Correlation of Alberta Stroke Program Early Computed Tomography Score With Computed Tomography Perfusion Core in Large Vessel Occlusion in Delayed Time Windows
Abstract
Background and Purpose:
The Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) and CT perfusion (CTP) are commonly used to predict the ischemic core in acute ischemic strokes. CT angiography source images (CTA-SI) can also provide additional information to identify the extent of ischemia. Our objective was to investigate the correlation of noncontrast CT (NCCT) ASPECTS and CTA-SI ASPECTS with CTP core volumes.
Methods:
We utilized a single institutional, retrospective registry of consecutive patients with acute ischemic stroke with large vessel occlusion between May 2016 and May 2018. We graded ASPECTS both on baseline NCCT and CTA-SI and measured CTP core using automated RAPID software (cerebral blood flow <30%). We used Spearman’s correlation coefficients to evaluate the correlation between continuous variables.
Results:
A total of 52 patients fit the inclusion criteria of large vessel occlusion in 6 to 24 hours and baseline imaging work up of NCCT, CTA, and CTP. The median age was 63 (interquartile range=53.5–75) and 38.46% were female. The median NCCT ASPECTS was 7 (interquartile range=6–9), CTA-SI ASPECTS was 5 (interquartile range=4–7), and CTP core was 14.5 mL (interquartile range=0–46 mL). There was a moderate correlation between NCCT ASPECTS and CTP core (rs=−0.55, P<0.0001) and between CTA-SI ASPECTS and CTP core (rs=−0.50, P=0.0002). The optimal NCCT ASPECTS cutoff score to detect CTP core ≤70 mL was ≥6 (sensitivity, 0.84; specificity, 0.57; positive predictive value, 0.93; negative predictive value, 0.36) and the optimal CTA-SI ASPECTS was ≥5 (sensitivity, 0.76; specificity, 0.71; positive predictive value, 0.94; negative predictive value, 0.31).
Conclusions:
There was a moderate correlation between NCCT and CTA-SI ASPECTS in predicting CTP defined ischemic core in delayed time windows. Further studies are needed to determine if NCCT and CTA imaging could be used for image-based patient selection when CTP imaging is not available.
Introduction
Recent endovascular trials DAWN (Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) established the strong clinical benefit of endovascular treatment (EVT) for anterior circulation large vessel occlusion ischemic strokes up to 24 hours from stroke onset.1,2 These trials shifted the paradigm for acute ischemic stroke imaging to include the use of automated computed tomography (CT) perfusion (CTP) to select for EVT eligibility in delayed time windows (beyond 6 hours). CTP provides valuable information about the ischemic core and penumbra, which can help in patient triage and selection. Consequently, standard acute ischemic stroke management is now guided by baseline noncontrast computed tomography (NCCT), computed tomography angiography (CTA), and CTP imaging.
Traditionally, Alberta Stroke Program Early Computed Tomography Score (ASPECTS) provides valuable assessment of early ischemic changes on NCCT and predicts functional outcomes and ischemic core volumes.3 NCCT ASPECTS has been correlated with CTP core volume in earlier time windows (under 6 hours).4 However, the relationship between ASPECTS and CTP core volume in delayed time windows (6–24 hours) has not entirely been studied. Additionally, ASPECTS can also be applied to CTA source images (CTA-SI), which can provide additional information to identify the extent of ischemia over NCCT alone.5 It is also unclear whether CTA-SI ASPECTS predicts ischemic core as well as or better than NCCT ASPECTS in delayed time windows. Thus, it is imperative that we understand the relationship between ASPECTS (NCCT and CTA-SI) and CTP core volume in the context of the real world, especially as automated CTP imaging may not be readily available at all centers receiving patients with acute stroke.
Our objective was to investigate the relationship between NCCT ASPECTS and CTA-SI ASPECTS with CTP core volume in delayed time windows (beyond 6 hours from stroke onset). We hypothesized that both NCCT ASPECTS and CTA-SI ASPECTS will correlate with automated CTP core volume beyond 6 hours.
