Final Infarct Volume Research Articles

Nerinetide Reduces Early Infarct Growth Among Stroke Patients Undergoing EVT Without Intravenous Alteplase

Background Nerinetide treatment was associated with better clinical outcomes among patients with stroke undergoing endovascular treatment who were not treated with concurrent alteplase in the randomized ESCAPE‐NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) trial. In patients receiving alteplase, no such effect was seen due to an inactivation of nerinetide by plasmin – the product of tissue plasminogen activation. We hypothesized that improved outcomes in the no‐alteplase patients were associated with reduced infarct growth, a radiological correlate of improved stroke outcomes. Methods Data are from the no‐alteplase stratum of the ESCAPE‐NA1 trial. Patients who underwent computer tomography perfusion (CTP) as part of routine clinical care were included. Admission CTP source data were processed using RAPID software. Infarct core at baseline was defined as areas of relative cerebral blood flow <30% on CTP. Final infarct volume was determined via manual segmentation on 24‐hour CT or magnetic resonance diffusion‐weighted imaging. We compared infarct growth (defined as 24‐hour infarct volume minus CTP‐estimated baseline infarct core) among no‐alteplase patients treated with versus without nerinetide. Results CTP maps were available in 413/1105 (37%) ESCAPE‐NA1 participants. Of these, 179 (43%) were treated without alteplase, 79 (44%) received nerinetide, and 100 (56%) received placebo. Prior administration of alteplase modified the treatment effect of nerinetide on infarct growth in a multivariable model that was adjusted for age, sex, baseline infarct core volume, expanded Thrombolysis in Cerebral Infarction score, and time from baseline imaging to reperfusion ( P = 0.005). In no‐alteplase patients, infarct growth was larger over 24 hours in the control (34.9 mL interquartile range[IQR] [6.8–127]) versus nerinetide (19.6 mL IQR [1.7–49.1]; P = 0.008) groups. In patients who received prior alteplase (n = 234), there was no difference in infarct growth between those who received placebo versus nerinetide (10.5 mL IQR [−1.3 to 67.4] versus 12.8 mL IQR [0.35–55.5]; P = 0.62). Conclusion Nerinetide was associated with decreased infarct growth in acute ischemic stroke patients undergoing thrombectomy without concurrent alteplase in the ESCAPE‐NA1 trial.

Abstract WMP89: Reperfusion Pattern as a Predictor of Final Infarct Growth in Patients With Anterior Large Vessel Occlusion Ischemic Stroke

Aim: The first pass effect (FPE) and complete sudden recanalization (cSR) have been identified as an indicator of favorable clinical outcome. We aimed to compare final infarct volume (FIV) according to different reperfusion pattern. Methods: We included consecutive patients admitted with an anterior LVO stroke (intracranial internal carotid artery, MCA-M1) who underwent endovascular treatment between January 2018 and April 2022. Patients with partial or no-reperfusion (eTICI 0-2b) were excluded. Final complete reperfusion (TICI 2c-3) was categorized as achieved at first pass (FPE) or in subsequent passes as sudden (cSR: from TICI 0-1 to TICI 2c-3 in a single pass) or progressive (PR: interim partial recanalization). FIV was quantified using an automatic segmentation tool (Methinks AI) on 24-hour NCCT. Aggregated infarct distribution heatmaps were generated to compare FIV distribution. Results: Of 316 consecutive patients, complete reperfusion was achieved in 202 patients (63.9%). Reperfusion patterns were as follows: FPE (109/202, 54.0%), cSR (28/202, 13.9%) and PR (65/202, 32.1%). The mean FIV was 28.1mL (95%CI 19.1-37.1), 49.5mL (95%CI 18.8-80.2) and 58.4mL (95% CI 37.6-79.2) in FPE patients, cSR and PR patients, respectively (p=0.014). After adjusting for confounders, FPE and cSR patterns were independently associated with a reduced FIV (FPE: -61.7%, 95%CI -77.2% to -35.8%, p<0.001; cSR: -39.7%, 95%CI -63.8% to 0.6%, p=0.05). The rate of excellent clinical outcome (mRS 90d 0-1) was higher in FPE (36.1%) and cSR (35.7%) groups compared to the PR group (20.3%, p=0.081). Conclusion: Improved clinical outcomes in patients with FPE and cSR patterns seem to be influenced by reduced infarct volume in a stepwise manner (FIV FPE<cSR<PR). PR may reflect clot fragmentation and embolization, contributing to infarct growth and worse outcomes. Reperfusion patterns should be explored for selecting target populations for adjunctive neuroprotective therapies during EVT.

