For patients with acute ischemic stroke (AIS), timely reperfusion therapy, which can effectively save recoverable tissues and improve the prognosis of patients, is very important.
Recently, several randomized studies indicated that patients with AIS can be selected for endovascular treatment (EVT) up to 24 hours after symptom onset following the neuroimaging concept of a “tissue window” rather than “time window.” 1,2 The ischemic core and penumbra volumes assessed using computed tomography perfusion (CTP) are critical for screening out EVT candidates, which would improve the prognosis and decrease complications. 3–5
Several studies have pointed out that there is a good agreement between the ischemic core volume on CTP and final infarct volume on magnetic resonance imaging (MRI).
Currently, several commercial CTP software packages are available for semiautomated determination of ischemic core and penumbra volumes in patients with AIS based on different selected thresholds for different postprocessing algorithms. The main examples are the singular value decomposition plus (SVD+) algorithm, Bayesian algorithm, and maximum slope method. 6,7
A few studies have shown that the ischemic core volumes obtained using the SVD+ algorithm and Bayesian algorithm are highly consistent with infarct volume on MRI
; however, few studies have analyzed the relationship of core volumes with prognosis. In this regard, we compared the ischemic core volumes obtained using OleaSphere (Bayesian algorithm) and 8,9 Vitrea software (SVD+ algorithm) with infarct volume on MRI and analyzed their relationship with prognosis in patients with AIS who received EVT. MATERIALS AND METHODS
This was a retrospective study, and all patient information was anonymized. Institutional review board approval was obtained, and the need for informed consent was waived. One hundred five patients from January 2016 to December 2020 were included in this study. All AIS patients with large vessel occlusion in the anterior circulation underwent 1-stop computed tomography angiography–CTP scans at our institution. The inclusion criteria were as follows: (1) patients with AIS within 24 hours of onset, (2) large vessel occlusion in the anterior circulation, (3) EVT performed within 24 hours after symptom onset, and (4) 2- to 7-day MRI (diffusion-weighted imaging [DWI]) data available. The following exclusion criteria were applied: (1) noncontrast CT indicating hemorrhage; (2) severe motion artifacts; (3) comorbid severe cardiac, hepatic, renal, or pulmonary disease; and (4) history of iodine allergy.
Aquilion ONE (Canon Medical Systems, Otawara, Japan) was used to obtain 1-stop whole-brain dynamic volume computed tomography angiography–CTP data, using a 320 × 0.5-mm detector row CT and covering 160 mm per rotation. Iopamidol or Omnipaque 370 (40–50 mL) was injected according to achieve an iodine concentration per weight of 0.6 mL/kg followed by 30 mL saline, using a 2-channel high-pressure injector. The tube voltage and current were 80 kVp/100 mAs, and Adaptive Iterative Dose Reduction 3-dimensional iterative reconstruction was used. Nineteen phases with a total of 6080 frames of dynamic volume data (320 × 0.5 mm) were acquired and transferred to the workstation (
Vitrea, Vital Images, Minnetonka, Minnesota; OleaSphere, Olea Medical, La Ciotat, France) for postprocessing.
Diffusion-weighted imaging sequences were obtained on a Siemens (Erlangen, Germany) 3T or a GE (Chicago, Illinois) 3T MRI with an echo time of 50 to 70 milliseconds, repetition time of 2900 to 8000 milliseconds,
b values of 0 and 1000 s/mm 2, and slice thickness of 5 mm with a 1.5-mm gap. CTP and MRI Analysis
Imaging data analysis was semiautomated using OleaSphere and
Vitrea software. The ischemic core and penumbra volumes were obtained.
OleaSphere (v3.0) defines the ischemic core as a region with a relative cerebral blood flow less than 25% that of the contralateral side and with time to peak (TTP) >5 seconds that of the contralateral side (dTTP). The penumbra was defined as the area with a TTP >5 seconds than that of healthy tissue (excluding the infarct volume). The arterial input function and venous output function were autoselected by the software.
Vitrea (version 6.7.2) defines the ischemic core as a region with relative cerebral blood volume less than 38% that of the contralateral side and with a 5.3-second increase in TTP. The penumbra was defined as the region where the TTP was 5.3 seconds greater than that of the healthy tissue (excluding the ischemic core volume).
