Decoding the biology and clinical implication of neutrophils in intracranial aneurysm.

OBJECTIVE: Abundant neutrophils have been identified in both ruptured and unruptured intracranial aneurysm (IA) domes, with their function and clinical implication being poorly characterized. MATERIALS AND METHODS: We employed single-cell RNA sequencing (scRNA-Seq) datasets of both human and murine model, and external bulk mRNA sequencing datasets to thoroughly explore the features and functional heterogeneous of neutrophils infiltrating the IA dome. RESULTS: We found that both unruptured and ruptured IA dome contain a substantial population of neutrophils, characterized by FCGR3B, G0S2, CSF3R, and CXCR2. These cells exhibited heterogeneity in terms of function and differentiation. Despite similar transcriptional activation, neutrophils in IA dome expressed a repertoire of gene programs that mimicked transcriptomic alterations observed from bone marrow to peripheral blood, showing self-similarity. In addition, the recruitment of neutrophils in unruptured IA was primarily mediated by monocytes/macrophages, and once ruptured, both neutrophils, and a specific subset of inflammatory smooth muscle cells (SMCs) were involved in the process. The receiver operator characteristic curve (ROC) analysis indicated that distinct neutrophil subclusters were associated with IA formation and rupture, respectively. By reviewing current studies, we found that neutrophils play a detrimental role to IA wall integrity through secreting specific ligands, ferroptosis driven by ALOX5AP and PTGS2, and the formation of neutrophil extracellular traps (NETs) mediated by PADI4. INTERPRETATION: This study delineated the biology and potential clinical implications of neutrophils in IA dome and provided a reliable basis for future researches.

Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single-Cell RNA Sequencing.

BACKGROUND: Intracranial aneurysm (IA) is common and occasionally results in life-threatening hemorrhagic strokes. However, the cell architecture and inflammation in the IA dome remain less understood. METHODS AND RESULTS: Single-cell RNA sequencing was performed on ruptured and unruptured human IA domes for delineating the cell atlas, gene expression perturbations, and inflammation features. Two external bulk mRNA sequencing-based data sets and serological results of 126 patients were collected for validation. As a result, a total of 21 332 qualified cells were captured. Vascular cells, including endothelial cells, smooth muscle cells, fibroblasts, and pericytes, were assigned in extremely sparse numbers (4.84%), and were confirmed by immunofluorescence staining. Pericytes, characterized by ABCC9 and HIGD1B, were identified in the IA dome for the first time. Abundant immune cells were identified, with the proportion of monocytes/macrophages and neutrophils being remarkably higher in ruptured IA. The lymphocyte compartment was also thoroughly categorized. By leveraging external data sets and machine learning algorithms, macrophages were robustly associated with IA rupture, irrespective of their polarization status. The single nucleotide polymorphism rs2280543, which is identified in East Asian populations, was associated with macrophage metabolic reprogramming through regulating TALDO1 expression. CONCLUSIONS: This study provides insights into the cellular architecture and inflammatory features in the IA dome and may enlighten novel therapeutics for unruptured IA.

Ivy Sign: Usefulness in Diagnosis and Prognosis Prediction of Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) cannot be found commonly as a rare type compared with other vascular disease, such as aneurysm. However, it cannot be ignored for its high fatality and disability rates. In addition, exact pathogenesis study of this disease is still on the way. The ivy sign is always observed in MMD, but the clinical importance of this sign in MMD isn't clearly known. The main purpose of this research was to specifically investigate the clinical significance. METHODS: In this retrospective cohort study to gather the baseline clinical and imaging study, the patients with MMD were hospitalized from January 2016 to 2020. In the analysis, univariate and multivariate logistic regression was used to testify whether ivy sign was independently associated with MMD characteristics including cerebrovascular morphology, cerebral hemodynamics, cerebrovascular events, and postoperative collateral formation (PCF). RESULTS: We included 156 patients with 312 hemispheres. As for the result of multivariate logistic regression analysis, we could discover a fact that ivy sign was tightly connected to the Suzuki stage ≥IV (odds ratio [OR], 1.386; 95% confidence interval [CI], 1.055-1.822; P = 0.019), cerebral blood flow (CBF) decreased type (OR, 2.330; 95% CI, 1.733-3.133; P = 0.000), age acted as a protective factor for CBF (OR, 0.966; 95% CI, 0.946-0.986; P = 0.001), the elder was more likely associated with decreased CBF. Ivy sign also played a significant role in ischemic cerebrovascular events (OR, 5.653; 95% CI, 3.092-10.336; P = 0.003), their remarkable connection could be seen on the study. We could also find that ivy sign was closely connected to the good PCF (OR, 2.830; 95% CI, 1.329-6.027; P = 0.007), and we couldn't ignore the fact that age was associated with good PCF as well (OR, 0.933; 95% CI, 0.882-0.987; P = 0.015). DISCUSSION: We could be more aware of the connection between ivy sign and Moyamoya disease from this study in order to implement diagnosis, treatment, and prognosis more efficiently.

