兔囊状动脉瘤模型不同造影复查方法的比较性研究
摘要
研究背景：
介入技术及栓塞材料越来越多的应用于颅内动脉瘤的治疗中，评价介入栓塞技术及栓塞材料的治疗效果、安全性显得尤为重要，目前动脉瘤模型及制作方法多种多样，实验动物包括鼠、兔、犬、猪、灵长类动物等，制作方法包括：改变血流动力学、血管移植、弹性蛋白酶、局部动脉管壁破坏等方法。其中弹性蛋白酶诱发的兔动脉瘤模型是近几年新建立的模型，该法为应用弹力蛋白酶消化右侧颈总动脉，从而获得动脉瘤模型。该模型在动脉瘤形态、病理结构、血流动力学、临床行为与人类动脉瘤都非常相似，费用低廉，易于获得，广泛应用于动脉瘤研究的各个领域。模型动脉瘤栓塞后如何正确评价栓塞治疗效果，对评价栓塞材料的治疗作用至关重要，目前评定动脉瘤栓塞效果主要依靠影像学检查和病理组织学检查。影像学评价是模型动脉瘤栓塞后长期随访复查的主要手段，影像学评价包括数字血管造影（DSA）、CT血管造影（CTA）、磁共振血管造影（MRA）。数字血管造影（DSA）为其最佳方法，经股动脉入路为最常用手段，但是由于兔血管较细，尤其是进行液态栓塞材料的实验性研究时往往需结扎双侧股动脉，从而导致了经股动脉入路造影复查无法进行。今年来研究者多采用经兔耳缘静脉血管造影进行复查，然而我们认为该手段所获得的造影图片清晰度较差。也有研究者通过耳中央动脉入路进行复查，不过我们通过实验认为该法仍不能达到理想效果。兔颅内主要由椎基底动脉系统供血，约占80%左右，双侧颈总动脉供血只占20%左右，左侧颈总动脉毗邻兔模型动脉瘤，故我们尝试经左侧颈总动脉血管造影显示弹性蛋白酶诱导兔动脉瘤大小及形态，对其可行性及效果进行初步分析。
实验目的：
探讨经左侧颈总动脉造影显示兔囊状动脉瘤的可行性，比较不同血管造影途径显示兔囊状动脉瘤的特点。
实验方法：
成年健康中国大耳白兔10只，采用介入球囊封堵技术结合弹性蛋白酶诱导兔模型动脉瘤。
动脉模型制作三周后，10只大耳白兔分别经左侧股动脉、右侧耳缘静脉、左侧耳中央动脉、左侧颈总动脉血管造影显示模型动脉瘤。
两名放射线科医师独立应用数字减影血管造影机（Siemens，德国）工作站内置测量仪测量囊状动脉瘤瘤体的宽径、长径及瘤颈，取两者平均值为实验结果。
实验结果：
经左侧颈总动脉显示动脉瘤长径、宽径及颈宽与经股动脉无统计学差异，经左侧耳中央动脉、右侧耳缘静脉显示动脉瘤长径、宽径及颈宽与经股动脉有统计学差异
结论：
不同血管造影途径具有不同的特点，经左侧颈总动脉造影可以获得更加清晰的图像和更加准确的测量数据。
Background：
Intracranial aneurysm is a very common disease. Autopsy studies have shown that theoverall frequency in the general population ranges from1to5percent. Most of the patientsare ranging from40to60, and the ratio between men and women is2:3. Just followedCerebral thrombosis and Hypertensive intracerebral hemorrhage, intracranial aneurysm rankthird in patients who suffer from cerebrovascular accident.It has high morbidity andmortality which imposes great loads on families ana society. The symptoms include thereaspects which are hemorrhage, ischemia and mass effects. CTA (computed tomographyangiography) and MRA (magnetic resonance angiography) were more and more used todiagnosis this disease, but DSA (Digital subtraction angiography) is still the golden standard.There are there choices to treat intracranial aneurysms including conservative treatment,clipping and embolizing. In2002ISAT (International Subarachnoid Aneurysm Trial)reported that there is no differences in mortality and recurrence at one later after surgerybetween surgical treatment and endovascular treatment. However endovascular dramaticallyimprove the quality of life of the patients with little invasiveness. Recently embolicaltechniques and materials have made great progress,including remodling, stent, coated coils,liquid embolical materials and so on.It is especially important to evaluate medical functionand safety of embolid techniques and materials.It is also important to make animal aneurysmmodel which are similar to human aneurysms in histology and haemodynamic.Elastae-inducee aneurysm model in rabbits are very similar to human aneurysms inmorphology, pathology, haemodynamic, clinical manifestations. They are very cheap andeasily acquired, which are broadly used in every aspects of aneurismal research. How tocorrectly evaluate therapeutic effect of embolical aneurysms is critical to assess medicaleffect of embolic materials. Image and pathology are means to evaluate therapeutic effect ofembolical aneurysms. Image is mainly mean in long term follow-up of embolical aneurysms,which incude DSA, CTA, MRA. DSA divide into femoral arterial angiography, ear marginvein angiography in rabbits, middle arterial angiography in rabbits ear, and femoral arterialangiography is gold standard.However bilateral femoral arteries have been ligated afterembolization, and there is statistical difference among femoral arterial angiography, ear margin vein angiography in rabbits, middle arterial angiography in rabbits ear. Ear marginvein angiography in rabbits and middle arterial angiography in rabbits ear cannot comparewith femoral arterial angiography in image resolution. Vertebrobasilar artery system mainlysupply brain in rabbits, accounting for approximate80%, while bilateral common carotidarteries account for20%in blood supply. Left carotid artery adjacent to model aneurysms inrabbits, so we will show elastase-induced aneurysms in rabbits through left common carotidartery, and analyse its feasibility and treatmen effect.
