Stroke

BRIEF REPORT

Optimal Tissue Reperfusion Estimation by

Computed Tomography Perfusion Post-
Thrombectomy in Acute Ischemic Stroke
Zefeng Tan , MD, PhD; Mark Parsons , MD, PhD; Andrew Bivard, MD, PhD; Gagan Sharma, MD, PhD;
Peter Mitchell , MD, PhD; Richard Dowling, MD, PhD; Steven Bush, MD, PhD; Anding Xu , MD, PhD; Bernard Yan , MD, PhD

BACKGROUND AND PURPOSE: Modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b is defined as successful reperfusion.
However, mTICI has rarely been correlated with dynamic perfusion imaging postendovascular therapy for acute stroke. We
aimed to study the proportion of tissue optimal reperfusion (TOR) postendovascular therapy across different grades of mTICI.

METHODS: We conducted a single-center retrospective analysis of patients with acute ischemic strokes who had endovascular
therapy between 2018 and 2019. Computer tomography perfusion or magnetic resonance perfusion was performed before
and after endovascular therapy. Tmax+6 volume reduction of >90% was defined as TOR. Comparisons of proportions of
TOR in different grades of mTICI were performed. In the present study, the requirement for informed consents was waived.

RESULTS: Eighty-two patients were included. The difference in the proportion of TOR for TICI categories was statistically
significant (mTICI score 0, 0%, mTICI score 2A, 0%, mTICI score 2b, 50.0%, mTICI score 2c, 80.0%, mTICI score 3, 81.3%,
χ2=14.035, P=0.003). Multivariable logistic regression showed that lower age (odds ratio, 0.932, P=0.017), onset-to-tissue-
type plasminogen activator time (odds ratio, 0.980, P=0.005) and TOR (odds ratio, 8.764, P=0.031) were associated with
favorable functional outcome.
Downloaded from http://ahajournals.org by on January 20, 2022

CONCLUSIONS: The proportion of TOR achieved by mTICI score of 2b was significantly lower than mTICI score of 2c and
mTICI score of 3. TOR was associated with favorable functional outcome, and the degree of reperfusion was more strongly
correlated with outcomes than the mTICI scores.

GRAPHIC ABSTRACT: An online graphic abstract is available for this article.

Key Words:  cerebral infarction ◼ ischemic stroke ◼ odds ratio ◼ reperfusion ◼ tomography

S
uccessful reperfusion is a predictor of favorable
functional outcome after endovascular therapy (EVT)
for acute stroke due to large vessel occlusion.1–8
The different levels of modified Thrombolysis in Cerebral
Infarction score (mTICI) achieved by EVT procedures will
result in various penumbra areas’ reperfusion, affecting
clinical outcomes. A recent multicenter registry showed
that mTICI score of 2b was associated with independent
functional state in 40%, and 55% if mTICI score of 3 was
achieved.9 Clinical interventionalist generally use mTICI
post-EVT as a substitute index of reperfusion status, and
mTICI score of 2b/3 was considered as a proxy for suc-
cessful reperfusion in the international thrombectomy
guidelines,10,11 and few studies had explored the associa-
tion between tissue reperfusion and TICI status.12,13
Most recent literature reviews reported mTICI score of
2c/3 as a potential better standard of successful recanaliza-
tion, leading to better functional outcome than mTICI score of
2b.14,15 Therefore, we hypothesized that mTICI score of 2c/3
recanalization might lead to better reperfusion than TICI 2b.

 
Correspondence to: Bernard Yan, MD, PhD, Melbourne Brain Centre, Royal Melbourne Hospital, Parkville, Melbourne, Victoria 3050, Australia, Email bernard.yan@
mh.org.au
This manuscript was sent to Ru-Lan Hsieh, Guest Editor, for review by expert referees, editorial decision, and final disposition.
The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.121.034581.
For Sources of Funding and Disclosures, see page e762.
© 2021 American Heart Association, Inc.
Stroke is available at www.ahajournals.org/journal/str

e760   December 2021 Stroke. 2021;52:e760–e763. DOI: 10.1161/STROKEAHA.121.034581

