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Collaterals in Ischemic Stroke

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 REVIEW

Collaterals in Ischemic Stroke

Konark Malhotra1, David S. Liebeskind2

1 Vascular Neurology, UCLA, Department of Neurology

2 Neurology and Director, Neurovascular Imaging Research Core

Neuroscience Research Building, 635 Charles E Young Drive South, Suite 225 Los Angeles, CA 90095-7334

Abstract
Collateral flow plays a pivotal role, both in acute and chronic phases of cerebral ischemia. Recruitment of these redundant vascular
networks maintains cerebral blood flow to ischemic areas, while primary arterial conduits are obstructed either due to steno-occlusive
or acute occlusive lesion. Until recently, a heavy focus had been placed solely on such impaired antegrade flow, while the contribu-
tion from primary and secondary collateral pathways has been largely disregarded. Imaging of the brain with focus on delineating
the collateral circulation has been critical to interpret the mechanism of vascular remodeling that occurs with ischemic injury. Recent
multimodal imaging modalities have encouraged physicians to assess collateral flow and hemodynamics from a temporal perspective,
distinguishing individual cases to tailor 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 comprehensive review
on the role of collaterals and its therapeutic applications during cerebral ischemia.

How to cite this article: Malhotra K, Liebeskind DS (2016) Collaterals in Ischemic Stroke. Proc Neurosci 1(2):106-113.

Introduction Secondary collaterals, comprising of leptomeningeal ves-

Acute ischemic stroke (AIS) has a high recurrence rate with
an elevated global burden of stroke that mandates aggressive
evaluation and management from the moment of symptom
onset (Lazzaro, Malhotra, and Mohammad 2010; Hackett
et al. 2015). 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 perfusion in conjunction with
pathophysiologic changes. Recruitment of these anastomotic
pathways is a major component of cerebral homeostatic re-
sponse to ischemia when the primary conduits fail to provide
perfusion to critical parts of the brain (Liebeskind 2003).
Cerebral collaterals are alternate arterial routes that come
into play when primary antegrade blood flow is obstructed.
These anastomotic conduits include the relatively more
proximal primary collaterals as a part of the circle of
willis (COW), while their distal counterpart include lepto-
meningeal or pial vessels that are referred as secondary
collaterals (Liebeskind 2005). 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.
sels and opthalmic artery, are less direct and diminutive
connections that evolve gradually and provide added sup-
port at times of cerebral ischemia. These form anastomotic
connections between internal and ternal carotid artery via
middle meningeal, occipital, facial, and maxillary arteries.
Leptomeningeal collaterals are present over the pial surface
and anastomose with small distal cortical vessels during
ischemic event. Acute cerebral ischemia usually triggers the
recruitment of both Willisian collaterals that provid flow to
adjoining territories as well as leptomeningeal vessels that
supply cortical blood flow in a retrograde fashion. Similarly,
venous collaterals work as a major or element to maintains
the cerebral blood volume, a critical variable that quantifies
the amount of nutrient blood for the ischemic brain.
Beyond the existence of these robust anastomotic path-
ways, development of new vessels have been studied that
arise from pre-existing vascular structures secordary to any
ischemic insult as an inciting factor (Chen J 2012). 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
(Dor and Keshet 1997). Development of new arterioles

