Vessel wall image as a marker of cerebral aneurysm instability

Abstract

Background:

Intracranial aneurysms affect 3% of the population, with advancements in radiology enabling more diagnoses of unruptured aneurysms. The black blood magnetic resonance imaging (bbMRI) is a valuable noninvasive method to study of the inflammatory process in the wall of intracranial arteries. This study aimed to correlate wall enhancement of aneurysms through bbMRI with known risk factors.

Methods:

A retrospective analysis was conducted on patients who had microsurgery for ruptured and unruptured intracranial aneurysms from June 2020 to March 2023. Patient demographics and radiological findings were reviewed with qualitative variables analyzed using Fisher’s exact test and quantitative variables using the Mann‒ Whitney.

Results:

We analyzed 120 patients and 139 aneurysms. All patients underwent microsurgery for clipping at least one aneurysm. Female was more prone to exhibit ruptured aneurysms than males (28% vs. 8%, P + 0.03, odds ratio [OR] = 0.2, 95% confidence interval [CI] 95% = 0.04–0.9). Ruptured aneurysms were more likely to have a diameter ≥7 mm (50% ruptured vc. 23.8% unruptured, P = 0.05, OR = 0.3, 95% CI = 0.1–0.6). bbMRI was positive in 76.5% of ruptured aneurysms and 23.5% were negative (P < 0.0001). In the unruptured aneurysm group, the larger the aneurysm was, the greater the chance of positive bbMRI (OR = 0.1, 95% CI = 0.05–0.3). In this subgroup, either size or positive bbMRI was associated with rupture.

Conclusion:

Our analysis demonstrated that ruptured aneurysms are more prone to be positive on bbMRI, that is, aneurysm wall enhancement after the administration of contrast. This reinforces the association between positive bbMRI and aneurysm instability.

INTRODUCTION

Intracranial saccular aneurysms affect 3% of the population, and the majority of incidental aneurysms are small, measuring approximately 3–4 mm.[6,11,16] The chance of rupturing is estimated to be 0.25%.[11] The rupture of an intracranial aneurysm resulting in subarachnoid hemorrhage (SAH) is a life-threatening condition. The modality of treatment of each patient is chosen by comparing the risk of rupture and the natural history of the unruptured aneurysm.[8,2] The need to make the decision to treat unruptured aneurysms is so relevant that studies were designed to determine and calculate risk factors for aneurysm rupture, which assists in decision-making for appropriate treatment.[6]

A widely used method in clinical practice available to calculate the risk of rupture is the PHASES score, which considers population, hypertension, age, history of earlier SAH, and size and site of the aneurysm.[1] Other risk factors associated with aneurysm rupture are smoking and a familial history of SAH.[18,19] However, these studies did not take into account novel magnetic resonance imaging (MRI) features to predict the risk of aneurysm rupture.

Improvements in radiological methods have allowed the more frequent diagnosis of unruptured intracranial aneurysms (UIAs) and raised the dilemma regarding the choice of the best treatment. Until recent years, interest was focused on endoluminal studies such as angiotomography, magnetic resonance angiography (MRA), and digital angiography. However, it is worth mentioning that changes in blood vessel walls play an important role in the pathogenesis of these conditions, which has led to the emergence of new imaging techniques that allow focusing the study on pathophysiological changes.[5,13,14,17]

The black blood sequence in T1 in high-resolution 3D MRI is a useful noninvasive imaging method in the study of the inflammatory process in the wall thickness of intracranial arteries and veins. It can be identified by this sequence by observing an enhancement in the wall of the aneurysm after contrast administration or with evidence of a thin wall.[3,5,7,12-14,17]

The enhancement of the aneurysm wall in the black blood MRI (bbMRI) sequence after gadolinium administration has been associated with inflammation involving macrophage infiltration, neovascularization, presence of vasa vasorum, atherosclerotic changes, and thrombus adherence to the vessel wall.[7,15]

Aneurysms with a higher clinical risk for rupture had a greater and more diffuse wall enhancement and a thinner wall.[5] In addition, unstable unruptured aneurysms present more circumferential wall enhancement than stable aneurysms.[5] The current literature supports that arterial wall enhancement and thinning in the bbMRI sequence can be used as indirect markers of vessel wall inflammation and, therefore, as potential markers of aneurysm instability, which would allow the use of this sequence as a predictor of rupture.[5,7,13,14,17]

We aimed to study the correlation between wall enhancement of aneurysms using the bbMRI technique and some of the previously described risk factors. In addition, we investigated whether positive neuroimaging is associated with aneurysmal instability, predominantly presented as rupture.