Abstract TP206: Transcranial Doppler Markers of Increased Microvascular Resistance After Successful Endovascular Revascularization Are Associated With Larger Infarct Volumes

Background: Markers of increased microvascular resistance on Transcranial Doppler (TCD) obtained shortly after successful endovascular therapy (EVT) in patients with large-vessel occlusion (LVO) stroke have been associated with unfavorable outcomes. We aim to investigate whether post-EVT pulsatility index (PI) correlates with final infarct volume in this population. Methods: We analyzed consecutive anterior circulation LVO patients who underwent successful EVT (mTICI 2c-3) from 2012 to 2022. Patients with available TCD within 48 hours of EVT and brain MRI during admission were included. The TCD-derived PI was obtained from the ipsilateral middle cerebral artery. The ABC/2 method was used to estimate the final infarct volume in mL on MRI diffusion-weighted imaging. Pearson correlation and adjusted linear regression analysis were used to investigate the relationship between post-EVT PI and final infarct volume. Linear regression analysis was adjusted for age, NIHSS, and ASPECTS. Results: Out of 155 LVO patients with successful EVT during the study period, 40 were included in the analysis (mean age, 69 ± 16.7 years; 57% female; median NIHSS 15 (IQR 10); and median ASPECTS 9 (IQR, 2)). The median time from EVT to TCD and EVT to MRI was 21 hours (IQR, 17 hours) and 41 hours (IQR, 33 hours), respectively. Post EVT PI displayed a positive moderate correlation with final infarct volume (r=0.39, p<0.01; Figure 1). Larger PI values were independently associated with larger infarct volumes (β = 42.2 mL, 95% CI 37.0 - 47.5 mL). Conclusion: TCD-derived PI shortly after EVT correlated with final infarct volume in successfully revascularized LVO patients. TCD may serve as a valuable tool to identify those at risk for infarct progression and reveal potential therapeutic targets to maximize EVT benefit in this population.

Abstract TP137: Quantitative Assessment of No-Reflow Zones Predicts Infarct Growth and Functional Outcome

Background: Technically successful but futile angiographic reperfusion (AR) has been reported in 20-50% of acute ischemic stroke patients undergoing endovascular treatment. Persistent occlusions at distal arteries and ischemic capillary bed (i.e. no-reflow phenomenon) have been shown as one of the culprits resulting in infarct growth and poor functional outcome despite thrombectomy. We aimed to quantify the residual no-reflow perfusion in patients who underwent successful AR and assess its effect on infarct growth and functional outcome. Methods: In this retrospective single institution study, patients with anterior circulation LVO, successful AR (TICI ≥ 2b), and pre and posttreatment MR perfusion (MRP) were included. Hypoperfusion volume along the affected territory was calculated on Tmax maps using thresholds >2, 4, and 6 sec on both pre and posttreatment MRP scans. Infarct growth was calculated by subtracting baseline ischemic core from the final infarct volume. A total of 12 variables including demographic, clinical, and Tmax thresholds were evaluated to predict infarct growth and functional outcome (90day mRS). Results: A total of 50 patients met inclusion criteria, of whom 19 had infarct growth ≥ 10 mL while 31 had < 10 mL infarct growth. Functional outcome was poor in 27 patients (90day mRS>2). Univariate analysis showed no statistical significance (p>0.05) for either of the baseline Tmax volumes in prediction of infarct growth or functional outcome. Posttreatment hypoperfusion (no-reflow volumes) was significant for prediction of infarct growth at all Tmax volumes (p=0.048, 0.023, 0.021 for Tmax > 2, 4, and 6 sec respectively). Volume of Tmax >6sec was significant (p=0.044) for prediction of poor functional outcome. Multivariate logistic regression analysis revealed Tmax >6 sec residual hypoperfusion volume as an independent variable for prediction of infarct growth ≥ 10 mL (p=0.002) and functional outcome (p=0.007). Conclusion: In conclusion, no-reflow zones following successful AR were associated with infarct growth at all Tmax thresholds, however volume of residual Tmax > 6 sec was independently associated with infarct growth > 10 ml and poor functional outcome.

Abstract 27: A Novel Adjuvant Strategy After Endovascular Therapy: Arterial Glyceryl Trinitrate in Acute Ischemic Stroke for Neuroprotection (AGAIN)