106 2016 Proc Neurosci

 Malhotra K, et al. / Proc Neurosci
most commonly occurs in chronic cerebral ischemic lesions
rather acute arterial occlusions (Toyoda, Minematsu, and
Yamaguchi 1994). With time, these small vessels tend to
develop layer of smooth muscle and reforms to evolve into
large caliber vessels (van Royen et al. 2001).
Collateral channels in conjunction with impaired antero-
grade flow determine the evolution of cerebral ischemia.
Acute arterial occlusion exerts ischemic demand on col-
lateral channels, while chronic atherosclerotic lesions may
allow vigorous collateralization 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 therapeutic value in decision-making. We also focus
on current and emerging diagnostic techniques to visualize
and assess the robustness of these circuits during acute and
chronic ischemic events.
Collateral screening: who has and who lacks?
The pace of ischemic changes is majorly determined by the
quality and quantity of collateral circulation (Liebeskind
2015). Collaterals have recently been studied with immense
interest due to their ability to restrict the growth of penum-
bral territory. However, the robustness and the efficacy of
these anastomotic pathways vary drastically across patient
profiles. Various factors have been elucidated that affect the
quality and the recruitment of such collateral pathways in
AIS (Shuaib et al. 2011). Few of these factors include age
of the patients, duration of ischemia, congenital variation
of primary collaterals, and other comorbidities including
impaired cardiac output, diffuse cerebral atherosclerosis,
tobacco abuse, dehydration, hyperglycemia, uric acid
levels and drugs with inhibitory effect on blood pressure
augmentation (Menon et al. 2013).
Age and blood pressure are paramount factors that pre-
dict collateral formation and have been broadly studied in
both clinical and animal models (Faber et al. 2011). Elderly
patients undergo attrition in number, luminal caliber and
functional compensatory range for these collateral pathways
(Brozici, van der Zwan, and Hillen 2003). Advanced intra-
cranial 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 (Malik et al. 2014; Arsava et
al. 2014). Various authors have speculated that chronically
elevated blood pressure impels down regulation of cerebral
vascular autoregulation (Coyle and Heistad 1991). Chronic
hypertension in AIS tends to impair the robustness of these
anastomotic vessels in animal models with limited data avail-
Proc Neurosci Volume 1 Issue 2
able in humans (Coyle and Heistad 1991; Lima et al. 2010).
Significant variability in the anatomy and configuration of
the COW exists. Lippert et al studied the incidence rates of
these profiles and observed lack of anterior communicating
artery in 1%, absent or hypoplastic anterior cerebral artery in
10%, and lack or hypoplasia of posterior communicating ar-
teries in 30% of patient population (Lippert H 1985). These
variants could pose challenge for adequate perfusion status
at times of ischemic demand; however many individuals
with these anatomic variants demostrate vascular pliancy
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 demonstrate no or minimal neurological deficits
(Powers 1991). Mere presence of collateral pathways does
not provide assurance of their persistence or effectiveness
during acute ischemic insults.
Diagnostic evaluation and grading of collateral
circulation
For decades, emphasis was placed over rapid recanalization
during any acute ischemic event involving arterial occlu-
sion, while the collateral profile has been largely neglected.
Advanced neuroimaging techniques are now available that
provide detailed information and allows meticulous interpre-
tation of collateral circulation. Recent advent of multimodal
imaging modalities supplements quantitative and functional
aspects of collateral circulation (Malhotra and Liebeskind
2015). The pendulum has 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 recana-
lization procedures (Kucinski et al. 2003; Higashida et al.
2003). The consensus is more clear that the combined efforts
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 cath-
eter based cerebral angiography. Many stroke centers have
incorporated noninvasive imaging methods to visualize col-
laterals including MRI or CT, MR/CT-angiography (MRA
or CTA) or perfusion scans (Kim et al. 2014; Campbell et al.
2013). Advent of these techniques provide direct correlation
of ischemic penumbra, emergence of collaterals and perfu-
sion status as a conglomerate (Lansberg et al. 1999). Using
non-invasive conventional neuroimaging studies, collaterals
can be visualized as hyperintensities on fluid-attenuated
inversion-recovery (FLAIR) sequence of MRI (Azizyan
et al. 2011). These subtle FLAIR vascular hyperintensities
107
 Malhotra K, et al. / Proc Neurosci