Purpose：
Investigate the feasibility of showing saccular aneurysms in rabbits through leftcommon carotid artery, and compare features of different angiography ways to showsaccular aneurysms in rabbits.
Methods：
We made model aneurysms in ten china rabbits through ballon occlusion technique andelastase.
We show model aneurysms separately through left femoral artery angiography, right earmargin vein angiography, left middle artery in rabbits ear, and left common carotid artery.
Two radiological doctors separately measure the width, length and neck width withmeasuring apparatus in DSA workstation, and take average as results.
Results：
There is no statistical difference between contrast via femoral artery anc left commoncarotid artery in showing width, length, neck width of model aneurysms. However, therehave a statistical difference between contrast via femoral artery and left ear middle artery,righe ear margin vein.
Conclusions：
Contrast via left common carotid artery could replace contrast via lefe ear middle arteryor right ear margin vein, and become the main way of evaluating model aneurysms infollow-up.
介入技术及栓塞材料越来越多的应用于颅内动脉瘤的治疗中，评价介入栓塞技术及栓塞材料的治疗效果、安全性显得尤为重要，目前动脉瘤模型及制作方法多种多样，实验动物包括鼠、兔、犬、猪、灵长类动物等，制作方法包括：改变血流动力学、血管移植、弹性蛋白酶、局部动脉管壁破坏等方法。其中弹性蛋白酶诱发的兔动脉瘤模型是近几年新建立的模型，该法为应用弹力蛋白酶消化右侧颈总动脉，从而获得动脉瘤模型。该模型在动脉瘤形态、病理结构、血流动力学、临床行为与人类动脉瘤都非常相似，费用低廉，易于获得，广泛应用于动脉瘤研究的各个领域。模型动脉瘤栓塞后如何正确评价栓塞治疗效果，对评价栓塞材料的治疗作用至关重要，目前评定动脉瘤栓塞效果主要依靠影像学检查和病理组织学检查。影像学评价是模型动脉瘤栓塞后长期随访复查的主要手段，影像学评价包括数字血管造影（DSA）、CT血管造影（CTA）、磁共振血管造影（MRA）。数字血管造影（DSA）为其最佳方法，经股动脉入路为最常用手段，但是由于兔血管较细，尤其是进行液态栓塞材料的实验性研究时往往需结扎双侧股动脉，从而导致了经股动脉入路造影复查无法进行。今年来研究者多采用经兔耳缘静脉血管造影进行复查，然而我们认为该手段所获得的造影图片清晰度较差。也有研究者通过耳中央动脉入路进行复查，不过我们通过实验认为该法仍不能达到理想效果。兔颅内主要由椎基底动脉系统供血，约占80%左右，双侧颈总动脉供血只占20%左右，左侧颈总动脉毗邻兔模型动脉瘤，故我们尝试经左侧颈总动脉血管造影显示弹性蛋白酶诱导兔动脉瘤大小及形态，对其可行性及效果进行初步分析。
实验目的：
探讨经左侧颈总动脉造影显示兔囊状动脉瘤的可行性，比较不同血管造影途径显示兔囊状动脉瘤的特点。
实验方法：
成年健康中国大耳白兔10只，采用介入球囊封堵技术结合弹性蛋白酶诱导兔模型动脉瘤。
动脉模型制作三周后，10只大耳白兔分别经左侧股动脉、右侧耳缘静脉、左侧耳中央动脉、左侧颈总动脉血管造影显示模型动脉瘤。
两名放射线科医师独立应用数字减影血管造影机（Siemens，德国）工作站内置测量仪测量囊状动脉瘤瘤体的宽径、长径及瘤颈，取两者平均值为实验结果。
实验结果：
经左侧颈总动脉显示动脉瘤长径、宽径及颈宽与经股动脉无统计学差异，经左侧耳中央动脉、右侧耳缘静脉显示动脉瘤长径、宽径及颈宽与经股动脉有统计学差异
结论：
不同血管造影途径具有不同的特点，经左侧颈总动脉造影可以获得更加清晰的图像和更加准确的测量数据。
Background：
Intracranial aneurysm is a very common disease. Autopsy studies have shown that theoverall frequency in the general population ranges from1to5percent. Most of the patientsare ranging from40to60, and the ratio between men and women is2:3. Just followedCerebral thrombosis and Hypertensive intracerebral hemorrhage, intracranial aneurysm rankthird in patients who suffer from cerebrovascular accident.It has high morbidity andmortality which imposes great loads on families ana society. The symptoms include thereaspects which are hemorrhage, ischemia and mass effects. CTA (computed tomographyangiography) and MRA (magnetic resonance angiography) were more and more used todiagnosis this disease, but DSA (Digital subtraction angiography) is still the golden standard.There are there choices to treat intracranial aneurysms including conservative treatment,clipping and embolizing. In2002ISAT (International Subarachnoid Aneurysm Trial)reported that there is no differences in mortality and recurrence at one later after surgerybetween surgical treatment and endovascular treatment. However endovascular dramaticallyimprove the quality of life of the patients with little invasiveness. Recently embolicaltechniques and materials have made great progress,including remodling, stent, coated coils,liquid embolical materials and so on.It is especially important to evaluate medical functionand safety of embolid techniques and materials.It is also important to make animal aneurysmmodel which are similar to human aneurysms in histology and haemodynamic.Elastae-inducee aneurysm model in rabbits are very similar to human aneurysms inmorphology, pathology, haemodynamic, clinical manifestations. They are very cheap andeasily acquired, which are broadly used in every aspects of aneurismal research. How tocorrectly evaluate therapeutic effect of embolical aneurysms is critical to assess medicaleffect of embolic materials. Image and pathology are means to evaluate therapeutic effect ofembolical aneurysms. Image is mainly mean in long term follow-up of embolical aneurysms,which incude DSA, CTA, MRA. DSA divide into femoral arterial angiography, ear marginvein angiography in rabbits, middle arterial angiography in rabbits ear, and femoral arterialangiography is gold standard.However bilateral femoral arteries have been ligated afterembolization, and there is statistical difference among femoral arterial angiography, ear margin vein angiography in rabbits, middle arterial angiography in rabbits ear. Ear marginvein angiography in rabbits and middle arterial angiography in rabbits ear cannot comparewith femoral arterial angiography in image resolution. Vertebrobasilar artery system mainlysupply brain in rabbits, accounting for approximate80%, while bilateral common carotidarteries account for20%in blood supply. Left carotid artery adjacent to model aneurysms inrabbits, so we will show elastase-induced aneurysms in rabbits through left common carotidartery, and analyse its feasibility and treatmen effect.
