• Tania A Pawade, Cartlidge Timothy R G TR 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 Me, William S A Jenkins, Philip D Adamson, Phillip Robson, Christophe Lucatelli, Edwin J R Van Beek, Bernard Prendergast, Alan R Denison, Laura Forsyth, James H F Rudd, Zahi A Fayad, Alison Fletcher, Sharon Tuck, David E Newby, and Marc R Dweck.
• 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.
• Circ Cardiovasc Imaging. 2016 Oct 1; 9 (10).

Background18F-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.Methods And ResultsFifteen 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).ConclusionsOptimized 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.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026.© 2016 The Authors.

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