Machine learning applications in stroke medicine:advancements,challenges,and future prospectives

Stroke is a leading cause of disability and mortality worldwide,necessitating the development of advanced technologies to improve its diagnosis,treatment,and patient outcomes.In recent years,machine learning techniques have emerged as promising tools in stroke medicine,enabling efficient analysis of large-scale datasets and facilitating personalized and precision medicine approaches.This abstract provides a comprehensive overview of machine learning’s applications,challenges,and future directions in stroke medicine.Recently introduced machine learning algorithms have been extensively employed in all the fields of stroke medicine.Machine learning models have demonstrated remarkable accuracy in imaging analysis,diagnosing stroke subtypes,risk stratifications,guiding medical treatment,and predicting patient prognosis.Despite the tremendous potential of machine learning in stroke medicine,several challenges must be addressed.These include the need for standardized and interoperable data collection,robust model validation and generalization,and the ethical considerations surrounding privacy and bias.In addition,integrating machine learning models into clinical workflows and establishing regulatory frameworks are critical for ensuring their widespread adoption and impact in routine stroke care.Machine learning promises to revolutionize stroke medicine by enabling precise diagnosis,tailored treatment selection,and improved prognostication.Continued research and collaboration among clinicians,researchers,and technologists are essential for overcoming challenges and realizing the full potential of machine learning in stroke care,ultimately leading to enhanced patient outcomes and quality of life.This review aims to summarize all the current implications of machine learning in stroke diagnosis,treatment,and prognostic evaluation.At the same time,another purpose of this paper is to explore all the future perspectives these techniques can provide in combating this disabling disease.

Emerging strategies for nerve repair and regeneration in ischemic stroke:neural stem cell therapy

Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

Perilipin-2 mediates ferroptosis in oligodendrocyte progenitor cells and myelin injury after ischemic stroke

Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.