Introduction: Although mechanical thrombectomy (MT) demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. The protective effect of NO donors has been shown to prevent ischemia-reperfusion injury through reduction of reactive oxygen species formation in cardiovascular studies. Glyceryl Trinitrate (GTN), a Food and Drug Administration-approved vasodilator, is one of the widely used exogenous NO donors used in the clinic and has been trialed for neuroprotection in AIS without successful clinical translation. The recent advances in MT for AIS have paved the way for promising new opportunities to supplementary neuroprotective therapies to patients after reperfusion. This study evaluated the safety, feasibility, and preliminary efficacy of intra-arterial administration of GTN after MT for neuroprotection. Methods: This is a prospective randomized controlled study (ID: ChiCTR2100045254). Eligible patients were randomized to receive 800μg GTN or same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (sICH), while secondary outcomes included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NOx). Results: A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. No significant difference was observed in mortality or rates of neurological deterioration and other complications. Favorable trends for both functional independence (mRS 0-2, 75.0% vs. 65.0%) at 90 days and reduction in final infarct volume (33.2 vs. 38.9 ml) have been observed in GTN group, although they did not reach the significant levels. Moreover, the concentration of blood NO X was increased (p<0.05) at 2 hours after GTN administration (26.2 vs 18.0 μmol/l). Conclusion: The AGAIN study suggests intra-arterial administration of GTN post MT is safe and feasible in AIS patient. The discernible positive trends may be due to the raised NO X levels, which potentially highlight the mechanistic reinforcement for these observed benefits.

Abstract WMP62: Infarct Core Volume Estimation on Non-Contrast Computed Tomography in Late Window Patients Using a Machine Learning Algorithm Software

Introduction: A simplified patient selection paradigm can reduce time to reperfusion and widen the eligibility of large vessel occlusions (LVO) for endovascular therapy (EVT). We developed and externally validated a machine learning (ML) algorithm to estimate infarct core volume (ICV) on non-contrast computed tomography (NCCT) in anterior circulation LVOs presenting in the late window (≥ 6-24 hours). Methods: LVOs from prospective databases in US and Spain were included. For development, 2858 stroke activations with NCCT/CT angiography[s1] were included. For validation, consecutive LVOs with admission NCCT/CT perfusion (CTP), post-EVT diffusion-weighted imaging (DWI) within 24 hours, and mTICI ≥2b were included. Neuroimaging experts adjudicated ASPECTS on NCCT and final infarct volume (FIV) on DWI (ground truth). ML algorithm was trained using UNet architecture with ResNet 34 encoder to identify ICV on NCCT. Estimated ICVs (algorithm, CTP [<30% cerebral blood flow], and ASPECTS) were compared to ground truth using correlations (intraclass correlation coefficient [ICC] and Spearman’s [r s ]) and Bland Altman plots. Superiority tests between correlations (to compare modalities) and subgroup analyses were performed. Results: 98 patients (median age, 70 years; IQR:59-80; 51% females) were included for validation. Median time to first imaging was 11.4 hours (IQR:9.0-14.7). Correlations (Table) were moderate with the ML algorithm (ICC:0.59) and poor with ASPECTS (r s :-0.31) and CTP ICV (ICC:0.42;). Bland Altman plots showed that ML algorithm had a mean difference closest to zero (-34.2 mL) while the CTP ICV had a larger mean difference (-45.8 mL). Superiority tests (Table), [s2] ML algorithm correlation showed superiority to both the CTP ( p sup =.018) and ASPECTS ( p sup =.003) correlations. Conclusion: On late window patients, estimation of ICV on NCCT with the ML algorithm seems to be superior to CTP and ASPECTS. Further prospective studies are needed.

Abstract WP125: The Presence of a Ghost Infarct Core is Associated With Fast Core Growth in Acute Ischemic Stroke

Introduction: The overestimation of ischemic core volume by computed tomography perfusion (CTP) is a critical concern in the selection of candidates for reperfusion therapy. This phenomenon is termed a ghost infarct core (GIC). Core growth rate has emerged as an indicator of ischemic severity. The aim of the present study was to elucidate the association between the presence of a GIC and the core growth rate. Methods: Consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent mechanical thrombectomy in our institute from March 2017 to July 2022 were enrolled. The initial ischemic core was measured by pretreatment CTP, and the final infarct volume (FIV) was measured by diffusion-weighted imaging. A GIC was defined by initial ischemic core volume minus FIV >10 mL. The core growth rate was calculated by dividing the initial ischemic core volume by time from stroke onset to CTP acquisition. Univariable analysis and a multivariable logistic regression model were used to evaluate the association between GIC-positive and the core growth rate; complete recanalization, onset to imaging time, and imaging to recanalization time were included as covariates. Results: Ninety-one patients were included in the study. Of these, 21 patients (23.1%) were GIC-positive. The GIC-positive group had higher core growth rate (14.2 [2.6-46.7] vs 4.8 [1.6-17.1] mL/h, p=0.021) and complete recanalization (n=15 (71.4%) vs 29 (41.4%), p=0.016) compared to the GIC-negative group. On receiver operating characteristic curve analysis, the optimal cutoff point of the core growth rate to predict GIC-positive was 22 mL/h (sensitivity, 0.48; specificity, 0.85; area under the curve, 0.67). Multivariable logistic regression analysis showed that core growth rate ≥22 mL/h (OR 6.44, 95% CI [1.59-26.10], p=0.006) and complete recanalization (OR 3.72, 95% CI [1.14-12.08], p=0.022) were independent predictors of GIC-positive. Conclusions: A GIC was associated with fast core growth in acute ischemic stroke. Overestimation of the initial ischemic core may be determined by core growth speed, not a clock time.

