Applications of Artificial Intelligence Based on Medical Imaging in Glioma: Current State and Future Challenges.

Glioma is one of the most fatal primary brain tumors, and it is well-known for its difficulty in diagnosis and management. Medical imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET), and spectral imaging can efficiently aid physicians in diagnosing, treating, and evaluating patients with gliomas. With the increasing clinical records and digital images, the application of artificial intelligence (AI) based on medical imaging has reduced the burden on physicians treating gliomas even further. This review will classify AI technologies and procedures used in medical imaging analysis. Additionally, we will discuss the applications of AI in glioma, including tumor segmentation and classification, prediction of genetic markers, and prediction of treatment response and prognosis, using MRI, PET, and spectral imaging. Despite the benefits of AI in clinical applications, several issues such as data management, incomprehension, safety, clinical efficacy evaluation, and ethical or legal considerations, remain to be solved. In the future, doctors and researchers should collaborate to solve these issues, with a particular emphasis on interdisciplinary teamwork.

Deep learning derived automated ASPECTS on non-contrast CT scans of acute ischemic stroke patients.

Ischemic stroke is the most common type of stroke, ranked as the second leading cause of death worldwide. The Alberta Stroke Program Early CT Score (ASPECTS) is considered as a systematic method of assessing ischemic change on non-contrast CT scans (NCCT) of acute ischemic stroke (AIS) patients, while still suffering from the requirement of experts' experience and also the inconsistent results between readers. In this study, we proposed an automated ASPECTS method to utilize the powerful learning ability of neural networks for objectively scoring CT scans of AIS patients. First, we proposed to use the CT perfusion (CTP) from one-stop stroke imaging to provide the golden standard of ischemic regions for ASPECTS scoring. Second, we designed an asymmetry network to capture features when comparing the left and right sides for each ASPECTS region to estimate its ischemic status. Third, we performed experiments in a large main dataset of 870 patients, as well as an independent testing dataset consisting of 207 patients with radiologists' scorings. Experimental results show that our network achieved remarkable performance, as sensitivity and accuracy of 93.7 and 92.4% in the main dataset, and 95.5 and 91.3% in the independent testing dataset, respectively. In the latter dataset, our analysis revealed a high positive correlation between the ASPECTS score and the prognosis of patients in 90DmRs. Also, we found ASPECTS score is a good indicator of the size of CTP core volume of an infraction. The proposed method shows its potential for automated ASPECTS scoring on NCCT images.

Risk factors of contrast extravasation and subsequent hemorrhagic transformation after thrombectomy.

OBJECTIVE: The risk factors associated with iodine contrast extravasation immediately after endovascular thrombectomy (EVT) and subsequent hemorrhagic transformation within 24 hours remain unclear. METHODS: Mixed images, iodine overlay maps, and virtual non-contrast images were reconstructed from 106 consecutive acute ischemic stroke patients who underwent dual energy computed tomography immediately and 24 hours after EVT. Multivariate analyses of clinical and radiological data were performed to explore independent predictors of iodine contrast extravasation and hemorrhagic transformation. RESULTS: Sixty-eight (64.2%) patients exhibited pure iodine contrast extravasation after EVT; 30.9% developed hemorrhagic transformation within 24 hours after EVT. The number of stent retriever passes was independently associated with both iodine contrast extravasation (odds ratio 1.608; 95% confidence interval (CI) 1.047-2.469) and subsequent hemorrhagic transformation (odds ratio 1.477; 95% CI 1.003-2.175). Patients with more than two stent retriever passes were more likely to exhibit iodine contrast extravasation (sensitivity = 68.2%, specificity = 81.5%), while those with more than three stent retriever passes more often exhibited hemorrhage after iodine contrast extravasation (sensitivity = 64.6%, specificity = 87.2%). CONCLUSIONS: The number of stent retriever passes was an independent predictor for both iodine contrast extravasation and subsequent hemorrhagic transformation.

MicroRNA miR-497 is closely associated with poor prognosis in patients with cerebral ischemic stroke.

