Brain Hemorrhages 1 (2020) 6–12

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Brain Hemorrhages
CHINESE ROOTS
GLOBAL IMPACT
journal homepage: www.keaipublishing.com/en/journals/brain-hemorrhages/

Review article

Collaterals in ischemic stroke

Konark Malhotra a, David S. Liebeskind b,⇑
a
Department of Neurology, Charleston Area Medical Center, West Virginia University – Charleston Division, WV 25301, USA
b
Department of Neurology and Neurovascular Imaging Research Core, University of California at Los Angeles, Los Angeles, CA 90095, USA

a r t i c l e i n f o a b s t r a c t

Article history: Collateral flow plays a pivotal role, both in acute and chronic phases of cerebral ischemia. Recruitment of
Received 19 December 2019 these redundant vascular networks maintains cerebral blood flow to ischemic areas, while primary arte-
Accepted 19 December 2019 rial conduits are obstructed either due to steno-occlusive or acute occlusive lesion. Until recently, a heavy
Available online 23 January 2020
focus had been placed solely on such impaired antegrade flow, while the contribution from primary and
secondary collateral pathways has been largely disregarded. Imaging of the brain with focus on delineat-
Keywords: ing the collateral circulation has been critical to interpret the mechanism of vascular remodeling that
Collaterals
occurs with ischemic injury. Recent multimodal imaging modalities have encouraged physicians to assess
Ischemic stroke
Imaging
collateral flow and hemodynamics from a temporal perspective, distinguishing individual cases to tailor
the treatment. Collateral status varies among individuals, correlating with stroke severity and reperfusion
outcomes. While new techniques to enhance collateral flow have been speculative, we provide a compre-
hensive review on the role of collaterals and its therapeutic applications during cerebral ischemia.
Ó 2020 Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction form anastomotic connections between internal and external caro-

Acute ischemic stroke (AIS) has a high recurrence rate with an
elevated global burden of stroke that mandates aggressive evalua-
tion and management from the moment of symptom onset.1,2
Cerebral ischemia results from acute arterial occlusion or severe
narrowing leading to impaired delivery of blood flow. Collateral
circulation is a dynamic system that tends to preserve cerebral per-
fusion in conjunction with pathophysiologic changes. Recruitment
of these anastomotic pathways is a major component of cerebral
homeostatic response to ischemia when the primary conduits fail
to provide perfusion to critical parts of the brain.3
Cerebral collaterals are alternate arterial routes that come into
play when primary antegrade blood flow is obstructed. These anas-
tomotic conduits include the relatively more proximal ‘primary
collaterals’ as a part of the circle of willis (COW), while their distal
counterpart include leptomeningeal or pial vessels that are
referred as ‘secondary collaterals’.4 Primary collaterals include
anterior and posterior communicating arteries that supply blood
flow to large portions of cerebral hemispheres in both anterior
and posterior circulations during acute ischemia. Secondary collat-
erals, comprising of leptomeningeal vessels and ophthalmic artery,
are less direct and diminutive connections that evolve gradually
and provide added support at times of cerebral ischemia. These
⇑ Corresponding author.
E-mail address: dliebeskind@mednet.ucla.edu (D.S. Liebeskind).
tid artery via middle meningeal, occipital, facial, and maxillary
arteries. Leptomeningeal collaterals are present over the pial sur-
face and anastomose with small distal cortical vessels during
ischemic event. Acute cerebral ischemia usually triggers the
recruitment of both Willisian collaterals that provide flow to
adjoining territories as well as leptomeningeal vessels that supply
cortical blood flow in a retrograde fashion. Similarly, venous collat-
erals work as a major element to maintain the cerebral blood vol-
ume, a critical variable that quantifies the amount of nutrient
blood for the ischemic brain. Along the microcirculation and
venous outflow, recent studies have discovered network of lym-
phatic channels that exit the skull base along sinuses and cranial
nerves.5
Beyond the existence of these robust anastomotic pathways,
development of new vessels has been studied that arise from
pre-existing vascular structures secondary to any ischemic insult
as an inciting factor.6 This process of arteriogenesis is propagated
by the release of vascular growth factors and is driven by pressure
gradient between proximal high and distal low perfusion regions.7
Development of new arterioles most commonly occurs in chronic
cerebral ischemic lesions rather acute arterial occlusions.8 With
time, these small vessels tend to develop layer of smooth muscle
and reforms to evolve into large caliber vessels.9
Collateral channels in conjunction with impaired anterograde
flow determine the evolution of cerebral ischemia. Acute arterial
occlusion exerts ischemic demand on collateral channels, while