Purpose：
Investigate the feasibility of showing saccular aneurysms in rabbits through leftcommon carotid artery, and compare features of different angiography ways to showsaccular aneurysms in rabbits.
Methods：
We made model aneurysms in ten china rabbits through ballon occlusion technique andelastase.
We show model aneurysms separately through left femoral artery angiography, right earmargin vein angiography, left middle artery in rabbits ear, and left common carotid artery.
Two radiological doctors separately measure the width, length and neck width withmeasuring apparatus in DSA workstation, and take average as results.
Results：
There is no statistical difference between contrast via femoral artery anc left commoncarotid artery in showing width, length, neck width of model aneurysms. However, therehave a statistical difference between contrast via femoral artery and left ear middle artery,righe ear margin vein.
Conclusions：
Contrast via left common carotid artery could replace contrast via lefe ear middle arteryor right ear margin vein, and become the main way of evaluating model aneurysms infollow-up.
引文
[1] Bouzeghrane F,Naggara O,Kallmes DF,et al.In vivo experimental intracranial aneurysmmodels:a systematic review[J]. AJNR Am J Neuroradiol.2010;31(3):418-423.
[2] Frosen J, Marjamaa J, Myllarniemi M, et al. Contribution of mural and bonemarrow-derived neointimal cells to thrombus organization and wall remodeling in amicrosurgical murine saccular aneurysm model[J]. Neurosurgery.2006;58(5):936–944.
[3] Raymond J, Lebel V, Ogoudikpe C, et al. Recanalization of arterial thrombus andinhibition with beta-radiation in a new murine carotid occlusion model: MRN Aexpression of angiopoietins, metalloproteinases, and their inhibitors[J].J Vasc Surg.2004;40(6):1190–1198.
[4] Abrahams JM, Forman MS, Grady MS, et al. Biodegradable polyglycolide endovascularcoils promote wall thickening and drug delivery in a rat aneurysmmodel[J].Neurosurgery.2001;49(5):1187–1193.
[5] Kadirvel R, Ding YH, Dai D, et al. Molecular indices of apoptosis activation inelastase-induced aneurysms after embolization with platinum coils[J].Stroke.2007;38(10):2787-2794．
[6] Ding YH, Dai D, Danielson MA, et al.Intra-Arterial Digital Subtraction AngiographyThrough the Ear Artery for Experimental Aneurysm Imaging[J]. AJNR Am J Neuroradiol.2006;27(8):1700-1702.
[7]谢谦宇,卢川,蒋雪梅.血管内球囊阻断结合弹力酶诱导法制作颅内动脉瘤动物模型及应用进展[J].介入放射学杂志.2009;18(10):786-788.
[8] Bo¨cher-Schwarz HG, Ringel K, Bohl J, et al. Histological findings in coilpackedexperimental aneurysms3months after embolization[J].Neurosurgery.2002;50,379–385.
[9] Spetzger U, Reul J, Weis J, et al. Microsurgically produced bifurcation aneurysms in arabbit model for endovascular coil embolization[J]. J Neurosurg.1996;85:488–495.
[10]Reul J, Weis J, Spetzger U, et al. Long-term angiographic and histopathologic findingsin experimental aneurysms of the carotid bifurcation embolized with platinum andtungsten coils[J]. AJNR Am J Neuroradiol.1997;18:35–42.
[11]Spetzger UJ, Reul J, Weis J. Endovascular coil embolization of microsurgicallyproduced experimental bifurcation aneurysms in rabbits[J].Surg Neurol.1998;49:491–504.
[12]Tsumoto T, Song JK, Niimi Y, et al. Interval change in size of venous pouch cani-nebifurcation aneurysms over a10-month period. AJNR Am J Neuroradiol.2008;29:1067–1070.
[13]Byrne JV, Hope JK, Hubbard N, et al. The nature of thrombosis induced by platinum andtungsten coils in saccular aneurysms[J]. AJNR Am J Neuroradiol.1997;18:29–33.
