Comparative Outcomes of Intravenous, Intranasal, and Intracerebroventricular Transplantation of Human Neural Stem Cells in Mice Model of Ischemic Stroke.

BACKGROUND: Transplantation of neural stem cells improves ischemic stroke outcomes in rodent models and is currently in the clinical test stage. However, the optimal delivery route to achieve improved efficacy remains undetermined. OBJECTIVE: This study aims to evaluate three more clinically feasible delivery routes: intravenous (IV), intranasal (IN), and intracerebroventricular (ICV). We compared the therapeutic efficacies of the three routes of transplanting human neural stem cells (hNSCs) into mice with permanent middle cerebral artery obstruction (pMCAO). METHODS: Behavioral tests and cresyl violet staining were used to evaluate the therapeutic efficacies of functional recovery and lesion volumes. The expression of proinflammatory cytokines and neurotrophic factors was measured by real-time PCR. The distribution and differentiation of hNSCs were determined by immunofluorescence staining. The effect on endogenous neurogenesis and astrocyte function were determined by immunofluorescence staining and western blot. RESULTS: hNSC transplantation using the three routes improved behavioral outcomes and reduced lesion volumes; IV transplantation of hNSCs results in earlier efficacy and improves the inflammatory microenvironment. The long-term distribution and differentiation of transplanted hNSCs in the peri-infarct areas can only be evaluated using ICV delivery. IV and ICV transplantation of hNSCs promote neurogenesis and modulate the dual function of astrocytes in the peri-infarct areas. CONCLUSION: IV and IN delivery is suitable for repeated administration of hNSCs to achieve improved prognosis. Comparatively, ICV transplantation provides long-term efficacy at lower doses and fewer administration times.

Predictive Value of the Diffusion Magnetic Resonance Imaging Technique for the Postoperative Outcome of Cervical Spondylotic Myelopathy.

BACKGROUND: Diffusion magnetic resonsance imaging (dMRI) can potentially predict the postoperative outcome of cervical spondylotic myelopathy (CSM). PURPOSE: To explore preoperative dMRI parameters to predict the postoperative outcome of CSM through multifactor correlation analysis. STUDY TYPE: Prospective. POPULATION: Post-surgery CSM patients; 102 total, 73 male (52.42 ± 10.60 years old) and 29 female (52.0 ± 11.45 years old). FIELD STRENGTH/SEQUENCE: 3.0 T/Turbo spin echo T1/T2-weighted, T2*-weighted multiecho gradient echo and dMRI. ASSESSMENT: Spinal cord function was evaluated using modified Japanese Orthopedic Association (mJOA) scoring at different time points: preoperative and 3, 6, and 12 months postoperative. Single-factor correlation and t test analyses were conducted based on fractional anisotropy (FA), mean diffusivity, intracellular volume fraction, isotropic volume fraction, orientation division index, increased signal intensity, compression ratio, age, sex, symptom duration and operation method, and multicollinearity was calculated. The linear quantile mixed model (LQMM) and the linear mixed-effects regression model (LMER) were used for multifactor correlation analysis using the combinations of the above variables. STATISTICAL TESTS: Distance correlation, Pearson's correlation, multiscale graph correlation and t tests were used for the single-factor correlation analyses. The variance inflation factor (VIF) was used to calculate multicollinearity. LQMM and LMER were used for multifactor correlation analyses. P < 0.05 was considered statistically significant. RESULTS: The single-factor correlation between all variables and the postoperative mJOA score was weak (all r < 0.3). The linear relationship was stronger than the nonlinear relationship, and there was no significant multicollinearity (VIF = 1.10-1.94). FA values in the LQMM and LMER models had a significant positive correlation with the mJOA score (r = 5.27-6.04), which was stronger than the other variables. DATA CONCLUSION: The FA value based on dMRI significantly positively correlated with CSM patient postoperative outcomes, helping to predict the surgical outcome and formulate a treatment plan before surgery. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Preclinical Studies on Neural Stem/Progenitor Cell Therapy for Ischemic Stroke: A Systematic Review.

BACKGROUND: Neural stem/progenitor cells (NSPCs) transplantation has been recognized in recent years as an effective strategy for the treatment of ischemic stroke. Several preclinical studies have demonstrated the feasibility, safety, and efficacy of NSPCs therapy. METHODS: We conducted a systematic review of the published literature in Pubmed reporting the use of NSPCs in preclinical studies between 2010 and 2021. Based on the articles reporting data, the key factors affecting efficacy were listed. RESULTS: A total of 71 preclinical studies, including 91 treatment arms, were identified. The results showed that several factors could influence the outcomes of NSPCs transplantation, including the type of donor cells, cell dose, time of administration after stroke, delivery route, and anesthetic. Treatment outcomes were measured by infarct volume, behavioral tests, and molecular and cellular level results. CONCLUSION: Most of the preclinical studies reported statistically significant effects and very few adverse reactions. Transplantation of NSPCs for ischemic stroke still needs to be optimized for several key factors. A standardized treatment outcome assessment could ease the translation of evidence in clinical settings.

Predicting postoperative recovery in cervical spondylotic myelopathy: construction and interpretation of T2*-weighted radiomic-based extra trees models.

