灵长类中风模型的磁共振成像

摘要/Abstract

摘要：

灵长类大脑在结构、生理、功能及神经学上与人类大脑非常相似. 因此，灵长类中风模型为研究大脑缺血的损伤机制和开发各种药物治疗方法提供了理想的动物模型. 该文介绍了近年来使用的各种灵长类中风模型，并总结了目前可用于该模型的各种磁共振成像（MRI）方法. 同时，还讨论了灵长类动物高分辩弥散张量成像（DTI）和磁共振灌注成像（PWI）的数据采集方法和心跳及呼吸引起的生理运动伪影的矫正方法. 这些方法改进了弥散一灌注失配（DWI－PWI MISMATCH）成像的精度和质量，有助于提高对脑缺血半暗带演化及其对药物治疗反应的精确评估，为更好地利用灵长类脑中风模型和当代磁共振成像技术进行中风机制研究和药物开发建立一个理想的研究平台.

关键词: 灵长类, 中风模型, 磁共振成像, 脑中动脉缺血, 弥散张量成像, 磁共振灌注成像, 生理运动伪影矫正

Abstract:

As the non-human primate (NHP) brain is gyroencephalic, structurally and functionally similar to the human brain, NHP stroke models provide an ideal platform for investigating the mechanism of ischemic brain injury and developing therapeutical treatment. In this paper, various NHP ischemic stroke models studied recently are summarized. The imaging protocols available for quantitative MRI measurements of NHP stroke models are introduced. In addition, data acquisition and physiological motion correction of high-resolution diffusion tensor imaging and continuous arterial-spin-labeling(CASL) based perfusion imaging for NHP are illustrated and discussed. The article provides an overview of NHP stroke models and approach for implementing quantitative multi-parameter MRI evaluation to characterize stroke injury for therapy and drug discovery.

Key words: non-human primate, ischemic stroke model, high-resolution MRI, diffusion-perfusion mismatch, physiological motion correction

中图分类号:

R445.2

张晓东. 灵长类中风模型的磁共振成像[J]. 波谱学杂志, 2010, 27(4): 548-561.

ZHANG Xiao-Dong. Magnetic Resonance Imaging of Non-Human Primate Ischemic Stroke Models[J]. Chinese Journal of Magnetic Resonance, 2010, 27(4): 548-561.

参考文献

[1] Hossmann K A. Experimental models for the investigation of brain ischemia[J]. Cardiovasc Res, 1998, 39(1): 106-120.

[2] Hossmann K A. Cerebral ischemia: models, methods and outcomes[J]. Neuropharmacology, 2008, 55(3): 257-270.

[3] Richard Green A, Odergren T, Ashwood T. Animal models of stroke: do they have value for discovering neuroprotective agents?[J]. Trends Pharmacol Sci, 2003, 24(8): 402-408.

[4] Bacigaluppi M, Comi G, Hermann D M. Animal models of ischemic stroke. Part two: modeling cerebral ischemia[J]. Open Neurol J, 2010, 4: 34-38.

[5] Durukan A, Tatlisumak T. Acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia[J]. Pharmacol Biochem Behav, 2007, 87(1): 179-197.

[6] Durukan A, Tatlisumak T. Animal models of ischemic stroke (Chapter 3)[M]. Handb Clin Neurol, 2008, 92: 43-66.

[7] Durukan A, Strbian D, Tatlisumak T. Rodent models of ischemic stroke: a useful tool for stroke drug development[J]. Curr Pharm Des, 2008, 14(4): 359-370.

[8] Donnan G A, Davis S M. Stroke drug development: usually, but not always, animal models[J]. Stroke, 2005, 36(10): 2 326.

[9] Feigin V L, Lawes C M, Bennett D A, et al. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century[J]. Lancet Neurol, 2003, 2(1): 43-53.

[10] Yepes M, Roussel B D, Ali C, et al. Tissue-type plasminogen activator in the ischemic brain: more than a thrombolytic[J]. Trends Neurosci, 2009, 32(1): 48-55.

[11] Sena E S, Briscoe C L, Howells D W, et al. Factors affecting the apparent efficacy and safety of tissue plasminogen activator in thrombotic occlusion models of stroke: systematic review and meta-analysis[J]. J Cereb Blood Flow Metab, 2010, in press.