COVPRIG robustly predicts the overall survival of IDH wild-type glioblastoma and highlights METTL1+ neural-progenitor-like tumor cell in driving unfavorable outcome.

BACKGROUND: Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate a Robust Prognostic Model for IDH wild-type GBM (COVPRIG) for the prediction of overall survival using a novel metric, gene-gene (G × G) interaction, and explore molecular and cellular underpinnings. METHODS: Univariate and multivariate Cox regression of four independent trans-ethnic cohorts containing a total of 800 samples. Prediction efficacy was comprehensively evaluated and compared with previous models by a systematic literature review. The molecular underpinnings of COVPRIG were elucidated by integrated analysis of bulk-tumor and single-cell based datasets. RESULTS: Using a Cox-ph model-based method, six of the 93,961 G × G interactions were screened to form an optimal combination which, together with age, comprised the COVPRIG model. COVPRIG was designed for RNA-seq and microarray, respectively, and effectively identified patients at high risk of mortality. The predictive performance of COVPRIG was satisfactory, with area under the curve (AUC) ranging from 0.56 (CGGA693, RNA-seq, 6-month survival) to 0.79 (TCGA RNAseq, 18-month survival), which can be further validated by decision curves. Nomograms were constructed for individual risk prediction for RNA-seq and microarray-based cohorts, respectively. Besides, the prognostic significance of COVPRIG was also validated in GBM including the IDH mutant samples. Notably, COVPRIG was comprehensively evaluated and externally validated, and a systemic review disclosed that COVPRIG outperformed current validated models with an integrated discrimination improvement (IDI) of 6-16%. Moreover, integrative bioinformatics analysis predicted an essential role of METTL1+ neural-progenitor-like (NPC-like) malignant cell in driving unfavorable outcome. CONCLUSION: This study provided a powerful tool for the outcome prediction for IDH wild-type GBM, and preliminary molecular underpinnings for future research.

Nomogram to Predict Good Collateral Formation After the STA-MCA Bypass Surgery in Adult Patients With Moyamoya Disease.

BACKGROUND: Collateral formation from the extracranial carotid artery to ischemic brain tissue determines the clinical success of superficial temporal artery (STA) to middle cerebral artery (MCA) bypass surgery in adult patients with moyamoya disease, but postoperative collateral formation (PCF) after STA-MCA bypass surgery is unpredictable. Accurate preoperative prediction of acceptable PCF could improve patient selection. This study aims to develop a prediction nomogram model for PCF in this patient population. METHODS: Adult patients with moyamoya disease undergoing the STA-MCA bypass surgery between January 2013 and December 2020 at a single institution were retrospectively or prospectively enrolled in this observational study. Data including potential clinical and radiological predictors were obtained from hospital records. A nomogram was generated based on a multivariate logistic regression analysis, to identify potential predictors associated with good PCF. The performance of the nomogram was evaluated for discrimination, calibration, and clinical utility. RESULTS: Data from 243 patients with moyamoya disease who underwent the STA-MCA bypass surgery were analyzed to build the nomogram. After 1-year follow-up, 162 (66.7%) hemispheres had good PCF and 81 (33.3%) had poor PCF. Good PCF is associated with 3 preoperative factors: age at operation, a diameter of donor branch of STA, and the preinfarction period stage. Incorporating these 3 factors, the model achieved a concordance index of 0.88 (95% CI, 0.84-0.92) and had a well-fitted calibration curve and good clinical application value. A cutoff value of 100 was determined to predict good PCF via this nomogram. CONCLUSIONS: The nomogram exhibits high accuracy in predicting good PCF after the STA-MCA bypass surgery in adult patients with moyamoya disease and may allow surgeons to better evaluate preoperatively candidacy for successful bypass surgery.