Cerebral ischemic stroke (CIS) is the most common type of stroke, which is highly hazardous. This investigation aims to analyze the correlation of miR-497 with CIS, so as to provide reliable evidence for clinical response to CIS and lay a solid foundation for follow-up research. Eighty-nine CIS patients and 39 concurrent physical examinees selected between June 2017 and October 2018 were enrolled as the research participants. Additionally, SD rats with increased miR-497 expression and normal SD rats were purchased for CIS modeling to observe the clinical implications of miR-497 in CIS, as well as the water content of brain tissue and neuronal apoptosis of rats. miR-497 expression was lower in CIS patients than in physical examinees, and that in patients with complete stroke (CS) was the lowest, which increased after treatment. As determined by the receiver operating characteristic curve (ROC) analysis, miR-497 had an outstanding diagnostic efficacy for CIS and was negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) and MDA concentration, while positively related to SOD concentration. Prognostic follow-up demonstrated that decreased miR-497 expression in patients after treatment predicted an increased risk of prognostic death and recurrence. However, observed in rats, the water content of the brain tissue of rats with increased miR-497 expression was reduced, and the neuronal apoptosis rate of the brain tissue was inhibited. Taken together, with low expression in CIS, miR-497 is strongly related to CIS progression and is a candidate CIS marker.

The Role of Dual Energy CT in Evaluating Hemorrhagic Complications at Different Stages After Thrombectomy.

Background: Contrast media extravasation can mimic hemorrhage after endovascular thrombectomy (EVT). Dual energy CT (DECT) has the potential to distinguish hemorrhage from iodine contrast. Methods: We retrospectively examined clinical and radiological data from 106 consecutive acute ischemic stroke patients who received EVT and underwent DECT immediately and 24 h after EVT. Iodine overlay map, virtual non-contrast, and mixed images are reconstructed. Results: With the use of DECT, the proportion of all patients diagnosed with hemorrhagic transformation on mixed images immediately after EVT was reduced from 74.5% (79 of 106) to 10.4% (11 of 106), with a very poor consistency (κ = 0.076, p = 0.041). Correspondingly, hemorrhagic transformation on mixed images 24 h after EVT was reduced from 41.5% (44 of 106) to 30.2% (32 of 106), with a moderate consistency (κ = 0.757, p < 0.001). Conclusions: The use of DECT both immediately and 24 h after EVT changes the diagnosis of hemorrhagic transformation in a considerable proportion of acute ischemic stroke patients with EVT. This could affect decision making with respect to antithrombotic strategy.

HbA1c and clinical outcomes after endovascular treatment in patients with posterior circulation large vessel occlusion: a subgroup analysis of a nationwide registry (BASILAR).

BACKGROUND AND AIMS: Recently, several clinical trials have shown that increased glycated hemoglobin (HbA1c) level is correlated with poor clinical outcomes in ischemic stroke patients after thrombolysis and possibly after mechanical thrombectomy. However, the effect of HbA1c on posterior circulation large vessel occlusion (PCLVO) patients treated with endovascular thrombectomy (EVT) remains unclear. This multicenter study assessed the association between the HbA1c levels and clinical outcomes in patients with PCLVO after EVT. METHODS: We studied 385 PCLVO ischemic stroke patients included in the EVT for acute basilar artery occlusion study (BASILAR). Patients were divided into a high HbA1c level group (HbA1c >6.5%) and a low HbA1c level group (HbA1c ⩽6.5%). The efficacy outcome was a 90-day favorable functional outcome (modified Rankin Scale 0-3). The safety outcomes included symptomatic intracerebral hemorrhage and mortality at 90 days after EVT. RESULTS: The frequency of a favorable outcome in patients with an HbA1c ⩽6.5% was significantly higher than that in the HbA1c >6.5% group (41.2% versus 26.2%, p = 0.001). In multivariate analysis with adjusted confounders, high HbA1c levels and favorable outcomes were significantly negatively correlated. There was also a significant association between high HbA1c levels and mortality after 3 months. The negative effects of high HbA1c levels on functional status after 3 months were exacerbated in patients aged ⩾65 years. CONCLUSION: Our multicenter study suggests that a higher serum HbA1c level (HbA1c >6.5%) is an independent predictor of a 90-day poor outcome and mortality in patients with PCLVO after EVT, particularly in those aged ⩾65 years.Clinical Trial Registry identifier: ChiCTR1800014759.

Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial.

BACKGROUND: Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. METHODS: We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556. FINDINGS: Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0-3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81-3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0-3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20-7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31-7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. INTERPRETATION: There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. FUNDING: Jiangsu Provincial Special Program of Medical Science.

A Study of GWAS-Supported Variants of rs9943582 in a Chinese Han Population with Ischemic Stroke: No Associations with Disease Onset and Clinical Outcomes.

BACKGROUND: The variant rs9943582 of APLNR (apelin receptor) was identified by a large-scale study to be associated with an increased risk of ischemic stroke in a Japanese population. We conducted this study to investigate the association between the variant and age of onset and clinical outcomes of ischemic stroke in a Chinese population. METHODS: Improved multiple ligase detection reaction was used to genotype the variant. We compared the mean age at ischemic stroke onset with one-way ANOVA. The Kaplan-Meier method, log-rank test, and Cox proportional hazards regression models were performed to analyze the association between the variant and clinical outcomes (recurrence and death). RESULTS: A total of 916 ischemic stroke patients were recruited for the study. For age at ischemic stroke onset, no significant association was identified with the variant in any genetic model. In addition, the variant was not strongly associated with recurrence and death risk of ischemic stroke, as shown by the results. CONCLUSIONS: The findings indicated that the variant rs9943582 was not associated with age at onset and clinical outcomes of ischemic stroke. However, evidence from well-designed studies with larger and in different ethnic populations are warranted to further explore the effects of APLNR on the ischemic stroke onset and clinical outcomes.

Multidrug resistance protein and topoisomerase 2 alpha expression in non-small cell lung cancer are related with brain metastasis postoperatively.

The aim of this study was to investigate association between expressions of multidrug resistance protein (MRP) and topoisomerase 2 alpha expression in non-small cell lung cancer (TOP2A) and brain metastasis operatively. The expression of MRP and TOP2A were performed using immunohistochemistry (IHC) staining, and the results were analyzed in correlation with clinicopathological data. A total of 286 NSCLC patients who underwent curative surgery between 2007 and 2013 were enrolled in this study. Positive expression of MRP and TOP2A were 62.2% and 37.8%. MRP positive expression in NSCLC was significantly correlated with tumor cell differentiation (P=0.028). TOP2A expression was significantly associated with patients' smoking status, tumor histological type (P<0.05). The positive MRP group had significantly inferior survival rates for 2-year BMFS than did the negative MRP group (79.0% vs. 93.4%, P=0.003) by the Kaplan-Meier method and a log-rank test. Similarly, the positive TOP2A expression was inversely correlated with 2-year BMFS (84.2% vs. 93.4%, P=0.030). Multivariate analysis showed that gender, MRP expression and TOP2A expression were independent prognostic factors for BMFS (P<0.05). Positive expressions of MRP and TOP2A in the tumor tissue are associated with increased risk of developing brain metastases in NSCLC.

Plasma adrenomedullin levels are associated with long-term outcomes of acute ischemic stroke.

Plasma adrenomedullin concentration has been found to be enhanced in ischemic stroke. Up to now, little is known about the association of plasma adrenomedullin concentration with clinical outcomes of ischemic stroke. This study recruited 138 patients with ischemic stroke and 138 healthy volunteers. Unfavorable outcome was defined as modified Rankin Scale score >2 at 3 months. Plasma adrenomedullin concentrations were determined by enzyme-linked immunosorbent assay. Plasma adrenomedullin concentrations were statistically significantly higher in patients than in healthy individuals (79.9±27.3pg/mL vs. 36.8±10.4pg/mL; P<0.001). 3-Month mortality was 20.3% (28/138) and sixty-six patients (47.8%) had unfavorable outcome in 3 months. A logistic regression analysis identified plasma adrenomedullin concentration as an independent predictor of 3-month mortality (odds ratio, 1.211; 95% confidence interval, 1.101-1.582; P=0.004) and unfavorable outcome (odds ratio, 1.193; 95% confidence interval, 1.082-1.447; P=0.006). Receiver operating characteristic curve analysis showed that plasma adrenomedullin concentration predicted 3-month mortality (area under curve, 0.806; 95% confidence interval, 0.730-0.868) and unfavorable outcome (area under curve, 0.816; 95% confidence interval, 0.742-0.877) with the high predictive value. Its predictive performance was similar to that of National Institutes of Health Stroke Scale score (P=0.694 or 0.206). Its combined use with National Institutes of Health Stroke Scale score did not improve the predictive value (P=0.236 or 0.590). Thus, adrenomedullin may aid to predict long-term clinical outcomes of patients with ischemic stroke.

