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1.
Comput Biol Med ; 120: 103759, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32421656

RESUMO

BACKGROUND: Computational fluid dynamics(CFD) of intracranial aneurysms requires flow boundary conditions(BCs) as inputs. Patient-specific BCs are usually unavailable and substituted by literature-derived generic BCs. Therefore, we investigated inter-patient BC variations and their influence on middle cerebral artery aneurysmal hemodynamics. METHOD: We retrospectively collected CT angiography and 7-T Phase-Contrast(PC)-MRI data from eight middle-cerebral-artery bifurcation aneurysms to reconstruct the geometry and measure the arterial flowrates, respectively. The coefficient of variation(CoV) was calculated for the inlet flowrate and the pulsatility index(PI). The outflow split estimated by Murray's law was compared with PC-MRI measurements. For each aneurysm, we performed seven simulations: "baseline" using PC-MRI-derived BCs and the other six with changing BCs to explore the influence of BC variations on hemodynamics. RESULTS: From PC-MRI, the inlet flowrate was 1.94 ± 0.71 cm3/s(CoV = 36%) and PI was 0.37 ± 0.13(CoV = 34%). The outflow split estimated by Murray's law deviated by 15.3% compared to PC-MRI. Comparing to "baseline" models, ±36% variations in inlet flowrate caused -61% to +89% changes in time-averaged wall shear stress(WSS), -37% to +32% in normalized WSS(NWSS; by parent-artery), and -42% to +126% in oscillatory shear index(OSI). The ±34% variations in PI caused, -46% to +67% in OSI. Applying ±15% variations in outflow split led to inflow jet deflection and -41% to +52% changes in WSS, -41% to +47% in NWSS, and -44% to +144% in OSI. CONCLUSION: Inflow rate and outflow split have a drastic impact on hemodynamics of intracranial aneurysms. Inlet waveform has a negligible impact on WSS and NWSS but major impact on OSI. CFD-based models need to consider such sensitivity.

2.
J Neurosurg ; : 1-10, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32217800

RESUMO

OBJECTIVE: Coverage of the anterior spinal artery (ASA) ostia is a source of considerable consternation regarding flow diversion (FD) in vertebral artery (VA) aneurysms due to cord supply. The authors sought to assess the association between coverage of the ASA, posterior spinal artery (PSA), or lateral spinal artery (LSA) ostia when placing flow diverters in distal VAs and clinical outcomes, with emphasis on cord infarction. METHODS: A multicenter retrospective study of 7 institutions in which VA aneurysms were treated with FD between 2011 and 2019 was performed. The authors evaluated the risk of ASA and PSA/LSA occlusion, associated thromboembolic complication, complications overall, aneurysm occlusion status, and functional outcome. RESULTS: Sixty patients with 63 VA and posterior inferior cerebellar artery aneurysms treated with FD were identified. The median aneurysm diameter was 7 mm and fusiform type was the commonest morphology (42.9%). During a procedure, 1 (61.7%) or 2 (33.3%) flow diverters were placed. Complete occlusion was achieved in 71.9%. Symptomatic thromboembolic complications occurred in 7.4% of cases and intracranial hemorrhage in 10.0% of cases. The ASA and PSA/LSA were identified in 51 (80.9%) and 35 (55.6%) complications and covered by the flow diverter in 29 (56.9%) and 13 (37.1%) of the procedures, respectively. Patency after flow diverter coverage on last follow-up was 89.2% for ASA and 100% for PSA/LSA, not significantly different between covered and noncovered groups (p = 0.5 and p > 0.99, respectively). No complications arose from coverage. CONCLUSIONS: FD aneurysm treatment in the posterior circulation with coverage of ASA or PSA/LSA was not associated with higher rates of occlusion of these branches or any instances of cord infarction.

3.
Curr Neurovasc Res ; 17(1): 58-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31987021

RESUMO

BACKGROUND: Endovascular treatment of intracranial aneurysms (IAs) by flow diverter (FD) stents depends on flow modification. Patient-specific modeling of FD deployment and computational fluid dynamics (CFD) could enable a priori endovascular strategy optimization. We developed a fast, simplistic, expansion-free balls-weeping algorithm to model FDs in patientspecific aneurysm geometry. However, since such strong simplification could result in less accurate simulations, we also developed a fast virtual stenting workflow (VSW) that explicitly models stent expansion using pseudo-physical forces. METHODS: To test which of these two fast algorithms more accurately simulates real FDs, we applied them to virtually treat three representative patient-specific IAs. We deployed Pipeline Embolization Device into 3 patient-specific silicone aneurysm phantoms and simulated the treatments using both balls-weeping and VSW algorithms in computational aneurysm models. We then compared the virtually deployed FD stents against experimental results in terms of geometry and post-treatment flow fields. For stent geometry, we evaluated gross configurations and porosity. For post-treatment aneurysmal flow, we compared CFD results against experimental measurements by particle image velocimetry. RESULTS: We found that VSW created more realistic FD deployments than balls-weeping in terms of stent geometry, porosity and pore density. In particular, balls-weeping produced unrealistic FD bulging at the aneurysm neck, and this artifact drastically increased with neck size. Both FD deployment methods resulted in similar flow patterns, but the VSW had less error in flow velocity and inflow rate. CONCLUSION: In conclusion, modeling stent expansion is critical for preventing unrealistic bulging effects and thus should be considered in virtual FD deployment algorithms. Also endowed with its high computational efficiency and superior accuracy, the VSW algorithm is a better candidate for implementation into a bedside clinical tool for FD deployment simulation.