Integrated genomic, transcriptomic, and epigenetic analyses identify a leukotriene synthesis-related M2 macrophage gene signature that predicts prognosis and treatment vulnerability in gliomas.

The pathological implications of tumor-associated macrophages in the glioma microenvironment have been highlighted, while there lacks a gene signature to characterize the functional status and clinical implications of these cells. Comprehensive bioinformatics approaches were employed to develop an M2 macrophage-associated gene signature at bulk-tumor and single-cell levels and explore immunological and metabolic features. Consequently, the PI3K pathway and fatty acid metabolism were correlated with the M2 fraction. Further distilling the pathway members resulted in a leukotriene synthesis-related gene signature (Macro index), including PIK3R5, PIK3R6, ALOX5, ALOX5AP, and ALOX15B, that was primarily expressed by monocytes/macrophages. Increased Macro index predicted IL13-induced macrophages, and was associated with T-cell dysfunction at both transcriptional and epigenetic levels and predicted an unfavorable outcome. Besides, the Macro index was proportional with PAI1 at the protein level, with high levels of the latter suggesting a decreased progression-free interval of glioblastoma. Notably, the monocytes/macrophages in the glioma environment contribute to the expression of immune checkpoints and the Macro index predicts glioma responsiveness to anti-PD1 treatment. Together, our study proposed a leukotriene synthesis-related M2 macrophage gene signature, which may provide insights into the role of these cells in the glioma microenvironment and facilitate individually tailored therapeutic strategies for the disease.

Novel macrophage-related gene prognostic index for glioblastoma associated with M2 macrophages and T cell dysfunction.

This study aims to construct a Macrophage-Related Gene Prognostic Index (MRGPI) for glioblastoma (GBM) and explore the underlying molecular, metabolic, and immunological features. Based on the GBM dataset from The Cancer Genome Atlas (n = 156), 13 macrophage-related hub genes were identified by weighted gene co-expression network (WGCNA) analysis. 5 prognostic genes screened by Kaplan-Meire (K-M) analysis and Cox regression model were used to construct the MRGPI, including GPR84, NCF2, HK3, LILRB2, and CCL18. Multivariate Cox regression analysis found that the MRGPI was an independent risk factor (HR = 2.81, CI95: 1.13-6.98, p = 0.026), leading to an unfavorable outcome for the MRGPI-high group, which was further validated by 4 validation GBM cohorts (n = 728). Thereafter, the molecular, metabolic, and immune features and the clinical implications of the MRGPI-based groups were comprehensively characterized. Gene set enrichment analysis (GSEA) found that immune-related pathways, including inflammatory and adaptive immune response, and activated eicosanoid metabolic pathways were enriched in the MRGPI-high group. Besides, genes constituting the MRGPI was primarily expressed by monocytes and macrophages at single-cell scope and was associated with the alternative activation of macrophages. Moreover, correlation analysis and receiver operating characteristic (ROC) curves revealed the relevance between the MRGPI with the expression of immune checkpoints and T cell dysfunction. Thus, the responsiveness of samples in the MRGPI-high group to immune checkpoint inhibitors (ICI) was detected by algorithms, including Tumor Immune Dysfunction and Exclusion (TIDE) and Submap. In contrast, the MRGPI-low group had favorable outcome, was less immune active and insensitive to ICI. Together, we have developed a promising biomarker to classify the prognosis, metabolic and immune features for GBM, and provide references for facilitating the personalized application of ICI in GBM.

Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Adults with Moyamoya Disease.

