Automated ASPECTS calculation may equal the performance of experienced clinicians: a machine learning study based on a large cohort.

OBJECTIVES: The Alberta Stroke Program Early CT Score (ASPECTS) is a semi-quantitative method to evaluate the severity of early ischemic change on non-contrast computed tomography (NCCT) in patients with acute ischemic stroke (AIS). In this work, we propose an automated ASPECTS method based on large cohort of data and machine learning. METHODS: For this study, we collected 3626 NCCT cases from multiple centers and annotated directly on this dataset by neurologists. Based on image analysis and machine learning methods, we constructed a two-stage machine learning model. The validity and reliability of this automated ASPECTS method were tested on an independent external validation set of 300 cases. Statistical analyses on the total ASPECTS, dichotomized ASPECTS, and region-level ASPECTS were presented. RESULTS: On an independent external validation set of 300 cases, for the total ASPECTS results, the intraclass correlation coefficient between automated ASPECTS and expert-rated was 0.842. The agreement between ASPECTS threshold of ≥ 6 versus < 6 using a dichotomized method was moderate (κ = 0.438, 0.391-0.477), and the detection rate (sensitivity) was 86.5% for patients with ASPECTS threshold of ≥ 6. Compared with the results of previous studies, our method achieved a slight lead in sensitivity (67.8%) and AUC (0.845), with comparable accuracy (78.9%) and specificity (81.2%). CONCLUSION: The proposed automated ASPECTS method driven by a large cohort of NCCT images performed equally well compared with expert-rated ASPECTS. This work further demonstrates the validity and reliability of automated ASPECTS evaluation method. CLINICAL RELEVANCE STATEMENT: The automated ASPECTS method proposed by this study may help AIS patients to receive rapid intervention, but should not be used as a stand-alone diagnostic basis. KEY POINTS: NCCT-based manual ASPECTS scores were poorly consistent. Machine learning can automate the ASPECTS scoring process. Machine learning model design based on large cohort data can effectively improve the consistency of ASPECTS scores.

PCSK9 expression in fibrous cap possesses a marker for rupture in advanced plaque.

BACKGROUND: To date, PCSK9 inhibitors are well known for eliminating cardiac and cerebral artery ischemia events by lowering the serum lipid level. However, the pathophysiological value of in-plaque PCSK9 expression is still unclear. METHODS: Advanced plaques removed by carotid endarterectomy were sectioned and stained to identify the PCSK9 expression pattern and its co-expression with rupture-relevant markers. To investigate the correlation of PCSK9 expression with regional blood shear flow, hemodynamic characteristics were analyzed using computational fluid dynamics, and representative parameters were compared between PCSK9 positive and negative staining plaques. To explore this phenomenon in vitro, human aortic vascular smooth muscle cells were used to overexpress and knock down PCSK9. The impacts of PCSK9 modulations on mechanical sensor activity were testified by western blot and immunofluorescence. Real-time polymerase chain reaction was used to evaluate the transcription levels of downstream rupture-prone effectors. RESULTS: PCSK9 distribution in plaque preferred cap and shoulder regions, residing predominantly in smooth muscle actin-positive cells. Cap PCSK9 expression correlated with fibrous cap thickness negatively and co-expressed with MMP-9, both pointing to the direction of plaque rupture. A hemodynamic profile indicated a rupture-prone feature of cap PCSK9 expression. In vitro, overexpression and knockdown of PCSK9 in human aortic vascular smooth muscle cells has positive modulation on mechanical sensor Yes-associated protein 1 (YAP) activity and transcription levels of its downstream rupture-prone effectors. Serial section staining verified in situ colocalization among PCSK9, YAP, and downstream effectors. CONCLUSIONS: Cap PCSK9 possesses a biomarker for rupture risk, and its modulation may lead to a novel biomechanical angle for plaque interventions.

Angiography-based Fractional Flow Reserve for the Prediction of Clinical Outcomes After Drug-coated Balloon or Plain Old Balloon Angioplasty.

