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Potential Effect of Fetal Origin of Posterior Cerebral Artery on the Arterial Spin Labeling Sequence
Journal Pre-proof Potential Effect of Fetal Origin of Posterior Cerebral Artery on the Arterial Spin Labeling Sequence Bert Geerts MD Bruno Law Ye MD Damien Galanaud MD PhD Didier Dormont MD Nadya Pyatigorskaya MD PhD
PII:
S0150-9861(19)30463-8
DOI:
https://doi.org/doi:10.1016/j.neurad.2019.08.006
Reference:
NEURAD 868
To appear in:
Journal of Neuroradiology
Please cite this article as: Geerts B, Ye BL, Galanaud D, Dormont D, Pyatigorskaya N, Potential Effect of Fetal Origin of Posterior Cerebral Artery on the Arterial Spin Labeling Sequence, Journal of Neuroradiology (2019), doi: https://doi.org/10.1016/j.neurad.2019.08.006
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier.
Potential Effect of Fetal Origin of Posterior Cerebral Artery on the Arterial Spin Labeling Sequence Bert Geerts, MD,1* Bruno Law Ye, MD,2 Damien Galanaud MD, PhD,2 Didier Dormont, MD,2 Nadya Pyatigorskaya, MD, PhD2 1 Department of Radiology, AZ Sint-Jan Brugge – Oostende AV, Bruges, Belgium 2 Assistance Publique Hôpitaux de Paris, Service de Neuroradiologie, Hôpital Pitié Salpêtrière, Paris, France * Corresponding author's contact details:
ro of
Bert Geerts E-mail: [email protected] Tel: + 32 50 45 21 19
-p
Adress: Ruddershove 10, 8000, Bruges, Belgium Ethical Standards and Patient Consent:
re
We declare that all human and animal studies have been approved by the local ethical committee of the institution Pitié Salpêtrière and have therefore been performed in accordance with the ethical
lP
standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.
Jo ur na
Author contributions:
Guarantor of integrity of the entire study: Bert Geerts Study concepts: Nadya Pyatigorskaya
Definition of intellectual content: Bert Geerts, Nadya Pyatigorskaya Literature research: Bert Geerts, Nadya Pyatigorskaya Data analysis: Bert Geerts
Manuscript preparation: Bert Geerts, Nadya Pyatigorskaya Manuscript editing and reviewing: Bert Geerts, Bruno Law-Ye, Damien Galanaud, Didier Dormont, Nadya Pyatigorskaya Highlights:
Arterial Spin Labeling (ASL) is prone to a number of artifacts, which may affect its diagnostic accuracy. 1 Page 1 of 8
Perfusion asymmetry in the posterior cerebral artery (PCA) territory can be induced by a fetaltype PCA. Include structural MRI sequences to rule out pathology mimickers.
Abstract
Arterial Spin Labeling (ASL) is prone to a number of artifacts, which may affect its diagnostic accuracy. To avoid these pitfalls, possible effects on the ASL measurements should be identified. Perfusion asymmetry in the posterior cerebral artery (PCA) territory may be induced by the fetal-type PCA. Whenever a posterior left-right asymmetry is observed on the ASL, structural MR images should be
ro of
taken into account to rule out cerebrovascular pathology mimickers such as unilateral fetal-type PCA.
Abbreviations: ASL = arterial spin labeling, CBF = cerebral blood flow, PCA = posterior cerebral artery,
-p
MR = magnetic resonance.
