The relationship between symptomatic status and aneurysm wall enhancement characteristics of single unruptured intracranial aneurysm

Unruptured intracranial aneurysms (UIAs) affect approximately 3% of adults [1] and can be a major source of subarachnoid hemorrhage, a condition associated with a higher risk of death or life-altering disabilities [2‐4]. Clinical symptoms primarily include headaches and cranial nerve palsy. Additionally, some patients may experience warning headaches, characterized by a severe headache that resolves within 72 h, 2 weeks before aneurysm rupture. A small amount of bleeding or deformed stretching of the aneurysm may cause this aura headache before the aneurysm ruptures [5]. Symptomatic and asymptomatic UIA comparisons revealed that the former had a significantly higher fracture risk than the latter, with an odds ratio of 4.4 (95% CI: 2.8–6.8; [6]). Symptomatic UIA has a higher risk of rupture and a relatively poor prognosis. However, the sensitivity and specificity of identifying symptomatic UIA based on clinical manifestations alone are insufficient, and more objective evidence is required.

In addition to symptoms, aneurysm wall enhancement (AWE) is more common in ruptured aneurysms than in UIAs [2] and has been observed in symptomatic or growing UIAs in some studies [7, 8]. This study used high-resolution magnetic resonance vascular wall imaging (HR-MR-VWI) to qualitatively analyze and rank AWE features of symptomatic UIAs. Through comprehensive multivariate analysis, this study explored the characteristics of the AWE that may be closely related to the condition of UIA in order to provide guidance for clinical treatment and contribute to improved outcomes.

Overall, 85 patients (females: 42, males: 43) met the inclusion criteria. This age group ranged from 45 to 70, averaging 58.69 ± 11.88. Among these patients, 39 were symptomatic and 46 were asymptomatic. Age, gender, smoking status, alcohol consumption, hypertension, diabetes, and hyperlipidemia did not differ significantly between the symptomatic and asymptomatic groups (p > 0.05). The baseline data between the two groups were balanced, indicating that the indicators in our study were comparable. Table 1 demonstrates the clinical features of the 85 patients.

The symptomatic group had a higher maximum size, height, and neck width than the asymptomatic group (p < 0.05, Table 2). The results showed that the proportion of UIAs with enhancement (79.5%) was higher than that of the asymptomatic control group (34.8%), with a statistically significant difference (Table 2). The enhancement characteristics of asymptomatic and symptomatic groups were also significantly different, including enhancement grade and range, as well as the difference in thickness enhancement rate (p < 0.001, Table 2).

The presence or absence of symptoms was used as the dependent variable (0 = none, 1 = yes), other variables were used as independent variables, and the influencing factors of the symptoms were analyzed. The results showed that as the grade of the enhancement range increased, the likelihood of symptoms occurring may increase (OR = 4.520; 95% CI: 1.037–8.074; Table 3). Figures 1 and 2 illustrate the HR-MR-VWI manifestations of symptomatic and asymptomatic UIAs at different locations.

This study analyzed the correlation between the symptom status of a single UIA and AWE. The results showed that the symptom status of a single UIA was related to the maximal size, AWE, enhancement degree, enhancement range, and thick-wall enhancement of UIA. Multivariate regression analysis demonstrated that only the range of AWE was independently related to symptom status. If the imaging features of diffuse and annular AWE on HR-MR-VWI can help identify symptomatic UIA, patients can receive timely and effective clinical interventions and treatments.

