Acute Stroke:

Prognostic Value of
Quantitative Collateral
Assessment at Perfusion CT

R1 Nachchakorn Kwankajonwong, M.D.

Advisor: Supada Prakkamakul, M.D. Radiologist
• Published online: Jan 08, 2019

• Published in print: Mar, 2019

Introduction
Introduction
• Collateral circulation in Acute ischemic stroke
(AIS)
 can maintain perfusion
 may contribute to prolonged penumbral sustenance
 associated with neurologic outcome

• Several grading methods have been proposed

 Tan scale
 Miteff scale
 Regional leptomeningeal collateral score
 Introduction

Tan scale Collateral

supply to the
occluded MCA
territory

0 absent

1 ≤50%but>0%

>50% but
2
<100%

3 100%

AJNR Am J Neuroradiol. 2009 Mar;30(3):525-31.

 Introduction

Miteff scale — grade MCA collateral

status with respect to the Sylvian
fissure

Vessels were reconstituted distal

good to the occlusion

Vessels could be seen within the

moderate Sylvian fissure

Contrast opacification was

poor merely seen in the distal
superficial branches

Brain. 2009 Aug;132(Pt 8):2231-8.

 Introduction

Regional leptomeningeal
collateral score. (rLMC score)

- Six ASPECTS cortical regions

(M1–M6) scored 0, 1, or 2
- Parasagittal ACA territory
- Basal ganglia

- Pial arteries within the scored 0, 2, or 4

Sylvian sulcus

AJNR Am J Neuroradiol. 2011 Oct;32(9):1640-5.

 Introduction
Regional leptomeningeal
collateral score. (rLMC score)
- M1–M6
- Parasagittal ACA territory scored 0, 1, or 2
- Basal ganglia
- Pial arteries within the scored 0, 2, or 4
Sylvian sulcus
Introduction
• Several grading methods have been proposed
• However, a reliable quantitative assessment of collateral
vessels based : not currently available.
 Introduction
• Hypothesis
 Perfusion CT-derived blood flow of collateral vessels
within the Sylvian fissure may reflect retrograde filling
via the leptomeningeal collateral in patients with large
artery occlusion of the anterior circulation.

• Aim
 To develop a technique for quantitative assessment of
collateral perfusion at CT and to investigate its value in
the prediction of outcome in patients with AIS.
Material and Methods
Study Population
• Retrospective analysis
• Patients with AIS who underwent thrombolytic therapy with or
without mechanical thrombectomy from May 2009 to August 2017
• Selection criteria
 (a) had a diagnosis of AIS confirmed with diffusion-weighted imaging or CT
 (b) underwent perfusion CT within 8 hours after stroke onset
 (c) had occlusion of the MCA-M1 segment with or without internal carotid
artery
 (d) underwent follow-up CT angiography or time-of-flight MR angiography at
24 hours
 (e) underwent unenhanced CT or susceptibility-weighted imaging at 24 hours
 (f) had clinical follow-up with assessment of the modified Rankin scale (mRS)
score at 90 days
• Excluded patients who had poor image quality due to motion artifacts or
incomplete imaging studies.
Data Collection
• Demographic, clinical, and radiologic data
 Age
 Sex
 Onset-to-needle time (ONT)
 Blood pressure
 Baseline National Institutes of Health Stroke Scale (NIHSS) score
 Prior antiplatelet use

• Risk factors
 Smoking history
 Hypertension
 Diabetes mellitus
 Hyperlipidemia
 History of stroke or transient ischemic attack
 Atrial fibrillation
 Data Collection
• Modified Rankin scale (mRS)
• Patients were dichotomized into groups with good (mRS score ≤2) or poor
(mRS score >2) outcome at 90 days.
Score Definition
0 No symptoms at all
1 No significant disability despite symptoms: able to carry out all usual duties
and activities Good
2 Slight disability: unable to carry out all previous activities but able to look outcome
after own affairs without assistance
3 Moderate disability: requiring some help, but able to walk without assistance

4 Moderately severe disability: unable to walk without assistance, and unable

Poor
to attend to own bodily needs without assistance
outcome
5 Severe disability: bedridden, incontinent, and requiring constant nursing
care and attention
6 Dead
Stroke. 1988 May;19(5):604-7.
 Image Analysis
• Recanalization was assessed with the arterial occlusive lesion
scale at 24-hour CT angiography or MR angiography.
 Arterial occlusive lesion grades 2 and 3 were defined as recanalization
 Arterial occlusive lesion grades 0 and 1 were defined as no recanalization

Stroke. 2013 Sep;44(9):2650-63.