A B
Figure 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.
(FVH), an indirect but effective method of collateral as-
sessment, demonstrate slow flow through leptomeningeal
collaterals that become prominent in the setting of ischemic
demand (Figure 1 B) (Sanossian et al. 2009).
Noninvasive imaging techniques have been the standard
for initial evaluation of primary and secondary collateral
circulation. Single phase CTA is used extensively as an initial
imaging modality but tends to overestimate the collateral sup-
ply due to its inferior temporal resolution. Multi-phase CTA
is non-invasive modality that captures snapshots in different
contrast bolus phases. It is widely available, provides great
inter-observer accuracy, has superior correlation with neu-
rological outcome and has proven its worth in various recent
endovascular trials (Goyal et al. 2015). 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 (Grond et al. 2002; Patrick et al. 1996). 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 (Ruland et al. 2009). Perfusion imaging
techniques including CT and MR perfusion accrue vital in-
formation on cerebral blood flow and collateral status. These
techniques infers mismatch between gross perfusion deficits
reflected by penumbra and evolving infarct core (Schlaug et
al. 1999). Delay in mean transit time perfusion maps indicate
ischemic penumbral tissue with adequate collateral supply.
Correlation of perfusion abnormalities with conventional
cerebral angiography provides detailed information on col-
lateral status, though functional and dynamic nature of
perfusion studies is studded with its own limitations. Few
other noninvasive imaging techniques such as transcranial
108
C D
Doppler (TCD) have been primarily used to evaluate flow
velocities and collateral circulation at COW (Malhotra et al.
2014). Reversal of blood flow direction especially in anterior
communicating and ophthalmic arteries, and flow diversion
between anterior and posterior circulation provide critical
information on ipsilateral collateral status (Kim et al. 2009).
TCD also evaluates cerebral vasomotor reactivity providing
further details on collateral circulation and autoregulatory re-
sponse to a specific vasodilatory stimulus (Gur and Bornstein
2001). Impairment of vasomotor reactivity correlates with
the degree of collaterals (Hofmeijer et al. 2002), though the
validation has been trivial (Pindzola et al. 2001). These non-
invasive techniques could potentially have limitations with
the resolution or accuracy. Digital subtraction angiography
(DSA) remains the gold standard, invasive technique, for
structural and functional evaluation of collaterals. It supple-
ments anatomic details for primary and secondary collaterals,
and determine hemodynamics of major routes including
COW, extracranial to intracranial anastomosis, and through
collateral vessels (Shuaib et al. 2011).
Mere assement for the presence of collateral routes in the
past has been transformed into substantive collateral scor-
ing grades to evaluate the adequacy and robustness of these
anastomotic pathways. Various objective collateral scoring
grades exist including the Alberta Stroke Program Early CT
Score (ASPECTS) on collaterals (Menon et al. 2011), scores
of Christoforidis et al (Christoforidis et al. 2005), Miteff et
al (Miteff et al. 2009) and the score of the American Society
of Interventional and Therapeutic Neuroradiology/Society
of Interventional Radiology (ASITN/SIR) based on con-
ventional angiography (Higashida et al. 2003). Comparative
studies involving these grading systems showed superior
correlation to infarct core volume and diffusion-perfusion
mismatch for ASPECTS on collaterals and modified ASITN/
Proc Neurosci Volume 1 Issue 2
 Malhotra K, et al. / Proc Neurosci
A B C Though, credence over these interventions limits early
D E F
Figure 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
SIR collateral grading scales (Seker et al. 2015). New imag-
ing techniques are on the horizon including multi- (Kim et al.
2012), tri-phase (Lee et al. 2000) and perfusion CT (Calleja
et al. 2013) to assess minute details of collateral circulation
(Figure 2). These collateral grading scores determine the rate
of recanalization, infarct core expansion and hemorrhagic
transformation (HT) (Bang et al. 2011). Patients with poor
collateral scores have been associated with lower recana-
lization rates, increased incidence of HT and poor clinical
outcomes (Kucinski et al. 2003; Kim et al. 2014).
Therapeutic value of collaterals
The therapeutic potential of collaterals has gradually been
recognized 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 collateral 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 (Diez-Tejedor
and Fuentes 2004). Proximal LVO or fluctuating neuro-
logical symptoms usually imply a substantial demand for
