Novel in vivo Assessment of Unruptured Intracranial Aneurysm Inflammatory Factors.
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ABSTRACT:
SUBMITTER: Cordina SM
PROVIDER: S-EPMC7283897 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Novel <i>in vivo</i> Assessment of Unruptured Intracranial Aneurysm Inflammatory Factors.
Cordina Steve M SM Afarian Shant S Gerthoffer William T WT Martino Anthony A Wilson Russell R Naritoku Dean K DK
Frontiers in neurology 20200603
<b>Background and Purpose:</b> The growth and eventual rupture of intracranial aneurysms may be due to an underlying inflammatory process as evidenced by pathological examination of aneurysm walls. We hypothesize that unruptured aneurysms have an increased inflammatory milieu within their lumen in comparison to the rest of the cerebral arterial vascular system. <b>Methods:</b> Blood was sampled from unruptured aneurysms in patients presenting for aneurysm coil embolization and C3 and C4 compleme ...[more]
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Project description:BackgroundThe rupture of an intracranial aneurysm (IA) causes devastating subarachnoid hemorrhages, yet most IAs remain undiscovered until they rupture. Recently, we found an IA RNA expression signature of circulating neutrophils, and used transcriptome data to build predictive models for unruptured IAs. In this study, we evaluate the feasibility of using whole blood transcriptomes to predict the presence of unruptured IAs.MethodsWe subjected RNA from peripheral whole blood of 67 patients (34 with unruptured IA, 33 without IA) to next-generation RNA sequencing. Model genes were identified using the least absolute shrinkage and selection operator (LASSO) in a random training cohort (n = 47). These genes were used to train a Gaussian Support Vector Machine (gSVM) model to distinguish patients with IA. The model was applied to an independent testing cohort (n = 20) to evaluate performance by receiver operating characteristic (ROC) curve. Gene ontology and pathway analyses investigated the underlying biology of the model genes.ResultsWe identified 18 genes that could distinguish IA patients in a training cohort with 85% accuracy. This SVM model also had 85% accuracy in the testing cohort, with an area under the ROC curve of 0.91. Bioinformatics reflected activation and recruitment of leukocytes, activation of macrophages, and inflammatory response, suggesting that the biomarker captures important processes in IA pathogenesis.ConclusionsCirculating whole blood transcriptomes can detect the presence of unruptured IAs. Pending additional testing in larger cohorts, this could serve as a foundation to develop a simple blood-based test to facilitate screening and early detection of IAs.
| S-EPMC7647097 | biostudies-literature
Project description:ObjectiveWe endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research.MethodsAn international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement).ResultsThe UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033).ConclusionsThis novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.
| S-EPMC4560059 | biostudies-literature
Project description:BACKGROUND:Intracranial aneurysms (IAs) are dangerous because of their potential to rupture. We previously found significant RNA expression differences in circulating neutrophils between patients with and without unruptured IAs and trained machine learning models to predict presence of IA using 40 neutrophil transcriptomes. Here, we aim to develop a predictive model for unruptured IA using neutrophil transcriptomes from a larger population and more robust machine learning methods. METHODS:Neutrophil RNA extracted from the blood of 134 patients (55 with IA, 79 IA-free controls) was subjected to next-generation RNA sequencing. In a randomly-selected training cohort (n?=?94), the Least Absolute Shrinkage and Selection Operator (LASSO) selected transcripts, from which we constructed prediction models via 4 well-established supervised machine-learning algorithms (K-Nearest Neighbors, Random Forest, and Support Vector Machines with Gaussian and cubic kernels). We tested the models in the remaining samples (n?=?40) and assessed model performance by receiver-operating-characteristic (ROC) curves. Real-time quantitative polymerase chain reaction (RT-qPCR) of 9 IA-associated genes was used to verify gene expression in a subset of 49 neutrophil RNA samples. We also examined the potential influence of demographics and comorbidities on model prediction. RESULTS:Feature selection using LASSO in the training cohort identified 37 IA-associated transcripts. Models trained using these transcripts had a maximum accuracy of 90% in the testing cohort. The testing performance across all methods had an average area under ROC curve (AUC)?=?0.97, an improvement over our previous models. The Random Forest model performed best across both training and testing cohorts. RT-qPCR confirmed expression differences in 7 of 9 genes tested. Gene ontology and IPA network analyses performed on the 37 model genes reflected dysregulated inflammation, cell signaling, and apoptosis processes. In our data, demographics and comorbidities did not affect model performance. CONCLUSIONS:We improved upon our previous IA prediction models based on circulating neutrophil transcriptomes by increasing sample size and by implementing LASSO and more robust machine learning methods. Future studies are needed to validate these models in larger cohorts and further investigate effect of covariates.
