Gadolinium-Enhanced Aneurysm Wall Imaging and Risk of Intracranial Aneurysm Growth or Rupture

Qingyuan Liu, MD1; Xin Nie, MD1; Mervyn D. I. Vergouwen, MD, PhD2; et al

2025년09월08일

JAMA Neurol. Published online: September 8, 2025.

DOI:10.1001/jamaneurol.2025.3209

Abstract

Importance  Recent longitudinal studies in patients with unruptured intracranial aneurysms (UIAs) suggested that aneurysm wall enhancement (AWE) on magnetic resonance imaging (MRI) predicts growth and rupture. However, because these studies were limited by small sample size and short follow-up duration, it remains unclear whether this radiological biomarker has predictive value for UIA instability.

Objective  To determine the 4-year risk of instability of UIAs with AWE and investigate whether AWE is an independent predictor of UIA instability.

Design, Setting, and Participants  Individual patient data were obtained from 3 prospective multicenter cohort studies conducted in 83 Chinese centers between January 2017 and December 2024. Included were patients aged 18 to 75 years with at least 1 asymptomatic, saccular UIA greater than or equal to 3 mm.

Exposures  All patients had 3-T MRI gadolinium-enhanced aneurysm wall imaging and computed tomography angiography (CTA) at baseline, and CTA at follow-up.

Main Outcomes and Measures  The primary outcome measure was aneurysm growth or rupture (instability) during follow-up. The absolute risk of aneurysm instability in UIAs with circumferential, focal, and no AWE was determined with Kaplan-Meier estimates at 4 years after baseline aneurysm wall imaging. Cox proportional hazards regression was used to investigate AWE as a potential predictor of instability.

Results  Of the 1453 patients who had baseline 3-T MRI aneurysm wall imaging, 41 patients were excluded because of loss to follow-up or no follow-up CTA, and 61 patients were excluded because of low-quality CTA. We included 1351 patients (median [IQR] age, 56 [48-63] years; 750 female [56%]) with 1416 UIAs and 4884 aneurysm-years of follow-up. Instability within 4 years occurred in 235 of 1416 UIAs (16.6%). The absolute cumulative risk of instability at 4 years was 36.8% (95% CI, 30.7%-43.0%) in UIAs with circumferential AWE, 17.2% (95% CI, 13.4%-21.1%) in UIAs with focal AWE, and 11.4% (95% CI, 11.9%-16.1%) in UIAs with no AWE. Circumferential AWE predicted 4-year instability (hazard ratio [HR], 3.80; 95% CI, 2.82-5.14) and after adjusting for size ratio, aneurysm location, aneurysm shape, and bifurcation configuration (adjusted HR, 2.21; 95% CI, 1.56-3.13).

Conclusions and Relevance  Within 4 years after baseline wall imaging, instability occurred in one-third of UIAs with circumferential AWE. These results suggest that MRI aneurysm wall imaging may be used for predicting the risk of aneurysm instability.

Key Points

Question  What is the 4-year risk of instability (growth/rupture) of unruptured intracranial aneurysms (UIAs) with aneurysm wall enhancement (AWE) on magnetic resonance imaging (MRI) at baseline?

Findings  In this cohort study including 1351 patients, the 4-year risk of instability occurred in one-third of UIAs with circumferential AWE. Circumferential AWE was an independent predictor of instability.

Meaning  Results suggest that MRI aneurysm wall imaging may be used for predicting the risk of aneurysm instability.

Figure 2.  Aneurysm Wall Imaging and Follow-Up Imaging of Representative Unruptured Intracranial Aneurysms (UIAs) With Different Aneurysm Wall Enhancement (AWE) Patterns

A, UIA of a 57-year-old female patient with hypertension. The UIA has a circumferential AWE pattern, is regular, and is located in the right internal carotid artery (ICA). The aneurysm size is 3.1 mm, and after 14.3 months of follow-up, the aneurysm had grown to 5.2 mm. B, UIA of a 39-year-old male patient with hypertension. The UIA has a focal AWE pattern, is regular, and is located in the right middle cerebral artery (MCA). The aneurysm size is 4 mm, and after 12.8 months of follow-up, the aneurysm ruptured. C, UIA of a 57-year-old male patient with no hypertension; UIA has a no AWE, is regular, and is located in the right ICA. The aneurysm size is 3.6 mm, and after 48 months of follow-up, no aneurysm rupture or growth was observed. White arrowheads indicate wall enhancement, the yellow arrowhead indicates hemorrhage caused by aneurysms, the pink arrowhead indicates aneurysms without AWE, and blue arrowheads indicate aneurysms.

