BackgroundMany patients with brachial plexus avulsion (BPA) suffer from neuropathic pain, but the mechanism remains elusive. Modifications of histones, the proteins responsible for organizing DNA, may play an important role in neuropathic pain. Lysine demethylase 4A (KDM4A), an essential component of histone demethylase, can modify the function of chromatin and thus regulate the vital gene expressions. However, the mechanism by which KDM4A regulates neuropathic pain following BPA remains unclear.MethodsThe pain model was developed in adult rats that received BPA surgery. Western blot, ELISA, and reverse transcription-PCR were used to examine the protein and mRNA levels of targeted genes. Immunofluorescence studies were conducted to analyze their cellular distribution in the spinal cord. Pharmacological and genetic methods were used to modulate the expression of KDM4A. Co-immunoprecipitation and chromatin immunoprecipitation PCR were used to assess the binding potential between KDM4A and the promoter of brain-derived neurotrophic factor (BDNF).ResultsKDM4A and BDNF levels were significantly upregulated in the ipsilateral spinal cord dorsal horn in the BPA group compared with the sham surgery group. Additionally, knockdown of KDM4A decreased BDNF expression and microgliosis and reduced neuropathic pain-like behaviors in BPA rats. Conversely, KDM4A overexpression increased BDNF expression and microgliosis and exacerbated neuropathic pain. BDNF inhibitors and activators also regulated the activation of spinal microglia and neuropathic pain. Importantly, we showed that KDM4A modulates BDNF expression by regulating the methylation of histone 3 lysine 9 and histone 3 lysine 36 in its promoter region.ConclusionCurrent findings suggest that the upregulation of KDM4A increases BDNF expression in the spinal cord in rats after BPA, contributing to microgliosis, neuroinflammation, and neuropathic pain.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with uncertain genetic predisposition in most sporadic cases. The spatial architecture of cell types and gene expression are the basis of cell-cell interactions, biological function and disease pathology, but are not well investigated in the human motor cortex, a key ALS-relevant brain region. Recent studies indicated single nucleus transcriptomic features of motor neuron vulnerability in ALS motor cortex. However, the brain regional vulnerability of ALS-associated genes and the genetic link between region-specific genes and ALS risk remain largely unclear.Here, we developed an entropy-weighted differential gene expression matrix-based tool (SpatialE) to identify the spatial enrichment of gene sets in spatial transcriptomics. We benchmarked SpatialE against another enrichment tool (multimodal intersection analysis) using spatial transcriptomics data from both human and mouse brain tissues. To investigate regional vulnerability, we analysed three human motor cortex and two dorsolateral prefrontal cortex tissues for spatial enrichment of ALS-associated genes. We also used Cell2location to estimate the abundance of cell types in ALS-related cortex layers. To dissect the link of regionally expressed genes and ALS risk, we performed burden analyses of rare loss-of-function variants detected by whole-genome sequencing in ALS patients and controls, then analysed differential gene expression in the TargetALS RNA-sequencing dataset.SpatialE showed more accurate and specific spatial enrichment of regional cell type markers than multimodal intersection analysis in both mouse brain and human dorsolateral prefrontal cortex. Spatial transcriptomic analyses of human motor cortex showed heterogeneous cell types and spatial gene expression profiles. We found that 260 manually curated ALS-associated genes are significantly enriched in layer 5 of the motor cortex, with abundant expression of upper motor neurons and layer 5 excitatory neurons. Burden analyses of rare loss-of-function variants in Layer 5-associated genes nominated NOMO1 as a novel ALS-associated gene in a combined sample set of 6814 ALS patients and 3324 controls (P = 0.029). Gene expression analyses in CNS tissues revealed downregulation of NOMO1 in ALS, which is consistent with a loss-of-function disease mechanism. In conclusion, our integrated spatial transcriptomics and genomic analyses identified regional brain vulnerability in ALS and the association of a layer 5 gene (NOMO1) with ALS risk. Using spatial transcriptomics and single-nucleus RNA sequencing, Guo et al. show that ALS-associated gene expression is enriched in layer 5 of the motor cortex. Genomic analyses revealed a novel association between a layer 5 gene called NOMO1 and ALS risk. Understanding region-specific vulnerability in ALS will aid precision medicine approaches.