OleaSphere software was applied to segment and measure the final infarct volume on MRI (DWI). After importing the data, we used the semiautomatic measurement to segment the infarct areas and obtained the final infarct volume (
Fig. 1). FIGURE 1:
A patient with left internal carotid artery occlusion (white arrow) seen on (A) a maximum intensity projection image. B, Diffusion-weighted imaging shows the resulting region of restricted diffusion (white arrow). The final infarct area was subsequently semiautomatically segmented from the DWI (B) image, using OleaSphere software, which showed a volume of 117.78 mL. Color overlay images from (C) OleaSphere and (D)
show, in both, the ischemic core as red and the penumbra in yellow. The volume of the ischemic core as determined by the OleaSphere software was 95.54 mL and, as measured by the
software, was 80.50 mL. The core area on OleaSphere and
was consistent with the extent and spatial location of the infarct on DWI MRI. Figure 1 can be viewed online in color at
Clinical and Imaging Information
Clinical information was collected from medical records. Baseline National Institutes of Health Stroke Scale (NIHSS) score, Alberta Stroke program early CT score (ASPECTS), modified Thrombolysis in Cerebral Infarction (mTICI), and relevant medical history were collected. The modified Rankin Scale (mRS) score acquired after 90 days was used to evaluate the outcome of patients. An mRS score of 0 to 2 indicated a good outcome, whereas an mRS score of 3 to 6 indicated a poor outcome. A score of 6 was recorded if patients died during the follow-up period.
Statistical analysis was performed with SPSS (26.0; IBM Corporation) and MedCalc (19.6; Mariakerke, Belgium). Continuous variables are described as the median (interquartile range [IQR]) for skewed data, and categorical data are represented as frequency distributions. The Mann-Whitney
U, Pearson χ 2, and Fisher exact tests were used to compare baseline information between the good and poor outcome groups. For ischemic core and penumbra volumes, correlation and agreement between OleaSphere, Vitrea, and MRI were assessed using the Spearman correlation test, intraclass correlation coefficient (ICC), and Bland-Altman plot. A correlation coefficient <0.30 was considered to be poor, 0.31 to 0.50 to be fair, 0.51 to 0.80 to be moderate, and >0.80 to be substantial. An ICC <0.4 was considered to be poor, 0.40 to 0.59 to be fair, 0.60 to 0.75 to be good, and >0.75 to be excellent.
Multivariate logistic regression analysis was used to identify prognostic value. Three models were developed: (1) clinical information (age, NIHSS, ASPECTS, mTICI) and MRI infarct volume, (2) clinical information (age, NIHSS, ASPECTS, mTICI) and OleaSphere ischemic core volume, and (3) clinical information (age, NIHSS, ASPECTS, mTICI) and
Vitrea ischemic core volume. The DeLong test was used to test differences in the area under the curve (AUC) of the receiver operating characteristics (ROCs). We calculated the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for different variables in relation to poor outcomes. RESULT
Patients' clinical and demographic data are summarized in
Table 1 along with the analysis of good (mRS 0–2) and poor (mRS 3–6) outcomes. A total of 105 patients were enrolled in our study, including 59 men (56.2%) and 46 women (43.8%). The median age of the patients was 76.0 years. The median baseline NIHSS and ASPECTS scores were 11.0 (IQR, 7.0–17.0) and 7.0 (IQR, 5.0–8.0), respectively. Occlusion sites were in the internal carotid artery (37 [35.2%]), middle cerebral artery (65 [61.9%]), and anterior cerebral artery (3 [2.9%]). All 105 patients underwent EVT, and 95 of them (90.5%) achieved successful vascular recanalization (with mTICI classification of grade 2b–3).
