Key-words: Anterior circulation acute ischemic stroke - computed tomography perfusion-Alberta
stroke program early computed tomography score - efficacy - endovascular treatment
- Thailand
Introduction
Radiologists and neurointerventionists have not yet conclusively identified the imaging
parameter or combination of imaging parameters that best assess parenchymal changes,
and that predict favorable clinical outcome after mechanical thrombectomy (MT) in
patients with anterior circulation ischemic stroke.
The area or quantity of brain ischemia or infarction is an important factor when attempting
to predict clinical outcome in this patient population. The common imaging parameter
for assessing brain parenchyma involvement is the Alberta Stroke Program Early Computed
Tomography (CT) Score (ASPECTS). Noncontrast CT (NCCT) of the brain is the first-line
diagnostic test in suspected acute stroke due to its widespread availability, fast
processing time, reasonable affordability, and its ability to exclude acute hemorrhage.
NCCT-ASPECTS is a widely accepted tool for guiding further treatment, and for predicting
clinical outcome in patients with acute ischemic stroke with large vessel occlusion,
mainly Middle cerebral artery (MCA) occlusion.[[1 ]] Hill et al.[[2 ]] reported a relative risk of the favorable outcome in the ASPECTS >7 group of 5.0
(95% confidence interval [CI]: 1.3–19.2), compared with 1.0 (95% CI: 0.6–1.9) in the
ASPECTS ≤7 group.
CT perfusion (CTP)-ASPECTS is a new imaging parameter that has been investigated for
its ability to predict the area of brain ischemia/infarction and clinical outcome.
Finlayson et al.[[3 ]] reported that total ASPECTS, when compared with NCCT brain, CT angiography (CTA)
brain, and CTP brain, had very good concordance, internal consistency, and internal
reliability. They also found that cerebral blood volume (CBV), which is one parameter
of CTP, had the best reliability for the evaluation of ischemic brain parenchyma in
all area of ASPECTS compared with NCCT brain, and in almost area of ASPECTS compared
with CTA brain. Lin et al.[[4 ]] found the accuracy of NCCT, CTA source images, and CTP CBV for detecting regional
infarct to be 80.0%, 84.3%, and 96.8%, respectively (P < 0.0001). They found correlations
between final ASPECTS and NCCT-ASPECTS, CTA-ASPECTS, and CBV-ASPECTS of r2 = 0.34,
r2 = 0.42, and r2 = 0.91, respectively. Aviv et al.[[5 ]] reported that CBV-ASPECTS ≥8 predicted major neurologic improvement (increase in
National Institutes of Health Stroke Scale [NIHSS] to ≥8 points at 24 h after recombinant
tissue plasminogen activator [rt-PA] treatment) (P = 0.02), and predicted good clinical
outcome (Modified Rankin Scale [mRS] ≤2 at 3 months after rt-PA treatment). That group
also found CBV-ASPECTS and NCCT-ASPECTS to have similar radiologic correlations (0.6
and 0.5, respectively) and best-predicted infarct size in the absence of major neurologic
improvement.
The identification of criteria that improves the selection of ischemic stroke patients
that is most suitable for MT will improve clinical outcomes. Accordingly, the aim
of this study was to identify the CT imaging parameter that best predicts the patients
who will benefit from endovascular treatment among patients with anterior circulation
ischemic stroke. More specifically, we set forth to identify association between CTP-assessment,
the CTP-ASPECTS, with variable CTP parameters and final treatment outcome (mRS) at
3 months in patients with ischemic anterior circulation stroke who were treated with
MT.
Materials and Methods
This study involved the retrospective review of the clinical and imaging findings
of 44 acute stroke patients who presented at Siriraj Hospital – Thailand's largest
and oldest medical school and national tertiary referral center – from the November
2009 to October 2016 study period. The protocol for this study was approved by the
Siriraj Institutional Review Board, Faculty of Medicine Siriraj Hospital, Mahidol
University, Bangkok, Thailand (COA no. Si 093/2017).