Exosomes:the next-generation therapeutic platform for ischemic stroke

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

China stroke surveillance report 2021

Since 2015,stroke has become the leading cause of death and disability in China,posing a significant threat to the health of its citizens as a major chronic non-communicable disease.According to the China Stroke High-risk Population Screening and Intervention Program,an estimated 17.8 million[95%confidence interval(CI)17.6–18.0million]adults in China had experienced a stroke in 2020,with 3.4 million(95%CI 3.3–3.5 million)experiencing their first-ever stroke and another 2.3 million(95%CI 2.2–2.4 million)dying as a result.Additionally,approximately 12.5%(95%CI 12.4%–12.5%)of stroke survivors were left disabled,as defined by a modified Rankin Scale score greater than 1,equating to 2.2 million(95%CI 2.1–2.2 million)stroke-related disabilities in 2020.As the population ages and the prevalence of risk factors like diabetes,hypertension,and hyperlipidemia continues to rise and remains poorly controlled,the burden of stroke in China is also increasing.A large national epidemiological survey initiated by the China Hypertension League in 2017 showed that the prevalence of hypertension was 24.7%;the awareness,treatment,and control rates in hypertensive patients were:60.1%,42.5%,and 25.4%,respectively.A nationally representative sample of the Chinese mainland population showed that the weighted prevalence of total diabetes diagnosed by the American Diabetes Association criteria was 12.8%,suggesting there are 120 million adults with diabetes in China,and the awareness,treatment,and control rates in diabetic patients were:43.3%,49.0%,and 49.4%,respectively.The“Sixth National Health Service Statistical Survey Report in 2018”showed that the proportion of the obese population in China was 37.4%,an increase of 7.2 points from 2013.Data from 1599 hospitals in the Hospital Quality Monitoring System and Bigdata Observatory Platform for Stroke of China(BOSC)showed that a total of 3,418,432 stroke cases[mean age±standard error(SE)was(65.700±0.006)years,and 59.1%were male]were admitted during 2020.Of those,over 80.0%(81.9%)were ischemic stroke(IS),14.9%were intracerebral hemorrhage(ICH)strokes,and 3.1%were subarachnoid hemorrhage(SAH)strokes.The mean±SE of hospitalization expenditures was Chinese Yuan(CNY)(16,975.6±16.3),ranging from(13,310.1±12.8)in IS to(81,369.8±260.7)in SAH,and out-of-pocket expenses were(5788.9±8.6),ranging from(4449.0±6.6)in IS to(30,778.2±156.8)in SAH.It was estimated that the medical cost of hospitalization for stroke in 2020 was CNY 58.0 billion,of which the patient pays approximately CNY 19.8 billion.In-hospital death/discharge against medical advice rate was 9.2%(95%CI 9.2%–9.2%),ranging from 6.4%(95%CI 6.4%–6.5%)for IS to 21.8%(95%CI 21.8%–21.9%)for ICH.From 2019 to 2020,the information about 188,648 patients with acute IS receiving intravenous thrombolytic therapy(IVT),49,845 patients receiving mechanical thrombectomy(MT),and 14,087 patients receiving bridging(IVT+MT)were collected through BOSC.The incidence of intracranial hemorrhage during treatment was 3.2%(95%CI 3.2%–3.3%),7.7%(95%CI 7.5%–8.0%),and 12.9%(95%CI 12.3%–13.4%),respectively.And in-hospital death/discharge against medical advice rate was 8.9%(95%CI 8.8%–9.0%),16.5%(95%CI 16.2%–16.9%),and 16.8%(95%CI 16.2%–17.4%),respectively.A prospective nationwide hospital-based study was conducted at 231 stroke base hospitals(Level III)from 31 provinces in China through BOSC from January 2019to December 2020 and 136,282 stroke patients were included and finished 12-month follow-up.Of those,over 86.9%were IS,10.8%were ICH strokes,and 2.3%were SAH strokes.The disability rate[%(95%CI)]in survivors of stroke at 3-month and 12-month was 14.8%(95%CI 14.6%–15.0%)and 14.0%(95%CI 13.8%–14.2%),respectively.The mortality rate[%(95%CI)]of stroke at 3-month and 12-month was 4.2%(95%CI 4.1%–4.3%)and 8.5%(95%CI 8.4%–8.6%),respectively.The recurrence rate[%(95%CI)]of stroke at 3-month and 12-month was 3.6%(95%CI 3.5%–3.7%)and 5.6%(95%CI 5.4%–5.7%),respectively.The Healthy China 2030 Stroke Action Plan was launched as part of this review,and the above data provide valuable guidelines for future stroke prevention and treatment efforts in China.

Platelet-to-neutrophil ratio predicts hemorrhagic transformation and unfavorable outcomes in acute ischemic stroke with intravenous thrombolysis

BACKGROUND Acute ischemic stroke(AIS)retains a notable stance in global disease burden,with thrombolysis via recombinant tissue plasminogen activator(rtPA)serving as a viable management approach,albeit with variable outcomes and the potential for complications like hemorrhagic transformation(HT).The platelet-to-neutrophil ratio(P/NR)has been considered for its potential prognostic value in AIS,yet its capacity to predict outcomes following rtPA administration demands further exploration.AIM To elucidate the prognostic utility of P/NR in predicting HT and clinical outcomes following intravenous rtPA administration in AIS patients.METHODS Data from 418 AIS patients treated with intravenous rtPA at Thammasat University Hospital from January 2018 to June 2021 were retrospectively analyzed.The relationship between P/NR and clinical outcomes[early neurological deterioration(E-ND),HT,delayed ND(D-ND),and 3-mo outcomes]was scrutinized.RESULTS Notable variables,such as age,diabetes,and stroke history,exhibited statistical disparities when comparing patients with and without E-ND,HT,D-ND,and 3-mo outcomes.P/NR prognostication revealed an optimal cutoff of 43.4 with a 60.3%sensitivity and a 52.5%specificity for 90-d outcomes.P/NR prognostic accuracy was statistically significant for 90-d outcomes[area under the curve(AUC)=0.562],D-ND(AUC=0.584),and HT(AUC=0.607).CONCLUSION P/NR demonstrated an association with adverse 3-mo clinical outcomes,HT,and D-ND in AIS patients post-rtPA administration,indicating its potential as a predictive tool for complications and prognoses.This infers that a diminished P/NR may serve as a novel prognostic indicator,assisting clinicians in identifying AIS patients at elevated risk for unfavorable outcomes following rtPA therapy.