Methods
Study Population and Selection Criteria
The data that support the findings of this study are available from the corresponding author upon reasonable request. We retrospectively identified all consecutive patients with acute ischemic stroke admitted to a comprehensive stroke center between May 1, 2016 and May 1, 2018. The inclusion criteria included the following: (1) presence of anterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery M1 or M2); (2) baseline imaging workup including NCCT, CTA, and CTP; and (3) stroke onset or last known well >6 hours. Figure 1 includes the workflow for patient selection. This study received local Institutional Review Board approval and patient consent was waived.
Data Collection and Imaging Analysis
Institutional EPIC medical records and Radiology Picture Archive and Communication System were utilized to obtain demographic data, baseline medical variables, initial stroke variables, and baseline imaging data (NCCT, CTA, CTP). We recorded clinical outcomes using the modified Rankin Scale at 90 days and EVT reperfusion results using the modified Thrombolysis in Cerebral Infarction scores.6 We classified hemorrhagic transformations according to the Heidelberg Bleeding Classification.7 We recorded baseline NCCT ASPECTS from clinical radiology reports (all interpreted by board certified neuroradiologists).3 We specifically used ASPECTS from multiple readers (rather than a central imaging core) to simulate the real-world ASPECTS scoring. A single reader (Dr Corcoran) interpreted all CTA-SI ASPECTS using baseline CTA source images (as these are not clinically reported by the radiologists).8
We analyzed CTP imaging using ISchemiaview RAPID automated software, where a threshold of relative cerebral blood flow <30% defines ischemic core.
Statistical Analysis
Descriptive analysis was performed to summarize the distribution of the variables of interest for the entire cohort. Spearman’s correlation coefficients were used to evaluate the correlation between continuous variables. Univariate linear regression models were used to assess the relationship between NCCT ASPECTS, CTA-SI ASPECTS, and CTP core volume. The association was illustrated by scatter plots with linear regression lines. Separate logistic regression models were developed using NCCT ASPECTS, CTA-SI ASPECTS, or combined to predict CTP core volume ≤70 mL. The area under the receiver operating characteristic curve (AUC) was used to compare different models and find the best NCCT and CTA-SI ASPECTS cutoff and the corresponding sensitivity and specificity to detect CTP core volume of ≤70 mL. The McNamar test was used to assess the disagreement of the number of ineligible patients for EVT using EVT selection guidelines consisting of NCCT ASPECTS, CTA-SI ASPECTS, and CTP core. All analyses were performed using SAS version 9.4. A P value <0.05 was considered statistically significant.
Results
Patient Characteristics
Out of 1840 patients admitted for acute ischemic stroke during the study time period, 158 patients received CTP imaging within 6 to 24 hours and 52 patients met the inclusion criteria. The median age was 63 years (interquartile range, 53.5–75) and 38.46% of patients were female. Median baseline National Institutes of Health Stroke Scale was 15 (11.5–20) and 69.23% of patients were treated endovascularly. Median NCCT ASPECTS was 7 (6–9), median CTA-SI ASPECTS was 5 (4–7), and median CTP core volume was 14.5 mL (0–46; Table 1).
Variable | Cohort (n=52) |
---|---|
Age, y; median (IQR) | 63 (53.5–75) |
Female, No. (%) | 20 (38.46) |
Race (White), No. (%)* | 39 (75) |
History of atrial fibrillation, No. (%) | 17 (32.69) |
History of congestive heart failure, No. (%) | 11 (21.15) |
History of hyperlipidemia, No. (%) | 31 (59.62) |
History of hypertension, No. (%) | 41 (78.85) |
History of diabetes, No. (%) | 23 (44.23) |
History of tobacco use, No. (%) | 24 (46.15) |
Baseline presentation NIHSS, median (IQR) | 15 (11.5–20) |
Time from last known well to CTP imaging, min; median (IQR)† | 632 (538–925) |
ICA occlusion, No. (%) | 9 (17.31) |
MCA occlusion, No. (%) | 37 (71.15) |
ICA+MCA occlusion, No. (%) | 6 (11.54) |
NCCT ASPECTS, median (IQR) | 7 (6–9) |
CTA-SI ASPECTS, median (IQR) | 5 (4–7) |
CTP core volume (CBF<30%; mL), median (IQR) | 14.5 (0–46) |
ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; CBF, cerebral blood flow; CTA-SI, computed tomography angiography source image; CTP, computed tomography perfusion; ICA, internal carotid artery; IQR, interquartile range; MCA, middle cerebral artery; NCCT, noncontrast computed tomography; and NIHSS, National Institutes of Health Stroke Scale.
