Ischemic Volume Research Articles

Quantitative Ischemic Characteristics and Prognostic Analysis of Crossed Cerebellar Diaschisis in Hyperacute Ischemic Stroke

ObjectivesCrossed cerebellar diaschisis (CCD) is a secondary phenomenon caused by supratentorial brain injury, characterized by hypoperfusion and hypometabolism of the contralateral cerebellum. This study aimed to investigate the correlation between the quantitative data of initial supratentorial ischemia and CCD, and to further explore the prognosis value of CCD in the hyperacute phase. Materials and MethodsThe imaging and clinical data of 109 patients with hyperacute ischemic stroke were analyzed retrospectively, univariate analysis and multivariate logistic regression were used to observe the relationship between the volume and degree of initial supratentorial ischemia and CCD, respectively, and to further analyze the effects of CCD in the hyperacute phase on neurological function and clinical prognosis. ResultsThe degree and volume of initial supratentorial ischemia was significantly correlated with hyperacute CCD. The volume of ischemic penumbra (OR=1.021 [95% CI: 1.009–1.033], P<0.001) and the reduction rate of cerebral blood volume (CBV) (OR=1.338 [95% CI: 1.073–1.668], P=0.01) were the main influencing factors of CCD; patients with hyperacute CCD had higher admission and discharge National Institutes of Health Stroke Scale (NIHSS) (P=0.046 and P=0.01), and more hemorrhagic transformation (P=0.021), but there was no significant difference in the final infarction volume (P=0.347) and the 90-day modified Rankin Scale (mRS) (P=0.757). ConclusionPatients with CCD had larger initial supratentorial ischemic volume and more severe ischemic degree in the hyperacute ischemic stroke, more short-term neurological impairment, and worse short-term treatment effect, however, but the long-term functional prognosis was not be affected.

Abstract 14: Receiver Operating Characteristics Curve Analysis Demonstrates That Quantitative Assessment Of Iodine Contrast Extravasation Post Reperfusion Therapy For Ischemic Stroke Predicts Reperfusion Injury And Discharge Modified Rankin

Introduction: We previously demonstrated that the quantitative volumetric assessment of iodinated contrast extravasation (ICE) present on post-intervention imaging was closely associated with the likelihood of an acute ischemic stroke patient having PH-1 or PH-2, and thus ICE may serve as a useful CT biomarker to assess risk of reperfusion injury (hemorrhagic conversion (HC) and blood brain barrier (BBB) disruption). Here we used receiver operator curve (ROC) analysis to compare the efficacy of ICE, infarct volume, and 24hr NIHSS change as a predictor of discharge mRS and HC post-reperfusion therapy. Method: Data on ischemic stroke patients treated with reperfusion therapy were obtained from our Institutional Review Board approved database from January 2017 to November 2019 that had evaluable images within 24 hours of admission. Ischemic volume (IV) was measured on diffusion-weighted imaging. ICE was measured on CT head. A freehand 3D region of interest tool on the Visage Imaging PACS System was used to measure volumes. Susceptibility weighted MRI sequences were used to grade HC. Data analysis was conducted with regression modeling and ROC analysis. Results: Of the 82 patients, median age was 73 (interquartile range (IQR) 61- 77, 49% were women, admission NIHSS was 12 (IQR 7 - 21), 24hr NIHSS change was 4 (IQR 0 -13), IV was 50.6 +/- 7.1 mL, 48% were treated with thrombectomy, 7% had PH-1 or PH-2 identified on MRI, median systolic blood pressure was 154 (IQR 137-175), 56% were MCA territory strokes, and 37% had a discharge mRS of 0-2. ICE volume was 2.6 +/- 1.0 mL. ICE increased the likelihood of PH-1 or PH-2 HC (odds ratio (OR) 14.34, 95% confidence interval (CI) 5.74 - 22.94) and decreased the likelihood of discharge with mRS of 0-2, OR of 0.09 (CI 0.008-0.972). IV was a better predictor of 0-2 mRS (ROC area under the curve (AUC) 0.832) than ICE (AUC 0.640) and 24hr NIHSS change (AUC 0.557), but ICE was a better predictor of PH-1 or PH-2 (AUC 0.942) than IV (AUC 0.667) and 24hr NIHSS change (AUC 0.447). Conclusion: ICE may predict reperfusion injury and functional outcome, but it is a better predictor of hemorrhagic conversion in patients treated with reperfusion therapy.