[12] Gilligan A K, Thrift A G, Sturm J W, et al. Stroke units, tissue plasminogen activator, aspirin and neuroprotection: which stroke intervention could provide the greatest community benefit?[J]. Cerebrovasc Dis, 2005, 20(4): 239-244.

[13] Wahlgren N G, Ahmed N. Neuroprotection in cerebral ischaemia: facts and fancies-the need for new approaches[J]. Cerebrovasc Dis, 2004, 17(Suppl 1): 153-166.

[14] Liebeskind D S, Kasner S E. Neuroprotection for ischaemic stroke: an unattainable goal?[J]. CNS Drugs, 2001, 15(3): 165-174.

[15] Lutsep H L, Clark W M. Neuroprotection in acute ischaemic stroke. Current status and future potential[J]. Drugs R D, 1999, 1(1): 3-8.

[16] Howells D W, Donnan G A. Where will the next generation of stroke treatments come from?[J]. PLoS Med, 2010, 7(3): e1000224.

[17] Ginsberg M D. Current status of neuroprotection for cerebral ischemia: synoptic overview[J]. Stroke, 2009, 40(3 Suppl): S111-S114.

[18] Ginsberg M D. Neuroprotection for ischemic stroke: past, present and future[J]. Neuropharmacology, 2008, 55(3): 363-389.

[19] Zivin J A, Grotta J C. Animal stroke models. They are relevant to human disease[J]. Stroke, 1990, 21(7): 981-983.

[20] STAIR. Recommendations for standards regarding preclinical neuroprotective and restorative drug development[J]. Stroke, 1999, 30(12): 2 752-2 758.

[21] Fukuda S, del Zoppo G J. Models of focal cerebral ischemia in the nonhuman primate[J]. ILAR J, 2003, 44(2): 96-104.

[22] Bihel E, Pro-Sistiaga P, Letourneur A, et al. Permanent or transient chronic ischemic stroke in the non-human primate: behavioral, neuroimaging, histological, and immunohistochemical investigations[J]. J Cereb Blood Flow Metab, 2009, 30(2): 273-285.

[23] D'Arceuil H E, Duggan M, He J, et al. Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution[J]. J Med Primatol, 2006, 35(2): 78-86.

[24] Marshall J W, Ridley R M. Assessment of cognitive and motor deficits in a marmoset model of stroke[J]. ILAR J, 2003, 44(2): 153-160.

[25] Roitberg B, Khan N, Tuccar E, et al. Chronic ischemic stroke model in cynomolgus monkeys: behavioral, neuroimaging and anatomical study[J]. Neurol Res, 2003, 25(1): 68-78.

[26] Spetzler R F, Selman W R, Weinstein P, et al. Chronic reversible cerebral ischemia: evaluation of a new baboon model[J]. Neurosurgery, 1980, 7(3): 257-261.

[27] de Crespigny A J, D'Arceuil H E, Maynard K I, et al. Acute studies of a new primate model of reversible middle cerebral artery occlusion[J]. J Stroke Cerebrovasc Dis, 2005, 14(2): 80-87.

[28] Jungreis C A, Nemoto E, Boada F, et al. Model of reversible cerebral ischemia in a monkey model[J]. AJNR Am J Neuroradiol, 2003, 24(9): 1 834-1 836.

[29] LaVerde G, Nemoto E, Jungreis C A, et al. Serial triple quantum sodium MRI during non-human primate focal brain ischemia[J]. Magn Reson Med, 2007, 57(1): 201-205.

[30] Bakker D, Pauwels E K. Stroke: the role of functional imaging[J]. Eur J Nucl Med, 1997, 24(1): 2-5.

[31] Bang O Y. Multimodal MRI for ischemic stroke: from acute therapy to preventive strategies[J]. J Clin Neurol, 2009, 5(3): 107-119.

[32] Novak V, Abduljalil A M, Novak P, et al. High-resolution ultrahigh-field MRI of stroke[J]. Magn Reson Imaging, 2005, 23(4): 539-548.