In clinical work, the magnetic resonance imaging markers of cerebral small vessel disease (CSVD) are frequently observed in moyamoya disease (MMD), but the clinical significance of these markers in MMD remains unclear. This study aimed to fill this gap and systematically investigate its clinical significance. In this retrospective cohort study, we screened all adult patients with MMD hospitalized from January 2016 to January 2020 and collected their baseline clinical and imaging information. Univariate and multivariate logistic regression analyses were then performed to determine which imaging markers were independently associated with MMD characteristics, including cerebrovascular morphology, cerebral hemodynamics, cerebrovascular events, and postoperative collateral formation (PCF). A total of 312 cerebral hemispheres images were collected from the 156 patients with MMD. Using multivariate logistic regression analysis, the following results were generated: (1) The presence of lacunes (OR, 2.094; 95% CI, 1.109-3.955; p = 0.023) and severe white matter hyperintensities (WMH) (OR, 3.204; 95% CI, 1.742-5.892; p < 0.001) were associated with a Suzuki stage ≥ IV; (2) the presence of lacunes (OR, 6.939; 95% CI, 3.384-14.230; p < 0.001), higher numbers of enlarged perivascular spaces in centrum semiovale (CSO-EPVS) (OR, 1.046; 95% CI, 1.024-1.067; p < 0.001), and severe WMH (OR, 2.764; 95% CI, 1.463-5.223; p = 0.002) were associated with the reduced regional cerebral blood flow; (3) the presence of lacunes (OR, 12.570; 95% CI, 2.893-54.624; p = 0.001), higher numbers of CSO-EPVS (OR, 1.103; 95% CI, 1.058-1.150; p < 0.001), and severe WMH (OR, 5.982; 95% CI, 1.727-20.716; p = 0.005) were associated with ischemic cerebrovascular events; (4) the higher number of CSO-EPVS (OR, 1.077; 95% CI, 1.026-1.131; p = 0.003) was associated with good PCF. The lacunes, WMH, and CSO-EPVS were independently associated with these MMD characteristics. In conclusion, this study provided a novel and potential framework for the practical assessment of MMD by magnetic resonance imaging.

Angiographic and Hemodynamic Features in Asymptomatic Hemispheres of Patients With Moyamoya Disease.

BACKGROUND AND PURPOSE: There is also a risk of stroke in the asymptomatic hemispheres of moyamoya disease (MMD), but it does not draw enough attention. The study investigated the differences between the three types of asymptomatic hemispheres in MMD and their associations with the two types of symptomatic hemispheres, respectively. METHODS: Retrospectively reviewed clinical and imaging characteristics of asymptomatic and symptomatic hemispheres in consecutive cases of single-center MMD patients, with an emphasis on imaging characterization regarding vascular morphology and cerebral perfusion. MMD hemispheres were categorized into 5 types: hemorrhagic hemispheres, ischemic hemispheres, asymptomatic hemispheres in unilateral hemorrhagic MMD, asymptomatic hemispheres in unilateral ischemic MMD, and bilateral asymptomatic hemispheres in MMD. Angiographic feature was assessed by Suzuki's angiographic stage, while hemodynamic feature was assessed by preinfarction period stage. RESULTS: One hundred ninety-four MMD patients with 388 hemispheres were enrolled. Asymptomatic hemispheres in unilateral hemorrhagic MMD were largely similar to hemorrhagic hemispheres, both had more advanced Suzuki's angiographic stage and lower degree of hemodynamic failure compared with bilateral asymptomatic hemispheres in MMD and asymptomatic hemispheres in unilateral ischemic MMD. Asymptomatic hemispheres in unilateral ischemic MMD were similar to ischemic hemispheres, both had less advanced Suzuki's angiographic stage and higher degree of hemodynamic failure compared with bilateral asymptomatic hemispheres in MMD and asymptomatic hemispheres in unilateral hemorrhagic MMD. Bilateral asymptomatic hemispheres in MMD were different from the other hemispheres and had less advanced Suzuki's angiographic stage and lower degree of hemodynamic failure. CONCLUSIONS: The three types of asymptomatic hemispheres in MMD are defined and have unique angiographic and hemodynamic features. Different combinations of the two features can reflect the tendency of pathological evolution in these different asymptomatic hemispheres.

Clinical and Hemodynamic Features in Moyamoya Disease with Intracranial Aneurysms.