https://doi.org/10.1016/j.hest.2019.12.003
2589-238X/Ó 2020 Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 K. Malhotra, D.S. Liebeskind / Brain Hemorrhages 1 (2020) 6–12
chronic atherosclerotic lesions may allow vigorous collateraliza-
tion over a longer period of time. The primary focus to achieve
favorable perfusion status during any ischemic event is powered
by a net balance between residual anterograde flow and retrograde
auxiliary flow. In this review, we have summarized the factors that
influence the evolution of collateral circuits along with their ther-
apeutic value in decision-making. We also focus on current and
emerging diagnostic techniques to visualize and assess the robust-
ness of these circuits during acute and chronic ischemic events.
2. Collateral screening: who has and who lacks?
The pace of ischemic changes is majorly determined by the
quality and quantity of collateral circulation.10 Collaterals have
recently been studied with immense interest due to their ability
to restrict the growth of penumbral territory. However, the robust-
ness and the efficacy of these anastomotic pathways vary drasti-
cally across patient profiles. Various factors have been elucidated
that affect the quality and the recruitment of such collateral path-
ways in AIS.11 Few of these factors include age of the patient, dura-
tion of ischemia, congenital variation of primary collaterals, and
other comorbidities including impaired cardiac output, diffuse
cerebral atherosclerosis, tobacco abuse, dehydration, hyper-
glycemia, uric acid levels and drugs with inhibitory effect on blood
pressure augmentation.12
Age and blood pressure are paramount factors that predict col-
lateral formation and have been broadly studied in both clinical
and animal models.13 Elderly patients undergo attrition in number,
luminal caliber and functional compensatory range for these col-
lateral pathways.14 Advanced intracranial atherosclerosis in elderly
patients promote resistance that lead to reduction in cerebral
blood flow, expansion of final infarct size, and worse outcomes
as compared to their younger counterparts.15,16 Various authors
have speculated that chronically elevated blood pressure impels
down regulation of cerebral vascular autoregulation.17 Chronic
hypertension in AIS tends to impair the robustness of these anasto-
motic vessels in animal models with limited data available in
humans.17,18
Significant variability in the anatomy and configuration of the
COW exists. Lippert et al studied the incidence rates of these pro-
files and observed lack of anterior communicating artery in 1%,
absent or hypoplastic anterior cerebral artery in 10%, and lack or
hypoplasia of posterior communicating arteries in 30% of patient
population.19 These variants could pose challenge for adequate
perfusion status at times of ischemic demand; however, many
individuals with these anatomic variants demonstrate vascular pli-
ancy and refrain from any occurrence of major cerebrovascular
events. The best examples of such resilience are the patients who
subsist with proximal large vessel occlusion (LVO), while demon-
strate no or minimal neurological deficits.20 Mere presence of col-
lateral pathways does not provide assurance of their persistence or
effectiveness during acute ischemic insults.
3. Diagnostic evaluation and grading of collateral circulation
For decades, emphasis was placed over rapid recanalization
during any acute ischemic event involving arterial occlusion, while
the collateral profile has been largely neglected. Cerebral
autoregulation is usually disturbed in ischemic stroke patients.
Evaluation of hemodynamics, autoregulation and collaterals is pru-
dent for clinical outcomes.21 Advanced neuroimaging techniques
are now available that provide detailed information and allows
meticulous interpretation of collateral circulation. Recent advent
of multimodal imaging modalities supplements quantitative and
functional aspects of collateral circulation.22 The pendulum has
7
swung for detailed evaluation of these collaterals especially in
the setting of acute proximal vessel occlusions to determine the
pathophysiology and clinical outcome thereafter. Several post-
hoc analyses have laid emphasis over assessment of collaterals
prior to recanalization procedures.23,24 The consensus is
clearer that the combined effort of collaterals and revision of
anterograde obstruction that equitably determines the fate of
penumbral tissue.
Characterization of the Willisian collaterals is readily performed
using basic imaging techniques, while the small leptomeningeal
collaterals till date required detailed catheter based cerebral
angiography. Many stroke centers have incorporated noninvasive
imaging methods to visualize collaterals including MRI or CT,
MR/CT-angiography (MRA or CTA) or perfusion scans.25,26 Advent
of these techniques provide direct correlation of ischemic penum-
bra, emergence of collaterals and perfusion status as a conglomer-
ate.27 Using non-invasive conventional neuroimaging studies,
collaterals can be visualized as hyperintensities on fluid-
attenuated inversion-recovery (FLAIR) sequence of MRI.28,29 These
subtle FLAIR vascular hyperintensities (FVH), an indirect but effec-
tive method of collateral assessment, demonstrate slow flow
through leptomeningeal collaterals that become prominent in the
setting of ischemic demand (Fig. 1B).30
Noninvasive imaging techniques have been the standard for ini-
tial evaluation of primary and secondary collateral circulation. Sin-
gle phase CTA is used extensively as an initial imaging modality
but tends to overestimate the collateral supply due to its inferior
temporal resolution. Multi-phase CTA is non-invasive modality
that captures snapshots in different contrast bolus phases.29 It is
widely available, provides great inter-observer accuracy, has supe-
rior correlation with neurological outcome and has proven its
worth in various recent endovascular trials.31 Both CTA and MRA
evaluate proximal LVO and concurrently assess the status of distal
collaterals. CTA source images (CTA-SI) provide more relevant data
regarding collateral flow, while MRA are only effective in assessing
primary or structural collaterals of COW.32,33 Various new MRI
techniques have emerged such as NOVA, which provides to-and-
fro blood flow data especially posterior to anterior circulation for
cases of steno-occlusive lesions in anterior circulation.34 Perfusion
imaging techniques including CT and MR perfusion accrue vital
information on cerebral blood flow and collateral status. These
techniques infer mismatch between gross perfusion deficits
reflected by penumbra and evolving infarct core.35 Delay in mean
transit time perfusion maps indicate ischemic penumbral tissue
with adequate collateral supply. Correlation of perfusion abnor-
malities with conventional cerebral angiography provides detailed
information on collateral status, though functional and dynamic
nature of perfusion studies is studded with its own limitations.
Few other noninvasive imaging techniques such as transcranial
Doppler (TCD) have been primarily used to evaluate flow velocities
and collateral circulation at COW.36 Reversal of blood flow direc-
tion especially in anterior communicating and ophthalmic arteries,
and flow diversion between anterior and posterior circulation pro-
vide critical information on ipsilateral collateral status.37 TCD also
evaluates cerebral vasomotor reactivity providing further details
on collateral circulation and autoregulatory response to a specific
vasodilatory stimulus.38 Impairment of vasomotor reactivity corre-
lates with the degree of collaterals,39 though the validation has
been trivial.40 These non-invasive techniques could potentially
have limitations with the resolution or accuracy. Digital subtrac-
tion angiography (DSA) remains the gold standard, invasive tech-
nique, for structural and functional evaluation of collaterals. It
supplements anatomic details for primary and secondary collater-
als, and determine hemodynamics of major routes including COW,
extracranial to intracranial anastomosis, and through collateral
vessels.11
8 K. Malhotra, D.S. Liebeskind / Brain Hemorrhages 1 (2020) 6–12