[14]Guglielmi G,Ji C,Massoud TF,et al.Experime-ntal saccular aneurysms.II.A new modelin swine.Neuroradiology[J].1994;36(7):547-550.
[15]Murayama Y, Vinuela F, Suzuki Y, et al. Development of the biologically activeGuglielmi detachable coil for the treatment of cerebral aneurysms. Part II. AnExperimental study in a swine aneurysm model[J]. AJNR Am J Neuroradiol1999;20:1992–1999.
[16]Raymond J, Venne D, Allas S, et al. Healing mechanisms in experimental aneurysms.I.Vascular smooth muscle cells and neointima formation[J]. J Neuroradiol.1999;26:7–20.
[17]Lee D, Yuki I, Murayama Y, et al. Thrombus organization and healing in the swineexperimental aneurysm model. Part I. A histological and molecular analysis[J]. JNeurosurg.2007;107:94–108.
[18] Zeng Z, Kallmes DF, Durka MJ,et al.Hemodynamics and Anatomy of Elastase-InducedRabbit Aneurysm Models: Similarity to Human Cerebral Aneurysms?[J] AJNR Am JNeuroradiol.2011;32(3):595-601.
[19] Yang XJ, Li L, Wu ZX.et al.A novel arterial pouch model of saccular aneurysm byconcomitant elastase and collagenase digestion[J].J Zhejiang Univ Sci B.2007;8(10):697-703.
[20] Hashimoto N, Handa H, Hazama F,et al.Experimentally induced cerebral aneurysms inrats[J].Surg Neurol.1979;11(4):299-304.
[21] Hashimoto N, Kim C, Kikuchi H,et al.Experimental induction of cerebral aneur-ysmsin monkeys. J Neurosurg[J].1987;67(6):903-905.
[22] Kim C, Kikuchi H, Hashimoto N,et al.Histopathological study of induced cerebralaneurysms in primates[J]. Surg Neurol.1989;32(1):45-50.
[23] Gao L, Hoi Y, Swartz DD,et al.Nascent aneurysm formation at the basilar terminusinduced by hemodynamics[J]. Stroke.2008;39(7):2085-2090.
[24] Meng H, Wang Z, Hoi Y, Complex hemodynamics at the apex of an arterial bifurcationinduces vascular remodeling resembling cerebral aneurysm initiation [J].Stroke.2007;38(6):1924-1931.
[25] German WJ,Black PW. Experimental production of carotid aneurysms.N Engl JMed[J].1954;250:104-106.
[26]杨志刚,刘建民,王奎重等,犬侧壁动脉瘤模型建立方法的改良及评价[J].介入放射学杂志.2009;18(10):748-752.
[27]赵丛海,杨新健,张金男等,一种经酶处理新型动脉瘤动物模型的建立[J].中华实验外科杂志.2005;22(7):873-874.
[28] Anidjar S, Salzmann JL, Gentric D, et al. Elastase-induced experimental aneurysms inrats[J]. Circulation.1990;82(3):973-981.
[29] Yamaguchi T,YokokawaM,SuzukiM,et al.The time course of elastin fiber degenerationin a rat aneurysm model[J]. Surg Today,2000;30(8):727-731.
[30] Miskolczi L,Guterman LR,Flaherty JD,et al.Saccular aneurysm induction by elastasedigestion of the arterial wall:a new animal model[J]. Neurosurgery,1998;43(3),595-601.
[31]孙正辉,许百男,周定标等,弹性蛋白酶制作囊性动脉瘤模型的实验研究[J].解放军医学杂志.2004;29(11):971-972.
[32] Cloft HJ, Altes TA, Marx WF, et al. Endovascular creation of an in vivo bifurcationaneurysm model in rabitt[J]. Radiology.1999;213(1):223-228.
[33] Thiex R, Hans FJ, Krings T, et al. Haemorrhagic tracheal necrosis as a lethalcomplication of an aneurysm model in rabbits via endoluminal incubation withelastase[J]. Acta Neurochir(Wien).2004;146(3):285-289.
[34] M ller-Hartmann W, Krings T, Stein KP, et al. Aberrant origin of the superior thyroidartery and the tracheoesophageal branch from the common carotid artery: a source offailure in elastase-induced aneurysms in rabbits[J]. AJR Am J Roentgenol.2003;181(3):739-741.
[35] Hoh BL, Rabinov JD, Pryor JC, et al. A modified technique for using elastase to createsaccular aneurysms in animals that histologically and hemodynamically Resembleaneurysms in human[J]. Acta Neurochir (Wien).2004;146(7):705-711.
[36] Quigley MR,Tuite GF,Cozzens JW.Histology and angiography in a bifurcationaneurysm model[J].Surg Neurol.1988;30(6):445-451.
[37] Marty B,von Segesser LK,Uhlschmid G,et al.Experimental aortic aneurysm withendovascular technique.Vasa[J],1995;24(2):184-189.
[38] Narayanan AS, Siegel RC, Martin GR,et al.On the inhibition of lysyl oxidase byβ-aminopropionitrile[J].Biochem Biophys Res Commun.1972;46(2):745-751.
[39] Tang SS, Trackman PC, Kagan HM,et al.Reaction of aortic lysyl oxidase withβ-aminopropionitrile[J]. J Biol Chem.1983;258(7):4331-4338.
[40] Barrow MV, Simpson CF, Miller EJ.Lathyrism: a review[J].Q Rev Biol.1974;49(2):101-128.
