Assessment of collateral flow using CT perfusion data in
acute ischemic stroke – a retrospective analysis
Scientific background:
The collateral circulation of the brain is defined as the artery-to-artery anastomotic
pathways that are capable of supplying nutrient perfusion to an ischemic brain region
whose primary supplying artery has been compromised.
Primary collaterals refer to the anastomotic arterial circle at the base of the brain (circle
of Willis). Those are substantially variable and relevant especially in carotid artery
occlusion rather than middle cerebral artery occlusion1. Secondary collaterals consist of
intracranial leptomeningeal anastomoses between the distal segments of the anterior,
middle, and posterior cerebral arteries; between the posterior cerebral and major
cerebellar arteries; and between branches of the external carotid artery (e.g., facial,
maxillary, middle meningeal and occipital arteries) and those of the internal carotid artery
(e.g., ophthalmic artery)2.
Collaterals have been shown to influence recanalization, reperfusion, hemorrhagic
transformation and neurological outcomes after stroke3-6. Subsequently they are a critical
component of acute ischemic stroke evaluation and treatment. Collaterals are typically
measured by the extent of arterial flow at conventional digital subtraction angiography
(DSA). Several DSA-based collateral scores have been established of whom the most
commonly used is the ASITN/SIR collateral score. However, DSA is invasive and timeconsuming and thus in ischemic stroke its use is typically restricted to the setting of acute
endovascular therapy (EVT).
There are several noninvasive imaging markers of collateral flow. Slow, reverse
collateral flow in arterial segments beyond an occlusion on MRI fluid-attenuated
inversion recovery (FLAIR) sequences is one example7. A variety of other MR-based
methods has been considered8. Biphasic CTA collateral scores have also been explored in
two recent studies: One study has compared DSA collateral score to multidetector CTA
Protocol assessment of Collateral flow in CTP Ver 1.0 Date 17APR2023
(MDCTA) collateral scores showing equal predictive performance9. Another study
developed multiphase (biphasic) flat-detector CTA collateral score and validated it
against the established ASITN/SIR collateral score10.
Computed Tomography Perfusion (CTP) is a functional imaging modality in which slices
of brain tissue are repeatedly scanned as an intravenous bolus of contrast passes through
them. The change in intensity of individual voxels as a function of time is analyzed to
produce a set of perfusion parameters. Additional post-processing produces maps of the
infracted core and penumbra. Currently, CTP algorithms focus on processing the
perfusion data of cerebral parenchyma. However, dynamic data on flow within the
cerebral arteries may also be extracted from the CTP images. Analysis of this widelyavailable data may enable assessment of collateral flow in a simple, non-invasive manner.
In the Shamir Medical Center (SMC), all acute ischemic stroke patients undergo CT
evaluation in the ER including non-contrast CT (NCCT), CT-Angiography (CTA) and
CTP. For those who eventually undergo intervention (roughly 200 patients per year),
CTP arterial flow curves may be compared to real-time angiographic flow data. This may
provide insights on the assessment of collaterals through CTP.
Study design:
In this study, we will search the SMC medical files for patients who have undergone both
EVT for acute ischemic stroke and had CTP and CTA performed in the acute phase.
Clinical and radiological data will be retrospectively extracted and analyzed.
The Holon Institute of Technology (HIT) is a multidisciplinary academic institution that
promotes the integration of science, engineering, design and management.
With the assistance of HIT scientists, CTA and CTP images will be merged and postprocessed to develop a dynamic "virtual DSA" (vDSA). vDSA images will be visually
analyzed and compared to standard DSA pictures. The second step in the analysis will be
to correlate vDSA data with radiological and clinical outcomes of stroke patients. The
aim is to produce a topographic vDSA collateral score that will predict tissue fate and the
expected benefit from EVT.
Protocol assessment of Collateral flow in CTP Ver 1.0 Date 17APR2023
Study hypothesis:
vDSA based on CTP arterial flow data can give valuable information on collateral
circulation that may be equivalent or even superior to standard DSA. It can identify the
main source of collateral supply, assess the quality of collateral flow and enable collateral
grading and tissue fate prediction.
Study Population:
All patients who have undergone EVT for acute ischemic anterior circulation stroke and
had CTA+CTP performed in the acute phase from January 2020 to June 2023. Estimated
number of patients is ~550. For the second step, patients who had ischemic stroke and CTP
but had not undergone EVT in the same period will also be included. Estimated number of
patients is ~250.
Data collection:
Demographics and relevant clinical data such as age, sex, EF%, baseline mRS score, time
from symptoms onset to CTP, NIHSS score at admission and mRS score discharge and at
3 months will be extracted from the electronic medical file by a trained student.
CTA data such as identity of the occluded artery/arteries and completeness of the circle
of Willis will be extracted by a trained neuroradiologist. DSA data such as type of
collateral supply (primary vs. secondary collaterals), main source of arterial collateral
supply and collateral grade using ASITN/SIR collateral flow grading system will be
extracted by a trained interventional neuroradiologist.