re
Keywords: cerebral blood flow; perfusion; posterior cerebral artery; arterial spin labeling. Introduction
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Imaging of the cerebral perfusion is an integrative part of the cerebrovascular disease and other brain disease investigation. Arterial spin labeling (ASL) is a noninvasive magnetic resonance perfusion method for visualizing brain perfusion and quantifying the cerebral blood flow (CBF) [1]. This technique
Jo ur na
is being increasingly incorporated into routine neuroimaging protocols for evaluating cerebrovascular disease as well as other cerebral pathologies [2]. In the ASL method, the arterial blood water is used as an endogenous freely diffusible tracer [3]. By administrating a selective inversion pulse, inflowing spins proximal to the imaging slab are tagged. The use of transit post-label delay (PLD) allows the tagged spins to enter the imaging plane, which results in the T1 decay of the label. Perfusion contrast is obtained by calculating the difference between the magnetization of the labeled and unlabeled control images, expressed in ml/100 g/min [3]. However, the ASL technique has certain drawbacks. Since most labeled arterial blood water will relax during its transit through the capillaries before exchanging with brain tissue water [4], inflowing labeled molecules account for only about 1% of the static tissue signal. This explains the relatively low signal-to-noise ratio (SNR) [2], which can be additionally deteriorated by the patient’s motion, vascular disease, or coil sensitivity artifacts [3]. In an attempt to maximize the SNR, multiple cycles of the labeled and control images are obtained, with a typical acquisition time of 4-6 min [2]. In addition, ASL is prone to a number of artifacts, which may affect the diagnostic accuracy and lead to possible diagnostic 2 Page 2 of 8
errors. To avoid these pitfalls and to fully use the ASL technical potential, each effect that can influence the ASL measurements should be taken into consideration and confronted with the clinical context. In this paper, we describe the possibility of physiological perfusion asymmetry in the subtracted brain tissue perfusion mapping due to fetal posterior cerebral artery (PCA), mimicking cerebrovascular pathology. Materials and Methods Selection of patients We retrospectively included two consecutive patients presenting with occipital hypo-perfusion on the
ro of
ASL sequence, which was discordant with the clinical symptoms. In both patients, this discrepancy was explained by the unilateral fetal cerebral posterior artery arising from the carotid artery. Image acquisition
-p
The MRI was performed on a 3T MR GE (HDxT, GE Healthcare, Milwaukee, USA) whole-body scanner, using an eight-channel head coil. The imaging protocol included, at least, axial diffusion-weighted
re
imaging (DWI), axial T2 gradient echo WI, susceptibility WI, and 3D Time- of-Flight (TOF) images. The ASL images were acquired using the pseudo-continuous ASL technique with a large number of short
lP
pulses simulating continuous labeling, which was performed 2 cm below the image acquisition plane. The imaging parameters were: TR/TE 4733/9.8 ms, NEX 3, post label delay 2025 ms, FOV 24 cm3, spiral acquisition with 8 arms and 512 points per arm, resulting in inplane resolution of 3.49*3.49*4 mm,
Jo ur na
scan time 4`41 min.
Magnetic resonance angiography (MRA) of the circle of Willis was performed using the routine noncontrast 3D TOF sequence with the following parameters: TR/TE 30/2.6 ms, flip angle 15°, slice thickness 2 mm, FOV 24 cm3, matrix 416*352, bandwidth 31.25 kHz. The maximum intensity projection reconstruction was generated on the basis of the source images obtained at multiple projection angles, which makes it possible to analyze vascular anatomy in detail. Image processing
The CBF maps were calculated using GE AW workstation (GE Healthcare, Milwaukee, USA), on the basis of the previously described formula [5]: 𝑆𝑇
𝐶𝐵𝐹 = 6000. 𝜆
𝑃𝐿𝐷
(1− 𝑒 𝑇1𝑡 )𝑒 𝑇1𝑏 2𝜖𝑇1𝑏(1−𝑒
−𝐿𝑇 ) 𝑇1𝑏
(
𝑃𝑊 𝑆𝐹𝑃𝑊𝑃𝐷
)
3 Page 3 of 8
T1 of blood (T1b) was assumed to be 1.6 s at 3.0T, T1 of tissue (T1t) was 1.2 s, partition coefficient () was 0.9, labeling efficiency () was 0.6, saturation time of PD (ST) was 2 s, labeling duration (LT) was 1.5 s, and PLD was 2025 ms. PW refers to perfusion-weighted image, SFPW - to the scaling factor of the PW sequence, and PD to the partial saturation of the reference image. First, CBF was visually assessed by two expert neuroradiologists, who had the experience of 8 and 20 years. Second, quantitative analysis was performed by placing two symmetrical regions of interest (ROI) in the PCA territories of the most visually relevant single slice. Results
ro of
Case 1 A 56-year-old male patient was presented to the emergency department with a left-side brachial-facial deficit. The CT scan showed no abnormalities. Subsequently, MRI with ASL was performed, which showed an asymmetric cerebral perfusion map in the occipital territories (Fig. 1A). The left occipital
-p
cortical/subcortical territory was hyper-perfused with the CBF ratio of 1.35 (57.4 vs 42.5 ml/100g/min).
showed no impairments whatsoever.