BACKGROUND: AccuFFRangio is a novel method for fast computation of fractional flow reserve (FFR) based on coronary angiography and computational fluid dynamics. The association between the AccuFFRangio and clinical outcomes after drug-coated balloon (DCB) or plain old balloon angioplasty (POBA) remains to be investigated. METHODS: This study included consecutive patients who underwent balloon angioplasty from December 2016 to October 2020. AccuFFRangio was calculated retrospectively based on the post-procedural angiography obtained immediately after angioplasty. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, vessel-related myocardial infarction, and repeat target vessel revascularization. RESULTS: A total of 169 patients were retrospectively analyzed in this study. Post-procedural AccuFFRangio (hazard ratio [HR] per 0.1 increase 0.33, 95% confidence interval [CI] 0.22-0.48, p < 0.001) was an independent predictor for MACE at 2-year follow-up. Post-procedural AccuFFRangio ≤ 0.87 was determined as the optimal cutoff value to predict MACE with an area under the curve (AUC) of 0.872 (95% CI 0.813-0.919, p < 0.001). CONCLUSIONS: AccuFFRangio measured immediately after balloon angioplasty is a promising predictor of unfavorable clinical outcomes.

Hemodynamic alterations of flow diverters on aneurysms at the fetal posterior communicating artery: A simulation study using CFD to compare the surpass streamline, pipeline flex, and tubridge devices.

PURPOSE: Traditional flow diverters (FDs) for treating aneurysms at the fetal posterior communicating artery are unsatisfactory. Surpass Streamline is a novel FD with different mesh characteristics; however, the outcomes for such aneurysms remain unclear. This study aimed to compare hemodynamic alterations induced by Surpass Streamline, Pipeline Flex, and Tubridge devices and explore possible strategies for aneurysms at the fetal posterior communicating artery. METHODS: Two simulated aneurysms (Case 1, Case 2) were constructed from digital subtraction angiography (DSA). The three FDs were virtually deployed, and hemodynamic analysis based on computational fluid dynamics was performed. Hemodynamic parameters, including the sac-averaged velocity magnitude (Velocity), high-flow volume (HFV), and wall shear stress (WSS), were compared between each FD and the untreated model (control). Surpass Streamline was performed in real life for two aneurysms and the clinical outcomes were collected for analysis. RESULTS: Compared to the control, the Surpass resulted in the most significant reduction in flow. In Case 1, the Velocity, HFV, and WSS were reduced by 51.6%, 78.1%, and 64.3%, respectively. In Case 2, the Velocity, HFV, and WSS were reduced by 48.0%, 81.1%, and 65.3%, respectively. Tubridge showed slightly larger changes in hemodynamic parameters than Pipeline. In addition, our analysis suggested that metal coverage was correlated with the WSS, Velocity, and HFV. The postoperative DSA showed that the aneurysm was nearly occluded in Case 1 and decreased in Case 2. CONCLUSION: Compared to that with the Pipeline and Tubridge, the Surpass resulted in the greatest reduction in hemodynamic parameters and might be effective for aneurysms at the fetal posterior communicating artery. Virtual FD deployment and computational fluid dynamics analysis may be used to predict the treatment outcomes.

Comparison of deep learning-based image segmentation methods for intravascular ultrasound on retrospective and large image cohort study.

OBJECTIVES: The aim of this study was to investigate the generalization performance of deep learning segmentation models on a large cohort intravascular ultrasound (IVUS) image dataset over the lumen and external elastic membrane (EEM), and to assess the consistency and accuracy of automated IVUS quantitative measurement parameters. METHODS: A total of 11,070 IVUS images from 113 patients and pullbacks were collected and annotated by cardiologists to train and test deep learning segmentation models. A comparison of five state of the art medical image segmentation models was performed by evaluating the segmentation of the lumen and EEM. Dice similarity coefficient (DSC), intersection over union (IoU) and Hausdorff distance (HD) were calculated for the overall and for subsets of different IVUS image categories. Further, the agreement between the IVUS quantitative measurement parameters calculated by automatic segmentation and those calculated by manual segmentation was evaluated. Finally, the segmentation performance of our model was also compared with previous studies. RESULTS: CENet achieved the best performance in DSC (0.958 for lumen, 0.921 for EEM) and IoU (0.975 for lumen, 0.951 for EEM) among all models, while Res-UNet was the best performer in HD (0.219 for lumen, 0.178 for EEM). The mean intraclass correlation coefficient (ICC) and Bland-Altman plot demonstrated the extremely strong agreement (0.855, 95% CI 0.822-0.887) between model's automatic prediction and manual measurements. CONCLUSIONS: Deep learning models based on large cohort image datasets were capable of achieving state of the art (SOTA) results in lumen and EEM segmentation. It can be used for IVUS clinical evaluation and achieve excellent agreement with clinicians on quantitative parameter measurements.