| S-EPMC7565814 | biostudies-literature
Project description:BackgroundThe presence of an intracranial aneurysm is contraindicated to recombinant tissue plasminogen activator (r-tPA) treatment for acute ischemic stroke. However, it is difficult to exclude asymptomatic intracranial aneurysms by using conventional, noncontrast head computed tomography (CT), which is the only neuroimaging suggested before r-tPA. Recent case reports and series have shown that administering r-tPA to patients with a pre-existing aneurysm does not increase the bleeding risk. However, Asians are known to have a relatively higher bleeding risk, and little evidence is available regarding the risk of using r-tPA on Asian patients with intracranial aneurysms.MethodsMedical records from the Shuang Ho hospital stroke registration between July 2010 and December 2014 were retrospectively reviewed, and 144 patients received r-tPA. Unruptured intracranial aneurysms were detected using CT, or magnetic resonance or conventional angiography after r-tPA. The primary and secondary outcomes were the difference in overall intracranial hemorrhage (ICH) and symptomatic ICH after r-tPA. The differences were analyzed using Fisher's exact or Mann-Whitney U tests, and p < 0.05 was defined as the statistical significance.ResultsA total of 144 patients were reviewed, and incidental unruptured intracranial aneurysms were found in 11 of them (7.6%). No significant difference was observed in baseline demographic data between the aneurysm and nonaneurysm groups. Among patients with an unruptured aneurysm, two had giant aneurysms (7.7 and 7.4 mm, respectively). The bleeding risk was not significant different between aneurysm group (2 out of 11, 18%) with nonaneurysm group (7 out of 133, 5.3%) (p = 0.14). None of the patients with an unruptured aneurysm had symptomatic ICH, whereas one patient without an aneurysm exhibited symptomatic ICH.ConclusionsThe presence of an unruptured intracranial aneurysm did not significantly increase the risk of overall and symptomatic ICH in Taiwanese patients after they received r-tPA.
| S-EPMC5491104 | biostudies-literature
Project description:An increasing number of unruptured intracranial aneurysms (UIAs) has been discovered in elderly patients in recent years, but the optimal treatment strategy for these patients remains controversial. We report our six-year experience treating UIAs in elderly patients (≥ 70 years old). A retrospective review was conducted of elderly patients who harbored UIAs treated by conservative observation, microsurgical clipping, or endovascular coiling between January 2009 and December 2014. The patients' clinical and imaging information was recorded. Treating methods, procedure-related complications, imaging results, and clinical outcomes were analyzed. A total of 141 consecutive elderly patients with 166 UIAs were enrolled in our study. In all, 64 patients with 79 aneurysms were treated with coiling, and 14 patients with 14 aneurysms were treated with clipping. The remaining 63 patients with 73 aneurysms were placed under conservative observation. The average modified Rankin scale was 0.99 (range 0-6) in the full cohort after a mean follow-up of 50.4 months (range 0-70 months). There was no significant difference of modified Rankin scale in patients with UIAs treated by different methods. Multivariate analysis showed that age (p=0.030) and aneurysm size (p=0.011) were independent risk factors for unfavorable outcome of UIAs in the elderly. Patient age (p=0.010) and aneurysm size (p=0.020) were also significantly associated with unfavorable outcome of UIAs managed with observation initially. Our results indicated that endovascular coil embolization and clipping were both safe and effective treatment methods for UIAs in the elderly. Aggressive treatment for UIAs in elderly patients with risk factors of aneurysm rupture should be considered positively.
