title: Comparison between voxel-based and subtraction methods for measuring diffusion-weighted imaging lesion growth after thrombolysis.
abstract: BACKGROUND
  Infarct growth (IG) is used as surrogate end-point in therapeutic trials. For practical reasons, infarct growth is commonly assessed using simple subtraction of acute from follow-up diffusion-weighted imaging (DWI) lesion volumes. However, the volume subtraction method will underestimate true infarct growth in case of diffusion-weighted imaging lesion reversal.
  
  
  OBJECTIVE
  To measure the size of the difference between true infarct growth on voxel-based coregistration and infarct growth approximated with simple volume subtraction.
  
  
  METHODS
  We retrospectively analyzed 322 consecutive stroke patients (median (IQR) age: 70 years (57-80), National Institute of Health Stroke Score at admission 14 (8-19)), who underwent a magnetic resonance imaging before (DWI1) and ≈24 h (DWI2) after i.v.-thrombolysis. IGvoxel-based was defined as the volume of signal changes on DWI2 that did not overlap with that on coregistered DWI1. This was compared with simply subtracting DWI1 from DWI2 lesion volume (IGsubtracted). We also compared these two metrics for the prediction of three-month unfavorable outcome (mRS ≥ 2) using c-statistics of multivariable models, adjusted for age, and National Institute of Health Stroke Score.
  
  
  RESULTS
  Infarct growth volume metrics were strongly correlated (ρ = 0.94), but IGsubtracted substantially underestimated IGvoxel-based (median (IQR): 9.52 (0.23-38.9) vs. 16.98 (4.4-45.4) mL). Of the 75 patients with shrinking or stable diffusion-weighted imaging lesion using volume subtraction, IGvoxel-based was ≥5 mL in 20 (27% of the subset, 6.2% of the whole population). Moreover, IGvoxel-based better predicted unfavorable outcome than IGsubtracted (c-statistics = 0.86 (95% CI, 0.82-0.90) vs. 0.82 (0.78-0.87), P = 0.003).
  
  
  CONCLUSIONS
  At early post-thrombolysis time points, the simple subtraction of lesion volumes masked substantial diffusion-weighted imaging lesion growth in 6.2% of patients. Although more time-consuming, the voxel-based method may impact results of trials that use infarct growth attenuation as an end-point.
authors.affiliation: Department of Radiology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France.
authors.forename: Wajih Ben
authors.initials: WB
authors.lastname: Hassen
authors.affiliation: Department of Radiology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Tisserand
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France Department of Neurology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Turc
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Charron
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France Department of Neurology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Seners
authors.affiliation: Department of Radiology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Edjlali
authors.affiliation: Department of Radiology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Legrand
authors.affiliation: Department of Radiology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lion
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France Department of Neurology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Calvet
authors.affiliation: Department of Radiology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Naggara
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France Department of Neurology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mas
authors.affiliation: Department of Radiology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Meder
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France Department of Neurology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Baron
authors.affiliation: Department of Radiology, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Paris, France Centre de Psychiatrie et Neurosciences, INSERM S894, DHU Neurovasc, Paris, France c.oppenheim@ch-sainte-anne.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Oppenheim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020520:Brain Infarction / Q000188:drug therapy* / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015912:Thrombolytic Therapy
keywords: MRI; coregistration; diffusion-weighted imaging; infarct growth; outcomes; thrombolysis