Abstract TP141: Understanding Potential Limitations of CTP Imaging in Early Window Large Vessel Anterior Circulation Strokes

Background: Computerized tomography perfusion (CTP) imaging serves as a valuable modality for the assessment of individuals with a large vessel anterior circulation stroke. Current literature proposes that employing CTP imaging in patients within the initial time frame of less than 8 hours, may lead to an overestimation of the projected infarct core, specifically when utilizing cerebral blood flow (CBF) less than 30%. The hypoperfusion intensity ratio (HIR) may result in overestimation. We sought to further investigate the interplay of CTP parameters in patients presenting within 8 hours of symptom onset of stroke, to assess the accuracy of core infarct estimation. Methods: A retrospective cohort study analyzing patients with large vessel anterior occlusion (LVAO) who underwent CTP and mechanical thrombectomy within 24 hours of symptom onset between January 2017 to December 2022. RAPID software estimates the infarct core using CBF <30%. DWI-MRI determined final infarct volume. A multivariate logistic regression model was employed to assess the impact of HIR and reperfusion success on outcomes. Results: Ninety-seven patients were identified within an 8-hour time window. CBF<30% overestimated core infarct volume (mL) in 22 patients (22.6%) with a mean of 15.72 (range 4.4-37.7) and a median of 22.85. Of these, 2 patients experienced poor reperfusion (9%) while 20 had successful reperfusion (91%). Of the patients who did have successful reperfusion, an average of 13.57mL core was overpredicted compared to the DWI volumes. A multivariate logistic regression model adjusting for degree of reperfusion, administration of thrombolytic, and time from symptom onset showed that HIR strongly predicted the probability of core estimation with an odds ratio of 148.6, 95% CI [21.0-1048.8], (p<0.001). Conclusion: HIR exceeding 0.4 demonstrates a predictive capacity for core overestimation in early-window LVAO patients. Our study affirms this observation with statistical significance. The integration of HIR as a parameter for early-window LVAO core computation shows promise, and has potential ramifications for patient selection for thrombectomy. In this context, utilization of further databases is imperative for validation and broader application of HIR.

The benefit of favorable venous outflow profile is mediated through reduced microvascular dysfunction in acute ischemic stroke.

Venous outflow (VO) is emerging as a marker of microvascular integrity in acute ischemic stroke. Using hemorrhagic transformation (HT) and infarct growth as mediators, we tested whether a favorable VO profile benefited functional outcome by reducing consequences of microvascular dysfunction. Patients receiving thrombectomy in three comprehensive stroke centers due to acute anterior circulation occlusion were included. VO was assessed semi-quantitatively by the opacification of ipsilateral vein of Labbé, Trolard and superficial middle cerebral vein. HT was graded on follow-up CT. Infarct growth volume (IGV) was the difference of final infarct volume and baseline core volume. The association of VO and functional independence (90-day modified Rankin Scale ⩽ 2) was examined by logistic regression. Mediation analysis was performed among VO, HT or IGV, and functional outcome in patients with or without recanalization, respectively. In 242 patients analyzed, VO was strongly correlated with functional independence and VO ⩾ 4 was defined favorable. In 175 patients recanalized, favorable VO was associated with a reduced risk of HT (OR = 0.82, 95% CI 0.71-0.95, p = 0.008), which accounted for 13.1% of the association between VO and favorable outcome. In 67 patients without recanalization, favorable VO was associated with decreased IGV (β = -0.07, 95% CI -0.11 to -0.02, p = 0.007). The association of favorable VO and functional independence was no longer significant (aOR = 4.84, 95% CI 0.87-38.87, p = 0.089) after including IGV in the model, suggesting a complete mediation. In patients with acute anterior large vessel occlusion, the clinical benefit of VO may be mediated through reduced microvascular dysfunction.

Overestimation of ischemic core on baseline MRI in acute stroke.

In patients with acute ischemic stroke (AIS), overestimation of ischemic core on MRI-DWI has been described primarily in regions with milder reduced diffusion. We aimed to assess the possibility of ischemic core overestimation on pretreatment MRI despite using more restricted reduced diffusion (apparent diffusion coefficient (ADC) ≤620 × 10-6 mm2/s) in AIS patients with successful reperfusion. In this retrospective single institutional study, AIS patients who had pretreatment MRI underwent successful reperfusion and had follow-up MRI to determine the final infarct volume were reviewed. Pretreatment ischemic core and final infarction volumes were calculated. Ghost core was defined as overestimation of final infarct volume by baseline MRI of >10 mL. Baseline clinical, demographic, and treatment-related factors in this cohort were reviewed. A total of 6/156 (3.8%) patients had overestimated ischemic core volume on baseline MRI, with mean overestimation of 65.6 mL. Three out of six patients had pretreatment ischemic core estimation of >70 mL, while the final infarct volume was <70 mL. All six patients had last known well-to-imaging <120 min, median (IQR): 65 (53-81) minutes. Overestimation of ischemic core, known as ghost core, is rare using severe ADC threshold (≤620 × 10-6 mm2/s), but it does occur in nearly 1 of every 25 patients, confined to hyperacute patients imaged within 120 min of symptom onset. Awareness of this phenomenon carries implications for treatment and trial enrollment.