Patients with proximal MCA with/without intracranial internal carotid artery (ICA)
occlusion within 6 h who underwent admission NCCT brain and CTP brain (cerebral blood
flow [CBF], [CBV], mean transit time [MTT], and time to peak (TTP]) and successful
MT were included. Patients with unsuccessful MT, with no mRS evaluation at 3-month
post-MT, and/or that were lost to follow-up were excluded.
Both authors (DS and TK) reviewed and scored by consensus the baseline NCCT and CTP
(CBF, CBV, MTT, and TTP); however, both authors were blinded to clinical information
and follow-up imaging.
The baseline NCCT brain was scored using ASPECTS for early ischemic changes [[Figure 1 ]]. Four perfusion mapping techniques of CTP, included CBF, CBV, MTT, and TTP, were
applied to assess ASPECTS (i.e., CBF-ASPECTS, CBV-ASPECTS, MTT-ASPECTS, and TTP-ASPECTS,
respectively). Cut points of 50% and 75% abnormality that correspond to a color scale
bar were used to define the ischemic/infarction area [[Figure 2 ]].
Figure 1: Alberta stroke program early computed tomography score Is assessed by systematically
scoring each of 10 regions on the computed tomography scan[2]
Figure 2: Four perfusion mapping techniques of CTP, including CBF (a), CBV (b), TTP (c), and
MTT (d) are shown. The color scale bar of CBF and CBV (e), and TTP and MTT (f), with
50% and 75% cut points. CTP - Computed tomography perfusion; CTA - Computed tomography
angiography; TTP - Time to peak; CBF - Cerebral blood flow; MTT - Mean transit time
Demographic data, stroke symptom onset time (duration from the last time point, the
patient was observed without stroke symptoms until the hospital arrival time), NIHSS,
and 90-day mRS were collected from the patient medical chart and/or telephone interview
with patients or relatives. Good clinical outcome was defined when the patients have
mRS ≤2 at 3 months after MT.
Imaging
A Discovery CT750 HD multi-section scanner (GE Healthcare, Milwaukee, WI, USA) was
used to scan all included patients. The stroke fast-track protocol is described in
[[Table 1 ]].
Table 1: Stroke fast track protocol
CTP 4-dimension with Advantage Workstation 4.6 (GE Healthcare), which is an image
processing software program designed for multiplanar reconstruction and volume rendering,
was used to create and evaluate images.
Alberta stroke program early computed tomography score
For NCCT-ASPECTS, ASPECTS was assessed by systematically scoring each of 10 regions
on the CT scan [[Figure 1 ]], and assigning a score of “1” for a normal region and “0” for a region showing
signs of ischemia.[[2 ]] Signs of ischemia were defined as hypoattenuation, loss of gray-white boundary
(which is due to hypoattenuation of the gray matter), and/or effacement of cortical
sulci. Only new areas of acute ischemia were scored. The regions include the subcortical
structures, including the caudate nucleus, lentiform nucleus, and internal capsule,
genu, and posterior limb only (3 points); and the MCA cortex, including the insular
cortex – M1 through M6 (7 points). The score combines localization and volume into
a semi-quantitative topographic score. A score of 10 implies, no evidence of new early
signs of ischemia in MCA territory, and a progressively lower score indicates more
extensive ischemic changes.
For CTP-ASPECTS, ASPECTS was assessed by systematically scoring each of 10 regions
on the CTP image (the same regions that were scored for NCCT-ASPECTS), and assigning
a score of “1” for a normal region and “0” for an ischemic region. We designed three
steps for scoring of brain ischemia in each region, as follows: (1) comparison between
bilateral cerebral hemispheres to identify the region of perfusion abnormality; (2)
define the abnormal perfusion region as an ischemic area by using cut point at 50%
of the color scale bar; and (3) define the same abnormal perfusion region identified
in step 2 as an ischemic area by using cut point at 75% of the color scale bar. We
applied this 3-step method for all perfusion mapping techniques of CTP (i.e., CBF,
CBV, MTT, and TTP). For CBF and CBV, regions of brain parenchyma that displayed color
scale <50% and 75% compared with the color scale bar were defined as ischemic. For
MTT and TTP, regions of brain parenchyma that displayed color scale >50% and 75% compared
with the color scale bar were defined as ischemic [[Figure 2 ]]. Therefore, two groups of CTP-ASPECTS data (one at 50% and one at 75%) were collected
for each patient.
