Computed Tomography Angiography Spot Research Articles

Predictors of severe intracerebral hemorrhage expansion

Background: Severe hematoma expansion (sHE) has the strongest impact on intracerebral hemorrhage (ICH) outcome. We investigated the predictors of sHE. Methods: Retrospective analysis of ICH patients admitted at nine sites in Italy, Germany, China, and Canada. The following imaging features were analyzed: non-contrast CT (NCCT) hypodensities, heterogeneous density, blend sign, irregular shape, and CT angiography (CTA) spot sign. The outcome of interest was sHE, defined as volume increase >66% and/or >12.5 from baseline to follow-up NCCT. Predictors of sHE were explored with logistic regression. Results: A total of 1472 patients were included (median age 73, 56.6% males) of whom 223 (15.2%) had sHE. Age (odds ratio (OR) per year, 95% confidence interval (CI), 1.02 (1.01–1.04)), Anticoagulant treatment (OR 3.00, 95% CI 2.09–4.31), Glasgow Coma Scale (OR 0.93, 95% CI 0.89–0.98), time from onset/last known well to imaging, (OR per h 0.96, 95% CI 0.93–0.99), and baseline ICH volume, (OR per mL 1.02, 95% CI 1.02–1.03) were independently associated with sHE. Ultra-early hematoma growth (baseline volume/baseline imaging time) was also a predictor of sHE (OR per mL/h 1.01, 95% CI 1.00–1.02). All NCCT and CTA imaging markers were also predictors of sHE. Amongst imaging features NCCT hypodensities had the highest sensitivity (0.79) whereas the CTA spot sign had the highest positive predictive value (0.51). Conclusions: sHE is common in the natural history of ICH and can be predicted with few clinical and imaging variables. These findings might inform clinical practice and future trials targeting active bleeding in ICH.

CT-based radiomics models predict spontaneous intracerebral hemorrhage expansion and are comparable with CT angiography spot sign.

This study aimed to investigate the efficacy of radiomics, based on non-contrast computed tomography (NCCT) and computed tomography angiography (CTA) images, in predicting early hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (SICH). Additionally, the predictive performance of these models was compared with that of the established CTA spot sign. A retrospective analysis was conducted using CT images from 182 patients with SICH. Data from the patients were divided into a training set (145 cases) and a testing set (37 cases) using random stratified sampling. Two radiomics models were constructed by combining quantitative features extracted from NCCT images (the NCCT model) and CTA images (the CTA model) using a logistic regression (LR) classifier. Additionally, a univariate LR model based on the CTA spot sign (the spot sign model) was established. The predictive performance of the two radiomics models and the spot sign model was compared according to the area under the receiver operating characteristic (ROC) curve (AUC). For the training set, the AUCs of the NCCT, CTA, and spot sign models were 0.938, 0.904, and 0.726, respectively. Both the NCCT and CTA models demonstrated superior predictive performance compared to the spot sign model (all P < 0.001), with the performance of the two radiomics models being comparable (P = 0.068). For the testing set, the AUCs of the NCCT, CTA, and spot sign models were 0.925, 0.873, and 0.720, respectively, with only the NCCT model exhibiting significantly greater predictive value than the spot sign model (P = 0.041). Radiomics models based on NCCT and CTA images effectively predicted HE in patients with SICH. The predictive performances of the NCCT and CTA models were similar, with the NCCT model outperforming the spot sign model. These findings suggest that this approach has the potential to reduce the need for CTA examinations, thereby reducing radiation exposure and the use of contrast agents in future practice for the purpose of predicting hematoma expansion.

