Application Value Of Magnetic Resonance Blood Flow And Vessel Wall Imaging In Assessing The Rupture Risk Associated With Structure Of Intracranial Aneurysms

Part 1 A Comparative Study of Hemodynamics,Morphology and Wall Enhancement Characteristics in Unruptured Intracranial Aneurysms with Different DiametersBackground and PurposeThe incidence rate of intracranial aneurysms is about 1.2%.Predicting rupture risk of unruptured intracranial aneurysms(UIAs)is critical for patient clinical decision-making and individualized management.Previous studies have shown that aneurysms with larger diameters accompanied with the higher rupture risk.Most of the up-regulated genes in larger UIAs are involved in inflammation and extracellular matrix(ECM)tissue formation.Hemodynamics is considered to be the initiating factor of this inflammation.Larger diameter aneurysms will grow when exposed to these adverse hemodynamic conditions,so the wall will show high degeneration or inflammation.Therefore,blood flow is involved in inflammatory changes and affects the natural process of aneurysms.The hemodynamic analysis of aneurysms was based on the simulation value of computational fluid dynamics(CFD)previously.Although it is widely examined by many researchers,its rigid wall setting and aneurysm inlet,as well as outlet conditions limit its exploration of real world vascular wall pulsation.As an advanced technology,four-dimensional flow magnetic resonance imaging(4D flow MRI)can obtain blood flow information in the real world.It is increasingly applied to intracranial aneurysms,arteriovenous malformations,intracranial atherosclerosis,and other diseases.In addition,the pathogenesis of many cerebrovascular diseases begins with the vascular wall.Nevertheless,traditional vascular imaging can not provide enough information and pathophysiological changes.With the gradual development of MR technology in intracranial vascular diseases,vessel wall imaging(VWI)has the advantages of high spatial and tissue resolution.It can present the vessel wall structure clearly and obtain accurate morphological parameters.And it exhibited aneurysm wall enhancement(AWE)which can evaluate the functional changes of aneurysm wall from the perspective of pathophysiology.AWE is related to the infiltration and aggregation of inflammatory cells and can be used as an in vivo imaging biomarker of aneurysm wall inflammation.However,the differences in hemodynamics,morphology,and AWE characteristics of UIAs with different diameters are still unclear.This study aimed to explore the differences and associations of these risk-related factors based on 4D flow MRI and VWI for aneurysms ≥7mm and<7mm in diameter,to further better understand their potential roles in predicting rupture risk.Materials and Methods1.The patients with unruptured intracranial saccular aneurysms diagnosed in our hospital from October 2019 to October 2021 were prospectively collected.The study used a 3.0 T Siemens Prisma magnetic resonance scanner with 64 channel head neck combined coil.All patients underwent digital subtraction angiography(DSA),3.0 T magnetic resonance gadolinium-enhanced vessel wall imaging(VWI),and four-dimensional flow magnetic resonance imaging(4D flow MRI).The clinical information was extracted from the picture archiving and communication systems(PACS).The morphological parameters of the aneurysm,such as diameter,neck,width,height,shape,location,and average parent vessel diameter were obtained based on DSA.The aspect ratio(AR),size ratio(SR),dome to neck ratio(DNR),and height to width ratio(HWR)of aneurysms were calculated based on the above parameters.Aneurysms were further grouped according to whether they were ≥7 mm in diameter.2.Two experienced neuroimaging physicians independently blind to determine AWE in UIAs based on PACS,and further measured the semi-quantitative AWE indicator-enhancement ratio(ER).3.The 4D flow MRI sequence was post-processed by the CVI 42 software(version:5.1.2).The aneurysm hemodynamic parameter WSS was obtained.4.SPSS 21.0 software was used for statistical analysis.The Shapiro-Wilk test was used to test the normality of the continuous variables,which was expressed by median(interquartile interval:IQR,Q1～Q3)or mean ±standard deviation(x±s).The comparison between different groups was adopted by the Mann-Whitney U test or t-test.The counting data were expressed by