re
There were no clinical arguments for any lesion in the PCA territory and diffusion-weighted imaging
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3D TOF imaging showed a unilateral fetal origin of the left PCA (Fig. 1B). Case 2
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A 57-year-old woman was referred to the emergency department for aphasia and right- sided hemiplegia. MRI showed a total occlusion of the middle cerebral artery M1 segment. A few days after successful thrombolysis and thrombectomy, control MRI with ASL showed the left median cerebral artery permeability and hemorrhagic transformation of the above ischemia area. However, the ASL perfusion map also revealed hyper-perfusion of the contra-lateral PCA territory (Fig. 2A). The CBF ratio of the right- and left-side territories was 1.29 (68.3 vs 52.9 ml/100g/min). Careful examination of the 3D TOF sequence supported the unilateral fetal origin of the right PCA (Fig. 2B). Discussion
In our study, hyper-perfusion in the posterior cerebral artery territory could only be explained by the fetal origin of the cerebral posterior artery since no other pathological or physiological explanation could be proposed and there were no clinical symptoms correlating with the images. However, radiologists blinded to the clinical history and TOF images mistakenly interpreted the PCA territory ipsilateral to the fetal PCA as a pathologic region of hyper-perfusion or suspected hypo-perfusion on the contralateral side. 4 Page 4 of 8
ASL, being a well-established technique in evaluating cerebrovascular disease, is an alternative to the frequently used dynamic susceptibility contrast (DSC)-MR bolus technique [3,6]. Nowadays, ASL is widely used in stroke imaging to detect hypo-perfusion, luxury hyper-perfusion, reperfusion related to the stroke onset and to evaluate stroke differential diagnoses, such as seizure or migraine with aura, and also in tumor and neurodegenerative investigations [7]. The prevalence of unilateral fetal origin of the posterior cerebral artery has been estimated at 11%29% [8]. The possible influence of this anatomical variation on brain perfusion, as studied by the DSC technique, was analyzed by Wentland et al [9]. It was shown that a fetal origin of the PCA arising from carotid artery results in a substantial left-right asymmetry, which may affect certain perfusion
ro of
measurements through alterations in the macro-vascular arterial transit. The authors found that the perfusion transit time in the PCA territories typically decreases with the increasing contribution of the anterior circulation relative to the posterior circulation. Since the anterior circulation has greater timeaveraged velocities and flow volumes as compared to the posterior circulation [10], it can be suggested
-p
that the fetal origin PCA allows passing more tagged spins into the ipsilateral posterior territory in the imaging plane. This, in turn, leads to an asymmetric hyper-perfused region as compared to the
re
contralateral side, with increased CBF. Barkeij Wolf et al. [11] studied the influence of this specific anatomical variation with pCASL and, similar to our results, found a significantly higher pCASL signal in
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the ipsilateral flow territory of the fetal posterior cerebral artery. In addition, reduced flow velocity in the basilar artery in subjects with a unilateral fetal PCA was reported. This may lead to a decreased pCASL signal in the contralateral side fed by the basilar artery, which means that less label reaches the
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tissue and, as a result, focal CBF is underestimated and, consequently, asymmetry increases. Thus it may be suggested that the asymmetry found in our cases can be due both to differences in the arterial transit times and to labeling efficiency. On the one hand, there is higher flow velocity on the ipsilateral side, which results in a higher number of tagged spins; on the other hand, according to the findings of Barkeij Wolf et al, there may be decreased flow velocity on the contralateral side. The left-right asymmetry is widely used as a visual cue by radiologists seeking for pathology, especially in semi-quantitative mapping and low spatial resolution imaging [9]. For this reason, the asymmetry between the two sides may be the source of substantial errors since it can mimic pathology either on the ipsilateral hyper-perfused side or on the contralateral side, which may be mistakenly interpreted as a pathologic region of cerebral hypo-perfusion. In stroke studies, the ASL sequence can be easily compared to the MRA results in order to rule out vascular variation pitfalls, like it was done in our examples of perfusion asymmetry. However, when ASL is used in non-vascular imaging, e.g., in assessing tumors [12] or neurodegenerative diseases [13],
5 Page 5 of 8
one should keep in mind the possibility of artifacts in the posterior hyper-perfusion origin. Particular attention should also be paid to the differential diagnosis in the cases of migraine and posterior reversible encephalopathy syndrome (PRES), which show posterior hyper-perfusion [7]. Our study presents new interesting observations confirming the influence of anatomical variations on ASL CBF maps. An asymmetric ASL signal caused by vascular variation has also been reported in other pathological cases. Localized hyper-perfusion was also observed in some vascular malformations, such as vascular shunt lesions or developmental venous abnormalities [7]. In these cases, the increase of CBF, actually, resulted from the increased intravenous ASL signal [14]. In contrast to this, vascular stenosis or arteriopathy were reported to induce homolateral hypo-perfusion due to reduced
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vascularization velocities [14]. For instance, in the moyamoya disease case, the signal decrease can be induced by the delayed blood flow and not by the actual decrease of parenchymal CBF [16]. Apart from the fetal origin of the PCA under physiological conditions, occipital posterior hyperperfusion can have other origins, such as visual cortex activation, which also induces bilateral posterior
-p
hyper-perfusion [16]. This kind of hyper-perfusion can also be induced by the head of the patient being
re
in a wrong, posterior extension position.