The Predictive Accuracy of the Delayed Spot Sign for Haematoma Expansion in Spontaneous Supratentorial Intracerebral Haemorrhage: A Systematic Review and Meta-Analysis

Previous studies have shown that spot signs on imaging modalities such as CT perfusion, delayed phase CTA or post contrast CT imaging reportedly have greater ability to predict haematoma expansion (HE) than the traditional CT angiography spot sign. We performed a systematic review and meta-analysis of the diagnostic accuracy of the spot sign on delayed imaging modalities in predicting haematoma expansion.Pubmed, Excerpta Medica Database, and the Cochrane library were searched on the 11 November 2019. The search strategy utilised the following terms: CT angiography OR post contrast CT OR CT perfusion OR CT AND intracerebral haemorrhage (or synonyms) AND spot sign OR delayed spot sign OR dynamic spot sign. The area under the summary of receiver operating curves for diagnostic accuracy of delayed spot sign in predicting HE was calculated using bivariate random effects meta-analysis.501 articles were identified, with 10 meeting inclusion criteria. The studies included 711 patients overall, with 272 (38%) demonstrating a spot sign. The presence of a delayed spot sign was associated with HE with a diagnostic odds ratio of 25.4 (12.7-50.9). Pooled sensitivity was 0.81 (0.72-0.88), with a pooled specificity of 0.82 (0.76-0.88). Pooled positive likelihood ratio was 4.30, with a pooled negative likelihood ratio of 0.26. The area under the receiver operating curve (AUC) was 0.88.The delayed spot sign has greater diagnostic accuracy in predicting haematoma expansion than the traditional CT angiography spot sign. Further research could determine the delayed imaging technique that has the greatest diagnostic accuracy.

Does tranexamic acid affect intraventricular hemorrhage growth in acute ICH? An analysis of the STOP-AUST trial.

Trials of tranexamic acid (TXA) in acute intracerebral hemorrhage (ICH) have focused on the imaging outcomes of intraparenchymal hematoma growth. However, intraventricular hemorrhage (IVH) growth is also strongly associated with outcome after ICH. Revised definitions of hematoma expansion incorporating IVH growth have been proposed. We sought to evaluate the effect of TXA on IVH growth. We analyzed data from the STOP-AUST trial, a prospective randomized trial comparing TXA to placebo in ICH patients presenting ≤ 4.5h from symptom onset with a CT-angiography spot sign. New IVH development at follow-up, any interval IVH growth, and IVH growth ≥ 1mL were compared between the treatment groups using logistic regression. The treatment effect of TXA against placebo using conventional (> 6mL or 33%), and revised definitions of hematoma expansion (> 6mL or 33% or IVH expansion ≥ 1mL, > 6mL or 33%, or any IVH expansion, and > 6mL or 33% or new IVH development) were also assessed. Treatment effects were adjusted for baseline ICH volume. The analysis population consisted of 99 patients (50 placebo, 49 TXA). New IVH development at follow-up was observed in 6/49 (12%) who received TXA and 13/50 (26%) who received placebo (aOR: 0.38 [95% CI: 0.13-1.13]). Any interval IVH growth was observed in 12/49 (25%) who received TXA versus 26/50 (32%) receiving placebo (aOR: 0.69 [95% CI: 0.28-1.66]). IVH growth ≥ 1mL did not differ between the two groups. Using revised definitions of hematoma expansion, no significant difference in treatment effect was observed between TXA and placebo. IVH may be attenuated by TXA following ICH; however, studies with larger cohorts are required to investigate this further. http://www.clinicaltrials.gov; Unique identifier: NCT01702636.

Identifying risk factors of intracerebral hemorrhage stability using explainable attention model.

