Optical Coherence Tomography of Plaque Erosion and Thrombus in Severe Vertebral Artery Stenosis

diagnostics

Interesting Images Optical Coherence Tomography of Plaque Erosion and Thrombus in Severe Vertebral Artery Stenosis

Lin Yan 1 , Adam A. Dmytriw 2,3 , Bin Yang 1 and Liqun Jiao 1,2,*

1 Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, China International Neuroscience Institute (China-INI), Beijing 100053, China; [email protected] (L.Y.); [email protected] (B.Y.) 2 Department of Interventional Neuroradiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; [email protected] 3 Neuroradiology & Neurointervention Service, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA * Correspondence: [email protected]

Abstract: A 69-year-old male presented with medically refractory vertebrobasilar insufficiency and paroxysmal subjective dizziness for six months. Severe stenosis of a dominant left V2 vertebral artery segment was identified on digital subtraction angiography (DSA) with an irregular intraluminal filling defect immediately above the stenosis. Optical coherence tomography (OCT) demonstrated a normal lumen at the distal end, with red thrombus detected distal to the stenosis. Atherosclerotic plaque containing fibro-lipid was also identified and treated with a drug-eluting stent. Distal red thrombi were not covered by stenting, indicating embolization risk in the future. Clear posterior fossa symptoms occurred after intervention, and treatment with a standard dual antiplatelet regimen and statin therapy was prescribed for one year. Six months after treatment, the symptoms improved, and six-minute walking distances were successful with no gait impairment. To our knowledge, this is the first V2 Citation: Yan, L.; Dmytriw, A.A.; segment stenosis assessed by OCT imaging before and after stenting, indicating an intact fibrous cap Yang, B.; Jiao, L. Optical Coherence with thrombus formation, as well as plaque erosion. Understanding the role and careful use of OCT Tomography of Plaque Erosion and Thrombus in Severe Vertebral Artery may improve the identification of red thrombus and plaque erosion when clinically indicated. Stenosis. Diagnostics 2021, 11, 638. https://doi.org/10.3390/ Keywords: vertebral artery stenosis; red thrombus; optical coherence tomography diagnostics11040638

Academic Editor: Eytan Raz A 69-year-old male presented with medically refractory vertebrobasilar insufficiency Received: 24 February 2021 and paroxysmal subjective dizziness for six months. The patient had a history of alcohol Accepted: 31 March 2021 use and cigarette smoking for more than 40 years, a four-year history of well-controlled Published: 1 April 2021 essential hypertension, and a one-month history of documented hyperlipemia. No prior stroke, transient ischemic attack (TIA), myocardial infarction, or significant family history Publisher’s Note: MDPI stays neutral was reported. There was no history of anticoagulation or antiplatelet use. The patient with regard to jurisdictional claims in presented with an unremarkable neurological examination. Severe stenosis of the dominant published maps and institutional affil- left vertebral artery V2 segment was identified on computed tomography angiography iations. (CTA), likely secondary to atherosclerosis, coexisting with an undeveloped left posterior cerebral artery (PCA) and leading to an incomplete circle of Willis, which was noted (Figure1A–D ). Digital subtraction angiography (DSA) demonstrated a corresponding irregular intraluminal filling defect with severe stenosis, and a plan to stent the left V2 Copyright: © 2021 by the authors. stenosis was made (Figure2A). Licensee MDPI, Basel, Switzerland. Optical coherence tomography (OCT) is an intravascular imaging method that acquires This article is an open access article images at a resolution of ~10 µm, and captures images with an axial resolution 10 times distributed under the terms and higher than intravascular ultrasound, enabling visualization of the blood vessel wall at near conditions of the Creative Commons histological resolution [1]. OCT has proven to be a useful modality in coronary angiography, Attribution (CC BY) license (https:// and may have similar applications in evaluating intracranial atherosclerotic disease. OCT creativecommons.org/licenses/by/ is able to detect ulceration, large lipid pools, fresh thrombus, and severe calcification laying 4.0/).