 Tan et al
In this study, we aimed to investigate the proportions
of successful reperfusion as defined by tissue optimal
reperfusion (TOR; reperfusion of the Tmax>6 seconds
over 90%) for different grades of mTICI. We hypothe-
sized (1) that TOR was higher in proportions in mTICI
score of 3 and (2) that TOR was associated with favor-
able outcome.
METHODS
Authors declare that all supporting data are available within the
article and in the Data Supplement. Extra data are available
from the corresponding author on reasonable request.
Study Population and Data Collection
Between January 2018 to April 2019, patients who underwent
EVT at Royal Melbourne Hospital (Victoria, Australia) for acute
ischemic stroke were included in this retrospective study. The
local institutional review board reviewed and approved this ret-
rospective study. All enrolled patients were treated according
to the current guideline for acute ischemic stroke. Inclusion
criteria (1) ischemic stroke with large vessel occlusion in the
anterior circulation, intracranial internal carotid artery, middle
cerebral artery M1 and M2; (2) underwent EVT for acute isch-
emic stroke; (3) post-EVT mTICI score of ≥2b; (4) preproce-
dural computed tomography (CT) perfusion and CT angiogram;
and (5) CT perfusion or magnetic resonance perfusion 24 to
36 hours after EVT.
Downloaded from http://ahajournals.org by on January 20, 2022
Imaging Evaluation
All digitally subtracted angiography images were reviewed
by 2 experienced neuroradiologists (B. Yan and P. Mitchell).
An mTICI (with additional mTICI score of 2c grading) score
was assigned based on the final angiogram of the endovas-
cular procedure.16,17 Automatic CT perfusion evaluation soft-
ware, RAPID (iSchema View, version 5.0.2, Menlo Park, CA),
was used to estimate the ischemic core and hypoperfused
volumes. The volume of hypoperfused tissue was defined as
a Tmax delay of >6 seconds (Tmax+6),18 and the ischemic
core was defined as relative cerebral blood flow<30% for CT
perfusion.6 The reperfusion status analysis was performed
after imaging artifacts had been manually removed. TOR was
defined as >90% reduction of the Tmax>6 seconds lesion vol-
umes between the baseline and the early follow-up perfusion
studies.12,13
Statistical Analysis
Variables were presented as appropriate medians or propor-
tions. The Mann-Whitney U test was used for continuous
variable comparison, and the Fisher exact test was used for
proportion comparison. The TOR proportions were compared
between mTICI groups using Kruskal-Wallis test for nonpara-
metric analysis. The baseline and treatment variables were
compared using a univariable regression analysis. We con-
ducted multivariable logistic regression analysis to calculate
adjusted odds ratios for all exposure variables with a P value
of <0.10 in univariable analysis. All tests were 2-tailed, with a
significance level of 0.05.
Stroke. 2021;52:e760–e763. DOI: 10.1161/STROKEAHA.121.034581
Optimal Tissue Reperfusion Post-Thrombectomy
RESULTS
Baseline Characteristics
Brief Report
The study population consisted of 82 patients, and their
baseline information and trial flowchart were presented
in the Data Supplement (Table I in the Data Supple-
ment and Figure).
Proportions of TOR Among mTICI Grades
The differences in TOR proportions for different TICI
categories were statistically significant (mTICI score
0, 0% versus, mTICI score 2A, 0%, mTICI score 2b,
50.0% versus, mTICI score 2c, 80.0%, mTICI score
3, 81.3%, χ2=14.035, P=0.003; Table II in the Data
Supplement). There was statistical difference in the
proportion of achieving TOR between the mTICI score
of 0-2A and mTICI score 2b-3 (0.0% versus 62.7%,
respectively, P=0.01) and in the proportion of achieving
TOR between mTICI score of 0-2A and mTICI score
of 2c-3 (44.9% versus 80.6%, χ2=10.012, P=0.002;
Table III in the Data Supplement).
Clinical Outcomes
In univariate logistic regression analysis, age (P=0.001),
National Institutes of Health Stroke Scale score (P=0.016),
onset-to-tissue-type plasminogen activator time (P=0.020),
TOR (P=0.005) were significantly associated with favor-
able functional outcome. No significant association was
found between mTICI score of >2b and favorable functional
outcome (P=0.076).In adjusting for age, baseline National
Institutes of Health Stroke Scale, rCBF, and mTICI score
of >2b, only age (odds ratio, 0.932, P=0.002), onset-to-
tissue-type plasminogen activator time (odds ratio, 0.980,
P=0.005), and TOR (odds ratio, 8.764, P=0.031) was an
independently associated factor of favorable functional out-
