title: Routine clinical evaluation of cerebrovascular reserve capacity using carbogen in patients with intracranial stenosis.
abstract: OBJECTIVE
  A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial stenosis is cerebrovascular reactivity (CVR) mapping using noninvasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated.
  
  
  METHODS
  In sequence with structural and angiographic imaging, blood oxygenation level-dependent carbogen-induced CVR scans were performed in patients with symptomatic intracranial stenosis (n=92) and control (n=10) volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow-weighted pseudocontinuous arterial spin labeling CVR. Subjects were stratified for 4 substudies to evaluate relationships between (1) carbogen and hypercarbic normoxic CVR in healthy tissue (n=10), (2) carbogen cerebral blood flow CVR and blood oxygenation level-dependent CVR in intracranial stenosis patients (n=57), (3) carbogen CVR and clinical measures of disease in patients with asymmetrical intracranial atherosclerotic (n=31) and moyamoya (n=29) disease, and (4) the CVR scan and immediate and longer-term complications (n=92).
  
  
  RESULTS
  Noninvasive blood oxygenation level-dependent carbogen-induced CVR values correlate with (1) lobar hypercarbic normoxic gas stimuli in healthy tissue (R=0.92; P<0.001), (2) carbogen-induced cerebral blood flow CVR in patients with intracranial stenosis (R=0.30-0.33; P<0.012), and (3) angiographic measures of disease severity both in atherosclerotic and moyamoya patients after appropriate processing. No immediate stroke-related complications were reported in response to carbogen administration; longer-term neurological events fell within the range for expected events in this patient population.
  
  
  CONCLUSIONS
  Carbogen-induced CVR elicited no added adverse events and provided a surrogate marker of cerebrovascular reserve consistent with intracranial vasculopathy.
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.); mj.donahue@vanderbilt.edu.
authors.forename: Manus J
authors.initials: MJ
authors.lastname: Donahue
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Dethrage
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Faraco
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Lori C
authors.initials: LC
authors.lastname: Jordan
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Paul
authors.initials: P
authors.lastname: Clemmons
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Robert
authors.initials: R
authors.lastname: Singer
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: J
authors.initials: J
authors.lastname: Mocco
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Aditi
authors.initials: A
authors.lastname: Desai
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Anne
authors.initials: A
authors.lastname: O'Duffy
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Derek
authors.initials: D
authors.lastname: Riebau
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Lisa
authors.initials: L
authors.lastname: Hermann
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: John
authors.initials: J
authors.lastname: Connors
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Howard
authors.initials: H
authors.lastname: Kirshner
authors.affiliation: From the Departments of Radiology (M.J.D., L.M.D., C.C.F., A.D., J.C., M.K.S.), Neurology (M.J.D., L.C.J., P.C., A.O., D.R., L.H., H.K.), Psychiatry (M.J.D.), Physics (M.J.D.), and Neurosurgery (J.M., J.C., M.K.S.) and Center for Quantitative Sciences (Y.S.), Vanderbilt University, Nashville, TN; and Department of Neurosurgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH (R.S.);
authors.forename: Megan K
authors.initials: MK
authors.lastname: Strother
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D002245:Carbon Dioxide; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003251:Constriction, Pathologic / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009072:Moyamoya Disease / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D010100:Oxygen
chemical_list: D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen
keywords: constriction, pathologic; hypercapnia; magnetic resonance imaging; regional blood flow; stroke