Diagnostics 2021, 11, 638. https://doi.org/10.3390/diagnostics11040638 https://www.mdpi.com/journal/diagnostics Diagnostics 2021, 11, 638 2 of 5

on the surface of the vessel. More importantly, stent apposition and expansion, plaque protrusion, and thrombus characteristics can also be clarified through OCT imaging during and post-interventional stenting, which is vital for subsequent therapy. All patients at our center who undergo stenting are pretreated with aspirin (100 mg/d) and clopidogrel (150 mg followed by 75 mg daily). Neurological assessment was performed before and after the procedure. The patients who undergo OCT sign explicit consent. OCT studies are conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Xuanwu Hospital (protocol code (20200913) and date of approval: 30 September 2020. Prior to stenting, standard guidewire placement via a percutaneous puncture of the right femoral artery is performed. A Dragonfly Duo (St. Jude Medical, Little Canada, MN, USA) OCT imaging catheter is placed prior to stenting in order to determine stent sizing, and OCT images in this case confirmed severe stenosis with atherosclerotic plaque formation, as well as fresh mural thrombus (i.e. red thrombus) at the distal end of the stenosis, which has not otherwise been clearly identified. The OCT images demonstrated that this as an irregularly high signal area into the lumen, with hypo-reflective signal attenuation in addition to a fibro-lipid plaque component (Figure2B–E). A 4.0 ×12 mm Xience Xpedition (Abbott International, Diegem, Belgium) everolimus-eluting coronary stent was used for left V2 segment stenting. Post-stenting DSA confirmed no residual stenosis (Figure3A), and OCT was then performed to check for stent apposition, stent expansion, and plaque or thrombus protrusion, which provided excellent visualization of the stent and vessel wall apposition. Good apposition regarding the proximal stenosis was seen, whereas red thrombus attached to the distal end was seen on OCT, suggesting possible future embolization risk (Figure3B–D ). Immediately after intervention, the patient experienced dizziness, confusion, vomiting, and diarrhea, and right cerebellar infarction was confirmed by magnetic resonance imaging (MRI) (Figure3E–H) . This was surmised to be based on the aforementioned red thrombus seen distally, and thus, treatment with a standard dual antiplatelet regimen and statin therapy was prescribed for one year. Six months after treatment, the symptoms improved, and six-minute walking distances were successful with no gait impairment. The incidence of red thrombus embolism with distal embolization is high, and pos- sesses a considerable mortality rate, but timely diagnosis is uncommon, and is usually arrived upon after a stroke has occurred. Ideally, this diagnosis should be made at the time of intervention if possible to avoid complications. While DSA has been considered an effective method for visualizing thrombus and embolism as filling defects, the structure of the lumen and the composition of thrombi is relatively poorly resolved. By contrast, OCT is an optical imaging technology characterized by real-time, dynamic intraluminal imaging and high resolution, and very much is its nascence within intracranial vasculature. The OCT imaging guidewire can be passed into distal small vessels for imaging, and OCT images have the ability to clearly depict the luminal structure without neurological complications and identify missed thrombi on DSA, as well as distinguish different types of thrombi, which may guide anticoagulant therapy [2]. OCT and other imaging modali- ties complement each other and may additionally aid in discriminating plaques that are eligible for stenting [3]. To this end, OCT has also shown promise in forensic pathology and radiology, with coronary dissection and rupture visible at virtual autopsy, in addition to micron-level changes in ocular and dermal tissue [4,5].In this case, red thrombus was quite readily confirmed by OCT, as it showed a hyperreflective protrusive mass with an irregular surface, causing marked posterior shadowing, the hallmarks of a large thrombi by this technique [6]. Moreover, representative images of plaque erosion in our patient with symptomatic left vertebral stenosis were also readily seen. Plaque erosion is considered to be one of the sources of embolic complication after stenting, and erosion distal to stent struts just after stent deployment was seen on OCT. This is, to our knowledge, the first report of pre and post-stenting V2 segment assessment with OCT imaging. DSA and OCT both indicated an intact fibrous cap with thrombus formation, illustrating plaque Diagnostics 2021, 11, x FOR PEER REVIEW 3 of 5