Accuracy of intravascular ultrasound-derived virtual fractional flow reserve (FFR) and FFR derived from computed tomography for functional assessment of coronary artery disease.

BACKGROUND: Coronary computed tomography-derived fractional flow reserve (CT-FFR) and intravascular ultrasound-derived fractional flow reserve (IVUS-FFR) are two functional assessment methods for coronary stenoses. However, the calculation algorithms for these methods differ significantly. This study aimed to compare the diagnostic performance of CT-FFR and IVUS-FFR using invasive fractional flow reserve (FFR) as the reference standard. METHODS: Six hundred and seventy patients (698 lesions) with known or suspected coronary artery disease were screened for this retrospective analysis between January 2020 and July 2021. A total of 40 patients (41 lesions) underwent intravascular ultrasound (IVUS) and FFR evaluations within six months after completing coronary CT angiography were included. Two novel CFD-based models (AccuFFRct and AccuFFRivus) were used to compute the CT-FFR and IVUS-FFR values, respectively. The invasive FFR ≤ 0.80 was used as the reference standard for evaluating the diagnostic performance of CT-FFR and IVUS-FFR. RESULTS: Both AccuFFRivus and AccuFFRct demonstrated a strong correlation with invasive FFR (R = 0.7913, P < 0.0001; and R = 0.6296, P < 0.0001), and both methods showed good agreement with FFR. The area under the receiver operating characteristic curve was 0.960 (P < 0.001) for AccuFFRivus and 0.897 (P < 0.001) for AccuFFRct in predicting FFR ≤ 0.80. FFR ≤ 0.80 were predicted with high sensitivity (96.6%), specificity (85.7%), and the Youden index (0.823) using the same cutoff value of 0.80 for AccuFFRivus. A good diagnostic performance (sensitivity 89.7%, specificity 85.7%, and Youden index 0.754) was also demonstrated by AccuFFRct. CONCLUSIONS: AccuFFRivus, computed from IVUS images, exhibited a high diagnostic performance for detecting myocardial ischemia. It demonstrated better diagnostic power than AccuFFRct, and could serve as an accurate computational tool for ischemia diagnosis and assist in clinical decision-making.

Diagnostic performance of deep learning and computational fluid dynamics-based instantaneous wave-free ratio derived from computed tomography angiography.

BACKGROUND AND OBJECTIVES: Both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are widely used to evaluate ischemia-causing coronary lesions. A new method of CT-iFR, namely AccuiFRct, for calculating iFR based on deep learning and computational fluid dynamics (CFD) using coronary computed tomography angiography (CCTA) has been proposed. In this study, the diagnostic performance of AccuiFRct was thoroughly assessed using iFR as the reference standard. METHODS: Data of a total of 36 consecutive patients with 36 vessels from a single-center who underwent CCTA, invasive FFR, and iFR were retrospectively analyzed. The CT-derived iFR values were computed using a novel deep learning and CFD-based model. RESULTS: Mean values of FFR and iFR were 0.80 ± 0.10 and 0.91 ± 0.06, respectively. AccuiFRct was well correlated with FFR and iFR (correlation coefficients, 0.67 and 0.68, respectively). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of AccuiFRct ≤ 0.89 for predicting FFR ≤ 0.80 were 78%, 73%, 81%, 73%, and 81%, respectively. Those of AccuiFRct ≤ 0.89 for predicting iFR ≤ 0.89 were 81%, 73%, 86%, 79%, and 82%, respectively. AccuiFRct showed a similar discriminant function when FFR or iFR were used as reference standards. CONCLUSION: AccuiFRct could be a promising noninvasive tool for detection of ischemia-causing coronary stenosis, as well as facilitating in making reliable clinical decisions.