*
Subjects missing (1).
†
Subjects missing (3).
In the total sample of 52 patients, 36 received EVT. Thirty-five patients were selected based on favorable CTP imaging using DAWN/DEFUSE 3 criteria.1,2 One patient was selected based on a favorable NCCT ASPECTS (≥6) as the CTP imaging was suboptimal. Two patients with favorable CTP imaging did not receive EVT as one patient had a chronic cervical internal carotid artery occlusion and one patient was in the DEFUSE 3 trial medical arm. Results of EVT are shown in Table 2.
Received EVT, No. (% of total sample) | 36 (69.23) |
Postprocedure mTICI, No. (% of patients with EVT) | |
mTICI 0 | 5 (13.89) |
mTICI 1 | 2 (5.56) |
mTICI 2a | 2 (5.56) |
mTICI 2b | 11 (30.56) |
mTICI 3 | 16 (44.44) |
Hemorrhagic transformation, No. (% of patients with EVT)* | 11 (30.56) |
Class 1a (HI1) | 0 |
Class 1b (HI2) | 8 (22.22) |
Class 1c (PH1) | 1 (2.78) |
Class 2 (PH2) | 1 (2.78) |
Class 3a | 0 |
Class 3b | 0 |
Class 3c | 1 (2.78) |
Class 3d | 0 |
90-d modified Rankin Scale, No. (% of patients with EVT)† | |
0 | 3 (8.33) |
1 | 4 (11.11) |
2 | 2 (5.56) |
3 | 10 (27.78) |
4 | 5 (13.89) |
5 | 4 (11.11) |
6 | 7 (19.44) |
EVT indicates endovascular treatment; and mTICI, modified Thrombolysis in Cerebral Infarction.
*
Hemorrhagic Transformations classified according to Heidelberg Bleeding Classification.
†
Subjects missing (1).
Relationship Between NCCT ASPECTS, CTA-SI ASPECTS, and CTP Core
We found a moderate correlation between NCCT ASPECTS and CTP core volume (rs=−0.55 [P<0.0001]) and between CTA-SI ASPECTS and CTP core volume (rs=−0.50 [P=0.0002]). NCCT ASPECTS had a slightly better correlation as compared with CTA-SI ASPECTS with CTP core (Figure 2). There was also a moderate correlation between NCCT ASPECTS and CTA-SI ASPECTS (rs=0.67 [P<0.0001]).
We performed a linear regression to determine if NCCT ASPECTS and CTA-SI ASPECTS predicted CTP core volume. In the univariate analysis, both NCCT and CTA-SI ASPECTS significantly predicted CTP core volume (coefficients=−11.9 and −8.7, P <0.0001 and 0.0004, respectively). The results are consistent with the findings using Spearman correlation coefficients. Because NCCT ASPECTS and CTA-SI ASPECTS are moderately correlated, we did not perform multivariable analysis because of multicollinearity.
We also assessed for an optimal threshold of NCCT ASPECTS and CTA-SI ASPECTS to predict an ischemic core ≤70 mL. We used core threshold of 70 mL, as this was one of the inclusion criteria in the DEFUSE 3 trial.1 The optimal cutoff for NCCT ASPECTS to predict CTP core ≤70 mL was ≥6 (sensitivity, 0.84; specificity, 0.57; Youden J, 0.42) and for CTA-SI ASPECTS was ≥5 (sensitivity, 0.76; specificity, 0.71; Youden J, 0.47). The AUC for NCCT ASPECTS (AUC=0.79 [95% CI, 0.60–0.98]) was slightly better as compared with CTA-SI ASPECTS (AUC=0.76 [95% CI, 0.55–0.96]) to predict core volume ≤70 mL (Figure 3). Using NCCT ASPECTS ≥6 yielded a positive predictive value of 0.93 and a negative predictive value of 0.36. Using CTA-SI ASPECTS ≥5 yielded a positive predictive value of 0.94 and negative predictive value of 0.31. Table 3 demonstrates the receiver operating characteristic analysis. Using NCCT ASPECTS and CTA-SI ASPECTS combined provided the highest AUC to predict CTP core ≤70 mL (AUC=0.80) as compared with NCCT ASPECTS alone (AUC=0.79) or CTA-SI ASPECTS alone (AUC=0.76).