Advances in glucocorticoid-mediated stroke-associated immunosuppression

Acute ischemic stroke is often accompanied by complications such as infection.After acute isch-emic stroke,immunosuppression can occur as a mechanism to prevent an excessive inflammatory response. Glucocorticoid,an important product of the hypothalamic-pituitary-adrenal axis,plays a crucial role in inducing immunosuppression in the early stage of acute cerebral infarction. Glucocorticoid not only affects the secretion of inflammatory cytokines but also influences the function of immune cells,ultimately leading to an increased risk of infection.

A novel phenotype of B cells associated with enhanced phagocytic capability and chemotactic function after ischemic stroke

Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration.However,the role of B cells in ischemic stroke remains unclear.In this study,we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45.Macrophage-like B cells chara cterized by co-expression of B-cell and macrophage markers,showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes.Gene Ontology analysis found that the expression of genes associated with phagocytosis,including phagosome-and lysosome-related genes,was upregulated in macrophage-like B cells.The phagocytic activity of macrophage-like B cells was ve rified by immunostaining and three-dimensional reconstruction,in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia.Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways.Single-cell RNA sequencing showed that the transdiffe rentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP fa mily to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage.Furthermore,this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury,Alzheimer’s disease,and glioblastoma.Overall,these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain.These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.

Perspectives on potential neuroprotective role of albumin in acute ischemic stroke

Albumin is the most abundant protein in plasma and is synthesized primarily in the liver.It has a variety of biological roles,such as increasing colloid osmotic pressure, and performing antioxidant, anti-inflam-matory,and substance transportation functions.Several studies have confirmed that albumin has neuroprotective effects and it has been used in the treatment of cerebral edema and increased intracranial pressure.In this review we focus on the neuroprotective effects of albumin in ischemic stroke,such as the reduction of cerebral edema, antioxidant effects, protection of neuronal cell membranes, and increased cerebral blood flow. In addition, we summarize preclinical and clinical studies of albumin in ischemic stroke. We believe that the neuroprotective role of albumin should be re-investigated in the era of reperfusion therapy.

Endothelial progenitor cells, potential biomarkers for diagnosis and prognosis of ischemic stroke: protocol for an observational case-control study

Ischemic stroke is a devastating,life altering event which can severely reduce patient quality of life.Despite years of research there have been minimal therapeutic advances.Endothelial progenitor cells(EPCs),stem cells involved in both vasculogenesis and angiogenesis,may be a potential therapeutic target.After a stroke,EPCs migrate to the site of ischemic injury to repair cerebrovascular damage,and their numbers and functional capacity may determine patients'outcome.This study aims to determine whether the number of circulating EPCs and their functional aspects may be used as biomarkers to identify the type(cortical or lacunar)and/or severity of ischemic stroke.The study will also investigate if there are any differences in these characteristics between healthy volunteers over and under 65 years of age.100 stroke patients(50 lacunar and 50 cortical strokes)will be recruited in this prospective,observational case-controlled study.Blood samples will be taken from stroke patients at baseline(within 48 hours of stroke)and days 7,30 and90.EPCs will be counted with flow cytometry.The plasma levels of pro-and anti-angiogenic factors and inflammatory cytokines will also be determined.Outgrowth endothelial cells will be cultured to be used in tube formation,migration and proliferation functional assays.Primary outcome is disability or dependence on day 90 after stroke,assessed by the modified Rankin Scale.Secondary outcomes are changes in circulating EPC numbers and/or functional capacity between patient and healthy volunteers,between patient subgroups and between elderly and young healthy volunteers.Recruitment started in February 2017,167 participants have been recruited.Recruitment will end in November 2019.West Midlands-Coventry&Warwickshire Research Ethics Committee approved this study(REC number:16/WM/0304)on September8,2016.Protocol version:2.0.The Bayraktutan Dunhill Medical Trust EPC Study was registered in ClinicalTrials.gov(NCT02980354)on November 15,2016.This study will determine whether the number of EPCs can be used as a prognostic or diagnostic marker for ischemic strokes and is a step towards discovering if transplantation of EPCs may aid patient recovery.

Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke

We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.

Association between Clinical Characteristics and Quality of Life in Older People with Stroke at Hospital Discharge

Objective: The number of people with stroke increases worldwide. The stroke survivors live with disabilities and those influence their quality of life (QOL). This study was aimed to investigate the association between clinical characteristics and QOL of the older people with stroke at discharge from the hospital. Methods: This is a cross-sectional study. The participants were 113 stroke survivors aged 60 years and older admitted to the stroke unit. Quality of life was the study’s outcome which measured by using the abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF). Primary clinical characteristics were measured by the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and Modified Rankin Scale (mRS). Potential confounding factors were age, sex, education levels, marital status, current occupation, and comorbidity (hypertension, diabetes mellitus, dyslipidemia, and heart disease). Multiple linear regression was used for data analysis. Results: The main effects of clinical outcomes were high BI Score that had a significant difference association with QOL (β = 0.312, 95% CI = 0.042, 0.296, P = 0.009), lower mRS score also had significant difference association with QOL (β= -0.371, 95%CI = -5.394, -1.162, P = 0.003) after all adjusting. Additional risk factor in this study was marital status (currently married) (β= 0.155, 95% CI = 0.226, 8.666, P = 0.039). Conclusion: Low function status and severe stroke disability as the clinical characteristics were associated with QOL in older people with stroke at hospital discharge. An additional factor was marital status (currently married).

The secretome of endothelial progenitor cells: a potential therapeutic strategy for ischemic stroke

Ischemic stroke continues to be a leading cause of mortality and morbidity in the world. Despite recent advances in the field of stroke medicine, thrombolysis with recombinant tissue plasminogen activator remains as the only pharmacological therapy for stroke patients. However, due to short therapeutic window(4.5 hours of stroke onset) and increased risk of hemorrhage beyond this point, each year globally less than 1% of stroke patients receive this therapy which necessitate the discovery of safe and efficacious therapeutics that can be used beyond the acute phase of stroke. Accumulating evidence indicates that endothelial progenitor cells(EPCs), equipped with an inherent capacity to migrate, proliferate and differentiate, may be one such therapeutics. However, the limited availability of EPCs in peripheral blood and early senescence of few isolated cells in culture conditions adversely affect their application as effective therapeutics. Given that much of the EPC-mediated reparative effects on neurovasculature is realized by a wide range of biologically active substances released by these cells, it is possible that EPC-secretome may serve as an important therapeutic after an ischemic stroke. In light of this assumption, this review paper firstly discusses the main constituents of EPC-secretome that may exert the beneficial effects of EPCs on neurovasculature, and then reviews the currently scant literature that focuses on its therapeutic capacity.

Diabetes mellitus and stroke: A clinical update

Cardiovascular disease including stroke is a major complication that tremendously increases the morbidity and mortality in patients with diabetes mellitus(DM). DM poses about four times higher risk for stroke. Cardiometabolic risk factors including obesity, hypertension, and dyslipidaemia often co-exist in patients with DM that add on to stroke risk. Because of the strong association between DM and other stroke risk factors, physicians and diabetologists managing patients should have thorough understanding of these risk factors and management. This review is an evidence-based approach to the epidemiological aspects, pathophysiology, diagnostic work up and management algorithms for patients with diabetes and stroke.

