Background: In stroke erythrocyte-rich thrombi are more sensitive to intravenous thrombolysis with recombinant tissue plasminogen activator (IV-rtPA) and have higher density on non-contrast CT (NCCT). We investigated the relationship between thrombus density and recanalization and whether persistent occlusions can be predicted by Hounsfield unit (HU) measurements. Methods: In 88 IV-rtPA-treated patients with intracranial ICA or MCA occluding thrombus and follow-up imaging, thrombus and contralateral vessel attenuation measurements were performed on thin-slice NCCT. Mean absolute and relative HU were compared between patients with persistent occlusion (modified Thrombolysis in Cerebral Infarction system, grade 0/1/2a) and recanalization (grade 2b/3). Univariate and multivariate (adjusted for stroke subtype, clot burden score, occlusion site and time to thrombolysis) odds ratios for persistent occlusion were calculated. Additional prognostic value for persistent occlusion was estimated by adding HU measurements to the area under the curve (AUC) of known determinants and calculating optimal cut-off values. Results: Patients with persistent occlusion (n = 19) had significant lower mean HU (absolute 52.2 ± 9.5, relative 1.29 ± 0.20) compared to recanalization (absolute 63.1 ± 10.7, relative 1.54 ± 0.23, both p < 0.0001). Odds ratios for persistent occlusion were 3.1 (95% confidence interval, CI 1.6-6.0) univariate and 3.1 (95% CI 1.7-5.7) multivariate per 10 absolute HU decrease and 3.2 (95% CI 1.6-6.5) univariate and 4.1 (95% CI 1.8-9.1) multivariate per 0.20 relative HU decrease. Attenuation measurements significantly increased the AUC (0.67) of the known determinants to 0.84 (absolute HU) and 0.86 (relative HU). Cut-off values of <56.5 absolute HU and <1.38 relative HU showed optimal predictive values for persistent occlusion. Conclusions: Thrombus density is related to recanalization rate. Lower absolute and relative HU are independently related to persistent occlusion and HU measurements significantly increase discriminative performances of known recanalization determinants.

Keywords:
CT, Stroke, Attenuation, Recanalization, IV-rtPA
1.
Rha JH, Saver JL: The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke 2007;38:967-973.
2.
Saver JL: Time is brain - quantified. Stroke 2006;37:263-266.
3.
Mazighi M, Serfaty JM, Labreuche J, Laissy JP, Meseguer E, Lavallee PC, Cabrejo L, Slaoui T, Guidoux C, Lapergue B, Klein IF, Olivot JM, Abboud H, Simon O, Niclot P, Nifle C, Touboul PJ, Raphaeli G, Gohin C, Claeys ES, Amarenco P: Comparison of intravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and confirmed arterial occlusion (RECANALISE study): a prospective cohort study. Lancet Neurol 2009;8:802-809.
4.
Jang IK, Gold HK, Ziskind AA, Fallon JT, Holt RE, Leinbach RC, May JW, Collen D: Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. A possible explanation for resistance to coronary thrombolysis. Circulation 1989;79:920-928.
5.
Caplan LR: Antiplatelet therapy in stroke prevention: present and future. Cerebrovasc Dis 2006;21(suppl 1):1-6.
6.
Kim EY, Lee SK, Kim DJ, Suh SH, Kim J, Heo JH, Kim DI: Detection of thrombus in acute ischemic stroke: value of thin-section noncontrast-computed tomography. Stroke 2005;36:2745-2747.
7.
Riedel CH, Zoubie J, Ulmer S, Gierthmuehlen J, Jansen O: Thin-slice reconstructions of nonenhanced CT images allow for detection of thrombus in acute stroke. Stroke 2012;43:2319-2323.
8.
Nam HS, Kim EY, Kim SH, Kim YD, Kim J, Lee HS, Nam CM, Heo JH: Prediction of thrombus resolution after intravenous thrombolysis assessed by CT-based thrombus imaging. Thromb Haemost 2012;107:786-794.
9.