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knowledge, the first report of pre and post-stenting V2 segment assessment with OCT imaging. DSA and OCT both indicated an intact fibrous cap with thrombus formation, erosionknowledge, in V2 the segment first report severe of pre stenosis and po [7].st-stenting Understanding V2 segment the role assessment of judicious with useOCT of illustrating plaque erosion in V2 segment severe stenosis [7]. Understanding the role of OCTimaging. may DSA improve and theOCT diagnosis both indicated of red thrombus an intact andfibrous plaque cap erosionwith thrombus in carefully formation, selected judicious use of OCT may improve the diagnosis of red thrombus and plaque erosion in patients,illustrating and plaque stands erosion to aid inin theV2 diagnosissegment severe of complex stenosis plaque, [7]. Understanding as well as the anticipationthe role of carefully selected patients, and stands to aid in the diagnosis of complex plaque, as well ofjudicious complications use of OCT relating may to improve these. the diagnosis of red thrombus and plaque erosion in carefullyas the anticipation selected patients, of complications and stands relating to aid to in these. the diagnosis of complex plaque, as well as the anticipation of complications relating to these.

FigureFigure 1. 1.Target Target vertebral vertebral artery artery anatomy anatomy before before endovascular endovascular intervention. intervention. (A (A,B,)B Computed) Computed tomography tomography angiography angiography of of the left V2 segment before intervention. Dominant left vertebral artery V2 segment severe stenosis ((A–C), red arrow) theFigure left V2 1. segmentTarget vertebral before intervention.artery anatomy Dominant before endovascular left vertebral intervention. artery V2 segment (A,B) severeComputed stenosis tomography ((A–C), red angiography arrow) and and an undeveloped left posterior cerebral artery, together with incomplete circle of Willis, are shown ((D), red arrow). anof undeveloped the left V2 segment left posterior before cerebralintervention. artery, Dominant together left with vertebral incomplete artery circle V2 ofsegment Willis, severe are shown stenosis ((D), (( redA–C arrow).), red arrow) and an undeveloped left posterior cerebral artery, together with incomplete circle of Willis, are shown ((D), red arrow).

Figure 2. Pre-stenting angiography and OCT images. (A) Digital subtraction angiography image of the left V2 segment Figure 2. Pre-stenting angiography and OCT images. (A) Digital subtraction angiography image of the left V2 segment Figureprior to 2. Pre-stentingstenting. Intraluminal angiography thrombus and OCT was images. seen as (A )an Digital irregular subtraction intraluminal angiography filling defect image (black of the leftarrow), V2 segment and severe prior priorstenosis to ofstenting. the underlying Intraluminal vessel thrombus was deemed was suitableseen as anfor irregularstenting. intraluminalAn intraluminal filling filling defect defect (black above arrow), the stenosis and severe was to stenting. Intraluminal thrombus was seen as an irregular intraluminal filling defect (black arrow), and severe stenosis of stenosisillustrated of bythe OCT underlying layer (dash). vessel Cross-sect was deemedional suitable OCT images for sten duringting. Anstandard intraluminal pullbac fillingk with defect the OCT above catheter the stenosis tip location was the underlying vessel was deemed suitable for stenting. An intraluminal filling defect above the stenosis was illustrated by illustratedindicated as by a OCT white layer arrow (dash). showed Cross-sect (B) normalional OCT lumen images proximally during withstandard no thrombus pullback withand (theC– DOCT) red catheter thrombus tip locationdistally OCTindicatedmanifested layer (dash).as as a anwhite Cross-sectionalirregular arrow hyper-refl showed OCT (ectiveB images) normal region during lumen projecting standard proximally into pullback the with lumen withno thrombus(*), the with OCT posterior and catheter (C– Dshadowing. tip) red location thrombus indicated(E) Eccentric distally as a whitemanifested arrow showedas an irregular (B) normal hyper-refl lumenective proximally region projecting with no thrombus into the lu andmen (C (*),–D )with red thrombusposterior shadowing. distally manifested (E) Eccentric as an irregularstenosis hyper-reflectiverelating to the atherosclerotic region projecting plaque into containing the lumen fibro-lipid (*), with components posterior shadowing. appears as (aE homogenous,) Eccentric stenosis hypo-reflective relating to theregion atherosclerotic (*). plaque containing fibro-lipid components appears as a homogenous, hypo-reflective region (*).