TABLE 1 -
Characteristic and Outcomes of All Patients With AIS
All (n = 105)
mRS 0–2 (n = 61)
mRS 3–6 (n = 44)
Age, median (IQR), y
NIHSS, median (IQR)
ASPECTS, median (IQR)
Site of occlusion
Internal carotid artery
Middle cerebral artery
Anterior cerebral artery
mTICI for thrombectomy cases
Coronary artery disease
CTP and MRI findings
Final MRI infarct volume, median (IQR), mL
OleaSphere ischemic core volume, median (IQR), mL
Vitrea ischemic core volume, median (IQR), mL 26.9 (9.4–55.7)
OleaSphere penumbra volume, median (IQR), mL
Vitrea penumbra volume, median (IQR), mL 82.4 (40.9–130.4)
Time from onset of stroke to perfusion imaging, median (IQR), min
Time from onset of stroke to treatment, median (IQR), min
Time from onset of stroke to recanalization, median (IQR), min
Based on patients' outcomes, we divided them into good (61 patients) and poor (44 patients) outcome groups. As shown in
Table 1, significant differences between the 2 groups in many variables were revealed, including age, NIHSS, ASPECTS, mTICI, atrial fibrillation, infarct volume on MRI, and ischemic core volumes on OleaSphere and Vitrea. Patients with good outcomes had a lower median age (71.0 [60.5–80.0] vs 80.5 [68.0–84.0] years, P < 0.01), lower NIHSS score (9.0 [6.0–14.0] vs 15.0 [10.0–21.0], P < 0.001), and higher median ASPECTS score (8.0 [6.0–8.5] vs 7.0 [4.5–8.0], P < 0.05). The rate of successful recanalization in the good outcome group was higher than that in the poor outcome group (96.7% vs 81.8%, P < 0.05). Correlation and Agreement Analysis of Ischemic Core and Penumbra Volumes for All Patients Who Underwent EVT
Overall, the median core volumes obtained using MRI, OleaSphere, and
Vitrea were 31.1, 27.5, and 26.9 mL, respectively. The median ischemic core volumes of OleaSphere and Vitrea were both smaller than the final infarct on MRI, but there was no significant difference (MRI vs OleaSphere, P = 0.362; MRI vs Vitrea, P = 0.502; OleaSphere vs Vitrea, P = 0.760). In the good outcome group, the median infarct volume on MRI was 20.5 mL, and the median ischemic core volumes on OleaSphere and Vitrea were 22.0 and 21.6 mL, respectively. In the poor outcome group, the median infarct volume was 80.3 mL on MRI, 48.7 mL on OleaSphere, and 51.1 mL on Vitrea. Patients with good outcomes had smaller core volumes than those in the poor group ( P < 0.001) as measured using all 3 methods. Regarding the penumbra, the median volumes on OleaSphere and Vitrea were 59.1 and 82.4 mL, and there was a significant difference between the 2 methods ( P = 0.009). For the 2 CTP software packages, there was no significant difference in penumbra volume between the good and poor groups.
The correlation and agreement between MRI- and CTP-measured volumes are shown in
Figures 2A–D and 3A–D. Both ischemic core volumes obtained using OleaSphere ( ρ = 0.84, P < 0.001) and Vitrea ( ρ = 0.80, P < 0.001) showed substantial correlation with MRI, and the OleaSphere data were more closely correlated with MRI than those of Vitrea. Regarding agreement, OleaSphere (ICC = 0.84) and Vitrea (ICC = 0.83) ischemic core volumes showed excellent agreement with MRI. In addition, the core ( ρ = 0.92, P < 0.001; ICC = 0.95) and penumbra ( ρ = 0.87, P < 0.001; ICC = 0.77) volumes of OleaSphere and Vitrea had substantial correlation and excellent agreement ( Table 2). The Bland-Altman plots confirmed interobserver reliability ( Figs. 3A–D). FIGURE 2:
Correlation between MRI infarct and CTP ischemic core volumes and between penumbra volumes on OleaSphere and
in all patients (A–D) and patients with successful recanalization (mTICI 2b–3; E–H). Spearman correlation coefficients are shown on each graph. Figure 2 can be viewed online in color at
Bland-Altman plots of differences between MRI infarct and CTP ischemic core volumes, as well as differences between penumbra volumes on OleaSphere and
in all patients (A–D) and patients with successful recanalization (mTICI score, 2b–3; E–H). Figure 3 can be viewed online in color at
TABLE 2 -
Spearman Correlation Coefficients and ICC on CTP and MRI Volumes
ICC (95% CI)
Patients Who Underwent Successful Vascular Recanalization (mTICI 2b–3)
In patients who underwent EVT but with poor recanalization (mTICI 0–2a), a larger final infarct volume was seen on MRI than ischemic core volume on CTP. As a result, we performed a subgroup analysis of patients who achieved successful recanalization to explore the relationship between ischemic core volume on CTP software and the final infarct volume on MRI.
The median core volumes obtained using MRI, OleaSphere, and
Vitrea were 29.3, 26.9, and 25.9 mL in patients with an mTICI classification of grade 2b–3, which suggests that the OleaSphere and Vitrea ischemic core volumes are closer to the MRI infarct volumes in the successful recanalization group.
The correlation and agreement of MRI and CTP volumes in the successful recanalization group are shown in
Figures 2E–H and 3E–H. In terms of Spearman correlation coefficients, the same coefficients were obtained between the successful recanalization group and all patient group, except for the correlation coefficient between OleaSphere and Vitrea (successful recanalization group, ρ = 0.91; all patients group, ρ = 0.92).
