Abstract
Purpose
Determinants of early loss of ischemic tissue (core) or its prolonged survival (penumbra) in acute ischemic stroke (AIS) are poorly understood. We aimed to identify radiological associations of core and penumbra volumes on CT perfusion (CTP) in a large cohort of AIS.
Methods
In the ASTRAL registry (2003–2016), we identified consecutive AIS patients with proximal middle cerebral artery (MCA) occlusion. We calculated core and penumbra volumes using established thresholds and the mismatch ratio (MR). We graded collaterals into three categories on CT-angiography. We used clot burden score (CBS) to quantify the clot length. We related CTP volumes to radiological variables in multivariate regression analyses, adjusted for time from stroke onset to first imaging.
Results
The median age of the 415 included patients was 69 years (IQR = 21) and 49% were female. Median admission NIHSS was 16 (11) and median delay to imaging 2.2 h (1.9). Lower core volumes were associated with higher ASPECTS (hazard ratio = 1.08), absence of hyperdense MCA sign (HR = 0.70), higher CBS (i.e., smaller clot, HR = 1.10), and better collaterals (HR = 1.95). Higher penumbra volumes were related to lower CBS (i.e., longer clot, HR = 1.08) and proximal intracranial occlusion (HR = 1.47), but not to collaterals. Higher MR was found in absence of hyperdense MCA sign (HR = 1.28), absence of distal intracranial occlusion (HR = 1.39), and with better collaterals (HR = 0.52).
Conclusions
In AIS, better collaterals were associated with lower core volumes, but not with higher penumbra volumes. This suggests a major role of collaterals in early tissue loss and their limited significance as marker of salvageable tissue.
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Abbreviations
- AIS:
-
Acute ischemic stroke
- ASPECTS:
-
Alberta Stroke Program Early CT Score
- CBS:
-
Clot burden score
- CTA:
-
CT-angiography
- CTP:
-
CT perfusion
- MCA:
-
Middle cerebral artery
- MR:
-
Mismatch ratio
- mRS:
-
Modified Rankin score
- NIHSS:
-
National Institutes of Health Stroke Scale
References
Miteff F, Levi CR, Bateman GA, Spratt N, McElduff P, Parsons MW (2009) The independent predictive utility of computed tomography angiographic collateral status in acute ischaemic stroke. Brain 132(Pt 8):2231–2238. https://doi.org/10.1093/brain/awp155
Shuaib A, Butcher K, Mohammad AA, Saqqur M, Liebeskind DS (2011) Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target. Lancet Neurol 10(10):909–921. https://doi.org/10.1016/S1474-4422(11)70195-8
Liebeskind DS (2010) Reperfusion for acute ischemic stroke: arterial revascularization and collateral therapeutics. Curr Opin Neurol 23(1):36–45. https://doi.org/10.1097/WCO.0b013e328334da32
Jung S, Gilgen M, Slotboom J, El-Koussy M, Zubler C, Kiefer C, Luedi R, Mono ML, Heldner MR, Weck A, Mordasini P, Schroth G, Mattle HP, Arnold M, Gralla J, Fischer U (2013) Factors that determine penumbral tissue loss in acute ischaemic stroke. Brain 136 (Pt 12:3554–3560. https://doi.org/10.1093/brain/awt246
Davis S, Donnan GA (2014) Time is penumbra: imaging, selection and outcome. The Johann jacob wepfer award 2014. Cerebrovasc Dis 38(1):59–72. https://doi.org/10.1159/000365503
Lansberg MG, Lee J, Christensen S, Straka M, De Silva DA, Mlynash M, Campbell BC, Bammer R, Olivot JM, Desmond P, Davis SM, Donnan GA, Albers GW (2011) RAPID automated patient selection for reperfusion therapy: a pooled analysis of the echoplanar imaging thrombolytic evaluation trial (EPITHET) and the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study 3. Stroke 42(6):1608–1614
Zhu G, Michel P, Aghaebrahim A, Patrie JT, Xin W, Eskandari A, Zhang W, Wintermark M (2013) Prediction of recanalization trumps prediction of tissue fate: the penumbra: a dual-edged sword. Stroke 44(4):1014–1019. https://doi.org/10.1161/STROKEAHA.111.000229
Campbell BC, Mitchell PJ, Investigators E-I (2015) Endovascular therapy for ischemic stroke. N Engl J Med 372(24):2365–2366. https://doi.org/10.1056/NEJMc1504715
Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD, Investigators ET (2015) Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 372(11):1019–1030. https://doi.org/10.1056/NEJMoa1414905
Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG, Investigators DT (2018) Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 378(1):11–21. https://doi.org/10.1056/NEJMoa1706442
Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG, Investigators D (2018) Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 378(8):708–718. https://doi.org/10.1056/NEJMoa1713973
Michel P, Odier C, Rutgers M, Reichhart M, Maeder P, Meuli R, Wintermark M, Maghraoui A, Faouzi M, Croquelois A, Ntaios G (2010) The acute stroke registry and analysis of Lausanne (ASTRAL): design and baseline analysis of an ischemic stroke registry including acute multimodal imaging. Stroke 41(11):2491–2498. https://doi.org/10.1161/STROKEAHA.110.596189
Blennow K, Wallin A, Uhlemann C, Gottfries CG (1991) White-matter lesions on CT in Alzheimer patients: relation to clinical symptomatology and vascular factors. Acta Neurol Scand 83(3):187–193
Puetz V, Dzialowski I, Hill MD, Demchuk AM (2009) The Alberta Stroke Program Early CT Score in clinical practice: what have we learned? 2. Int J Stroke 4(5):354–364
Wintermark M, Flanders AE, Velthuis B, Meuli R, van LM, Goldsher D, Pineda C, Serena J, van der Schaaf I, Waaijer A, Anderson J, Nesbit G, Gabriely I, Medina V, Quiles A, Pohlman S, Quist M, Schnyder P, Bogousslavsky J, Dillon WP, Pedraza S (2006) Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke. Stroke 37(4):979–985
Puetz V, Dzialowski I, Hill MD, Subramaniam S, Sylaja PN, Krol A, O'Reilly C, Hudon ME, Hu WY, Coutts SB, Barber PA, Watson T, Roy J, Demchuk AM (2008) Intracranial thrombus extent predicts clinical outcome, final infarct size and hemorrhagic transformation in ischemic stroke: the clot burden score. Int J Stroke 3(4):230–236
Tan JC, Dillon WP, Liu S, Adler F, Smith WS, Wintermark M (2007) Systematic comparison of perfusion-CT and CT-angiography in acute stroke patients. Ann Neurol 61(6):533–543. https://doi.org/10.1002/ana.21130
Kim JJ, Fischbein NJ, Lu Y, Pham D, Dillon WP (2004) Regional angiographic grading system for collateral flow: correlation with cerebral infarction in patients with middle cerebral artery occlusion. Stroke 35(6):1340–1344
Klein JP vH, Ibrahim JC, Scheike TH (2013) Handbook of Survival Analysis. CRC Press. https://doi.org/10.1201/b16248
Stef van Buuren KG-O (2011) Multivariate imputation by chained equations in R. J Stat Softw 45(3)
Haussen DC, Dehkharghani S, Rangaraju S, Rebello LC, Bouslama M, Grossberg JA, Anderson A, Belagaje S, Frankel M, Nogueira RG (2016) Automated CT perfusion ischemic core volume and noncontrast CT ASPECTS (Alberta Stroke Program Early CT Score): correlation and clinical outcome prediction in large vessel stroke. Stroke 47(9):2318–2322. https://doi.org/10.1161/STROKEAHA.116.014117
Vagal A, Menon BK, Foster LD, Livorine A, Yeatts SD, Qazi E, d'Esterre C, Shi J, Demchuk AM, Hill MD, Liebeskind DS, Tomsick T, Goyal M (2016) Association between CT angiogram collaterals and CT perfusion in the interventional management of stroke III trial. Stroke 47(2):535–538. https://doi.org/10.1161/STROKEAHA.115.011461
Fanou EM, Knight J, Aviv RI, Hojjat SP, Symons SP, Zhang L, Wintermark M (2015) Effect of collaterals on clinical presentation, baseline imaging, complications, and outcome in acute stroke. AJNR Am J Neuroradiol 36(12):2285–2291. https://doi.org/10.3174/ajnr.A4453
Agarwal S, Bivard A, Warburton E, Parsons M, Levi C (2018) Collateral response modulates the time-penumbra relationship in proximal arterial occlusions. Neurology 90(4):e316–e322. https://doi.org/10.1212/WNL.0000000000004858
von Baumgarten L, Thierfelder KM, Beyer SE, Baumann AB, Bollwein C, Janssen H, Reiser MF, Straube A, Sommer WH (2016) Early CT perfusion mismatch in acute stroke is not time-dependent but relies on collateralization grade. Neuroradiology 58(4):357–365. https://doi.org/10.1007/s00234-016-1643-8
Alves HC, Treurniet KM, Dutra BG, Jansen IGH, Boers AMM, Santos EMM, Berkhemer OA, Dippel DWJ, van der Lugt A, van Zwam WH, van Oostenbrugge RJ, Lingsma HF, Roos Y, Yoo AJ, Marquering HA, Majoie C, investigators MCt (2018) Associations between collateral status and thrombus characteristics and their impact in anterior circulation stroke. Stroke 49(2):391–396. https://doi.org/10.1161/STROKEAHA.117.019509