4.
Neurosurgery ; 86(Supplement_1): S21-S34, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31838536

RESUMO

Over the past decade, flow diverter technology for endocranial aneurysms has seen rapid evolution, with the development of new devices quickly outpacing the clinical evidence base. However, flow diversion has not yet been directly compared to surgical aneurysm clipping or other endovascular procedures. The oldest and most well-studied device is the Pipeline Embolization Device (PED; Medtronic), recently transitioned to the Pipeline Flex (Medtronic), which still has sparse data regarding outcomes. To date, other flow diverting devices have not been shown to outperform the PED, although information comes primarily from retrospective studies with short follow-up, which are not always comparable. Because of this lack of high-quality outcome data, no reliable recommendations can be made for choosing among flow diversion devices yet. Moreover, the decision to proceed with flow diversion should be individualized to each patient. In this work, we wish to provide a comprehensive overview of the technical specifications of all flow diverter devices currently available, accompanied by a succinct description of the evidence base surrounding each device.

5.
J Neurointerv Surg ; 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848217

RESUMO

BACKGROUND: Recurrence of intracranial aneurysms after endovascular coiling is a serious clinical concern. OBJECTIVE: We hypothesized that recurrence is associated with aneurysm morphology and flow, as well as the coil intervention and the induced flow modifications. METHODS: We collected 52 primary-coiling aneurysm cases that were either occluded (n=34) or recurrent (n=18) at >1 year follow-up. We created aneurysm models from pre-coiling digital subtraction angiographic images, calculated aneurysm morphology, simulated pre-coiling hemodynamics, modeled coil deployment, and obtained post-coiling hemodynamics for each case. We performed univariable analysis on 26 morphologic, treatment-specific, and hemodynamic parameters to distinguish between recurrent and occluded groups, and multivariable analysis to identify independently significant parameters associated with recurrence. Univariable analysis was also performed on ruptured and unruptured aneurysm subcohorts separately to investigate if they shared specific significant parameters. RESULTS: Recurrence was associated with pre-coiling aneurysm morphologic and flow parameters including larger size (maximum dimension and volume), larger neck (diameter, area, and neck-to-parent-artery ratio), and higher flow momentum and kinetic energy. Recurrence was also associated with lower coil packing (packing density and uncoiled volume), higher post-treatment flow (velocity, momentum, and kinetic energy), lower post-treatment washout time, and higher post-treatment impingement force at the neck. Multivariable analysis identified two aneurysmal characteristics (neck diameter and pre-coiling flow kinetic energy), one coil packing parameter (uncoiled volume), and one post-treatment hemodynamic parameter (flow momentum) that were independently associated with recurrence. In ruptured aneurysms, recurrence was associated with larger neck (diameter and area), whereas in unruptured aneurysms, recurrence was associated with larger size (maximum dimension and volume). In both subcohorts, recurrence was associated with higher post-coiling flow momentum and kinetic energy. CONCLUSION: Recurrence at >1 year after coil treatment is associated with intrinsic aneurysm characteristics, coiling itself, and flow changes induced by coiling. Larger aneurysm size and neck, less coil packing, and higher intra-aneurysmal flow before and after coiling predict recurrence.

