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International Journal of Stroke

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CT perfusion core and ASPECT score ! 2020 World Stroke Organization
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DOI: 10.1177/1747493020915141
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May Kim-Tenser1 , Michael Mlynash2, Maarten G Lansberg2 ,

Matthew Tenser3, Sebina Bulic1, Bharathi Jagadeesan4,
Soren Christensen2, Alexis Simpkins5, Gregory W Albers2 and
Michael P Marks6

Abstract
Background: The role of Alberta Stroke Program Early CT Score (ASPECTS) for thrombectomy patient selection and
prognostication in late time windows is unknown.
Aims: We compared baseline ASPECTS and core infarction determined by CT perfusion (CTP) as predictors of clinical
outcome in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE) 3 trial.
Methods: We included all DEFUSE 3 patients with baseline non-contrast CT and CTP imaging. ASPECTS and core
infarction were determined by the DEFUSE 3 core laboratory. Primary outcome was functional independence (modified
Rankin Scale (mRS) 2). Secondary outcomes included ordinal mRS shift at 90 days and final core infarction volume.
Results: Of the 142 patients, 85 patients (60%) had ASPECTS 8–10 and 57 (40%) had ASPECTS 5–7. Thirty-one patients
(36%) with ASPECTS 8–10 and 11 patients (19%) with ASPECTS 5–7 were functionally independent at 90 days (p ¼ 0.03).
In the primary and secondary logistic regression analysis, there was no difference in ordinal mRS shift (p ¼ 0.98) or
functional independence (mRS  2; p ¼ 0.36) at 90 days between ASPECTS 8–10 and ASPECTS 5–7 patients. Similarly,
primary and secondary logistic regression analyses found no difference in ordinal mRS shift (p ¼ 1.0) or functional
independence (mRS  2; p ¼ 0.87) at 90 days between patients with baseline small core ( < 50 ml) versus medium
core (50–70 ml).
Conclusions: Higher ASPECTS (8–10) correlated with functional independence at 90 days in the DEFUSE trial.
ASPECTS and core infarction volume did not modify the thrombectomy treatment effect, which indicates that patients
with a target mismatch profile on perfusion imaging should undergo thrombectomy regardless of ASPECTS or core
infarction volume in late time windows.

Keywords
Stroke, CT perfusion, ASPECTS, outcomes, core, endovascular thrombectomy

Received: 30 October 2019; accepted: 21 January 2020

Introduction
Endovascular thrombectomy is an effective treatment
1
for acute ischemic stroke (AIS) due to large vessel Department of Neurology, University of Southern California, Los
Angeles, CA, USA
occlusion (LVO) of the internal carotid artery or first 2
Department of Neurology, Stanford University, Palo Alto, CA, USA
part of the middle cerebral artery (M1).1–7 Patients 3
Department of Neurosurgery, University of Southern California, Los
most likely to benefit from thrombectomy have a Angeles, CA, USA
4
small amount of core infarction present at the time of Department of Radiology, University of Minnesota, Minneapolis, MN,
treatment,6,7 and the Alberta Stroke Program Early CT USA
5
Department of Neurology, University of Florida, Gainesville, FL, USA
Score (ASPECTS) is a standardized 10-point method to 6
Department of Radiology, Stanford University, Palo Alto, CA, USA
quantify the degree of ischemic injury on non-contrast
Corresponding author:
head CT.8 In early time windows, favorable ASPECTS May Kim-Tenser, Department of Neurology, University of Southern
(8–10) has been correlated with superior outcomes after California, 1540 Alcazar Street, CHP 215, Los Angeles, CA 90033, USA.
thrombectomy and has become an important selection Email: may.kim@med.usc.edu

