Automated Cerebral Infarct Detection on Computed Tomography Images Based on Deep Learning

The limited accuracy of cerebral infarct detection on CT images caused by the low contrast of CT hinders the desirable application of CT as a first-line diagnostic modality for screening of cerebral infarct. This research was aimed at utilizing convolutional neural network to enhance the accuracy of automated cerebral infarct detection on CT images. The CT images underwent a series of preprocessing steps mainly to enhance the contrast inside the parenchyma, adjust the orientation, spatially normalize the images to the CT template, and create a t-score map for each patient. The input format of the convolutional neural network was the t-score matrix of a 16 × 16-pixel patch. Non-infarcted and infarcted patches were selected from the t-score maps, on which data augmentation was conducted to generate more patches for training and testing the proposed convolutional neural network. The convolutional neural network attained a 93.9% patch-wise detection accuracy in the test set. The proposed method offers prompt and accurate cerebral infarct detection on CT images. It renders a frontline detection modality of ischemic stroke on an emergent or regular basis.

Yi-Zhi-Fang-Dai Formula Exerts Neuroprotective Effects Against Pyroptosis and Blood–Brain Barrier–Glymphatic Dysfunctions to Prevent Amyloid-Beta Acute Accumulation After Cerebral Ischemia and Reperfusion in Rats

Background: The dysfunctional blood–brain barrier (BBB)–glymphatic system is responsible for triggering intracerebral amyloid-beta peptide (Aβ) accumulation and acts as the key link between ischemic stroke and dementia dominated by Alzheimer’s disease (AD). Recently, pyroptosis in cerebral ischemia and reperfusion (I/R) injury is demonstrated as a considerable mechanism causing BBB–glymphatic dysfunctions and Aβ acute accumulation in the brain. Targeting glial pyroptosis to protect BBB–glymphatic functions after cerebral I/R could offer a new viewpoint to prevent Aβ accumulation and poststroke dementia. Yi-Zhi-Fang-Dai formula (YZFDF) is an herbal prescription used to cure dementia with multiple effects of regulating inflammatory responses and protecting the BBB against toxic Aβ-induced damage. Hence, YZFDF potentially possesses neuroprotective effects against cerebral I/R injury and the early pathology of poststroke dementia, which evokes our current study.Objectives: The present study was designed to confirm the potential efficacy of YZFDF against cerebral I/R injury and explore the possible mechanism associated with alleviating Aβ acute accumulation.Methods: The models of cerebral I/R injury in rats were built by the method of middle cerebral artery occlusion/reperfusion (MCAO/R). First, neurological function assessment and cerebral infarct measurement were used for confirming the efficacy of YZFDF on cerebral I/R injury, and the optimal dosage (YZFDF-H) was selected to conduct the experiments, which included Western blotting detections of pyroptosis, Aβ1-42 oligomers, and NeuN, immunofluorescence observations of glial pyroptosis, aquaporin-4 (AQP-4), and Aβ locations, brain water content measurement, SMI 71 (a specific marker for BBB)/AQP-4 immunohistochemistry, and Nissl staining to further evaluate BBB–glymphatic functions and neuronal damage.Results: YZFDF obviously alleviated neurological deficits and cerebral infarct after cerebral I/R in rats. Furthermore, YZFDF could inactivate pyroptosis signaling via inhibiting caspase-1/11 activation and gasdermin D cleavage, ameliorate glial pyroptosis and neuroinflammation, protect against BBB collapse and AQP-4 depolarization, prevent Aβ acute accumulation and Aβ1-42 oligomers formation, and reduce neuronal damage and increase neurons survival after reperfusion.Conclusion: Our study indicated that YZFDF could exert neuroprotective effects on cerebral I/R injury and prevent Aβ acute accumulation in the brain after cerebral I/R associated with inhibiting neuroinflammation-related pyroptosis and BBB–glymphatic dysfunctions.

Glymphatic Dysfunction in Patients With Ischemic Stroke

Objectives: Rodent experiments have provided some insight into the changes of glymphatic function in ischemic stroke. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with ischemic stroke. We aimed to investigate the changes of glymphatic function in ischemic stroke and the factors associated with the changes.Materials and Methods: A total of 50 patients (mean age 56.7 years; 30 men) and 44 normal subjects (mean age 53.3 years; 23 men) who had preoperative diffusion-tensor imaging for calculation of the analysis along the perivascular space (ALPS) index were retrospectively included. Information collected from each patient included sex, age, time since stroke onset, infarct location, hemorrhagic change, infarct volume, infarct apparent diffusion coefficient (ADC), infarct fractional anisotropy (FA), and ALPS index of both hemispheres. Interhemispheric differences in ALPS index (infarct side vs. contralateral normal side) were assessed with a paired t-test in all patients. ALPS index was normalized by calculating ALPS ratios (right-to-left and left-to-right) for comparisons between patients and normal subjects. Comparisons of ALPS ratios between patients and normal subjects were performed using analysis of covariance with adjustments for age and sex. Linear regression analyses were performed to identify factors associated with the ALPS index.Results: In patients, the mean ALPS index ipsilateral to infarct was 1.162 ± 0.126, significantly lower (P < 0.001) than that of the contralateral side (1.335 ± 0.160). The right-to-left ALPS index ratio of patients with right cerebral infarct was 0.84 ± 0.08, significantly lower (P < 0.001) than that of normal subjects (0.95 ± 0.07). The left-to-right ALPS ratio of patients with left cerebral infarct was 0.92 ± 0.09, significantly (P < 0.001) lower than that of normal subjects (1.05 ± 0.08). On multiple linear regression analysis, time since stroke onset (β = 0.794, P < 0.001) was the only factor associated with the ALPS index.Conclusion: The ALPS index showed lower values in ischemic stroke suggesting impaired glymphatic function. Following initial impairment, the ALPS index increased with the time since stroke onset, which is suggestive of glymphatic function recovery.

Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions

Introduction: The pleiotropic protective effects of high-density lipoproteins (HDLs) on cerebral ischemia have never been tested under acute hyperglycemic conditions. The aim of this study is to evaluate the potential neuroprotective effect of HDL intracarotid injection in a mouse model of middle cerebral artery occlusion (MCAO) under hyperglycemic conditions. Methods: Forty-two mice were randomized to receive either an intracarotid injection of HDLs or saline. Acute hyperglycemia was induced by an intraperitoneal injection of glucose (2.2 g/kg) 20 min before MCAO. Infarct size (2,3,5-triphenyltetrazolium chloride (TTC)-staining), blood–brain barrier leakage (IgG infiltration), and hemorrhagic changes (hemoglobin assay by ELISA and hemorrhagic transformation score) were analyzed 24 h post-stroke. Brain tissue inflammation (IL-6 by ELISA, neutrophil infiltration and myeloperoxidase by immunohisto-fluorescence) and apoptosis (caspase 3 activation) were also assessed. Results: Intraperitoneal D-glucose injection allowed HDL- and saline-treated groups to reach a blood glucose level of 300 mg/dl in the acute phase of cerebral ischemia. HDL injection did not significantly reduce mortality (19% versus 29% in the saline-injected group) or cerebral infarct size (p = 0.25). Hemorrhagic transformations and inflammation parameters were not different between the two groups. In addition, HDL did not inhibit apoptosis under acute hyperglycemic conditions. Conclusion: We observed a nonsignificant decrease in cerebral infarct size in the HDL group. The deleterious consequences of reperfusion such as hemorrhagic transformation or inflammation were not improved by HDL infusion. In acute hyperglycemia, HDLs are not potent enough to counteract the adverse effects of hyperglycemia. The addition of antioxidants to therapeutic HDLs could improve their neuroprotective capacity.

Eloquence-based reperfusion scoring and its ability to predict post-thrombectomy disability and functional status

Background Angiographic reperfusion after endovascular thrombectomy in acute ischemic stroke is commonly graded using volume-based reperfusion scores such as the modified thrombolysis in cerebral infarct score. The location of non-reperfused regions is not included in modified thrombolysis in cerebral infarct score. We studied the predictive ability of an eloquence-based reperfusion score. Methods Consecutive cases of endovascular thrombectomy for anterior circulation strokes performed between January 2018 and April 2020 were included. Digital subtraction angiograms were reviewed by two blinded neurointerventionalist operators. Incomplete reperfusion was further classified by lobar regions lacking reperfusion to create various cohorts. Outcomes were graded four to seven days post-procedure with the National Institute of Health Stroke Scale (NIHSS) and 90 days post-procedure with the modified Rankin Scale. Results One hundred patients were identified. Via multivariate analysis, we found that frontal lobe non-reperfusion (mean difference (MD) = −1.60, p = 0.002) and occipital lobe non-reperfusion (MD = −1.68, p = 0.001) were associated with worse mental status improvement while left-sided stroke (MD = 2.02, p < 0.001) featured better improvement post-thrombectomy. Occipital lobe non-reperfusion (MD = −0.734, p = 0.009) was associated with the worse improvement of visual fields. The non-reperfusion of the frontal lobe was associated with a 1.732-worse NIHSS hemibody strength score (95% confidence interval (95%CI) = −3.39 to −0.072, p = 0.041). Worse improvement in NIHSS scores was found to be associated with frontal lobe non-reperfusion (MD = −5.34, 95%CI = −9.52 to −1.18, p = 0.013) and occipital lobe non-reperfusion (MD = −6.35, 95%CI = −10.4 to −2.31, p = 0.002). Odds of achieving modified Rankin Scale of 0–2 at 90 days were decreased with frontal lobe non-reperfusion (odds ratio (OR) = 0.279, 95%CI = 0.090–0.869, p = 0.028) and left laterality (OR = 0.376, 95%CI = 0.153–0.922, p = 0.033). Conclusions Eloquence-based reperfusion assessment is an important predictor for functional outcomes after thrombectomy.