Segmentation of intracerebral hemorrhage (ICH) helps improve the quality of diagnosis, draft the desired treatment methods, and clinically observe the variations with healthy patients. The clinical utilization of various ICH progression scoring systems has limitations due to the systems' modest predictive value. This paper proposes a single pipeline of a multi-task model for end-to-end hemorrhage segmentation and risk estimation. We introduce a 3D spatial attention unit and integrate it into the state-of-the-art segmentation architecture, UNet, to enhance the accuracy by bootstrapping the global spatial representation. We further extract the geometric features from the segmented hemorrhage volume and fuse them with clinical features such as CT angiography (CTA) spot, Glasgow Coma Scale (GCS), and age to predict the ICH stability. Several state-of-the-art machine learning techniques such as multilayer perceptron (MLP), support vector machine (SVM), gradient boosting, and random forests are applied to train stability estimation and to compare the performances. To align clinical intuition with model learning, we determine the shapely values (SHAP) and explain the most significant features for the ICH risk scoring system. A total of 79 patients are included, of which 20 are found in critical condition. Our proposed single pipeline model achieves a segmentation accuracy of 86.3%, stability prediction accuracy of 78.3%, and precision of 82.9%; the mean square error of exact expansion rate regression is observed to be 0.46. The SHAP analysis reveals that CTA spot sign, age, solidity, location, and length of the first axis of the ICH volume are the most critical characteristics that help define the stability of the stroke lesion. We also show that integrating significant geometric features with clinical features can improve the ICH progression scoring by predicting long-term outcomes. Graphical abstract Overview of our proposed method comprising of spatial attention and feature extraction mechanisms. The architecture is trained on the input CT images, and the first step output is the predicted segmentation of the hemorrhagic region. The output is fed into a geometric feature extractor and is fused with clinical features to estimate ICH stability using a multilayer perceptron (MLP).

Prevalence and the predictive performance of the dynamic CT-angiography spot sign in an observational cohort with intracerebral hemorrhage.

The CT-angiography (CTA) spot sign is a predictor of hematoma expansion (HE). We have previously reported on the use of dynamic CTA (dCTA) to detect spot sign, and to study its formation over the acquisition period. In this study, we report the frequency of dCTA spot sign in acute intracerebral hemorrhage, its sensitivity and specificity to predict HE, and explore the rate of contrast extravasation in relation to hematoma growth.We enrolled consecutive patients presenting with primary intracerebral hemorrhage within 4.5 hours. All patients underwent a dCTA protocol acquired over 60 seconds following contrast injection. We calculated frequency of the dCTA spot sign, predictive performance, and rate of contrast extravasation. We compared extravasation rates to the dichotomous definition of significant HE (defined as 6 mL or 33% growth).In 78 eligible patients, dCTA spot sign frequency was 44.9%. In 61 patients available for expansion analysis, sensitivity and specificity of dCTA spot sign was 65.4% and 62.9%, respectively. Contrast extravasation rate did not significantly predict HE (Odds Ratio 15.6 for each mL/min [95% confidence interval 0.30–820.25], P = .17). Correlation between extravasation rate and HE was low (r = 0.297, P= .11). Patients with significant HE had a higher rate of extravasation as compared to those without (0.12 mL/min vs 0.04 mL/min, P = .03).Dynamic CTA results in a higher frequency of spot sign positivity, but with modest sensitivity and specificity to predict expansion. Extravasation rate is likely related to HE, but a single measurement may be insufficient to predict the magnitude of expansion.

Calculation of Prognostic Scores, Using Delayed Imaging, Outperforms Baseline Assessments in Acute Intracerebral Hemorrhage.

Background and Purpose- Patients with intracerebral hemorrhage (ICH) are often subject to rapid deterioration due to hematoma expansion. Current prognostic scores are largely based on the assessment of baseline radiographic characteristics and do not account for subsequent changes. We propose that calculation of prognostic scores using delayed imaging will have better predictive values for long-term mortality compared with baseline assessments. Methods- We analyzed prospectively collected data from the multicenter PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign). We calculated the ICH Score, Functional Outcome in Patients With Primary Intracerebral Hemorrhage (FUNC) Score, and modified ICH Score using imaging data at initial presentation and at 24 hours. The primary outcome was mortality at 90 days. We generated receiver operating characteristic curves for all 3 scores, both at baseline and at 24 hours, and assessed predictive accuracy for 90-day mortality with their respective area under the curve. Competing curves were assessed with nonparametric methods. Results- The analysis included 280 patients, with a 90-day mortality rate of 25.4%. All 3 prognostic scores calculated using 24-hour imaging were more predictive of mortality as compared with baseline: the area under the curve was 0.82 at 24 hours (95% CI, 0.76-0.87) compared with 0.78 at baseline (95% CI, 0.72-0.84) for ICH Score, 0.84 at 24 hours (95% CI, 0.79-0.89) compared with 0.76 at baseline (95% CI, 0.70-0.83) for FUNC, and 0.82 at 24 hours (95% CI, 0.76-0.88) compared with 0.74 at baseline (95% CI, 0.67-0.81) for modified ICH Score. Conclusions- Calculation of the ICH Score, FUNC Score, and modified ICH Score using 24-hour imaging demonstrated better prognostic value in predicting 90-day mortality compared with those calculated at presentation.