Kim EY, Heo JH, Lee SK, Kim DJ, Suh SH, Kim J, Kim DI: Prediction of thrombolytic efficacy in acute ischemic stroke using thin-section noncontrast CT. Neurology 2006;67:1846-1848.
10.
Moulin T, Tatu L, Vuillier F, Cattin F: Brain CT scan for acute cerebral infarction: early signs of ischemia (in French). Rev Neurol (Paris) 1999;155:649-655.
11.
Kirchhof K, Welzel T, Mecke C, Zoubaa S, Sartor K: Differentiation of white, mixed, and red thrombi: value of CT in estimation of the prognosis of thrombolysis phantom study. Radiology 2003;228:126-130.
12.
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. Toast. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41.
13.
Chen CJ, Tseng YC, Lee TH, Hsu HL, See LC: Multisection CT angiography compared with catheter angiography in diagnosing vertebral artery dissection. AJNR Am J Neuroradiol 2004;25:769-774.
14.
Kim YK, Schulman S: Cervical artery dissection: pathology, epidemiology and management. Thromb Res 2009;123:810-821.
15.
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: Intracranial thrombus extent predicts clinical outcome, final infarct size and hemorrhagic transformation in ischemic stroke: the clot burden score. Int J Stroke 2008;3:230-236.
16.
Tomsick T, Broderick J, Carrozella J, Khatri P, Hill M, Palesch Y, Khoury J: Revascularization results in the Interventional Management of Stroke II trial. AJNR Am J Neuroradiol 2008;29:582-587.
17.
Yoo AJ, Simonsen CZ, Prabhakaran S, Chaudhry ZA, Issa MA, Fugate JE, Linfante I, Liebeskind DS, Khatri P, Jovin TG, Kallmes DF, Dabus G, Zaidat OO: Refining angiographic biomarkers of revascularization: improving outcome prediction after intra-arterial therapy. Stroke 2013;44:2509-2512.
18.
Barreto AD, Albright KC, Hallevi H, Grotta JC, Noser EA, Khaja AM, Shaltoni HM, Gonzales NR, Illoh K, Martin-Schild S, Campbell MS 3rd, Weir RU, Savitz SI: Thrombus burden is associated with clinical outcome after intra-arterial therapy for acute ischemic stroke. Stroke 2008;39:3231-3235.
19.
Saqqur M, Uchino K, Demchuk AM, Molina CA, Garami Z, Calleja S, Akhtar N, Orouk FO, Salam A, Shuaib A, Alexandrov AV: Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke 2007;38:948-954.
20.
Murphy A, Symons SP, Hopyan J, Aviv RI: Factors influencing clinically meaningful recanalization after IV-rtPA in acute ischemic stroke. AJNR Am J Neuroradiol 2013;34:146-152.
21.
Molina CA, Alexandrov AV, Demchuk AM, Saqqur M, Uchino K, Alvarez-Sabin J: Improving the predictive accuracy of recanalization on stroke outcome in patients treated with tissue plasminogen activator. Stroke 2004;35:151-156.
22.
Kimura K, Iguchi Y, Shibazaki K, Aoki J, Watanabe M, Matsumoto N, Yamashita S: Early stroke treatment with IV t-PA associated with early recanalization. J Neurol Sci 2010;295:53-57.
23.
Swets JA: Measuring the accuracy of diagnostic systems. Science 1988;240:1285-1293.
24.
DeLong ER, DeLong DM, Clarke-Pearson DL: Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837-845.
25.
Puig J, Pedraza S, Demchuk A, Daunis IEJ, Termes H, Blasco G, Soria G, Boada I, Remollo S, Banos J, Serena J, Castellanos M: Quantification of thrombus Hounsfield units on noncontrast CT predicts stroke subtype and early recanalization after intravenous recombinant tissue plasminogen activator. AJNR Am J Neuroradiol 2012;33:90-96.
26.
Moftakhar P, English JD, Cooke DL, Kim WT, Stout C, Smith WS, Dowd CF, Higashida RT, Halbach VV, Hetts SW: Density of thrombus on admission CT predicts revascularization efficacy in large vessel occlusion acute ischemic stroke. Stroke 2013;44:243-245.
