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, 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
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.
Keywords: 18F-Fluoride; aortic valve stenosis; calcification; disease progression; echocardiography; positron emission tomography.
Conflict of interest statement
None.
© 2016 The Authors.
Figures
References
- Pawade TA, Newby DE, Dweck MR. Calcification in a ortic atenosis: the skeleton key. J Am Coll Cardiol. 2015;66:561–577. doi: 10.1016/j.jacc.2015.05.066.
- Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359:1343–1356. doi: 10.1056/NEJMoa0804602.
- Irkle A, Vesey AT, Lewis DY, Skepper JN, Bird JL, Dweck MR, Joshi FR, Gallagher FA, Warburton EA, Bennett MR, Brindle KM, Newby DE, Rudd JH, Davenport AP. Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography. Nat Commun. 2015;6:7495. doi: 10.1038/ncomms8495.
- Dweck MR, Jenkins WS, Vesey AT, Pringle MA, Chin CW, Malley TS, Cowie WJ, Tsampasian V, Richardson H, Fletcher A, Wallace WA, Pessotto R, van Beek EJ, Boon NA, Rudd JH, Newby DE. 18F-sodium fluoride uptake is a marker of active calcification and disease progression in patients with aortic stenosis. Circ Cardiovasc Imaging. 2014;7:371–378. doi: 10.1161/CIRCIMAGING.113.001508.
- Dweck MR, Jenkins WS, Vesey AT, Pringle MA, Chin CW, Malley TS, Cowie WJ, Tsampasian V, Richardson H, Fletcher A, Wallace WA, Pessotto R, van Beek EJ, Boon NA, Rudd JH, Newby DE. 18F-sodium fluoride uptake is a marker of active calcification and disease progression in patients with aortic stenosis. Circ Cardiovasc Imaging. 2014;7:371–378. doi: 10.1161/CIRCIMAGING.113.001508.
- Dweck MR, Jones C, Joshi NV, Fletcher AM, Richardson H, White A, Marsden M, Pessotto R, Clark JC, Wallace WA, Salter DM, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation. 2012;125:76–86. doi: 10.1161/CIRCULATIONAHA.111.051052.
- Jenkins W, Pringle M, Cowie WJ, Richardson H, Fletcher A, Pessotto R, Boon NA, Rudd J, Newby D, Dweck M. 18F-NaF is a predictor of progression and outcome in aortic valve disease. J Am Coll Cardiol. 2014;63 doi: 101016/S0735-1097(14)60995-5.
- Litmanovich DE, Ghersin E, Burke DA, Popma J, Shahrzad M, Bankier AA. Imaging in transcatheter aortic valve replacement (TAVR): role of the radiologist. Insights Imaging. 2014;5:123–145. doi: 10.1007/s13244-013-0301-5.
- Chen W, Dilsizian V. PET assessment of vascular inflammation and atherosclerotic plaques: SUV or TBR? J Nucl Med. 2015;56:503–504. doi: 10.2967/jnumed.115.154385.
- Fayad ZA, Mani V, Woodward M, Kallend D, Abt M, Burgess T, Fuster V, Ballantyne CM, Stein EA, Tardif JC, Rudd JH, Farkouh ME, Tawakol A dal-PLAQUE Investigators. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet. 2011;378:1547–1559. doi: 10.1016/S0140-6736(11)61383-4.
- Critchley LA, Critchley JA. A meta-analysis of studies using bias and precision statistics to compare cardiac output measurement techniques. J Clin Monit Comput. 1999;15:85–91.
- Aikawa E, Nahrendorf M, Sosnovik D, Lok VM, Jaffer FA, Aikawa M, Weissleder R. Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation. 2007;115:377–386. doi: 10.1161/CIRCULATIONAHA.106.654913.
- Deck JD, Thubrikar MJ, Schneider PJ, Nolan SP. Structure, stress, and tissue repair in aortic valve leaflets. Cardiovasc Res. 1988;22:7–16.
- Clavel MA, Messika-Zeitoun D, Pibarot P, Aggarwal SR, Malouf J, Araoz PA, Michelena HI, Cueff C, Larose E, Capoulade R, Vahanian A, Enriquez-Sarano M. The complex nature of discordant severe calcified aortic valve disease grading: new insights from combined Doppler echocardiographic and computed tomographic study. J Am Coll Cardiol. 2013;62:2329–2338. doi: 10.1016/j.jacc.2013.08.1621.
- Dweck MR, Chin C, Newby DE. Small valve area with low-gradient aortic stenosis: beware the hard hearted. J Am Coll Cardiol. 2013;62:2339–2340. doi: 10.1016/j.jacc.2013.08.1620.
- Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, Yates D, LaMuraglia GM, Furie K, Houser S, Gewirtz H, Muller JE, Brady TJ, Fischman AJ. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818–1824. doi: 10.1016/j.jacc.2006.05.076.
- Rubeaux M, Joshi NV, Dweck MR, Fletcher A, Motwani M, Thomson LE, Germano G, Dey D, Li D, Berman DS, Newby DE, Slomka PJ. Motion correction of 18F-NaF PET for imaging coronary atherosclerotic plaques. J Nucl Med. 2016;57:54–59. doi: 10.2967/jnumed.115.162990.
- Jenkins WS, Vesey AT, Shah AS, Pawade TA, Chin CW, White AC, Fletcher A, Cartlidge TR, Mitchell AJ, Pringle MA, Brown OS, Pessotto R, McKillop G, Van Beek EJ, Boon NA, Rudd JH, Newby DE, Dweck MR. Valvular (18)F-fluoride and (18)F-fluorodeoxyglucose uptake predict disease progression and clinical outcome in patients with aortic stenosis. J Am Coll Cardiol. 2015;66:1200–1201. doi: 10.1016/j.jacc.2015.06.1325.
- Rudd JH, Myers KS, Bansilal S, Machac J, Rafique A, Farkouh M, Fuster V, Fayad ZA. (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol. 2007;50:892–896. doi: 10.1016/j.jacc.2007.05.024.
Source: PubMed