Automated detection of early signs of irreversible ischemic change on CTA source images in patients with large vessel occlusion.

To create and validate an automated pipeline for detection of early signs of irreversible ischemic change from admission CTA in patients with large vessel occlusion (LVO) stroke. We retrospectively included 368 patients for training and 143 for external validation. All patients had anterior circulation LVO stroke, endovascular therapy with successful reperfusion, and follow-up diffusion-weighted imaging (DWI). We devised a pipeline to automatically segment Alberta Stroke Program Early CT Score (ASPECTS) regions and extracted their relative Hounsfield unit (rHU) values. We determined the optimal rHU cut points for prediction of final infarction in each ASPECT region, performed 10-fold cross-validation in the training set, and measured the performance via external validation in patients from another institute. We compared the model with an expert neuroradiologist for prediction of final infarct volume and poor functional outcome. We achieved a mean area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of 0.69±0.13, 0.69±0.09, 0.61±0.23, and 0.72±0.11 across all regions and folds in cross-validation. In the external validation cohort, we achieved a median [interquartile] AUC, accuracy, sensitivity, and specificity of 0.71 [0.68-0.72], 0.70 [0.68-0.73], 0.55 [0.50-0.63], and 0.74 [0.73-0.77], respectively. The rHU-based ASPECTS showed significant correlation with DWI-based ASPECTS (rS = 0.39, p<0.001) and final infarct volume (rS = -0.36, p<0.001). The AUC for predicting poor functional outcome was 0.66 (95%CI: 0.57-0.75). The predictive capabilities of rHU-based ASPECTS were not significantly different from the neuroradiologist's visual ASPECTS for either final infarct volume or functional outcome. Our study demonstrates the feasibility of an automated pipeline and predictive model based on relative HU attenuation of ASPECTS regions on baseline CTA and its non-inferior performance in predicting final infarction on post-stroke DWI compared to an expert human reader.

Factors influencing the reliability of a CT angiography-based deep learning method for infarct volume estimation.

CT angiography (CTA)-based machine learning methods for infarct volume estimation have shown a tendency to overestimate infarct core and final infarct volumes (FIV). Our aim was to assess factors influencing the reliability of these methods. The effect of collateral circulation on the correlation between convolutional neural network (CNN) estimations and FIV was assessed based on the Miteff system and hypoperfusion intensity ratio (HIR) in 121 patients with anterior circulation acute ischaemic stroke using Pearson correlation coefficients and median volumes. Correlation was also assessed between successful and futile thrombectomies. The timing of individual CTAs in relation to CTP studies was analysed. The strength of correlation between CNN estimated volumes and FIV did not change significantly depending on collateral status as assessed with the Miteff system or HIR, being poor to moderate (r = 0.09-0.50). The strongest correlation was found in patients with futile thrombectomies (r = 0.61). Median CNN estimates showed a trend for overestimation compared to FIVs. CTA was acquired in the mid arterial phase in virtually all patients (120/121). This study showed no effect of collateral status on the reliability of the CNN and best correlation was found in patients with futile thrombectomies. CTA timing in the mid arterial phase in virtually all patients can explain infarct volume overestimation. CTA timing seems to be the most important factor influencing the reliability of current CTA-based machine learning methods, emphasizing the need for CTA protocol optimization for infarct core estimation.

Severely Hypoperfused Brain Tissue Correlates with Final Infarct Volume Despite Recanalization in DMVO Stroke.

