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Objective: Aneurysm wall inflammation is associated with lesion instability in unruptured intracranial aneurysms (UIAs). However, most UIAs remain unruptured during lifelong follow-ups because of simultaneous protective remodeling against the inflammatory response. The protective effects of osteoprotegerin (OPG) in intracranial and abdominal aortic aneurysms have been suggested using rodent models; however, the role of this protein in UIAs in humans remains unclear. Herein, the authors examined the relationship between OPG expression and aneurysm wall integrity in intraoperatively resected UIAs by using immunohistochemical and immunofluorescence staining., Methods: Sixteen UIA wall tissue specimens resected between 2017 and 2022 were analyzed. Aneurysm growth was defined as an enlargement > 1 mm or an obvious morphological change over the course of more than 6 months. Three high-power fields were randomly selected from areas expressing high and low levels of OPG within the same aneurysm. To clarify the role of OPG in the human aneurysm wall, the authors compared averaged values for the following pathological features between the 2 OPG expression groups: aneurysm wall thickness, collagen, macrophages, smooth muscle cells, and transforming growth factor beta 1 (TGF-β1). Immunohistochemical staining within the entire tissue area was also analyzed to determine the relationships between OPG expression and different aneurysm growth patterns. Pathological findings were compared between high and low OPG expression levels using the Wilcoxon signed-rank test., Results: The heterogeneous expression of OPG was detected in the walls of UIAs. Lesions expressing high OPG levels had thicker aneurysm walls (327 vs 180 μm, p = 0.002) and higher expression levels of TGF-β1 (8.5% vs 5.4%, p = 0.002) than those expressing low OPG levels. The expression of TGF-β1 was colocalized with that of OPG mainly in the tunica media. Furthermore, lesions expressing high OPG levels had larger α-SMA+ areas (25% vs 13%, p = 0.002). Aneurysm growth was observed in 6 of 9 UIAs with available data: whole sac expansion in 4 and secondary aneurysm formation in 2. Among the 6 UIAs with aneurysm growth, OPG expression was relatively higher in the UIAs with an internal elastic lamina than in those without (17% vs 6.9%)., Conclusions: Aneurysm wall integrity was associated with OPG expression in the aneurysm wall. Collectively, the study results indicated that OPG is associated with protective remodeling, which may contribute to the retention of aneurysm wall structures.

Background: Unstable intracranial aneurysms (UIAs) are more likely to rupture and cause serious consequences. Evaluating the stability of unruptured aneurysms facilitates clinical management stratification., Purpose: To compare and evaluate the predictive performance of qualitative and quantitative wall enhancement (aneurysmal wall enhancement [AWE], circumferential aneurysmal wall enhancement [CAWE], wall enhancement ratio [WER]) on high-resolution magnetic resonance imaging (MRI) of the vessel wall to predict the presence of UIA., Material and Methods: Original articles describing the depiction of aneurysmal wall enhancement on 3.0-T or 1.5-T high-resolution vessel wall imaging were retrieved from the Web of Science, Medline/PubMed, the Cochrane Library, and EMBASE databases up to 15 February 2022. The combined sensitivity, specificity, and summary area under the receiver operating characteristic curve (AUC) were calculated, and meta-regression analysis was performed., Results: In total, 12 original articles involving 1619 intracranial aneurysms (IAs) were included. The combined sensitivity and specificity of AWE, CAWE, and WER were 91% and 67%, 59% and 83%, and 86% and 75%, respectively, in the diagnosis of UIA. The summary AUC values of these items were, in order from high to low, 0.88 (WER), 0.84 (AWE), and 0.77 (CAWE), and the differences among them were significant ( z  = 2.976, P  = 0.003 and z  = 2.950, P  = 0.003). The meta-regression analysis identified average size and 2D/3D magnetic imaging technology as possible sources of heterogeneity., Conclusion: Qualitative and quantitative wall enhancement showed moderate accuracy in predicting UIA, and WER had the highest accuracy among them in this meta-analysis. Two covariates were found to explain the heterogeneity.