Economic Evaluation of Regular Transfusions for Cerebral Infarct Recurrence in the Silent Cerebral Infarct Transfusion Trial

In 2020, the American Society of Hematology published evidence-based guidelines for cerebrovascular disease in individuals with sickle cell anemia (SCA). While guidelines were based on NIH-sponsored randomized controlled trials, no cost-effectiveness analysis was completed for children with SCA and silent cerebral infarcts. We conducted a cost-effectiveness analysis comparing regular blood transfusion versus standard care using Silent Cerebral Infarct Transfusion (SIT) Trial participants. This analysis included a modified societal perspective with direct costs (hospitalization, emergency room visit, transfusion, outpatient care, iron chelation) and indirect costs (special education). Direct medical costs were estimated from hospitalizations from SIT hospitals and unlinked aggregated hospital and outpatient costs from SIT sites using the Pediatric Health Information System. Indirect costs were estimated from published literature. Effectiveness was prevention of infarct recurrence. Incremental cost-effectiveness ratio using a 3-year time horizon (mean SIT trial participant follow-up) compared transfusion versus standard care. A total of 196 participants received transfusions (N=90) or standard care (N=106), with a mean age of 10.0 years. Annual hospitalization costs were reduced by 54% for transfusions than standard care ($4,929 vs. $10,802), but transfusion group outpatient costs added $22,454 to $137,022 per year. Special education costs savings was $2,634 over three years for every infarct prevented. Transfusion therapy had an incremental cost-effectiveness ratio of $22,025 per infarct prevented. Children with pre-existing silent cerebral infarcts receiving blood transfusions have lower hospitalization but higher outpatient costs, primarily associated with oral iron chelator deferasirox. Regular blood transfusion therapy is cost-effective for infarct recurrence in children with SCA. This trial is registered at www.clinicaltrials.gov as NCT00072761.

Factors Associated With Decreased Accuracy of Modified Thrombolysis in Cerebral Infarct Scoring Among Neurointerventionalists During Thrombectomy

Background and Purpose: The modified thrombolysis in cerebral infarct (mTICI) score is used to grade angiographic outcome after endovascular thrombectomy. We sought to identify factors that decrease the accuracy of intraprocedural mTICI. Methods: We performed a 2-center retrospective cohort study comparing operator (n=6) mTICI scores to consensus scores from blinded adjudicators. Groups were also assessed by dichotomizing mTICI scores to 0–2a versus 2b–3. Results: One hundred thirty endovascular thrombectomy procedures were included. Operators and adjudicators had a pairwise agreement in 96 cases (73.8%). Krippendorff α was 0.712. Multivariate analysis showed endovascular thrombectomy overnight (odds ratio [OR]=3.84 [95% CI, 1.22–12.1]), lacking frontal (OR, 5.66 [95 CI, 1.36–23.6]), or occipital (OR, 7.18 [95 CI, 2.12–24.3]) region reperfusion, and higher operator mTICI scores (OR, 2.16 [95 CI, 1.16–4.01]) were predictive of incorrectly scoring mTICI intraprocedurally. With dichotomized mTICI scores, increasing number of passes was associated with increased risk of operator error (OR, 1.93 [95 CI, 1.22–3.05]). Conclusions: In our study, mTICI disagreement between operator and adjudicators was observed in 26.2% of cases. Interventions that took place between 22:30 and 4:00, featured frontal or occipital region nonperfusion, higher operator mTICI scores, and increased number of passes had higher odds of intraprocedural mTICI inaccuracy.

14,15-EET Reduced Brain Injury from Cerebral Ischemia and Reperfusion via Suppressing Neuronal Parthanatos

To investigate the effect of 14,15-EET on the parthanatos in neurons induced by cerebral ischemia and reperfusion, middle cerebral artery occlusion and reperfusion (MCAO/R) and oxygen glucose deprivation/reoxygenation (OGD/R) were used to simulate cerebral ischemia reperfusion in vivo and in vitro, respectively. TTC staining and the Tunel method were used to detect cerebral infarct volume and neuronal apoptosis. Western blot and immunofluorescence were used to detect poly (ADP-ribose) polymerase-1 (PARP-1) activation and AIF nuclear translocation. The production of reactive oxygen species (ROS) and the expression of antioxidant genes were detected by Mito SOX, DCFH-DA and qPCR methods. MCAO/R increased cerebral infarct volume and neuronal apoptosis in mice, while 14,15-EET pretreatment increased cerebral infarct volume and neuronal apoptosis. OGD/R induced reactive oxygen species generation, PARP-1 cleavage, and AIF nuclear translocation in cortical neurons. 14,15-EET pretreatment could enhance the antioxidant gene expression of glutathione peroxidase (GSH-Px), heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) in cortical neurons after ischemia and reperfusion. 14,15-EET inhibits the neuronal parthanatos induced by MCAO/R through upregulation of the expression of antioxidant genes and by reducing the generation of reactive oxygen species. This study advances the EET neuroprotection theory and provides a scientific basis for targeted clinical drugs that reduce neuronal parthanatos following cerebral ischemia and reperfusion.