6.
PLoS One ; 14(12): e0226421, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31881029

RESUMO

BACKGROUND: Computer modeling of endovascular coiling intervention for intracranial aneurysm could enable a priori patient-specific treatment evaluation. To that end, we previously developed a finite element method (FEM) coiling technique, which incorporated simplified assumptions. To improve accuracy in capturing real-life coiling, we aimed to enhance the modeling strategies and experimentally test whether improvements lead to more accurate coiling simulations. METHODS: We previously modeled coils using a pre-shape based on mathematical curves and mechanical properties based on those of platinum wires. In the improved version, to better represent the physical properties of coils, we model coil pre-shapes based on how they are manufactured, and their mechanical properties based on their spring-like geometric structures. To enhance the deployment mechanics, we include coil advancement to the aneurysm in FEM simulations. To test if these new strategies produce more accurate coil deployments, we fabricated silicone phantoms of 2 patient-specific aneurysms in duplicate, deployed coils in each, and quantified coil distributions from intra-aneurysmal cross-sections using coil density (CD) and lacunarity (L). These deployments were simulated 9 times each using the original and improved techniques, and CD and L were calculated for cross-sections matching those in the experiments. To compare the 2 simulation techniques, Euclidean distances (dMin, dMax, and dAvg) between experimental and simulation points in standardized CD-L space were evaluated. Univariate tests were performed to determine if these distances were significantly different between the 2 simulations. RESULTS: Coil deployments using the improved technique agreed better with experiments than the original technique. All dMin, dMax, and dAvg values were smaller for the improved technique, and the average values across all simulations for the improved technique were significantly smaller than those from the original technique (dMin: p = 0.014, dMax: p = 0.013, dAvg: p = 0.045). CONCLUSION: Incorporating coil-specific physical properties and mechanics improves accuracy of FEM simulations of endovascular intracranial aneurysm coiling.


Assuntos
Procedimentos Endovasculares/instrumentação , Aneurisma Intracraniano/cirurgia , Prótese Vascular , Análise de Elementos Finitos , Humanos , Modelos Biológicos
7.
BMC Med Genomics ; 12(1): 149, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666072

RESUMO

BACKGROUND: Genetics play an important role in intracranial aneurysm (IA) pathophysiology. Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are linked to IA but how they affect disease pathobiology remains poorly understood. We used Encyclopedia of DNA Elements (ENCODE) data to investigate the epigenetic landscapes surrounding genetic risk loci to determine if IA-associated SNPs affect functional elements that regulate gene expression and if those SNPs are most likely to impact a specific type of cells. METHODS: We mapped 16 highly significant IA-associated SNPs to linkage disequilibrium (LD) blocks within the human genome. Within these regions, we examined the presence of H3K4me1 and H3K27ac histone marks and CCCTC-binding factor (CTCF) and transcription-factor binding sites using chromatin immunoprecipitation-sequencing (ChIP-Seq) data. This analysis was conducted in several cell types relevant to endothelial (human umbilical vein endothelial cells [HUVECs]) and inflammatory (monocytes, neutrophils, and peripheral blood mononuclear cells [PBMCs]) biology. Gene ontology analysis was performed on genes within extended IA-risk regions to understand which biological processes could be affected by IA-risk SNPs. We also evaluated recently published data that showed differential methylation and differential ribonucleic acid (RNA) expression in IA to investigate the correlation between differentially regulated elements and the IA-risk LD blocks. RESULTS: The IA-associated LD blocks were statistically significantly enriched for H3K4me1 and/or H3K27ac marks (markers of enhancer function) in endothelial cells but not in immune cells. The IA-associated LD blocks also contained more binding sites for CTCF in endothelial cells than monocytes, although not statistically significant. Differentially methylated regions of DNA identified in IA tissue were also present in several IA-risk LD blocks, suggesting SNPs could affect this epigenetic machinery. Gene ontology analysis supports that genes affected by IA-risk SNPs are associated with extracellular matrix reorganization and endopeptidase activity. CONCLUSION: These findings suggest that known genetic alterations linked to IA risk act on endothelial cell function. These alterations do not correlate with IA-associated gene expression signatures of circulating blood cells, which suggests that such signatures are a secondary response reflecting the presence of IA rather than indicating risk for IA.

8.
World Neurosurg ; 129: e831-e837, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207378

RESUMO

BACKGROUND: Treatment of unruptured intracranial aneurysms (IAs) in elderly patients is associated with a high risk of morbidity and mortality, necessitating a thorough understanding of the potential rupture risk. The aim of this study was to identify morphologic parameters and anatomic locations that could discriminate ruptured IAs in patients ≥70 years old. METHODS: Retrospective analysis was performed of three-dimensional angiograms and medical records of 344 patients with 411 saccular IAs. Patients ≥70 years old were defined as elderly. IAs were subdivided into ruptured and unruptured. Morphologic parameters and anatomic locations were compared in elderly and younger (<70 years old) patients with ruptured and unruptured IAs. RESULTS: The study included 266 patients <70 years old and 78 patients ≥70 years old with 411 aneurysms (102 ruptured and 309 unruptured). In the elderly group, 22 of 95 aneurysms were ruptured (23.15%) compared with 80 of 316 (25.3%) in the younger group. Size ratio and aspect ratio were higher in ruptured IAs, but only in the younger group. Undulation index, indicating IA shape irregularity, was significantly different between ruptured and unruptured IAs in younger and elderly groups. The only variables associated with rupture in the elderly group were undulation index (0.11 ± 0.07 vs. 0.07 ± 0.06, P = 0.02) and location (P = 0.001). CONCLUSIONS: Aneurysm size, size ratio, and aspect ratio may not be reliable discriminants of rupture in elderly patients. Unruptured IAs in elderly patients should be evaluated on the basis of shape irregularity and anatomic location.