[33] Larkman D J, Nunes R G. Parallel magnetic resonance imaging[J]. Phys Med Biol, 2007, 52(7): R15-R55.

[34] Liu X, Zhu T, Gu T, et al. Optimization of in vivo high-resolution DTI of non-human primates on a 3T human scanner[J]. Methods, 2010, 50(3): 205-13.

[35] Hu X, Norris D G. Advances in high-field magnetic resonance imaging[J]. Annu Rev Biomed Eng, 2004, 6: 157-184.

[36] Jahng G H, Weiner M W, Schuff N. Improved arterial spin labeling method: applications for measurements of cerebral blood flow in human brain at high magnetic field MRI[J]. Med Phys, 2007, 34(11): 4 519-4 525.

[37] Jones S C, Kharlamov A, Yanovski B, et al. Stroke onset time using sodium MRI in rat focal cerebral ischemia[J]. Stroke, 2006, 37(3): 883-888.

[38] Thulborn K R, Davis D, Snyder J, et al. Sodium MR imaging of acute and subacute stroke for assessment of tissue viability[J]. Neuroimaging Clin N Am, 2005, 15(3): 639-653, xi-xii.

[39] Thulborn K R, Gindin T S, Davis D, et al. Comprehensive MR imaging protocol for stroke management: tissue sodium concentration as a measure of tissue viability in nonhuman primate studies and in clinical studies[J]. Radiology, 1999, 213(1): 156-166.

[40] Wang Y, Hu W, Perez-Trepichio A D, et al. Brain tissue sodium is a ticking clock telling time after arterial occlusion in rat focal cerebral ischemia[J]. Stroke, 2000, 31(6): 1 386-1 391; discussion 1392.

[41] Marks M P, Tong D C, Beaulieu C, et al. Evaluation of early reperfusion and i.v. tPA therapy using diffusion and perfusion weighted MRI[J]. Neurology, 1999, 52(9): 1 792-1 798.

[42] de Crespigny A J, Tsuura M, Moseley M E, et al. Perfusion and diffusion MR imaging of thromboembolic stroke[J]. J Magn Reson Imaging, 1993, 3(5): 746-754.

[43] Minematsu K, Fisher M, Li L M, et al. Diffusion and perfusion magnetic-resonance-imaging studies to evaluate a noncompetitive N-methyl-D-aspartate antagonist and reperfusion in experimental stroke in rats[J]. Stroke, 1993, 24(12): 2 074-2 081.

[44] Tatlisumak T, Li F. Use of diffusion and perfusion weighted magnetic resonance imaging in drug development for ischemic stroke[J]. Curr Drug Targets CNS Neurol Disord, 2003, 2(2): 131-141.

[45] Tatlisumak T, Strbian D, Abo Ramadan U, et al. The role of diffusion- and perfusion-weighted magnetic resonance imaging in drug development for ischemic stroke: from laboratory to clinics[J]. Curr Vasc Pharmacol, 2004, 2(4): 343-355.

[46] Jensen U R, Liu J R, Eschenfelder C, et al. The correlation between quantitative T2' and regional cerebral blood flow after acute brain ischemia in early reperfusion as demonstrated in a middle cerebral artery occlusion/reperfusion model of the rat[J]. J Neurosci Methods, 2009, 178(1): 55-58.

[47] Melhem E R, Mori S, Mukundan G, et al. Diffusion tensor MR imaging of the brain and white matter tractography[J]. AJR Am J Roentgenol, 2002, 178(1): 3-16.

[48] Gillard J H, Papadakis N G, Martin K, et al. MR diffusion tensor imaging of white matter tract disruption in stroke at 3 T[J]. Br J Radiol, 2001, 74(883): 642-647.

[49] Chen Z, Ni P, Zhang J, et al. Evaluating ischemic stroke with diffusion tensor imaging[J]. Neurol Res, 2008, 30(7): 720-726.

[50] Mukherjee P. Diffusion tensor imaging and fiber tractography in acute stroke[J]. Neuroimaging Clin N Am, 2005, 15(3): 655-665, xii.

[51] Sotak C H. The role of diffusion tensor imaging in the evaluation of ischemic brain injury - a review[J]. NMR Biomed, 2002,15(7/8): 561-569.