Diagnostic accuracy of coronary computed tomography angiography-derived fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) is a widely used gold standard to evaluate ischemia-causing lesions. A new method of non-invasive approach, termed as AccuFFRct, for calculating FFR based on coronary computed tomography angiography (CCTA) and computational fluid dynamics (CFD) has been proposed. However, its diagnostic accuracy has not been validated. OBJECTIVES: This study sought to present a novel approach for non-invasive computation of FFR and evaluate its diagnostic performance in patients with coronary stenosis. METHODS: A total of 54 consecutive patients with 78 vessels from a single center who underwent CCTA and invasive FFR measurement were retrospectively analyzed. The CT-derived FFR values were computed using a novel CFD-based model (AccuFFRct, ArteryFlow Technology Co., Ltd., Hangzhou, China). Diagnostic performance of AccuFFRct and CCTA in detecting hemodynamically significant coronary artery disease (CAD) was evaluated using the invasive FFR as a reference standard. RESULTS: Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for AccuFFRct in detecting FFR ≤ 0.8 on per-patient basis were 90.7, 89.5, 91.4, 85.0 and 94.1%, respectively, while those of CCTA were 38.9, 100.0, 5.71, 36.5 and 100.0%, respectively. The correlation between AccuFFRct and FFR was good (r = 0.76 and r = 0.65 on per-patient and per-vessel basis, respectively, both p < 0.0001). Area under the curve (AUC) values of AccuFFRct for identifying ischemia per-patient and per-vessel basis were 0.945 and 0.925, respectively. There was much higher accuracy, specificity and AUC for AccuFFRct compared with CCTA. CONCLUSIONS: AccuFFRct computed from CCTA images alone demonstrated high diagnostic performance for detecting lesion-specific ischemia, it showed superior diagnostic power than CCTA and eliminated the risk of invasive tests, which could be an accurate and time-efficient computational tool for diagnosing ischemia and assisting clinical decision-making.

Automatic segmentation of coronary lumen and external elastic membrane in intravascular ultrasound images using 8-layer U-Net.

BACKGROUND: Intravascular ultrasound (IVUS) is the golden standard in accessing the coronary lesions, stenosis, and atherosclerosis plaques. In this paper, a fully automatic approach by an 8-layer U-Net is developed to segment the coronary artery lumen and the area bounded by external elastic membrane (EEM), i.e., cross-sectional area (EEM-CSA). The database comprises single-vendor and single-frequency IVUS data. Particularly, the proposed data augmentation of MeshGrid combined with flip and rotation operations is implemented, improving the model performance without pre- or post-processing of the raw IVUS images. RESULTS: The mean intersection of union (MIoU) of 0.937 and 0.804 for the lumen and EEM-CSA, respectively, were achieved, which exceeded the manual labeling accuracy of the clinician. CONCLUSION: The accuracy shown by the proposed method is sufficient for subsequent reconstruction of 3D-IVUS images, which is essential for doctors' diagnosis in the tissue characterization of coronary artery walls and plaque compositions, qualitatively and quantitatively.

Are hemodynamics of irregular small carotid-ophthalmic aneurysms different from those of regular ones and large aneurysms based on numerical simulation?

PURPOSE: The purpose of this study is to investigate whether hemodynamics of unruptured, irregular small intracranial aneurysms (SIAs) are different from those of regular ones and large intracranial aneurysms (LIAs) in ophthalmic artery segment of internal carotid artery (ICA). METHODS: Between April 2015 and June 2018, 106 carotid-ophthalmic artery aneurysms were retrospectively analyzed using 3D angiographic images and computational fluid dynamics (CFD). Three categories were stratified: regular SIAs, irregular SIAs and LIAs. Statistical comparisons of the differences in clinical, morphological and hemodynamic parameters among regular SIA, irregular SIA and LIA groups were performed by one-way analysis of variance (ANOVA) or Kruskal-Wallis Test. RESULTS: The median maximal height of regular SIA, irregular SIA and LIA were 3.03 (interquartile range: 2.49-4.22) mm, 4.59 (interquartile range: 3.86-5.32) mm and 11.06 (interquartile range: 9.28-13.69) mm, all P < 0.05). Low shear-stress area percentage (LSA%) and oscillatory shear index (OSI) of irregular SIAs and LIAs were not significantly different (P = 0.72, P = 0.27 respectively), and were significantly higher than those of regular SIAs (all P < 0.01). Wall shear stress (WSS) and normalized wall shear stress (NWSS) of irregular SIAs were significantly higher than those of LIAs (P < 0.01, P < 0.01 respectively), but lower than those of regular SIAs (P < 0.01, P < 0.01 respectively). CONCLUSIONS: Special unruptured irregular SIAs share a similarity of hemodynamic characteristics with LIAs in high LSA% and high OSI, and are different from regular SIAs in hemodynamics.