Variable | AUC | AUC: 95% CI | Sensitivity | Specificity | Youden | Cutoff | PPV | NPV | |
---|---|---|---|---|---|---|---|---|---|
NCCT ASPECTS | 0.79 | 0.60 | 0.98 | 84% | 57% | 0.42 | ≥6 | 0.93 | 0.36 |
CTA-SI ASPECTS | 0.76 | 0.55 | 0.96 | 76% | 71% | 0.47 | ≥5 | 0.94 | 0.31 |
Receiver operating characteristic curve analysis of NCCT and CTA-SI ASPECTS demonstrates cutoff values to predict CTP core volume ≤70 mL and better AUC for NCCT ASPECTS compared with CTA-SI ASPECTS. PPVs and NPVs are shown. ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; AUC, area under the receiver operating characteristic curve; CTA-SI, computed tomography angiography source image; CTP, computed tomography perfusion; NCCT, noncontrast computed tomography; NPV, negative predictive value; and PPV, positive predictive value.
We further assessed whether using CTP criteria is more inclusive or exclusive for patient selection for EVT, as compared with using NCCT and CTA-SI ASPECTS. Eleven (21.15%) patients would be excluded from EVT, using the guideline of NCCT ASPECTS <6 as compared with 7 (13.46%) patients who would be excluded using CTP criteria (core >70 mL). This suggests that the CTP is more inclusive as more patients would be treated based on CTP criteria in the delayed time windows. Eighteen (34.62%) patients would be excluded from EVT, using best cutoffs provided by our study of NCCT ASPECTS and CTA-SI ASPECTS combined as compared with 7 (13.46%) patients who would be excluded using CTP criteria (core >70 mL). This also suggests that CTP criteria is more inclusive. The proportion of patients who are ineligible for EVT by different imaging guidelines (NCCT ASPECTS <6 versus CTP core >70 mL and NCCT ASPECTS and CTA-SI ASPECTS combined versus CTP core >70 mL) was not significantly different (P=0.21 and P=0.06, respectively). We have provided cases with disagreement between ASPECTS and CTP imaging in Figures I and II in the Data Supplement.
There were 3 patients with an unknown stroke onset time (wake up stroke). After excluding these, we performed correlations on the subset of patients with known stroke onset times and again found a moderate correlation between NCCT ASPECTS and CTP core (rs=−0.54, P<0.0001) and between CTA-SI ASPECTS and CTP core (rs=−0.51, P=0.0002).
Discussion
In this study, we assessed the relationship between baseline NCCT ASPECTS and CTA-SI ASPECTS with automated CTP core volumes in patients with large vessel occlusion in delayed time windows (6–24 hours). We identified a moderate correlation between NCCT ASPECTS and CTA-SI ASPECTS with CTP core.