China interventional stroke registry: rationale and study design.

BACKGROUND: Angioplasty and stenting have recently become attractive options for cerebral large artery stenosis in China. However, there are limited data on safety and long-term outcomes in Chinese patients having undergone cerebral interventional procedures. To address this need, we set up a common database - the China Interventional Stroke Registry (CISR) - to describe patient characteristics, interventional images, periprocedural complications and long-term clinical outcomes and to determine how adherence to guideline-based treatments in the 'real world' works in China. METHODS: Six medical centers have participated since 2004. They entered into an Internet-based database data on demographics, clinical history and angiography of patients undergoing angioplasty with/without stenting in extracranial arteries (carotid, vertebral and subclavian arteries) and/or intracranial arteries (middle cerebral artery, vertebral artery and basilar artery) in China. CISR is a research-funded project. RESULTS: As of October 2012, we have already collected detailed clinical information on 1,356 patients (age: 63.6 ± 10.2 years, male: 1,084, 79.9%). The overall data quality is good. Site data quality control is supported via detailed monthly feedback reports and quarterly data monitoring meetings. CONCLUSIONS: The CISR is the first and the largest registry for angioplasty with/without stents in China. The database will provide the characteristics and outcomes of patients and the situation of adherence to guideline-based treatments under 'real-world' conditions in China.

Prognostic significance of plasma visfatin levels in patients with ischemic stroke.

Plasma visfatin concentration has been enhanced in ischemic stroke. The aim of the current investigation was to test whether determination of visfatin in plasma is associated with 6-month clinical outcomes including mortality and unfavorable outcome (modified Rankin Scale score>2) in the patients with ischemic stroke. Between July 2009 and January 2012, plasma visfatin concentrations of 186 patients and 100 healthy individuals were quantified by enzyme-linked immunosorbent assay. Plasma visfatin concentrations were higher in patients than in healthy individuals (108.5±41.1 ng/mL vs. 13.8±3.9 ng/mL, P<0.001). A logistic regression analysis selected plasma visfatin concentration as an independent predictor for 6-month clinical outcomes (both P<0.01). Using receiver operating characteristic curve analysis, plasma visfatin concentration was found to predict 6-month clinical outcomes with the high predictive performance. The predictive value of visfatin was in the range of National Institutes of Health Stroke Scale score (both P>0.05). Combined use of visfatin and National Institutes of Health Stroke Scale score did not improve the predictive significance (both P>0.05). Thus, visfatin may help in the prediction of long-term clinical outcomes in patients with ischemic stroke.

Downregulation of parkin damages antioxidant defenses and enhances proteasome inhibition-induced toxicity in PC12 cells.

Loss-of-function mutations in the parkin gene have recently been shown to be responsible for autosomal recessive juvenile Parkinsonism. However, the exact mechanism of pathogenesis remains unclear. This study explores the effect of Parkin downregulation on dopaminergic cells in Parkinson's disease. We generated small interfering RNA plasmids that target the parkin gene and transfected them into PC12 cells to mimic in vivo loss-of-function. We found that these small plasmids were able to effectively inhibit endogenous Parkin expression in PC12 cells. Downregulation of Parkin decreased the amount of glutathione and superoxide dismutase activity without affecting the amount of malondialdehyde. Moreover, Parkin knockdown rendered PC12 cells more susceptible to cell death induced by the proteasome inhibitor lactacystin. These results indicate that downregulation of Parkin may damage the antioxidation defenses of dopaminergic cells and increase their susceptibility to proteasome inhibitor-induced toxicity.