Albers GW (2018) Late window paradox. Stroke 49(3):768–771. https://doi.org/10.1161/STROKEAHA.117.020200
Evans JW, Graham BR, Pordeli P, Al-Ajlan FS, Willinsky R, Montanera WJ, Rempel JL, Shuaib A, Brennan P, Williams D, Roy D, Poppe AY, Jovin TG, Devlin T, Baxter BW, Krings T, Silver FL, Frei DF, Fanale C, Tampieri D, Teitelbaum J, Iancu D, Shankar J, Barber PA, Demchuk AM, Goyal M, Hill MD, Menon BK, Investigators ET (2018) Time for a time window extension: insights from late presenters in the ESCAPE trial. AJNR Am J Neuroradiol 39(1):102–106. https://doi.org/10.3174/ajnr.A5462
Smit EJ, Vonken EJ, van Seeters T, Dankbaar JW, van der Schaaf IC, Kappelle LJ, van Ginneken B, Velthuis BK, Prokop M (2013) Timing-invariant imaging of collateral vessels in acute ischemic stroke. Stroke 44(8):2194–2199. https://doi.org/10.1161/STROKEAHA.111.000675
Kaschka IN, Kloska SP, Struffert T, Engelhorn T, Golitz P, Kurka N, Kohrmann M, Schwab S, Doerfler A (2016) Clot burden and collaterals in anterior circulation stroke: differences between single-phase CTA and multi-phase 4D-CTA. Clin Neuroradiol 26(3):309–315. https://doi.org/10.1007/s00062-014-0359-6
Menon BK, d'Esterre CD, Qazi EM, Almekhlafi M, Hahn L, Demchuk AM, Goyal M (2015) Multiphase CT angiography: a new tool for the imaging triage of patients with acute ischemic stroke. Radiology 275(2):510–520. https://doi.org/10.1148/radiol.15142256
Ahn SH, d'Esterre CD, Qazi EM, Najm M, Rubiera M, Fainardi E, Hill MD, Goyal M, Demchuk AM, Lee TY, Menon BK (2015) Occult anterograde flow is an under-recognized but crucial predictor of early recanalization with intravenous tissue-type plasminogen activator. Stroke 46(4):968–975. https://doi.org/10.1161/STROKEAHA.114.008648
Austein F, Riedel C, Kerby T, Meyne J, Binder A, Lindner T, Huhndorf M, Wodarg F, Jansen O (2016) Comparison of perfusion CT software to predict the final infarct volume after thrombectomy. Stroke 47(9):2311–2317. https://doi.org/10.1161/STROKEAHA.116.013147
Acknowledgements
We thank Melanie Price Hirt for English language correction and editing.
Funding
This study was funded by the European Academy of Neurology and the Swiss Heart Foundation.
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SN studied the concept and design and helped in the analysis and interpretation and preparation of the article. CWC, GS and DS helped in the interpretation of data and critical revision of the article for important intellectual content. DL carried out data analysis and interpretation and helped in the preparation of the article. AE helped in data acquisition and analysis. VD helped in data acquisition and critical revision of the article for important intellectual content. MW contributed to the conception and design and helped in the interpretation of data. PM studied the concept and design and helped in the data acquisition, analysis, and interpretation and critical revision of the article for important intellectual content, study supervision.
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In the last 3 years, PM received research grants from the Swiss Heart Foundation, Boehringer-Ingelheim and BMS through his institution; speaker fees from Boehringer-Ingelheim, Bayer, Daiichi-Sankyo, Medtronic and Amgen; honoraria from scientific advisory boards from Boehringer-Ingelheim, Bayer, Pfizer and BMS; and consulting fees from Medtronic, Astra-Zeneca and Amgen. PM's institution (CHUV) receives all of the support for stroke education and research. GS served on scientific advisory boards for Amgen and Daiichi-Sankyo. CWC received research grants from the Swiss Heart Foundation, Advisory Board of Research (EOC) and Boehringer-Ingelheim in the last 3 years through his institution, and honoraria from scientific advisory boards from Boehringer-Ingelheim, Bayer and Pfizer.
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Nannoni, S., Cereda, C.W., Sirimarco, G. et al. Collaterals are a major determinant of the core but not the penumbra volume in acute ischemic stroke. Neuroradiology 61, 971–978 (2019). https://doi.org/10.1007/s00234-019-02224-x
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DOI: https://doi.org/10.1007/s00234-019-02224-x