Abstract TP192: Plasma Mid-regional Pro-adrenomedullin Reflects Ischemic Penumbra In Acute Ischemic Stroke

Background: Adrenomedullin (AM), an endogenous peptide, is secreted in response to cerebral ischemia, contributing to neuroprotection by exerting anti-inflammatory and vasodilatory effects. Although previous studies showed elevated levels of mid-regional fragment of pro-AM (MR-proAM), a stable marker of AM, predict unfavorable outcome in acute ischemic stroke (AIS), the role of the biomarker remains to be determined. Methods: Firstly, plasma MR-proAM levels were measured in consecutively enrolled patients with AIS within 4.5 hours of the onset and compared with those of healthy controls. Propensity score was used to match the baseline difference. Secondly, variables associated with the increased MR-proAM levels were evaluated in AIS. Finally, it was determined whether MR-proAM levels are associated with a large penumbra which was defined as ICA/M1 occlusion with NIH stroke scale ≥ 6 and ischemic core volume ≤ 50 ml calculated by the RAPID software. Results: MR-proAM levels in AIS (n = 122; median age, 77 years; male, 59%; median NIHSS 6.5) were higher (median 0.68 vs. 0.42 nmol/L, p &lt; 0.001) compared with controls (n = 1298; median age, 58 years; male, 33%). The difference remained after matching of baseline (p=0.004). In patients with AIS, MR-proAM levels were correlated with NIHSS (r = 0.367, p &lt; 0.001) and eGFR (r = -0.527, p &lt; 0.001). MR-proAM levels did not correlate with ischemic core volume (r = 0.065, p = 0.478), but significantly increased in AIS patients with cardioembolic stroke (CES) (n = 53) (0.80 vs. 0.59 nmol/L, p &lt; 0.001) and ICA/M1 occlusion (n = 40) (0.78 vs. 0.63 nmol/L, p = 0.048). Interestingly, MR-proAM levels were higher (0.85 vs. 0.62, p &lt; 0.001) in AIS patients with a large penumbra (n = 24) compared to those without (n = 98), and the difference remained after adjustment of baseline factors (OR [95% confidence interval], 1.43 [1.10-2.02], p = 0.004). Conclusions: MR-proAM levels increase in patients with AIS, especially in those with large vessel occlusion and clinical imaging mismatch. MR-proAM is a potential biomarker for ischemic penumbra.

Abstract 91: Large Vessel Occlusion Stroke Patients With Rapid Early Infarct Progression And Poor Collaterals Are Vulnerable To Blood Pressure Reductions

Introduction: The precise interactions between collateral perfusion, hemodynamics, and infarct growth after large vessel occlusion (LVO) require further definition. This study examined whether patients with poor collateral circulation and rapid early infarct progression are more vulnerable to reductions in blood pressure (BP). Methods: We prospectively enrolled patients with LVO stroke who underwent thrombectomy. Volumes of arterial tissue delay and relative cerebral blood flow (CBF) were estimated with RAPID software; a poor collateral profile was defined by a hypoperfusion intensity ratio &gt;0.4. Early infarct growth rate (EIGR) was defined as ischemic core volume (CBF&lt;30%) divided by the time from symptom onset to imaging. A fast progressor profile was assigned to patients whose EIGR was &gt;10 mL/h. The final infarct growth rate (FIGR) was the quotient of final infarct volume (FIV) and time from symptom onset to reperfusion. BP reduction was measured as the difference between admission mean arterial pressure (MAP) and lowest MAP before reperfusion. Results: Fifty-five patients (mean age 69 + 15, mean NIHSS 13) with successful reperfusion (TICI 2B/3) were included in the analysis. The median MAP reduction was 17 (IQR 9, 32). Poor collateral perfusion and EIGR were independent predictors of FIV after adjusting for age and admission NIHSS (mean FIV 70 vs. 31 mL, p=0.012 and 60 vs. 29 mL, p=0.01, respectively). A significant interaction was found between MAP reduction and both collateral status (p=0.04) and progressor profile (p=0.01). For every 10 mmHg MAP reduction, patients with poor collaterals experienced an average increase in FIGR of 3.6 mL/h (Fig. 1A). Above a critical MAP reduction threshold of 30 mmHg, mean FIV was significantly larger in patients with rapidly progressing infarcts (p&lt;0.01, Fig. 1B). Conclusions: Patients with poor collaterals and rapid early infarct growth are at higher risk of accelerated infarct growth and larger FIV related to BP reductions.

Abstract 42: The Effect Of Anesthesia On Thrombectomy Outcomes Is Modified By Collateral Flow: Pooled Patient Level Analysis From EXTEND-IA, EXTEND-IA TNK Part I And II, And SELECT

Background: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. Methods: In a pooled patient level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II and SELECT, EVT Functional outcomes (mRS distribution) were compared between general anesthesia (GA) vs non-general anesthesia (non-GA). Further, we assessed the impact of collateral flow on perfusion imaging evaluated by hypoperfusion intensity ratio (HIR) - Tmax10 sec/Tmax6 sec) on the association between anesthesia type and EVT outcomes. Results: Of 731 treated with EVT, 305 (42%) received GA and 426 (58%) non-GA. The baseline characteristics were similar, except for presentation NIHSS (median [IQR] GA 18 [13-22], non-GA 16[11-20], p&lt;0.001) and ischemic core volume (GA 14.1mL [3-37] vs non-GA 9mL [0-31], p=0.002). GA was associated with longer LKW to arterial access (203min [158-267] vs 186min [138-252], p=0.002), but similar procedural time (36min [23-59] vs 34min [22-54], p=0.36). Non-GA was independently associated with improved functional outcomes (adj cOR 1.42, 95%CI 1.05-1.93, p=0.024) and lower mortality (17% vs 11.3%, p=0.025). Patients with poor collaterals (HIR≥0.4) had improved functional outcomes with non-GA (adj cOR 1.53, 95%CI 1.02-2.29, p=0.038), while no difference was observed in those with good collaterals-HIR&lt;0.4 (adj cOR 1.38, 95% CI 0.84-2.27, p=0.21). Conclusion: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals. These findings have implications for randomized trials of GA vs non-GA.