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2 International Journal of Stroke 0(0)
criterium for thrombectomy treatment.2–4 However, the
importance of ASPECTS in the evaluation of AIS
patients with LVO who present in late time windows
(6–24 h) has not been described.
Endovascular Therapy Following Imaging
Evaluation for Ischemic Stroke 3 (DEFUSE 3) is a
prospective, randomized, open-label trial comparing
thrombectomy to medical management for patients
with symptoms between 6 and 16 h, with a documented
occlusion in the internal carotid artery or proximal
middle cerebral artery.7 DEFUSE 3 demonstrated the
effectiveness of thrombectomy in late time windows
when patients are selected with a target mismatch pro-
file on perfusion imaging. Eligible patients were
required to have a favorable target mismatch profile
on perfusion imaging using RAPID (iSchemaView,
Menlo Park, CA), which is an automated CT postpro-
cessing system. Core infarct was defined as cerebral
blood flow <30% of normal tissue, and hypoperfusion
was defined as tissue with Tmax >6 s. A favorable mis-
match profile was defined as a core infarct <70 ml, a
ratio of hypoperfusion to core infarct of 1.8 or more,
and potentially reversible volume of 15 ml or more.
Patients with ASPECTS <6 or a core infarction greater
than 70 ml on baseline imaging were excluded from
enrollment.
The purpose of this study was to determine whether
ASPECTS on baseline CT predicted favorable clinical
outcome 90 days after thrombectomy in the DEFUSE 3
study. The relationship between ASPECTS and core
infarction volume, as determined by CT perfusion
(CTP), was also assessed.
Methods
The data that support the findings of this study are
available from the corresponding author upon reason-
able request.
DEFUSE 3 study and patients
DEFUSE 3 was a multicenter, randomized trial that
compared endovascular thrombectomy with medical
management for the treatment of AIS due to an anter-
ior circulation LVO in patients last known to be normal
6 to 16 h prior to enrollment.7,9 All included patients or
their next of kin provided informed consent for inclu-
sion in DEFUSE 3, and this study was approved by our
institutional review board.
This analysis of ASPECTS as a predictor of clinical
outcome was a pre-specified analysis, and all DEFUSE
3 patients who underwent baseline imaging by CT with
CTA and CTP were included. Patients who were
screened for DEFUSE 3 inclusion, but who were not
randomized, were also included in parts of the analysis
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in order to understand better the relationship between
ASPECTS and core infarction on baseline imaging.
ASPECTS was assessed by one rater.
Imaging analysis
All imaging studies were interpreted by the DEFUSE 3
core laboratory in a blinded manner.7,9 ASPECTS was
determined on non-contrast head CT from the qualify-
ing imaging study at the time of patient enrollment.
Good ASPECTS was defined as 8–10 and poor
ASPECTS was defined as 5–7; although ASPECTS
<6 were excluded from enrollment, there were two
patients who were enrolled with ASPECTS of 5 upon
core laboratory review on the qualifying imaging.
Baseline core infarction and penumbra volumes were
quantified using RAPID. Baseline core infarctions
were dichotomized into small core (<50 ml) and large
core (50–70 ml). Reperfusion was assessed on 24-h MR
or CTP studies. Infarction growth was defined as the
difference between the baseline core infarction volume
and the 24-h core infarction volume.
Clinical definitions and outcomes
Stroke severity was quantified using the National
Institutes of Health Stroke Scale (NIHSS). Primary
outcome was ordinal modified Rankin Scale (mRS) at
90 days. Secondary outcomes included dichotomized
favorable clinical outcome (mRS 0–2) at 90 days, symp-
tomatic intracranial hemorrhage, stroke related death,
and core infarction growth at 24 h.
Statistical analysis
Differences in the proportions were compared using
chi-square test or Fisher’s exact test, while continuous
and ordinal variables were compared using Mann–
Whitney U test. Odd ratios were estimated and if neces-
sary compared using Breslow-Day test. To assess
treatment effect between ASPECTS groups adjusted
for other factors and covariates, we conducted binary