Objective: The objective of this study is to investigate the relationship between the thrombus signal intensity and aneurysm wall thickness in partially thrombosed intracranial aneurysms in vivo with magnetization-prepared rapid acquisition gradient echo (MPRAGE) taken using 7T magnetic resonance imaging (MRI) and correlate the findings to wall instability., Methods: Sixteen partially thrombosed intracranial aneurysms were evaluated using a 7T whole-body MR system with nonenhanced MPRAGE. To normalize the thrombus signal intensity, its highest signal intensity was compared to that of the anterior corpus callosum of the same subject, and the signal intensity ratio was calculated. The correlation between the thrombus signal intensity ratio and the thickness of the aneurysm wall was analyzed. Furthermore, aneurysmal histopathological specimens from six tissue samples were compared with radiological findings to detect any correlation., Results: The mean thrombus signal intensity ratio was 0.57 (standard error of the mean [SEM] 0.06, range 0.25-1.01). The mean thickness of the aneurysm wall was 1.25 (SEM 0.08, range 0.84-1.55) mm. The thrombus signal intensity ratio significantly correlated with the aneurysm wall thickness ( p < 0.01). The aneurysm walls with the high thrombus signal intensity ratio were significantly thicker. In histopathological examinations, three patients with a hypointense thrombus had fewer macrophages infiltrating the thrombus and a thin degenerated aneurysmal wall. In contrast, three patients with a hyperintense thrombus had abundant macrophages infiltrating the thrombus., Conclusion: The thrombus signal intensity ratio in partially thrombosed intracranial aneurysms correlated with aneurysm wall thickness and histologic features, indicating wall instability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sato, Matsushige, Chen, Gembruch, Dammann, Jabbarli, Forsting, Junker, Maderwald, Quick, Ladd, Sure and Wrede.)

Purpose: For the evaluation and rupture risk assessment of intracranial aneurysms, clinical, morphological and hemodynamic parameters are analyzed. The reliability of intracranial hemodynamic simulations strongly depends on the underlying models. Due to the missing information about the intracranial vessel wall, the patient-specific wall thickness is often neglected as well as the specific physiological and pathological properties of the vessel wall., Methods: In this work, we present a model for structural simulations with patient-specific wall thickness including different tissue types based on postmortem histologic image data. Images of histologic 2D slices from intracranial aneurysms were manually segmented in nine tissue classes. After virtual inflation, they were combined into 3D models. This approach yields multiple 3D models of the inner and outer wall and different tissue parts as a prerequisite for subsequent simulations., Result: We presented a pipeline to generate 3D models of aneurysms with respect to the different tissue textures occurring in the wall. First experiments show that including the variance of the tissue in the structural simulation affect the simulation result. Especially at the interfaces between neighboring tissue classes, the larger influence of stiffer components on the stability equilibrium became obvious., Conclusion: The presented approach enables the creation of a geometric model with differentiated wall tissue. This information can be used for different applications, like hemodynamic simulations, to increase the modeling accuracy.

Purpose: Currently no detailed in vivo imaging of the intracranial vessel wall exists. Ex vivo histologic images can provide information about the intracranial aneurysm (IA) wall composition that is useful for the understanding of IA development and rupture risk. For a 3D analysis, the 2D histologic slices must be incorporated in a 3D model which can be used for a spatial evaluation of the IA's morphology, including analysis of the IA neck., Methods: In 2D images of histologic slices, different wall layers were manually segmented and a 3D model was generated. The nuclei were automatically detected and classified as round or elongated, and a neural network-based wall type classification was performed. The information was combined in a software prototype visualization providing a unique view of the wall characteristics of an IA and allowing interactive exploration. Furthermore, the heterogeneity (as variance of the wall thickness) of the wall was evaluated., Result: A 3D model correctly representing the histologic data was reconstructed. The visualization integrating wall information was perceived as useful by a medical expert. The classification produces a plausible result., Conclusion: The usage of histologic images allows to create a 3D model with new information about the aneurysm wall. The model provides information about the wall thickness, its heterogeneity and, when performed on cadaveric samples, includes information about the transition between IA neck and sac.

Intracranial aneurysms are heterogeneous in histopathology and imaging appearance. The biological behavior of different types of aneurysms is now known to depend on the structure and physiology of the aneurysm wall itself in addition to intraluminal flow and other luminal features. Aneurysm wall structure and imaging markers of physiology such as aneurysm wall enhancement have been assessed in many prior investigations using conventional-resolution MRI. Recently, high-resolution vessel wall imaging (HR-VWI) techniques with MRI have been introduced. Reports of findings on high-resolution imaging have already emerged for many types of aneurysms demonstrating detailed characterization of wall enhancement, thickness, and components, but many questions remain unexplored. This review discusses the key HR-VWI literature to date. Aneurysm wall findings on conventional-resolution MRI are also discussed as these may help one understand the potential utility and findings on HR-VWI for various aneurysm types. The authors have illustrated these points with several examples demonstrating both features already described in the literature and novel cases demonstrating the potential for future clinical and research applications.