Assuntos
Aneurisma Roto/patologia , Aneurisma Intracraniano/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
J Cyst Fibros ; 18(2): 194-202, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29941318

RESUMO

BACKGROUND: There is no effective way to predict cystic fibrosis (CF) pulmonary exacerbations (CFPE) before they become symptomatic or to assess satisfactory treatment responses. METHODS: RNA sequencing of peripheral blood neutrophils from CF patients before and after therapy for CFPE was used to create transcriptome profiles. Transcripts with an average transcripts per million (TPM) level > 1.0 and a false discovery rate (FDR) < 0.05 were used in a cosine K-nearest neighbor (KNN) model. Real time PCR was used to corroborate RNA sequencing expression differences in both neutrophils and whole blood samples from an independent cohort of CF patients. Furthermore, sandwich ELISA was conducted to assess plasma levels of MRP8/14 complexes in CF patients before and after therapy. RESULTS: We found differential expression of 136 transcripts and 83 isoforms when we compared neutrophils from CF patients before and after therapy (>1.5 fold change, FDR-adjusted P < 0.05). The model was able to successfully separate CF flare samples from those taken from the same patients in convalescence with an accuracy of 0.75 in both the training and testing cohorts. Six differently expressed genes were confirmed by real time PCR using both isolated neutrophils and whole blood from an independent cohort of CF patients before and after therapy, even though levels of myeloid related protein MRP8/14 dimers in plasma of CF patients were essentially unchanged by therapy. CONCLUSIONS: Our findings demonstrate the potential of machine learning approaches for classifying disease states and thus developing sensitive biomarkers that can be used to monitor pulmonary disease activity in CF.

10.
J Transl Med ; 16(1): 373, 2018 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-30593281

RESUMO

BACKGROUND: Intracranial aneurysms (IAs) are dangerous because of their potential to rupture and cause deadly subarachnoid hemorrhages. Previously, we found significant RNA expression differences in circulating neutrophils between patients with unruptured IAs and aneurysm-free controls. Searching for circulating biomarkers for unruptured IAs, we tested the feasibility of developing classification algorithms that use neutrophil RNA expression levels from blood samples to predict the presence of an IA. METHODS: Neutrophil RNA extracted from blood samples from 40 patients (20 with angiography-confirmed unruptured IA, 20 angiography-confirmed IA-free controls) was subjected to next-generation RNA sequencing to obtain neutrophil transcriptomes. In a randomly-selected training cohort of 30 of the 40 samples (15 with IA, 15 controls), we performed differential expression analysis. Significantly differentially expressed transcripts (false discovery rate < 0.05, fold change ≥ 1.5) were used to construct prediction models for IA using four well-known supervised machine-learning approaches (diagonal linear discriminant analysis, cosine nearest neighbors, nearest shrunken centroids, and support vector machines). These models were tested in a testing cohort of the remaining 10 neutrophil samples from the 40 patients (5 with IA, 5 controls), and model performance was assessed by receiver-operating-characteristic (ROC) curves. Real-time quantitative polymerase chain reaction (PCR) was used to corroborate expression differences of a subset of model transcripts in neutrophil samples from a new, separate validation cohort of 10 patients (5 with IA, 5 controls). RESULTS: The training cohort yielded 26 highly significantly differentially expressed neutrophil transcripts. Models using these transcripts identified IA patients in the testing cohort with accuracy ranging from 0.60 to 0.90. The best performing model was the diagonal linear discriminant analysis classifier (area under the ROC curve = 0.80 and accuracy = 0.90). Six of seven differentially expressed genes we tested were confirmed by quantitative PCR using isolated neutrophils from the separate validation cohort. CONCLUSIONS: Our findings demonstrate the potential of machine-learning methods to classify IA cases and create predictive models for unruptured IAs using circulating neutrophil transcriptome data. Future studies are needed to replicate these findings in larger cohorts.


Assuntos
Aneurisma Roto/sangue , Aneurisma Roto/diagnóstico , Biomarcadores/sangue , Aneurisma Intracraniano/sangue , Aneurisma Intracraniano/diagnóstico , Neutrófilos/metabolismo , Transcriptoma/genética , Aneurisma Roto/genética , Bases de Dados Genéticas , Feminino , Ontologia Genética , Humanos , Aneurisma Intracraniano/genética , Pessoa de Meia-Idade , Modelos Biológicos , Valor Preditivo dos Testes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes
11.
Neurosurg Focus ; 45(5): E7, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30453461