This case report discusses a unique instance of pulsatile tinnitus (PT) caused by a rare type of intracranial dural arteriovenous fistula (DAVF) located in the sphenoid wing (SW) region, with PT being the sole presenting symptom. The patient initially received multiple misdiagnoses and sought medical attention at various hospitals before being correctly diagnosed. Imaging studies revealed the DAVF’s presence in the SW region, which led to the patient’s referral to interventional radiology/neurology, although she chose conservative observation without surgical intervention. Remarkably, the patient’s PT spontaneously ceased after 30 months without any apparent cause, and follow-up imaging confirmed the absence of DAVF-related abnormalities. The case highlights the importance of considering DAVF as a potential cause of PT, even when there are no evident abnormalities in proximity to the auditory apparatus. It also emphasizes the need for otolaryngologists to extend their examination to include regions beyond the temporal bone, such as the sphenoid bone and orbital areas, when PT is the exclusive symptom. The case underscores the significance of early detection and intervention for DAVFs, as they can lead to debilitating complications, despite the rare occurrence of spontaneous symptom resolution in this case.

Abstract ANXA11 mutations link to multisystem proteinopathy (MSP), typically affecting motor neurons. This report describes a 55-year-old man with a rare concurrent presentation of inclusion body myopathy (IBM), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), alongside cardiac issues, confirmed by genetic testing as ANXA11-related MSP with a c.118G > T (p.D40Y) mutation. This case underscores ANXA11's broad impact and its critical role in MSP, highlighting unusual multisystem involvement including the cardiac system, thus expanding our understanding of ANXA11 mutation spectra.

Background This study represented the inaugural effort to develop predictive survival nomograms for metastatic soft tissue sarcoma (mSTS) patients in the era of immune checkpoint inhibitors.Method From the Surveillance, Epidemiology, and End Results (SEER) program database, we extracted 3078 eligible patients with mSTS between 2016 and 2022. Kaplan-Meier survival analysis, univariate and multivariable Cox analyses, and univariate and multivariable logistic analyses were conducted. Subsequently, predictive nomograms were constructed. Clinical effectiveness was validated using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA) methods.Results We used the SEER database to include 3078 eligible patients with mSTS between 2016 and 2022. All the eligible patients were randomly allocated in a ratio of 6:4 and stratified into a training group (n = 1846) and a validation group (n = 1232). In the multivariate Cox analysis, age, race, marital status, pathological grade, histologic subtype, surgery, and chemotherapy were identified as independent prognostic factors. These factors were used to construct the nomogram to predict the 1-, 3-, and 5-year OS of mSTS patients. The C-index for the training cohort and the validation cohort was 0.722(95% confidence interval [CI]: 0.708-0.736), and 0.716(95% CI: 0.698-0.734), respectively. The calibration curves for 1-, 3-, and 5-year OS probability demonstrated excellent calibration between the predicted and the actual survival. The AUC values of the nomogram at 1-, 3-, and 5-year were 0.785, 0.767, and 0.757 in the training cohort, 0.773, 0.754, and 0.751 in the validation cohort, respectively. Furthermore, DCA indicated the favorable clinical utility of the nomogram in both cohorts. The risk stratification system was constructed using the established nomogram, which enhanced prediction accuracy, aided clinicians in identifying high-risk patients and informing treatment decisions.Conclusion This study marked the inaugural effort in constructing predictive survival nomograms mSTS patients in the era of immune checkpoint inhibitors. The robustly constructed nomograms, alongside actual outcomes, offered valuable insights to inform follow-up management strategies.

