Relevant Study On Fusiform Aneurysm Flow Field Characteristics And Pathological Changes

Part one:Multi-Factor Analysis of Vertebral Artery Fusiform Aneurysm Geometry Parameters for Different Flow Field CharacteristicsOBJECTIVE: We measured geometry parameters of fusiform aneurysms of vertebral artery V4 segment and analyze the flow field type to determine the main geometry parameters which lead to helical flow field by Multi-Factor Analysis.METHODS: We searched all cases of fusiform aneurysm at vertebral artery V4 segment from November 2011 to October 2015 in our center.According to the inclusion criteria and exclusion criteria,all selected aneurysms were measured the geometry parameters of lumen and parent artery.The flow field analysis was performed by using CFD software.There were nine geometry parameters,representing shape,size and space position relations.According to the flow pattern map,the aneurysm is divided into helical flow field group and none-helical flow field group.The consistency of the interpretation of flow field characteristics was measured by Kappa test.Logistic regression analysis was implemented to find the main geometry parameters which lead to helical flow field.RESULTS: A total of 157 aneurysms were included in the study,including 89 cases with helical flow field and 68 cases with none-helical flow field.The consistency of the interpretation of flow field characteristics was well(Kappa = 0.896,P < 0.001).After single factor Logistic regression analysis and multi-factor Logistic regression analysis,the result shows that the proximal parent artery entrance angle(OR = 7.964,P = 7.964),distal parent artery exit angle(OR = 4.892,P = 4.892),distance between the axis of entrance plane and axis of entrance exit plane(OR = 0.015,P < 0.001)were the influence factors of the flow field characteristics.CONCLUSION: proximal parent artery entrance angle,distal parent artery exit angle,distance between the axis of the entrance plane and axis of entrance exit plane affect flow field characteristics.Aneurysms with helical flow field have smaller proximal parent artery entrance angle,smaller distal parent artery exit angle,the further distance between the axis of the entrance plane and axis of entrance exit plane.Tortuous fusiform aneurysms and parent artery was likely with helical flow field.Part two:Establishment of Fusiform Aneurysm Models ith Helical Flow Field in the RabbitPURPOSE:Injury intimal or(and)the outer membrane of the rabbit carotid artery by the combination of elastase,Ca Cl2 solution and physical expansion,and change the geometry parameters of the parent artery.We compared the different methods to introduce an optimized method for establishment of fusiform aneurysm models with helical flow field.METHODS: Forty New Zealand rabbits were divided into four groups(10 in each group): group A was the control group.A short blood vessel cavity was made by temporarily block.The indwelling needle was punctured into the closed a short blood vessel cavity,injected with normal saline for 15 min under 2 atm.Group B was treated with 0.5 M Ca Cl2 solution in the closed a short blood vessel cavity for 15 min under 2 atm.Group C: The method was similar to group A,the difference was that 0.15 U / ?l elastase was injected into the closed vessel cavity for digestion for 3 minutes instead of normal saline.The outer membrane was immersed in 0.5 M Ca Cl2 solution for 15 minutes.Group D was similar to group C.The difference was that 0.5 M Ca Cl2 was injected into the closed vessel cavity and outer membrane was immersed in 3 U / ?l elastase for 3 minutes.Geometry parameters of parent artery were changed by muscle staggered suture,resulting in a micro-environment that caused the helical flow field.After 4 weeks,MRA examination and flow field analysis were performed to measure the expansion rate((aneurysm maximal diameter-distal and proximal vessel mean diameter)/ distal and proximal vessel mean diameter),fusiform aneurysm formation rate(expansion rate ? 50%),stenosis and occlusion rate,helical flow rate.After the animals were sacrificed,the intima and medial thickness of the specimens,the area fraction of the elastic fiber area,the area fraction of the collagen fibers,and the degree of damage of the elastic layer were compared.RESULTS: MRA showed that the average expansion rates of group A,B,C and D were 13.51%,36.2%,69.1% and 77.7% respectively.Fusiform aneurysm formation rates(P <0.05)were 0%,30%,60%,90%,respectively.The average dilatation rate in group C and D was higher than that in group B(P <0.01),and there was no significant difference between group C and group D(P = 0.460).C and D were significantly higher than those in group A and B(P <0.001),and group C was similar to group D(P = 0.303).Vascular occlusions were occurred in 0 cases,1 case,3 cases,1 case respectively.3 cases in group C and 1 case in group D had stenosis.Stenosis rate of group C was higher than that the other three groups(P <0.05).Flow