CTP data such as core infarct and penumbral volume and radiological mismatch will be
extracted from the CTP summary maps in a blinded manner using the Syngo.via client
(Siemens AG Healthcare Sector) by a trained neurologist.
For the purpose of this project, HIT scientists will receive de-identified data including
raw imaging data from non-contrast head CT (NCCT), CTP, CTA, and Digital
subtraction angiography (DSA) of the patients in the study population. Provision of
Protocol assessment of Collateral flow in CTP Ver 1.0 Date 17APR2023
access to the above data will be according to SMC regulations and instructions relating to
data security and privacy and after obtaining the necessary SMC approvals.
Data analysis:
The project will be divided into two phases:
1. Phase 1 – Development of a novel vDSA tool for assessment of collateral flow
HIT scientists will initially receive de-identified imaging data of ~100 patients with
anterior circulation (Internal carotid artery / middle cerebral artery) occlusion. They will
co-register CTP images with CTA images to produce a unified colored map of cerebral
vessels (color vDSA) in which different values of Time-To-Peak (TTP) will be
represented with different colors. Similar techniques will be used to build a 2D/3D
dynamic pictures of cerebral vessels (cine vDSA). These will be visually assessed and
compared to the formal DSA pictures to obtain optimal performance of these tools.
2. Phase 2 - Further exploration of vDSA as a clinical tool in acute ischemic stroke
The color vDSA and cine vDSA of the first 100 patients will be independently assessed
by two invasive neuroradiologists and a stroke neurologist to evaluate for potential
clinical uses.
The de-identified imaging data of up to 300 more patients will be transferred to HIT for
further exploration of the flow data using artificial intelligence (AI) and deep machine
learning (DML). Patients with posterior circulation occlusions and patients who were not
treated with EVT will also be included in this phase.
Enhancement curves in occluded and retrograde flowing arteries will be analyzed on the
unified maps and compared to contralateral normal-flowing arteries with the aim of
describing and quantifying pre-occlusion, post-occlusion and retrograde flow patterns.
Data from patients vDSA-derived data will be analyzed and each patient will be given a
topographic vDSA collateral score similar to the topographic representation of the
Alberta stroke programme early CT score (ASPECTS). We will study the correlation of
Protocol assessment of Collateral flow in CTP Ver 1.0 Date 17APR2023
the vDSA collateral score with CTP-core ASPECTS, final infarct ASPECTS and final
infarct volume. The vDSA collateral score will also be correlated with clinical outcomes
of stroke patients including early neurological improvement, 90-days mRS score and
good functional outcome. The aim will be to produce a topographic vDSA collateral
score that will predict tissue fate and the expected benefit from EVT.
References:
1. Ryu, J., Hu, X., Shadden, S.C., 2015. A coupled lumped-parameter and
distributed network model for cerebral pulse-wave hemodynamics. J. Biomech.
Eng. 137, 101009.
2. Liebeskind, D.S., 2003. Collateral circulation. Stroke 34, 2279e2284.
3. Bang OY, Saver JL, Kim SJ, et al. Collateral flow predicts response to
endovascular therapy for acute ischemic stroke. Stroke 2011;42:693–9.
4. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid
endovascular treatment of ischemic stroke. N Engl J Med 2015;372:1019–30.
5.
Bang OY, Saver JL, Kim SJ, et al. Collateral flow averts hemorrhagic
transformation after endovascular therapy for acute ischemic stroke. Stroke
2011;42:2235–9.
6. Fanou EM, Knight J, Aviv RI, et al. Effect of Collaterals on Clinical Presentation,
Baseline Imaging, Complications, and Outcome in Acute Stroke. AJNR Am J
Neuroradiol 2015;36:2285–91.
7. Sanossian, N., Saver, J.L., Alger, J.R., Kim, D., Duckwiler, G.R., Jahan, R.,
Vinuela, F., Ovbiagele, B., Liebeskind, D.S., 2009. Angiography reveals that
fluid-attenuated inversion recovery vascular hyperintensities are due to slow flow,
not thrombus. AJNR Am. J. Neuroradiol. 30, 564e568.
8. Raymond, S.B., Schaefer, P.W., 2017. Imaging brain collaterals: quantification,
scoring, and potential significance. Top. Magn. Reson Imaging 26, 67e75.
9. CT angiography-based collateral flow and time to reperfusion are strong
predictors of outcome in endovascular treatment of patients with stroke. Sallustio
F, Motta C, Pizzuto S, Diomedi M, Giordano A, D'Agostino VC, Samֳ D,
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Mangiafico S, Saia V, Legramante JM, Konda D, Pampana E, Floris R, Stanzione
P, Gandini R, Koch G. J Neurointerv Surg. 2017 Oct;9(10):940-943
10. Validation of collateral scoring on flat-detector multiphase CT angiography in
patients with acute ischemic stroke. Maier IL, Scalzo F, Leyhe JR, Schregel K,
Behme D, Tsogkas I, Psychogios MN, Liebeskind DS. PLoS One. 2018 Aug
24;13(8)
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