Abstract WP48: How To Optimize Population Access To Acute Stroke Expertise

Objective: Many U.S. emergency departments (EDs) lack access to stroke neurologists to support decision-making for thrombolytics and identification of thrombectomy-eligible patients. We outline a strategy to identify hospitals where telestroke might improve access and estimate potential gains in both the number of patients receiving reperfusion treatment and lives saved. Methods: We identified all EDs that provided ischemic stroke care for a Medicare beneficiary during 2018. We then excluded those with clear stroke expertise or with another ED with stroke expertise within 20 miles. At these EDs, we used annual ischemic stroke volumes and previously-derived risk ratios to quantify estimated marginal benefits (additional patients receiving reperfusion and additional lives saved) with the introduction of telestroke. Results: Among 4657 US EDs that provided stroke care in 2018, 1057 had limited stroke capabilities in their ED or within 20 miles. Of these 1057 EDs, 83.1% were in rural communities, and they cared for a median of 6 ischemic stroke patients per year. We estimate telestroke introduction to all 1057 would lead to 164 (95% CI 93-247) additional patients receiving reperfusion treatment and 90 (95% CI 2-180) additional lives saved annually (Figure). If only 263 EDs in the the top quartile of marginal benefit were targeted, this would capture over half of the estimated benefits. Conclusions: We estimate that approximately a quarter of U.S. EDs, primarily small rural EDs, would benefit most from new telestroke capacity. Our strategy may be used to improve stroke systems of care and maximize specialist access for the U.S. population.

Association of Ischemic Core Imaging Biomarkers With Post-Thrombectomy Clinical Outcomes in the MR CLEAN Registry.

Background: A considerable proportion of acute ischemic stroke patients treated with endovascular thrombectomy (EVT) are dead or severely disabled at 3 months despite successful reperfusion. Ischemic core imaging biomarkers may help to identify patients who are more likely to have a poor outcome after endovascular thrombectomy (EVT) despite successful reperfusion. We studied the association of CT perfusion-(CTP), CT angiography-(CTA), and non-contrast CT-(NCCT) based imaging markers with poor outcome in patients who underwent EVT in daily clinical practice.Methods: We included EVT-treated patients (July 2016–November 2017) with an anterior circulation occlusion from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry with available baseline CTP, CTA, and NCCT. We used multivariable binary and ordinal logistic regression to analyze the association of CTP ischemic core volume, CTA-Collateral Score (CTA-CS), and Alberta Stroke Program Early CT Score (ASPECTS) with poor outcome (modified Rankin Scale score (mRS) 5-6) and likelihood of having a lower score on the mRS at 90 days.Results: In 201 patients, median core volume was 13 (IQR 5-41) mL. Median ASPECTS was 9 (IQR 8-10). Most patients had grade 2 (83/201; 42%) or grade 3 (28/201; 14%) collaterals. CTP ischemic core volume was associated with poor outcome [aOR per 10 mL 1.02 (95%CI 1.01–1.04)] and lower likelihood of having a lower score on the mRS at 90 days [aOR per 10 mL 0.85 (95% CI 0.78–0.93)]. In multivariable analysis, neither CTA-CS nor ASPECTS were significantly associated with poor outcome or the likelihood of having a lower mRS.Conclusion: In our population of patients treated with EVT in daily clinical practice, CTP ischemic core volume is associated with poor outcome and lower likelihood of shift toward better outcome in contrast to either CTA-CS or ASPECTS.

Assessment of computed tomography perfusion RAPID estimated core volume accuracy in patients following thrombectomy

Background: Computed Tomography Perfusion (CTP) maps ischemic core volume (CV) and penumbra following a stroke; however, its accuracy in early symptom onset is not well studied. We compared the accuracy of CTP RAPID estimated CV with diffusion weighted imaging (DWI) infarct volume (IV) in patients following thrombectomy. Methods: Charts of anterior circulation large vessel occlusion post-thrombectomy cases with thrombolysis in cerebral infarction (TICI) 2b/3 reperfusion from 2017 to 2019 were reviewed. CTP time was dichotomized as 0-3 hours and ≥ 3 hours from the last known normal (LKN) cognition. The volumetric difference (VD), defined as DWI IV minus CTP CV, core volume overestimation (CVO), defined as CTP CV minus DWI IV and Alberta stroke programme early CT score (ASPECTS) were calculated. Large CV was defined as ≥ 50 ml CV. Modified Rankin Score (mRS) at 90 days were reviewed. We performed independent sample t-test and Spearman correlation coefficient test. Results: Total cases (n) were 61. In < 3 hours window from LKN (n = 27), the mean VD was 58.3 ± 0.1 ml (P = 0.990) and CVO (n = 11; 40.7%) was 39.6 ± 35.7 ml (P = 0.008). Mean large CV (n = 8) was 78.3 ± 25.4 ml with median ASPECTS of 8 [interquartile range (IQR) = 6.5-9.0] and median mRS at 90 days of 2 (IQR = 0.8-3.3). In ≥ 3 hours window from LKN (n = 34), CVO (n = 5) was uncommon and large CV had median mRS at 90 days of 5 (IQR = 4.0-6.0). Conclusion: CTP more frequently overestimates CV in patients who are < 3 hours from LKN. The treated patients with large CV in < 3 hours and > 3 hours had good and poor functional outcomes, respectively.