Fig. 1. A 57-year-old male presented with left visual field hemianopia and neglect with summated NIHSS of 4. A): DWI sequence of MRI brain demonstrated acute infarction
in right insular and temporal region. B): FLAIR sequence demonstrates hyperintense vessels due to distal slow flow. C): MRA head/neck shows proximal right M1 occlusion.
D): Digital subtraction angiogram demonstrates robust collateral flow from the right ACA and PCA territories into the MCA territory.

3.1. Arterial collaterals
Mere assessment for the presence of collateral routes in the past
has been transformed into substantive collateral scoring grades to
evaluate the adequacy and robustness of these anastomotic path-
ways. Various objective collateral scoring grades exist including
the Alberta Stroke Program Early CT Score (ASPECTS) on collater-
als,41 scores of Christoforidis et al.,42 Miteff et al.,43 and the score
of the American Society of Interventional and Therapeutic Neuro-
radiology/Society of Interventional Radiology (ASITN/SIR) based
on conventional angiography.24 Comparative studies involving
these grading systems showed superior correlation to infarct core
volume and diffusion-perfusion mismatch for ASPECTS on collater-
als and modified ASITN/SIR collateral grading scales.44 New imag-
ing techniques are on the horizon including multi-phase,45 tri-
phase46 and perfusion CT47 to assess minute details of collateral
circulation (Fig. 2). Various novel non-invasive techniques such
as fractional flow reserve (FFR) detects pressure gradient across
intracranial stenotic lesions, suggesting impaired collaterals and
hemodynamics due to ICAD that portends high stroke risk.48 These
collateral grading scores determine the rate of recanalization,
infarct core expansion and hemorrhagic transformation (HT).49
Patients with poor collateral scores have been associated with
lower recanalization rates, increased incidence of HT and poor clin-
ical outcomes.23,25
3.2. Venous collaterals
In addition to arterial collateral assessment, venous outflow
provides indirect but precise measurement of microcirculatory
perfusion. Venous collaterals supply blood flow to downstream
microcirculation and adjacent venous conduits in the setting of