BackgroundDural sinus wall thickness and wall enhancement index (WEI) of dural arteriovenous fistulae (DAVFs) have not been well characterized. This study aimed to measure the sinus wall thickness and WEI by using magnetic resonance vessel wall imaging (MR-VWI).MethodsA total 27 DAVF patients and 30 normal healthy individuals were enrolled in this study. All participants were scanned by a 3 T MR scanner with the black blood sequence. The wall thickness and the WEI of the great cerebral vein, the intracranial main dural sinuses with DAVFs, and the contralateral sinuses were measured by two independent neuroradiologists.ResultsThe DAVF-affected sinuses had significantly thicker walls (2.277 ± 0.311 mm vs. 1.446 ± 0.188 mm, P < 0.001) and significantly higher WEI (2.253 ± 0.462 vs. 1.173 ± 0.418, P < 0.001) compared to the contralateral ones. They also had significantly thicker walls (2.277 ± 0.311 mm vs. 1.643 ± 0.173 mm, P < 0.001) and significantly higher WEI (2.253 ± 0.462 vs. 1.124 ± 0.254, P < 0.001) compared to the normal controls. Neither the sinus wall thickness (r = −0.317, P = 0.107) nor the WEI (r = 0.019, P = 0.923) was significantly correlated with the Cognard types in DAVF patients. The WEI of the DAVF draining vein was significantly higher compared to the static venous wall (1.972 ± 0.629 vs. 0.532 ± 0.243, P < 0.001).ConclusionT1-CUBE MRI is useful in measuring sinus all thickness and WEI of DAVFs, providing a new method for diagnosing this disease.

Objectives. Tube feeding is an effective way to provide nutritional support for amyotrophic lateral sclerosis (ALS) patients with severe dysphagia. Currently, the predictors of tube feeding and the survival affected by tube feeding were poorly studied in Chinese ALS patients. Therefore, we aimed to explore predictive factors and establish a prediction model to quantitatively predict the risk of tube feeding. Furthermore, we explored the survival benefit provided by tube feeding. Methods. In this longitudinal, prospective cohort study, we included patients diagnosed with ALS using the Awaji criteria at the ALS clinic in Huashan Hospital. Follow-up was conducted by telephone interview from January 1, 2019, to December 30, 2021, or until death. All statistical analyses were performed using R software. Results. Overall, 218 patients were recruited for the study. The multivariate Cox regression analysis showed a high ALSFRS-R slope (adjusted hazard ratio aHR = 4.94 (95% confidence interval (95% CI: 2.26-10.81), p < 0.001 ), low bulbar score ( aHR = 0.81 (95% CI: 0.69-0.96), p = 0.01 ), history of ischemic stroke ( aHR = 5.69 (95% CI: 1.3-24.82), p = 0.02 ), and bulbar involvement ( aHR = 11.87 (95% CI: 1.42-99.31), p = 0.02 ) as independent risk factors of tube feeding. The nomogram model was established with moderate discrimination and calibration. Among 71 ALS patients with tube feeding indication, 33.8% accepted gastrostomy suggestion and 14.1% had nasogastric tube (NGT) insertion. However, gastrostomy and NGT did not accelerate disease progression ( aHR = 0.57 (95% CI: 0.20-1.67), p = 0.31 and aHR = 1.72 (95% CI: 0.43-6.88), p = 0.43 , respectively). Conclusions. We developed a nomogram that could be a prediction tool to predict individual timing of tube feeding for ALS patients. In addition, we found that gastrostomy and NGT did not affect ALS patients’ survival.

Objective: Genetic mutations of fused in sarcoma (FUS) causing amyotrophic lateral sclerosis (ALS) may disrupt mRNA splicing events. For example, the FUS c.1394-2delA variant was reported in two western ALS patients, but its molecular mechanism is unclear. In this study, we aim to investigate FUS splice site mutations in Chinese ALS patients. Methods: Sanger sequencing was used to identify FUS splicing mutations in Chinese ALS patients. We combined a deep learning tool (SpliceAI), RNA sequencing, and RT-PCR/RT-qPCR to analyze the effect of FUS c.1394-2delA mutation on RNA splicing and expression. AlphaFold was used to predict the protein structure of mutant FUS. In transfected cell lines, we used immunofluorescence to assess cytoplasmicmislocalization of mutant FUS protein. Results: We identified a de novo FUS splice acceptor site mutation (c.1394-2delA, p. Gly466Valfs*14) in one Chinese sporadic ALS patient, which is linked to exon 14 skipping, and upregulated total FUS mRNA expression. The FUS splice site mutation was predicted to be translated into a truncated protein product at Cterminal. In vitro studies revealed that the FUS mutation increased cytoplasmic mislocalization in both HEK293T and SH-SY5Y cells. Conclusions: We identified a de novo FUS splicing mutation (c.1394-2delA, p. Gly466Valfs*14) in 1 out of 233 Chinese ALS patients. It caused abnormal RNA splicing, upregulated gene expression, truncated FUS translation, and cytosolic mislocalization. Our findings suggested that FUS splice site mutation is rare in Chinese ALS patients and extended our knowledge of molecular mechanisms of the FUS c.1394-2delA mutation.