Diagnostic accuracy of using Alberta Stroke Program Early Computed Tomography Score on CT perfusion map to predict a target mismatch in patients with acute ischemic stroke.

To assess the diagnostic accuracy of using Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on CT perfusion (CTP) map to predict a volumetric target mismatch in patients with acute ischemic stroke (AIS). Three-hundred and seven AIS patients with an onset time within 24h or unclear onset time who underwent CTP evaluation for large vessel occlusion of anterior circulation were enrolled. CTP ASPECTS was evaluated on cerebral blood flow (CBF) and time-to-maximum (Tmax) colored maps, respectively. Automated perfusion analysis software was used to calculate the volumes of ischemic core (volumeCBF<30%) and tissue at risk (volumeTmax>6s). Target mismatch was defined as volumeCBF< 30%<70ml, volumemismatch≥15ml, and volumeTmax >6s/volume CBF< 30%≥1.8. Spearman correlation and receiver operating characteristic curves were used for statistical analyses. Strong correlations were found between CBF ASPECTS and volumeCBF<30%, and between Tmax ASPECTS and volumeTmax>6s for overall population (ρ=-0.872, -0.757) and late-arriving patients (ρ=-0.900, -0.789). Mismatch ASPECTS moderately correlated with mismatch volume for overall population (ρ=0.498) and late-arriving patients (ρ=0.407). A CBF ASPECTS≥5 optimally predicted an ischemic core volume<70ml in overall population (sensitivity, 94.4%; specificity, 80.4%) and late-arriving patients (sensitivity, 89.5%; specificity, 90.5%). A CBF ASPECTS≥6 combined with a Mismatch ASPECTS≥1 optimally identified a target mismatch in overall population (sensitivity, 84.5%; specificity, 77.0%) and late-arriving patients (sensitivity, 83.7%; specificity, 90.0%). CTP ASPECTS might be useful in predicting target mismatch derived from automated perfusion analysis software, and assisting in patient selection for endovascular therapy.

The Relationship of LDH and Hematological Parameters with Ischemic Volume and Prognosis in Cerebrovascular Disease.

To determine whether lactate dehydrogenase (LDH), platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR) values can be used as a prediction for their relationship with stroke volume (SV) and for in-hospital mortality in stroke patients in Emergency Department (ED). Analytical study. Balikesir University, Turkey from 24/03/2021 to 30/06/2021. Patients aged 18 years or older, diagnosed with stroke in ED, were included in the study. Stroke volumes were calculated from diffusion-weighted images (DWi) with 3D slicer software using image-based semi-automatic and manual segmentation methods. Of the 265 patients, 128 (48.3%) were males. SV was significantly higher in the non-survivor group than in the survivor group (p=0.007). NLR was significantly higher in the non-survivor group than in the survivor group (p=0.018). The ratios of NLR and SV stand out as practical parameters for the estimation of mortality, prognosis, and management of patients diagnosed with acute stroke. Taking into account, these parameters in the diagnosis process and prognosis management in EDs will provide convenience. Key Words: Ischemia, NLR, Stroke volume, Cerebrovasular accident, Prognosis.

Correlation between the CT Perfusion Parameter Values and Response to Recanalization in Patients with Acute Ischemic Stroke.

CT perfusion (CTP) provides various hemodynamic parameters. However, it is unclear which CTP parameters are useful in predicting clinical outcome in patients with acute ischemic stroke (AIS). Between February 2019 and June 2021, patients with anterior circulation large-vessel occlusion who achieved successful recanalization within 8 hours after stroke onset were included. The relative CTP parameter values analyzed by the reformulated singular value decomposition (SVD) method in the affected middle cerebral artery territories compared to those in the unaffected side were calculated. In addition, the ischemic core volume (ICV) was evaluated using a Bayesian Vitrea. The final infarct volume (FIV) was assessed by 24-hour MRI. The correlation between these CTP-derived values and clinical outcome was assessed. Forty-two patients were analyzed. Among the CTP-related parameters, the ICV, relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) showed a strong correlation with the FIV (ρ = 0.74, p <0.0001; ρ = -0.67, p <0.0001; and ρ = -0.66, p <0.0001, respectively). In multivariate analysis, rCBV, rMTT, and ICV were significantly associated with good functional outcome, which was defined as a modified Rankin Scale score ≤2 (OR, 6.87 [95% CI, 1.20-39.30], p = 0.0303; OR, 11.27 [95% CI, 0.97-130.94], p = 0.0269; and OR, 36.22 [95% CI, 2.78-471.18], p = 0.0061, respectively). Among the CTP parameters analyzed by the SVD deconvolution algorithms, rCBV and rMTT could be useful imaging predictors of response to recanalization in patients with AIS, and the performances of these variables were similar to that of the ICV calculated by the Bayesian Vitrea.

