title: Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis.
abstract: BACKGROUND
  18F-Fluoride positron emission tomography (PET) and computed tomography (CT) can measure disease activity and progression in aortic stenosis. Our objectives were to optimize the methodology, analysis, and scan-rescan reproducibility of aortic valve 18F-fluoride PET-CT imaging.
  
  
  RESULTS
  Fifteen patients with aortic stenosis underwent repeated 18F-fluoride PET-CT. We compared nongated PET and noncontrast CT, with a modified approach that incorporated contrast CT and ECG-gated PET. We explored a range of image analysis techniques, including estimation of blood-pool activity at differing vascular sites and a most diseased segment approach. Contrast-enhanced ECG-gated PET-CT permitted localization of 18F-fluoride uptake to individual valve leaflets. Uptake was most commonly observed at sites of maximal mechanical stress: the leaflet tips and the commissures. Scan-rescan reproducibility was markedly improved using enhanced analysis techniques leading to a reduction in percentage error from ±63% to ±10% (tissue to background ratio MDS mean of 1.55, bias -0.05, limits of agreement -0·20 to +0·11).
  
  
  CONCLUSIONS
  Optimized 18F-fluoride PET-CT allows reproducible localization of calcification activity to different regions of the aortic valve leaflet and commonly to areas of increased mechanical stress. This technique holds major promise in improving our understanding of the pathophysiology of aortic stenosis and as a biomarker end point in clinical trials of novel therapies.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026.
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.). tania.pawade@ed.ac.uk.
authors.forename: Tania A
authors.initials: TA
authors.lastname: Pawade
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Timothy R G
authors.initials: TR
authors.lastname: Cartlidge
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: William S A
authors.initials: WS
authors.lastname: Jenkins
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Philip D
authors.initials: PD
authors.lastname: Adamson
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Phillip
authors.initials: P
authors.lastname: Robson
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Christophe
authors.initials: C
authors.lastname: Lucatelli
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Edwin J R
authors.initials: EJ
authors.lastname: Van Beek
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Bernard
authors.initials: B
authors.lastname: Prendergast
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Alan R
authors.initials: AR
authors.lastname: Denison
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Laura
authors.initials: L
authors.lastname: Forsyth
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Alison
authors.initials: A
authors.lastname: Fletcher
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Sharon
authors.initials: S
authors.lastname: Tuck
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: From the BHF/Centre for Cardiovascular Science (T.A.P., T.R.G.C., W.S.A.J., P.D.A., D.E.N., M.R.D.), Clinical Research Imaging Centre, Queen's Medical Research Institute (C.L., E.J.R.V.B., A.F.), and Edinburgh Clinical Trials Unit, Western General Hospital (L.F.), University of Edinburgh, United Kingdom; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York (P.R., Z.A.F.); Guy's and St Thomas' Hospitals NHS Foundation Trust, London, United Kingdom (B.P.); Institute for Education in Medical and Dental Sciences, University of Aberdeen, United Kingdom (A.R.D.); Division of Cardiovascular Medicine, University of Cambridge, United Kingdom (J.H.F.R.); and Wellcome Trust Clinical Research Facility, Western General Hospital Edinburgh, United Kingdom (S.T.).
authors.forename: Marc R
authors.initials: MR
authors.lastname: Dweck
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002114:Calcinosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D055424:Cardiac-Gated Imaging Techniques; D003287:Contrast Media / Q000008:administration & dosage; D004562:Electrocardiography; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D015203:Reproducibility of Results; D012606:Scotland; D012720:Severity of Illness Index
chemical_list: D003287:Contrast Media; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: 18F-Fluoride; aortic valve stenosis; calcification; disease progression; echocardiography; positron emission tomography