We believe that our findings, in addition to the study of Barkeij Wolf et al. regarding a variant type of
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the circle of Willis will contribute to better understanding the factors influencing ASL signal that remains still debated, [17], and increase the reliability and diagnostic value of the method. Obviously, additional studies of the effect of vascular variations on ASL should be conducted, with a
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larger number of subjects. However, at the present stage, it is important to emphasize the possible pitfalls in the ASL interpretation caused by anatomical vascular variations and the need for acquiring additional structural MRI sequences to be compared with the results of ASL in order to support their interpretation. Conclusions
When a posterior left-right asymmetry is observed on the CBF maps derived from the ASL sequence, structural MRI, including a magnetic resonance angiography sequence, should be acquired to rule out cerebrovascular pathology mimickers, such as unilateral fetal-type PCA. Conflict of interest: We declare to have no conflict of interest. Acknowledgements: There was no funding for this study. 6 Page 6 of 8
Glossary:
Arterial Spin Labeling (ASL): a noninvasive magnetic resonance perfusion method for visualizing brain perfusion and quantifying the cerebral blood flow (CBF)
Post Labeling Decay (PLD): the time, following the labeling phase, for the blood to travel to the tissue.
References
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[7] [8] [9] [10] [11]
[12]
[13]
[14] [15]
[16]
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[5]
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[4]
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[3]
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[2]
Hartkamp N., Van Osch MJ., Kappelle J, Bokkers RP. Arterial spin labeling magnetic resonance perfusion imaging in cerebral ischemia. Curr Opin Neurol. 2014;27(1):42-53. Curr Opin Neurol 2014;27:42–53. Grade M, Hernandez J., Pizzine F., Achten E, Golay X, Smits M. A neuroradiologist’s guide to arterial spin labeling MRI in clinical practice. Neuroradiology 2015;57:1181–202. Deibler A., Pollock J., Kraft R., Tan H, Burdette J., Maldjian J. Arterial Spin-labeling in routine clinical practice, part 1: technique and artifacts. AJNR 2008;29:1228–35. Wolf R., Wang J, Detre J., Zager E., Hurst R. Arteriovenous shunt visualization in arteriovenous malformations with arterial spin-labeling MR imaging. AJNR 2008;29:681–7. Wong A., Yan F-X, Liu H-L. Comparison of Three-Dimensional Pseudo-continuous Arterial Spine Labeling Perfusion Imaging With Gradient-Echo and Spin-Echo Dynamic Susceptibility Contrast MRI. J Magn Reson Imaging 2014;39:427–33. Viallon M, Cuvinciuc V, Delattre B, Merlini L, Barnaure-Nachbar I, Toso-Patel S, et al. State-ofthe-art MRI techniques in neuroradiology: principles, pitfalls, and clinical applications. Neuroradiology. 2015. 57:441-467. Neuroradiology 2015;57:441–67. Deibler A., Pollock J., Kraft R., Tan H, Burdette J., Maldjian J. Arterial Spin-labeling in routine clinical practice, part 3: hyperperfusion patterns. AJNR 2008;29:1428–35. Van Raamt A., Mali WPT., van Laar P., van der Graaf Y. The fetal variant of the circle of willis and its influence on the cerebral collateral circulation. Cerebrovasc Dis 2006;22:217–24. Wentland A., Rowley H., Vigen K., Field A. Fetal origin of the posterior cerebral artery produces left-right asymmetry on perfusion imaging. AJNR 2010;31:448–53. Schöning M, Walter J, Scheel P. Estimation of cerebral blood flow through color duplex sonography of the carotid and vertebral arteries in healthy adults. Stroke 1994;25:17–22. Barkeij Wolf JJH., Foster-Dingley JC., Moonen JEF., van Osch MJP., de Craen A., de Ruijter W., van der Mast RC., van der Grond J. Unilateral fetal-type circle of Willis anatomy causes right-left asymmetry in cerebral blood flow with pseudo-continuous arterial spin labeling: A limiation of arterial spin labeling-based cerebral flow measurements? J Cerebral Blood Flow Metab 2016;36:1570-1578. Järnum H, Steffensen E., Knutsson L, Fründ E-T, Simonsen C.W C., Lunbye-Christensen S, et al. Perfusion MRI of brain tumours: a comparative study of pseudo-continuous arterial spin labelling and dynamic susceptibility contrast imaging. Neuroradiology 2010;52:307–17. Kim S., Kim M., Rhee H., Ryu C-W, Kim E-J, Petersen E., et al. Regional cerebral perfusion in patients with Alzheimer’s disease and mild cognitive impairment: effect of APOE Epsilon4 allele 2013;55:25–35. Telischak N., Detre J., Zaharchuk G. Arterial spin labeling MRI: clinical applications in the brain. J Magn Reson Imaging 2015;41:1165–80. Bulder M., Bokkers R., Hendrikse J, Kappelle L., Braun K., Klijn C. Arterial spin labeling perfusion MRI in children and young adults with previous ischemic stroke and unilateral intracranial arteriopathy. Cerebrovas dis 2014;37:14–21. Amukotuwa SA, Yu C, Zaharchuk G. 3D Pseudocontinuous arterial spin labeling in routine clinical practice: A review of clinically significant artifacts. J Magn Reson Imaging JMRI 2016;43:11–27.