MATERIALS AND METHODS

We performed a retrospective analysis of patients who underwent microsurgery for ruptured and UIAs at our institution from June 2020 to March 2023. All procedures were approved by the Ethics Committee of our institution (56709222.0.3001.5483).

All medical records were reviewed to describe patient demographics: sex; age; comorbidities (arterial hypertension and smoking); and Hunt-Hess grade if it was a ruptured aneurysm.

Radiological findings were analyzed through computed tomography to classify ruptured aneurysms according to the modified Fisher scale. Digital subtraction angiography, angiotomography, and MRA scans were analyzed to identify the aneurysm site and to measure the maximum diameter of the aneurysm domus. We also analyzed the vessel wall MRI (3-T imager) before and after gadolinium injection to classify it into two groups: enhancement wall (focal or diffuse) and no enhancement aneurysm wall. An example is demonstrated in Figure 1 and Figure 2.

Figure 1:

(a,d) Saccular aneurysm originating from the posterior wall of the distal supraclinoid segment of the right internal carotid artery, immediately adjacent to the origin of the posterior communicating artery, which lies medial to the lesion. The aneurysm demonstrates a short neck and a posterolateral orientation, producing mass effect on the anterolateral aspect of the mesencephalic transition zone (red circle in panel d). Its dimensions are approximately 1.5 × 1.5 × 1.0 cm, with an estimated neck width of 0.3 cm. (b,c): Comparison of pre-contrast and (e, f) post-contrast imagesreveal marked, smooth, and uniform enhancement of the aneurysmal wall on black-blood MRI, consistent with mural inflammation. This represents a case of positive vessel-wall imaging.

Figure 2:

(a-b): Saccular aneurysm arising from the right middle cerebral artery. Comparison between pre-contrast and (c-d)post-contrast images demonstrate marked, smooth, and homogeneous enhancement of the aneurysmal wall on black-blood MRI, consistent with active mural pathology. Panel (e) shows the intraoperative view of the aneurysm.

Qualitative variables were analyzed by contingency tests using Fisher’s exact test, depending on the sample size and the adequacy of the normal distribution for each set of samples. The Mann‒Whitney test was used to analyze quantitative variables if the samples had a distribution pattern that was not normal. An α ≤ 0.05 was considered significant. Data analysis and graph creation were performed using GraphPad Prism 8 for macOS version 8.0.1.

bbMRI protocol

Neuroimaging of the vessel wall, namely, bbMRI, was performed in a 3 Tesla (3T) device (Siemens-Skyra, Erlangen, Germany) and GE (GE Health Care, HDTX, Milwaukee, USA) through a coil with 32 and eight channels. The scheduled protocol for the acquisition of high-resolution images was established as follows: sagittal T1-weighted images with field-of-view (FOV) of 240 mm, slice thickness of 5.0 mm, repetition time (TR) of 2000 ms, and time to echo (TE) of 9.5 ms with a time of 2 min and 12 s; axial FLAIR with FOV of 240 mm, slice thickness of 5.0 mm, TR of 9000 ms, and TE of 81 ms with a time of 2 min and 42 s; axial T2 with FOV of 240 mm, slice thickness of 5.0 mm, TR of 4230 ms, and TE of 97 ms with a time of 1 min and 29 s; axial diffusion with FOV of 240 mm, slice thickness of 5.0 mm, TR of 4530 ms, and TE of 64 ms with a time of 2 min and 4 s; axial susceptibility-weighted imaging with FOV of 240 mm, slice thickness of 3.0 mm, TR of 27 ms, and TE of 20 ms with a time of 2 min and 48 s; 3D sagittal T2 volumetric (CUBE) with FOV of 250 mm, slice thickness of 0.9 mm, TR 1830 ms, and TE of 2.41 ms with a time of 4 min and 12 s each acquisition; axial T1-weighted volumetric FSPGR pre and post gadolinium with FOV of 240 mm, slice thickness of 1.0 mm, TR 3200 ms, and TE of 408 ms with a time of 3 min and 22 s; MRA in the 3D TOF technique without gadolinium, for vascular analysis, with a thickness of 0.75 mm, matrix of 384 × 256, FOV of 18 × 18, voxel of 0.2 × 0.2 × 0.8 mm, and time of 6 min and 50 s; and isotropic volumetric T1 sagittal sequence pre- and post-gadolinium (Space/Spair and CUBE) with a thickness of 0.9 mm, matrix of 288 × 288 mm, FOV of 23 × 23 mm, and time of 6 min and 14 s, with TE of 16 ms and TR of 600 ms.