Recent research has reported that AWE in HR-MR-VVI plays a major role in infiltrating inflammatory cells, vascular constriction, thrombus formation, and weakening vascular elasticity [14, 15]. The inflammatory effect may cause endothelial cell and smooth muscle cell rupture injury, destroying the elastic layer in the tube wall, remodeling the tube wall, aggravating wall damage, and increasing the risk of rupture. The more pronounced the AWE, the less stable the aneurysm [16]. According to Edjlal et al. [13], the AWE characteristics of 263 IA patients showed that circumferential aneurysmal wall enhancement (CAWE) had high specificity (84.4%) and a high negative predictive value (94.3%) for identifying unstable IA. Omodaka et al. [17] indicated that the number of aneurysms developing CAWE was significantly higher than stable Ias and lower than ruptured Ias. Similarly, Edjlali et al. [18] reported that CAWE was detected more frequently in unstable Ias than in stable Ias (27/31,87% vs. 22/77, 28.5%; p < 0.0001), indicating that Ias with a larger range of enhancement have higher instability. In a previous small study (n = 25; [19]), AWE was more common in patients with symptomatic UIA. However, other factors correlated with these symptoms cannot be verified statistically. Symptoms aneurysms usually tend to be larger than asymptomatic aneurysms. Combining our research, we can interpret these variables with the analysis, indicating that the enhancement range is the most meaningful parameter when comparing enhanced MR images. Wang et al. [20] observed 89 Ias in 80 patients and discovered that symptomatic Ias had higher enhancement. Recent explorations by a research team led by Zhu [9] revealed a remarkable correlation between the AWE area and the symptoms of UIA patients. This study result is consistent with our findings, but some patients in these studies had multiple aneurysms. All participants included in this study had a single UIA to exclude the influence of factors such as changes in the pathological structure of ruptured and multiple aneurysms.

Currently, there are obvious differences in evaluating UIA enhancements. A previous study defined AWE with or without enhancement [7]. Several studies are graded based on the pituitary infundibulum [21], and another study reported circumferential aneurysmal wall enhancement (CAWE) and thick-walled CAWE [13]. However, AWE signatures may indicate varying degrees of inflammation or nutrient vessel density in the vessel wall, requiring a detailed and comprehensive analysis. This study conducted a comprehensive and detailed analysis of enhancement characteristics, such as AWE, enhancement degree, enhancement range, and thick-wall enhancement, and discovered that the enhancement range and thick-wall enhancement were the most significant factors associated with symptoms. The histological findings were consistent. Quan et al. [22] performed a comparative analysis of the histopathological data of aneurysm wall specimens and HR-MR-VWI characteristics of aneurysm wall specimens in 54 patients with UIA undergoing surgery; the results depicted focal wall enhancement of the aneurysm. Both the annular enhancement and aneurysm wall were linked to the inflammatory reaction of the aneurysm wall, but the inflammation of the annular enhancement was more prominent than that of the focal enhancement. A histological study by Matsushige [23] demonstrated that diffuse or annular AWE may be due to the presence of an intraluminal thrombus with a loose fibrous reticular structure and many neutrophils at the rupture site, whereas focal AWE is likely to be the result of contrast agent stagnation in the loose fibrous network of fresh intraluminal thrombus. The above studies indicate that the histopathological characteristics of AWE are related to factors such as inflammatory cell infiltration, pathological vasa vasorum hyperplasia, and intravascular thrombosis. When the aneurysm wall undergoes an inflammatory reaction and the formation of pathological feeder vessels, the normal endothelial barrier is destroyed and the contrast agent penetrates it, thus displaying the AWE. The larger the AWE range, the more severe and extensive the inflammatory impact on the arterial walls, which may threaten the stability of the aneurysm.

Currently, the clinical management of UIA mainly depends on its size and location. Most clinicians do not hesitate to choose a surgical intervention for large or symptomatic aneurysms. However, our study can offer objective evidence to help patients in better clinical management of borderline cases, such as those with a maximal size of approximately 5–6 mm or with only nonspecific symptoms, such as headaches. Zwarzanyet et al. [16] proposed that despite small intracranial aneurysms, it is important to analyze the risk factors for rupture, suggesting that we should be vigilant against smaller UIAs with abnormal enhancement. Consequently, we recommend active surgical intervention when diffuse or annular enhancement appears on HR-MR-VWI in borderline cases.

Recent studies [24] have demonstrated that a portion of AWE is correlated with slow blood flow, and the implementation of a slow-flow suppression module can effectively reduce these artifacts. In their experiments, researchers observed that only a small fraction of AWE was affected by applying slow-flow suppression pulses, suggesting that most AWE may still represent true enhancement of the vessel wall itself. However, it should be noted that AWE and low wall shear stress are linked to an increased risk of aneurysm growth and rupture. Therefore, caution must still be exercised when detecting AWE related to slow-flow artifacts.

A larger range of aneurysm wall enhancement range is an independent risk factor for symptomatic single unruptured intracranial aneurysm (UIA). This factor may be a marker of UIA instability and may provide appropriate clinical workup and improve patient outcomes.