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[1]
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[17] Law-ye B., Geerts B., Galanaud D., Dormont D., Pyatigorskaya N. Pseudo-asymmetry of cerebral blood flow in arterial spin labeling caused by unilateral fetal-type circle of Willis: Technical limitation or a way to better understanding physiological variations of cerebral perfusion and improving arterial spin labeling acquisition? J Cereb Blood Flow Metab 2016:36:1641-1643. Figure captions: Fig. 1 Left occipital hyper-perfusion. A. The cerebral perfusion map shows a hyper-perfused left occipital cortical/subcortical territory. Measurements on both occipital regions revealed a CBF ratio of 1.35. B: 3D-TOF shows a unilateral fetal origin of the left PCA (blue arrow), responsible for the perfusion asymmetry described in A.
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lP
re
-p
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Fig. 2 Right occipital hyper-perfusion. A. The cerebral perfusion map shows an asymmetric hyperperfused right occipital PCA region. The CBF ratio of the right- and left-side territories is 1.29. B. 3D TOF sequence shows a unilateral fetal origin of the right PCA (blue arrow).
8 Page 8 of 8
PII:
S0150-9861(19)30463-8
DOI:
https://doi.org/doi:10.1016/j.neurad.2019.08.006
Reference:
NEURAD 868
To appear in:
Journal of Neuroradiology
Please cite this article as: Geerts B, Ye BL, Galanaud D, Dormont D, Pyatigorskaya N, Potential Effect of Fetal Origin of Posterior Cerebral Artery on the Arterial Spin Labeling Sequence, Journal of Neuroradiology (2019), doi: https://doi.org/10.1016/j.neurad.2019.08.006
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier.
Potential Effect of Fetal Origin of Posterior Cerebral Artery on the Arterial Spin Labeling Sequence Bert Geerts, MD,1* Bruno Law Ye, MD,2 Damien Galanaud MD, PhD,2 Didier Dormont, MD,2 Nadya Pyatigorskaya, MD, PhD2 1 Department of Radiology, AZ Sint-Jan Brugge – Oostende AV, Bruges, Belgium 2 Assistance Publique Hôpitaux de Paris, Service de Neuroradiologie, Hôpital Pitié Salpêtrière, Paris, France * Corresponding author's contact details:
ro of
Bert Geerts E-mail: [email protected] Tel: + 32 50 45 21 19
-p
Adress: Ruddershove 10, 8000, Bruges, Belgium Ethical Standards and Patient Consent:
re
We declare that all human and animal studies have been approved by the local ethical committee of the institution Pitié Salpêtrière and have therefore been performed in accordance with the ethical
lP
standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.
Jo ur na
Author contributions:
Guarantor of integrity of the entire study: Bert Geerts Study concepts: Nadya Pyatigorskaya
Definition of intellectual content: Bert Geerts, Nadya Pyatigorskaya Literature research: Bert Geerts, Nadya Pyatigorskaya Data analysis: Bert Geerts
Manuscript preparation: Bert Geerts, Nadya Pyatigorskaya Manuscript editing and reviewing: Bert Geerts, Bruno Law-Ye, Damien Galanaud, Didier Dormont, Nadya Pyatigorskaya Highlights:
Arterial Spin Labeling (ASL) is prone to a number of artifacts, which may affect its diagnostic accuracy. 1 Page 1 of 8
Perfusion asymmetry in the posterior cerebral artery (PCA) territory can be induced by a fetaltype PCA. Include structural MRI sequences to rule out pathology mimickers.