Abstract TP338: The Dynamic CT Angiography Spot Sign: Prevalence, Predictive Value, and Rate of Contrast Extravasation

Introduction: Hematoma expansion is a predictor of poor clinical outcome in intracerebral hemorrhage (ICH). The CT angiography (CTA) spot sign is a validated predictor of hematoma expansion, but its predictive performance is modest. This is in part because traditional “static” CTA can miss delayed spot signs, depending on the timing of image acquisition. Dynamic CTA (dCTA) can detect delayed spot sign formation and allows calculation of contrast extravasation rate. However, the predictive performance of a delayed “dynamic spot” and the relationship between rate of extravasation and hematoma expansion are not known. Our primary objective was to calculate the prevalence and predictive performance of the dynamic spot sign with dCTA. Our secondary objective was to determine whether the rate of contrast extravasation predicts significant hematoma expansion. Methods: We prospectively enrolled 79 patients who presented with primary ICH and underwent dCTA within 6 hours from onset. Primary outcomes were the prevalence of dCTA spot sign and its predictive performance for significant hematoma expansion (increase in hematoma by 6mL or 33% from baseline). For the secondary objective, we calculated the rate of contrast extravasation as the slope of the time curve from the first appearance of contrast at a spot sign to the maximal volume of contrast in 19 acquisitions over 60 seconds. We assessed the relationship between rate of extravasation and hematoma expansion using Mann-Whitney U test and logistic regression. Results: The prevalence of the dCTA spot sign was 45.6% (95% CI, 34.5-56.6%). Significant HE was seen in 58.1% (18/31) of spot-positive patients versus 29.0% (9/31) of spot-negative patients (P=0.04). The sensitivity and specificity of the dCTA spot sign in predicting significant HE was 67% and 63%, respectively. Median rate of extravasation was 0.0022 mL/min in patients with hematoma expansion vs 0.0013 mL/min in those without (p=0.05). Conclusion: Dynamic CTA had a higher spot sign prevalence than conventional CTA. While the sensitivity in predicting expansion was higher with dCTA, the specificity was lower, possibly due to a lower risk of expansion with delayed spot signs. The rate of extravasation was roughly double in patients with hematoma expansion.

BAT Score Versus Spot Sign in Predicting Intracerebral Hemorrhage Expansion

The BAT score is a novel prediction score of hematoma expansion based on noncontrast computed tomography (CT) and consists of the blend sign, hypodensities, and time interval from onset to CT. This study aimed to compare the BAT score and the spot sign on CT angiography in a cohort of patients with spontaneous intracerebral hemorrhage. Eligible patients with spontaneous intracerebral hemorrhage were analyzed retrospectively. The BAT score and the spot sign were assessed according to the criteria described in previous studies. Receiver operating curve analysis was used to assess the performance of the BAT score and the spot sign in hematoma expansion prediction. In 225 included patients, 34 (15.1%) had a BAT score ≥3. The spot sign was shown in 68 (30.2%) patients. Hematoma expansion was identified in 56 (24.9%) patients. In multivariate analysis, both BAT score ≥3 and presence of spot sign were independently correlated with hematoma expansion. BAT score ≥3 had 0.41 sensitivity and 0.93 specificity, and spot sign had 0.64 sensitivity and 0.81 specificity. The area under the curve of BAT score ≥3 and area under the curve of spot sign were 0.673 and 0.727, respectively (P= 0.386). The BAT score based on noncontrast CT is a good predictor of hematoma expansion. When CT angiography spot sign is unobtainable, the BAT score can be used to predict hematoma expansion.