OBJECTIVE: Intracranial aneurysms (IAs) are occasionally associated with moyamoya disease (MMD). The purpose of this study was to elucidate differences between patients with MMD with and without IAs and differences between patients with IAs at different locations. METHODS: Between May 2012 and December 2017, consecutive patients with MMD were enrolled in a retrospective single-center study. IAs were classified as circle of Willis (CoW) or peripheral aneurysms according to the anatomic location. Clinical characteristics and hemodynamic parameters were collected and analyzed. A hemispheric analysis was performed for Suzuki stage and computed tomography perfusion parameters. RESULTS: The study included 31 patients with MMD with IAs and 279 patients with MMD without IAs. The patients with IAs had more severe neurological dysfunction, more advanced Suzuki stage, and less hemodynamic dysfunction than the patients without IAs (P < 0.05). Of patients with MMD with IAs, 17 had CoW aneurysms, and 13 had peripheral aneurysms. Patients with CoW aneurysms were older and had more advanced Suzuki stage than patients with peripheral aneurysms (P < 0.05). CONCLUSIONS: Patients with MMD with IAs had different clinical and hemodynamic features compared with patients with MMD without IAs. CoW aneurysms and peripheral aneurysms may occur at different stages of MMD, which may explain their differences in anatomical location, type of hemorrhage, and treatment strategy.

CT Perfusion for Identification of Patients at Risk for Delayed Cerebral Ischemia during the Acute Phase after Aneurysmal Subarachnoid Hemorrhage: A Meta-analysis.

BACKGROUND: It has been acknowledged that delayed cerebral ischemia (DCI) can be diagnosed by computed tomography perfusion (CTP) when it occurs following aneurysmal subarachnoid hemorrhage (aSAH); however, the clinical role of CTP in the prediction of DCI remains unclear. We performed a meta-analysis to investigate the role of CTP in the identification of patients at risk for DCI during the acute phase (<4 days) after aSAH. MATERIALS AND METHODS: Relevant articles were systematically searched for analysis on PubMed, EMBASE, and Cochrane databases. The best CTP parameter or the definition of abnormal CTP scan result were collected, and the data with the greatest overall predictive value for DCI was extracted to assess the strength of association between a positive CTP result and an impending DCI. In addition, pooled estimates of sensitivity and specificity were determined. RESULTS: Three relevant articles involving 128 patients were included in the analysis wherein DCI developed in 48 patients (37.5%). The pooled odds ratio was 32.15 (95% CI, 9.92-104.21), suggesting that the patients with a positive CTP test in the acute phase after aSAH were approximately 32 times as likely to develop DCI compared with those without aSAH. The pooled sensitivity and specificity of CTP for detecting impending DCI after aSAH was 65% (95% CI: 0.49-0.78) and 91% (95% CI: 0.83-0.96). CONCLUSIONS: CTP can detect abnormal brain perfusion before the occurrence of DCI. This may allow close monitoring and preemptive therapy for improvement in the prognosis in patients with aSAH.

CT perfusion diagnoses delayed cerebral ischemia in the early stage of the time-window after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: It has been acknowledged that delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) can be diagnosed by CT perfusion (CTP) in the DCI time-window. We evaluated the diagnostic accuracy of CTP for DCI during the early stage of the time-window. MATERIALS AND METHODS: We prospectively enrolled patients with aneurysmal SAH. DCI was defined as both new cerebral infarction and clinical deterioration after SAH. CTP was performed by using a standardized protocol with predefined regions of interest in 4 to 6 days after SAH. We quantitatively evaluated the diagnostic accuracy of eight CTP parameters (4 for absolute parameters and 4 for relative parameters). The receiver operator characteristic (ROC) curves of all parameters were generated and the optimal threshold values were derived for the calculation of sensitivities and specificities. RESULTS: Fifty-three patients were enrolled and 20 patients were diagnosed with DCI. In the analysis of absolute CTP parameters, CBF and MTT had areas under the curve (AUC) >0.75 and the optimal threshold value was 40.4mL/100g/min and 3.78seconds, respectively. Through the evaluation of relative CTP parameters, all 4 parameters had AUC >0.75 and the optimal threshold value was 0.9 for CBV ratio, 0.85 for CBF ratio, 0.32seconds for MTT difference and 1.31seconds for TTP difference. CONCLUSIONS: Besides two absolute CTP parameters (CBV and TTP), all six CTP parameters can be used as good diagnostic tests for DCI in the early stage of the time-window.

Evaluating the diagnostic accuracy of CT perfusion in patients with cerebral vasospasm after aneurysm rupture: a meta-analysis.