27.
Yilmaz U, Roth C, Reith W, Papanagiotou P: Thrombus attenuation does not predict angiographic results of mechanical thrombectomy with stent retrievers. AJNR Am J Neuroradiol 2013;34:2184-2186.
28.
Ahmed N, Wahlgren N, Grond M, Hennerici M, Lees KR, Mikulik R, Parsons M, Roine RO, Toni D, Ringleb P: Implementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR. Lancet Neurol 2010;9:866-874.
29.
Yeo LL, Paliwal P, Teoh HL, Seet RC, Chan BP, Liang S, Venketasubramanian N, Rathakrishnan R, Ahmad A, Ng KW, Loh PK, Ong JJ, Wakerley BR, Chong VF, Bathla G, Sharma VK: Timing of recanalization after intravenous thrombolysis and functional outcomes after acute ischemic stroke. JAMA Neurol 2013;70:353-358.
30.
Niesten JM, van der Schaaf IC, Biessels GJ, van Otterloo AE, van Seeters T, Horsch AD, Luitse MJ, van der Graaf Y, Kappelle LJ, Mali WP, Velthuis BK: Relationship between thrombus attenuation and different stroke subtypes. Neuroradiology 2013;55:1071-1079.
31.
Cho KH, Lee DH, Kwon SU, Choi CG, Kim SJ, Suh DC, Kim JS, Kang DW: Factors and outcomes associated with recanalization timing after thrombolysis. Cerebrovasc Dis 2012;33:255-261.
32.
Molina CA, Montaner J, Arenillas JF, Ribo M, Rubiera M, Alvarez-Sabin J: Differential pattern of tissue plasminogen activator-induced proximal middle cerebral artery recanalization among stroke subtypes. Stroke 2004;35:486-490.
33.
Rocha S, Pires A, Gomes J, Rocha J, Sousa F, Pinho J, Rodrigues M, Ferreira C, Machado A, Mare R, Fontes JR: Intravenous thrombolysis is more effective in ischemic cardioembolic strokes than in non-cardioembolic? Arq Neuropsiquiatr 2011;69:905-909.
34.
Hsia AW, Sachdev HS, Tomlinson J, Hamilton SA, Tong DC: Efficacy of IV tissue plasminogen activator in acute stroke: does stroke subtype really matter? Neurology 2003;61:71-75.
35.
Riedel CH, Zimmermann P, Jensen-Kondering U, Stingele R, Deuschl G, Jansen O: The importance of size: successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length. Stroke 2011;42:1775-1777.
36.
Ernst R, Pancioli A, Tomsick T, Kissela B, Woo D, Kanter D, Jauch E, Carrozzella J, Spilker J, Broderick J: Combined intravenous and intra-arterial recombinant tissue plasminogen activator in acute ischemic stroke. Stroke 2000;31:2552-2557.
37.
Tandberg Askevold E, Naess H, Thomassen L: Predictors for recanalization after intravenous thrombolysis in acute ischemic stroke. J Stroke Cerebrovasc Dis 2007;16:21-24.
38.
Roberts HC, Dillon WP, Furlan AJ, Wechsler LR, Rowley HA, Fischbein NJ, Higashida RT, Kase C, Schulz GA, Lu Y, Firszt CM: Computed tomographic findings in patients undergoing intra-arterial thrombolysis for acute ischemic stroke due to middle cerebral artery occlusion - results from the PROACT II trial. Stroke 2002;33:1557-1565.
39.
Manelfe C, Larrue V, von Kummer R, Bozzao L, Ringleb P, Bastianello S, Iweins F, Lesaffre E: Association of hyperdense middle cerebral artery sign with clinical outcome in patients treated with tissue plasminogen activator. Stroke 1999;30:769-772.
40.
Fitzsimmons PR, Biswas S, Hill AM, Kumar R, Cullen C, White RP, Sharma AK, Durairaj R: The hyperdense internal carotid artery sign: prevalence and prognostic relevance in stroke thrombolysis. Stroke Res Treat 2011;2011:843607.
© 2014 S. Karger AG, Basel
2014
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.