A Prospective Follow-up Study On Risk Factors To Predict The Progression Of Unruptured Intracranial Aneurysms On Enhanced HR-MRI

Backgrounds and objectives:Many studies have proposed that aneurysm wall enhancement(AWE)of unruptured intracranial aneurysms(UIAs)on gadolinium-enhanced high-resolution magnetic resonance imaging(HR-MRI)is associated with active aneurysm inflammation in the aneurysm wall and therefore may indirectly predicts the instability of aneurysms,these aneurysms are more likely to grow or rupture in the future.However,the paucity of prospective data limits the clinical verification of the prediction accuracy of AWE.We aimed to find out risk factors for the progression of UIAs during follow-up,and to prospectively investigate the potential correlation between qualitative and quantitative assessment of AWE observed on initial enhanced HR-MRI imaging and aneurysm progression during follow-up.Material and methods:From June 2016 to January 2021,we prospectively recruited patients with UIAs for enhanced HR-MRI examination at our institution.The patients’ demographic and clinical data were collected,including patients’ gender,age,hypertension,heart disease,diabetes mellitus,hyperlipidaemia,cerebral vascular sclerosis,previous history of aneurysmal subarachnoid haemorrhage(ASAH),smoking history,alcohol consumption,and symptoms associated with UIAs(sentinel headache or oculomotor nerve pals,etc.).The aneurysm characteristics and morphological parameters were recorded in detail,including multiplicity,aneurysm size,neck width,diameter of the parent artery(DP),shape(regular,or irregular such as the presence of a daughter sac,bubbles,or lobulation),bifurcation(presence or absence),location,enhanced wall thickness,flow angle;and two calculated secondary geometric indices: aspect ratio(AR,depth/neck width)and size ratio(SR,depth/DP);The AWE features of the UIAs on HR-MRI were assessed,including enhancement pattern(0=no enhancement,1=partial enhancement,2=circumferential enhancement),enhancement degree(0=no enhancement,1=slight enhancement,2=significant enhancement),and a quantitative index: enhancement rate(ER,ER =(SImax-SIpre)/SIpre×100%).After baseline imaging,patients were followed up and monitored,and the imaging review(MRA or CTA examination)was performed after an interval of 12 months.Then,the measurements on the baseline imaging were compared with those on the follow-up images to determine whether these IAs had progressed during follow-up period.The next step was to perform statistical analyses.Firstly,the traditional single factor analysis method was used to analyze the distribution difference of means or rates in basic clinical information and aneurysm characteristics between the progressive and non-progressive IA groups.Categorical data were compared using chi-square test(Pearson’s chi-squared test or Fisher’s exact test).Quantitative data were analyzed by independent samples t-test(normally distributed data)or non-parametric test(Mann-Whitney rank test)(non-normally distributed data).Finally,all clinical characteristics and aneurysm parameters of patients(including demographic information,clinical history,and aneurysm characteristics)in the progressive and stable IA groups were included in Cox proportional hazards regression model for regression analysis.Firstly,all possible risk factors were included in univariate Cox regression analysis to determine whether there was a potential correlation between each factor and IA progression.For those factors that reached p≤0.05,further multivariate Cox regression analysis was then performed to determine the independent risk factors associated with the development of UIA progression during follow-up and to calculate their corresponding hazard ratios(HR)and 95% confidence intervals(95% CI).Next,a receiver operating characteristic(ROC)analysis was performed based on the final statistical model,then,the area under the curve(AUC)for predicting UIA progression during follow-up of each independent risk factor was obtained,and the combined effect of significant predictors was evaluated,and the corresponding sensitivity and specificity were determined at the same time to show the diagnostic value of risk factors in predicting the progression of intracranial aneurysms during follow-up.Results:A total of seventy-seven patients with 95 UIAs met our research criteria,with a mean age of 56 ± 9 years,the median follow-up time was 15.7 months(interquartile range [IQR]:13.3 ～ 31.4 months).Progression was observed in 18 aneurysms during follow-up;the remaining 77 aneurysms remained stable.Progressive UIAs were larger in size at baseline imaging compared with nonprogressive UIAs(progressive group vs.stable group: 6.2 mm [IQR:5.5–8.4 mm] vs.4.6 mm [IQR: 3.7–5.8 mm]),and aneurysms in the progressive group more frequently displayed obvious AWE and showed a higher ER(progressive group vs.stable group,0.48 [IQR: 0.29–1.12] vs.0.06 [IQR: 0.03–0.16]).Univariate Cox regression analysis showed that symptoms,aneurysm size,irregular shape,arterial bifurcation,enhanced wall thickness,enhancement pattern,enhancement degree,ER,AR,SR,and flow angle were all associated with aneurysm progression(p<0.05).Further multivariate Cox proportional hazards regression analyses showed that both ER(hazard ratio [HR]: 6.304,p<0.001)and aneurysm size(HR: 1.343,p=0.014)were independent risk factors for aneurysm progression during follow-up.The ROC curve demonstrated that the AUC of ER and size for predicting UIA progression during follow-up were 0.857(95% confidence interval [95%CI]: 0.770–0.920,p<0.001)and 0.806(95% CI:0.712–0.880,p<0.001),respectively.The combination of ER and aneurysm size achieved the highest AUC of 0.920(95% CI: 0.846–0.966,p<0.001)for the prediction of aneurysm progression,with a sensitivity of 88.9% and specificity of 87.0%.Conclusion:Our prospective follow-up study suggests that a higher ER value of the aneurysm wall and a larger aneurysm size on initial enhanced HR-MRI may predict an increased risk of aneurysm progression during follow-up,which suggests that monitoring by imaging or preventive intervention may be required for the clinical management of these aneurysms.Our findings may help to promote the widespread application of HR-MRI in routine clinical practice of intracranial aneurysms.