Numerical simulation of patient-specific endovascular stenting and coiling for intracranial aneurysm surgical planning.

BACKGROUND: In this study, we develop reliable and practical virtual coiling and stenting methods for intracranial aneurysm surgical planning. Since the purpose of deploying coils and stents is to provide device geometries for subsequent accurate post-treatment computational fluid dynamics analysis, we do not need to accurately capture all the details such as the stress and force distribution for the devices and vessel walls. Our philosophy for developing these methods is to balance accuracy and practicality. METHODS: We consider the mechanical properties of the devices and recapitulate the clinical practice using a finite element method (FEM) approach. At the same time, we apply some simplifications for FEM modeling to make our methods efficient. For the virtual coiling, the coils are modeled as 3D Euler-Bernoulli beam elements, which is computationally efficient and provides good geometry representation. During the stent deployment process, the stent-catheter system is transformed according to the centerline of the parent vessel since the final configuration of the stent is not dependent of the deployment history. The aneurysm and vessel walls are assumed to be rigid and are fully constrained during the simulation. All stent-catheter system and coil-catheter system are prepared and packaged as a library which contains all types of stents, coils and catheters, which improves the efficiency of surgical planning process. RESULTS: The stent was delivered to the suitable position during the clinical treatment, achieving good expansion and apposition of the stent to the arterial wall. The coil was deployed into the aneurysm sac and deformed to different shapes because of the stored strain energy during coil package process and the direction of the microcatheter. CONCLUSIONS: The method which we develop here could become surgical planning for intracranial aneurysm treatment in the clinical workflow.

Flow diverter effect of LVIS stent on cerebral aneurysm hemodynamics: a comparison with Enterprise stents and the Pipeline device.

BACKGROUND: The aim of this study was to quantify the effect of the new Low-profile Visualized Intraluminal Support (LVIS®D) device and the difference of fluid diverting effect compared with the Pipeline device and the Enterprise stent using computational fluid dynamics (CFD). METHODS: In this research, we simulated three aneurysms constructed from 3D digital subtraction angiography (DSA). The Enterprise, LVIS and the Pipeline device were virtually conformed to fit into the vessel lumen and placed across the aneurysm orifice. Computational fluid dynamics analysis was performed to compare the hemodynamic differences such as WSS, Velocity and Pressure among these stents. RESULTS: Control referred to the unstented model, the percentage of hemodynamic changes were all compared to Control. A single LVIS stent caused more wall shear stress reduction than double Enterprise stents (39.96 vs. 30.51 %) and velocity (23.13 vs. 18.64 %). Significant reduction in wall shear stress (63.88 %) and velocity (46.05 %) was observed in the double-LVIS stents. A single Pipeline showed less reduction in WSS (51.08 %) and velocity (37.87 %) compared with double-LVIS stent. The double-Pipeline stents resulted in the most reduction in WSS (72.37 %) and velocity (54.26 %). Moreover, the pressure increased with minuscule extent after stenting, compared with the unstented model. CONCLUSIONS: This is the first study analyzing flow modifications associated with LVIS stents. We found that the LVIS stent has certain hemodynamic effects on cerebral aneurysms: a single LVIS stent caused more flow reductions than the double-Enterprise stent but less than a Pipeline device. Nevertheless, the double-LVIS stent resulted in a better flow diverting effect than a Pipeline device.

Flow Instability Detected by High-Resolution Computational Fluid Dynamics in Fifty-Six Middle Cerebral Artery Aneurysms.