Image Analysis
• Hemorrhagic transformation was assessed with 24-hour
susceptibility-weighted imaging or unenhanced CT
• The Alberta Stroke Program Early CT Score (ASPECTS)
 Assessed by a neurologist with about 5 years of experience (C.L.)

• Baseline infarct core volume

 Pretreatment relative CBF of less than 30% at perfusion CT

• Final infarct volume

 A neurologist with about 10 years of experience (Z.C.) and another
neurologist with about 3 years of experience (X.G.) used 24-hour
diffusion-weighted imaging or unenhanced CT

• Baseline hypoperfused volume

 A threshold of time-to-peak of the residual function (Tmax) of more
than 6 seconds at perfusion CT
Collateral Status
• Qualitative Assessment
 By two neurologists (Z.C., X.G.) according to predefined criteria
at artery peak phase of CT angiograms, which were
reconstructed from perfusion CT source images
 Modified Tan scale
 Good: ≥50% collateral supply to the occluded MCA territory
 Poor: <50% collateral supply to the occluded MCA territory
 Miteff scale
 Regional leptomeningeal collateral score

• Quantitative Assessment
 Collateral Status: Quantitative
Assessment

Reconstructed CT - Temporally MIP - Each ROI was then Merged images were
(tMIP) maps copied to the obtained by
angiograms
- An 20-year corresponding CBF overlaying the CBF
experienced blinded map
map onto the tMIP
neurologist (M.L.) - Maximum CBF
value within each
map with an opacity
outlines the whole
ROI was of 20%.
visible vessels within
the Sylvian fissure on subsequently
each image section achieved The highest CBF value from all sections
(usually 2-3 sections). was recorded as cCBFmax.
Interobserver Concordance
• For the cCBFmax , 5-year experienced blinded neurologist
(M.L.) also delineated the ROIs.
 Compare to assess interobserver concordance

• The interobserver concordance were calculated

 Qualitative collateral assessments
 Final infarct volume measurement
Statistical Analysis

Continuous variables

Median (interquartile
range)
Statistical Analysis

Continuous variables

Correlations between two

variables were assessed
with Spearman ρ
Statistical Analysis

Categorical variables

Number of patients
(Percentage)
Statistical Analysis

Categorical variables

the Mann-
Whitney U test was used
to compare differences
between two groups
Statistical Analysis

For categorical variables

the χ2 test was used to
compare differences
among groups.
Statistical Analysis

For continuous variables,

the Mann-Whitney U test
was used to compare
differences between two
groups
Statistical Analysis

The variables with P < .1 at

univariable analysis were
included in the multivariable
logistic regression analysis.
 Statistical Analysis

• The nonparametric receiver operating characteristic (ROC) analyses  AUC

• Optimal cutoff values were derived from ROC curves, and sensitivity and
specificity were calculated based on these best cutoff values.
Statistical Analysis
• Interobserver reliability was assessed with the
intraclass correlation coefficient (ICC) based on a
two-way random-effects model.

• All statistical analyses were performed by using

 SPSS, version 22.0 (IBM, Armonk, NY) and
 Stata 14.0 (Stata, College Station, Tex)

•P < .05 indicated a significant difference.

Results
 Patient Characteristics
Patients excluded
VS
Patients included
• Excluded patients had
 a lower rate of hypertension
(P = .04)
 a higher rate of stroke or
transient ischemic attack
history (P = .006)

• No significant difference
in other baseline
characteristics,
hemorrhagic
transformation, or good
outcome (all P > .05).
 Patient Characteristics and cCBFmax

Median cCBFmax was 66 mL/100 g/min (IQR, 46–88 mL/100 g/min).

 Patient Characteristics and cCBFmax

The cCBFmax has mild negative correlation

with
- Age (ρ = −0.26, P < .001)
- Baseline NIHSS score (ρ = −0.31, P < .001)

Median cCBFmax was 66 mL/100 g/min (IQR, 46–88 mL/100 g/min).

 Patient Characteristics and cCBFmax

The cCBFmax was lower in patients with

- Hypertension (61 [40–84] vs 72 [53–95]; P = .02)
- Atrial fibrillation (61 [42–82 ] vs 69 [51–103]; P = .03)

Median cCBFmax was 66 mL/100 g/min (IQR, 46–88 mL/100 g/min).

 Patient Characteristics and cCBFmax

Median cCBFmax was 66 mL/100 g/min (IQR, 46–88 mL/100 g/min).