Statistical analysis
The study data were analyzed using SPSS Statistics version 21 (SPSS, Inc., Chicago,
IL, USA). Two-sample t-test was used to test the difference in quantitative variables
with and without normal distribution between patients with favorable and unfavorable
clinical outcome. Pearson's correlation coefficient was used to test association between
NCCT-ASPECTS and CTP-ASPECTS (CBF-ASPECTS, CBV-ASPECTS, MTT-ASPECTS, and TTP-ASPECTS).
Pearson's Chi-square test or Fisher's exact test was used to test the difference in
qualitative variables (e.g., gender, side of cerebral hemisphere, and CTP mismatch)
between groups. Data are presented as mean ± standard deviation or number and percentage.
Receiver Operating Characteristic curve was used to evaluate the score that predicts
clinical outcome after treatment. A two-tailed P < 0.05 was considered to be statistically
significant.
Results
Data from 44 acute MCA stroke patients that underwent successful MT were included
in the final analysis. Eight patients had tandem ICA/proximal MCA occlusion, 34 patients
had occlusion of M1 segment of MCA, one patient had occlusion of M2 segment of MCA,
and one patient had occlusion of M1 and M2 segment of MCA.
Seventeen patients (38.6%) had favorable clinical outcome (mRS at 3 months: 0–2),
and 27 patients (61.4%) had unfavorable clinical outcome (mRS at 3 months: 3–6; 5
patients (11.4%) died). Patients with favorable clinical outcome were significantly
more likely to be younger (P = 0.009) and to have higher NCCT-ASPECTS (P = 0.751),
more presence of CTP mismatch (P = 1.000), and smaller CTP core infarction (P = 1.000)
than those with the unfavorable clinical outcome. Females and those with left-sided
MCA occlusion were more likely to have an unfavorable clinical outcome (P = 0.096
and P = 0.054, respectively).
For CTP-ASPECTS at the 50% cut point, patients with favorable clinical outcome had
higher CBV-ASPECTS (P = 0.630) and higher MTT-ASPECTS (P = 0.731) than those with
unfavorable clinical outcome. For CTP-ASPECTS at the 75% cut point, patients with
favorable clinical outcome had a higher CBV-ASPECTS (P = 0.817), CBF-ASPECTS (P =
0.603), and MTT-ASPECTS (P = 0.063) than those with unfavorable clinical outcome [[Table 2 ]], [[Figure 3 ]] and [[Figure 4 ]].