collateral boost that usually warrants these interventions.
Proc Neurosci Volume 1 Issue 2
rehabilitative measures in AIS patients.
Collateral therapeutic measures may show promise in
proximal middle cerebral artery (MCA) occlusions due
to the related pathophysiology of anastomotic leptomen-
ingeal vessels. Flow diversion is primarily observed from
anterior or posterior cerebral vessels towards distal MCA
territorial zones, likely due to reduced perfusion pressure
(Liebeskind 2003). Marked pressure gradient also develops
from maximal vasodilation of distal arterial segments lead-
ing to retrograde blood flow through these anastomosis.
These perfusion dependent zones are largely dependent
over gravitational forces, especially the head positioning
(Schwarz et al. 2002). Pressure gradient determines the
competency of leptomeningeal vessels distal to occlusion,
while supine positioning improves anterograde cerebral
blood flow and perfusion pressure across the gradient.
Physicians based on their initial clinical evaluation tend
to prefer supine positioning with the patients 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
detrimental effect of elevation in intracranial pressure
(Schwarz et al. 2002).
Collateral failure and hemodynamic alterations
Oxygen is the primary ingredient of the blood that is re-
quired for energy generation and metabolism. It has been
hypothesized that increased oxygen gradient and extraction
by penumbral tissue leads to proximal arteriolar oxygen
loss, leading to detrimental quality of blood supply deliv-
ered to distal leptomeningeal collaterals (Liebeskind 2004).
The pathophysiology behind collateral failure in acute to
subacute stage of ischemic stroke, involving either delivery
of deoxygenated blood or hemodynamic failure remains a
conjecture. Though theoretically it remains of prime im-
portance, oxygen supplementation in AIS remains disputed
with minimal success in clinical human studies (Rusyniak
et al. 2003). Future clinical trials with meticulous selection
of patients with LVO or collateral-dependent-penumbra
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 mea-
sures of hemodynamic remodeling including hemodilution,
volume expansion and induced hypertension are theoreti-
cally efficacious, but have practical limitations with their
applicability (Bhalla et al. 2003). Supplementation of in-
travenous fluid leading to hemodilution and plasma volume
expansion tends to resolve acute neurological symptoms
especially in LVO cases. This effect is primarily related to
109
 Malhotra K, et al. / Proc Neurosci
recruitment 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 isch-
emia. Electrical stimulation of sphenopalatine ganglia
results in vasodilation and elevated ipsilateral cerebral
blood flow (Suzuki et al. 1990). It was used in animal
models to show increase in blood flow and subsequent
reduction in core infarct volume (Bar-Shir et al. 2010),
though few studies are currently under investigation in hu-
man beings ("Implant for Augmentation of Cerebral Blood
Flow Trial, Effectiveness and Safety in a 24 Hour Window
(ImpACT-24)"). Diversion of aortic blood towards cerebral
vasculature has been tested in AIS patients using partial
aortic occlusion devices (Hammer et al. 2012). This tech-
nique did not increase hemorrhagic risk in patients receiving
IV tPA (Emery et al. 2011), though could not justify their
superiority from standard medical treatment arm (Shuaib
et al. 2011). Similarly, external counterpulsation devices
and antigravity suits have been investigated in AIS patient,
though efficacy data is scarce (Berthet et al. 2010; Han and
Wong 2008). Recently, surgical transposition of superficial
temporal artery (STA) has been investigated with either
direct STA-MCA bypass or indirect encephaloduroarte-
riosynangiosis. These techniques in previous studies were
shown to support collateral anastomosis and thus improve
the regional blood flow (Kim et al. 2002), though further
studies are needed to confirm the results.
Temporal patterns for collateral circulation
Chronic disease
Both the structural and functional aspects of collateral flow
are critical to assess the risk of ischemic event due to athero-
sclerotic lesions. The downstream components influencing
the hemodynamic changes are usually deferred, while as-
sessment 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 (Halliday et
al. 2004). Various authors have studied the correlation of im-
paired collateral circulation due to chronic steno-occlusive
disease and subsequent risk of cerebrovascular ischemia
(King et al. 2011; Kimiagar et al. 2010). Authors of War-
farin Aspirin Symptomatic Intracranial Disease (WASID)
trial (Liebeskind, Cotsonis, Saver, Lynn, Cloft, et al. 2011)
showed that severe intracranial atherosclerosis is associated
