title: 18F-Fluoride and18F-Fluorodeoxyglucose Positron Emission Tomography After Transient Ischemic Attack or Minor Ischemic Stroke: Case-Control Study.
abstract: BACKGROUND
  Combined positron emission tomography (PET) and computed tomography (CT) can assess both anatomy and biology of carotid atherosclerosis. We sought to assess whether18F-fluoride or18F-fluorodeoxyglucose can identify culprit and high-risk carotid plaque.
  
  
  RESULTS
  We performed18F-fluoride and18F-fluorodeoxyglucose PET/CT in 26 patients after recent transient ischemic attack or minor ischemic stroke: 18 patients with culprit carotid stenosis awaiting carotid endarterectomy and 8 controls without culprit carotid atheroma. We compared standardized uptake values in the clinically adjudicated culprit to the contralateral asymptomatic artery, and assessed the relationship between radiotracer uptake and plaque phenotype or predicted cardiovascular risk (ASSIGN score [Assessing Cardiovascular Risk Using SIGN Guidelines to Assign Preventive Treatment]). We also performed micro PET/CT and histological analysis of excised plaque. On histological and micro PET/CT analysis,18F-fluoride selectively highlighted microcalcification. Carotid18F-fluoride uptake was increased in clinically adjudicated culprit plaques compared with asymptomatic contralateral plaques (log10standardized uptake valuemean0.29±0.10 versus 0.23±0.11,P=0.001) and compared with control patients (log10standardized uptake valuemean0.29±0.10 versus 0.12±0.11,P=0.001).18F-Fluoride uptake correlated with high-risk plaque features (remodeling index [r=0.53,P=0.003], plaque burden [r=0.51,P=0.004]), and predicted cardiovascular risk [r=0.65,P=0.002]). Carotid18F-fluorodeoxyglucose uptake appeared to be increased in 7 of 16 culprit plaques, but no overall differences in uptake were observed in culprit versus contralateral plaques or control patients. However,18F-fluorodeoxyglucose did correlate with predicted cardiovascular risk (r=0.53,P=0.019), but not with plaque phenotype.
  
  
  CONCLUSIONS
  18F-Fluoride PET/CT highlights culprit and phenotypically high-risk carotid plaque. This has the potential to improve risk stratification and selection of patients who may benefit from intervention.
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom. avesey@staffmail.ed.ac.uk.
authors.forename: Alex T
authors.initials: AT
authors.lastname: Vesey
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: William S A
authors.initials: WS
authors.lastname: Jenkins
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Agnese
authors.initials: A
authors.lastname: Irkle
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Alastair
authors.initials: A
authors.lastname: Moss
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Greg
authors.initials: G
authors.lastname: Sng
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Rachael O
authors.initials: RO
authors.lastname: Forsythe
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Clark
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Gemma
authors.initials: G
authors.lastname: Roberts
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Fletcher
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lucatelli
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Davenport
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Mills
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Rustam
authors.initials: R
authors.lastname: Al-Shahi Salman
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Dennis
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: William N
authors.initials: WN
authors.lastname: Whiteley
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Edwin J R
authors.initials: EJ
authors.lastname: van Beek
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Dweck
authors.affiliation: From the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (A.T.V., W.S.A.J., A.M., G.S., R.O.F., N.L.M., E.J.R.v.B., M.R.D., D.E.N.); Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.I., J.R., A.P.D.); and Clinical Research Imaging Centre (T.C., G.R., A.F., C.L., E.J.R.v.B., M.R.D., D.E.N.) and Centre for Clinical Brain Sciences (R.A.-S.S., M.D., W.W.), University of Edinburgh, United Kingdom.
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging* / Q000601:surgery; D016893:Carotid Stenosis / Q000150:complications / Q000000981:diagnostic imaging* / Q000601:surgery; D016022:Case-Control Studies; D016894:Endarterectomy, Carotid; D005260:Female; D005459:Fluorides / Q000008:administration & dosage*; D005462:Fluorine Radioisotopes / Q000008:administration & dosage*; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D058226:Plaque, Atherosclerotic; D000072078:Positron Emission Tomography Computed Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000000981:diagnostic imaging / Q000209:etiology*; D055114:X-Ray Microtomography
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005459:Fluorides
keywords: carotid stenosis; fluorides; inflammation; nuclear medicine; phenotype; stroke