Recent high-resolution computational fluid dynamics (CFD) studies have detected persistent flow instability in intracranial aneurysms (IAs) that was not observed in previous in silico studies. These flow fluctuations have shown incidental association with rupture in a small aneurysm dataset. The aims of this study are to explore the capabilities and limitations of a commercial cfd solver in capturing such velocity fluctuations, whether fluctuation kinetic energy (fKE) as a marker to quantify such instability could be a potential parameter to predict aneurysm rupture, and what geometric parameters might be associated with such fluctuations. First, we confirmed that the second-order discretization schemes and high spatial and temporal resolutions are required to capture these aneurysmal flow fluctuations. Next, we analyzed 56 patient-specific middle cerebral artery (MCA) aneurysms (12 ruptured) by transient, high-resolution CFD simulations with a cycle-averaged, constant inflow boundary condition. Finally, to explore the mechanism by which such flow instabilities might arise, we investigated correlations between fKE and several aneurysm geometrical parameters. Our results show that flow instabilities were present in 8 of 56 MCA aneurysms, all of which were unruptured bifurcation aneurysms. Statistical analysis revealed that fKE could not differentiate ruptured from unruptured aneurysms. Thus, our study does not lend support to these flow instabilities (based on a cycle-averaged constant inflow as opposed to peak velocity) being a marker for rupture. We found a positive correlation between fKE and aneurysm size as well as size ratio. This suggests that the intrinsic flow instability may be associated with the breakdown of an inflow jet penetrating the aneurysm space.

Hemodynamic alterations after stent implantation in 15 cases of intracranial aneurysm.

BACKGROUND: Stent-assisted coiling technology has been widely used in the treatment of intracranial aneurysms. In the current study, we investigated the intra-aneurysmal hemodynamic alterations after stent implantation and their association with the aneurysm location. METHODS: We first retrospectively studied 15 aneurysm cases [8 internal carotid artery-ophthalmic artery (ICA-OphA) aneurysms and 7 posterior communicating artery (PcoA) aneurysms] treated with Enterprise stents and coils. Then, based on the patient-specific geometries before and after stenting, we built virtual stenting computational fluid dynamics (CFD) simulation models. RESULTS: Before and after the stent deployment, the average wall shear stress (WSS) on the aneurysmal sac at systolic peak changed from 7.04 Pa (4.14 Pa, 15.77 Pa) to 6.04 Pa (3.86 Pa, 11.13 Pa), P = 0.001; the spatially averaged flow velocity in the perpendicular plane of the aneurysm dropped from 0.5 m/s (0.28 m/s, 0.7 m/s) to 0.33 m/s (0.25 m/s, 0.49 m/s), P = 0.001, respectively. Post stent implantation, the WSS in ICA-OphA aneurysms and PcoA aneurysms decreased by 14.4 % (P = 0.012) and 16.6 % (P = 0.018), respectively, and the flow velocity also reduced by 10.3 % (P = 0.029) and 10.5 % (P = 0.013), respectively. Changes in the WSS, flow velocity, and pressure were not significantly different between ICA-OphA and PcoA aneurysms (P > 0.05). Stent implantation did not significantly change the peak systolic pressure in either aneurysm type. CONCLUSION: After the stent implantation, both the intra-aneurysmal flow velocity and WSS decreased independently of aneurysm type (ICA-OphA and PcoA). Little change was observed in peak systolic pressure.

Silencing of Long Non-Coding RNA MALAT1 Promotes Apoptosis of Glioma Cells.

The metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) is a highly conserved long non-coding RNA (lncRNA) gene. However, little is known about the pathological role of lncRNA MALAT1 in glioma. In the present study, we explored the expression level of lncRNA MALAT1 in primary glioma tissues as well as in U87 and U251 glioma cell lines. Using qRT-PCR, we found that the expression of lncRNA MALAT1 was significantly increased in glioma tissues compared with that of paracancerous tissues. Meanwhile, the expression of MALAT1 was highly expressed in U98 and U251 cells. In order to explore the function of MALAT1, the expression of MALAT1 was greatly reduced in U87 and U251 cells transfected with siRNA specifically targeting MALAT1. Consequently, cell viability of U87 and U251 cells were drastically decreased after the knockdown of MALAT1. Concomitantly, the apoptosis rate of the two cell lines was dramatically increased. Furthermore, the expression levels of some tumor markers were reduced after the knockdown of MALAT1, such as CCND1 and MYC. In summary, the current study indicated a promoting role of MALAT1 in the development of glioma cell.

The Computational Fluid Dynamics Rupture Challenge 2013--Phase II: Variability of Hemodynamic Simulations in Two Intracranial Aneurysms.