Apolipoprotein E polymorphisms increase the risk of post-stroke depression

Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.

Expert consensus on the diagnosis and treatment of heat stroke in China

Heat stroke(HS)is a fatal disease caused by thermal damage in the body,and it has a very high mortality rate.In 2015,the People’s Liberation Army Professional Committee of Critical Care Medicine published the first expert consensus on HS in China,Expert consensus on standardized diagnosis and treatment for heat stroke.With an increased understanding of HS and new issues that emerged during the HS treatment in China in recent years,the 2015 consensus no longer meet the requirements for HS prevention and treatment.It is necessary to update the consensus to include the latest research evidence and establish a new consensus that has broader coverage,is more practical and is more in line with China’s national conditions.This new expert consensus includes new concept of HS,recommendations for laboratory tests and auxiliary examinations,new understanding of diagnosis and differential diagnosis,On-site emergency treatment and In-hospital treatment,translocation of HS patients and prevention of HS.

Application of MAGnetic resonance imaging compilation in acute ischemic stroke

BACKGROUND Synthetic magnetic resonance imaging(MRI)MAGnetic resonance imaging compilation(MAGiC)is a new MRI technology.Conventional T1,T2,T2-fluidattenuated inversion recovery(FLAIR)contrast images,quantitative images of T1 and T2 mapping,and MAGiC phase sensitive inversion recovery(PSIR)Vessel cerebrovascular images can be obtained simultaneously through post-processing at the same time after completing a scan.In recent years,studies have reported that MAGiC can be applied to patients with acute ischemic stroke.We hypothesized that the synthetic MRI vascular screening scheme can evaluate the degree of cerebral artery stenosis in patients with acute ischemic stroke.AIM To explore the application value of vascular images obtained by synthetic MRI in diagnosing acute ischemic stroke.METHODS A total of 64 patients with acute ischemic stroke were selected and examined by MRI in the current retrospective cohort study.The scanning sequences included traditional T1,T2,and T2-FLAIR,three-dimensional time-of-flight magnetic resonance angiography(3D TOF MRA),diffusion-weighted imaging(DWI),and synthetic MRI.Conventional contrast images(T1,T2,and T2-FLAIR)and intracranial vessel images(MAGiC PSIR Vessel]were automatically reconstructed using synthetic MRI raw data.The contrast-to-noise ratio(CNR)values of traditional T1,T2,and T2-FLAIR images and MAGiC reconstructed T1,T2,and T2-FLAIR images in DWI diffusion restriction areas were measured and compared.MAGiC PSIR Vessel and TOF MRA images were used to measure and calculate the stenosis degree of bilateral middle cerebral artery stenosis areas.The consistency of MAGiC PSIR Vessel and TOF MRA in displaying the degree of vascular stenosis with computed tomography angiography(CTA)was compared.RESULTS Among the 64 patients with acute ischemic stroke,79 vascular stenosis areas showed that the correlation between MAGiC PSIR Vessel and CTA(r=0.90,P<0.01)was higher than that between TOF MRA and CTA(r=0.84,P<0.01).With a degree of vascular stenosis>50%assessed by CTA as a reference,the area under the receiver operating characteristic(ROC)curve of MAGiC PSIR Vessel[area under the curve(AUC)=0.906,P<0.01]was higher than that of TOF MRA(AUC=0.790,P<0.01).Among the 64 patients with acute ischemic stroke,39 were scanned for traditional T1,T2,and T2-FLAIR images and MAGiC images simultaneously,and CNR values in DWI diffusion restriction areas were measured,which were:Traditional T2=21.2,traditional T1=-6.7,and traditional T2-FLAIR=11.9;and MAGiC T2=7.1,MAGiC T1=-3.9,and MAGiC T2-FLAIR=4.5.CONCLUSION The synthetic MRI vascular screening scheme for patients with acute ischemic stroke can accurately evaluate the degree of bilateral middle cerebral artery stenosis,which is of great significance to early thrombolytic interventional therapy and improving patients’quality of life.