Table 2: Demographic, clinical, and imaging data compared between the favorable and unfavorable
outcome groups
Figure 3: A 57-year-old man presented with left hemiparesis for 2 h, with favorable outcome
after successful mechanical thrombectomy. Axial NCCT brain at ganglionic level (a)
and supraganglionic level (b) showed hypodense area at right MCA cortex lateral to
the insular ribbon (M2), and at the superior territory of the right lateral MCA (M5);
NCCT-ASPECTS was 8 points. CTA brain axial (c) and coronal (d) images showed filling
defect along cavernous and supraclinoid parts of right ICA, and the M1 and M2 segments
of right MCA (red arrow). CTP brain at ganglionic level (e-h) and supraganglionic
level (i-l) showed mismatch area between CBV (f and j) and MTT (h and l) at rightfrontoparietal
area. (CTP-ASPECTS at 50% cut point: CBF-ASPECTS = 1, CBV-ASPECTS = 8, TTP-ASPECTS
= 0, MTT-ASPECTS = 1; CTP-ASPECTS at 75% cut point: CBF-ASPECTS = 2, CBV-ASPECTS =
9, TTP-ASPECTS = 4, MTT-ASPECTS = 6). Cerebral angiogram AP view of right CCA pre-IAT
(m) showed total occlusion at right carotid bulb and M1 segment of right MCA. AP view
of right ICA post-IAT (n) showed recanalization of the right carotid bulb and M1 segment
of right MCA. TICI 2b was achieved, and the patient's mRS score at 3 months was 1
point. NCCT - Noncontrast computed tomography; CTP - Computed tomography perfusion;
CTA - Computed tomography angiography; MCA - Middle cerebral artery; TTP - Time to
peak; CBF - Cerebral blood flow; IAT - Immunoaugmentative therapy; ASPECTS - Alberta
stroke program early computed tomography score; MTT - Mean transit time; AP - Anteroposterior
Figure 4: A 76-year-old woman with history of diabetes mellitus type 2 and hypertension presented
with right hemiparesis for approximately 2 h, with unfavorable outcome after successful
mechanical thrombectomy. Axial NCCT brain at ganglionic level (a) and supraganglionic
level (b) showed hypodense area at left insular cortex, left lentiform nucleus, left
anterior MCA cortex (M1), and superior territory of left lateral MCA (M5); NCCT-ASPECTS
was 6 points. CTA brain axial (c) and coronal (d) images showed abrupt filling defect
at M1 segment of left MCA (red arrow). CTP brain at ganglionic level (e-h) and supraganglionic
level (i-l) showed core infarction at left lentiform nucleus (less than 1/3 of left
MCA territory) and mismatch area between CBV (f and j) and MTT (h and l) at left frontotemporoparietal
area (CTP-ASPECTS at 50% cut point: CBF-ASPECTS = 1, CBV-ASPECTS = 6, TTP-ASPECTS
= 2, MTT-ASPECTS = 2; CTP-ASPECTS at 75% cut point: CBF-ASPECTS = 0, CBV-ASPECTS =
8, TTP-ASPECTS = 2, MTT-ASPECTS = 2). Cerebral angiogram AP view of left ICA pre-IAT
(m) showed total occlusion atM1segment of left MCA (red arrow). The same view post-IAT
(n) showed recanalization of M1 segment of left MCA. Although TICI 3 was achieved,
the patient's mRS score at 3 months was 5 points. NCCT - Noncontrast computed tomography;
CTP - Computed tomography perfusion; CTA - Computed tomography angiography; MCA -
Middle cerebral artery; TTP - Time to peak; CBF - Cerebral blood flow; IAT - Immunoaugmentative
therapy; ASPECTS - Alberta stroke program early computed tomography score; MTT - Mean
transit time; AP - Anteroposterior
Regarding association between NCCT-ASPECTS and CTP-ASPECTS, CBV-ASPECTS at the 50%
cut point had the highest correlation with NCCT-ASPECTS (r = 0.514), while TTP-ASPECTS
at the 50% cut point had the lowest correlation with NCCT-ASPECTS (r = 0.026) [[Table 3 ]].
Table 3: Correlation between noncontrast computed tomography-Alberta stroke program early
computed tomography score and computed tomography perfusion-Alberta stroke program
early computed tomography score
The distribution of CTP-ASPECTS data for all measured parameters was not significantly
different between the favorable and unfavorable clinical outcome groups. Therefore,
no appropriate score to predict the clinical outcome after treatment in this setting
was revealed in this study [[Figure 5 ]].