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Diagnostics 2021, 11, 638 4 of 5 stenosis relating to the atherosclerotic plaque containing fibro-lipid components appears as a homogenous, hypo-reflective region (*).

Figure 3.3. Post-stentingPost-stenting angiography angiography and and OCT OCT images images and and post-procedural post-procedural MRI. MRI. (A) DSA (A) ofDSA the of left the V2 left segment V2 segment post-stenting post- stenting showed marked improvement in previously severe stenosis, well-covered by the stent (black arrow). Cross-sec- showed marked improvement in previously severe stenosis, well-covered by the stent (black arrow). Cross-sectional OCT tional OCT images during standard pullback demonstrating (B) normal lumen proximally with no thrombus and (C) images during standard pullback demonstrating (B) normal lumen proximally with no thrombus and (C) satisfactory stent satisfactory stent wall apposition (white arrow), whereas (D) distally a hyper-reflective area (*) projecting into the lumen wallwith appositionapparent posterior (white arrow),shadowing whereas indica (Dted) distally red thrombus a hyper-reflective (white arrow) area attached, (*) projecting which had into no the stent lumen coverage with apparent on OCT, posteriorsuggesting shadowing embolization indicated risk. (E–H red thrombus) MRI images (white following arrow) attached,intervention which when had the no patient stent coverage developed on OCT,clear suggestingsymptoms embolizationdemonstrate right risk. cerebellar (E–H) MRI infarction images following(red arrow), intervention presumed whento be related the patient to red developed thrombus, clear which symptoms was not covered. demonstrate right cerebellar infarction (red arrow), presumed to be related to red thrombus, which was not covered. Author Contributions: Conceptualization, L.Y. and L.J.; methodology, B.Y.; software, B.Y.; validation,Author L.Y., Contributions: A.A.D. andConceptualization, L.J.; formal analysis, L.Y. L.Y.; and investigation, L.J.; methodology, L.Y.; B.Y.;resources, software, L.J.; B.Y.; data validation, curation,L.Y., L.Y.; A.A.D. writing—original and L.J.; formal draft analysis, preparation, L.Y.; investigation, L.Y.; writing—review L.Y.; resources, and editing, L.J.; data A.A.D.; curation, visuali- L.Y.; zation, A.A.D.; supervision, L.J.; project administration, B.Y.; funding acquisition, L.J. All authors writing—original draft preparation, L.Y.; writing—review and editing, A.A.D.; visualization, A.A.D.; have read and agreed to the published version of the manuscript. supervision, L.J.; project administration, B.Y.; funding acquisition, L.J. All authors have read and Funding:agreed to This the published work was version supported of the by manuscript.the National Key Research and Development Project (2016YFC1301703) and the Beijing Scientific and Technologic Project (D161100003816002). Funding: This work was supported by the National Key Research and Development Project Institutional(2016YFC1301703) Review and Board the Beijing Statement: Scientific The andOCT Technologic study was conducted Project (D161100003816002). according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Xuanwu Hospital Institutional Review Board Statement: The OCT study was conducted according to the guidelines (protocol code (20200913) and date of approval: 30 September 2020. REB number: 20200913; ap- of the Declaration of Helsinki, and approved by the Institutional Review Board of Xuanwu Hospital proval date: 30 September 2020. (protocol code (20200913) and date of approval: 30 September 2020. REB number: 20200913. Informed Consent Statement: Written informed consent for publication was obtained from all sub- Informed Consent Statement: Written informed consent for publication was obtained from all jects involved in the study. subjects involved in the study. Data Availability Statement: The data presented in this study are available on request from the Data Availability Statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to patient privacy. corresponding author. The data are not publicly available due to patient privacy. Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design design of the study; in the collection, analyses, or interpretation of data; in the writing of the man- of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or uscript, or in the decision to publish the results. in the decision to publish the results. Abbreviations Abbreviations TIA Transient ischemic attack CTATIA Transient Computed ischemic tomography attack angiography DSACTA ComputedDigital tomographysubtraction angiography angiography OCTDSA DigitalOptical subtraction coherence angiography tomography DESOCT OpticalDrug-eluting coherence tomographystent DES Drug-eluting stent MRI Magnetic resonance imaging MRI Magnetic resonance imaging

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