With the increased availability of computational resources, the past decade has seen a rise in the use of computational fluid dynamics (CFD) for medical applications. There has been an increase in the application of CFD to attempt to predict the rupture of intracranial aneurysms, however, while many hemodynamic parameters can be obtained from these computations, to date, no consistent methodology for the prediction of the rupture has been identified. One particular challenge to CFD is that many factors contribute to its accuracy; the mesh resolution and spatial/temporal discretization can alone contribute to a variation in accuracy. This failure to identify the importance of these factors and identify a methodology for the prediction of ruptures has limited the acceptance of CFD among physicians for rupture prediction. The International CFD Rupture Challenge 2013 seeks to comment on the sensitivity of these various CFD assumptions to predict the rupture by undertaking a comparison of the rupture and blood-flow predictions from a wide range of independent participants utilizing a range of CFD approaches. Twenty-six groups from 15 countries took part in the challenge. Participants were provided with surface models of two intracranial aneurysms and asked to carry out the corresponding hemodynamics simulations, free to choose their own mesh, solver, and temporal discretization. They were requested to submit velocity and pressure predictions along the centerline and on specified planes. The first phase of the challenge, described in a separate paper, was aimed at predicting which of the two aneurysms had previously ruptured and where the rupture site was located. The second phase, described in this paper, aims to assess the variability of the solutions and the sensitivity to the modeling assumptions. Participants were free to choose boundary conditions in the first phase, whereas they were prescribed in the second phase but all other CFD modeling parameters were not prescribed. In order to compare the computational results of one representative group with experimental results, steady-flow measurements using particle image velocimetry (PIV) were carried out in a silicone model of one of the provided aneurysms. Approximately 80% of the participating groups generated similar results. Both velocity and pressure computations were in good agreement with each other for cycle-averaged and peak-systolic predictions. Most apparent "outliers" (results that stand out of the collective) were observed to have underestimated velocity levels compared to the majority of solutions, but nevertheless identified comparable flow structures. In only two cases, the results deviate by over 35% from the mean solution of all the participants. Results of steady CFD simulations of the representative group and PIV experiments were in good agreement. The study demonstrated that while a range of numerical schemes, mesh resolution, and solvers was used, similar flow predictions were observed in the majority of cases. To further validate the computational results, it is suggested that time-dependent measurements should be conducted in the future. However, it is recognized that this study does not include the biological aspects of the aneurysm, which needs to be considered to be able to more precisely identify the specific rupture risk of an intracranial aneurysm.

Endovascular management of adjacent tandem intracranial aneurysms: utilization of stent-assisted coiling and flow diversion.

BACKGROUND: Tandem intracranial aneurysms are aneurysms located along a single intracranial vessel. Adjacent tandem aneurysms arise within the same vascular segment and their presence often suggests diffuse parent vessel anomaly. Endovascular management of these rare lesions has not been well studied. In this retrospective observational study, we describe our experience treating adjacent tandem intracranial aneurysms with endovascular embolization. METHODS: We retrospectively reviewed records of patients with these lesions who underwent endovascular treatment between 2008 and 2013. RESULTS: Thirteen patients (mean age 60.8 years; 12 women) with 28 adjacent tandem aneurysms were treated during the study timeframe. Aneurysms were located along the clinoidal, ophthalmic, and communicating segments of the internal carotid artery in 12 patients and at the basilar apex in one patient. Average size was 8.4 mm. Six patients (12 aneurysms) were treated by flow diversion via the Pipeline embolization device (PED) and seven (16 aneurysms) by stent-assisted coiling, with coils successfully placed in 11 aneurysms. Clinical follow-up was available for an average of 26.1 months; postprocedural angiography was performed for 12 patients. Complete occlusion was achieved in nine of ten (90 %) PED-treated aneurysms and eight of 11 (72.7 %) treated by stent-assisted coiling (p = 0.44). Two patients treated by stent-assisted coiling required re-coiling for aneurysm recanalization. Overall, modified Rankin scale scores were 0-1 for 12 patients and 3 for one patient. CONCLUSIONS: Adjacent tandem intracranial aneurysms can be safely and effectively treated by either stent-assisted coiling or flow diversion. We prefer PED flow diversion due to better parent vessel reconstruction and lower recanalization risk.

Modified classification and repair of perineal soft tissue injuries associated with open pelvic fractures.