or ordinal logistic regression analyses, accordingly. All
statistical tests were two-sided and considered signifi-
cant at  < 0.05. Analysis was done with SAS 9.4.
Results
To determine the relationship between ASPECTS and
core infarction on baseline CT, we examined both
patients who were consented and enrolled, as well as
enrolled but not randomized. There were 114 patients
who were enrolled but not randomized, and included
patients with lower ASPECTS, including patients with
ASPECTS  3 that had large core infarctions
Kim-Tenser et al.
Figure 1. Relationship between baseline core infarction volume and ASPECTS in the DEFUSE 3 study. Whisker plots showing the
relationship between baseline core infarction volume and ASPECTS in the DEFUSE 3 study. (a) Core volume and ASPECTS in
patients who were screened for enrollment in DEFUSE 3, but who were not randomized. (b) Core volume and ASPECTS in
patients who were enrolled in the DEFUSE 3 study.
(Figure 1). However, in both patients who were not
randomized and those who were enrolled, there was
overall a poor correlation between baseline ASPECTS
and core infarction volume. The Rho (Spearman’s
Rank correlation coefficient) is 0.34 (p < 0.001) for
ASPECTS versus core volume for the DEFUSE 3 ran-
domized patients, which can be interpreted as low
(weak) negative correlation. Rho for consented non-
randomized patients was0.82 (p < 0.001), which can
be interpreted as strong negative correlation (Figure 1).
We then analyzed only patients enrolled in DEFUSE
3 to determine the relationship between ASPECTS and
clinical outcome. Of 182, 142 (78%) patients in
DEFUSE 3 met inclusion criteria, and these patients
were dichotomized into ASPECTS 8–10 (85 patients,
60%) and ASPECTS 5–7 (57 patients, 40%) groups.
The rest were excluded because they underwent MRI.
There were no differences in demographics, past med-
ical history, or stroke presentation and treatment
details between these groups (Table 1). Patients with
ASPECTS 5–7 were more likely to have internal carotid
artery (ICA) occlusions (53% vs. 33%; p ¼ 0.02), larger
baseline core infarctions (13.8 (IQR 7.9–41.7) ml vs. 5.5
(IQR 0–13.6) ml; p < 0.001), and larger penumbra vol-
umes (131.5 (IQR 87.4–176.9) versus 109.9 (IQR 75.0–
145.8); p ¼ 0.02). These data are summarized in Table 1.
There was no difference in the frequency of thromb-
ectomy, time to thrombectomy arterial puncture, time
to reperfusion, or frequency of revascularization or
reperfusion between ASPECTS 8–10 and ASPECTS
5–7 patients (Table 2). ASPECTS 8–10 patients had
smaller infarct volumes at 24 h (30.5 ml (IQR 12.8–
3
67.0) vs. 75.7 (IQR 36.9–146.9) in ASPECTS 5–7
patients; p < 0.001). There was no difference in symp-
tomatic intracranial hemorrhage or death between
these two groups (Table 2). A greater percentage of
ASPECTS 8–10 patients were functionally independent
(mRS 0–2) at 90 days (36%) compared to ASPECTS
5–7 patients (19%; p ¼ 0.03). The ordinal distribution
of 90 day mRS scores is shown in Figure 2. ASPECTS
and baseline core infarction did not modify thrombec-
tomy treatment effect but there was a non-significant
trend toward better outcomes in patients with
ASPECTS 8–10 and lower core volumes (<50 ml).
In the primary outcome regression analysis, there
was no difference between ASPECTS 8–10 (OR 2.4;
95% CI, 1.1–5.3) and ASPECTS 5–7 (OR 2.9; 95%
CI, 0.9–6.0) for a better ordinal mRS shift at 90 days
associated with treatment (p ¼ 0.98; Table 3). In the
secondary outcome analysis, there was also no differ-
ence between ASPECTS 8–10 (OR 2.6; 95% CI, 1.0–
6.7) or ASPECTS 5–7 (OR 6.4; 95% CI, 1.2–32.0) for
association of functional independence at 90 days with
treatment (mRS 0–2, p ¼ 0.36; Table 3). After adjust-
ment for age, presentation NIHSS, blood glucose level,
no difference between ASPECTS 8–10 (OR 2.5; 95%
CI, 1.1–5.4) or ASPECTS 5–7 (OR 3.6; 95% CI, 1.4–
9.3) for treatment association with favorable mRS shift
was found (p ¼ 0.56; Table 3). Similarly, there was no
difference between ASPECTS 8–10 (OR 4.4; 95% CI,
1.3–15.4) or ASPECTS 5–7 (OR 11.3; 95% CI,
1.7–75.8) for treatment association with functional
independence at 90 days (mRS 0–2, p ¼ 0.41) in the
adjusted analysis (Table 3).
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Table 1. Patient demographics and stroke presentation details