Black blood magnetic resonance imaging (MRI)is a promising imaging tool in predicting aneurysm rupture. Could it be also valuable in evaluating the treatment effect of endovascular and conservative treated aneurysms? Two patients were treated with stent and coil and one with Aspirine (ASS). Correlation of treatment response and contrast enhancement of the aneurysm wall is examined. In the first case stenting failed to treat the aneurysm and contrast enhancement in the wall did never subside during follow up black blood MRI. In the second case the aneurysm responded well to stenting and decreased in size, which was correlating significantly with attenuation of contrast enhancement in black blood MRI. In the third case the aneurysm responded to ASS treatment by decreasing in size as shown in follow up MR-angiography and the contrast enhancement in its wall decreased after 8 months of therapy. Black blood MRI seems to be a promising tool not only in predicting aneurysms at risk of rupture, but also in observing treatment responses after endovascular procedures or even Aspirine administration. When contrast enhancement decreases, aneurysm treatment seems to be successful as can be shown in decreasing size in the follow up angiography., Competing Interests: Conflict of interest: the authors have no conflict of interest.

Introduction: The aneurysm wall has been reported to play a critical role in the formation, development, and even rupture of an aneurysm. We used high-resolution magnetic resonance imaging (HRMRI) to investigate the aneurysm wall in an effort to identify evidence of inflammation invasion and define its relationship with aneurysm behavior., Methods: Patients with intracranial aneurysms who were prospectively evaluated using HRMRI between July 2013 and June 2014 were enrolled in this study. The aneurysm's wall enhancement and evidence of inflammation invasion were determined. In addition, the relationship between aneurysm wall enhancement and aneurysm size and symptoms, including ruptured aneurysms, giant unruputred intracranial aneurysms (UIAs) presenting as mass effect, progressively growing aneurysms, and aneurysms associated with neurological symptoms, was statistically analyzed., Results: Twenty-five patients with 30 aneurysms were available for the current study. Fourteen aneurysms showed wall enhancement, including 6 ruptured and 8 unruptured aneurysms. Evidence of inflammation was identified directly through histological studies and indirectly through intraoperative investigations and clinical courses. The statistical analysis indicated no significant correlation between aneurysm wall enhancement and aneurysm size. However, there was a strong correlation between wall enhancement and aneurysm symptoms, with a kappa value of 0.86 (95 % CI 0.68-1)., Conclusions: Aneurysm wall enhancement on HRMRI might be a sign of inflammatory change. Symptomatic aneurysms exhibited wall enhancement on HRMRI. Wall enhancement had a high consistent correlation of symptomatic aneurysms. Therefore, wall enhancement on HRMRI might predict an unsteady state of an intracranial saccular aneurysm.

Reports on histological changes of vascular wall following clipping surgery have been scarce. The authors experienced a case of unruptured cerebral aneurysm in which the tissue occluded by clip blades for 6 years was obtained and histologically examined. The aneurysmal wall following clipping showed granulomatous inflammation with necrosis, and occluded aneurysmal walls were found with collagenous fibrous tissue. Mild infiltration by lymphocytes and fibrous thickened intima occurred., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To determine if complete flow obliteration by covered stents reduces intra-aneurysm pressures in internal carotid artery (ICA) aneurysms., Methods: A single lumen microcatheter was placed into the aneurysm sac prior to covered stent deployment in 3 patients and connected to a pressure monitoring system. The intra-aneurysm pressure was continuously monitored, and readings were recorded prior to and immediately after stent deployment and at 5-minute intervals up to 20 minutes after stent placement. Complete occlusion of flow into the aneurysms was confirmed by carotid angiography., Results: There was no change in mean pressure within the aneurysm before and immediately after stent placement (80 mmHg) in any patient, nor was there a change in waveform of the intra-aneurysm pressure recording. The average of intra-aneurysm pressures among the 3 patients was higher (99 mmHg) at 10 and 15 minutes after stent placement. In 2 patients, the microcatheter was retracted into the parent arterial lumen; no difference in pressure was noted., Conclusion: Our observations suggest no change in the pressures within the aneurysm after complete flow cessation (flow-independent). These findings may assist clinicians in better understanding aneurysm hemodynamics and rupture after covered stent deployment.