We sought to assess whether there were any parameter(s) on baseline computed-tomography-perfusion (CTP) strongly correlating with final-infarct-volume, and infarct volume progression after endovascular recanalization of acute ischemic stroke (AIS) with primary distal, medium vessel occlusion (DMVO). We performed a retrospective analysis of consecutive AIS patients who were successfully recanalized by thrombectomy for DMVO. By comparing baseline CTP and follow-up MRI, we evaluated the correlation between baseline infarct and hypoperfusion volumes, and final infarct volume and infarct volume progression. We also examined their effect on good clinical outcome at 3 months (defined as an mRS score of 0 to 2). Between January 2018 and January 2021, 38 patients met the inclusion criteria (76% [29/38] female, median age 75 [66-86] years). Median final infarct volume and infarct volume progression were 8.4 mL [IQR: 5.2-44.4] and 7.2 mL [IQR: 4.3-29.1] respectively. TMax > 10 sec volume was strongly correlated with both (r = 0.831 and r = 0.771 respectively, p < 0.0001), as well as with good clinical outcome (-0.5, p = 0.001). A higher baseline TMax > 10 sec volume increased the probability of a higher final-infarct-volume (r2 = 0.690, coefficient = 0.83 [0.64-1.00], p < 0.0001), whereas it decreased the probability of good clinical outcome at 3 months (odds ratio = -0.67 [-1.17 to -0.18], p = 0.008). TMax > 10 sec volume on baseline CTP correlates strongly with final infarct volume as well as with clinical outcome after mechanical thrombectomy for an AIS with DMVO.

Association between intraprocedural drops in blood pressure and infarct growth rate patterns after acute large-vessel occlusions

BackgroundInfarct growth rate (IGR) differs among patients with acute ischemic stroke due to large vessel occlusion (LVO-AIS), and this variability has critical clinical repercussions. We explored IGR patterns and their...

Automated assessment of ischemic core on non-contrast computed tomography: a multicenter comparative analysis with CT perfusion

BackgroundApplication of machine learning (ML) algorithms has shown promising results in estimating ischemic core volumes using non-contrast CT (NCCT).ObjectiveTo assess the performance of the e-Stroke Suite software (Brainomix) in assessing...

Abstract 013: Infarct density: a novel imaging biomarker of long‐term functional outcome after endovascular thrombectomy

Introduction Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the reduction in final infarct volume only accounts for 10‐15% of the treatment benefit. There is a clear need for imaging biomarkers that are strongly associated with long‐term functional outcome after EVT, both in clinical practice and clinical trial design (surrogate outcome measure). Here we aimed to quantify the relationship between functional outcome and a range of ADC thresholds on post‐EVT MRI. Methods A single‐center cohort of consecutive acute stroke patients with anterior circulation large vessel occlusion, successful recanalization via EVT (mTICI ≥ 2b), and MRI of the brain between 12 hours and 7 days after EVT was evaluated. Imaging was processed via RAPID software. Final infarct volume was based on the traditional ADC &lt;620 threshold. Logistic regression quantified the association of lesion volumes and good functional outcome (90‐day modified Rankin Scale ≤ 2) at a range of lower ADC thresholds (&lt;570, &lt;520, and &lt;470). Infarct density was calculated as the percentage of the final infarct volume below the ADC threshold with the greatest effect size. Univariate and multivariate logistic regression quantified the association between clinical/imaging variables and functional outcome. A receiver operating characteristics (ROC) analysis was used to calculated areas under the curve (AUC) with 95% confidence intervals for the final model. The Delong test compared this AUC with two additional models: (1) the final multivariate model without infarct density and (2) the final model without infarct density and final infarct volume. Results Of the 120 patients who underwent MRI after successful EVT, lesion volume based on the ADC threshold &lt;470 had the strongest association with good outcome (OR: 0.81 per 10mL; 95% CI: 0.66–0.99). In a multivariate model, infarct density (volume &lt;470/volume &lt;620 * 100) was independently associated with good outcome (aOR 0.68 per 10%; 95% CI: 0.49–0.95). In the multivariate model, final infarct volume was no longer associated with outcome (aOR 0.98 per 10mL; 95% CI: 0.85–1.14). The ROC analysis of the multivariate model with only clinical variables (age, sex, and NIHSS) yielded a good ability to distinguish patients with good and bad outcome (AUC = 0.77; 95% CI: 0.69 – 0.84). Adding infarct volume improved classification performance (AUC = 0.82; 95% CI: 0.75 – 0.88), but this was further improved by adding infarct density (AUC = 0.84, 95% CI: 0.78 – 0.91); p=0.02 comparing all three AUCs (Figure 1). Conclusion The degree of tissue injury after EVT is topographically heterogeneous, and more profound tissue injury manifests as lower ADC values. Here, we operationalized the severity of infarct as infarct density, which is independently associated with long‐term clinical outcome and provides greater prognostic information than final infarct volume. This technique may hold value as a surrogate outcome measure in early phased clinical trials.

