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Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials
  1. Anna M M Boers1,2,3,
  2. Ivo G H Jansen2,
  3. Ludo F M Beenen2,
  4. Thomas G Devlin4,
  5. Luis San Roman5,
  6. Ji Hoe Heo6,
  7. Marc Ribó7,
  8. Scott Brown8,
  9. Mohammed A Almekhlafi9,
  10. David S Liebeskind10,
  11. Jeanne Teitelbaum11,
  12. Hester F Lingsma12,
  13. Wim H van Zwam13,
  14. Patricia Cuadras14,
  15. Richard du Mesnil de Rochemont15,
  16. Marine Beaumont16,
  17. Martin M Brown17,
  18. Albert J Yoo18,
  19. Robert J van Oostenbrugge19,
  20. Bijoy K Menon20,
  21. Geoffrey A Donnan21,
  22. Jean Louis Mas22,
  23. Yvo B W E M Roos23,
  24. Catherine Oppenheim24,
  25. Aad van der Lugt25,
  26. Richard J Dowling26,
  27. Michael D Hill27,
  28. Antoni Davalos28,
  29. Thierry Moulin29,
  30. Nelly Agrinier30,
  31. Andrew M Demchuk27,
  32. Demetrius K Lopes31,
  33. Lucia Aja Rodríguez32,
  34. Diederik W J Dippel33,
  35. Bruce C V Campbell34,
  36. Peter J Mitchell26,
  37. Fahad S Al-Ajlan35,
  38. Tudor G Jovin36,
  39. Jeremy Madigan37,
  40. Gregory W Albers38,
  41. Sebastien Soize39,
  42. Francis Guillemin30,
  43. Vivek K Reddy36,
  44. Serge Bracard40,
  45. Jordi Blasco5,
  46. Keith W Muir41,
  47. Raul G Nogueira42,
  48. Phil M White43,
  49. Mayank Goyal27,
  50. Stephen M Davis34,
  51. Henk A Marquering1,2,
  52. Charles B L M Majoie2
  1. 1 Department of Biomedical Engineering and Physics, Academic Medical Centre, Amsterdam, The Netherlands
  2. 2 Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
  3. 3 Department of Robotics and Mechatronics, University of Twente, Enschede, The Netherlands
  4. 4 Department of Neurology, Erlanger Hospital, University of Tennessee, Chattanooga, Tennessee, USA
  5. 5 Department of Interventional Neuroradiology, Hospital Clinic of Barcelona, Barcelona, Spain
  6. 6 Department of Neurology, Yonsei University, Seoul, South Korea
  7. 7 Department of Neurology, Vall d’Hebron University Hospital, Barcelona, Spain
  8. 8 Altair Biostatistics, Mooresville, North Carolina, USA
  9. 9 Department of Neurology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
  10. 10 Department of Neurology, University of California, Los Angeles, California, USA
  11. 11 Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal University, Montreal, Canada
  12. 12 Department of Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  13. 13 Department of Radiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands
  14. 14 Department of Radiology, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
  15. 15 Institute of Neuroradiology, University of Frankfurt, Frankfurt, Germany
  16. 16 CHRU-Nancy, Inserm, Université de Lorraine, CIC-Innovation Technologique, F-54000 Nancy, France
  17. 17 Institute of Neurology, University College London, London, UK
  18. 18 Division of Neurointervention, Texas Stroke Institute, Dallas, Texas, USA
  19. 19 Department of Neurology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands
  20. 20 Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada
  21. 21 The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia
  22. 22 Department of Neurology, INSERM U894, Sainte-Anne Hospital, Paris-Descartes University, Paris, France
  23. 23 Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands
  24. 24 Department of Neuroradiology, INSERM U894, Sainte-Anne Hospital, Paris-Descartes University, Paris, France
  25. 25 Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  26. 26 Department of Radiology, Melbourne Brain Centre, University of Melbourne, Melbourne, Victoria, Australia
  27. 27 Department of Clinical Neurosciences, Department of Radiology and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  28. 28 Department of Neuroscience, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
  29. 29 Department of Neurology, University Hospital of Besançon, University of Franche-comte, Besançon, France
  30. 30 Universite de Lorraine, CHRU Nancy, Inserm, CIC1433-Epidemiologie Clinique, Nancy, France
  31. 31 Department of Neurological Surgery, Rush University Medical Center, Chicago, Illinois, USA
  32. 32 Neuroradiology Department, Hospital Universitari de Bellvitge, Barcelona, Spain
  33. 33 Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  34. 34 Department of Medicine and Neurology, University of Melbourne, Melbourne, Victoria, Australia
  35. 35 Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  36. 36 Department of Neurology, Stroke Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
  37. 37 St George’s University Hospital, London, UK
  38. 38 Department of Neurology, Stanford Stroke Center, Palo Alto, California, USA
  39. 39 Department of Neuroradiology, University Hospital of Reims, Reims, France
  40. 40 Department of Diagnostic and Interventional Neuroradiology, INSERM U 947, University of Lorraine, University Hospital of Nancy, Nancy, France
  41. 41 Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK
  42. 42 Department of Neurology, Neurosurgery and Radiology, Grady Memorial Hospital, Emory University School of Medicine, Atlanta, Georgia, USA
  43. 43 Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
  1. Correspondence to Anna M M Boers; amm.boers{at}


Background Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement.