[52] Weih K S, Driesel W, von Mengershausen M, et al. Online motion correction for diffusion-weighted segmented-EPI and FLASH imaging
[J]. MAGMA, 2004, 16(6): 277-283.

[53] Ulug A M, Barker P B, van Zijl P C. Correction of motional artifacts in diffusion-weighted images using a reference phase map[J]. Magn Reson Med, 1995, 34(3): 476-480.

[54] Huang S, Zhang X. Physiological motion artifact correction in segmented DTI measurement of anesthetized non-human primates[M]. Honolulu: Proc Intl Soc Mag Reson Med, 2009. 1 503.

[55] Detre J A, Leigh J S, Williams D S, et al. Perfusion imaging[J]. Magn Reson Med, 1992, 23(1): 37-45.

[56] Wang J, Zhang Y, Wolf R L, et al. Amplitude-modulated continuous arterial spin-labeling 3.0 T perfusion MR imaging with a single coil: feasibility study[J]. Radiology, 2005, 235(1): 218-228.

[57] Talagala S L, Ye F Q, Ledden P J, et al. Wholebrain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil[J]. Magn Reson Med, 2004, 52(1): 131-140.

[58] Kim S G. Quantification of relative cerebral blood flow change by flow-sensitive alternating inversion recovery (FAIR) technique: application to functional mapping[J]. Magn Reson Med, 1995, 34(3): 293-301.

[59] Zhang X, Nagaoka T, Auerbach E J, et al. Quantitative basal CBF and CBF fMRI of rhesus monkeys using three-coil continuous arterial spin labeling[J]. Neuroimage, 2007, 34(3): 1 074-1 083.

[60] Restom K, Behzadi Y, Liu T T. Physiological noise reduction for arterial spin labeling functional MRI[J]. Neuroimage, 2006, 31(3): 1 104-1 115.

[61] Pfeuffer J, Van de Moortele P F, Ugurbil K, et al. Correction of physiologically induced global off-resonance effects in dynamic echoplanar and spiral functional imaging[J]. Magn Reson Med, 2002, 47(2): 344-353.

[62] Van de Moortele P F, Pfeuffer J, Glover G H, et al. Respiration-induced B₀ fluctuations and their spatial distribution in the human brain at 7 Tesla[J]. Magn Reson Med, 2002, 47(5): 888-895.

[63] Hu X, Le T H, Parrish T, et al. Retrospective estimation and correction of physiological fluctuation in functional MRI[J]. Magn Reson Med, 1995, 34(2): 201-212.

[64] Zhang X, Nagaoka T, Champion R, et al. Physiological motion correction of ASL fMRI measurement of rhesus monkey[M]. Toronto: Proc Intl Soc Mag Reson Med, 2008. 3 129.

[65] Huang J, Mocco J, Choudhri T F, et al. A modified transorbital baboon model of reperfused stroke[J]. Stroke, 2000, 31(12): 3 054-3 063.
[66] West G A, Golshani K J, Doyle K P, et al. A new model of cortical stroke in the rhesus macaque[J]. J Cereb Blood Flow Metab, 2009, 29(6): 1 175-1 186.

[67] Chin Y, Sato Y, Mase M, et al. Transient decrease in cerebral motor pathway fractional anisotropy after focal ischemic stroke in monkey[J]. Neurosci Res, 2010, 66(4): 406-411.

[68] Marshall J W, Ridley R M, Baker H F, et al. Serial MRI, functional recovery, and long-term infarct maturation in a non-human primate model of stroke[J]. Brain Res Bull, 2003, 61(6): 577-585.

[69] Coon A L, Arias-Mendoza F, Colby G P, et al. Correlation of cerebral metabolites with functional outcome in experimental primate stroke using in vivo ¹H-magnetic resonance spectroscopy[J]. AJNR Am J Neuroradiol, 2006, 27(5): 1 053-1 058.

[70] LaVerde G C, Jungreis C A, Nemoto E, et al. Sodium time course using ²³Na MRI in reversible focal brain ischemia in the monkey[J]. J Magn Reson Imaging, 2009, 30(1): 219-223.