Fig. 2. A 46-year-old male with recent mitral valve repair had sudden onset of right sided weakness, numbness and aphasia with a summated NIHSS 7. A) Initial NCCT shows
early hypodensity in left anterior temporal lobe. B) Arterial phase of CT angiogram of brain demonstrates focal occlusion at the junction of left M1-M2 segments. C & D)
Venous and delayed venous phase of CT angiogram of head demonstrate good collateral vessels on comparison to contralateral hemisphere. E) CT perfusion shows elevated
MTT or Tmax in inferior division of left MCA territory. F) 24-hour NCCT demonstrates evolution of left temporal and insular infarction.
 K. Malhotra, D.S. Liebeskind / Brain Hemorrhages 1 (2020) 6–12
proximal arterial occlusion. Detailed assessment and quantifica-
tion of venous flow in downstream ischemic territory further
improves our understanding of collateral perfusion.
Various venous grading scales have been discussed that provide
additional information to arterial collateral evaluation during ther-
apeutic decisions. Prognostic evaluation based on cortical vein
score difference in stroke (PRECISE) score helps in quantification
of collateral outflow based on venous contrast enhancement, pre-
dicts perfusion mismatch, and prognosticates the stroke out-
comes.50 Presence of cortical venous drainage and a high PRECISE
score (4) independently predicts poor clinical outcomes. Subse-
quently, a combined arterial and venous grading (CRISP) scale
was introduced that compared previous existent imaging scoring
systems.51 CRISP grading scale was a reliable venous outflow score,
better than individual arterial or PRECISE scores, to predict stroke
outcomes in patients with proximal arterial occlusions.
4. Therapeutic value of collaterals
The therapeutic potential of collaterals has gradually been rec-
ognized by clinicians and now seems to be a major factor that
determines the prognosis of AIS early in the course. Various non-
pharmacological measures are applied initially to support collat-
eral circulation and thus increase the dwindling perfusion supply
in ischemic zone. These interventions including supine positioning,
intravenous fluid support and supplementation of oxygen, are well
recognized though the data on their efficacy and utility for various
stroke subtypes remain ambiguous.52 Proximal LVO or fluctuating
neurological symptoms usually imply a substantial demand for
collateral boost that usually warrants these interventions. Though,
credence over these interventions limits early rehabilitative mea-
sures in AIS patients.
Collateral therapeutic measures may show promise in proximal
middle cerebral artery (MCA) occlusions due to the related patho-
physiology of anastomotic leptomeningeal vessels. Flow diversion
is primarily observed from anterior or posterior cerebral vessels
towards distal MCA territorial zones, likely due to reduced perfu-
sion pressure.3 Marked pressure gradient also develops from max-
imal vasodilation of distal arterial segments leading to retrograde
blood flow through these anastomoses. These perfusion dependent
zones are largely dependent over gravitational forces, especially
the head positioning.53 Pressure gradient determines the compe-
tency of leptomeningeal vessels distal to occlusion, while supine
positioning improves anterograde cerebral blood flow and perfu-
sion pressure across the gradient. Physicians based on their initial
clinical evaluation tend to prefer supine positioning with the
patient’s head turned towards left in left MCA syndrome or
towards right in right MCA syndrome for logical reasons. Though,
these measures seem to be beneficial theoretically may have detri-
mental effect of elevation in intracranial pressure.53
5. Collateral failure and hemodynamic alterations
Oxygen is the primary ingredient of the blood that is required
for energy generation and metabolism. It has been hypothesized
that increased oxygen gradient and extraction by penumbral tissue
lead to proximal arteriolar oxygen loss, leading to detrimental
quality of blood supply delivered to distal leptomeningeal collater-
als.54 The pathophysiology behind collateral failure in acute to sub-
acute stage of ischemic stroke, involving either delivery of
deoxygenated blood or hemodynamic failure remains a conjecture.
Though theoretically it remains of prime importance, oxygen sup-
plementation in AIS remains disputed with minimal success in