Figure 5: Distribution of computed tomography score-Alberta stroke program early computed tomography
score in the favorable (top section of each bar graph) clinical outcome and unfavorable
(bottom section of each bar graph) clinical outcome groups
Discussion
The identification of criteria that improves the selection of ischemic stroke patients
most suitable for MT will improve clinical outcomes. ASPECTS is a well-known and widely
accepted scoring tool that is easy to learn and easy to teach. ASPECTS provides those
who are not expert in CT scan interpretation with a framework to assess acute stroke
using CT imaging.[[6 ]],[[7 ]] Additionally, ASPECTS is more sensitive to smaller areas of ischemic change than
the one-third MCA rule. ASPECTS was first used as a method for scoring NCCT brain
to predict clinical outcome.[[2 ]],[[8 ]] Recent studies using contrast-enhanced CT techniques, such as the multiphase CTA
study by Menon et al.[[9 ]] found benefit for triage of anterior circulation stroke regardless of whether the
patient would or would not benefit from immunoaugmentative therapy (IAT) treatment.
CTP, an imaging tool that is good for the evaluation of affected brain parenchyma
is currently being investigated for its ability to predict clinical outcome after
MT in anterior circulation acute ischemic stroke. Given the relative scarcity of data
about CTP-ASPECTS,[[5 ]],[[6 ]] we set forth to further investigate the efficacy of CTP-ASPECTS for predicting
clinical outcome in the immediately aforementioned clinical setting.
Regarding qualitative variables, we found that younger patients were significantly
more likely to have a favorable outcome (mRS: 0–2) after MT than older patients (P
= 0.009). That result corresponds with the result of a study by Beumer et al.[[10 ]] that found a significant inverse association between age and good functional outcome
(mRS 0–2) (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.66–0.98) after IAT for every
10-year increase in age. They also reported a significant association between age
and the occurrence of all adverse events (aOR: 1.27, 95% CI: 1.08–1.50), as well as
the occurrence of nonneurologic adverse events (aOR: 1.34, 95% CI: 1.11–1.61).
Concerning quantitative variables, a recent study by Hill et al.[[2 ]] reported the relative risk of favorable outcome in the NCCT-ASPECTS >7 and ≤7 groups
of 5.0 (95% CI: 1.3–19.2) and 1.0 (95% CI: 0.6–1.9), respectively. In contrast, our
study found no significant difference for NCCT-ASPECTS (P = 0.751) between the favorable
and unfavorable clinical outcome groups.
CT perfusion (CTP) has been used for evaluation of patients with acute stroke for
a while.[[11 ]],[[12 ]],[[13 ]],[[14 ]] A recent study by Benson et al.[[15 ]] described the strong correlation between the core infarction on the CTP summary
map and the volume of the infarct on diffusion-weighted image relative to reliable
estimation of the actual infarct volume. Area infarction is known to be associated
with the final clinical outcome. However, our study found no significant difference
for any perfusion abnormality on CTP, either area matched or mismatched between outcome
groups. Favorable clinical outcome patients had more presence of CTP mismatch (P =
1.000) and smaller CTP core infarction (P = 1.000) than unfavorable clinical outcome
patients. Thus, the use of the established CTP reporting method is likely to be of
little value.
Finlayson et al.[[3 ]] reported that CBV had the best reliability for evaluating ischemic brain parenchyma
in all areas of ASPECTS compared with NCCT brain, and in almost all areas of ASPECTS
compared with CTA brain. Lin et al.[[4 ]] showed the accuracy of NCCT, CTA source images, and CTP (CBV) for detecting regional
infarct to be 80.0%, 84.3%, and 96.8%, respectively (P < 0.0001). Based on the findings
of those two studies, area with a different degree of ischemia and area of infarction
is considered to be easily separated.
We then set forth to predict the clinical outcome by assessing the degree of parenchymal
ischemia/infarction using CTP-ASPECTS, which was determined using cut points at 50%
and 75% of abnormality as observed on the color scale bar. The results our analysis
showed no statistically significant differences for CTP-ASPECTS (CBF-ASPECTS, CBV-ASPECTS,
MTT-ASPECTS, and TTP-ASPECTS) at the 50% and 75% cut points of abnormality between
the favorable and unfavorable clinical outcome groups. Of all measured parameters,
MTT-ASPECTS at the 75% cut point was the parameter that came closest to significantly
predicting clinical outcome (P = 0.063).
