1233-1244.
- 13. Shultz SR, Cardamone L, Liu YR, et al. Can structural or functional changes following traumatic brain injury in the rat predict epileptic outcome?. Epilepsia, 2013, 54(10):1240-1250.
- 14. Vivash L, Gregoire MC, Lau EW, et al. 18F-flumazenil:a gamma aminobutyric acid A-specific PET radiotracer for the localization ofdrug-resistant temporal lobe epilepsy. J Nucl Med, 2013, 54(3):1270-1277.
- 15. Van Paesschen W. Qualitative and quantitative imaging of the hippocampus in mesial temporal lobe epilepsy with hippocampal sclerosis. Neuroimaging Clin N Am, 2004, 14(s2):373-400, vii.
- 16. Liefaard LC, Ploeger BA, Molthoff CF, et al. Changes in GAB A Areceptor properties in amygdala kindled animals:in vivo studies using[11C]flumazenil and positron emission tomography. Epilepsia, 2009, 50(12):88-98.
- 17. Syvanen S, Labots M, Tagawa Y, et al. Altered GABA A receptor density and unaltered blood-brain barrier transport in a kainate modelof epilepsy:an in vivo study using 11C-flumazenil and PET. J NuclMed, 2012, 53(7):1974-1983.
- 18. Vivash L, Tostevin A, Liu DS, et al. Changes in hippocampal GABA A/cBZR density during limbic epileptogenesis:relationship tocell loss and mossy fibre sprouting. Neurobiol Dis, 2011, 41(12):227-236.
- 19. Dedeurwaerdere S, Gregoire MC, Vivash L, et al. In-vivo imaging characteristics of two fluorinated flumazenil radiotracers in the rat. EurJ Nucl Med Mol Imaging, 2009, 36(3):958-965.
- 20. Vivash L, Gregoire MC, Bouilleret V, et al. In vivo measurement of hippocampal GABAA/cBZR density with[(18)F]-flumazenil PET forthe study of disease progression in an animal model of temporal lobeepilepsy. PLoS ONE, 2014, 9(1):e86722.
- 21. Delforge J, Pappata S, Millet P, et al. Quantification of benzodiazepine receptors in human brain using PET,[11C]flumazenil, and a single experiment protocol. J Cereb Blood Flow Metab, 1995, 15(6):284-300.
- 22. Yakushev IY, Dupont E, Buchholz HG, et al. In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy. Epilepsia, 2010, 51(3):415-422.
- 23. Feldman M, Asselin MC, Liu J, et al. P-glyco protein expression and function in patients with temporal lobe epilepsy:a case-control study.Lancet Neurol, 2013, 12(5):777-785.
- 24. Syvanen S, Luurtsema G, Molthoff CF, et al. (R)-[11C]verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate induced status epilepticus. BMC Med Imaging, 2011, 11(6):1.
- 25. Syvanen S, Russmann V, Verbeek J, et al.[(11)C]quinidine and[(11)C]laniquidar PET imaging in a chronic rodent epilepsy model:impactof epilepsy and drug-responsiveness. Nucl Med Biol, 2013, 40(7):764-775.
- 26. Bartmann H, Fuest C, la Fougere C, et al. Imaging of P-glycoprotein mediated pharmaco resistance in the hippocampus:proof-of-concept ina chronic rat model of temporal lobe epilepsy. Epilepsia, 2010, 51(6):1780-1790.
- 27. Bankstahl JP, Bankstahl M, Kuntner C, et al. A novel positronemission tomography imaging protocol identifies seizure-induced regional over activity of P-glycoprotein at the blood-brain barrier.J Neurosci, 2011, 31(11):8803-8811.
- 28. Dedeurwaerdere S, Friedman A, Fabene PF, et al. Finding a better drug for epilepsy:anti inflammatory targets. Epilepsia, 2012, 53(7):1113-1118.
- 29. Vezzani A, French J, Bartfai T, et al. The role of inflammation in epilepsy. Nat Rev Neurol, 2011, 7(8):31-40.
- 30. Dedeurwaerdere S, Callaghan PD, Pham T, et al. PET imaging of brain inflammation during early epileptogenesis in a rat model oftemporal lobe epilepsy. EJNMMI Res, 2012, 2(1):60.
- 31. Jones DK. Studying connections in the living human brain with diffusion MRI. Cortex, 2008, 44(7):936-952.
- 32. Engel J Jr, Thompson PM, Stern JM, et al. Connectomics and epilepsy.Curr Opin Neurol, 2013, 26(10):186-194.
- 33. Bernhardt BC, Hong S, Bernasconi A, et al. Imaging structural and functional brain networks in temporal lobe epilepsy. Front Hum Neurosci, 2013, 7(3):624.
- 34. Engelhorn T, Hufnagel A, Weise J, et al. Monitoring of acute generalized status epilepticus using multilocal diffusion MR imaging:early prediction of regional neuronal damage. AJNR Am J Neuroradiol, 2008, 28(6):321-327.