To enhance precision in assessing aneurysmal wall enhancement (AWE), we subclassified bbMRI findings into circumferential and focal enhancement. Circumferential AWE was defined as smooth and continuous enhancement involving more than 75% of the aneurysm wall circumference. Focal AWE referred to discrete or patchy enhancement affecting <75% of the circumference. Both patterns were recorded based on consensus reading by two neuroradiologists with experience in vessel wall imaging.

RESULTS

We analyzed 120 patients, and 139 aneurysms treated at our institution between June 2020 and March 2023. All patients underwent microsurgery for clipping at least one aneurysm. The mean age was 54.1 years (ranging from 17 to 79 years). There were 21 male (17.5%) and 99 (82.5%) female patients. Regarding comorbidities, 71 patients (59%) had a diagnosis of arterial hypertension, and 54 (45%) were smokers. Among the 139 aneurysms, 34 (24.4%) were ruptured, and 105 (75.5%) were unruptured. The median aneurysm size was 4 mm, ranging from 1-26 mm. The most common site of aneurysm was the middle cerebral artery (42, 30%), followed by the anterior communicating complex (25, 18%), communicating segment of the internal carotid artery (ICA) (24, 17.2%), ophthalmic segment of the ICA artery (22, 15.8%), ICA bifurcation (12, 8%), choroidal segment of the ICA (6, 4%), and pericallosal (6, 4%). Basilar and posterior inferior cerebellar artery aneurysms were the minority, with only 1 case each (0.7%). When the aneurysm was ruptured, there was a mean delay time of 12 days between the ictus and the MRI scan.

When comparing the groups of ruptured and unruptured aneurysms, we found no significant difference regarding mean age (52.1 vs. 54.7, P = 0.3), arterial hypertension (47% vs. 52.3%, P = 0.6), and tobacco use (50% vs. 35.2%, P = 0.1). Female patients were more prone to exhibit ruptured aneurysms than males: 28% for the former and 8% for the latter, P = 0.03 (odds ratio [OR] = 0.2, 95% confidence interval [CI] 95% = 0.04–0.9).

Analyzing the domus size, the ruptured aneurysms were more likely to exhibit the largest diameter ≥ 7 mm, 50% ruptured vs. 23.8% unruptured group, P = 0.05 (OR = 0.3, 95% CI = 0.1–0.6). The vessel wall MRI was more prone to be positive (namely, vessel wall enhancement after gadolinium administration) with ruptured aneurysms (76.5% ruptured aneurysms were positive bbMRI and 23.5% were negative, P < 0.0001). The demographic, clinical, and radiological characteristics of the patients from each group are provided in Table 1.

Table 1:

Comparison between the groups of ruptured and unruptured aneurysms.

Among the 58 aneurysms with positive bbMRI, 38 (65.5%) exhibited circumferential AWE and 20 (34.5%) showed focal AWE. Ruptured aneurysms were significantly more likely to exhibit circumferential enhancement (22/26, 84.6%) compared to unruptured aneurysms (16/32, 50.0%) (P = 0.01).

In an analysis of the ruptured aneurysm subgroup, there was no significant difference between positive and negative vessel wall enhancement aneurysms regarding age (mean age, respectively, 53 and 46.5 years, P = 0.6), arterial hypertension (87.5% vs. 12.5%, P = 0.2), and smoking (82.3% vs. 70.5%, P = 0.6). In the subgroup analysis of the unruptured aneurysms, there was no significant difference between positive and negative vessel wall enhancement aneurysms regarding age (mean age, respectively, 59 and 55 years, P = 0.9), arterial hypertension (25.5% vs. 74.5%, P = 0.2), and smoking (22% vs. 77.7%, P = 0.2).