 Patient Characteristics and cCBFmax

The cCBFmax has positive correlation with

- Baseline CT-ASPECTS (ρ = 0.31, P < 0.001)

The cCBFmax has negative correlation with

- Baseline infarct core volume (ρ = −0.53, P < 0.001)
- Hypoperfusion volume (ρ = −0.41, P < 0.001)

Median cCBFmax was 66 mL/100 g/min (IQR, 46–88 mL/100 g/min).

 cCBFmax and Qualitative Assessments of
Collaterals

80 [65–107]
47 [27–62] 75 [62–98]
61 [43–94]
46 [25–59]

• Difference in cCBFmax among • cCBFmax was

Poor collateral flow had lower
poor, moderate, and good positively
cCBFmax than good flow collateral status groups associated with
(P < 0.001)
• Kruskal-Wallis and Dunn tests
rLMC score
(P < 0.001). • (ρ = 0.56, P < 0.001)
cCBFmax and Clinical Outcome
cCBFmax and Clinical Outcome :
1. Final infarct volume

cCBFmax had a negative

correlation with final infarct
volume
(ρ = −0.57, P < .001)
 cCBFmax and Clinical Outcome :
2. Hemorrhagic transformation

cCBFmax was lower in patients with

hemorrhagic transformation
cCBFmax and Clinical Outcome :
3. Recanalization

No difference in cCBFmax between

recanalization and no recanalization
(P = .14)
cCBFmax and Clinical Outcome :
4. Good outcome at 90-day (mRS ≤2 )

The cCBFmax was higher in patients

with good outcome (90-day mRS ≤2)
Ability to Discriminate Clinical Outcome Using ROC
Analyses

AUC of cCBFmax higher than

AUC of rLMC score (P = .007)
AUC of modified Tan scale (P = 0.01)
AUC of Miteff scale (P = .003)
But no difference with AUC of baseline NIHSS (P = .53)
Ability to Discriminate Clinical Outcome Using ROC
Analyses

higher Good collateral Multivariable analyses:

circulation [n = 106] Good collateral circulation =
cCBFmax
Independent predictor of good
Cutoff outcome (OR, 5.43;
64 mL/100 g/min 95% CI: 2.48, 11.89; P < .001)
Poor collateral
lower circulation [n = 98]
Reproducibility Assessment
• Excellent interobserver reproducibility
 Measurement of cCBFmax ICC = 0.92

• Goodinterobserver agreement in qualitative

assessments
 Modified Tan scale ICCs = 0.86
 Miteff scale ICCs = 0.84
 rLMC score ICCs = 0.85

• Theinterobserver agreement for final infarct

volume
 ICC > 0.99
Discussion
Discussion
• Quantitative indicator (cCBFmax ) for collateral status
assessment on CBF maps derived from perfusion CT.
• Higher cCBFmax : independent predictor for
 lower risk of hemorrhagic transformation
 better neurologic outcome

• cCBFmax threshold of 64 mL/100 g/min for differentiation of

patients with good outcome VS poor outcome.
 Excellent Interobserver reproducibility
 Superior to existing qualitative indexes of collateral flow
Discussion
• cCBFmax combines Anatomic information + Temporal resolution
• To assess both structure and function of the collateral pathway

• Theoretically, cCBFmax has a positive correlation with the blood

velocity in collateral vessels
• cCBFmax reflects the capacity of collateral circulation
Discussion
• cCBFmax : First quantitative collateral assessment revealed on
a CBF map

• Used to predict neurologic outcome after reperfusion therapy in

patients with AIS.
Discussion
• cCBFmax might be able to facilitate appropriate patient triage

• The 2018 AHA and ASA guidelines recommend mechanical

thrombectomy in selected patients with AIS within 6–24 hours
of last known normal status who have large vessel occlusion in
the anterior circulation and meet other DAWN or DEFUSE-3
eligibility criteria.
• The time window of substantial clinical benefit may be longer
in patients with good collateral status
Limitation
• Retrospective study :
 Potential risk of selection bias

• Included only proximal occlusion of the anterior circulation :

 Not applicable to small or posterior circulation stroke

• Did not analyze imaging markers, such as contrast

attenuation and length of the thrombus :
 Might have affected the outcome
Conclusion
• cCBFmax was evaluated in patients with large anterior
artery occlusions who underwent reperfusion therapy.
• cCBFmax was independently associated with neurologic
outcome and compared favorably to existing qualitative
metrics of collateral perfusion.
• cCBFmax may facilitate appropriate patient triage and guide
prognosis and management in the acute stage of ischemic
stroke.
Thank you
Journal Appraisal
Acute Stroke:
Prognostic Value of
Quantitative Collateral
Assessment at Perfusion CT

R3 Kumpol Tankittiwat, M.D.