RESUMO

OBJECTIVEFlow diverters (FDs) are designed to occlude intracranial aneurysms (IAs) while preserving flow to essential arteries. Incomplete occlusion exposes patients to risks of thromboembolic complications and rupture. A priori assessment of FD treatment outcome could enable treatment optimization leading to better outcomes. To that end, the authors applied image-based computational analysis to clinically FD-treated aneurysms to extract information regarding morphology, pre- and post-treatment hemodynamics, and FD-device characteristics and then used these parameters to train machine learning algorithms to predict 6-month clinical outcomes after FD treatment.METHODSData were retrospectively collected for 84 FD-treated sidewall aneurysms in 80 patients. Based on 6-month angiographic outcomes, IAs were classified as occluded (n = 63) or residual (incomplete occlusion, n = 21). For each case, the authors modeled FD deployment using a fast virtual stenting algorithm and hemodynamics using image-based computational fluid dynamics. Sixteen morphological, hemodynamic, and FD-based parameters were calculated for each aneurysm. Aneurysms were randomly assigned to a training or testing cohort in approximately a 3:1 ratio. The Student t-test and Mann-Whitney U-test were performed on data from the training cohort to identify significant parameters distinguishing the occluded from residual groups. Predictive models were trained using 4 types of supervised machine learning algorithms: logistic regression (LR), support vector machine (SVM; linear and Gaussian kernels), K-nearest neighbor, and neural network (NN). In the testing cohort, the authors compared outcome prediction by each model trained using all parameters versus only the significant parameters.RESULTSThe training cohort (n = 64) consisted of 48 occluded and 16 residual aneurysms and the testing cohort (n = 20) consisted of 15 occluded and 5 residual aneurysms. Significance tests yielded 2 morphological (ostium ratio and neck ratio) and 3 hemodynamic (pre-treatment inflow rate, post-treatment inflow rate, and post-treatment aneurysm averaged velocity) discriminants between the occluded (good-outcome) and the residual (bad-outcome) group. In both training and testing, all the models trained using all 16 parameters performed better than all the models trained using only the 5 significant parameters. Among the all-parameter models, NN (AUC = 0.967) performed the best during training, followed by LR and linear SVM (AUC = 0.941 and 0.914, respectively). During testing, NN and Gaussian-SVM models had the highest accuracy (90%) in predicting occlusion outcome.CONCLUSIONSNN and Gaussian-SVM models incorporating all 16 morphological, hemodynamic, and FD-related parameters predicted 6-month occlusion outcome of FD treatment with 90% accuracy. More robust models using the computational workflow and machine learning could be trained on larger patient databases toward clinical use in patient-specific treatment planning and optimization.


Assuntos
Embolização Terapêutica/métodos , Hidrodinâmica , Aneurisma Intracraniano/terapia , Aprendizado de Máquina , Stents Metálicos Autoexpansíveis , Idoso , Embolização Terapêutica/instrumentação , Embolização Terapêutica/tendências , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/fisiopatologia , Aprendizado de Máquina/tendências , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis/tendências , Resultado do Tratamento
12.
Curr Neurovasc Res ; 15(4): 312-325, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30484404

RESUMO

BACKGROUND: The neurovasculature dynamically responds to changes in cerebral blood flow by vascular remodeling processes. Serial imaging studies in mouse models could help characterize pathologic and physiologic flow-induced remodeling of the Circle of Willis (CoW). METHOD: We induced flow-driven pathologic cerebral vascular remodeling in the CoW of mice (n=3) by ligation of the left Common Carotid Artery (CCA), and the right external carotid and pterygopalatine arteries, increasing blood flow through the basilar and the right internal carotid arteries. One additional mouse was used as a wild-type control. Magnetic Resonance Imaging (MRI) at 9.4 Tesla (T) was used to serially image the mouse CoW over three months, and to obtain threedimensional images for use in Computational Fluid Dynamic (CFD) simulations. Terminal vascular corrosion casting and scanning electron microscope imaging were used to identify regions of macroscopic and microscopic arterial damage. RESULTS: We demonstrated the feasibility of detecting and serially measuring pathologic cerebral vascular changes in the mouse CoW, specifically in the anterior vasculature. These changes were characterized by bulging and increased vessel tortuosity on the anterior cerebral artery and aneurysm- like remodeling at the right olfactory artery origin. The resolution of the 9.4T system further allowed us to perform CFD simulations in the anterior CoW, which showed a correlation between elevated wall shear stress and pathological vascular changes. CONCLUSION: In the future, serial high-resolution MRI could be useful for characterizing the flow environments corresponding to other pathologic remodeling processes in the mouse CoW, such as aneurysm formation, subarachnoid hemorrhage, and ischemia.