A dural arteriovenous fistula (DAVF) is an abnormal linkage connecting the arterial and venous systems within the intracranial dura mater. A basicranial emissary vein DAVF drains into the cavernous sinus and the ophthalmic vein, similar to a cavernous sinus DAVF. Precise preoperative identification of the DAVF location is a prerequisite for appropriate treatment. Treatment options include microsurgical disconnection, endovascular transarterial embolization (TAE), transvenous embolization (TVE), or a combination thereof. TVE is an increasingly popular approach for the treatment of DAVFs and the preferred approach for skull base locations, due to the risk of cranial neuropathy caused by dangerous anastomosis from arterial approaches. Multimodal magnetic resonance imaging (MRI) can provide anatomical and hemodynamic information for TVE. The therapeutic target must be precisely embolized in the emissary vein, which requires guidance via multimodal MRI. Here, we report a rare case of successful TVE for a basicranial emissary vein DAVF, utilizing multimodal MRI assistance. The fistula had vanished, pterygoid plexus drainage had improved, and the inferior petrosal sinus had recanalized, as observed on 8-month follow-up angiography. Symptoms and signs of double vision, caused by abduction deficiency, disappeared. Detailed anatomic and hemodynamic assessment by multimodal MRI is the key to guiding successful diagnosis and treatment.

Background and purpose Previous studies have stimulated debates on low-dose alteplase administration in acute ischemic stroke (AIS) among the Asian population. We sought to evaluate the safety and efficacy of low-dose alteplase in Chinese patients with AIS using a real-world registry. Methods We analyzed data from the Shanghai Stroke Service System. Patients receiving alteplase intravenous thrombolysis within 4.5 hours were included. These patients were divided into the low-dose alteplase group (0.55–0.65 mg/kg) and the standard-dose alteplase group (0.85–0.95 mg/kg). Baseline imbalances were adjusted by using the propensity score matching. The primary outcome was mortality or disability, which was defined as the modified Rankin scale (mRS) score ranging from 2 to 6 at discharge. The secondary outcomes were in-hospital mortality, symptomatic intracranial hemorrhage (sICH) and functional independence (mRS score 0–2). Results From January 2019 to December 2020, a total of 1,334 patients were enrolled and 368 (27.6%) were treated with low-dose alteplase. The median age of the patients was 71 years, and 38.8% were female. Our study showed that the low-dose group had significantly higher rates of death or disability (adjusted odds ratio (aOR) = 1.49, 95% confidence interval (CI) [1.12, 1.98]) and less functional independence (aOR = 0.71, 95%CI [0.52, 0.97]) than the standard-dose group. There was no significant difference in sICH or in-hospital mortality between the standard-dose and low-dose alteplase groups. Conclusions Low-dose alteplase was related to a poor functional outcome without lowering the risk of sICH, compared with standard-dose alteplase for AIS patients in China.

Endovascular embolization of arteriovenous malformations (AVMs) in the brain usually requires injecting liquid embolic agents (LEAs) to reduce blood flow through the malformation. In clinical procedures, the feeding artery into which the LEAs are injected, and the amount of LEAs needs to be carefully planned preoperatively. Computational fluid dynamics can simulate the injecting process of LEAs in nidus and evaluate the therapeutic effects of different procedures preoperatively. Applying a porous media model avoided the difficulties of geometric modeling of AVMs, and the complex vascular network structure within the nidus was reproduced. The multi-phase flow was applied to simulate the interaction between LEAs and blood. The viscosity of LEAs is determined by the concentration of its solute ethylene-vinyl alcohol copolymer (EVOH). The diffusion process of the solvent dimethyl sulfoxide (DMSO) was calculated by solving the species transport equation. The coagulation of LEAs was simulated by constructing the relationship between the concentration of EVOH and viscosity. The numerical simulation method of LEAs for injection and coagulation was tested on two patient-specific AVMs. The calculations predicted the flow direction of the LEAs in the nidus. The morphology of the injected LEAs could be well visualized by 3D rendering. Quantitative analysis was conducted, including flow rate changes at the feeding arteries and draining veins. The embolization process of AVMs with LEAs can be simulated by computational fluid dynamics (CFD) methods to show the therapeutic effects of different embolization procedure planning, the optimal treatment plan can be determined.

