Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke

Emilie M M Santos; Henk A Marquering; Mark D den Blanken; Olvert A Berkhemer; Anna M M Boers; Albert J Yoo; Ludo F Beenen; Kilian M Treurniet; Carrie Wismans; Kim van Noort; Hester F Lingsma; Diederik W J Dippel; Aad van der Lugt; Wim H van Zwam; Yvo B W E M Roos; Robert J van Oostenbrugge; Wiro J Niessen; Charles B Majoie; MR CLEAN Investigators

doi:10.1161/STROKEAHA.115.011187

Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke

Stroke. 2016 Mar;47(3):732-41. doi: 10.1161/STROKEAHA.115.011187. Epub 2016 Feb 4.

Authors

Emilie M M Santos¹, Henk A Marquering², Mark D den Blanken², Olvert A Berkhemer², Anna M M Boers², Albert J Yoo², Ludo F Beenen², Kilian M Treurniet², Carrie Wismans², Kim van Noort², Hester F Lingsma², Diederik W J Dippel², Aad van der Lugt², Wim H van Zwam², Yvo B W E M Roos², Robert J van Oostenbrugge², Wiro J Niessen², Charles B Majoie²; MR CLEAN Investigators

Collaborators

MR CLEAN Investigators:
Puck S S Fransen, Debbie Beumer, Lucie A van den Berg, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke J H Wermer, Marianne A A van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A van Oostayen, Geert J Lycklama À Nijeholt, Jelis Boiten, Patrick A Brouwer, Bart J Emmer, Sebastiaan F de Bruijn, Lukas C van Dijk, L Jaap Kappelle, Rob H Lo, Ewoud J van Dijk, Joost de Vries, Paul L M de Kort, Jan S P van den Berg, Boudewijn A A M van Hasselt, Leo A M Aerden, René J Dallinga, Marieke C Visser, Joseph C J Bot, Patrick C Vroomen, Omid Eshghi, Tobien H C M L Schreuder, Roel J J Heijboer, Koos Keizer, Alexander V Tielbeek, Heleen M den Hertog, Dick G Gerrits, Renske M van den Berg-Vos, Giorgos B Karas, Marieke E S Sprengers, Sjoerd F M Jenniskens, René van den Berg, Peter J Koudstaal, Jelis Boiten, Ewoud J van Dijk, Marieke J H Wermer, H Zwenneke Flach, Ewout W Steyerberg, Martin M Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich P Mattle, Nils Wahlgren, Peter J Koudstaal, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Annemieke Lindl-Velema, Corina Puppels, Wilma Pellikaan, Kirsten Janssen, Nicole Aaldering, Marjan Elfrink, Joke de Meris, Annet Geerlings, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Willy Struijk, Tiny Simons, Gert Messchendorp, Friedus van der Minne, Hester Bongenaar, Karin Bodde, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia

Affiliations

¹ From the Departments of Radiology (E.M.M.S., H.A.M., O.A.B., A.M.M.B., L.F.B., K.M.T., C.W., K.N., C.B.M.), Biomedical Engineering and Physics (E.M.M.S., H.A.M., M.D.B., A.M.M.B.), and Neurology (Y.B.W.E.M.R.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Radiology (E.M.M.S., A.L., W.J.N.), Medical Informatics (E.M.M.S., W.J.N.), Neurology (O.A.B., D.W.J.D.), and Public Health (H.F.L.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Robotics and Mechatronics, University of Twente, Twente, The Netherlands (A.M.M.B.); Division of Interventional Neuroradiology, Department of Radiology, Texas Stroke Institute, Plano (A.J.Y.); Departments of Radiology (W.H.Z.) and Neurology (R.J.O.), and Cardiovascular Research Institute Maastricht (W.H.Z., R.J.O.), Maastricht University MC, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands (W.H.Z.); and Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands (W.J.N.). e.m.santos@amc.uva.nl.
² From the Departments of Radiology (E.M.M.S., H.A.M., O.A.B., A.M.M.B., L.F.B., K.M.T., C.W., K.N., C.B.M.), Biomedical Engineering and Physics (E.M.M.S., H.A.M., M.D.B., A.M.M.B.), and Neurology (Y.B.W.E.M.R.), Academic Medical Center, Amsterdam, The Netherlands; Departments of Radiology (E.M.M.S., A.L., W.J.N.), Medical Informatics (E.M.M.S., W.J.N.), Neurology (O.A.B., D.W.J.D.), and Public Health (H.F.L.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Robotics and Mechatronics, University of Twente, Twente, The Netherlands (A.M.M.B.); Division of Interventional Neuroradiology, Department of Radiology, Texas Stroke Institute, Plano (A.J.Y.); Departments of Radiology (W.H.Z.) and Neurology (R.J.O.), and Cardiovascular Research Institute Maastricht (W.H.Z., R.J.O.), Maastricht University MC, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands (W.H.Z.); and Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands (W.J.N.).

PMID: 26846859
DOI: 10.1161/STROKEAHA.115.011187

Abstract

Background and purpose: Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We hypothesize that the combination of computed tomographic angiography and noncontrast computed tomography imaging allows measurement of contrast agent penetrating a permeable thrombus, and it is associated with improved outcome.

Methods: Thrombus and contralateral artery attenuations in noncontrast computed tomography and computed tomographic angiography images were measured in 184 Multicenter Randomized Clinical trial of Endovascular treatment of acute ischemic stroke in the Netherlands (MR CLEAN) patients with thin-slice images. Two quantitative estimators of the thrombus permeability were introduced: computed tomographic angiography attenuation increase (Δ) and thrombus void fraction (ε). Patients were dichotomized as having a pervious or impervious thrombus and associated with outcome, recanalization, and final infarct volume.

Results: Patients with Δ≥10.9 HU (n=81 [44%]) and ε≥6.5% (n=77 [42%]) were classified as having a pervious thrombus. These patients were 3.2 (95% confidence interval, 1.7-6.4) times more likely to have a favorable outcome, and 2.5 (95% confidence interval, 1.3-4.8) times more likely to recanalyze, for Δ based classification, and similarly for ε. These odds ratios were independent from intravenous or intra-arterial treatment. Final infarct volume was negatively correlated with both perviousness estimates (correlation coefficient, -0.39 for Δ and -0.40 for ε).

Conclusions: This study shows that simultaneous measurement of thrombus attenuation in noncontrast computed tomography and computed tomographic angiography allows for quantification of thrombus perviousness. Thrombus perviousness is strongly associated with improved functional outcome, smaller final infarct volume, and higher recanalization rate.

Keywords: arteries; permeability; reperfusion; stroke; thrombosis.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Brain Ischemia / diagnostic imaging*
Brain Ischemia / epidemiology
Brain Ischemia / therapy
Capillary Permeability / physiology*
Endovascular Procedures / methods
Endovascular Procedures / trends*
Female
Humans
Intracranial Thrombosis / diagnostic imaging*
Intracranial Thrombosis / epidemiology
Intracranial Thrombosis / therapy
Male
Middle Aged
Netherlands / epidemiology
Radiography
Stroke / diagnostic imaging*
Stroke / epidemiology
Stroke / therapy
Thrombosis / diagnostic imaging
Thrombosis / epidemiology
Thrombosis / therapy
Treatment Outcome