Assuntos
Circulação Cerebrovascular/fisiologia , Círculo Arterial do Cérebro/diagnóstico por imagem , Imageamento Tridimensional , Aneurisma Intracraniano/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Remodelação Vascular/fisiologia , Animais , Modelos Animais de Doenças , Hemodinâmica/fisiologia , Aneurisma Intracraniano/patologia , Ligadura/efeitos adversos , Masculino , Camundongos
13.
World Neurosurg ; 119: e541-e550, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30075262

RESUMO

OBJECTIVE: Precise morphologic evaluation is important for intracranial aneurysm (IA) management. At present, clinicians manually measure the IA size and neck diameter on 2-dimensional (2D) digital subtraction angiographic (DSA) images and categorize the IA shape as regular or irregular on 3-dimensional (3D)-DSA images, which could result in inconsistency and bias. We investigated whether a computer-assisted 3D analytical approach could improve IA morphology assessment. METHODS: Five neurointerventionists evaluated the size, neck diameter, and shape of 39 IAs using current and computer-assisted 3D approaches. In the computer-assisted 3D approach, the size, neck diameter, and undulation index (UI, a shape irregularity metric) were extracted using semiautomated reconstruction of aneurysm geometry using 3D-DSA, followed by IA neck identification and computerized geometry assessment. RESULTS: The size and neck diameter measured using the manual 2D approach were smaller than computer-assisted 3D measurements by 2.01 mm (P < 0.001) and 1.85 mm (P < 0.001), respectively. Applying the definitions of small IAs (<7 mm) and narrow-necked IAs (<4 mm) from the reported data, interrater variation in manual 2D measurements resulted in inconsistent classification of the size of 14 IAs and the necks of 19 IAs. Visual inspection resulted in an inconsistent shape classification for 23 IAs among the raters. Greater consistency was achieved using the computer-assisted 3D approach for size (intraclass correlation coefficient [ICC], 1.00), neck measurements (ICC, 0.96), and shape quantification (UI; ICC, 0.94). CONCLUSIONS: Computer-assisted 3D morphology analysis can improve accuracy and consistency in measurements compared with manual 2D measurements. It can also more reliably quantify shape irregularity using the UI. Future application of computer-assisted analysis tools could help clinicians standardize morphology evaluations, leading to more consistent IA evaluations.


Assuntos
Angiografia Digital/métodos , Angiografia Cerebral/métodos , Imageamento Tridimensional/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Humanos , Variações Dependentes do Observador , Reconhecimento Automatizado de Padrão/métodos
14.
Stroke ; 49(4): 856-864, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29535267

RESUMO

BACKGROUND AND PURPOSE: Many ruptured intracranial aneurysms (IAs) are small. Clinical presentations suggest that small and large IAs could have different phenotypes. It is unknown if small and large IAs have different characteristics that discriminate rupture. METHODS: We analyzed morphological, hemodynamic, and clinical parameters of 413 retrospectively collected IAs (training cohort; 102 ruptured IAs). Hierarchal cluster analysis was performed to determine a size cutoff to dichotomize the IA population into small and large IAs. We applied multivariate logistic regression to build rupture discrimination models for small IAs, large IAs, and an aggregation of all IAs. We validated the ability of these 3 models to predict rupture status in a second, independently collected cohort of 129 IAs (testing cohort; 14 ruptured IAs). RESULTS: Hierarchal cluster analysis in the training cohort confirmed that small and large IAs are best separated at 5 mm based on morphological and hemodynamic features (area under the curve=0.81). For small IAs (<5 mm), the resulting rupture discrimination model included undulation index, oscillatory shear index, previous subarachnoid hemorrhage, and absence of multiple IAs (area under the curve=0.84; 95% confidence interval, 0.78-0.88), whereas for large IAs (≥5 mm), the model included undulation index, low wall shear stress, previous subarachnoid hemorrhage, and IA location (area under the curve=0.87; 95% confidence interval, 0.82-0.93). The model for the aggregated training cohort retained all the parameters in the size-dichotomized models. Results in the testing cohort showed that the size-dichotomized rupture discrimination model had higher sensitivity (64% versus 29%) and accuracy (77% versus 74%), marginally higher area under the curve (0.75; 95% confidence interval, 0.61-0.88 versus 0.67; 95% confidence interval, 0.52-0.82), and similar specificity (78% versus 80%) compared with the aggregate-based model. CONCLUSIONS: Small (<5 mm) and large (≥5 mm) IAs have different hemodynamic and clinical, but not morphological, rupture discriminants. Size-dichotomized rupture discrimination models performed better than the aggregate model.