OBJECTIVES: Conventional MRI may not be ideal for predicting cervical spondylotic myelopathy (CSM) prognosis. In this study, we used radiomics in predicting postoperative recovery in CSM. We aimed to develop and validate radiomic feature-based extra trees models. METHODS: There were 151 patients with CSM who underwent preoperative T2-/ T2*-weighted imaging (WI) and surgery. They were divided into good/poor outcome groups based on the recovery rate. Datasets from multiple scanners were randomised into training and internal validation sets, while the dataset from an independent scanner was used for external validation. Radiomic features were extracted from the transverse spinal cord at the maximum compressed level. Threshold selection algorithm, collinearity removal, and tree-based feature selection were applied sequentially in the training set to obtain the optimal radiomic features. The classification of intramedullary increased signal on T2/T2*WI and compression ratio of the spinal cord on T2*WI were selected as the conventional MRI features. Clinical features were age, preoperative mJOA, and symptom duration. Four models were constructed: radiological, radiomic, clinical-radiological, and clinical-radiomic. An AUC significantly > 0.5 was considered meaningful predictive performance based on the DeLong test. The mean decrease in impurity was used to measure feature importance. p < 0.05 was considered statistically significant. RESULTS: On internal and external validations, AUCs of the radiomic and clinical-radiomic models, and radiological and clinical-radiological models ranged from 0.71 to 0.81 (significantly > 0.5) and 0.40 to 0.55, respectively. Wavelet-LL first-order variance was the most important feature in the radiomic model. CONCLUSION: Radiomic features, especially wavelet-LL first-order variance, contribute to meaningful predictive models for CSM prognosis. KEY POINTS: • Conventional MRI features may not be ideal in predicting prognosis. • Radiomics provides greater predictive efficiency in the recovery from cervical spondylotic myelopathy.

Utility of Advanced DWI in the Detection of Spinal Cord Microstructural Alterations and Assessment of Neurologic Function in Cervical Spondylotic Myelopathy Patients.

BACKGROUND: Diffusion-weighted imaging (DWI) can quantify the microstructural changes in the spinal cord. It might be a substitute for T2 increased signal intensity (ISI) for cervical spondylotic myelopathy (CSM) evaluation and prognosis. PURPOSE: The purpose of the study is to investigate the relationship between DWI metrics and neurologic function of patients with CSM. STUDY TYPE: Retrospective. POPULATION: Forty-eight patients with CSM (18.8% females) and 36 healthy controls (HCs, 25.0% females). FIELD STRENGTH/SEQUENCE: 3 T; spin-echo echo-planar imaging-DWI; turbo spin-echo T1/T2; multi-echo gradient echo T2*. ASSESSMENT: For patients, conventional MRI indicators (presence and grades of T2 ISI), DWI indicators (neurite orientation dispersion and density imaging [NODDI]-derived isotropic volume fraction [ISOVF], intracellular volume fraction, and orientation dispersion index [ODI], diffusion tensor imaging [DTI]-derived fractional anisotropy [FA] and mean diffusivity [MD], and diffusion kurtosis imaging [DKI]-derived FA, MD, and mean kurtosis), clinical conditions, and modified Japanese Orthopaedic Association (mJOA) were recorded before the surgery. Neurologic function improvement was measured by the 3-month follow-up recovery rate (RR). For HCs, DWI, and mJOA were measured as baseline comparison. STATISTICAL TESTS: Continuous (categorical) variables were compared between patients and HCs using Student's t-tests or Mann-Whitney U tests (chi-square or Fisher exact tests). The relationships between DWI metrics/conventional MRI findings, and the pre-operative mJOA/RR were assessed using correlation and multivariate analysis. P < 0.05 was considered statistically significant. RESULTS: Among patients, grades of T2 ISI were not correlated with pre-surgical mJOA/RR (P = 0.717  and 0.175, respectively). NODDI ODI correlated with pre-operative mJOA (r = -0.31). DTI FA, DKI FA, and NODDI ISOVF were correlated with the recovery rate (r = 0.31, 0.41, and -0.34, respectively). In multivariate analysis, NODDI ODI (DTI FA, DKI FA, NODDI ISOVF) significantly contributed to the pre-operative mJOA (RR) after adjusting for age. DATA CONCLUSION: DTI FA, DKI FA, and NODDI ISOVF are predictors for prognosis in patients with CSM. NODDI ODI can be used to evaluate CSM severity. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 5.

Intensification of NO x Conversion over Activated Coke by Ozone Oxidation for Sintering Flue Gas at Low Temperatures.

Denitration (De-NO x ) over activated cokes (ACs) for sintering flue gas needs intensification. Gaseous reactions in a gas mixture containing NO, NO2, and NH3, with the effect of O2 concentration and moisture, were taken into consideration in the study of NO x conversion over ACs. Experimental studies on NO x conversion with and without NH3 over ACs were conducted using a fixed-bed reactor at 100 °C. The results demonstrated that moisture significantly affected NO x removal over ACs, especially the NO2 conversion. Under dry conditions, a disproportionation reaction of NO2 over ACs dominated NO x conversion with no NH3, whereas apparent fast selective catalytic reduction (SCR) over the ACs was observed in the presence of NH3. Regardless of the presence of absence of NH3 in wet mixtures, NO2 adsorption on ACs via the disproportionation route dominated the NO x conversion. Increasing the NO2/NO ratio in the simulated flue gas enhanced the NO x conversion rate over ACs. -C(ONO2) deposition on ACs generated by the disproportionation route inhibited NO x conversion with time. O3 oxidation was found to be efficient in increasing the NO2/NO ratio and intensifying the NO x conversion compared with commercially direct NH3-SCR over ACs. Increasing the temperature and decreasing the gas hourly space velocity can promote NO x conversion over ACs after O3 oxidation. NO oxidized with O3 coupled with NH3 spray and continuous regeneration of ACs is a potential method for removing NO x from sintering flue gas.