number(%),using χ2 test or Fisher exact probability method for the comparison between groups.The variables with P value<0.1 were further included in the multivariate logistic regression analysis and obtained the factors independently related to the UIAs in diameter ≥7mm,as well as the regression coefficient,standard error(SE),odds ratio(OR),95%confidence interval(CI),and P values.Spearman’s rank correlation analysis was used to analyze the correlation between WSS and aneurysm diameter,SR,and ER.The r was represented as the correlation coefficient.The Cohen κ coefficient was used to evaluate the intraobserver agreement with AWE.The intraclass correlation coefficient(ICC)was used to evaluate the intraobserver agreement with the semi-quantitative AWE and hemodynamic parameter.P<0.05(bilateral)was considered the statistical significance.Results1.85 patients with 100 unruptured intracranial saccular aneurysms were recruitd.There was a good agreement for the evaluation of AWE with κ value of 0.87.The interobserver agreement was excellent for the measurements of ER(ICC=0.946,95%CI,0.920 to 0.963,P<0.001),and WSS(ICC=0.871,95%CI,0.815 to 0.912,P<0.001).2.Early subarachnoid hemorrhage(SAH)history,SR,DNR,irregular shape,AWE,ER,and WSS had significant differences between aneurysms with different diameters(P<0.05).Further analysis indicated that early SAH history(OR,2.052;95%CI,1.223 to 3.443;P=0.007),SR(OR,1.549;95%CI,1.142 to 2.102;P=0.005),irregular shape(OR,1.526;95%CI,1.039 to 2.241;P=0.031),and ER(OR,1.904;95%CI,1.151 to 3.150;P=0.012)were independent risk factors for UIAs ≥7mm in diameter.3.There was a significant highly negative correlation between WSS and the aneurysm diameter,SR,and ER(r=-0.70,-0.67,-0.63,respectively,all P<0.001).Conclusions1.Large aneurysmal diameter is closely related to risk factors in hemodynamics,morphology and wall enhancement characteristics,suggesting that imaging features can be used as a marker to evaluate the risk of aneurysm rupture.2.Hemodynamics is significantly negatively correlated with morphological parameters and enhancement ratio,demonstrating that comprehensive analysis of rupture risk factors is a better individualized evaluation and clinical decision-making.Part 2 Qualitative and Quantitative Wall Enhancement Analyses in Unruptured Intracranial Aneurysms Are Associated With an Increased Risk of Aneurysm InstabilityBackground and PurposeWith the rapid development and advancement of imaging technology,more asymptomatic unruptured intracranial aneurysms(UIAs)have been detected.Measuring the rupture rate of UIAs and the incidence of complications after surgical treatment is of great importance to patients’ clinical decision-making and individual management.The change of morphological parameters of aneurysms is the key link in the process of aneurysm rupture.More and more histopathological studies have shown that the basic mechanism of aneurysm rupture is an increase in the structural fragility of the aneurysm wall caused by inflammation,which in turn leads to aneurysm growth or rupture.According to a series of pathology-imaging control studies,it was found that aneurysm wall enhancement(AWE)is related to the infiltration and aggregation of inflammatory cells,as well as closely related to aneurysm instability.The advantage of high spatial and tissue resolution of vessel wall imaging(VWI)can accurately obtain morphological parameters and evaluate the inflammatory changes of aneurysm wall from the perspective of pathophysiology.However,the relationship between the imaging marker of aneurysms in vivo and traditional risk factors of rupture has not been fully studied,and previous studies estimated the qualitative AWE patterns finitely,which cause the result was influenced by human observation to a certain extent.Therefore,the present study used a large sample of asymptomatic unruptured intracranial aneurysms and collected qualitative AWE patterns and quantitative wall enhancement index(WEI)based on VWI,to explore the correlation between AWE characteristics and aneurysm instability(growth and rupture risk).So it is helpful for us to better understand the value of AWE,as a noninvasive biological imaging marker in prospectively predicting the risk of aneurysm rupture.Materials and Methods1.The patients with asymptomatic unruptured intracranial saccular aneurysms diagnosed by our hospital from October 2014 