[41] Kallmes DF, Fujiwara NH, Berr SS, et al. Elastase-Induced Saccular Aneurysms inRabbits: A Dose-Escalation Study[J]. AJNR Am J Neuroradiol.2002;23(2):295-298.
[42] Altes TA, Cloft HJ, Short JG, et al. Short Creation of Saccular Aneurysms in theRabbit:A Model Suitable for Testing Endovascular Devices[J]. AJR Am J Roentgenol.2000;174(2):349-354.
[43] Thiex R, M ller-Hartmann W, Hans FJ, et al. Are the configuration and neckmorphology of experimental aneurysms predictable? A technical approach[J].Neuroradiology.2004;46(5):571-576.
[44]卢川,谢谦宇,刘林祥.血管结扎结合弹力酶诱导法兔动脉瘤模型的制作[J].介入放射学杂志.2010;19(9):722-725.
[45] Ding YH, Dai D, Lewis DA, et al. Long-Term Patency of Elastase-Induced AneurysmModel in Rabbits[J].AJNR Am J Neuroradiol.2006;27(1):139-141.
[46]祝胜，刘建民,王奎重等.兔囊性动脉瘤模型静脉造影的应用经验[J].介入放射学杂志.2009;18(7):518-520.
[47] Fujiwara NH, Cloft HJ, Marx WF, et al. Serial Angiography in an Elastase inducedAneurysm Model in Rabbits:Evidence for Progressive Aneurysm Enlargement afterCreation[J]. AJNR Am J Neuroradiol.2001;22(4):698-703.
[48] Doerfler A, Becker W, Wanke I,et al. Multimodal imaging in the elastase-inducedaneurysm model in rabbits:a comparative study using serial DSA,MRA and CTA[J].Rofo.2004;176(4):590-596.
[49] Miskolczi L, Nemes B, Cesar L, et al. Contrast Injection via the Central Artery of theLeft Ear in Rabbits: A New Technique to Simplify Follow-Up Studies[J]. AJNR Am JNeuroradiol.2005;26(8):1964-1966.
[50] Adams WM, Laitt RD, Jackson A. The role of MR angiography in the pretreatmentassessment of intracranial aneurysms: a comparative study. AJNR Am J Neuroradiol[J].2000;21(9):1618–1628.
[51] Okahara M, Kiyosue H, Yamashita M, et al. Diagnostic accuracy of magnetic resonanceangiography for cerebral aneurysms in correlation with3D-digital subtractionangiographic images: a study of133aneurysms[J]. Stroke.2002;33(7):1803-1808.
[52] Korogi Y, Takahashi M, Mabuchi N, et al. Intracranial aneurysms: diagnostic accuracyof MR angiography with evaluation of maximum intensity projection and sourceimages[J]. Radiology.1996;199(1):199–207.
[53] AAssar OS,Fujiwara NH, Marx WF, et al.Aneurysm growth, elastinolysis,and attempteddoxycyline inhibition of elastase-induced aneurysms in rabbits[J].J. Vas IntervRadiol.2003;14:1427-1432.
[54] Mangrum WI, Farassati F, Kadirvel R.mRNA expressi-on in rabbit experimentalaneurysms: a study using gene chip microarrays[J]. AJNR Am J Neuroradiol2007;28(5):864-869.
[55] Krings T, Hans FJ, Moller-Hartmann W et al. Time-of-flight-, phase contrast andcontrast enhanced magnetic resonance angiography for pre-interventional determinationof aneurysm size, configuration, and neck morphology in an aneurysm model inrabbits[J]. Neurosci Lett.2002;326:46–50
[56] Chung TS, Joo JY, Lee SK et al. Evaluation of cerebral aneurysms with high-resolutionMR angiography using a section-interpolation technique:correla-tion with digitalsubtraction angiography[J]. AJNR Am J Neuroradiol.1999;20:229-235
[57] Kallmes DF,Fujiwara NH,New expandable hydrogel-platinum coil hybrid device foraneurysm embolization[J].AJNR Am J Neuroradiol.2002;23:1580-1588.
[58] Gupta R, Mehndiratta A, Mitha AP,et al. Temporal resolution of dynamic angiog-raphyusing flat panel volume CT: in vivo evaluation of time-dependent vascularpathologies[J]. AJNR Am J Neuroradiol.2011;32(9):1688-1696.
[59] Struffert T, Doelken M, Adamek E Flat-detector computed tomography with intr-avenous contrast material application in experimental aneurysms: comparison withmultislice CT and conventional angiography. Acta Radiol.2010;51(4):431-437.
[60] Turk AS, Aagaard-Kienitz B, Niemann D, et al. Natural history of the canine vein pouchaneurysm model[J]. AJNR Am J Neuroradiol.2007;28:531–532
[61] Ding YH, Dai D, Lewis DA, et al. Angiographic and Histologic Analysis ofExperimental Aneurysms Embolized with Platinum Coils, Matrix, and HydroCoil[J].AJNR Am J Neuroradiol.2005;26(7):1757-1763.
[62] Ding YH, Dai D, Danielson MA, et al. Control of Aneurysm Volume by Adjus-ting thePosition of Ligation During Creation of Elastase-Induced Aneurysms:A ProspectiveStudy[J]. AJNR Am J Neuroradiol.2007;28(5):857-859.
[63] Kallmes DF, Ding YH, Dai D, et al. A New Endoluminal, Flow-Disrupting Devi-ce forTreatment of Saccular Aneurysms[J]. Stroke.2007;38(8):2346-2352.