- 35. van Eijsden P, Notenboom RG, Wu O, et al. In vivo 1H magnetic resonance spectroscopy, T2-weighted and diffusion-weighted MRI during lithium-pilocarpine-induced status epilepticus in the rat. BrainRes, 2004, 1030(7):11-18.
- 36. Wall CJ, Kendall EJ, Obenaus A. Rapid alterations in diffusion weightedimages with anatomic correlates in a rodent model of status epilepticus. AJNR Am J Neuroradiol, 2000, 21(6):1841-1852.
- 37. Zhong J, Petroff OAC, Prichard JW, et al. Changes in water diffusionand relaxation properties of rat cerebrum during status epilepticus.Magn Reson Med, 1993, 30(8):241-246.
- 38. Kharatishvili I, Immonen R, Grohn O, et al. Quantitative diffusion MRI of hippocampus as a surrogate marker for post-traumatic epileptogenesis. Brain, 2007, 130(23):3155-3168.
- 39. Frey L, Lepkin A, Schickedanz A, et al. ADC mapping and T1-weighted signal changes on post-injury MRI predict seizure susceptibility after experimental traumatic brain injury. Neurol Res, 2014, 36(11):26-37.
- 40. Parekh MB, Carney PR, Sepulveda H, et al. Early MR diffusion and relaxation changes in the parahippocampal gyrus precede the onset of spontaneous seizures in an animal model of chronic limbic epilepsy.Exp Neurol, 2010, 224(21):258-270.
- 41. Sierra A, Laitinen T, Lehtimaki K, et al. Diffusion tensor MRI with tract-based spatial statistics and histology reveals undiscovered lesioned areas in kainate model of epilepsy in rat. Brain Struct Funct, 2011, 216(10):123-135.
- 42. Farquharson S, Tournier JD, Calamante F, et al. White matter fiber tractography:why we need to move beyond DTI. J Neurosurg, 2013, 118(10):1367-1377.
- 43. Chahboune H, Mishra AM, DeSalvo MN, et al. DTI abnormalities inanterior corpus callosum of rats with spike-wave epilepsy. Neuroimage, 2009, 47(10):459-466.
- 44. Jeurissen B, Leemans A, Tournier JD, et al. Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging. Hum Brain Mapp, 2013, 34(5):2747-2766.
- 45. Shultz SR, Zheng P, Wright DK, et al. Tractography and magnetic resonance spectroscopy in acquired epilepsy models. WONOEP XII meeting planner, 2013, QC, Canada.
- 46. Jones DK, Knosche TR, Turner R. White matter integrity, fiber count,and other fallacies:the do's and dont's of diffusion MRI. Neuroimage, 2013, 73(12):239-254.
- 47. Ogawa S, Lee TM, Nayak AS, et al. Oxygenation-sensitive contrast inmagnetic resonance image of rodent brain at high magnetic fields.Magn Reson Med, 1990, 14(7):68-78.
- 48. Blumenfeld H. Functional MRI studies of animal models in epilepsy.Epilepsia, 2007, 48(Suppl. 4):18-26.
- 49. Mirsattari SM, Ives JR, Leung LS, et al. EEG monitoring during functional MRI in animal models. Epilepsia, 2007, 48(Suppl. 4):37-46.
- 50. Nersesyan H, Hyder F, Rothman DL, et al. Dynamic fMRI and EEG recordings during spike-wave seizures and generalized tonic-clonic seizures in WAG/Rij rats. J Cereb Blood Flow Metab, 2004, 24(8):589-599.
- 51. Tenney JR, Duong TQ, King JA, et al. FMRI of brain activation in agenetic rat model of absence seizures. Epilepsia, 2004, 45(5):576-582.
- 52. Meeren HK, Pijn JP, Van Luijtelaar EL, et al. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci, 2002, 22(6):1480-1495.
- 53. Nersesyan H, Herman P, Erdogan E, et al. Relative changes in cerebral blood flow and neuronal activity in local microdomains during generalized seizures. J Cereb Blood Flow Metab, 2004, 24(11):1057-1068.
- 54. Mishra AM, Ellens DJ, Schridde U, et al. Where fMRI and electrophysiology agree to disagree:corticothalamic and striatal activity patterns in the WAG/Rij rat. J Neurosci, 2011, 31(12):15053-15064.
- 55. Aghakhani Y, Bagshaw AP, Benar CG, et al. fMRI activation during spike and wave discharges in idiopathic generalized epilepsy. Brain, 2004, 127(3):1127-1144.
- 56. Archer JS, Abbott DF, Waites AB, et al. fMRI "deactivation" of the posterior cingulate during generalized spike and wave. Neuroimage, 2003, 20(6):1915-1922.
- 57. Gotman J, Grova C, Bagshaw A, et al. Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. Proc Natl Acad Sci USA, 2005, 102(3):15236-15240.
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