field analysis showed that the formation rate of helical flow field was 10%,44.4%,28.6% and 88.9%,respectively.Group A,B,C and D were higher than those in group A(P<0.0125).The Histopathology showed that elastic layer destruction in group B,C and D.And elastic fibers were significantly lower than those in group A(P <0.001),and group C and D were significantly lower than those in group B(P <0.001).The collagen fibers in group B and group C were significantly higher than those in group A and D(P <0.01).The thickness of fusiform aneurysm wall of group B was significantly thicker than that of group A,C and D(P <0.05).There was no significant difference between group A and group C.A part of models in group B and D(55.56%,66.67%)showed neointimal neovascularization.CONCLUSION: The model of fusiform aneurysm established by Ca Cl2 endo-perfusion combined with elastase outer membrane digestion method has the advantages of higher rate of fusiform aneurysm formation and lower stenosis and occlusion,with helical flow field and pathological features similar to human fusiform aneurysms.It is the appropriate model for the study of the correlation between hemodynamics and pathology.Part three: Effects of Different Flow Fields on orphology and Pathological Changes of Fusiform neurysmsOBJECTIVE: To compare the effects of two different flow field characteristics on the morphology and pathological changes of fusiform aneurysms.METHODS: Thirty-six New Zealand white rabbits were used,4 as controls,and 32 were divided into two groups.Group W was the experimental group: a short blood vessel cavity was made by temporarily block.The indwelling needle was punctured into the closed a short blood vessel cavity,injected with 0.5 M Ca Cl2 for 15 min under 2 atm.The outer membrane was immersed in 3 U / ?l elastase for 3 minutes.Geometry parameters of parent artery were changed,causing the helical flow field.The group Z was the control group: the chemical treatment was similar to the W group,except that the treated blood vessels were kept straight to form a non-helical flow field.At 6 weeks,all animals receive MRA,USPIO enhanced MRI,flow field analysis.They were divided into helical flow field group and non-helical flow field group.Aneurysm dilatation rate,stenosis and occlusion rate,MRI average SNR decline rate and other morphological indicators were compared between the two groups.After executing half of the animals,endometrial and medial thickness,elastic fiber area fraction,collagen fiber area fraction,MMP-2,MMP-9 and ?-SMA and other pathological indicators were compared.At 9 weeks,the same comparison was performed between the two groups,while comparison also performed between two time points.RESULTS: At the 6th week,there were 2 cases of occlusion in both groups.1.Flow field characteristics: all 14 cases in group Z were non-helical flow field;13 cases of group W were helical flow field,and 1 was non-helical flow field,which was analyzed as group Z.2.Morphology: The average expansion rate of group W(helical flow field)was significantly larger than that of group Z(non-helical flow field)(P = 0.001).3.Histopathology: Elastic fiber area fraction and ?-SMA area fraction of group W lower(P <0.05).4.Molecular pathology: The expression of MMP-9,MMP-2 and NF-?B in group W was significantly higher than those in group Z(P <0.01).9 weeks: 1.Flow field characteristics: all 7 cases in group Z were non-helical type;all 7 cases in group W were helical type.2.Morphology: Compared with the group Z,the average expansion rate of group W was higher(P <0.001).3.Histopathology: The thickness of intima and medial membrane of group W was thicker(P = 0.047).The collagen fibers area fraction and the area ?-SMA area fraction were lower in group W(P <0.05).4.Molecular pathology: The expression of MMP-9,MMP-2 and NF-?B in W group was significantly increased(P <0.01).9 weeks and 6 weeks: 1.Morphology: average expansion rate of group Z has been significantly reduced(P = 0.001),while the average expansion rate of group W had no significant changes.The expression of MMP-2,MMP-9 and NF-?B in the group Z was significantly decreased at 9 weeks(P <0.05).However,only the expression of MMP-2 in group W was decreased(P = 0.032),while the expression of MMP-9 and NF-?B did not decrease.USPIO enhanced MRI: After injection of USPIO,the normal blood vessel SNR did not change significantly,aneurysm wall SNR of group W and group Z were significantly decreased(P <0.001).CONCLUSION: Compared with the non-helical flow field,helical flow field promoted the expression of NF-?B,MMP-9 and MMP-2 in the aneurysm wall,and decreased the content of elastic fibers,collagen fibers and synthetic smooth muscle cells,resulting in a larger aneurysm lumen.The animal model can repair the fusiform aneurysms themselves,and the persistence of the helical flow field hinders its own repair process.USPIO can change the MRI signal value of fusiform aneurysm wall,suggesting that it can be used for MRI diagnosis.