Considering "Trifecta" as a Single Outcome when Comparing Robotic With Open Partial Nephrectomy: A Mathematical Model of Volume Conservation and Systematic Review.

Trifecta represents a composite outcome reflecting the quality level of treatment in nephron sparing surgery. However, there is substantial heterogeneity concerning the criteria required for its fulfilment. The present study aimed to highlight the potential of a unified view for the different definitions of trifecta when comparing robotic and open approaches in partial nephrectomy. A systematic literature search was carried out for all relevant comparative studies published until April 2022. Trifecta definitions were clustered according to two criteria for postoperative renal function reduction. The first set as an upper limit the 10% decrease in the estimated glomerular filtration rate, while the second set as an upper limit 25 min of ischemia. To mathematically investigate the point of intersection between the above two groups, a suitable model of volume conservation equations was formulated. A total of 11 studies were investigated for their methodological features and grouped accordingly. The ischemic zone volume surrounding the tumor resection site emerged as the central parameter connecting the two main definitions. Specifically, for patients with solitary renal masses, a given change in the value of one parameter resulted in a fixed change in the value of the other. The two main definitions of the "trifecta outcome" extracted from the international literature represent the two sides of the same coin. Thus, trifecta achievement rates could be utilized by future studies as aggregate data to yield a quantitative estimate of the comparative effect between robotic and open approaches in partial nephrectomy procedures.

Preliminary Application of a Quantitative Collateral Assessment Method in Acute Ischemic Stroke Patients With Endovascular Treatments: A Single-Center Study.

Objectives: To develop an efficient and quantitative assessment of collateral circulation on time maximum intensity projection CT angiography (tMIP CTA) in patients with acute ischemic stroke (AIS).Methods: Eighty-one AIS patients who underwent one-stop CTA-CT perfusion (CTP) from February 2016 to October 2020 were retrospectively reviewed. Single-phase CTA (sCTA) and tMIP CTA were developed from CTP data. Ischemic core (IC) volume, ischemic penumbra volume, and mismatch ratio were calculated. The Tan scale was used for the qualitative evaluation of collateral based on sCTA and tMIP CTA. Quantitative collateral circulation (CCq) parameters were calculated semi-automatically with software by the ratio of the vascular volume (V) on both hemispheres, including tMIP CTA VCCq and sCTA VCCq. Spearman correlation analysis was used to analyze the correlation of collateral-related parameters with final infarct volume (FIV). ROC and multivariable regression analysis were calculated to compare the significance of the above parameters in clinical outcome evaluation. The analysis time of the observers was also compared.Results: tMIP CTA VCCq (r = 0.61, p < 0.01), IC volume (r = 0.66, p < 0.01), Tan score on tMIP CTA (r = 0.52, p < 0.01) and mismatch ratio (r = 0.60, p < 0.01) showed moderate negative correlations with FIV. tMIP CTA VCCq showed the best prognostic value for clinical outcome (AUC = 0.93, p < 0.001), and was an independent predictive factor of clinical outcome (OR = 0.14, p = 0.009). There was no difference in analysis time of tMIP CTA VCCq among observers (p = 0.079).Conclusion: The quantitative evaluation of collateral circulation on tMIP CTA is associated with clinical outcomes in AIS patients with endovascular treatments.

Comparison of Two Automated Computed Tomography Perfusion Applications to Predict the Final Infarct Volume After Thrombolysis in Cerebral Infarction 3 Recanalization.

Several automated computed tomography perfusion software applications have been developed to provide support in the definition of ischemic core and penumbra in acute ischemic stroke. However, the degree of interchangeability between software packages is not yet clear. Our study aimed to evaluate 2 commonly used automated perfusion software applications (Syngo.via and RAPID) for the indication of ischemic core with respect to the follow-up infarct volume (FIV) after successful recanalization and with consideration of the clinical impact. Retrospectively, 154 patients with large vessel occlusion of the middle cerebral artery or the internal carotid artery, who underwent endovascular therapy with a consequent Thrombolysis in Cerebral Infarction 3 result within 2 hours after computed tomography perfusion, were included. Computed tomography perfusion core volumes were assessed with both software applications with different thresholds for relative cerebral blood flow (rCBF). The results were compared with the FIV on computed tomography within 24 to 36 hours after recanalization. Bland-Altman was applied to display the levels of agreement and to evaluate systematic differences. Highest correlation between ischemic core volume and FIV without significant differences was found at a threshold of rCBF<38% for the RAPID software (r=0.89, P<0.001) and rCBF<25% for the Syngo software (r=0.87, P<0.001). Bland-Altman analysis revealed best agreement in these settings. In the vendor default settings (rCBF<30% for RAPID and rCBF<20% for Syngo) correlation between ischemic core volume and FIV was also high (RAPID: r=0.88, Syngo: r=0.86, P<0.001), but mean differences were significant (P<0.001). The risk of critical overestimation of the FIV was higher with rCBF<38% (RAPID) and rCBF<25% (Syngo) than in the default settings. By adjusting the rCBF thresholds, comparable results with reliable information on the FIV after complete recanalization can be obtained both with the RAPID and Syngo software. Keeping the software specific default settings means being more inclusive in patient selection, but forgo the highest possible accuracy in the estimation of the FIV.