Advisor: Supada Prakkamakul, M.D. Radiologist
25.11.2019
•

•
Published online: Jan 08, 2019

Published in print: Mar, 2019

Impact factor: 7.608
Study objectives
• To develop a technique for quantitative assessment of collateral perfusion at
CT.

• To investigate its value in the prediction of outcome in patients with AIS.

(M1 Occlusion)
Critical Appraisal of Prognostic study
• Step 1: Are the results of the study valid?

• Step 2: What were the results?

• Step 3: Will these results help me in caring for my patients?

Step 1: Are the results of the study
valid?
• Was the defined representative sample of patients assembled at a
common point in the course of their disease?

• Retrospective analysis
 ( from May 2009 to Aug 2017 )

• Between sample and excluded patients

 No sig. difference in baseline characteristics
and outcome, except lower rate of HT
and higher rate of stroke/TIA history
in excluded group.
Step 1: Are the results of the study
valid?
• Was patient follow-up sufficiently long and complete?

• Clinical outcome
 Occurrence of hemorrhagic transformation ( at 24hr NECT or SWI )
 Final infarct volume ( at 24hr NECT or DWI )
 Recanalization ( at 24hr CTA or MRA)
 Outcome at 90 days (mRS ≤ 2 or > 2)

• No dropout.
Step 1: Are the results of the study
valid?
• Were outcome criteria either objective or applied in a ‘blind’
fashion?

• Tool: cCBFmax calculated from ROI drawn by one investigator (M.L.)

blinded from clinical information.

• Clinical outcome
 Occurrence of hemorrhagic transformation - objective
 Final infarct volume ( at 24hr NECT or DWI ) - objective
 Recanalization ( at 24hr CTA or MRA) – using Arterial occlusive lesion scale ( grade
0-1 or grade 2-3)
 Outcome at 90 days (mRS ≤ 2 or > 2) - objective
Step 2: What were the results?
• The cCBFmax:

• Mild negative correlation with: Age, Baseline NIHSS score.

• Lower in patients with Hypertension, Atrial fibrillation.

• Positive correlation with Baseline CT-ASPECTS.

• Negative correlation with Baseline infarct core volume, Hypoperfusion

volume.

• Agree with qualitative assessments of collaterals.

• ( modified Tan scale, Miteff scale and rLMC score)
Step 2: What were the results?
• The cCBFmax and outcome:

• Lower in patients with hemorrhagic transformation

• Negative correlation with final infarct volume

• No difference between recanalization and no recanalization

• Higher in patients with good outcome (90-day mRS ≤ 2)

Step 2: What were the results?
• The ability of cCBFmax to discriminate outcome:

• Better than modified Tan scale, Miteff scale, rLMC score but not baseline
NIHSS score or any pairs of assessment and baseline scale. (AUC values in
ROC analysis)
• Optimal cutoff cCBFmax = 64 mL/100 g/min.
 Sensitivity = 79.2% (68.0 – 87.8)
 Specificity = 62.9% (54.0 – 71.1)
 Also an independent predictor of good outcome OR = 5.43 ( p < .001 )
Step 3: Will these results help me in
caring for my patients?
• Are the study results applicable to the patient in your practice?

Courtesy of Dr. Sasitorn Petcharunpaisan

Step 3: Will these results help me in
caring for my patients?
• Were the methods for performing the test described in sufficient
detail to permit replication?

The highest CBF value

from all sections was
recorded as cCBFmax

ICC = 0.92

Reconstructed CT - Temporally MIP (10mm) - Each ROI copied to

outlines the whole the corresponding
angiograms
visible vessels within CBF map for
the Sylvian fissure on - Maximum CBF
each image section. within each ROI
Step 3: Will these results help me in
caring for my patients?
• Were the methods for performing the test described in sufficient
detail to permit replication?
• CT brain perfusion protocol.

Imaging parameters Article (Somatom Definition Flash) KCMH (GE Revolution)

Delayed after injection (s) 4 5
Total imaging duration (s) 74.5 70
kV 80 80
mA 120 110
Slice thickness(mm) 1.5 5
Detector coverage (mm) 150 160
Total scans 26 37
Contrast medium/ Vol. Iopamidol (60 mL) Iopamiro (50 mL)
Flow rate (mL/s) 6 5
 Step 3: Will these results help me in
caring for my patients?
• Will the result change your management strategy?

• In prognosis; maybe yes.

• In management; may be not – need more evidence.

± Courtesy of Dr. Sasitorn Petcharunpaisan

Thank you