The ICC was improved for all parameters in the successful recanalization group (
Table 2), with excellent agreement (>0.75) for both the core and penumbra. The parameters in the successful recanalization group showed better agreement, indicating that the difference between the MRI infarct volume and initial CTP ischemic core volume was smaller in the successful recanalization group. Prognostic Value of Baseline Characteristics and Infarct Volumes on MRI and CTP
Table 3 summarizes the results of 3 multivariable models. The NIHSS score, mTICI, and core volumes were independent predictors of clinical outcome in each model.
TABLE 3 -
Three Multivariable Models to Predict 90-Day Poor Outcome
OR With 95% CI
Model 1 (MRI Infarct)
Model 2 (OleaSphere Core)
Model 3 (
Age (OR per year)
NIHSS (OR per point)
ASPECTS (OR per point)
MRI infarct volume
OleaSphere core volume
Vitrea core volume —
AUC (95% CI)
P value compared with model 1 —
*OR significantly different from 1 (
P < 0.05).
Increasing the NIHSS score was associated with a significantly higher risk of poor prognosis (model 1 and model 2: odds ratio [OR], 1.13 [95% CI, 1.04–1.23]; model 3: OR, 1.12 [95% CI, 1.03–1.22]). There was a substantially greater probability of a poor outcome for patients with poor recanalization (mTICI 0–2a; model 1: OR, 7.37 [95% CI, 1.11–48.77]; model 2: OR, 8.45 [95% CI, 1.41–50.77]; model 3: OR, 9.90 [95% CI, 1.65–59.42]). Moreover, larger core volume was associated with an increased risk of poor prognosis (model 1: OR, 1.03 [95% CI, 1.01–1.04]; model 2 and model 3: OR, 1.02 [95% CI, 1.01–1.04]).
Receiver operating characteristic curve analysis (
Fig. 4) of the AUC of all 3 models found no statistically significant difference (DeLong test; model 1 vs model 2, P = 0.18; model 1 vs model 3, P = 0.18) between model 1 (AUC, 0.86; 95% CI, 0.78–0.92), 2 (AUC, 0.84; 95% CI, 0.75–0.90) and 3 (AUC, 0.83; 95% CI, 0.75–0.90), suggesting that all 3 models have good predictive performance and were reliable in predicting 90-day unfavorable prognosis in patients with AIS. FIGURE 4:
Receiver operating characteristic curves of the 3 different multivariable models. Model 1 with MRI infarct volumes, model 2 with OleaSphere core volume, and model 3 with
core volume. Figure 4 can be viewed online in color at
Criterion Values and Coordinates of the ROC Analysis Regarding 90-Day Poor Outcome
Receiver operating characteristic analysis was performed for the statistically significant variables in each model, and the AUC, 95% CI, Youden Index, cutoff value, sensitivity, and specificity were obtained (
Table 4). The optimal cutoff points and AUC of each parameter regarding the 90-day mRS are shown in the ROC curves in Figure 5.
TABLE 4 -
Criterion Values and Coordinates of the ROC Analysis Regarding 90-Day Poor Outcome
MRI Infarct Volume
OleaSphere Core Volume
Vitrea Core Volume
P value compared with NIHSS —
Receiver operating characteristic curves for NIHSS score, MRI infarct volumes, and OleaSphere and
core volumes. Figure 5 can be viewed online in color at
The NIHSS score had the largest AUC (AUC, 0.75; 95% CI, 0.65–0.83), with a cutoff value of 13.00 for predicting a poor outcome. Magnetic resonance imaging infarct volumes (AUC, 0.73; 95% CI, 0.63–0.81; DeLong test,
P = 0.81), OleaSphere ischemic volumes (AUC, 0.69; 95% CI, 0.59–0.77; DeLong test, P = 0.34), and Vitrea ischemic volumes (AUC, 0.71; 95% CI, 0.61–0.79; DeLong test, P = 0.52) showed no statistical difference in AUC compared with the NIHSS score. Receiver operating characteristic curve analysis showed that the optimal cutoff values that predicted a poor outcome were 60.12 mL (MRI), 49.18 mL (OleaSphere), and 45.51 mL ( Vitrea), respectively ( Table 4, Fig. 5). DISCUSSION
This study analyzed the correlation and agreement of infarct, ischemic core, or penumbra volumes obtained from MRI and 2 CTP software with different postprocessing algorithms.