Abstract
Arterial Spin Labeling (ASL) is prone to a number of artifacts, which may affect its diagnostic accuracy. To avoid these pitfalls, possible effects on the ASL measurements should be identified. Perfusion asymmetry in the posterior cerebral artery (PCA) territory may be induced by the fetal-type PCA. Whenever a posterior left-right asymmetry is observed on the ASL, structural MR images should be
ro of
taken into account to rule out cerebrovascular pathology mimickers such as unilateral fetal-type PCA.
Abbreviations: ASL = arterial spin labeling, CBF = cerebral blood flow, PCA = posterior cerebral artery,
-p
MR = magnetic resonance.
re
Keywords: cerebral blood flow; perfusion; posterior cerebral artery; arterial spin labeling. Introduction
lP
Imaging of the cerebral perfusion is an integrative part of the cerebrovascular disease and other brain disease investigation. Arterial spin labeling (ASL) is a noninvasive magnetic resonance perfusion method for visualizing brain perfusion and quantifying the cerebral blood flow (CBF) [1]. This technique
Jo ur na
is being increasingly incorporated into routine neuroimaging protocols for evaluating cerebrovascular disease as well as other cerebral pathologies [2]. In the ASL method, the arterial blood water is used as an endogenous freely diffusible tracer [3]. By administrating a selective inversion pulse, inflowing spins proximal to the imaging slab are tagged. The use of transit post-label delay (PLD) allows the tagged spins to enter the imaging plane, which results in the T1 decay of the label. Perfusion contrast is obtained by calculating the difference between the magnetization of the labeled and unlabeled control images, expressed in ml/100 g/min [3]. However, the ASL technique has certain drawbacks. Since most labeled arterial blood water will relax during its transit through the capillaries before exchanging with brain tissue water [4], inflowing labeled molecules account for only about 1% of the static tissue signal. This explains the relatively low signal-to-noise ratio (SNR) [2], which can be additionally deteriorated by the patient’s motion, vascular disease, or coil sensitivity artifacts [3]. In an attempt to maximize the SNR, multiple cycles of the labeled and control images are obtained, with a typical acquisition time of 4-6 min [2]. In addition, ASL is prone to a number of artifacts, which may affect the diagnostic accuracy and lead to possible diagnostic 2 Page 2 of 8
errors. To avoid these pitfalls and to fully use the ASL technical potential, each effect that can influence the ASL measurements should be taken into consideration and confronted with the clinical context. In this paper, we describe the possibility of physiological perfusion asymmetry in the subtracted brain tissue perfusion mapping due to fetal posterior cerebral artery (PCA), mimicking cerebrovascular pathology. Materials and Methods Selection of patients We retrospectively included two consecutive patients presenting with occipital hypo-perfusion on the
ro of
ASL sequence, which was discordant with the clinical symptoms. In both patients, this discrepancy was explained by the unilateral fetal cerebral posterior artery arising from the carotid artery. Image acquisition
-p
The MRI was performed on a 3T MR GE (HDxT, GE Healthcare, Milwaukee, USA) whole-body scanner, using an eight-channel head coil. The imaging protocol included, at least, axial diffusion-weighted
re
imaging (DWI), axial T2 gradient echo WI, susceptibility WI, and 3D Time- of-Flight (TOF) images. The ASL images were acquired using the pseudo-continuous ASL technique with a large number of short
lP
pulses simulating continuous labeling, which was performed 2 cm below the image acquisition plane. The imaging parameters were: TR/TE 4733/9.8 ms, NEX 3, post label delay 2025 ms, FOV 24 cm3, spiral acquisition with 8 arms and 512 points per arm, resulting in inplane resolution of 3.49*3.49*4 mm,
Jo ur na
scan time 4`41 min.