ASPECTS 8–10 (n ¼ 85) ASPECTS 5–7 (n ¼ 57) p value

Age, median (IQR) 71 (62–78) 66 (57–80) 0.37

Female, N (%) 43 (51) 25 (44) 0.43

Hispanic ethnicity, N (%) 11 (13) 5 (9) 0.43

Caucasian ethnicity, N (%) 70 (82) 52 (91) 0.14

HTN, N (%) 68 (80) 45 (79) 0.88

HLD, N (%) 41 (48) 26 (46) 0.76

Atrial fibrillation, N (%) 33 (39) 17 (30) 0.27

Diabetes mellitus, N (%) 28 (33) 17 (30) 0.70

Prior stroke, N (%) 16 (19) 7 (12) 0.30

Presentation NIHSS, median (IQR) 15 (11–20) 18 (14–20) 0.08

Treated with IV-tPA, N (%) 6 (7) 5 (9) 0.71

Right sided stroke, N (%) 38 (45) 29 (51) 0.47

ICA occlusion, N (%) 28 (33) 30 (53) 0.02

MCA occlusion, N (%) 57 (67) 27 (47)

Ischemic core (mL), median (IQR) 5.5 (0–13.6) 13.8 (7.9–41.7) <0.001

Perfusion lesion (mL), median (IQR) 109.9 (75.0–145.8) 131.5 (87.4–176.9) 0.02

Mismatch volume (mL), median (IQR) 95.5 (66.5–136.4) 105.6 (69.1–151.5) 0.30

Time from last known well to baseline 10:32 (8:47–11:59) 10:39 (8:14–12:42) 0.85
imaging (h:min), median (IQR)
ASPECTS: Alberta Stroke Program Early CT Score; HLD: hyperlipidemia; HTN: hypertension; ICA: internal carotid artery; IQR: interquartile range;
IV-tPA: intravenous tissue plasminogen activator; MCA: middle cerebral artery; NIHSS: National Institutes of Health Stroke Scale.

We also performed a regression analysis for the pri-

mary and secondary outcomes and baseline core infarc-
tion (Table 3). In the unadjusted model, baseline core
infarction did not pass the proportionality assumptions
test. After adjustment for age, presentation NIHSS,
blood glucose level, the primary outcome (ordinal
mRS shift at 90 days) regression analysis found an
OR for treatment effect of 10.7 (95% CI, 1.1–109.0)
for patients with a moderate baseline core infarction
of 50–70 ml versus OR 2.7 (95% CI, 1.4–5.1) for
patients with a small baseline core infarction of
<50 ml (p ¼ 0.26), but these differences were not signifi-
cant. Similarly, the logistic regression for the secondary
outcome measure (mRS  2 at 90 days) did not find a
significant difference between baseline core 50–70 ml
and baseline core <50 ml in an unadjusted or adjusted
analysis (Table 3).
Discussion
In this study of DEFUSE 3 patients, we found that
patients with ASPECTS 8–10 were more likely to be
functionally independent (mRS 2) at 90 days com-
pared to patients with less favorable ASPECTS 5–7.
Interestingly, we also found a poor correlation between
baseline core infarction as determined by CTP and
ASPECTS.
ASPECTS is a standardized 10-point scale to assess
cerebral infarction through the quantification of hypo-
density within specific regions of the brain on non-
contrast head CT.8 In early time windows, patients
with ASPECTS 6–10 are likely to benefit from thromb-
ectomy,2–4 and ASPECTS is frequently used for
thrombectomy patient selection in patients presenting
within 6 h of symptom onset. In this study, we found

