title: Occult anterograde flow is an under-recognized but crucial predictor of early recanalization with intravenous tissue-type plasminogen activator.
abstract: OBJECTIVE
  Thrombolysis depends on the ability of blood and thrombolytic agents to permeate thrombus. We devised a novel technique to quantify blood permeating through thrombi and determine whether this parameter predicts early recanalization with intravenous tissue-type plasminogen activator.
  
  
  METHODS
  Intravenous tissue-type plasminogen activator-treated patients with stroke and complete occlusion on computed tomographic angiography were analyzed using perfusion computed tomography and a delay insensitive algorithm. We generated maps that measure delay in arrival time of contrast within the intracranial arterial tree (T0 maps). A positive sloped regression line of T0 values measured along artery silhouette distal to thrombus was defined as marker of permeable thrombus (occult anterograde flow). Median T0 values at proximal and distal thrombus interface were measured. Early recanalization was assessed on first angiography of subsequent intra-arterial procedure or on a 4-hour computed tomographic angiography.
  
  
  RESULTS
  Of 66 patients, occult anterograde flow was detected in 17 (25.8%). Early recanalization was more in patients with occult anterograde flow versus not (66.7 versus 29.7%; P=0.031). Median T0 value (in s) at distal thrombus interface (1.5 versus 3.8; P=0.006) and difference in median T0 value between proximal and distal thrombus interface (1.3 versus 3.7; P=0.014) were less in early recanalizers versus in nonrecanalizers. In multivariable analysis, patients with occult anterograde flow and T0 value difference between proximal and distal thrombus interface ≤2 s recanalized most (71.4%; odds ratio, 12.15; 95% confidence interval, 2.05-71.91), whereas patients with retrograde flow and T0 value difference >2 s recanalized least (25.9%; odds ratio, 1).
  
  
  CONCLUSIONS
  Occult anterograde flow through thrombus can be assessed by perfusion computed tomography T0 maps and predicts early recanalization with intravenous tissue-type plasminogen activator robustly.
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Christopher D
authors.initials: CD
authors.lastname: d'Esterre
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Emmad M
authors.initials: EM
authors.lastname: Qazi
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Mohammed
authors.initials: M
authors.lastname: Najm
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Marta
authors.initials: M
authors.lastname: Rubiera
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Enrico
authors.initials: E
authors.lastname: Fainardi
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hill
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Mayank
authors.initials: M
authors.lastname: Goyal
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Demchuk
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.).
authors.forename: Ting Y
authors.initials: TY
authors.lastname: Lee
authors.affiliation: From the Calgary Stroke Program, Department of Clinical Neurosciences (S.H.A., C.D.d'E., E.M.Q., M.N., M.D.H., M.G., A.M.D., B.K.M.), Department of Radiology (C.D.d'E., M.D.H., M.G., A.M.D., T.Y.L., B.K.M.), Department of Community Health Sciences (M.D.H.), and Seaman Family MR Center (S.H.A., C.D.d'E., E.M.Q., M.N., M.G., A.M.D., B.K.M.), University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute (M.D.H., M.G., A.M.D., B.K.M.); Department of Neurology, Chosun University School of Medicine, Gwang Ju, South Korea (S.H.A.); Department of Neurology, Hospital Vall d'Hebron, Ps. Vall d'Hebron, Barcelona, Spain (M.R.); Department of Neurosciences and Rehabilitation, University Hospital, Ferrara, Italy (E.F.); and Lawson Health Research Institute and Robarts Research Institute, London, Ontario, Canada (T.Y.L.). Bijoy.Menon@Albertahealthservices.ca.
authors.forename: Bijoy K
authors.initials: BK
authors.lastname: Menon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015901:Angiography, Digital Subtraction; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D020767:Intracranial Thrombosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000502:physiology*; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: perfusion imaging; recanalization; stroke; thrombolytic therapy