[18F]-Fluorodeoxyglucose PET/CT imaging as a marker of carotid plaque inflammation: Comparison to immunohistology and relationship to acuity of events

Myra S Cocker; J David Spence; Robert Hammond; Robert A deKemp; Cheemun Lum; George Wells; Jordan Bernick; Andrew Hill; Sudhir Nagpal; Grant Stotts; Murad Alturkustani; Adebayo Adeeko; Yulia Yerofeyeva; Katey Rayner; Joan Peterson; Ali R Khan; Ann C Naidas; Linda Garrard; Martin J Yaffe; Eugene Leung; Frank S Prato; Jean-Claude Tardif; Rob S B Beanlands; Canadian Atherosclerosis Imaging Network (CAIN) - Project II

doi:10.1016/j.ijcard.2018.05.057

[18F]-Fluorodeoxyglucose PET/CT imaging as a marker of carotid plaque inflammation: Comparison to immunohistology and relationship to acuity of events

Int J Cardiol. 2018 Nov 15:271:378-386. doi: 10.1016/j.ijcard.2018.05.057. Epub 2018 Jun 2.

Authors

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; Canadian Atherosclerosis Imaging Network (CAIN) - Project II

Affiliations

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.

PMID: 30007487
DOI: 10.1016/j.ijcard.2018.05.057

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 (SUV_max) and tissue-to-blood ratio (TBR_max) 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 (TBR_max: r = 0.51, p < 0.001), and total-plaque leukocyte CD45 expression (TBR_max: r = 0.632, p = 0.009, p < 0.001). ¹⁸FDG TBR_max 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 (SUV_max: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.

Keywords: (18)FDG PET/CT; Acuity; Carotid plaque inflammation; Leukocyte; Macrophage; Symptoms; [(18)-F]-fluorodeoxyglucose.

Publication types

Comparative Study

MeSH terms

Aged
Carotid Stenosis / diagnostic imaging*
Carotid Stenosis / metabolism*
Carotid Stenosis / surgery
Cohort Studies
Endarterectomy, Carotid / methods
Female
Fluorodeoxyglucose F18 / metabolism*
Humans
Male
Middle Aged
Plaque, Atherosclerotic / diagnostic imaging*
Plaque, Atherosclerotic / metabolism*
Plaque, Atherosclerotic / surgery
Positron Emission Tomography Computed Tomography / methods*
Prospective Studies

Substances

Fluorodeoxyglucose F18