| S-EPMC6686429 | biostudies-literature
Project description:Cerebral arteries (CAs) are prone to the saccular aneurysm formation. Since aneurysms may be considered as balloon-like dilations of the locally weakened arterial wall, it should be determined whether the presence of intracranial aneurysm is related to the generalized weakening of CAs. Among 184 consecutive forensic autopsies, eight brains with a single unruptured saccular aneurysm were identified. Aneurysms with adjacent CAs and specific CA segments were excised, namely: the anterior communicating artery complex, and bifurcations of the basilar artery, internal carotid arteries, and middle cerebral arteries. Then, aneurysm and CA specimens were subjected to pressure-inflation tests until rupture occurred at the arterial bifurcation or at the wall of the CA or aneurysm. The same protocol was applied to the control group composed of CAs excised from eight brains without aneurysm. No significant differences were noted between the experimental and control groups, depending on the mean rupture pressure (1054 vs. 1048 mmHg) and rupture site (bifurcation vs. wall) of the analyzed specimens. These findings indicate that the presence of unruptured saccular aneurysm is not related to generalized weakening of CAs among autopsy subjects. Moreover, the CA bifurcations do not represent regions of decreased wall strength.
| S-EPMC9206654 | biostudies-literature
Project description:Background and purposePrediction of intracranial aneurysm growth risk can assist physicians in planning of follow-up imaging of conservatively managed unruptured intracranial aneurysms. We therefore aimed to externally validate the ELAPSS (Earlier subarachnoid hemorrhage, aneurysm Location, Age, Population, aneurysm Size and Shape) score for prediction of the risk of unruptured intracranial aneurysm growth.MethodsFrom 11 international cohorts of patients ?18 years with ?1 unruptured intracranial aneurysm and ?6 months of radiological follow-up, we collected data on the predictors of the ELAPSS score, and calculated 3- and 5-year absolute growth risks according to the score. Model performance was assessed in terms of calibration (predicted versus observed risk) and discrimination (c-statistic).ResultsWe included 1,072 patients with a total of 1,452 aneurysms. During 4,268 aneurysm-years of follow-up, 199 (14%) aneurysms enlarged. Calibration was comparable to that of the development cohort with the overall observed risks within the range of the expected risks. The c-statistic was 0.69 (95% confidence interval [CI], 0.64 to 0.73) at 3 years, compared to 0.72 (95% CI, 0.68 to 0.76) in the development cohort. At 5 years, the c-statistic was 0.68 (95% CI, 0.64 to 0.72), compared to 0.72 (95% CI, 0.68 to 0.75) in the development cohort.Conclusions The ELAPSS score showed accurate calibration for 3- and 5-year risks of aneurysm growth and modest discrimination in our external validation cohort. This indicates that the score is externally valid and could assist patients and physicians in predicting growth of unruptured intracranial aneurysms and plan follow-up imaging accordingly.
| S-EPMC6780020 | biostudies-literature
Project description:BackgroundTo compare the effects of endovascular coiling and neurosurgical clipping in patients with unruptured intracranial aneurysm.MethodsSixteen electronic databases were searched for articles published between 1950 and July 2010 to compare clinical outcomes of clipping and coiling. Researchers reviewed all searched articles and extracted data independently. The quality of studies and evidence were evaluated using MINORS and GRADEprofiler, respectively. The odds ratio (OR) was calculated using the inverse variance meta-analysis method for each study outcome. To assess heterogeneity of ORs across cohorts, Cochran's Q statistic and I² were used.ResultsOf 4160 studies, 24 were identified (n = 31865). Clipping resulted in significantly higher disability using the Glasgow Outcome Scale (OR, 2.38; 95% CI, 1.33-4.26) and Modified Rankin Scale (OR, 2.83; 95% CI, 1.42-5.63) when compared with coiling. ORs for complications were also higher with clipping (ORs for neurological and cardiac complications were 1.94 with a 95% confidence interval [CI] of 1.09-3.47 and 2.51 with a 95% CI of 1.15-5.50). Clipping resulted in significantly greater disability in the short term (?6 m)(OR on the Glasgow Outcome Scale, 2.72; 95% CI, 1.16-6.34), but not in the long term (>6 m)(OR for Glasgow Outcome Scale, 2.12; 95% CI, 0.93-4.84).ConclusionsCoiling was a better procedure for treatment of unruptured intracranial aneurysm in terms of disability, complications, especially in the short term. Because of the limitations of the reviewed studies, further studies are required to support the present results.