[64]王奎重,刘建民,杨志刚等.渐变网格球扩支架治疗兔囊状动脉瘤[J].中国微侵袭神经外科杂志.2009;14(9):426-429.
[65] Krings T, M ller-Hartmann W, Hans FJ, et al. refined method for creating saccularaneurysms in the rabbit[J]. Neuroradiology.2003;45(7):423-429.
[66] Massoud TF,Guglielmi G,Ji C,et al.Experimental saccular aneurysms.I.Review ofsurgically-constructed models and their laboratory applications[J]. Neuroradiolo-gy.1994;36(7):537-546.
[67] Martin DE Ⅲ, Nasbeth DC,RoweMI,et al.Production of experimental aneurysms withpancreatic elastase[J].Surg Forum,1962;8:237-239.
[68] Rigamonti D,Saleh J,Liu AM,et al.Dolichoectatic aneurysm of common carotidartery:an animal model with histological correlation[J]. Pathobiology,1994;62(1):8-13.
[69] Miskolczi L,Guterman LR,Flaherty JD,et al.Saccular aneurysm induction by elastasedigestion of the arterial wall:a new animal model[J]. Neurosurgery,1998;43(3):595-600;discussion600-601.
[70]刘小杰,陈启和,孙桥.弹性蛋白酶的研究进展中国食品添加剂[J].2004;4:29-32.
[2] Frosen J, Marjamaa J, Myllarniemi M, et al. Contribution of mural and bonemarrow-derived neointimal cells to thrombus organization and wall remodeling in amicrosurgical murine saccular aneurysm model[J]. Neurosurgery.2006;58(5):936–944.
[3] Raymond J, Lebel V, Ogoudikpe C, et al. Recanalization of arterial thrombus andinhibition with beta-radiation in a new murine carotid occlusion model: MRN Aexpression of angiopoietins, metalloproteinases, and their inhibitors[J].J Vasc Surg.2004;40(6):1190–1198.
[4] Abrahams JM, Forman MS, Grady MS, et al. Biodegradable polyglycolide endovascularcoils promote wall thickening and drug delivery in a rat aneurysmmodel[J].Neurosurgery.2001;49(5):1187–1193.
[5] Kadirvel R, Ding YH, Dai D, et al. Molecular indices of apoptosis activation inelastase-induced aneurysms after embolization with platinum coils[J].Stroke.2007;38(10):2787-2794．
[6] Ding YH, Dai D, Danielson MA, et al.Intra-Arterial Digital Subtraction AngiographyThrough the Ear Artery for Experimental Aneurysm Imaging[J]. AJNR Am J Neuroradiol.2006;27(8):1700-1702.
[7]谢谦宇,卢川,蒋雪梅.血管内球囊阻断结合弹力酶诱导法制作颅内动脉瘤动物模型及应用进展[J].介入放射学杂志.2009;18(10):786-788.
[8] Bo¨cher-Schwarz HG, Ringel K, Bohl J, et al. Histological findings in coilpackedexperimental aneurysms3months after embolization[J].Neurosurgery.2002;50,379–385.
[9] Spetzger U, Reul J, Weis J, et al. Microsurgically produced bifurcation aneurysms in arabbit model for endovascular coil embolization[J]. J Neurosurg.1996;85:488–495.
[10]Reul J, Weis J, Spetzger U, et al. Long-term angiographic and histopathologic findingsin experimental aneurysms of the carotid bifurcation embolized with platinum andtungsten coils[J]. AJNR Am J Neuroradiol.1997;18:35–42.
[11]Spetzger UJ, Reul J, Weis J. Endovascular coil embolization of microsurgicallyproduced experimental bifurcation aneurysms in rabbits[J].Surg Neurol.1998;49:491–504.
[12]Tsumoto T, Song JK, Niimi Y, et al. Interval change in size of venous pouch cani-nebifurcation aneurysms over a10-month period. AJNR Am J Neuroradiol.2008;29:1067–1070.
[13]Byrne JV, Hope JK, Hubbard N, et al. The nature of thrombosis induced by platinum andtungsten coils in saccular aneurysms[J]. AJNR Am J Neuroradiol.1997;18:29–33.
[14]Guglielmi G,Ji C,Massoud TF,et al.Experime-ntal saccular aneurysms.II.A new modelin swine.Neuroradiology[J].1994;36(7):547-550.
[15]Murayama Y, Vinuela F, Suzuki Y, et al. Development of the biologically activeGuglielmi detachable coil for the treatment of cerebral aneurysms. Part II. AnExperimental study in a swine aneurysm model[J]. AJNR Am J Neuroradiol1999;20:1992–1999.
[16]Raymond J, Venne D, Allas S, et al. Healing mechanisms in experimental aneurysms.I.Vascular smooth muscle cells and neointima formation[J]. J Neuroradiol.1999;26:7–20.
[17]Lee D, Yuki I, Murayama Y, et al. Thrombus organization and healing in the swineexperimental aneurysm model. Part I. A histological and molecular analysis[J]. JNeurosurg.2007;107:94–108.
[18] Zeng Z, Kallmes DF, Durka MJ,et al.Hemodynamics and Anatomy of Elastase-InducedRabbit Aneurysm Models: Similarity to Human Cerebral Aneurysms?[J] AJNR Am JNeuroradiol.2011;32(3):595-601.
[19] Yang XJ, Li L, Wu ZX.et al.A novel arterial pouch model of saccular aneurysm byconcomitant elastase and collagenase digestion[J].J Zhejiang Univ Sci B.2007;8(10):697-703.