with robust distal pial anastomosis, while no similar cor-
110
relation was observed for cases with mild-moderate degree
of stenosis (Liebeskind, Cotsonis, Saver, Lynn, Turan, et al.
2011). Recent analysis showed cogent association between
impaired cerebrovascular reserve (CVR) and ensuing stroke
or TIA due to carotid stenosis (Gupta et al. 2012). Treat-
ment procedures involving angioplasty or endarterectomy
have shown to ameliorate the CVR and prevent impending
cerebrovascular event (Attye et al. 2014).
The pace of stenosis or occlusion has major ramifica-
tions with the quality and quantity of collateral formation.
Gradual progression of stenosis in large vessels such as in-
ternal carotid artery (ICA) at the level of carotid bifurcation
due to atherosclerosis or distal intracranial ICA segments
secondary to moyamoya disease (Zipfel, Fox, and Rivet
2005) results in contiguous collateral anastomotic changes
as compared to sudden arterial occlusion. Moyamoya dis-
ease is an exemplary illustration of robust collateralization
over a chronic facet involving 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 (Liu et al. 2013). Assessment of
collateral supply in this progressive vasculopathy remains
critical to make therapeutic decisions, as the disease imposes
gradual challenge to secondary collateral circulation.
Acute disease
The detection and functional assessment of collateral circu-
lation 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 circula-
tory level ('Tissue plasminogen activator for acute ischemic
stroke. The National Institute of Neurological Disorders and
Stroke rt-PA Stroke Study Group' 1995). The concept of
tissue is brain has recently been promulgated, yet the onset
of symptoms might not completely correlate with the tissue
damage in specific or individual cases. With the advent of
multimodal imaging techniques, this theory evolved with
further clarification that stroke symptoms could more likely
be a manifestation of collateral failure (Liebeskind 2009).
There have been continous efforts to expand the window
time for thrombolysis, both for intravenous and endovascu-
lar therapies. Few authors have suggested that prior assess-
ment of collaterals could likely elucidate suitable perfusion
profiles in case of LVO, that could safely increase IV tPA
window up to 6 hours (Albers et al. 2006). Robust collater-
als could potentially extend the window period to intervene
for endovascular procedures (Ribo et al. 2011). Collaterals
Proc Neurosci Volume 1 Issue 2
 Malhotra K, et al. / Proc Neurosci
play an important role in viability of penumbral tissue that
was further studied as a potential target to investigate pro-
tracted time windows for select befitting 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 (Maas et al. 2009).
Recent success of endovascular trials with major support
from patient selection based on collateral profiling, finally
coaxed physicians to accept the mantra of tissue is brain
(Kidwell et al. 2013; Broderick et al. 2013).
Collateral assessment in a specific region determines the
eventual infarct core size and predicts the clinical outcome
in acute proximal LVO (Cheng et al. 2011). Adequate mean
arterial pressure with intact COW is associated with better
clinical outcomes (Schellinger et al. 2013), while poor col-
lateral grades based on angiography correlates with large
territory infarction in setting of proximal LVO (Lima et al.
2010). Higher collateral grades have been associated with
better recanalization rates, while patients with poor col-
laterals tend to have worse outcome even with complete
recanalization of parent occlusion (Bang et al. 2011).
Significance of collateral circuits in
decision-making
Recent stroke trials, especially involving endovascular
techniques, provide significant insight into the utility of
collateral circulation assessment. Each individual patient
has inherent distinct collateral profile based on anatomy
and pathophysiology at baseline 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. Collateral grading systems
have been formulated that support meticulous selection
criteria for patient enrollment and also to extend the time
window to intervene for ET cases (Bartolini et al. 1995).
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.
Conclusion
Collateral circulation comprise 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 func-
tional constituents regarding this circulation. Robustness
of collateral vessels determines early recanalization and
clinical outcome with both intravenous and/or intra-arterial
Proc Neurosci Volume 1 Issue 2
reperfusion therapies. Recent success of clinical trials has
elucidated the beneficial influence of initial assessment 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 collaterals in therapeutic decisions.
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