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Kim-Tenser et al. 5

Table 2. Imaging and clinical outcomes in patients with good versus poor ASPECTS

ASPECTS 8–10 (n ¼ 85) ASPECTS 5–7 (n ¼ 57) p value

Randomized to thrombectomy, N (%) 48 (57) 28 (49) 0.39

Time from last known well to femoral 12:11 (10:29–13:15) 11:07 (8:39–12:51) 0.22
puncture (h:min), median (IQR)

Time from last known well to reperfusion 13:05 (11:22–14:35) 11:45 (9:32–13:17) 0.11
(h:min), median (IQR)

24-h infarct volume (mL), median (IQR) 30.5 (12.8–67.0) 75.7 (36.9–146.9) <0.001

Reperfusion >90%, N (%) 35 (57) 20 (43) 0.13

Complete recanalization on CTA/MRA, N (%) 40 (54) 24 (48) 0.51

Reperfusion and/or recanalization, N (%) 41 (55) 21 (40) 0.11

Symptomatic ICH, N (%) 5 (6) 2 (4) 0.70

mRS 0–2 at 90 days, N (%) 31 (36) 11 (19) 0.03

Mortality, N (%) 17 (20) 12 (21) 0.88

ASPECTS: Alberta Stroke Program Early CT Score; CTA: computed tomography angiography; ICH: intracerebral hemorrhage; MRA: magnetic res-
onance angiography; mRS: modified Rankin Scale.

Figure 2. Distribution of mRS scores at 90 days stratified by baseline ASPECTS and treatment arm. Modified Rankin Scale scores
in DEFUSE 3 patients at 90 days after enrollment in patients with ASPECTS 8–10 and ASPECTS 5–7. Patients are further separated
into medical and endovascular treatment groups.

90-day mRS distribution stratified by

ASPECTS 8-10 vs. 5-7
0 1 2 3 4 5 6

endovasc
10 23 13 15 19 6 15
ASPECTS 8-10

(n=48)

medical
16 5 3 16 16 16 27
(n=37)

endovasc
7 7 18 18 25 11 14
(n=28)
ASPECTS 5-7

medical
03 3 17 34 14 28
(n=29)

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
%

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Table 3. Logistic regression to determine treatment effect by baseline ASPECTS and CTP core

OR
(unadjusted) 95% CI p value OR (adjusted) 95% CI p value

Ordinal regression for mRS at 90 days

ASPECTS

ASPECTS 8–10 OR 2.4 1.1–5.25 0.980 OR (8–10) 2.5 1.1–5.4 0.56

ASPECTS 7 OR 2.9 0.94–6.0 OR (7) 3.6 1.4–9.3

CTP corea
Moderate core (50–70 ml) – 1.0 OR (50–70 ml) 10.7 1.05–109 0.26

Small core (<50 ml) – <0.001 OR (<50 ml) 2.7 1.4–5.1

Logistic regression for mRS 0–2 at 90 days

ASPECTS

ASPECTS 8–10 OR 2.6 1.03–6.7 0.358 OR (8–10) 4.4 1.3–15.4 0.41

ASPECTS 7 OR 6.4 1.2–32.0 OR (7) 11.3 1.7–75.8

CTP Core
Moderate core (50–70 ml) OR 4.3 0.11–177 0.871 OR (50–70 ml) 50.8 0.77–>1000 0.27

Small core (<50 ml) OR 3.2 1.4–7.0 OR (<50 ml) 4.7 (infinity) 1.7–13.1
ASPECTS: Alberta Stroke Program Early CT Score; CI: confidence interval; CTP: CT perfusion; mRS: modified Rankin Scale; OR: odds ratio.
Unadjusted p values estimated by Mann–Whitney. Adjustments for age, NIHSS, and glucose.
a
Unadjusted ordinal analysis for CTP core did not pass proportionality assumption test, so no OR is provided.