[20] Hashimoto N, Handa H, Hazama F,et al.Experimentally induced cerebral aneurysms inrats[J].Surg Neurol.1979;11(4):299-304.
[21] Hashimoto N, Kim C, Kikuchi H,et al.Experimental induction of cerebral aneur-ysmsin monkeys. J Neurosurg[J].1987;67(6):903-905.
[22] Kim C, Kikuchi H, Hashimoto N,et al.Histopathological study of induced cerebralaneurysms in primates[J]. Surg Neurol.1989;32(1):45-50.
[23] Gao L, Hoi Y, Swartz DD,et al.Nascent aneurysm formation at the basilar terminusinduced by hemodynamics[J]. Stroke.2008;39(7):2085-2090.
[24] Meng H, Wang Z, Hoi Y, Complex hemodynamics at the apex of an arterial bifurcationinduces vascular remodeling resembling cerebral aneurysm initiation [J].Stroke.2007;38(6):1924-1931.
[25] German WJ,Black PW. Experimental production of carotid aneurysms.N Engl JMed[J].1954;250:104-106.
[26]杨志刚,刘建民,王奎重等,犬侧壁动脉瘤模型建立方法的改良及评价[J].介入放射学杂志.2009;18(10):748-752.
[27]赵丛海,杨新健,张金男等,一种经酶处理新型动脉瘤动物模型的建立[J].中华实验外科杂志.2005;22(7):873-874.
[28] Anidjar S, Salzmann JL, Gentric D, et al. Elastase-induced experimental aneurysms inrats[J]. Circulation.1990;82(3):973-981.
[29] Yamaguchi T,YokokawaM,SuzukiM,et al.The time course of elastin fiber degenerationin a rat aneurysm model[J]. Surg Today,2000;30(8):727-731.
[30] Miskolczi L,Guterman LR,Flaherty JD,et al.Saccular aneurysm induction by elastasedigestion of the arterial wall:a new animal model[J]. Neurosurgery,1998;43(3),595-601.
[31]孙正辉,许百男,周定标等,弹性蛋白酶制作囊性动脉瘤模型的实验研究[J].解放军医学杂志.2004;29(11):971-972.
[32] Cloft HJ, Altes TA, Marx WF, et al. Endovascular creation of an in vivo bifurcationaneurysm model in rabitt[J]. Radiology.1999;213(1):223-228.
[33] Thiex R, Hans FJ, Krings T, et al. Haemorrhagic tracheal necrosis as a lethalcomplication of an aneurysm model in rabbits via endoluminal incubation withelastase[J]. Acta Neurochir(Wien).2004;146(3):285-289.
[34] M ller-Hartmann W, Krings T, Stein KP, et al. Aberrant origin of the superior thyroidartery and the tracheoesophageal branch from the common carotid artery: a source offailure in elastase-induced aneurysms in rabbits[J]. AJR Am J Roentgenol.2003;181(3):739-741.
[35] Hoh BL, Rabinov JD, Pryor JC, et al. A modified technique for using elastase to createsaccular aneurysms in animals that histologically and hemodynamically Resembleaneurysms in human[J]. Acta Neurochir (Wien).2004;146(7):705-711.
[36] Quigley MR,Tuite GF,Cozzens JW.Histology and angiography in a bifurcationaneurysm model[J].Surg Neurol.1988;30(6):445-451.
[37] Marty B,von Segesser LK,Uhlschmid G,et al.Experimental aortic aneurysm withendovascular technique.Vasa[J],1995;24(2):184-189.
[38] Narayanan AS, Siegel RC, Martin GR,et al.On the inhibition of lysyl oxidase byβ-aminopropionitrile[J].Biochem Biophys Res Commun.1972;46(2):745-751.
[39] Tang SS, Trackman PC, Kagan HM,et al.Reaction of aortic lysyl oxidase withβ-aminopropionitrile[J]. J Biol Chem.1983;258(7):4331-4338.
[40] Barrow MV, Simpson CF, Miller EJ.Lathyrism: a review[J].Q Rev Biol.1974;49(2):101-128.
[41] Kallmes DF, Fujiwara NH, Berr SS, et al. Elastase-Induced Saccular Aneurysms inRabbits: A Dose-Escalation Study[J]. AJNR Am J Neuroradiol.2002;23(2):295-298.
[42] Altes TA, Cloft HJ, Short JG, et al. Short Creation of Saccular Aneurysms in theRabbit:A Model Suitable for Testing Endovascular Devices[J]. AJR Am J Roentgenol.2000;174(2):349-354.
[43] Thiex R, M ller-Hartmann W, Hans FJ, et al. Are the configuration and neckmorphology of experimental aneurysms predictable? A technical approach[J].Neuroradiology.2004;46(5):571-576.
[44]卢川,谢谦宇,刘林祥.血管结扎结合弹力酶诱导法兔动脉瘤模型的制作[J].介入放射学杂志.2010;19(9):722-725.
[45] Ding YH, Dai D, Lewis DA, et al. Long-Term Patency of Elastase-Induced AneurysmModel in Rabbits[J].AJNR Am J Neuroradiol.2006;27(1):139-141.
[46]祝胜，刘建民,王奎重等.兔囊性动脉瘤模型静脉造影的应用经验[J].介入放射学杂志.2009;18(7):518-520.