clinical human studies.55 Future clinical trials with meticulous
selection of patients with LVO or collateral-dependent-penumbra
9
might be effective for significance of oxygen saturation of collateral
vessels.
Hemodynamic changes have been the fundamental aspect of
stroke therapy in acute cerebral ischemia. Various measures of
hemodynamic remodeling including hemodilution, volume expan-
sion and induced hypertension are theoretically efficacious, but
have practical limitations with their applicability.56 Supplementa-
tion of intravenous fluid leading to hemodilution and plasma vol-
ume expansion tends to resolve acute neurological symptoms
especially in LVO cases. This effect is primarily related to recruit-
ment of collateral anastomotic vessels and improved reperfusion
status. Identification of these cases that are collateral dependent
and providing additional support via hemodynamic remodeling
renders protracted favorable opportunity to actively prevent
expansion of infarct size and treat AIS patients.
Various experimental techniques to increase cerebral blood
flow have been investigated in acute cerebral ischemia. Electrical
stimulation of sphenopalatine ganglia results in vasodilation and
elevated ipsilateral cerebral blood flow.57 It was used in animal
models to show increase in blood flow and subsequent reduction
in core infarct volume,58 though few studies are currently under
investigation in human beings.59 Diversion of aortic blood towards
cerebral vasculature has been tested in AIS patients using partial
aortic occlusion devices.60 This technique did not increase hemor-
rhagic risk in patients receiving IV tPA,61 though could not justify
their superiority from standard medical treatment arm.11 Simi-
larly, external counterpulsation devices and antigravity suits have
been investigated in AIS patient, though efficacy data is scarce.62,63
Recently, surgical transposition of superficial temporal artery (STA)
has been investigated with either direct STA-MCA bypass or indi-
rect encephaloduroarteriosynangiosis. These techniques in previ-
ous studies were shown to support collateral anastomosis and
thus improve the regional blood flow,64 though further studies
are needed to confirm the results.
6. Temporal patterns for collateral circulation in acute and
chronic ischemic disease states
6.1. Chronic disease
Both the structural and functional aspects of collateral flow are
critical to assess the risk of ischemic event due to atherosclerotic
lesions. The downstream components influencing the hemody-
namic changes are usually deferred, while assessment of the
degree of proximal carotid stenosis remains the primary focus. This
information is especially crucial in selected asymptomatic cases
since limited data is available on the benefit of revascularization
procedures.65 Various authors have studied the correlation of
impaired collateral circulation due to chronic steno-occlusive dis-
ease and subsequent risk of cerebrovascular ischemia.66,67 Authors
of Warfarin Aspirin Symptomatic Intracranial Disease (WASID)
trial68 showed that severe intracranial atherosclerosis is associated
with robust distal pial anastomosis, while no similar correlation
was observed for cases with mild-moderate degree of stenosis.69
Recent analysis showed cogent association between impaired cere-
brovascular reserve (CVR) and ensuing stroke or TIA due to carotid
stenosis.70 Treatment procedures involving angioplasty or
endarterectomy have shown to ameliorate the CVR and prevent
impending cerebrovascular event.71
The pace of stenosis or occlusion has major ramifications with
the quality and quantity of collateral formation. Gradual progres-
sion of stenosis in large vessels such as internal carotid artery
(ICA) at the level of carotid bifurcation due to atherosclerosis or
distal intracranial ICA segments secondary to moyamoya disease72
results in contiguous collateral anastomotic changes as compared
10 K. Malhotra, D.S. Liebeskind / Brain Hemorrhages 1 (2020) 6–12
to sudden arterial occlusion. Moyamoya disease is an exemplary
illustration of robust collateralization over a chronic facet involv-
ing leptomeningeal and deep parenchymal anastomotic vessels.
The disease typically is characterized by fibrocellular thickening
of distal portions of proximal intracranial vessels, especially distal
terminal segments of ICA, and further progression with formation
of thin perforating vessels.73 Assessment of collateral supply in this