Dural arteriovenous fistulas (DAVFs) include a wide range of pathological conditions that are associated with intracranial vessel abnormalities. While some types of DAVFs present with typical neuroimaging characteristics, others share overlapping pathological and neuroimaging features that can hinder accurate differentiation. Hence, misclassification of the various types of DAVFs is common. Thorough knowledge of DAVF imaging findings is essential to avoid such misinterpretations. Traditional digital subtraction angiography (DSA) is considered the gold standard for diagnosing and evaluating DAVFs. However, angiography cannot detect changes in a patient's brain structure. Conventional magnetic resonance imaging (MRI) sequences, including MR angiography (MRA), allow the evaluation of DAVFs without ionizing radiation or invasiveness. Advanced MRI techniques, such as susceptibility-weighted imaging (SWI) and dynamic contrast-enhanced MRA, provide added value to real-time physio-pathological data regarding the hemodynamics of DAVFs. Beyond these techniques, new insights using high-resolution vascular wall MRI are incorporated for the noninvasive evaluation of DAVFs. This article reviews the pathophysiology of DAVFs, focusing on the specifics of MRI findings that facilitate their classification. The role of conventional and advanced MRI sequences for DAVFs was assessed using insights derived from the data provided by structured reports of multimodal MRIs to evaluate DAVFs.

© Author(s) (or their employer(s)) 2022. Reuse permitted under CC BYNC. No commercial reuse. See rights and permissions. Published by BMJ. Acute basilar artery occlusion (BAO) may lead to severe disability or death in about 70% of patients. 2 Previous studies have established endovascular treatment (EVT) as the standard treatment for patients with acute anterior circulation occlusions. However, the ideal effective treatment for acute BAO remains controversial. Two previously published randomised control studies (RCTs), BEST (Basilar Artery Occlusion Endovascular Intervention versus Standard Medical Treatment) and BASICS (Basilar Artery International Cooperation Study), failed to achieve an advantage of EVT over standard medical treatment (SMT) . 11 Recently, two other RCTs from China, ATTENTION (Endovascular Treatment For Acute Basilar Artery Occlusion: A Multicentre Randomised Clinical Trial) and BAOCHE (Basilar Artery Occlusion Chinese Endovascular), were presented at the European Stroke Organisation Conference 2022. 13 The ATTENTION trial showed that EVT was associated with the better functional outcomes at 90 days, achieving a higher rate of modified Rankin Scale (mRS) score of ≤3 (46.0% vs 22.8%; adjusted relative risk (aRR) 2.1, 95% CI 1.5 to 3.0, p<0.001; number needed to treat (NNT)=4) and mRS≤2 (33.2% vs 10.5%; aRR 3.2, 95% CI 1.8 to 5.4, p<0.001; NNT=4.4). There was also a significantly lower risk of 90day mortality (36.7% vs 55.3%; aRR 0.7, 95% CI 0.5 to 0.8, p<0.001; NNT=5.4) but a higher incidence of symptomatic intracranial haemorrhage (sICH, Safe Implementation of Thrombolysis in Stroke—Monitoring Study (SITSMOST) criteria, EVT 5.3% vs SMT 0%, p=0.001; NNT=19). Likewise, the BAOCHE trial demonstrated that patients receiving EVT had a higher rate of mRS 0–3 (46.4% vs 24.3%, adjusted OR 2.92, 95% CI 1.56 to 5.47, p=0.001; NNT=4.5), trends towards lower mortality (EVT 30.9% vs SMT 42.1%, p=0.088) and a higher risk of sICH (SITSMOST criteria, EVT 5.9% vs SMT 1.1%, p=0.125). These findings showed the efficacy of EVT, which could be a turning point for the treatment of acute BAO. Here, we provided a brief metaanalysis of the aggregate data from BASICS, BEST, ATTENTION and BAOCHE trials according to the intentiontotreat principle. Key features of the design of included trials are summarised in online supplemental table 1. We found that EVT for ischaemic stroke due to acute BAO was correlated with improved functional outcomes compared with SMT. The pooled RR for 90day mRS 0–3 was 1.54 (95% CI 1.16 to 2.04; heterogeneity I=60%) (figure 1A). The pooled RR for 90day mRS 0 to 2 was 1.83 (95% CI 1.08 to 3.08; heterogeneity I=79%). Although there was a higher risk of sICH (RR 7.77, 95% CI 2.36 to 25.59; heterogeneity I=0%) (figure 1B), EVT significantly decreased the risk of 90day mortality (RR 0.76, 95% CI 0.65 to 0.89; heterogeneity I=0%) (figure 1C). We found no evidence of publication bias using Egger’s test (p>0.05).