Assuntos
Aneurisma Roto/epidemiologia , Hemodinâmica , Aneurisma Intracraniano/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/diagnóstico por imagem , Angiografia Digital , Angiografia Cerebral , Análise por Conglomerados , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Imageamento Tridimensional , Aneurisma Intracraniano/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Reprodutibilidade dos Testes , Estudos Retrospectivos , Ruptura Espontânea
15.
PLoS One ; 13(1): e0191407, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29342213

RESUMO

BACKGROUND: Unruptured intracranial aneurysms (IAs) are typically asymptomatic and undetected except for incidental discovery on imaging. Blood-based diagnostic biomarkers could lead to improvements in IA management. This exploratory study examined circulating neutrophils to determine whether they carry RNA expression signatures of IAs. METHODS: Blood samples were collected from patients receiving cerebral angiography. Eleven samples were collected from patients with IAs and 11 from patients without IAs as controls. Samples from the two groups were paired based on demographics and comorbidities. RNA was extracted from isolated neutrophils and subjected to next-generation RNA sequencing to obtain differential expressions for identification of an IA-associated signature. Bioinformatics analyses, including gene set enrichment analysis and Ingenuity Pathway Analysis, were used to investigate the biological function of all differentially expressed transcripts. RESULTS: Transcriptome profiling identified 258 differentially expressed transcripts in patients with and without IAs. Expression differences were consistent with peripheral neutrophil activation. An IA-associated RNA expression signature was identified in 82 transcripts (p<0.05, fold-change ≥2). This signature was able to separate patients with and without IAs on hierarchical clustering. Furthermore, in an independent, unpaired, replication cohort of patients with IAs (n = 5) and controls (n = 5), the 82 transcripts separated 9 of 10 patients into their respective groups. CONCLUSION: Preliminary findings show that RNA expression from circulating neutrophils carries an IA-associated signature. These findings highlight a potential to use predictive biomarkers from peripheral blood samples to identify patients with IAs.


Assuntos
Aneurisma Intracraniano/genética , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/genética , Biomarcadores/sangue , Angiografia Cerebral , Estudos de Coortes , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Humanos , Aneurisma Intracraniano/sangue , Aneurisma Intracraniano/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Fatores de Risco , Transcriptoma
16.
J Biomech Eng ; 139(12)2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28857116

RESUMO

Computational fluid dynamics (CFD) is a promising tool to aid in clinical diagnoses of cardiovascular diseases. However, it uses assumptions that simplify the complexities of the real cardiovascular flow. Due to high-stakes in the clinical setting, it is critical to calculate the effect of these assumptions in the CFD simulation results. However, existing CFD validation approaches do not quantify error in the simulation results due to the CFD solver's modeling assumptions. Instead, they directly compare CFD simulation results against validation data. Thus, to quantify the accuracy of a CFD solver, we developed a validation methodology that calculates the CFD model error (arising from modeling assumptions). Our methodology identifies independent error sources in CFD and validation experiments, and calculates the model error by parsing out other sources of error inherent in simulation and experiments. To demonstrate the method, we simulated the flow field of a patient-specific intracranial aneurysm (IA) in the commercial CFD software star-ccm+. Particle image velocimetry (PIV) provided validation datasets for the flow field on two orthogonal planes. The average model error in the star-ccm+ solver was 5.63 ± 5.49% along the intersecting validation line of the orthogonal planes. Furthermore, we demonstrated that our validation method is superior to existing validation approaches by applying three representative existing validation techniques to our CFD and experimental dataset, and comparing the validation results. Our validation methodology offers a streamlined workflow to extract the "true" accuracy of a CFD solver.


Assuntos
Hidrodinâmica , Aneurisma Intracraniano/fisiopatologia , Modelagem Computacional Específica para o Paciente , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Imagens de Fantasmas
17.
Immunology ; 148(4): 407-19, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27213693

RESUMO

Blood-brain barrier (BBB) dysfunction complicates central nervous system lupus, an important aspect of systemic lupus erythematosus. To gain insight into the underlying mechanism, vascular corrosion casts of brain were generated from the lupus mouse model, MRL/lpr mice and the MRL/MpJ congenic controls. Scanning electron microscopy of the casts showed loss of vascular endothelial cells in lupus mice compared with controls. Immunostaining revealed a significant increase in caspase 3 expression in the brain vascular endothelial cells, which suggests that apoptosis could be an important mechanism causing cell loss, and thereby loss of BBB integrity. Complement activation occurs in lupus resulting in increased generation of circulating C5a, which caused the endothelial layer to become 'leaky'. In this study, we show that C5a and lupus serum induced apoptosis in cultured human brain microvascular endothelial cells (HBMVECs), whereas selective C5a receptor 1 (C5aR1) antagonist reduced apoptosis in these cells, demonstrating C5a/C5aR1-dependence. Gene expression of initiator caspases, caspase 1 and caspase 8, and pro-apoptotic proteins death-associated protein kinase 1, Fas-associated protein (FADD), cell death-inducing DNA fragmentation factor 45 000 MW subunit A-like effector B (CIDEB) and BCL2-associated X protein were increased in HBMVECs treated with lupus serum or C5a, indicating that both the intrinsic and extrinsic apoptotic pathways could be critical mediators of brain endothelial cell apoptosis in this setting. Overall, our findings suggest that C5a/C5aR1 signalling induces apoptosis through activation of FADD, caspase 8/3 and CIDEB in brain endothelial cells in lupus. Further elucidation of the underlying apoptotic mechanisms mediating the reduced endothelial cell number is important in establishing the potential therapeutic effectiveness of C5aR1 inhibition that could prevent and/or reduce BBB alterations and preserve the physiological function of BBB in central nervous system lupus.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Encéfalo/patologia , Complemento C5a/metabolismo , Endotélio Vascular/imunologia , Proteína de Domínio de Morte Associada a Fas/metabolismo , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Encéfalo/metabolismo , Caspase 3/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Humanos , Camundongos , Camundongos Endogâmicos MRL lpr , Peptídeos Cíclicos/farmacologia , Receptor da Anafilatoxina C5a/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
18.
Anat Rec (Hoboken) ; 298(11): 1903-10, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26248728