progressive vasculopathy remains critical to make therapeutic
decisions, as the disease imposes gradual challenge to secondary
collateral circulation.
6.2. Acute disease
The detection and functional assessment of collateral circula-
tion has gradually emerged as a prime focus in AIS. For decades,
the mantra of ‘time is brain’ has streamlined the initial ischemic
stroke evaluation with a primary focus over last known well time
and thrombolysis, while has neglected hemodynamic alterations
that occur at the collateral circulatory level.74 The concept of ‘tis-
sue is brain’ has recently been promulgated, yet the onset of symp-
toms might not completely correlate with the tissue damage in
specific or individual cases. With the advent of multimodal imag-
ing techniques, this theory evolved with further clarification that
stroke symptoms could more likely be a manifestation of collateral
failure.75
There have been continuous efforts to expand the window time
for thrombolysis, both for intravenous and endovascular therapies.
Few authors have suggested that prior assessment of collaterals
could likely elucidate suitable perfusion profiles in case of LVO,
that could safely increase IV tPA window up to 6 h.76 Robust collat-
erals could potentially extend the window period to intervene for
endovascular procedures.77 Collaterals play an important role in
viability of penumbral tissue that was further studied as a poten-
tial target to investigate protracted time windows for select befit-
ting cases with robust collaterals. Recruitment of collateral vessels
is itself a time-dependent process that tends to stabilize clinical
symptoms followed by improved clinical outcomes.78 Recent suc-
cess of endovascular trials with major support from patient selec-
tion based on collateral profiling, finally coaxed physicians to
accept the mantra of ‘tissue is brain’.79,80
Collateral assessment in a specific region determines the even-
tual infarct core size and predicts the clinical outcome in acute
proximal LVO.81 Adequate mean arterial pressure with intact
COW is associated with better clinical outcomes.82 while poor col-
lateral grades based on angiography correlates with large territory
infarction in setting of proximal LVO.18 Higher collateral grades
have been associated with better recanalization rates, while
patients with poor collaterals tend to have worse outcome even
with complete recanalization of parent occlusion.49
6.3. Significance of collateral circuits in decision-making
Recent stroke trials, especially involving endovascular tech-
niques, provide significant insight into the utility of collateral cir-
culation assessment. Each individual patient has inherent distinct
collateral profile based on anatomy and pathophysiology at base-
line that is extremely pragmatic in making therapeutic decisions
upfront. The impact of collateral status at presentation has been
correlated with clinical symptoms, recanalization or reperfusion
success and functional outcome at discharge. Cogent rationale
now exists for imaging assessment to guide physicians in the pre-
cision medicine of stroke care.83 Collateral grading systems have
been formulated that support meticulous selection criteria for
patient enrollment and also to extend the time window to inter-
vene for ET cases.84,85 On the contrary, dilemma continues among
physicians regarding endovascular approach and clinical outcome
for patients with poor collateral scores who arrive early after their
symptom onset.
7. Conclusion
Collateral circulation comprises of robust anastomotic cerebral
vessels that are beneficial in stroke. Varied rapid non-invasive
diagnostic techniques have loomed recently that are rife with
cogent details about structural and functional constituents regard-
ing this circulation. Robustness of collateral vessels determines
early recanalization and clinical outcome with both intravenous
and/or intra-arterial reperfusion therapies. Recent success of clini-
cal trials has elucidated the beneficial influence of initial assess-
ment of collateral adequacy for improved clinical outcomes.
Clinical trials with more refined techniques are expected that shall
provide clinical equipoise towards more judicial utilization of col-
laterals in therapeutic decisions.
Disclosure/conflict of interest
The authors have no conflict of interest.
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