Figure 3.  Time to Instability by Different Aneurysm Wall Enhancement (AWE) Patterns

요약

·         중요성 : 최근 비파열성 두개내 동맥류(unruptured intracranial aneurysms, UIAs) 환자를 대상으로 한 종단 연구에서, 자기공명영상(MRI)에서의 동맥류 벽 조영증강(aneurysm wall enhancement, AWE) 이 동맥류의 성장 및 파열을 예측할 수 있다는 보고가 있었다. 그러나 기존 연구들은 표본 수가 적고 추적 기간이 짧아, 이 영상 바이오마커가 UIA 불안정성(instability)을 예측할 수 있는지 여부는 명확하지 않다.

·         목적 : AWE가 UIA 불안정성의 독립적인 예측 인자인지를 규명하고, AWE가 있는 UIA의 4년 내 불안정성 위험을 평가하는 것

·         설계, 환경 및 참가자 :

-연구 유형: 전향적 다기관 코호트 연구(3개 코호트 통합 분석)

-연구 기간: 2017년 1월 ~ 2024년 12월

-참여 센터: 중국 내 83개 센터

-대상자: 18세 이상 75세 이하

무증상 UIA ≥ 3mm, 낭상(saccular) 형태

최소 1개 이상의 UIA 보유

·         노출 : 모든 환자는 3T MRI 가돌리늄 조영증강 동맥류 벽 영상 및 CTA(CT 혈관조영)를 기저선 시점에서 시행. 추적 관찰 시 CTA를 재시행하여 동맥류 상태 평가

·         주요 평가지표 : 

-1차 평가 지표: 추적 관찰 기간 동안의 동맥류 성장 또는 파열 → “불안정성(instability)”으로 정의

-분석 방법:  Kaplan-Meier 추정법으로 4년 누적 불안정성 위험도 산출

Cox 비례위험회귀(Cox proportional hazards regression)로 AWE가 독립적인 예측

인자인지 평가

·          결과 :

-연구 대상: 1453명 중

▪ 41명: 추적 관찰 실패 또는 CTA 미시행 → 제외

▪ 61명: CTA 화질 저하 → 제외→ 최종 분석 환자 1351명, UIA 1416개

-환자 특성:

▪ 중앙 연령: 56세 (IQR 48–63세)

▪ 여성: 750명 (56%)

-추적 기간: 총 4,884 동맥류-연수(aneurysm-years)

-4년 내 불안정성:

▪ 전체 UIA 중 235/1416개 (16.6%)

-AWE에 따른 4년 누적 불안정성 위험:

▪ 원형(circumferential) AWE: 36.8% (95% CI, 30.7–43.0%)

▪ 국소(focal) AWE: 17.2% (95% CI, 13.4–21.1%)

▪ AWE 없음: 11.4% (95% CI, 11.9–16.1%)

-예측력(Hazard Ratio, HR):

▪ 원형 AWE → 불안정성 위험 3.80배 증가 (95% CI, 2.82–5.14)

▪ 다변량 보정 후(adjusted HR): 2.21 (95% CI, 1.56–3.13)(보정 요인: 크기 비율, 동맥류 위치, 형태, 분지 구조)

·         결론 및 의의 :

-MRI에서 원형 AWE를 보이는 UIA 중 약 1/3이 4년 내 불안정성을 보임

-3T MRI 가돌리늄 조영증강 동맥류 벽 영상은 UIA의 성장 및 파열 위험을 예측하는 데 임상적으로 유용한 도구가 될 수 있음을 시사함