Finlayson, et al.[[3 ]] also reported that total ASPECTS, when compared with NCCT brain CTA brain, and
CTP brain, had very good concordance, internal consistency, and internal reliability.
Regarding the correlation between NCCT-ASPECTS and CTP-ASPECTS (included their mean
value), CBV-ASPECTS at the 50% cut point was found to have the highest correlation
with NCCT-ASPECTS (r = 0.514), while TTP-ASPECTS at the 50% cut point had the lowest
correlation with NCCT-ASPECTS (r = 0.026). No statistically significant association
was observed between NCCT-ASPECTS and CTP-ASPECTS (CBF-ASPECTS, CBV-ASPECTS, MTT-ASPECTS,
and TTP-ASPECTS) at 50% and 75% cut points in this study. Our small study population
may have limited our ability to identify a statistically significant association between
these parameters. Our finding is consistent with that of Aviv et al.[[5 ]] who reported a cut point for CBV-ASPECTS of ≥8 for predicting major neurologic
improvement (increase in NIHSS to ≥8 points at 24 h after tPA treatment) (P = 0.02),
and good clinical outcome (mRS of ≤2 at 3 months after tPA treatment).
Color images from any type of CTP are better able to demonstrate abnormality when
compared with gray-scale images from NCCT. However and in general, CTP-ASPECTS was
not shown to be a suitable alternative to NCCT-ASPECTS. Only CBV-ASPECTS was shown
to be closely correlated with NCCT-ASPECTS, and is, therefore, the only parameter
that we can recommend for use in routine practice. The reason the other CTP parameters
did not correlate with NCCT-ASPECTS is unclear, but it could be due to the way that
the image processes and represents the pathology. NCCT-ASPECTS demonstrates ischemic/infarction
area by process of cytotoxicity with or without vasogenic edema, which results in
increased brain water that, in turn, results in a reduction of brain parenchyma density
and hypodensity. In contrast, changes on CTP were related to changes in cerebral blood
perfusion and brain reaction that happens earlier than the process of edema. Changes
in the parameter related to blood flow (CBF) and the parameters related to time (TTP
and MTT) that convey the blood to the brain parenchyma are generally vivid, exaggerated,
and unequal to CBV, which reflects the volume of blood change. These factors influence
our visualization and scoring of CTP-ASPECTS, which was originally developed on NCCT.
Based on the findings of this study and from our experience in routine practice, we
recommend the use of CTP-ASPECTS, especially CBV-ASPECTS, in borderline NCCT-ASPECTS
(NCCT-ASPECTS 6–7) that has clinical-imaging mismatch, which indicates that there
is probably some salvageable area remaining that may benefit from MT. The use of CTP-ASPECTS
in combination with the old method of CTP-interpretation (the mismatched concept)
is a cause of potential concern. Further study for this issue might be helpful in
find out the best imaging for selection patient who will benefit from MT.
The present study was unable to identify a cut point for any of the measured CTP-ASPECTS
parameters at either 50% abnormality or 75% abnormality for predicting clinical outcome
after thrombectomy. It is important to note that no cut point for any of the studied
parameters has been previously reported in this setting.
The limitations of this study were its single-center retrospective design and its
small study population, which was due to the fact that we included only MCA occlusion
that underwent successful MT. Further study with a larger sample size may have more
power to identify significant associations or differences between groups and also
benefit in additional radiation dose from CTP.
Conclusions
CTP-ASPECTS at the 50% and 75% cut points of abnormality could not predict the clinical
outcome of anterior ischemic stroke after MT. Of the ASPECTS evaluated in this study,
MTT-ASPECTS at the 75% cut point was the most predictive CT parameter. Older age was
associated with unfavorable clinical outcome after MT.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form, the patients have given their consent for their images and other clinical
information to be reported in the journal. The patient understands that name and initials
will not be published, and due efforts will be made to conceal identity, but anonymity
cannot be guaranteed.