In the unruptured aneurysm group, the larger the aneurysm was, the greater the chance of positive bbMRI (OR = 0.1, 95% CI = 0.05–0.3). In this subgroup, either size or positive bbMRI were associated with rupture. It is reasonable to understand the bbMRI positivity in the unruptured group in larger aneurysms, as greater sizes are risk factors for rupture. In the ruptured aneurysm group, there was no statistically significant association between size and rupture. The subgroup data are provided in Tables 2 and 3.

Table 2:

Comparison between the groups of the positive and negative vessel wall from ruptured aneurysms.

Table 3.

Comparison between the groups of the positive and negative vessel wall from unruptured aneurysms.

DISCUSSION

Our analysis demonstrated that ruptured aneurysms are more prone to be positive on bbMRI, which means aneurysm wall enhancement after the administration of contrast. This is in accordance with previously published studies. An earlier study demonstrated that 90% of growing and ruptured aneurysms and only 30% of stable aneurysms (P < 0.0001) demonstrated AWE. It was concluded that thick circumferential enhancement had the highest specificity accuracy to distinguish unstable from stable unruptured aneurysms, and the pattern of enhancement could justify and favor invasive aneurysm management.[4] Another study calculated that almost 100% of ruptured aneurysms exhibited enhancement, and only <20% of unruptured aneurysms demonstrated AWE.[14]

Analyzing unruptured aneurysms separately, of those positive bbMRI, 20% were <7 mm and 64% were ≥7 mm (P < 0.0001). As already demonstrated by prior studies, aneurysm size is a risk factor for aneurysm instability for unruptured aneurysms.[1,18,20] In contrast, when they are ≥7 mm, there is a significant tendency to be positive on bbMRI. This is not verified by analyzing ruptured aneurysms when the risk factor becomes an event. It is notable that the subgroup analysis demonstrated that AWE is still associated with aneurysm instability even when ruptured aneurysms are excluded.

bbMRI is a useful method to study the inflammatory condition of the vessel wall. The enhancement of the aneurysm wall in the bbMRI sequence after gadolinium administration has been associated with inflammation involving macrophage infiltration, neovascularization, the presence of vasa vasorum, atherosclerotic changes, and thrombus adherence to the vessel wall.[7,15] This examination may be of great use when evaluating large artery atherosclerosis, dissections, moyamoya vasculopathy, and intracranial aneurysms.[3,9]

One relevant factor potentially influencing AWE is the timing of MRI acquisition post-rupture. In our cohort, there was a mean delay of 12 days between ictus and imaging for ruptured aneurysms. Prior studies have suggested that vessel wall enhancement may decrease or evolve over time following rupture due to the resolution of acute inflammation or clot retraction. Therefore, delayed imaging may underestimate the true extent of AWE in some ruptured cases. This temporal aspect should be considered when interpreting vessel wall MRI findings, particularly in the acute setting.

Vessel wall MRI was first demonstrated to be an important tool for determining the site of rupture in patients with aneurysmal SAH.[13] Subsequent studies compared the risk of aneurysm rupture calculated by the PHASES score and the pattern of enhancement at the intracranial vessel wall image, concluding that this examination may differentiate stable and unstable aneurysms.[7,10] Previous studies demonstrated that circumferential AWE is a marker of aneurysm instability, that is, ruptured, morphological modification, and symptomatic aneurysms.[5]

Our study has limitations, such as its observational retrospective nature. There was no follow-up of aneurysms undergoing vessel wall imaging, and it is not possible to assume that positive bbMRI for an unruptured aneurysm predicts aneurysm rupture in our cohort. There was heterogeneity in the pattern of enhancement, and we considered positive bbMRI both focal and diffuse AWE, whereas some studies categorized the type and thickness of the enhancement.

CONCLUSION

Our analysis demonstrated that ruptured aneurysms are more prone to be positive on bbMRI, that is, aneurysm wall enhancement after the administration of contrast. This reinforces the association between positive bbMRI and aneurysm instability.

Ethical approval:

The research/study approved by the Institutional Review Board at Ethics Committee of the Federal University of São Paulo, number 56709222.0.3001.5483, dated October 10, 2023.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

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