As one of the common complications, vascular cognitive impairment (VCI) comprises a range of cognitive disorders related to cerebral vessel diseases like moyamoya disease (MMD), and it is reversible by surgical revascularization in its early stage. However, diagnosis of VCI is time-consuming and less accurate if it solely relies on neuropsychological examination. Even if some existing research connected VCI with medical image, most of them were solely statistical methods with single modality. Therefore, we propose a graph-based framework to integrate both dual-modal imaging information (rs-fMRI and DTI) and non-imaging information to identify VCI in adult MMDs. Unlike some previous studies based on node-level classification, the proposed graph-level model can fully utilize imaging information and improve interpretability of results. Specifically, we firstly design two different graphs for each subject based on characteristics of different modalities and feed them to a dual-modal graph convolution network to extract complementary imaging features and select important brain biomarkers for each subject. Node-based normalization and constraint item are further devised to weakening influence of over-smoothing and natural difference caused by non-imaging information. Experiments on a real dataset not only achieve accuracy of $$80.0\%$$ , but also highlight some salient brain regions related to VCI in adult MMDs, demonstrating the effectiveness and clinical interpretability of our proposed method.

Spinal epidural hemorrhages (SEDH) caused by spinal epidural arteriovenous fistulas (SEAVFs) are rare; thus, their specific pathogenesis has not been explained. Furthermore, the standard treatment for SEAVFs has not yet been defined. Here we report the case of a 36-year-old Chinese man who experienced acute onset chest pain and tightness. His symptoms rapidly aggravated until the lower limbs were unable to support him. Spinal magnetic resonance angiography (MRA) revealed a localized SEAVF and a secondary spinal cord lesion at the T4 level. Digital subtraction angiography (DSA) confirmed the presence of the SEDH/SEAVF at the T3–4 level with the left radicular artery feeding the fistula. Based on DSA and MRA findings, SEDH, local spinal cord infarction, and spinal venous reflux disorder were conditionally diagnosed. Using the arterial route, Onyx-34 was injected into the fistula to embolize the feeding arteries and the venous system. Angiography was performed after the microcatheter was withdrawn, and no residual fistula or anterior spinal artery was observed. The six-week follow-up MRI showed acceptable healing of the SEAVF, and the patient improved neurologically. This case suggests that endovascular treatment with Onyx-34 embolization should be considered a promising treatment strategy for this type of complicated SEAVF.

Amyotrophic lateral sclerosis(ALS)is an idiopathic and fatal neurodegenerative disorder leading to progressive mus-cle atrophy,dysarthria,dysphagia,and respiratory failure[1].More than 80 different drugs have been tested since the 1980s,but only two,riluzole and edaravone,have been approved for ALS treatment.Riluzole is an anti-excitotoxic drug that may moderately prolong ALS patients'survival by 2-3 months,and edaravone is an antioxidant that could sup-press neurodegeneration in early-stage patients.But neither can significantly prevent the rapid disease progression[2].Therefore,searching for effective disease-modifying treat-ment for ALS remains essential.