that patients with favorable ASPECTS 8–10 are more
likely to be functionally independent at 90 days com-
pared to patients with less favorable ASPECTS 5–7,
which is consistent with early window time studies.2–4
It is important to note that ASPECTS <6 was used an
exclusion criterium in DEFUSE 3, and our study did
not test the hypothesis that ASPECTS 6–10 is appro-
priate for thrombectomy candidate selection in late
time windows. Therefore, the use of ASPECTS for
thrombectomy triage in late time windows requires fur-
ther study.
We overall found a poor correlation between
ASPECTS and core infarction volume, as determined
by CTP, in our study. When we considered both
patients enrolled and those who were screened but
not enrolled in DEFUSE 3, we found that patients
with very high ASPECTS (ASPECTS 9–10) had small
core infarction volumes. Conversely, patients with very
low ASPECTS (ASPECTS 0–2) had very large core
infarction volumes. However, there was very poor cor-
relation between core infarction volume and ASPECTS
in the middle range (ASPECTS 3–8). Therefore, it is
difficult to accurately assess the volume of core
infarction in patients with ASPECTS ranging from 3
to 7, which suggests that studies using ASPECTS as an
enrollment criterium may inadvertently treat patients
with very large core infarctions despite a favorable
ASPECTS. This hypothesis is consistent with results
from the Randomized Trial of Revascularization with
Solitaire FR Device vs Best Medical Therapy in the
Treatment of Acute Stroke Due to Anterior
Circulation Large Vessel Occlusion Presenting within
Eight Hours of Symptom Onset (REVASCAT) trial,3
which selected patients for thrombectomy if CT
ASPECTS was >6 or MRI ASPECTS was >5. The
benefit of thrombectomy declined over time, and
patients ASPECTS 6–7 had a markedly reduced fre-
quency of good outcomes.3,10 We hypothesize that the
lack of correlation between ASPECTS and core infarc-
tion reflects the superior evaluation of brain perfusion
offered by CTP relative to non-contrast head CT, which
is known to be relatively insensitive to the detection of
cerebral ischemia.11–13
Our finding that baseline ASPECTS and core infarc-
tion volume do not modify the treatment effect of
thrombectomy is surprising. This result suggests that

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Kim-Tenser et al.
patients with a target mismatch profile on perfusion
imaging should be considered for thrombectomy
regardless of ASPECTS and core infarction volume.
This observation also has implications for future stu-
dies designed to test the hypothesis that thrombectomy
might lead to improved outcomes in patients with a
large baseline core infarction (>70 ml) compared to
medical therapy.
Conclusions
CT ASPECTS score of 8–10 was correlated with func-
tional independence at 90 days. CT ASPECTS did not
correlate with baseline CTP core infarction in the
DEFUSE 3 trial.
Acknowledgements
We thank the DEFUSE 3 Primary Investigators and the
National Institutes of Neurological Disorders and Stroke.
Clinical Trial Registration: https://clinicaltrials.gov/ct2/
show/NCT02586415.
Declaration of conflicting interests
The author(s) declared the following potential conflicts of
interest with respect to the research, authorship, and/or pub-
lication of this article: MGL: Novo Nordisk, Genentech/
Roche, Biogen and Moleac. Principal investigator on research
grants from the NIH and from Neofect. GWA: iSchemaView,
Inc (equity and consulting); Medtronic (consulting). JJH:
iSchemaView, Inc (Medical and Scientific Advisory Board);
Medtronic (consulting); MicroVention (consulting).
Funding
The author(s) disclosed receipt of the following financial sup-
port for the research, authorship, and/or publication of this
article: Funding was provided by grants from the National
Institutes of Neurological Disorders and Stroke
(U10NS086487 and U01NS092076).
ORCID iDs
May Kim-Tenser https://orcid.org/0000-0003-0555-0661
Maarten G Lansberg https://orcid.org/0000-0002-3545-
6927
7
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