Abstract WP437: The CT Angiography Spot Sign, Hematoma Expansion and Functional Outcome in Spontaneous Cerebellar ICH

Background: The CT angiography (CTA) spot sign is associated with hematoma expansion, mortality and poor functional outcome in supratentorial and pontine spontaneous intracerebral hemorrhage (ICH). However, no studies are available on the spot sign in patients with spontaneous cerebellar ICH. We therefore aim to assess its association with hematoma expansion and outcome in cerebellar ICH. Methods: We investigated consecutive patients with spontaneous cerebellar ICH treated non-surgically at three academic hospitals between 2002 and 2017. We determined patient characteristics, presence of the CTA spot sign, baseline hematoma volumes, hematoma expansion (&gt;33% or &gt;6ml), speed of expansion (baseline hematoma volume/time onset-CT scan) and in-hospital and 90-day mortality and functional outcome. Associations were tested using uni- and multivariable logistic regression. Results: We included 358 patients with cerebellar ICH of which 181 (51%) underwent a CTA. Of these 181 patients, 60 (33%) were treated surgically and therefore excluded from this study. This resulted in 121 patients of which 15 (12%) had a CTA spot sign. In univariable analyses, patients with a CTA spot sign presented with larger hematoma volumes [median (IQR): 22 (7-41) vs. 6 (3-14), p=0.005], higher rates of hematoma expansion [50% vs. 24%, p=0.167] and higher speed of expansion [median (IQR): 9 (21-2) vs. 2 (5-0), p=0.015]. Patients also had higher mortality at discharge [80% vs. 18%, p=&lt;.001] and 90-days [80% vs. 26%, p=&lt;0.001] and higher rates of poor functional outcome (mRS 4-6) at discharge [93% vs. 63%, p=0.020] and 90-days [93% vs. 53%, p=0.006]. In multivariable analyses correcting for age, sex and speed of expansion, the presence of the CTA spot sign is independently associated with 90-days mortality [OR 3.9, 95%CI 1.5-12.9] and 90-days poor functional outcome [OR 4.1, 95%CI 1.2-21.0]. Conclusions: In patients with spontaneous cerebellar ICH, the CTA spot sign is associated with hematoma expansion, speed of hematoma expansion, mortality, and poor functional outcome. This may assist physicians in the risk stratification of patients with spontaneous cerebellar ICH.

External Validation of Hematoma Expansion Scores in Spontaneous Intracerebral Hemorrhage in an Asian Patient Cohort.

Hematoma expansion (HE) occurs in approximately one-third of patients with intracerebral hemorrhage (ICH) and is known to be a strong predictor ofneurological deterioration as well as poor functional outcome. This study aims to externally validate three risk prediction models of HE (PREDICT, 9-point, and BRAIN scores) in an Asian population. A prospective cohort of 123 spontaneous ICH patients admitted to a tertiary hospital (certified stroke center) in Singapore was recruited. Logistic recalibrations were performed to obtain updated calibration slopes and intercepts for all models. The discrimination (c-statistic), calibration (Hosmer-Lemeshow test, le Cessie-van Houwelingen-Copas-Hosmer test, Akaike information criterion), overall performance (Brier score, R2), and clinical usefulness (decision curve analysis) of the risk prediction models were examined. Overall, the recalibrated PREDICT performed best among the three models in our study cohort based on the novel matrix comprising of Akaike information criterion and c-statistic. The PREDICT model had the highest R2 (0.26) and lowest Brier score (0.14). Decision curve analyses showed that recalibrated PREDICT was more clinically useful than 9-point and BRAIN models over the greatest range of threshold probabilities. The two scores (PREDICT and 9-point) which incorporated computed tomography (CT) angiography spot sign outperformed the one without (BRAIN). To our knowledge, this is the first study to validate HE scores, namely PREDICT, 9-Point and BRAIN, in a multi-ethnic Asian ICH patient population. The PREDICT score was the best performing model in our study cohort, based on the performance metrics employed in this study. Our findings also showed support for CT angiography spot sign as a predictor of outcome after ICH. Although the models assessed are sufficient for risk stratification, the discrimination and calibration are at best moderate and could be improved.

Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data

SummaryBackgroundIntracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.MethodsIn a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.FindingsOf 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).InterpretationIn this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.FundingUK Medical Research Council and British Heart Foundation.

Combining Spot Sign and Intracerebral Hemorrhage Score to Estimate Functional Outcome: Analysis From the PREDICT Cohort.

The intracerebral hemorrhage (ICH) score is the most commonly used grading scale for stratifying functional outcome in patients with acute ICH. We sought to determine whether a combination of the ICH score and the computed tomographic angiography spot sign may improve outcome prediction in the cohort of a prospective multicenter hemorrhage trial. Prospectively collected data from 241 patients from the observational PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign) were analyzed. Functional outcome at 3 months was dichotomized using the modified Rankin Scale (0-3 versus 4-6). Performance of (1) the ICH score and (2) the spot sign ICH score-a scoring scale combining ICH score and spot sign number-was tested. Multivariable analysis demonstrated that ICH score (odds ratio, 3.2; 95% confidence interval, 2.2-4.8) and spot sign number (n=1: odds ratio, 2.7; 95% confidence interval, 1.1-7.4; n>1: odds ratio, 3.8; 95% confidence interval, 1.2-17.1) were independently predictive of functional outcome at 3 months with similar odds ratios. Prediction of functional outcome was not significantly different using the spot sign ICH score compared with the ICH score alone (spot sign ICH score area under curve versus ICH score area under curve: P=0.14). In the PREDICT cohort, a prognostic score adding the computed tomographic angiography-based spot sign to the established ICH score did not improve functional outcome prediction compared with the ICH score.

Comparison of the clinical efficacy of craniotomy and craniopuncture therapy for the early stage of moderate volume spontaneous intracerebral haemorrhage in basal ganglia: Using the CTA spot sign as an entry criterion

ObjectivesSurgical treatment is widely used for haematoma removal in spontaneous intracerebral haemorrhage (ICH) patients, but there is controversy about the selection of surgical methods. The CT angiography (CTA) spot sign has been proven to be a promising factor predicting haematoma expansion and is recommended as an entry criterion for haemostatic therapy in patients with ICH. This trial was designed to evaluate the clinical efficacy of two surgical methods (haematoma removal by craniotomy and craniopuncture combined with urokinase infusion) for patients in the early stage (≤6h from symptom onset) of spontaneous ICH with a moderate haematoma volume (30 ml – 60 ml). Patients and MethodsFrom January 2012 to July 2017, 196 eligible patients treated in our institution were enrolled according to the inclusion criteria. The patients were divided into the CTA spot sign positive type and CTA spot sign negative type according to the presence or absence of the CTA spot sign. For each type, the patients were randomly assigned to two groups, i.e., the craniotomy group, in which patients underwent craniotomy with haematoma removal, and the craniopuncture group, in which patients underwent minimally invasive craniopuncture combined with urokinase infusion therapy. Neurological function was evaluated with the Scandinavian Stroke Scale (SSS) at day 14. The disability level and the activities of daily living were assessed using a modified Rankin Scale (mRS) and Barthel Index (BI) at day 90. Case fatalities were recorded at day 14 and 90. Complications were recorded during hospitalization. ResultsFor the CTA spot sign positive type, the craniotomy group had a higher SSS than that in the craniopuncture group (P < 0.05) at day 14. The rebleeding rate was higher in the craniopuncture group than that in the craniotomy group (P < 0.05) during hospitalization. The craniotomy group had a lower mRS than that in the craniopuncture group (P < 0.01) and had a higher BI than that in the craniopuncture group (P < 0.05) at day 90. There was no statistically significant difference in the fatality rate between the two groups. For the CTA spot sign negative type, there were no significant differences in the SSS, mRS, BI, fatality rate and complication rate between the two groups. ConclusionICH can be divided into the CTA spot sign positive and negative type according to the presence or absence of the CTA spot sign. For the CTA spot sign positive type, patients can benefit from craniotomy with haematoma removal, which can reduce the postoperative rebleeding rate and improve the prognosis. For the CTA spot sign negative type, both craniotomy and craniopuncture are applicable. Considering simple procedure and minor surgical injury, craniopuncture can be a more reasonable choice.