A more consistent intraluminal rhesus monkey model of ischemic stroke

Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group： middle cerebral artery occlusion at origin segment （M1） and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique （1 mm × 10 cm） （undetachable）, to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.

Evaluation of right-to-left shunt on contrast-enhanced transcranial Doppler in patent foramen ovale-related cryptogenic stroke: Research based on imaging

BACKGROUND Cardiogenic embolism caused by patent foramen ovale(PFO)is a common etiology of cryptogenic stroke(CS),particularly in young and middle-aged patients.Studies about right-to-left shunt(RLS)detection using contrast-enhanced transcranial Doppler(c-TCD)are numerous.According to the time phase and number of microbubbles detected on c-TCD,RLS can be classified and graded.We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS.AIM To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD.METHODS We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital.In total,111 PFO-related CS patients were divided according to whether RLS was permanent(microbubbles detected both at resting state and after the Valsalva maneuver)or latent(microbubbles detected only after the Valsalva maneuver)on c-TCD.Each group was subdivided into small,mild and large RLS according to the grade of shunt on c-TCD.A normal control group was composed of 33 patients who suffered from simple dizziness.Intragroup and intergroup differences were analyzed in terms of clinical,laboratory and diffusion-weighted imaging lesion characteristics.The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed.RESULTS In 111 patients with PFO-related CS,68 had permanent RLS and 43 had latent RLS.Clinical characteristics and laboratory tests were not significantly different among the permanent RLS,latent RLS and normal control groups.The proportion of patients with multiple territory lesions in the permanent RLS group(50%)was larger than that in the latent RLS group(27.91%;P=0.021).Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group(30.23%vs 8.82%,P=0.004).Permanent-large and latent-large RLS were both more likely to be related to multiple(P_(trend)=0.017 and 0.009,respectively),small(P_(trend)=0.035 and 0.006,respectively)and cortical(P_(trend)=0.031 and 0.033,respectively)lesions.The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography(r=0.758,P<0.001).CONCLUSION Distribution of the infarct suggested the possible type of RLS.Multiple,small and cortical infarcts suggest large RLS induced by a large PFO.

Congenital Cardiac Defects, Such as Eustachian Valve, May Increase the Risk of Cryptogenic Stroke: A Case Report

Eustachian valve is an embryonic endocardial heart structure;after birth it becomes an embryogenic residue and its persistance in adult life is unusual. The literature reports some cases of association between Eustachian valve and PFO and is known that the prominent Eustachian valve can represent a way facilitating systemic embolism.Several studies also investigated the role of Eustachian valve in the pathophysiology of both migraine and cerebral embolism. In addiction is known how Eustachian valve may increase the risk of endocarditis, which mostly affects intravenous drug abusers or those with implanted medical devices or central venous catheters. The most commonly identified organism is Staphylococcus aureus (approximately 53% of cases). We present a case of a 46-year-old woman with known migraine. She was hospitalized in Stroke Unit for a cryptogenic stroke with a right-to-left shunt detected with transcranial doppler ultrasound with “bubble test” and a patent foramen ovale with right-to-left shunt with a fenestration of atrial septum and a voluminous Eustachian valve detected with transesophageal echocardiography;she developed fever with a blood cultures positive for methicillin-resis- tant Staphylococcus aureus (MRSA), even if without evidence of endocarditis vegetations. In summary, the objective of our paper is to present an example of a correlation between the persistence of the Eustachian valve with bothcryptogenetic stroke, possible valve infection and migraine.