Abstract 268: Validation of an automated method to assess 24‐hour infarct volume in stroke patients

Introduction In stroke patients, accurate infarct volume assessment at 24 hours typically requires manual segmentation of lesions that often are not well defined. We aimed to validate an automated machine learning algorithm (MethinksFIV) specifically trained to automatically segment and measure subacute infarcts on non‐contrast CT (NCCT) scans. Methods We retrospectively studied stroke patients with a large vessel occlusion prospectively admitted to a comprehensive stroke center. The final infarct volume was segmented on the 24h NCCT manually (man‐FIV) and with the automated method (auto‐FIV). Both measurements were correlated with clinical outcomes. Results We included 346 patients. On 24h‐NCCT median auto‐FIV was lower than man‐FIV (8.6 ml [2.3‐40.7] vs. 16.9 ml [1.1‐70.8], p&lt;0.001). Auto‐FIV and man‐FIV were highly correlated (r=0.8; p&lt;0.001; mean dice coefficient of 0.61). The Auto‐FIV correlated better than man‐FIV with 24h (r=0.54 vs. r=0.51, both p&lt;0.001) and discharge NIHSS (r=0.59 vs r=0.54, both p&lt;0.001). An increase of 1 ml in auto‐FIV was associated with an increase in the odds of higher ordinal mRS at three months (OR=1.01 95%CI 1.01‐1.02, p&lt;0.001). Auto‐FIV was a better predictor of mRS&gt;2 at three months (OR: 1.02 95%CI 1.01‐1.13, p=0.002) than manual segmentation (OR=1.01, 95%CI 1.00‐1.01, p=0.01). In a multivariable analysis, only auto‐FIV remained a significant predictor of mRS&gt;2 at three months (aOR: 1.03 95% CI 1.01‐1.05, p=0.004). Conclusion An automated method to measure subacute infarct volumes in stroke patients is accurate and correlates well with further clinical outcomes. The method appears to outperform manual segmentation and may be used to facilitate infarct characterization in large clinical trials.

Abstract 203: Predicting Outcomes After Mechanical Thrombectomy: Early vs Delayed Neurological Improvement in the SELECT Database

Introduction Understanding of patient benefit and improvement following mechanical thrombectomy in ischemic stroke has made tremendous strides in recent years, however clinicians still struggle to accurately predict patient outcomes and long‐term neurological functioning following large vessel occlusion and endovascular therapy. These limitations are further complicated by a highly variable time course of improvement following intervention that spans from minutes to months. Prior literature has shown that successful reperfusion is associated with better outcomes even in the absence of early improvement. Delayed neurological improvement may be the result of microvasculature effects and inflammatory changes, and is likely multifactorial. Improved understanding of predictors of early versus delayed neurological improvement in this population may help inform goals of care, aid in clinical decision making, and manage patient and family expectations. Methods Patient data from the SELECT database was retrospectively analyzed. The SELECT study was a prospective, non‐randomized, multicenter cohort study that enrolled patients with acute ischemic stroke due to anterior circulation large vessel occlusion at nine US centers between 1/2016 and 2/2018, with patients falling into either the mechanical thrombectomy or medical management arm. Only patients in the mechanical thrombectomy arm (n=149) were included in this analysis. Possible predictors of early vs late neurological improvement were segregated into pre‐procedure (age, NIHSS at baseline, IV thrombolytic therapy, transfer status, occlusion location, ischemic core, ischemic penumbra, hypoperfusion intensity ratio, successful reperfusion, type of anesthesia, time from last known well to puncture, time from puncture to reperfusion) and post‐procedure (NIHSS at 24‐hour follow‐up, ASPECTS on follow‐up imaging, ASPECTS point loss from baseline, infarct volume on follow‐up imaging, infarct growth from baseline ischemic core, neurological worsening, midline shift, hemorrhagic transformation and type). Backwards stepwise regression was used to identify significant predictors of early and delayed improvement. Results Pre‐procedure predictors of early neurological improvement (defined as mRS 0‐2 at discharge) were age (p=0.001), NIHSS score (p=0.002), ischemic core volume (p=0.001), transfer status (p=0.019), and successful reperfusion (defined as mTICI 2b or better, p=0.001). Post‐procedure predictor of early neurological improvement was NIHSS score at 24 hours (p&lt;0.001). Pre‐procedure predictor of delayed neurological improvement (defined as mRS 0‐2 at 90 days among those who did not achieve early neurological improvement) was ischemic core volume (p=0.003). Post‐procedure predictors of delayed neurological improvement were final infarct volume (p=0.012), change in ASPECTS on follow‐up imaging (p=0.001), and growth in infarct size (p=0.030). Pre‐procedure predictors of early excellent outcome (defined as mRS 0‐1 at discharge) were age (p=0.001), NIHSS score (p&lt;0.001), successful reperfusion (p=0.001), ischemic core volume (p=0.004), and infarct growth rate (p=0.034). Pre‐procedure predictor of delayed excellent outcome (defined as mRS 0‐1 at 90 days among those who did not achieve early excellent outcome) was NIHSS score (p=0.002). Additionally, midline shift of 5mm or more at 24 hours was associated with poor outcome at 90 days. Conclusion Several demographic, imaging, and clinical factors were found to correlate with either early or delayed neurological improvement. Further investigation may help delineate how these predictors can be utilized to inform clinical decisions and discussions regarding stroke patients receiving mechanical thrombectomy.