Electroacupuncture of "Shuigou"(GV26) improves neurological function by promoting angioge-nesis and Shh signaling in ischemic cerebral tissue of rats with cerebral infarction

To observe the effect of electroacupuncture (EA) of "Shuigou" (GV26) on the activities of sonic hedgehog(Shh) signaling molecules (Shh, Ptch, Smo，Gli and Gli2) in ischemic brain tissues in rats with cerebral ischemia (CI), so as to explore its mechanisms underlying improvement of CI. Male Wistar rats were randomly divided into blank control group(n=10), sham operation group (n=90), model group(n=90) and EA group (n=90). The CI model was established by occlusion of the right middle cerebral artery (MCAO). According to the postoperative time points of MCAO, the later three groups were further divided into 1, 3, 6, 9, 12 and 24 h, and 3, 7 and 12 d subgroups, with 10 rats in each subgroup. EA (15 Hz, 2 mA) was applied to GV26 for 20 min. The 1 h to 24 h subgroups were treated immediately after modeling, the 3-12 d subgroups treated one time a day. The neurological severity score (NSS, 0 to 18 points) was used to evaluate the rats' neurological function, and TTC staining was employed to assess the cerebral ischemic volume (percentage of cerebral infarct volume, CIV). Western blot was employed to detect the expression of Shh, Ptch, Smo, Gli1 and Gli2 proteins in the ischemic cerebral tissue. Compared with the sham operation group, the NSS scores of the model group increased at all time points (P<0.01). The percentages of CIV of the model group from 3 h to 12 d were obviously higher than those of the sham operation group (P<0.01). The NSS scores at 3, 7 and 12 d and the percentages of CIV at 1, 3, 7 and 12 d after MCAO were significant lower in the EA group than in the model group (P<0.05). The protein expression levels of Shh from 12 h to 12 d (i.e. 12 h, 24 h, 3, 7 and 12 d), Ptch from 6 h to 12 d, Smo from 9 h to 12 d, Gli1 at 9 h, 12 h, and from 3 d to 12 d, Gli2 at 6, 9 and 12 h, and 3 d were significantly higher in the model group than in the sham operation group (P<0.05, P<0.01), while those of Shh at 3, 7 and 12 d, Ptch from 24 h to 7 d, Smo from 12 h to 7 d, Gli1 from 24 h to 7 d, Gli2 at 12 h, 3 and 7 d were significantly higher in the EA group than in the model group (P<0.05, P<0.01). No statistical significances were found between the sham operation and the blank control groups in all the indexes mentioned above (P>0.05). EA of GV26 can improve neurological function and reduce infarct volume in MCAO rats, which may be related to its function in up-regulating the activities of Shh signaling pathway in the ischemic cerebral tissues.

Cerebrovascular Collateral Integrity in Pediatric Large Vessel Occlusion: Analysis of the Save ChildS Study.

Robust cerebrovascular collaterals in adult patients with large vessel occlusion stroke have been associated with longer treatment windows, better recanalization rates, and improved outcomes, but the role of collaterals in pediatric stroke is not known. The primary aim was to determine whether favorable collaterals correlated with better radiographic and clinical outcomes in children with ischemic stroke who underwent thrombectomy. This study analyzed a subset of children enrolled in SaveChildS, a retrospective, multicenter, observational cohort study of 73 pediatric patients with stroke who underwent thrombectomy between 2000 and 2018 at 27 US and European centers. Included patients had baseline angiographic imaging and follow-up modified Rankin Scale scores available for review. Posterior circulation occlusions were excluded. Cerebrovascular collaterals were graded on acute neuroimaging by 2 blinded neuroradiologists according to the Tan collateral score, in which favorable collaterals are defined as >50% filling and unfavorable collaterals as <50% filling distal to the occluded vessel. Collateral status was correlated with clinical and neuroimaging characteristics and outcomes. Between-group comparisons were performed with the Wilcoxon rank-sum test for continuous variables or Fisher exact test for binary variables. Thirty-three children (mean age 10.9 [SD ±4.9]) years were included; 14 (42.4%) had favorable collaterals. Median final stroke volume as a percent of total brain volume (TBV) was significantly lower in patients with favorable collaterals (1.35% [interquartile range (IQR) 1.14%-3.76%] vs 7.86% [IQR 1.54%-11.07%], p = 0.049). Collateral status did not correlate with clinical outcome, infarct growth, or final Alberta Stroke Program Early CT Score (ASPECTS) in our cohort. Patients with favorable collaterals had higher baseline ASPECTS (7 [IQR 6-8] vs 5.5 [4-6], p = 0.006), smaller baseline ischemic volume (1.57% TBV [IQR 1.09%-2.29%] vs 3.42% TBV [IQR 1.26%-5.33%], p = 0.035), and slower early infarct growth rate (2.4 mL/h [IQR 1.5-5.1 mL/h] vs 10.4 mL/h [IQR 3.0-30.7 mL/h], p = 0.028). Favorable collaterals were associated with smaller final stroke burden and slower early infarct growth rate but not with better clinical outcome in our study. Prospective studies are needed to determine the impact of collaterals in childhood stroke. This study provides Class II evidence that in children with ischemic stroke undergoing thrombectomy, favorable collaterals were associated with improved radiographic outcomes but not with better clinical outcomes.