AIM: Computed tomography perfusion (CTP) has recently been used to identify regions of potential ischemia due to cerebral vasospasm, and CTP parameters are able to quantitatively evaluate brain parenchymal perfusion. We performed a meta-analysis as an update of a previous paper published in 2010 and aimed at evaluating the diagnostic accuracy of CTP and CTP parameters for vasospasm after aneurysm rupture. MATERIAL AND METHODS: Relevant articles published between January 2005 and May 2013 were systematically searched for analysis without language restrictions from the PubMed/MEDLINE, Embase, and Cochrane databases. The data of CTP parameters, including CBV, CBF, MTT and TTP, were extracted for analysis, and the pooled sensitivity, specificity, PLR, NLR, DOR and the sROC curve were determined. RESULTS: Three relevant articles and a total of 98 patients were finally involved in the analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of CTP for diagnosing cerebral vasospasm were 94%, 90%, 8.22, 0.06, 141.09, and 0.9802, respectively. Through the evaluation of CTP parameters, MTT had a higher sensitivity (91%) while CBF had a higher specificity (93%). CONCLUSION: CT perfusion has a great diagnostic value to detect cerebral vasospasm compared with DSA in patients with aneurysmal subarachnoid hemorrhage (aSAH). As CTP parameters, CBF and MTT quantitatively evaluate brain parenchymal perfusion.

Accuracy of computed tomography perfusion in detecting delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage: a meta-analysis.

BACKGROUND AND PURPOSE: In recent years, significant literature shows that computed tomography perfusion (CTP) can provide sufficient information on cerebral hemodynamics and effectively indicate delayed cerebral ischemia (DCI) before the development of infarction. We aimed at performing a meta-analysis to provide a more full and accurate evaluation of CTP and CTP parameters in detecting DCI in patients with aneurysmal subarachnoid hemorrhage. MATERIALS AND METHODS: We searched the PubMed, MedLine, Embase and Cochrane databases for analysis published from February 2005 to February 2013. We extracted CTP parameters, including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), interhemispheric ratios for CBV and CBF and interhemispheric differences for MTT and TTP. Pooled estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the summary receiver-operating characteristic curve were determined. RESULTS: Four research studies are met the inclusion criteria for the analysis. The pooled sensitivity, specificity, PLR, NLR and DOR of CTP for detecting the DCI were 82%, 82%, 4.56, 0.22 and 20.96, respectively. Through the evaluation of absolute CTP parameters, CBF and MTT showed diagnostic value for DCI, but CBF and TTP did not. Moreover, CBF ratio, MTT difference and TTP difference showed more diagnostic value than CBV ratio in DCI detection by the assessment of relative CTP parameters. CONCLUSIONS: As a non-invasive and short time consuming screening method, CTP own a high diagnostic value for the detection of DCI after aneurysm rupture.

Diagnosing residual or recurrent cerebral aneurysms after clipping by computed tomographic angiography: Meta-analysis.

BACKGROUND: A cerebral aneurysm with incomplete treatment may re-grow and cause new bleeding. This meta-analysis calculates the sensitivity and specificity of computed tomographic angiography (CTA) in the detection of the residual or recurrent cerebral aneurysms after clipping, in comparison with digital subtraction angiography (DSA). MATERIALS AND METHODS: Between October 1997 and October 2012, relevant data were systematically and prospectively collected without language restrictions from the PUBMED and EMBASE databases for analysis. A total of 10 eligible studies compared CTA with DSA in the detection of the residual or recurrent cerebral aneurysms after clipping by two independent observers. The sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated on a per-aneurysm basis, and the area under the sROC curve (AUC), heterogeneity, and publication bias also were evaluated. RESULTS: A total of 487 aneurysms were included for meta-analysis. The pooled sensitivity, specificity, +LR, -LR, DOR, and AUC of CTA for detecting the residual or recurrent aneurysms after clipping were 71%, 94%, 9.39, 0.32, 28.32, and 0.8558, respectively. The between-study heterogeneity of DOR and the presence of publication bias were not statistically significant. CONCLUSIONS: As a noninvasive and convenient screening method, CTA has a high diagnostic value for the detection of the residual or recurrent aneurysms after clipping. In the future, it may be used as a routine diagnostic tool for evaluation of aneurysms after clipping.