Magnetic resonance angiography (MRA) of the circle of Willis was performed using the routine noncontrast 3D TOF sequence with the following parameters: TR/TE 30/2.6 ms, flip angle 15°, slice thickness 2 mm, FOV 24 cm3, matrix 416*352, bandwidth 31.25 kHz. The maximum intensity projection reconstruction was generated on the basis of the source images obtained at multiple projection angles, which makes it possible to analyze vascular anatomy in detail. Image processing
The CBF maps were calculated using GE AW workstation (GE Healthcare, Milwaukee, USA), on the basis of the previously described formula [5]: 𝑆𝑇
𝐶𝐵𝐹 = 6000. 𝜆
𝑃𝐿𝐷
(1− 𝑒 𝑇1𝑡 )𝑒 𝑇1𝑏 2𝜖𝑇1𝑏(1−𝑒
−𝐿𝑇 ) 𝑇1𝑏
(
𝑃𝑊 𝑆𝐹𝑃𝑊𝑃𝐷
)
3 Page 3 of 8
T1 of blood (T1b) was assumed to be 1.6 s at 3.0T, T1 of tissue (T1t) was 1.2 s, partition coefficient () was 0.9, labeling efficiency () was 0.6, saturation time of PD (ST) was 2 s, labeling duration (LT) was 1.5 s, and PLD was 2025 ms. PW refers to perfusion-weighted image, SFPW - to the scaling factor of the PW sequence, and PD to the partial saturation of the reference image. First, CBF was visually assessed by two expert neuroradiologists, who had the experience of 8 and 20 years. Second, quantitative analysis was performed by placing two symmetrical regions of interest (ROI) in the PCA territories of the most visually relevant single slice. Results
ro of
Case 1 A 56-year-old male patient was presented to the emergency department with a left-side brachial-facial deficit. The CT scan showed no abnormalities. Subsequently, MRI with ASL was performed, which showed an asymmetric cerebral perfusion map in the occipital territories (Fig. 1A). The left occipital
-p
cortical/subcortical territory was hyper-perfused with the CBF ratio of 1.35 (57.4 vs 42.5 ml/100g/min).
showed no impairments whatsoever.
re
There were no clinical arguments for any lesion in the PCA territory and diffusion-weighted imaging
lP
3D TOF imaging showed a unilateral fetal origin of the left PCA (Fig. 1B). Case 2
Jo ur na
A 57-year-old woman was referred to the emergency department for aphasia and right- sided hemiplegia. MRI showed a total occlusion of the middle cerebral artery M1 segment. A few days after successful thrombolysis and thrombectomy, control MRI with ASL showed the left median cerebral artery permeability and hemorrhagic transformation of the above ischemia area. However, the ASL perfusion map also revealed hyper-perfusion of the contra-lateral PCA territory (Fig. 2A). The CBF ratio of the right- and left-side territories was 1.29 (68.3 vs 52.9 ml/100g/min). Careful examination of the 3D TOF sequence supported the unilateral fetal origin of the right PCA (Fig. 2B). Discussion
In our study, hyper-perfusion in the posterior cerebral artery territory could only be explained by the fetal origin of the cerebral posterior artery since no other pathological or physiological explanation could be proposed and there were no clinical symptoms correlating with the images. However, radiologists blinded to the clinical history and TOF images mistakenly interpreted the PCA territory ipsilateral to the fetal PCA as a pathologic region of hyper-perfusion or suspected hypo-perfusion on the contralateral side. 4 Page 4 of 8
ASL, being a well-established technique in evaluating cerebrovascular disease, is an alternative to the frequently used dynamic susceptibility contrast (DSC)-MR bolus technique [3,6]. Nowadays, ASL is widely used in stroke imaging to detect hypo-perfusion, luxury hyper-perfusion, reperfusion related to the stroke onset and to evaluate stroke differential diagnoses, such as seizure or migraine with aura, and also in tumor and neurodegenerative investigations [7]. The prevalence of unilateral fetal origin of the posterior cerebral artery has been estimated at 11%29% [8]. The possible influence of this anatomical variation on brain perfusion, as studied by the DSC technique, was analyzed by Wentland et al [9]. It was shown that a fetal origin of the PCA arising from carotid artery results in a substantial left-right asymmetry, which may affect certain perfusion
ro of
measurements through alterations in the macro-vascular arterial transit. The authors found that the perfusion transit time in the PCA territories typically decreases with the increasing contribution of the anterior circulation relative to the posterior circulation. Since the anterior circulation has greater timeaveraged velocities and flow volumes as compared to the posterior circulation [10], it can be suggested
-p
that the fetal origin PCA allows passing more tagged spins into the ipsilateral posterior territory in the imaging plane. This, in turn, leads to an asymmetric hyper-perfused region as compared to the
re
contralateral side, with increased CBF. Barkeij Wolf et al. [11] studied the influence of this specific anatomical variation with pCASL and, similar to our results, found a significantly higher pCASL signal in
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the ipsilateral flow territory of the fetal posterior cerebral artery. In addition, reduced flow velocity in the basilar artery in subjects with a unilateral fetal PCA was reported. This may lead to a decreased pCASL signal in the contralateral side fed by the basilar artery, which means that less label reaches the