Lack of Early Improvement Predicts Poor Outcome Following Acute Intracerebral Hemorrhage.

There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes. Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]). Neurocritical and ICUs. Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients. None. We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4-6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2-6, 3-6, 5-6, 6). We employed Youden's J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four-hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden's method showed an optimum cut point at -0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25-7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity, 98%; positive predictive value, 91%; adjusted odds ratio, 12.24 [CI, 4.08-36.66]). All definitions reproduced well in the validation cohort. Lack of clinical improvement at 24 hours robustly predicted poor outcome and showed good discrimination for individual patients who would do poorly. These findings are useful for prognostication and may also present as a potential early surrogate outcome for future intracerebral hemorrhage treatment trials.

Author response: Blood pressure reduction and noncontrast CT markers of intracerebral hemorrhage expansion.

We thank Drs. Lattanzi and Silvestrini for their interest in our article.1 Increased blood pressure variability may lead to poor outcome after acute intracerebral hemorrhage (ICH) but a post hoc analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2) showed that this association was not mediated by an increased risk of ICH growth.2 Hematoma expansion is a very early event in the natural history of ICH and, therefore, we agree that time is a key factor. Ischemic stroke treatment in mobile stroke units reduces the time from symptom onset to treatment.3 Early identification and treatment of patients with ICH at high risk of hematoma growth may become feasible in the prehospital setting using mobile stroke units equipped with noncontrast CT (NCCT). In a previous analysis, we showed that intrahematoma hypodensities, timing of baseline NCCT, and presence of the CT angiography spot sign predicted ICH expansion independently from each other.4 Further studies are needed to investigate whether the integration of different imaging markers provides additional value in the identification of ICH patients at high risk of hemorrhage growth.

Early Hematoma Enlargement in Primary Intracerebral Hemorrhage.

Early hematoma growth is not uncommon in patients with intracerebral hemorrhage. It is a devastating complication that independently predicts poor outcome. The early hematoma enlargement is usually defined as an absolute increase in hematoma volume of greater than 33% on repeat CT scan. To date, no ideal animal model can mimic the exact pathophysiological process of early hematoma growth. This review of early hematoma enlargement in primary intracerebral hemorrhage discusses definitions, pathophysiology, risk factors, and novel treatment options aimed at improving outcomes. Novel imaging predictors such as CT angiography spot sign and CT blend sign may predict early hematoma growth in patients with intracerebral hemorrhage. Monitoring and modulation of blood pressure may improve outcomes. Rapid reduction of blood pressure to &lt;140 mm Hg may be safe in patients with intracerebral hemorrhage.

Phantom-based standardization of CT angiography images for spot sign detection.

The CT angiography (CTA) spot sign is a strong predictor of hematoma expansion in intracerebral hemorrhage (ICH). However, CTA parameters vary widely across centers and may negatively impact spot sign accuracy in predicting ICH expansion. We developed a CT iodine calibration phantom that was scanned at different institutions in a large multicenter ICH clinical trial to determine the effect of image standardization on spot sign detection and performance. A custom phantom containing known concentrations of iodine was designed and scanned using the stroke CT protocol at each institution. Custom software was developed to read the CT volume datasets and calculate the Hounsfield unit as a function of iodine concentration for each phantom scan. CTA images obtained within 8h from symptom onset were analyzed by two trained readers comparing the calibrated vs. uncalibrated density cutoffs for spot sign identification. ICH expansion was defined as hematoma volume growth >33%. A total of 90 subjects qualified for the study, of whom 17/83 (20.5%) experienced ICH expansion. The number of spot sign positive scans was higher in the calibrated analysis (67.8 vs 38.9% p<0.001). All spot signs identified in the non-calibrated analysis remained positive after calibration. Calibrated CTA images had higher sensitivity for ICH expansion (76 vs 52%) but inferior specificity (35 vs 63%) compared with uncalibrated images. Normalization of CTA images using phantom data is a feasible strategy to obtain consistent image quantification for spot sign analysis across different sites and may improve sensitivity for identification of ICH expansion.