come 90 days (Table IV in the Data Supplement).
DISCUSSION
Our study showed significant differences in TOR propor-
tions among the different grades of mTICI after EVT in
anterior circulation large vessel occlusion and TOR was
associated with favorable functional outcomes. In a post
hoc analysis of DEFUSE1 and DEFUSE2 (Diffusion and
Perfusion Imaging Evaluation for Understanding Stroke
Evolution Study), clinical outcome was strongly asso-
ciated with the degree of reperfusion, and each 10%
increase in the degree of reperfusion had an odds ratio
of 1.31 (95% CI, 1.14–1.50) for good functional out-
come.12 The target mismatch patients with reperfusion
(Tmax >6 seconds reperfusion over 90%) achieved a
similar rate of favorable clinical outcome (75%) com-
pared with our findings 66% (31/47).12 In DEFUSE 3,
79% of patients who achieved ≥90% reperfusion had a
December 2021   e761
 Tan et al
Brief Report
strong correlation between the baseline ischemic core
and 24-hour postrandomization infarct volume (r=0.83;
Downloaded from http://ahajournals.org by on January 20, 2022
P<0.0001).13 Considering the TOR proportions are sig-
nificantly different among different mTICI categories in
our study, we think that achieving reperfusion of ≥90%
might be an optimal target for reperfusion therapies.
There were limitations to our study. First, due to the
study’s retrospective nature, some patients were not
included because of incomplete perfusion examination.
Second, the interval of perfusion examination in this study
was 24 hours, and the re-occlusion of vessels within 24
hours may affect the evaluation of perfusion status.
CONCLUSIONS
The proportion of TOR achieved by mTICI score of 2b
was significantly lower than mTICI score of 2c and mTICI
score of 3. TOR was associated with good functional out-
come, and the degree of reperfusion was more strongly
correlated with outcomes than the mTICI scores.
ARTICLE INFORMATION
Received March 19, 2021; final revision received June 4, 2021; accepted June
24, 2021.
Affiliations
Department of Neurology, the First Affiliated Hospital, Jinan University, Guang-
zhou, Guangdong, China (Z.T., A.X.). Department of Neurology, Shun De Hospital
of Jinan University, Guangzhou, Guangdong, China (Z.T.). Melbourne Brain Cen-
tre, Royal Melbourne Hospital, University of Melbourne, Australia (Z.T., M.P., A.B.,
e762   December 2021
Optimal Tissue Reperfusion Post-Thrombectomy
Figure. Trial flowchart.
CTP indicates computed tomography
perfusion; EVT, endovascular therapy; ICA,
internal carotid artery; and mTICI, modified
Thrombolysis in Cerebral Infarction.
G.S., B.Y.). Neurointervention Service, Department of Radiology, Royal Melbourne
Hospital, Australia (P.M., R.D., S.B., B.Y.).
Sources of Funding
None.
Disclosures
Dr Parsons reports research collaborations (discounted software) with Siemens,
Canon, and Apollo Medical Imaging (MIStar) and works as a member of advisory
board of Boehringer Ingelheim. Dr Mitchell reports education at international con-
ference provided by stryker and research support from Medtronic, outside of the
submitted work. The other authors report no conflicts.
Supplemental Materials
Online Tables I–IV
REFERENCES
1. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo
AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, et al; MR CLEAN
Investigators. A randomized trial of intraarterial treatment for acute ischemic
stroke. N Engl J Med. 2015;372:11–20. doi: 10.1056/NEJMoa1411587
2. Menon BK, Hill MD, Davalos A, Roos Y, Campbell B, Dippel D, Guillemin
F, Saver JL, van der Lugt A, Demchuk AM, etal. Efficacy of endovascular
thrombectomy in patients with M2 segment middle cerebral artery occlu-
sions: meta-analysis of data from the HERMES Collaboration. J Neurointerv
Surg. 2019;11:1065–1069. doi: 10.1136/neurintsurg-2018-014678
3. Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B,
Dowling RJ, Parsons MW, Oxley TJ, et al; EXTEND-IA Investigators. Endo-
vascular therapy for ischemic stroke with perfusion-imaging selection. N
Engl J Med. 2015;372:1009–1018. doi: 10.1056/NEJMoa1414792
4. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J,
Roy D, Jovin TG, Willinsky RA, Sapkota BL, et al; ESCAPE Trial Inves-
tigators. Randomized assessment of rapid endovascular treatment of
ischemic stroke. N Engl J Med. 2015;372:1019–1030. doi: 10.1056/
NEJMoa1414905
5. Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers
GW, Cognard C, Cohen DJ, Hacke W, et al; SWIFT PRIME Investigators.
Stroke. 2021;52:e760–e763. DOI: 10.1161/STROKEAHA.121.034581
 Tan et al
Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.
N Engl J Med. 2015;372:2285–2295. doi: 10.1056/NEJMoa1415061
6. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez
S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, et al; DEFUSE
3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selec-
tion by Perfusion Imaging. N Engl J Med. 2018;378:708–718. doi:
10.1056/NEJMoa1713973
7. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira
A, San Román L, Serena J, Abilleira S, Ribó M, et al; REVASCAT
Trial Investigators. Thrombectomy within 8 hours after symptom
onset in ischemic stroke. N Engl J Med. 2015;372:2296–2306. doi:
10.1056/NEJMoa1503780
8. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM,
Dávalos A, Majoie CB, van der Lugt A, de Miquel MA, et al; HERMES col-
laborators. Endovascular thrombectomy after large-vessel ischaemic stroke:
a meta-analysis of individual patient data from five randomised trials. Lancet.
2016;387:1723–1731. doi: 10.1016/S0140-6736(16)00163-X
9. Goyal N, Tsivgoulis G, Frei D, Turk A, Baxter B, Froehler MT, Mocco J,
Ishfaq MF, Malhotra K, Chang JJ, et al. Comparative safety and efficacy of
modified TICI 2b and TICI 3 reperfusion in acute ischemic strokes treated
with mechanical thrombectomy. Neurosurgery. 2019;84:680–686. doi:
10.1093/neuros/nyy097
10. Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, Schellinger
PD, Toni D, de Vries J, White P, et al. European Stroke Organisation
(ESO)- European Society for Minimally Invasive Neurological Therapy
(ESMINT) guidelines on mechanical thrombectomy in acute isch-
emic stroke. J Neurointerv Surg. 2019;11:535–538. doi: 10.1136/
neurintsurg-2018-014568
11. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC,
Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, et al. Guidelines
for the early management of patients with acute ischemic stroke: 2019
update to the 2018 guidelines for the early management of acute ischemic
stroke: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2019;50:e344–e418.
doi: 10.1161/STR.0000000000000211
Downloaded from http://ahajournals.org by on January 20, 2022
Stroke. 2021;52:e760–e763. DOI: 10.1161/STROKEAHA.121.034581
Optimal Tissue Reperfusion Post-Thrombectomy
12. Inoue M, Mlynash M, Straka M, Kemp S, Jovin TG, Tipirneni A, Hamilton
SA, Marks MP, Bammer R, Lansberg MG, et al; DEFUSE 1 and 2
Investigators. Clinical outcomes strongly associated with the degree
Brief Report
of reperfusion achieved in target mismatch patients: pooled data from
the diffusion and perfusion imaging evaluation for understanding
stroke evolution studies. Stroke. 2013;44:1885–1890. doi: 10.1161/
STROKEAHA.111.000371
13. Rao V, Christensen S, Yennu A, Mlynash M, Zaharchuk G, Heit J, Marks MP,
Lansberg MG, Albers GW. Ischemic core and hypoperfusion volumes cor-
relate with infarct size 24 hours after randomization in DEFUSE 3. Stroke.
2019;50:626–631. doi: 10.1161/STROKEAHA.118.023177
14. Tung EL, McTaggart RA, Baird GL, Yaghi S, Hemendinger M, Dibiasio EL,
Hidlay DT, Tung GA, Jayaraman MV. Rethinking thrombolysis in cerebral
infarction 2b: which thrombolysis in cerebral infarction scales best define
near complete recanalization in the modern thrombectomy era? Stroke.
2017;48:2488–2493. doi: 10.1161/STROKEAHA.117.017182
15. Dargazanli C, Fahed R, Blanc R, Gory B, Labreuche J, Duhamel A, Marnat
G, Saleme S, Costalat V, Bracard S, et al; ASTER Trial Investigators.
Modified thrombolysis in cerebral infarction 2C/Thrombolysis in cerebral
infarction 3 reperfusion should be the aim of mechanical thrombectomy:
insights from the ASTER Trial (Contact Aspiration Versus Stent Retriever
for Successful Revascularization). Stroke. 2018;49:1189–1196. doi:
10.1161/STROKEAHA.118.020700
16. Almekhlafi MA, Mishra S, Desai JA, Nambiar V, Volny O, Goel A, Eesa M,
Demchuk AM, Menon BK, Goyal M. Not all “successful” angiographic reper-
fusion patients are an equal validation of a modified TICI scoring system.
Interv Neuroradiol. 2014;20:21–27. doi: 10.15274/INR-2014-10004
17. Goyal M, Fargen KM, Turk AS, Mocco J, Liebeskind DS, Frei D, Demchuk
AM. 2C or not 2C: defining an improved revascularization grading scale and
the need for standardization of angiography outcomes in stroke trials. J
Neurointerv Surg. 2014;6:83–86. doi: 10.1136/neurintsurg-2013-010665
18. Zaro-Weber O, Moeller-Hartmann W, Heiss WD, Sobesky J. Maps of time to
maximum and time to peak for mismatch definition in clinical stroke studies
validated with positron emission tomography. Stroke. 2010;41:2817–2821.
doi: 10.1161/STROKEAHA.110.594432
December 2021   e763