Substantial correlation and excellent agreement were obtained between CTP ischemic core and MRI infarct volumes. Similarly, there was substantial correlation and excellent agreement between penumbra volumes assessed using OleaSphere and 8,9 Vitrea. This suggested that ischemic core and penumbra volumes obtained using Bayesian and SVD+ algorithms are reliable, which is consistent with previous studies. We found that the median ischemic core volumes of OleaSphere and Vitrea were both smaller than the final infarct on MRI, which supports the findings of previous studies, possibly attributable to an increase in tissue volume during the time from the CTP scan to recanalization and to MRI. 10,11 In addition, MRI infarct volumes may be overestimated in the subacute phase because of cerebral vasogenic edema caused by the influx of water and cations after the breakdown of the blood-brain barrier. 12,13 14–16
We noted a significant difference between the median penumbra volume obtained using OleaSphere and
Vitrea when using the Mann-Whitney U test, possibly because of differences in the algorithms. Further studies with larger samples are needed to define a “criterion standard” for the penumbra volume by which to compare these results. Nevertheless, we found good agreement between OleaSphere and Vitrea penumbra volumes using the Bland-Altman plot and ICC ( Fig. 3D), indicating that either may be used in routine clinical work. 8
In this study, patients in the good outcome group were younger, and had lower NIHSS scores, higher ASPECTS scores, a higher proportion with successful recanalization, and smaller final infarct size.
We found that the NIHSS score, mTICI, CTP ischemic core volume, and MRI infarct volume were independent predictors of clinical outcome. 17–19 The prognosis of stroke is associated with a variety of risk factors, including age, sex, subtype, hypertension, diabetes, coronary artery disease, hypercholesterolemia, smoking, alcohol consumption, severity, and treatment. 20–22 The lack of statistically significant correlation between age, ASPECTS score, and clinical factors in our study may be due to the spatial location of infarcts, sample size, and choice of treatment. 23,24
Baseline NIHSS score reflects the degree of neurological impairment, and a higher NIHSS score is associated with a significantly higher risk of poor prognosis.
The mTICI score is used to evaluate recanalization of the brain vessels after EVT, and TICI 2b/3 is defined as the successful recanalization, which reflects a good outcome. 18 Thrombolysis in Cerebral Infarction 0–2a reflects poor recanalization, and affected patients are at a higher risk of poor outcomes. Several studies have revealed that MRI infarct volume is a strong predictor of prognosis in patients with AIS. 21 Yoo et al 25,26 found that preprocedure DWI volumes ≥70 mL were highly likely to yield poor clinical outcomes regardless of recanalization results, and our results back up their findings. Our study showed that there were no significant differences in the prognostic value of OleaSphere and 27 Vitrea core volumes versus MRI to predict outcomes at 90 days, suggesting that ischemic core volumes obtained using CTP on admission may predict clinical outcomes, and the core volumes predicting poor prognosis were 60.12 mL (MRI), 49.18 mL (OleaSphere), and 45.51 mL ( Vitrea). According to the HERMES collaboration meta-analysis, each 10-mL increase in baseline ischemic core volume on CTP reduced the likelihood of 90-day functional independence by 20% to 30% (OR, 0.77; 95% CI, 0.69–0.86). Our research supported the aforementioned viewpoints that preintervention CTP parameters were useful in predicting MRI infarct volume and 90-day outcome. 28
Some patients had MRI infarct volumes larger than CTP ischemic core volumes (
Figs. 2, 3) and “outliners” attributable to malignant middle cerebral artery infarction (MMI), a complication in patients with large hemispheric infarction who progress to fatal brain edema. Thomalla's study showed that DWI lesion volume > 82 mL within 6 hours of symptom onset was an independent predictor of malignant middle cerebral artery infarction (sensitivity, 52%; specificity, 98%). 29–31
There were some limitations in our study. First, this was a retrospective study with patients from a single stroke center. Second, the infarct volumes may have been overestimated because of the presence of vasogenic and postoperative edema. Third, the study included only patients with EVT.
In conclusion, the ischemic core volumes measured using OleaSphere and
Vitrea showed moderate correlation and good agreement with MRI. Moreover, there were no significant differences in the predictive value of the 3 models (MRI, OleaSphere, and Vitrea), suggesting that we can use the core volumes obtained using the 2 CTP software packages with different algorithms to predict the prognosis of patients with AIS. ACKNOWLEDGMENT
We would like to thank Editage (
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