AbstractObjectiveTo investigate the relationship between fibrin deposition and “no‐reflow” within microcirculation after thrombolysis in acute ischemic stroke (AIS).Materials and methodsExperiments were approved by the institutional animal care and use committee. An experimental AIS model was induced in C57BL/6 mice by middle cerebral artery occlusion (MCAO) via the photothrombotic method. Mice were randomly assigned to non‐thrombolytic or thrombolytic treated groups (n = 12 per group). The modified Neurological Severity Score and Fast Beam Balance Test were performed by a researcher blinded to the treatment method. MRI was utilized to evaluate all of the mice. An FXIIIa‐targeted probe was applied to detect fibrin deposition in acute ischemic brain regions by fluorescence imaging. Necrosis and pathological changes of brain tissue were estimated via Hematoxylin and eosin staining while fibrin deposition was observed by immunohistochemistry.ResultsThrombolytic therapy improved AIS clinical symptoms. The infarct area of non‐thrombolytic treated mice was significantly greater than that of the thrombolytic treated mice (p < .0001). Fluorescent imaging indicated fibrin deposition in ischemic brain tissue in both groups, with less fibrin in non‐thrombolytic treated mice than thrombolytic treated mice, though the difference was not significant. Brain cells with abnormal morphology, necrosis, and liquefication were observed in the infarcted area for both groups. Clotted red blood cells (RBCs) and fibrin build‐up in capillaries were found near the ischemic area in both non‐thrombolytic and thrombolytic treated groups of mice.ConclusionFibrin deposition and stacked RBCs contribute to microcirculation no‐reflow in AIS after thrombolytic therapy.

Background: A variety of emerging medical imaging technologies based on artificial intelligence have been widely applied in many diseases, but they are still limitedly used in the cerebrovascular field even though the diseases can lead to catastrophic consequences. Objective: This work aims to discuss the current challenges and future directions of artificial intelligence technology in cerebrovascular diseases through reviewing the existing literature related to applications in terms of computer-aided detection, prediction and treatment of cerebrovascular diseases. Methods: Based on artificial intelligence applications in four representative cerebrovascular diseases including intracranial aneurysm, arteriovenous malformation, arteriosclerosis and moyamoya disease, this paper systematically reviews studies published between 2006 and 2021 in five databases: National Center for Biotechnology Information, Elsevier Science Direct, IEEE Xplore Digital Library, Web of Science and Springer Link. And three refinement steps were further conducted after identifying relevant literature from these databases. Results: For the popular research topic, most of the included publications involved computer-aided detection and prediction of aneurysms, while studies about arteriovenous malformation, arteriosclerosis and moyamoya disease showed an upward trend in recent years. Both conventional machine learning and deep learning algorithms were utilized in these publications, but machine learning techniques accounted for a larger proportion. Conclusion: Algorithms related to artificial intelligence, especially deep learning, are promising tools for medical imaging analysis and will enhance the performance of computer-aided detection, prediction and treatment of cerebrovascular diseases.

PURPOSE:Early identification of ischemic stroke lesion regions plays a vital role in its treatments like thrombolytic therapy and patients' recovery. Noncontrast computed tomography (ncCT) is the most widespread imaging modality in emergency departments. Unfortunately, it is extremely hard to distinguish the lesion from healthy tissue during the hyper-acute phase of stroke. In this paper, a two-stage convolutional neural network-based method was proposed to identify the invisible ischemic stroke from ncCT. METHODS:In order to combine the global and local information of images effectively, a cascaded structure with two coordinated networks was used to detect the suspicious stroke regions on the whole and optimize the detailed localization. In the first stage, an end-to-end U-net with adaptive threshold was proposed to integrate global position, symmetry and gray texture information to detect the suspicious regions. After reducing the interference from most normal regions, a ResNet-based patch classification network was used to eliminate some false positive samples on suspicious regions by mining deeper image features, contributing to a more precise localization of stroke. Finally, a MAP model was used to optimize the result by combining the classification results of each patch with their spatial constraint information. RESULTS:Three independent experiments, that is, training and testing on dataset from one hospital, on the combination of two, and on the two respectively, were performed on a total of 277 cases from two hospitals to validate the proposed model, The proposed method achieved identification accuracy of 91.89%, 87.21%, and 85.71% in the three experiments, and the final localization accuracy in terms of precise localization of stroke were 82.35%, 83.02%, and 81.40%, respectively, which indicated the robustness and clinical values of the method. CONCLUSIONS:There are some deep image feature differences between stroke region and normal region on ncCT images. The proposed two-stage convolutional neural network model can well seize these features and use them to effectively identify and locate stroke.