Abstract 050: Intraarterial cooling combined with mechanical thrombectomy in acute stroke patients: systematic review and meta‐analysis

Introduction Mechanical thrombectomy (MT) plays an important role in the treatment of intracranial large vessel occlusion (LVO) with recanalization success rate of 60%‐95%. Although the restoration of blood flow can ensue excess generation of reactive oxygen species (ROS) and inflammation which leads to cellular damage known as reperfusion injury. Recent studies have shown promising neuroprotection by reducing body temperature with the mechanism of limiting ROS and immune cells’ response. Although systemic hypothermia is associated with several adverse events and limited hypothermia affecting the specific ischemic brain tissue. Intra‐arterial cooling (IAC) combined with mechanical thrombectomy is a novel method for localized cooling. Methods Embase, and Web of Science were screened for English‐language papers including case reports/series, cohort studies and clinical trials. Studies were reviewed by 2 independent reviewers for inclusion criteria as patients with the age of &gt;18 years old who had LVO and underwent mechanical thrombectomy combined with cold Saline infusion during mechanical thrombectomy (before or after recanalization). Statistical analyses were performed using R software version R‐4.3, P Value of &lt;0.05 was considered significant. Results Four studies were included from initial 1177 studies, including 204 cases with MT combined with IAC (intra‐arterial 4°C saline infusion before or after recanalization) and 219 control with MT. Patients with MT+IAC had lower final infarct volume (MD=25, 95%CI [‐34.02, ‐15.98], P &lt;0.0001), and better modified Rankin scale (mRS) after 90 days (RR=1.42, 95%CI [1.14, 1.77, P= 0.0015). There was no significant difference between MT+IAC and IAC group regarding deterioration of NIHSS in 24 hours(RR=1.09, 95%CI [0.42, 1.3, P=0.287), recanalization at 24 hours (RR=1.03, 95%CI [0.93, 1.14], P= 0.622), vascular spasm in 10 minutes (RR=2.90, , 95%CI [0.78, 10.80], P= 0.111), symptomatic intracranial hemorrhage (RR=0.78, 95%CI [0.48, 1.27], P= 0.322), coagulation abnormality (RR=0.94, , 95%CI [0.35, 2.54], P= 0.902), pneumonia (RR=1.09, 95%CI [0.79, 1.50], P= 0.585), and mortality in 90 days (RR=0.78, 95%CI [0.51, 1.20], P= 0.265). Conclusion Preliminary data is showing Intraarterial cooling combined with mechanical thrombectomy in acute stroke is a feasible and safe method for localized brain tissue cooling to prevent reperfusion injury and maximize long term outcome of MT.

The value of computed tomography perfusion deficit volumes in acute isolated brainstem infarction.

Diagnosis of acute isolated brainstem infarction is challenging owing to non-specific, variable symptoms, and the effectiveness of non-contrast computed tomography (NCCT) is poor owing to limited spatial resolution and artifacts. Computed tomography perfusion (CTP) imaging parameters are significantly associated with functional outcomes in posterior circulation acute ischemic stroke; however, the role of CTP in isolated brainstem infarction remains unclear. We aimed to determine the value of CTP imaging parameters in predicting functional outcomes for affected patients. In total, 116 consecutive patients with isolated pontine/midbrain hypoperfusion who underwent CTP and follow-up by magnetic resonance imaging (MRI) between January 2018 and March 2022, were retrospectively analyzed. Perfusion deficit volumes on all maps, and the final infarction volume (FIV) on MRI were quantified. "Good" functional outcome was defined as a 90-day modified Rankin Scale score of 0 and 1. Statistical analysis included uni- and multivariate regression analyses, binary logistic regressions, and receiver operating characteristics (ROC) analyses. In total, 113 patients had confirmed isolated pontine/midbrain infarction on follow-up MRI. Onset-to-scan time, visibility of ischemic lesions on NCCT, the baseline National Institutes of Health Stroke Scale (NIHSS) score, and perfusion deficit volumes on all CTP maps were significantly associated with FIV (p < 0.05). In a multivariate linear regression model, adjusted for age, sex, NIHSS score, onset-to-scan time, and visibility of NCCT, perfusion deficit volumes remained significantly associated with FIV. In binary logistic regression analyses, perfusion deficit volumes on all CTP maps remained independent predictors of a good functional outcome. In ROC analyses, the cerebral blood flow deficit volume showed a slightly higher discriminatory value with the largest area under the curve being 0.683 [(95% CI, 0.587-0.780), p = 0.001]. Perfusion deficit volumes of CTP imaging could reflect the FIV and contain prognostic information on functional outcomes in patients with acute isolated brainstem infarction.