Combined In-silico and Machine Learning Approaches Toward Predicting Arrhythmic Risk in Post-infarction Patients.

Background: Remodeling due to myocardial infarction (MI) significantly increases patient arrhythmic risk. Simulations using patient-specific models have shown promise in predicting personalized risk for arrhythmia. However, these are computationally- and time- intensive, hindering translation to clinical practice. Classical machine learning (ML) algorithms (such as K-nearest neighbors, Gaussian support vector machines, and decision trees) as well as neural network techniques, shown to increase prediction accuracy, can be used to predict occurrence of arrhythmia as predicted by simulations based solely on infarct and ventricular geometry. We present an initial combined image-based patient-specific in silico and machine learning methodology to assess risk for dangerous arrhythmia in post-infarct patients. Furthermore, we aim to demonstrate that simulation-supported data augmentation improves prediction models, combining patient data, computational simulation, and advanced statistical modeling, improving overall accuracy for arrhythmia risk assessment.Methods: MRI-based computational models were constructed from 30 patients 5 days post-MI (the “baseline” population). In order to assess the utility biophysical model-supported data augmentation for improving arrhythmia prediction, we augmented the virtual baseline patient population. Each patient ventricular and ischemic geometry in the baseline population was used to create a subfamily of geometric models, resulting in an expanded set of patient models (the “augmented” population). Arrhythmia induction was attempted via programmed stimulation at 17 sites for each virtual patient corresponding to AHA LV segments and simulation outcome, “arrhythmia,” or “no-arrhythmia,” were used as ground truth for subsequent statistical prediction (machine learning, ML) models. For each patient geometric model, we measured and used choice data features: the myocardial volume and ischemic volume, as well as the segment-specific myocardial volume and ischemia percentage, as input to ML algorithms. For classical ML techniques (ML), we trained k-nearest neighbors, support vector machine, logistic regression, xgboost, and decision tree models to predict the simulation outcome from these geometric features alone. To explore neural network ML techniques, we trained both a three - and a four-hidden layer multilayer perceptron feed forward neural networks (NN), again predicting simulation outcomes from these geometric features alone. ML and NN models were trained on 70% of randomly selected segments and the remaining 30% was used for validation for both baseline and augmented populations.Results: Stimulation in the baseline population (30 patient models) resulted in reentry in 21.8% of sites tested; in the augmented population (129 total patient models) reentry occurred in 13.0% of sites tested. ML and NN models ranged in mean accuracy from 0.83 to 0.86 for the baseline population, improving to 0.88 to 0.89 in all cases.Conclusion: Machine learning techniques, combined with patient-specific, image-based computational simulations, can provide key clinical insights with high accuracy rapidly and efficiently. In the case of sparse or missing patient data, simulation-supported data augmentation can be employed to further improve predictive results for patient benefit. This work paves the way for using data-driven simulations for prediction of dangerous arrhythmia in MI patients.

Symmetric CTA Collaterals Identify Patients with Slow-progressing Stroke Likely to Benefit from Late Thrombectomy.

Background Understanding ischemic core growth rate (IGR) is key in identifying patients with slow-progressing large vessel occlusion (LVO) stroke who may benefit from delayed endovascular thrombectomy (EVT). Purpose To evaluate whether symmetric collateral pattern at CT angiography (CTA) can help to identify patients with low IGR and small 24-hour diffusion-weighted MRI ischemic core volume in patients with LVO not treated with reperfusion therapies. Materials and Methods In this secondary analysis of clinical trial data from before EVT became standard of care from January 2007 to June 2009, patients with anterior proximal LVO not treated with reperfusion therapies were evaluated. All patients underwent admission CTA and at least three MRI examinations at four time points over 48 hours. Arterial phase CTA collaterals at presentation were categorized as symmetric, malignant, or other. Diffusion-weighted MRI ischemic core volume and IGR at multiple time points were determined. The IGR at presentation was defined as follows: (ischemic core volume in cubic centimeters)/(time since stroke symptom onset in hours). Multivariable analyses and receiver operator characteristic analyses were used. Results This study evaluated 31 patients (median age, 71 years; interquartile range, 61-81 years; 19 men) with median National Institutes of Health Stroke Scale (NIHSS) score of 13. Collaterals were symmetric (45%; 14 of 31), malignant (13%; four of 31), or other (42%; 13 of 31). Median ischemic core volume was different between collateral patterns at all time points. Presentation was as follows: symmetric, 16 cm3; other, 69 cm3; and malignant, 104 cm3 (P < .001). At 24 hours, median ischemic core volumes were as follows: symmetric, 28 cm3; other, 156 cm3; and malignant, 176 cm3 (P < .001). Median IGR was also different, and most pronounced at presentation: symmetric, 4 cm3 per hour; other, 17 cm3 per hour; and malignant, 20 cm3 per hour (P < .001). After multivariable adjustment, independent determinants of higher presentation IGR included only higher NIHSS (parameter estimate [β = 0.20; 95% CI: 0.05, 0.36; P = .008) and worse collaterals (β = -2.90; 95% CI: -4.31, -1.50; P < .001). The only independent determinant of 24-hour IGR was worse collaterals (β = -2.03; 95% CI: -3.28, -0.78; P = .001). Symmetric collaterals had sensitivity of 87% (13 of 15) and specificity of 94% (15 of 16) for 24-hour ischemic core volume less than 50 cm3 (area under the receiver operating characteristic curve, 0.92; 95% CI: 0.81, 1.00; P < .001). Conclusion In patients with large vessel occlusion not treated with reperfusion therapies, symmetric collateral pattern at CT angiography was common and highly specific for low ischemic core growth rate and small 24-hour ischemic core volume as assessed at diffusion-weighted MRI. After further outcome studies, collateral status at presentation may prove useful in triage for endovascular thrombectomy, especially when MRI and CT perfusion are unavailable. Clinical trial registration no. NCT00414726. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Messina in this issue.