| S-EPMC3519507 | biostudies-literature
Project description:PurposeThis study aimed to investigate whether a deep learning model for automated detection of unruptured intracranial aneurysms on time-of-flight (TOF) magnetic resonance angiography (MRA) can achieve a target diagnostic performance comparable to that of human radiologists for approval from the Korean Ministry of Food and Drug Safety as an artificial intelligence-applied software.Materials and methodsIn this single-center, retrospective, confirmatory clinical trial, the diagnostic performance of the model was evaluated in a predetermined test set. After sample size estimation, the test set consisted of 135 aneurysm-containing examinations with 168 intracranial aneurysms and 197 aneurysm-free examinations. The target sensitivity and specificity were set as 87% and 92%, respectively. The patient-wise sensitivity and specificity of the model were analyzed. Moreover, the lesion-wise sensitivity and false-positive detection rate per case were also investigated.ResultsThe sensitivity and specificity of the model were 91.11% [95% confidence interval (CI): 84.99, 95.32] and 93.91% (95% CI: 89.60, 96.81), respectively, which met the target performance values. The lesion-wise sensitivity was 92.26%. The overall false-positive detection rate per case was 0.123. Of the 168 aneurysms, 13 aneurysms from 12 examinations were missed by the model.ConclusionThe present deep learning model for automated detection of unruptured intracranial aneurysms on TOF MRA achieved the target diagnostic performance comparable to that of human radiologists. With high standalone performance, this model may be useful for accurate and efficient diagnosis of intracranial aneurysm.
| S-EPMC8542476 | biostudies-literature
Project description:IntroductionPositron emission tomography (PET) imaging can be used to evaluate arterial wall inflammation in extracranial vascular diseases. However, the application of PET imaging in unruptured intracranial aneurysms (UIA) remains unexplored. Our objective is to investigate feasibility of PET imaging using 18F-FDG and 68Ga-DOTANOC tracers to evaluate arterial wall inflammation in UIA.Methods and analysisThis PET imaging feasibility study will enrol patients scheduled for surgical treatment of UIA. The study subjects will undergo PET imaging of the intracranial arteries within 1 month before planned surgery. The imaging protocol includes 18F-FDG PET MRI, MRA with gadolinium enhancement, and 68Ga-DOTANOC PET CT. The study will also involve preoperative blood samples, intraoperative cerebrospinal fluid (CSF) samples, and aneurysm sac biopsy. Planned sample size is at least 18 patients. Primary outcome is uptake of 18F-FDG or 68Ga-DOTANOC in intracranial arterial aneurysms compared with contralateral normal vessel as maximum standardised uptake value or target-to-blood pool ratio and correlation of uptake of 18F-FDG or 68Ga-DOTANOC to aneurysm histological findings. Secondary outcomes include estimating the correlations between uptake of 18F-FDG or 68Ga-DOTANOC and histological findings with blood and CSF miRNA-levels, arterial wall enhancement in gadolinium enhanced MRA, aneurysm size and shape, smoking, hypertension, and location of the aneurysm.Ethics and disseminationThis study is approved by the Human Research Ethics Committee of the Hospital District of Southwest Finland, Finnish Medicines Agency Fimea, and Turku University Hospital. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences.Trial registration numberNCT04715503.
| S-EPMC10882366 | biostudies-literature