Abstract 215: Does the CT Angiography Spot Sign Identify Intracerebral Hemorrhage Patients More Likely to Benefit From Intensive Blood Pressure Reduction?

Background and Purpose: the computed tomography angiography (CTA) spot sign is a strong predictor of intracerebral hemorrhage (ICH) expansion, and may mark those most likely to benefit from intensive blood pressure (BP) reduction. The Spot Sign score in restricting ICH growth (SCORE-IT) study analyzed whether intensive BP reduction improved outcome in Spot Sign positive patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) clinical trial. Methods: In ATACH-2, patients with ICH were randomly assigned to intensive (systolic BP target: 110-139 mmHg) versus standard (systolic BP target: 140-179 mmHg) BP treatment within 4.5 h from stroke onset. This analysis included patients with a CTA performed within 8 hours from onset. The association between intensive BP lowering, ICH expansion and functional outcome was investigated with a multivariable logistic regression model. Results: 133 subjects met the inclusion criteria, of whom 53 (39.9%) had a spot sign and 24/123 (19.5%) experienced ICH expansion. A total of 56/123 patients had a 90 day modified Rankin scale (mRS) &gt;3 (45.5%). Among Spot positive patients, 74.1% of those in the intensive BP lowering group had poor outcome, compared with 50.0% of those in the standard group (p=0.31). After adjustment for potential confounders, intensive BP lowering was not associated with a significant reduction of ICH expansion (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.27 - 2.51, p = 0.74) or improved functional outcome (OR for mRS&gt;3 1.24, 95% CI 0.53 - 2.91, p = 0.62) in spot sign positive ICH patients. Conclusions: We found no evidence that ICH patients with a spot sign specifically benefit from intensive BP reduction.

Negative spot sign in primary intracerebral hemorrhage: potential impact in reducing imaging.

Intracerebral hemorrhage (ICH) is one of the most devastating and costly diagnoses in the USA. ICH is a common diagnosis, accounting for 10-15% of all strokes and affecting 20 out of 100,000 people. The CT angiography (CTA) spot sign, or contrast extravasation into the hematoma, is a reliable predictor of hematoma expansion, clinical deterioration, and increased mortality. Multiple studies have demonstrated a high negative predictive value (NPV) for ICH expansion in patients without spot sign. Our aim is to determine the absolute NPV of the spot sign and clinical characteristics of patients who had ICH expansion despite the absence of a spot sign. This information may be helpful in the development of a cost effective imaging protocol of patients with ICH. During a 3-year period, 204 patients with a CTA with primary intracerebral hemorrhage were evaluated for subsequent hematoma expansion during their hospitalization. Patients with intraventricular hemorrhage were excluded. Clinical characteristics and antithrombotic treatment on admission were noted. The number of follow-up NCCT was recorded. Of the resulting 123 patients, 108 had a negative spot sign and 7 of those patients subsequently had significant hematoma expansion, 6 of which were on antithrombotic therapy. The NPV of the CTA spot sign was calculated at 0.93. In patients without antithrombotic therapy, the NPV was 0.98. In summary, the negative predictive value of the CTA spot sign for expansion of ICH, in the absence of antithrombotic therapy and intraventricular hemorrhage (IVH) on admission, is very high. These results have the potential to redirect follow-up imaging protocols and reduce cost.