Our study adds to the body of evidence correlating NCCT ASPECTS with automated CTP core volumes.4 NCCT ASPECTS has been previously compared with ASPECTS assessed on CTP, which demonstrated a nonsignificant correlation (r=0.18, P=1.0)9; however, these studies were in the early time window (<6 hours). Our study is significant as it focused on the delayed stroke time windows of 6 to 24 hours, a time frame that is now gathering real-world experience for EVTs. To the best of our knowledge, there is only one other study that included a delayed time window (105 patients presenting >6 hours) to study the association of baseline ASPECTS and CTP core.10
For comparison between NCCT and CTA-SI, our study is in contrast with previous studies,5,11–13 which showed that CTA-SI are more reliable than NCCT for ASPECTS scoring in early time windows. We found that baseline NCCT ASPECTS had a slightly better correlation as compared with CTA-SI ASPECTS with CTP core. One explanation is that ischemic changes are relatively more difficult to assess on NCCT in the early time windows. Ionic edema, cytotoxic edema, intracellular and interstitial water influx progress with time and severity of infarction. Hence, NCCT ASPECTS may be heavily influenced by time from stroke onset.14,15 CTA-SI, in contrast, detects changes in cerebral blood volume, and more recently has been discovered to detect cerebral blood flow with newer scanners, resulting in better delineation of early infarcts.5,11,16
Our study has important clinical implications. To the best of our knowledge, the performance of automated CTP core as compared with ASPECTS both on NCCT and CTA-SI in delayed time windows of 6 to 24 hours has not been previously studied. CTP provides valuable information of volumetric assessment of core and salvageable tissue and is important in triage decisions, particularly in delayed time windows. However, CTP imaging and automated post-processing is not ubiquitously available, especially for primary stroke centers. The results from our study suggest that NCCT and CTA-SI are important tools to determine ischemic core, especially if CTP imaging is not available. ASPECTS evaluation is particularly relevant to centers who rely on NCCT and CTA evaluation for triage decisions. Even when CTP imaging is available, it is important to assess both NCCT and CTA-SI, given the numerous pitfalls of automated CTP.17 Our study also revealed a trend that CTP is more inclusive for EVT selection compared with NCCT ASPECTS or CTA-SI ASPECTS as more patients would be treated based on CTP criteria in the delayed time windows; however, this was not statistically significant in our small sample size.
Our study has multiple important limitations including the retrospective study design and a small sample size. In addition, ASPECTS itself is a semiquantitative method of assessing early ischemic changes and is relatively subjective with interrater variability.18 However, we consider the latter as both a limitation and a strength of this study as ASPECTS evaluated by local investigators is the primary tool for acute stroke decision making in the real-world scenario. It is also important to note that CTP represents cerebral blood flow information at a single time point through the dynamic evolution of ischemia and hypoperfusion during a stroke event. There are inherent uncertainties in accurately determining definite tissue death using CTP core thresholds. We also did not control for additional imaging findings such as collateral status, which can create variability in CTP core volume.
Conclusions
Our study demonstrates that NCCT ASPECTS and CTA-SI ASPECTS have moderate correlations with automated CTP core volumes in large vessel occlusion in delayed time windows. Further studies are needed to determine if NCCT and CTA imaging could be used for image-based patient-selection when CTP imaging is not available.
Footnote
Nonstandard Abbreviations and Acronyms
- ASPECTS
- Alberta Stroke Program Early Computed Tomography Score
- AUC
- area under the receiver operating characteristic curve
- CTA
- computed tomography angiography
- CTA-SI
- CTA source image
- CTP
- computed tomography perfusion
- DAWN
- Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo
- DEFUSE 3
- Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke
- EVT
- endovascular treatment
- NCCT
- noncontrast computed tomography
- NIHSS
- National Institutes of Health Stroke Scale
Supplemental Material
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© 2021 American Heart Association, Inc.
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History
Received: 4 May 2020
Revision received: 20 October 2020
Accepted: 23 November 2020
Published online: 7 January 2021
Published in print: February 2021
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Disclosures
Disclosures Dr Vagal reports the following grant support: R01 National Institutes of Health (NIH)/NINDS NS103824-01, R01 NINDS NS100417, NIH/NINDS 1U01NS100699, R01 NIH/NINDS NS30678. She also receives funding from Johnson & Johnson, Cerenovus for the ENDOLOW trial (Endovascular Therapy for Low NIHSS Ischemic Strokes). Dr Khatri reports funding from Cerenovus (grant), Nervive (grant), Lumosa (consulting fees), Diamedica (scientific advisory board), and she has received fees from Bayer (trial leader). Dr Mistry reports grant support from NIH/NINDS K23NS113858. The other authors report no conflicts.
Sources of Funding
This work is supported by National Institutes of Health/NINDS grant NS103824.
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