Endovascular Thrombectomy Versus Medical Therapy Alone in Patients With Large Core Based on Computed Tomography Perfusion

Background Patients presenting with large vessel occlusion and a large ischemic core (&gt;50 mL) have been consistently undersampled in the major endovascular thrombectomy (ET) trials. As such, equipoise exists as to whether ET is associated with improved outcomes over medical therapy alone in this population. Methods Prospectively collected databases from 4 US centers were reviewed to identify patients with baseline ischemic cores &gt;50 mL based on computed tomography perfusion imaging using RAPID software (iSchemaView), who were treated with ET or medical therapy alone between January 2014 and October 2019. Baseline characteristics, procedural information, and clinical follow‐up data were collected. A matched‐control comparison of these patients was performed. Results A total of 167 patients were included, of whom 92 received medical therapy alone and 75 underwent ET. Seventy‐five pairs were obtained after matching for baseline ischemic core volume, National Institutes of Health Stroke Scale score, and age. Rate of 90‐day good outcome was significantly higher in the ET arm (28.4% versus 4.9%, P =0.002). In univariate analysis of ET patients, the rate of good outcome was significantly higher among patients treated within &lt;6 hours compared with ≥6 hours (44.2% versus 17.4%, P =0.02). Predictors of good outcome included age ( P =0.008), ischemic core volume ( P =0.01), and time from last known well to groin puncture ( P =0.004). Conclusions ET was associated with improved outcomes in patients with large ischemic core based on computed tomography perfusion. This association was more pronounced in patients who present early (&lt;6 hours from last seen well) with an adequate target mismatch. These results may guide the practice until data from ongoing randomized trials become available.

Regulation of heme oxygenase-1 (HO-1), antioxidant, mediated with autophagy in trophoblasts

Acute myocardial ischemia has several characteristic ECG findings, including clinically detectable ST-segment deviations. However, the sensitivity and specificity of diagnosis based on ST-segment changes are low. Furthermore, ST-segment deviations have been shown to be transient and spontaneously recover without any indication the ischemic event has subsided.Assess the transient recovery of ST-segment deviations on remote recording electrodes during a partial occlusion cardiac stress test and compare them to intramyocardial ST-segment deviations.We used a previously validated porcine experimental model of acute myocardial ischemia with controllable ischemic load and simultaneous electrical measurements within the heart wall, on the epicardial surface, and on the torso surface. Simulated cardiac stress tests were induced by occluding a coronary artery while simultaneously pacing rapidly or infusing dobutamine to stimulate cardiac function. Postexperimental imaging created anatomical models for data visualization and quantification. Markers of ischemia were identified as deviations in the potentials measured at 40% of the ST-segment. Intramural cardiac conduction speed was also determined using the inverse gradient method. We assessed changes in intramyocardial ischemic volume proportion, conduction speed, clinical presence of ischemia on remote recording arrays, and regional changes to intramyocardial ischemia. We defined the peak deviation response time as the time interval after onset of ischemia at which maximum ST-segment deviation was achieved, and ST-recovery time was the interval when ST deviation returned to below thresholded of ST elevation.In both epicardial and torso recordings, the peak ST-segment deviation response time was 4.9±1.1 min and the ST-recovery time was approximately 7.9±2.5 min, both well before the termination of the ischemic stress. At peak response time, conduction speed was reduced by 50% and returned to near baseline at ST-recovery. The overall ischemic volume proportion initially increased, on average, to 37% at peak response time; however, it recovered to only 30% at the ST-recovery time. By contrast, the subepicardial region of the myocardial wall showed 40% ischemic volume at peak response time and recovered much more strongly to 25% as epicardial ST-segment deviations returned to baseline.Our data show that remote ischemic signal recovery correlates with a recovery of the subepicardial myocardium, whereas subendocardial ischemic development persists.