Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis

Tania A Pawade, Timothy R G Cartlidge, 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, Marc R Dweck

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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.

METHODS AND 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.

CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026.

Original languageEnglish
Article numbere005131
JournalCirculation. Cardiovascular imaging
Volume9
Issue number10
DOIs
Publication statusPublished - 12 Oct 2016

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Aortic Valve Stenosis
Fluorides
Aortic Valve
Positron-Emission Tomography
Mechanical Stress
Electrocardiography
Clinical Trials
Blood Vessels
Disease Progression
Positron Emission Tomography Computed Tomography
Biomarkers
Tomography

Keywords

  • 18F-Fluoride
  • aortic valve stenosis
  • calcification
  • disease progression
  • echocardiography
  • positron emission tomography

Cite this

Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis. / Pawade, Tania A; Cartlidge, Timothy R G; Jenkins, William S A; Adamson, Philip D; Robson, Phillip; Lucatelli, Christophe; Van Beek, Edwin J R; Prendergast, Bernard; Denison, Alan R; Forsyth, Laura; Rudd, James H F; Fayad, Zahi A; Fletcher, Alison; Tuck, Sharon; Newby, David E; Dweck, Marc R.

In: Circulation. Cardiovascular imaging, Vol. 9, No. 10, e005131, 12.10.2016.

Research output: Contribution to journalArticle

Pawade, TA, Cartlidge, TRG, Jenkins, WSA, Adamson, PD, Robson, P, Lucatelli, C, Van Beek, EJR, Prendergast, B, Denison, AR, Forsyth, L, Rudd, JHF, Fayad, ZA, Fletcher, A, Tuck, S, Newby, DE & Dweck, MR 2016, 'Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis', Circulation. Cardiovascular imaging, vol. 9, no. 10, e005131. https://doi.org/10.1161/CIRCIMAGING.116.005131, https://doi.org/10.1161/CIRCIMAGING.116.005131/-/DC1
Pawade, Tania A ; Cartlidge, Timothy R G ; Jenkins, William S A ; Adamson, Philip D ; Robson, Phillip ; Lucatelli, Christophe ; Van Beek, Edwin J R ; Prendergast, Bernard ; Denison, Alan R ; Forsyth, Laura ; Rudd, James H F ; Fayad, Zahi A ; Fletcher, Alison ; Tuck, Sharon ; Newby, David E ; Dweck, Marc R. / Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis. In: Circulation. Cardiovascular imaging. 2016 ; Vol. 9, No. 10.
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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.METHODS AND 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.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026.",
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author = "Pawade, {Tania A} and Cartlidge, {Timothy R G} and Jenkins, {William S A} and Adamson, {Philip D} and Phillip Robson and Christophe Lucatelli and {Van Beek}, {Edwin J R} and Bernard Prendergast and Denison, {Alan R} and Laura Forsyth and Rudd, {James H F} and Fayad, {Zahi A} and Alison Fletcher and Sharon Tuck and Newby, {David E} and Dweck, {Marc R}",
note = "Sources of Funding The study was funded by the British Heart Foundation (FS/14/78/31020). Drs Pawade, Cartlidge, Jenkins, Dweck, and Newby are supported by the British Heart Foundation (SS/CH/09/002/26360, FS/13/77/30488, SS/CH/09/002/2636, FS/14/78/31020, and CH/09/002). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr Dweck is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015. Dr Adamson is supported by New Zealand Overseas Training and Research Fellowship (1607) and Edinburgh and Lothians Health Foundation (50–534). The Wellcome Trust Clinical Research Facility and the Clinical Research Imaging Centre are supported by NHS Research Scotland (NRS) through NHS Lothian. Dr Rudd is partly supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trust. The Data Supplement is available at http://circimaging.ahajournals.org/lookup/suppl/doi:10.1161/CIRCIMAGING.116.005131/-/DC1.",
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TY - JOUR

T1 - Optimization and Reproducibility of Aortic Valve 18F-Fluoride Positron Emission Tomography in Patients With Aortic Stenosis

AU - Pawade, Tania A

AU - Cartlidge, Timothy R G

AU - Jenkins, William S A

AU - Adamson, Philip D

AU - Robson, Phillip

AU - Lucatelli, Christophe

AU - Van Beek, Edwin J R

AU - Prendergast, Bernard

AU - Denison, Alan R

AU - Forsyth, Laura

AU - Rudd, James H F

AU - Fayad, Zahi A

AU - Fletcher, Alison

AU - Tuck, Sharon

AU - Newby, David E

AU - Dweck, Marc R

N1 - Sources of Funding The study was funded by the British Heart Foundation (FS/14/78/31020). Drs Pawade, Cartlidge, Jenkins, Dweck, and Newby are supported by the British Heart Foundation (SS/CH/09/002/26360, FS/13/77/30488, SS/CH/09/002/2636, FS/14/78/31020, and CH/09/002). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr Dweck is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015. Dr Adamson is supported by New Zealand Overseas Training and Research Fellowship (1607) and Edinburgh and Lothians Health Foundation (50–534). The Wellcome Trust Clinical Research Facility and the Clinical Research Imaging Centre are supported by NHS Research Scotland (NRS) through NHS Lothian. Dr Rudd is partly supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trust. The Data Supplement is available at http://circimaging.ahajournals.org/lookup/suppl/doi:10.1161/CIRCIMAGING.116.005131/-/DC1.

PY - 2016/10/12

Y1 - 2016/10/12

N2 - 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.METHODS AND 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.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026.

AB - 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.METHODS AND 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.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02132026.

KW - 18F-Fluoride

KW - aortic valve stenosis

KW - calcification

KW - disease progression

KW - echocardiography

KW - positron emission tomography

U2 - 10.1161/CIRCIMAGING.116.005131

DO - 10.1161/CIRCIMAGING.116.005131

M3 - Article

C2 - 27733431

VL - 9

JO - Circulation. Cardiovascular imaging

JF - Circulation. Cardiovascular imaging

SN - 1941-9651

IS - 10

M1 - e005131

ER -