Objective To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality.

Methods Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated.

Results Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14–120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15–131) vs 22 mL (IQR 8–71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively).

Conclusions In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.

  • brain
  • stroke
  • thrombectomy
  • mri
  • ct

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  • AMMB and IGHJ contributed equally.

  • HAM and CBLMM contributed equally.

  • Contributors All four criteria for authorship are met: AMMB and IGHJ prepared the first draft. AMMB, IGHJ, MG, and MDH conducted the literature research. AMMB, CBLMM, HAM, WHvZ, HFL, AJY, DSL, MG, MDH, AMD, BCVC, PJM, DWJD, and PW participated in the study design. AMMB, CBLMM, WHvZ, RJvO, AvdL, LFMB, AJY, DSL, NA, MB, SeB, FG, JLM, TM, CO, SS, JT, JHH, MAA, AMD, BKM, BCVC, RGN, PJM, RdMdR, PW, KWM MMB, DWJD, YBWEMR, AD, TGJ, and MR participated in data collection. ScB did the statistical analysis. AMMB, IGHJ, CBLMM, HAM, WHvZ, HFL, RJvO, AvdL, IGHJ, AJY, ScB, DSL, NA, SeB, FG, JLM, TM, CO, JT, MG, MDH, AMD, BKM, BCVC, RGN, GWA, KWM, LSR, MR, JB, PC, DWJD, TGJ, and LA participated in data interpretation. All authors critically reviewed the manuscript and approved the final version. AMMB and IGHJ contributed equally, as did CBLMM and HAM.

  • Funding This work was supported by Medtronic through an unrestricted grant to the University of Calgary.

  • Competing interests MG reports grants from Covidien, personal fees from Covidien, during the conduct of the study; MG has a patent for diagnosing strokes (PCT/ CA2013/000761) licensed to GE Healthcare. BKM reports membership of the Steering and Executive Committee, ESCAPE trial that received support from Covidien Inc., Site Principal Investigator, SOCRATES Trial, sponsored by Astra Zeneca, honoraria from Penumbra Inc., a provisional patent 62/086077 for triaging systems in ischemic stroke, research funding from CIHR, HSFC, AIHS, HBI and the Faculty of Medicine, University of Calgary and board membership of QuikFlo Health Inc. WHvZ reports Honoraria; Modest; Stryker (paid to Institution). DWJD reports honoraria; Modest; Stryker (paid to Institution). PJM reports unrestricted grant funding for the EXTEND-IA trial to the Florey Institute of Neuroscience and Mental Health from Covidien (Medtronic), has served as an unpaid consultant to Codman Johnson and Johnson, his organization has received unrestricted research funding and grants from Codman Johnson and Johnson, Medtronic, and Stryker. AMD reports grant support and personal fees from Covidien (Medtronic). AD reports consultant/Advisory Board; Modest; Medtronic Neurovascular (Steering Committee STAR). CBLMM reports speakers' Bureau; Modest; Stryker (paid to institution). GAD reports grants from the Australian National Health & Medical Research Council, non-financial support from, and has served on advisory boards for Boehringer Ingelheim, Astra Zeneca, Bristol Meyers-Squibb, Merck Sharp & Dohme outside the submitted work. BCVC reports research support from the National Health and Medical Research Council of Australia (GNT1043242, GNT1035688), Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation, National Stroke Foundation of Australia and unrestricted grant funding for the EXTEND-IA trial to the Florey Institute of Neuroscience and Mental Health from Covidien (Medtronic). MDH reports unrestricted grant funding for the ESCAPE trial to University of Calgary from Covidien (Medtronic), and active/in-kind support consortium of public/charitable sources (Heart & Stroke Foundation, Alberta Innovates Health Solutions, Alberta Health Services) and the University of Calgary (Hotchkiss Brain Institute, Departments of Clinical Neurosciences and Radiology, and Calgary Stroke Program); personal fees from Merck, non-financial support from Hoffmann-La Roche Canada Ltd, outside the submitted work; MDH has a patent Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients pending to US Patent office Number: 62/086,077 and owns stock in Calgary Scientific Incorporated, a company that focuses on medical imaging software. AMMB and HAM own stock in Nico.lab, a company that focuses on medical imaging software. TGJ has consulted for Codman Neurovascular and Neuravi, holds stock in Silk Road and Blockade; has acted as an unpaid consultant to Stryker as PI of the DAWN trial and served as an unpaid member of a Medtronic Advisory Board. SMD reports lecture fees from Covidien (Medtronic). ScB acts as consultant for Medtronic. GWA reports equity and consulting for iSchemaView (imaging software) and consulting for Medtronic.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.