RESUMO

Increased cerebral blood flow has been shown to induce pathological structural changes in the Circle of Willis (CoW) in experimental models. Previously, we reported flow-induced aneurysm-like remodeling in the CoW secondary to flow redistribution after bilateral common carotid artery (CCA) ligation in rabbits. In the current study, we tested the hypothesis that loading rabbits with biological risk factors for vascular disease would increase flow-induced aneurysmal remodeling in the CoW. In the same series as the previously-reported bilateral CCA-ligation-alone (n = 6) and sham surgery (n = 3) groups, eight additional female rabbits (the experimental group in this study) were subjected to two risk factors for intracranial aneurysm (hypertension and estrogen deficiency) and then bilateral CCA ligation. Upon euthanasia at 6 months, vascular corrosion casts of the CoW were created and analyzed by scanning electron microscopy for morphological changes and aneurysmal damage. In rabbits with hypertension and estrogen deficiency, arterial caliber increased throughout the CoW, similar to rabbits with CCA ligation alone. However, aneurysmal remodeling (i.e., local bulging) in the CoW was significantly greater than in CCA-ligation-only rabbits and was more widespread, presenting in regions that did not show aneurysmal changes after CCA ligation alone. Furthermore, hypertension and estrogen deficiency caused greater increases in vessel length and tortuosity. These results suggest that hypertension and estrogen deficiency make the CoW more vulnerable to flow-induced aneurysmal remodeling and tortuosity. We propose they do so by lowering the tolerance of vascular tissue to hemodynamic forces caused by CCA ligation, thus lowering the threshold necessary to incite vascular damage.


Assuntos
Doenças das Artérias Carótidas/patologia , Círculo Arterial do Cérebro/patologia , Estrogênios/deficiência , Hipertensão/complicações , Aneurisma Intracraniano/patologia , Animais , Doenças das Artérias Carótidas/complicações , Circulação Cerebrovascular , Modelos Animais de Doenças , Feminino , Hipertensão/patologia , Aneurisma Intracraniano/etiologia , Ligadura , Microscopia Eletrônica de Varredura , Coelhos , Índice de Gravidade de Doença
19.
J Cereb Blood Flow Metab ; 34(3): 415-24, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24326393

RESUMO

Carotid occlusions are associated with de novo intracranial aneurysm formation in clinical case reports, but this phenomenon is not widely studied. We performed bilateral carotid ligation (n=9) in rabbits to simulate carotid occlusion, and sham surgery (n=3) for control. Upon euthanasia (n=3 at 5 days, n=6 at 6 months post ligation, and n=3 at 5 days after sham operation), vascular corrosion casts of the circle of Willis (CoW) were created. Using scanning electron microscopy, we quantified gross morphologic, macroscopic, and microscopic changes on the endocasts and compared findings with histologic data. At 5 days, CoW arteries of ligated animals increased caliber. The posterior communicating artery (PCom) increased length and tortuosity, and the ophthalmic artery (OA) origin presented preaneurysmal bulges. At 6 months, calibers were unchanged from 5 days, PComs further increased tortuosity while presenting segmental dilations, and the OA origin and basilar terminus presented preaneurysmal bulges. This exploratory study provides evidence that flow increase after carotid occlusion produces both compensatory arterial augmentation and pathologic remodeling such as tortuosity and saccular/fusiform aneurysm. Our findings may have considerable clinical implications, as these lesser-known consequences should be considered when managing patients with carotid artery disease or choosing carotid ligation as a therapeutic option.


Assuntos
Doenças das Artérias Carótidas/patologia , Artéria Carótida Primitiva/ultraestrutura , Círculo Arterial do Cérebro/ultraestrutura , Aneurisma Intracraniano/patologia , Animais , Doenças das Artérias Carótidas/complicações , Modelos Animais de Doenças , Feminino , Aneurisma Intracraniano/etiologia , Microscopia Eletrônica de Varredura , Coelhos , Índice de Gravidade de Doença
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