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tissue and, as a result, focal CBF is underestimated and, consequently, asymmetry increases. Thus it may be suggested that the asymmetry found in our cases can be due both to differences in the arterial transit times and to labeling efficiency. On the one hand, there is higher flow velocity on the ipsilateral side, which results in a higher number of tagged spins; on the other hand, according to the findings of Barkeij Wolf et al, there may be decreased flow velocity on the contralateral side. The left-right asymmetry is widely used as a visual cue by radiologists seeking for pathology, especially in semi-quantitative mapping and low spatial resolution imaging [9]. For this reason, the asymmetry between the two sides may be the source of substantial errors since it can mimic pathology either on the ipsilateral hyper-perfused side or on the contralateral side, which may be mistakenly interpreted as a pathologic region of cerebral hypo-perfusion. In stroke studies, the ASL sequence can be easily compared to the MRA results in order to rule out vascular variation pitfalls, like it was done in our examples of perfusion asymmetry. However, when ASL is used in non-vascular imaging, e.g., in assessing tumors [12] or neurodegenerative diseases [13],
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one should keep in mind the possibility of artifacts in the posterior hyper-perfusion origin. Particular attention should also be paid to the differential diagnosis in the cases of migraine and posterior reversible encephalopathy syndrome (PRES), which show posterior hyper-perfusion [7]. Our study presents new interesting observations confirming the influence of anatomical variations on ASL CBF maps. An asymmetric ASL signal caused by vascular variation has also been reported in other pathological cases. Localized hyper-perfusion was also observed in some vascular malformations, such as vascular shunt lesions or developmental venous abnormalities [7]. In these cases, the increase of CBF, actually, resulted from the increased intravenous ASL signal [14]. In contrast to this, vascular stenosis or arteriopathy were reported to induce homolateral hypo-perfusion due to reduced
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vascularization velocities [14]. For instance, in the moyamoya disease case, the signal decrease can be induced by the delayed blood flow and not by the actual decrease of parenchymal CBF [16]. Apart from the fetal origin of the PCA under physiological conditions, occipital posterior hyperperfusion can have other origins, such as visual cortex activation, which also induces bilateral posterior
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hyper-perfusion [16]. This kind of hyper-perfusion can also be induced by the head of the patient being
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in a wrong, posterior extension position.
We believe that our findings, in addition to the study of Barkeij Wolf et al. regarding a variant type of
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the circle of Willis will contribute to better understanding the factors influencing ASL signal that remains still debated, [17], and increase the reliability and diagnostic value of the method. Obviously, additional studies of the effect of vascular variations on ASL should be conducted, with a
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larger number of subjects. However, at the present stage, it is important to emphasize the possible pitfalls in the ASL interpretation caused by anatomical vascular variations and the need for acquiring additional structural MRI sequences to be compared with the results of ASL in order to support their interpretation. Conclusions
When a posterior left-right asymmetry is observed on the CBF maps derived from the ASL sequence, structural MRI, including a magnetic resonance angiography sequence, should be acquired to rule out cerebrovascular pathology mimickers, such as unilateral fetal-type PCA. Conflict of interest: We declare to have no conflict of interest. Acknowledgements: There was no funding for this study. 6 Page 6 of 8
Glossary:
Arterial Spin Labeling (ASL): a noninvasive magnetic resonance perfusion method for visualizing brain perfusion and quantifying the cerebral blood flow (CBF)
Post Labeling Decay (PLD): the time, following the labeling phase, for the blood to travel to the tissue.
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[17] Law-ye B., Geerts B., Galanaud D., Dormont D., Pyatigorskaya N. Pseudo-asymmetry of cerebral blood flow in arterial spin labeling caused by unilateral fetal-type circle of Willis: Technical limitation or a way to better understanding physiological variations of cerebral perfusion and improving arterial spin labeling acquisition? J Cereb Blood Flow Metab 2016:36:1641-1643. Figure captions: Fig. 1 Left occipital hyper-perfusion. A. The cerebral perfusion map shows a hyper-perfused left occipital cortical/subcortical territory. Measurements on both occipital regions revealed a CBF ratio of 1.35. B: 3D-TOF shows a unilateral fetal origin of the left PCA (blue arrow), responsible for the perfusion asymmetry described in A.
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Fig. 2 Right occipital hyper-perfusion. A. The cerebral perfusion map shows an asymmetric hyperperfused right occipital PCA region. The CBF ratio of the right- and left-side territories is 1.29. B. 3D TOF sequence shows a unilateral fetal origin of the right PCA (blue arrow).
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