Editorial
Clots, Collaterals, and the Intracranial Arterial Tree
Bijoy K. Menon, MD, MSc; Mayank Goyal, MD
See related article, p XXX
thrombus lysis is accumulating.3–8 In their article, Santos et
al8 showed that thrombus permeability as measured by comparing attenuation increase within the thrombus on computed
tomographic angiography (CTA) when compared with attenuation of thrombus on the noncontrast CT is associated with
increased likelihood of recanalization (measured at 24–48
hours) in patients administered with alteplase. Moreover,
thrombus permeability is also associated with better clinical
outcome in their study. Santos et al8 thus substantiate previous evidence about thrombus porosity identified using such
imaging constructs like residual flow through thrombus on CT
angiography and occult anterograde flow through thrombus on
CT perfusion that are imaging markers of early thrombus lysis
with alteplase.3,7 Other imaging constructs like thrombus location on CTA and Trans-cranial Doppler, thrombus length on
noncontrast CT and CTA, clot burden score on CTA, forward
flow through clot on dynamic CTA, collateral status on CTA
and CT perfusion, Gradient Echo blooming on magnetic resonance imaging have all been shown to be markers of thrombus
lysis with alteplase.2–8 Taken together, this growing body of
literature is helping treating physicians who predict the likelihood of treatment success with alteplase in patients with acute
ischemic stroke.
Although progress in understanding thrombus lysis
within the intracranial tree in patients with acute ischemic
stroke is gratifying, more needs to be achieved before this
research can directly influence treatment decisions. Since
time is of essence in determining stroke treatment outcome, studies testing the above imaging constructs need to
use early recanalization as the primary outcome measure.
Thrombi are also likely to differ in constitution across
their entire length. We have previously demonstrated that
a thrombus within the intracranial tree may have 2 components, that is, the original thrombus (either embolic or
forming in situ because of adjacent arterial pathology, such
as atherosclerotic plaque) and de novo thrombus formation
around this original thrombus.2 This is in keeping with our
personal experience where after successful endovascular
thrombectomy the part of the thrombus that is captured
on the stent retriever is significantly shorter than what was
seen on the CT angiogram. If true, it is likely that these
components may behave differently. Moreover, constitution of thrombi can evolve over time.2 Future studies need
to account for this heterogeneity in thrombus constitution
spatially and temporally when predicting recanalization
with alteplase. Larger prospective studies collecting data
on early recanalization with alteplase are needed because
they can provide us with more precise estimates of early
recanalization and consequently more reliable prediction
models. Moreover, research needs to identify the value of
each individual imaging construct vis a vis others and the
rich interaction among them when building and validating
A
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cute ischemic stroke is a story of two parts; a thrombus
blocks anterograde blood flow within the intracranial arterial tree while tiny vessels called collaterals sustain the brain until
the thrombus is cleared. The location, size, and type of thrombus
along with the degree and extent of collaterals likely determine
the patient’s clinical symptoms, the likelihood of treatment success and the patient’s prognosis. A major focus of acute stroke
research has been to image and measure various thrombus and
collateral characteristics that help predict patient outcomes.
In vitro studies show that larger clots are less likely to lyse
with thrombolytic agents, whereas clots with more surface
area exposed to flowing blood are more likely to lyse early.1
This information can be used to create a theoretical framework for thrombus lysis within the intracranial arterial tree.2
Thrombi in proximal arteries such as the internal carotid or the
M1 segment of the middle cerebral artery are likely to have
greater volume than thrombi in smaller more distal arteries.
Independent of thrombus volume, longer thrombi within the
cylindrical framework of the intracranial arterial tree are likely
to have less relative surface area (at the proximal and distal
ends) exposed to blood flow. Poor collateral status is likely
to result in less blood flow at the distal end of any thrombi
within the arterial tree.2 Less number of arterial branches at
the proximal and distal ends of thrombi are more likely to
result in stasis of blood flow at the ends of thrombi.2 Thrombi
that are structurally porous are likely to have more surface
area exposed to blood flow. Thus, thrombus lysis within the
intracranial tree will depend on the following characteristics:
1.Location
2.Length
3.Collateral status
4.Angioarchitecture of cerebral arterial tree
5.Thrombus porosity
Empirical evidence from studies in patients with acute
ischemic stroke supporting this theoretical framework of
The opinions expressed in this article are not necessarily those of the
editors or of the American Heart Association.
From the Departments of Clinical Neurosciences (B.K.M., M.G.),
Radiology (B.K.M., M.G.), Community Health Sciences (B.K.M., M.G.),
and Medicine (B.K.M., M.G.), Cumming School of Medicine, University
of Calgary, Calgary, Canada; and The Hotchkiss Brain Institute, Calgary,
Canada (B.K.M.).
Correspondence to Mayank Goyal, MD, Department of Radiology,
Seaman Family MR Research Centre, Foothills Medical Centre, 1403 –
29th St NW, Calgary AB T2N 2T9, Canada. E-mail [email protected]
(Stroke. 2016;47:00-00.
DOI: 10.1161/STROKEAHA.116.013829.)
© 2016 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.116.013829
1
2 Stroke August 2016
these prediction models. Imaging modalities such as magnetic resonance imaging and transcranial Doppler, although
less practical currently in the hyper-acute stroke workflow,
may also help in this effort in the future.2,4
A theoretical framework of in vivo thrombus lysis
within the intracranial arterial tree supported by empirical
research is likely to help physicians make treatment decisions about the risks and benefits of thrombolysis. This evidence-supported framework also has the potential to inform
future research on augmented thrombolysis technologies
and better mechanical thrombectomy devices, thus improving clinical outcome in patients with acute ischemic stroke.
This research by Santos et al8 is yet another important step
toward this broad goal.
Disclosures
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Dr Menon reports membership of the Steering and Executive
Committee, ESCAPE trial (Endovascular Treatment for Small
Core and Anterior Circulation Proximal Occlusion With Emphasis
on Minimizing CT to Recanalization Times) that received support
from Covidien Inc, Site Principal Investigator, SOCRATES trail
(Acute Stroke or Transient Ischaemic Attack Treated With Aspirin or
Ticagrelor and Patient Outcomes), sponsored by Astra Zeneca, honoraria from Penumbra Inc, a provisional patent 62/086077 for triaging
systems in ischemic stroke, research funding from Canadian Institute
of Health Research, Heart and Stroke Foundation of Canada, Alberta
Innovates Health Solutions, Hotchkiss Brain Institute, and the Faculty
of Medicine, University of Calgary. Dr Goyal reports partial support
for ESCAPE trial provided to University of Calgary. He also helped
in design and conduct of the SWIFT PRIME trial (Solitaire With the
Intention for Thrombectomy as Primary Endovascular Treatment);
Compensation: Significant (>$10k or 5%). In addition, Dr Goyal
has received compensation for speaking engagements from Covidien
Inc (significant) and Stryker Inc (modest). He also has a patent for
Systems of stroke diagnosis licensed to GE Healthcare (compensation significant).
References
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Key Words: Editorials ◼ brain ◼ middle cerebral artery ◼ prognosis ◼ stroke
Clots, Collaterals, and the Intracranial Arterial Tree
Bijoy K. Menon and Mayank Goyal
Stroke. published online June 23, 2016;
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