Myra S Cocker1, J David Spence2, Robert Hammond3, Robert A deKemp4, Cheemun Lum5, George Wells6, Jordan Bernick7, Andrew Hill8, Sudhir Nagpal9, Grant Stotts10, Murad Alturkustani11, Adebayo Adeeko12, Yulia Yerofeyeva13, Katey Rayner14, Joan Peterson15, Ali R Khan16, Ann C Naidas17, Linda Garrard18, Martin J Yaffe19, Eugene Leung20, Frank S Prato21, Jean-Claude Tardif22, Rob S B Beanlands23. 1. Molecular Function and Imaging Program and the National Cardiac PET Centre, Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: MCocker@ottawaheart.ca. 2. Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, Western University, London, Ontario, Canada. Electronic address: dspence@robarts.ca. 3. Department of Pathology, Western University, London, Ontario, Canada. Electronic address: Robert.Hammond@lhsc.on.ca. 4. Molecular Function and Imaging Program and the National Cardiac PET Centre, Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: RAdeKemp@ottawaheart.ca. 5. Department of Radiology, University of Ottawa and The Ottawa Hospital, Ottawa, Ontario, Canada. Electronic address: chlum@toh.on.ca. 6. Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: GAWells@ottawaheart.ca. 7. Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: JBernick@ottawaheart.ca. 8. Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: ahill@toh.on.ca. 9. Division of Vascular Surgery, Department of Surgery, University of Ottawa and The Ottawa Hospital, Ottawa, Ontario, Canada. Electronic address: snagpal@toh.on.ca. 10. Division of Neurology, Department of Medicine, University of Ottawa and The Ottawa Hospital, Ottawa, Ontario, Canada. Electronic address: gstotts@toh.on.ca. 11. Department of Pathology, Western University, London, Ontario, Canada. 12. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: aadeeko@sri.utoronto.ca. 13. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: yulia@sri.utoronto.ca. 14. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: KRayner@ottawaheart.ca. 15. Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: jpeterson@ohri.ca. 16. Department of Medical Biophysics, Robarts Research Institute, Western University, London, Ontario, Canada. Electronic address: alik@robarts.ca. 17. Department of Pathology, Western University, London, Ontario, Canada. Electronic address: anaidas@uwo.ca. 18. Molecular Function and Imaging Program and the National Cardiac PET Centre, Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: LGarrard@ottawaheart.ca. 19. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: martin.yaffe@sri.utoronto.ca. 20. Division of Nuclear Medicine, Department of Medicine, University of Ottawa and The Ottawa Hospital, Ottawa, Ontario, Canada. Electronic address: euleung@toh.on.ca. 21. Lawson Health Research Institute, London, Ontario, Canada. Electronic address: prato@lawsonimaging.ca. 22. Division of Cardiology, Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada. Electronic address: Jean-Claude.Tardif@icm-mhi.org. 23. Molecular Function and Imaging Program and the National Cardiac PET Centre, Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Radiology, University of Ottawa and The Ottawa Hospital, Ottawa, Ontario, Canada; Division of Nuclear Medicine, Department of Medicine, University of Ottawa and The Ottawa Hospital, Ottawa, Ontario, Canada. Electronic address: rbeanlands@ottawaheart.ca.
Abstract
BACKGROUND: [18F]-fluorodeoxyglucose (18FDG) uptake imaged with positron emission tomography (PET) and computed tomography (CT) may serve as a biomarker of plaque inflammation. This study evaluated the relationship between carotid plaque 18FDG uptake and a) intraplaque expression of macrophage and macrophage-like cellular CD68 immunohistology; b) intraplaque inflammatory burden using leukocyte-sensitive CD45 immunohistology; c) symptomatic patient presentation; d) time from last cerebrovascular event. METHODS: 54 patients scheduled for carotid endarterectomy underwent 18FDG PET/CT imaging. Maximum 18FDG uptake (SUVmax) and tissue-to-blood ratio (TBRmax) was measured for carotid plaques. Quantitative immunohistological analysis of macrophage-like cell expression (CD68) and leukocyte content (CD45) was performed. RESULTS: 18FDG uptake was related to CD68 macrophage expression (TBRmax: r = 0.51, p < 0.001), and total-plaque leukocyte CD45 expression (TBRmax: r = 0.632, p = 0.009, p < 0.001). 18FDG TBRmax uptake in carotid plaque associated with patient symptoms was greater than asymptomatic plaque (3.58 ± 1.01 vs. 3.13 ± 1.10, p = 0.008). 18FDG uptake differed between an acuity threshold of <90 days and >90 days (SUVmax:3.15 ± 0.87 vs. 2.52 ± 0.45, p = 0.015). CONCLUSIONS: In this CAIN cohort, 18FDG uptake imaged with PET/CT serves a surrogate marker of intraplaque inflammatory macrophage, macrophage-like cell and leukocyte burden. 18FDG uptake is greater in plaque associated with patient symptoms and those with recent cerebrovascular events. Future studies are needed to relate 18FDG uptake and disease progression.
BACKGROUND:[18F]-fluorodeoxyglucose (18FDG) uptake imaged with positron emission tomography (PET) and computed tomography (CT) may serve as a biomarker of plaque inflammation. This study evaluated the relationship between carotid plaque 18FDG uptake and a) intraplaque expression of macrophage and macrophage-like cellular CD68 immunohistology; b) intraplaque inflammatory burden using leukocyte-sensitive CD45 immunohistology; c) symptomatic patient presentation; d) time from last cerebrovascular event. METHODS: 54 patients scheduled for carotid endarterectomy underwent 18FDG PET/CT imaging. Maximum 18FDG uptake (SUVmax) and tissue-to-blood ratio (TBRmax) was measured for carotid plaques. Quantitative immunohistological analysis of macrophage-like cell expression (CD68) and leukocyte content (CD45) was performed. RESULTS:18FDG uptake was related to CD68 macrophage expression (TBRmax: r = 0.51, p < 0.001), and total-plaque leukocyte CD45 expression (TBRmax: r = 0.632, p = 0.009, p < 0.001). 18FDGTBRmax uptake in carotid plaque associated with patient symptoms was greater than asymptomatic plaque (3.58 ± 1.01 vs. 3.13 ± 1.10, p = 0.008). 18FDG uptake differed between an acuity threshold of <90 days and >90 days (SUVmax:3.15 ± 0.87 vs. 2.52 ± 0.45, p = 0.015). CONCLUSIONS: In this CAIN cohort, 18FDG uptake imaged with PET/CT serves a surrogate marker of intraplaque inflammatory macrophage, macrophage-like cell and leukocyte burden. 18FDG uptake is greater in plaque associated with patient symptoms and those with recent cerebrovascular events. Future studies are needed to relate 18FDG uptake and disease progression.
Authors: John Joseph McCabe; Nicola Giannotti; Jonathan McNulty; Sean Collins; Sarah Coveney; Sean Murphy; Mary Barry; Joseph Harbison; Simon Cronin; David Williams; Gillian Horgan; Eamon Dolan; Tim Cassidy; Ciaran McDonnell; Eoin Kavanagh; Shane Foley; Martin O'Connell; Michael Marnane; Peter Kelly Journal: BMJ Open Date: 2020-07-19 Impact factor: 2.692