[47] Fujiwara NH, Cloft HJ, Marx WF, et al. Serial Angiography in an Elastase inducedAneurysm Model in Rabbits:Evidence for Progressive Aneurysm Enlargement afterCreation[J]. AJNR Am J Neuroradiol.2001;22(4):698-703.
[48] Doerfler A, Becker W, Wanke I,et al. Multimodal imaging in the elastase-inducedaneurysm model in rabbits:a comparative study using serial DSA,MRA and CTA[J].Rofo.2004;176(4):590-596.
[49] Miskolczi L, Nemes B, Cesar L, et al. Contrast Injection via the Central Artery of theLeft Ear in Rabbits: A New Technique to Simplify Follow-Up Studies[J]. AJNR Am JNeuroradiol.2005;26(8):1964-1966.
[50] Adams WM, Laitt RD, Jackson A. The role of MR angiography in the pretreatmentassessment of intracranial aneurysms: a comparative study. AJNR Am J Neuroradiol[J].2000;21(9):1618–1628.
[51] Okahara M, Kiyosue H, Yamashita M, et al. Diagnostic accuracy of magnetic resonanceangiography for cerebral aneurysms in correlation with3D-digital subtractionangiographic images: a study of133aneurysms[J]. Stroke.2002;33(7):1803-1808.
[52] Korogi Y, Takahashi M, Mabuchi N, et al. Intracranial aneurysms: diagnostic accuracyof MR angiography with evaluation of maximum intensity projection and sourceimages[J]. Radiology.1996;199(1):199–207.
[53] AAssar OS,Fujiwara NH, Marx WF, et al.Aneurysm growth, elastinolysis,and attempteddoxycyline inhibition of elastase-induced aneurysms in rabbits[J].J. Vas IntervRadiol.2003;14:1427-1432.
[54] Mangrum WI, Farassati F, Kadirvel R.mRNA expressi-on in rabbit experimentalaneurysms: a study using gene chip microarrays[J]. AJNR Am J Neuroradiol2007;28(5):864-869.
[55] Krings T, Hans FJ, Moller-Hartmann W et al. Time-of-flight-, phase contrast andcontrast enhanced magnetic resonance angiography for pre-interventional determinationof aneurysm size, configuration, and neck morphology in an aneurysm model inrabbits[J]. Neurosci Lett.2002;326:46–50
[56] Chung TS, Joo JY, Lee SK et al. Evaluation of cerebral aneurysms with high-resolutionMR angiography using a section-interpolation technique:correla-tion with digitalsubtraction angiography[J]. AJNR Am J Neuroradiol.1999;20:229-235
[57] Kallmes DF,Fujiwara NH,New expandable hydrogel-platinum coil hybrid device foraneurysm embolization[J].AJNR Am J Neuroradiol.2002;23:1580-1588.
[58] Gupta R, Mehndiratta A, Mitha AP,et al. Temporal resolution of dynamic angiog-raphyusing flat panel volume CT: in vivo evaluation of time-dependent vascularpathologies[J]. AJNR Am J Neuroradiol.2011;32(9):1688-1696.
[59] Struffert T, Doelken M, Adamek E Flat-detector computed tomography with intr-avenous contrast material application in experimental aneurysms: comparison withmultislice CT and conventional angiography. Acta Radiol.2010;51(4):431-437.
[60] Turk AS, Aagaard-Kienitz B, Niemann D, et al. Natural history of the canine vein pouchaneurysm model[J]. AJNR Am J Neuroradiol.2007;28:531–532
[61] Ding YH, Dai D, Lewis DA, et al. Angiographic and Histologic Analysis ofExperimental Aneurysms Embolized with Platinum Coils, Matrix, and HydroCoil[J].AJNR Am J Neuroradiol.2005;26(7):1757-1763.
[62] Ding YH, Dai D, Danielson MA, et al. Control of Aneurysm Volume by Adjus-ting thePosition of Ligation During Creation of Elastase-Induced Aneurysms:A ProspectiveStudy[J]. AJNR Am J Neuroradiol.2007;28(5):857-859.
[63] Kallmes DF, Ding YH, Dai D, et al. A New Endoluminal, Flow-Disrupting Devi-ce forTreatment of Saccular Aneurysms[J]. Stroke.2007;38(8):2346-2352.
[64]王奎重,刘建民,杨志刚等.渐变网格球扩支架治疗兔囊状动脉瘤[J].中国微侵袭神经外科杂志.2009;14(9):426-429.
[65] Krings T, M ller-Hartmann W, Hans FJ, et al. refined method for creating saccularaneurysms in the rabbit[J]. Neuroradiology.2003;45(7):423-429.
[66] Massoud TF,Guglielmi G,Ji C,et al.Experimental saccular aneurysms.I.Review ofsurgically-constructed models and their laboratory applications[J]. Neuroradiolo-gy.1994;36(7):537-546.
[67] Martin DE Ⅲ, Nasbeth DC,RoweMI,et al.Production of experimental aneurysms withpancreatic elastase[J].Surg Forum,1962;8:237-239.
[68] Rigamonti D,Saleh J,Liu AM,et al.Dolichoectatic aneurysm of common carotidartery:an animal model with histological correlation[J]. Pathobiology,1994;62(1):8-13.
[69] Miskolczi L,Guterman LR,Flaherty JD,et al.Saccular aneurysm induction by elastasedigestion of the arterial wall:a new animal model[J]. Neurosurgery,1998;43(3):595-600;discussion600-601.
[70]刘小杰,陈启和,孙桥.弹性蛋白酶的研究进展中国食品添加剂[J].2004;4:29-32.