BACKGROUND: This study describes a modified classification and management protocol for perineal soft tissue injuries associated with pelvic fractures. METHODS: A total of 11 patients with perineal soft tissue injuries associated with open pelvic fractures were studied retrospectively. The patients were classified into three types based on the area of defect: type A (urogenital zone), type B (anal zone), and type C (both urogenital and anal zones). Each type included the following subclasses: A1 (without urethra injuries), A2 (with urethra injuries), B1 (without anorectal injuries), B2 (with anorectal injuries), C1 (with types A1 and B1), C2 (with types A2 and B1), C3 (with types A1 and B2), and C4 (with types A2 and B2). The management protocol was planned according to the individual classifications. Protocol A1 (for type A1) involved skin graft or myocutaneous flap transplantation. Protocol A2 (for type A2) involved the same protocol combined with urine diversion. Protocol B1 (for type B1) involved skin graft or myocutaneous flap transplantation. Protocol B2 (for type B2) involved the same management combined with fecal diversion. Protocol C involved the correspondent protocol used for each subtype of type C. RESULTS: Out of the 11 patients, there were 5, 3, and 3 cases of types A, B, and C, respectively. One patient died due to sepsis, and the wounds of the remaining patients healed well. No anal incontinence had occurred. CONCLUSIONS: Perineal soft tissue injuries associated with pelvic fractures can be classified into three types, and the management protocol can be planned according to the classification.

A Meta-Analysis for Postoperative Complications in Tibial Plafond Fracture: Open Reduction and Internal Fixation Versus Limited Internal Fixation Combined With External Fixator.

The treatment of tibial plafond fractures is challenging to foot and ankle surgeons. Open reduction and internal fixation and limited internal fixation combined with an external fixator are 2 of the most commonly used methods of tibial plafond fracture repair. However, conclusions regarding the superior choice remain controversial. The present meta-analysis aimed to quantitatively compare the postoperative complications between open reduction and internal fixation and limited internal fixation combined with an external fixator for tibial plafond fractures. Nine studies with 498 fractures in 494 patients were included in the present study. The meta-analysis found no significant differences in bone healing complications (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.68 to 2.01, p = .58], nonunion (RR 1.09, 95% CI 0.51 to 2.36, p = .82), malunion or delayed union (RR 1.24, 95% CI 0.57 to 2.69, p = .59), superficial (RR 1.56, 95% CI 0.43 to 5.61, p = .50) and deep (RR 1.89, 95% CI 0.62 to 5.80) infections, arthritis symptoms (RR 1.20, 95% CI 0.92 to 1.58, p = .18), or chronic osteomyelitis (RR 0.31, 95% CI 0.05 to 1.84, p = .20) between the 2 groups.

AneuGuide™ software-assisted vs. manual measurements in sizing for pipeline embolization device: An agreement study.

Sizing of flow diverters (FDs) is a challenging task in the treatment of intracranial aneurysms due to their foreshortening behavior. The purpose of this study is to evaluate the difference between the sizing results from the AneuGuide™ software and from conventional 2D measurement. Ninety-eight consecutive patients undergoing pipeline embolization device (PED) treatment between October 2018 and April 2023 in the First Medical Center of Chinese PLA General Hospital (Beijing, China) were retrospectively analyzed. For all cases, the optimal PED dimensions were both manually determined through 2D measurements on pre-treatment 3D-DSA and computed by AneuGuide™ software. The inter-rater reliability between the two sets of sizing results for each methodology was analyzed using intraclass correlation coefficient (ICC). The degree of agreement between manual sizing and software sizing were analyzed with the Bland-Altman plot and Pearson's test. Differences between two methodologies were analyzed with Wilcoxon signed rank test. Statistical significance was defined as p < 0.05. There was better inter-rater reliability between AneuGuide™ measurements both for diameter (ICC 0.92, 95%CI 0.88-0.95) and length (ICC 0.93, 95%CI 0.89-0.96). Bland-Altman plots showed a good agreement for diameter selection between two methodologies. However, the median length proposed by software group was significantly shorter (16 mm versus 20 mm, p < 0.001). No difference was found for median diameter (4.25 mm versus 4.25 mm). We demonstrated that the AneuGuide™ software provides highly reliable results of PED sizing compared with manual measurement, with a shorter stent length. AneuGuide™ may aid neurointerventionalists in selecting optimal dimensions for FD treatment.