to October 2019 were retrospectively analyzed.The asymptomatic aneurysms were detected by physical examination or occasional discovery.The study used a 3.0 T Siemens Prisma MRI scanner(64 channel head neck combined coil).All patients underwent digital subtraction angiography(DSA),routine brain plain scan sequence,three-dimensional time of flight magnetic resonance angiography(3D-TOF MRA),and gadolinium-enhanced three-dimensional sampling perfection with application optimized contrast using different flip angle evolutions magnetic resonance imaging(3D-SPACE MRI).The general clinical data of patients were obtained from picture archiving and communication systems(PACS).2.Two senior neuroimaging physicians independently blind to determine the AWE,focal aneurysm wall enhancement,and circumferential enhancement of UIAs based on the PACS,and further measured the WEI respectively.3.The 3-and 5-year growth risk,as well as 5-year rupture risk of each aneurysm were calculated based on ELAPSS and PHASES scores.4.The SPSS 21.0 software was used for data analysis.The continuous variables were expressed as median(interquartile range)or mean ± standard deviation(x±s).The counting data were express as number(%).The univariate analysis included the Mann-Whitney U test and χ2 test to determine variables significantly associated with AWE.The variables with P<0.2 in univariate analysis were further included in the multivariate logistic regression analysis,and obtained the factors independently related to AWE,as well as the regression coefficient,standard error(SE),odds ratio(OR),95%confidence interval(CI),and P values.Spearman’s rank correlation analysis was used to evaluate the correlation between qualitative and quantitative wall enhancement and aneurysm size as well as estimated aneurysm instability.Cohen κcoefficient was used to evaluate the intraobserver agreement of AWE patterns.The intraclass correlation coefficient(ICC)was used to evaluate the intraobserver agreement of WEI.P<0.05(bilateral)was considered statistically significant.Results1.144 patients with 213 asymptomatic unruptured saccular intracranial aneurysms were retrospectively included.The intraobserver agreement of AWE patterns and WEI measurement were both excellent(κ=0.91,P<0.001;ICC=0.966,95%CI,0.956 to 0.974,P<0.001).2.Aneurysm size,posterior circulation location,and irregular shape were significantly correlated with AWE(P<0.05).The multivariate logistic regression analysis showed that aneurysm size(OR,1.302;95%CI,1.171 to 1.447;P<0.001),posterior circulation location(OR,3.118;95%CI,1.400 to 6.943;P=0.005),and irregular shape(OR,2.782;95%CI,1.366 to 5.665;P=0.005)were independently correlated with AWE.There were significant differences in the proportion of UIAs with different enhancement patterns in aneurysm size,location,ELAPSS score,and PHASES score(P<0.001,P=0.045,P<0.001,and P<0.001,respectively).There were significant differences in wall enhancement index in different aneurysm sizes,locations,ELAPSS scores,and PHASES scores(P<0,001,P=0.047,P<0.001,and P<0.001,respectively).There was a significant positive correlation between AWE and WEI value and aneurysm size(r=0.43 and 0.43,respectively;P<0.001).3.The estimated growth risk of aneurysms in the enhancement group[17.5(11.7,42.7)and 28.1(19.3,60.8)at 3-and 5-years,respectively)]was 1.5-2.5 times higher than that in the non-enhancement group[7.8(7.8,17.5)and 13(13,28.1),respectively;all P<0.001)].Similarly,the 5-year rupture risk in the enhancement group was more than 3 times higher than that in the non-enhancement group[1.3(0.9,4.3)vs 0.7(0.4,1.3),all P<0.001)].The enhancement patterns and WEI measurement were significantly positively correlated with 3-and 5-year growth risk and 5-year rupture risk(r=0.49 and 0.39,r=0.49 and 0.39,r=0.33 and 0.22,all P<0.001).Conclusions1.The traditional risk factors of aneurysm rupture are closely related to aneurysm wall enhancement,which shows the interaction and connection of morphological imaging pattern in assessing the aneurysm rupture risk.2.Qualitative and quantitative wall enhancement characteristics are positively correlated with aneurysm instability,suggesting that quantitative AWE measurement can be considered in large-scale longitudinal research in the future.The imaging bio maker can more objectively and accurately evaluate its potential value in aneur ysm risk management.