Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging

Implications for cardiovascular risk stratification and clinical trials

Mark A. Ahlman, Davis M. Vigneault, Veit Sandfort, Roberto Maass-Moreno, Jenny Dave, Ahmed Sadek, Marissa B. Mallek, Mariana A.F. Selwaness, Peter Herscovitch, Nehal N. Mehta, David A. Bluemke

Research output: Contribution to journalArticle

Abstract

Introduction: 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake in the artery wall correlates with active inflammation. However, in part due to the low spatial resolution of PET, variation in the apparent arterial wall signal may be influenced by variation in blood FDG activity that cannot be fully corrected for using typical normalization strategies. The purpose of this study was to evaluate the ability of the current common methods to normalize for blood activity and to investigate alternative methods for more accurate quantification of vascular inflammation. Materials and methods: The relationship between maximum FDG aorta wall activity and mean blood activity was evaluated in 37 prospectively enrolled subjects aged 55 years or more, treated for hyperlipidemia. Target maximum aorta standardized uptake value (SUV) and mean background reference tissue activity (blood, spleen, liver) were recorded. Target-to-background ratios (TBR) and arterial maximum activity minus blood activity were calculated. Multivariable regression was conducted, predicting uptake values based on variation in background reference and target tissue FDG uptake; adjusting for gender, age, lean body mass (LBM), blood glucose, blood pool activity, and glomerular filtration rate (GFR), where appropriate. Results: Blood pool activity was positively associated with maximum artery wall SUV (β = 5.61, P< 0.0001) as well as mean liver (β = 6.23, P<0.0001) and spleen SUV (β = 5.20, P<0.0001). Artery wall activity divided by blood activity (TBRBlood) or subtraction of blood activity did not remove the statistically significant relationship to blood activity. Blood pool activity was not related to TBRliver and TBRspleen (β = −0.36, P = NS and β = −0.58, P = NS, respectively) Conclusions: In otherwise healthy individuals treated for hyperlipidemia, blood FDG activity is associated with artery wall activity. However, variation in blood activity may mask artery wall signal reflective of inflammation, which requires normalization. Blood-based TBR and subtraction do not sufficiently adjust for blood activity. Warranting further investigation, background reference tissues with cellular uptake such as the liver and spleen may better adjust for variation in blood activity to improve assessment of vascular activity.

Original languageEnglish (US)
Article numbere0187995
JournalPLoS One
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2017
Externally publishedYes

Fingerprint

blood vessels
Blood Vessels
clinical trials
Blood
inflammation
Clinical Trials
image analysis
Tissue
Inflammation
Imaging techniques
blood
arteries
uptake mechanisms
Arteries
Liver
positron-emission tomography
spleen
Positron emission tomography
Spleen
tissues

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging : Implications for cardiovascular risk stratification and clinical trials. / Ahlman, Mark A.; Vigneault, Davis M.; Sandfort, Veit; Maass-Moreno, Roberto; Dave, Jenny; Sadek, Ahmed; Mallek, Marissa B.; Selwaness, Mariana A.F.; Herscovitch, Peter; Mehta, Nehal N.; Bluemke, David A.

In: PLoS One, Vol. 12, No. 11, e0187995, 01.11.2017.

Research output: Contribution to journalArticle

Ahlman, MA, Vigneault, DM, Sandfort, V, Maass-Moreno, R, Dave, J, Sadek, A, Mallek, MB, Selwaness, MAF, Herscovitch, P, Mehta, NN & Bluemke, DA 2017, 'Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials', PLoS One, vol. 12, no. 11, e0187995. https://doi.org/10.1371/journal.pone.0187995
Ahlman, Mark A. ; Vigneault, Davis M. ; Sandfort, Veit ; Maass-Moreno, Roberto ; Dave, Jenny ; Sadek, Ahmed ; Mallek, Marissa B. ; Selwaness, Mariana A.F. ; Herscovitch, Peter ; Mehta, Nehal N. ; Bluemke, David A. / Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging : Implications for cardiovascular risk stratification and clinical trials. In: PLoS One. 2017 ; Vol. 12, No. 11.
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AU - Ahlman, Mark A.

AU - Vigneault, Davis M.

AU - Sandfort, Veit

AU - Maass-Moreno, Roberto

AU - Dave, Jenny

AU - Sadek, Ahmed

AU - Mallek, Marissa B.

AU - Selwaness, Mariana A.F.

AU - Herscovitch, Peter

AU - Mehta, Nehal N.

AU - Bluemke, David A.

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N2 - Introduction: 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) uptake in the artery wall correlates with active inflammation. However, in part due to the low spatial resolution of PET, variation in the apparent arterial wall signal may be influenced by variation in blood FDG activity that cannot be fully corrected for using typical normalization strategies. The purpose of this study was to evaluate the ability of the current common methods to normalize for blood activity and to investigate alternative methods for more accurate quantification of vascular inflammation. Materials and methods: The relationship between maximum FDG aorta wall activity and mean blood activity was evaluated in 37 prospectively enrolled subjects aged 55 years or more, treated for hyperlipidemia. Target maximum aorta standardized uptake value (SUV) and mean background reference tissue activity (blood, spleen, liver) were recorded. Target-to-background ratios (TBR) and arterial maximum activity minus blood activity were calculated. Multivariable regression was conducted, predicting uptake values based on variation in background reference and target tissue FDG uptake; adjusting for gender, age, lean body mass (LBM), blood glucose, blood pool activity, and glomerular filtration rate (GFR), where appropriate. Results: Blood pool activity was positively associated with maximum artery wall SUV (β = 5.61, P< 0.0001) as well as mean liver (β = 6.23, P<0.0001) and spleen SUV (β = 5.20, P<0.0001). Artery wall activity divided by blood activity (TBRBlood) or subtraction of blood activity did not remove the statistically significant relationship to blood activity. Blood pool activity was not related to TBRliver and TBRspleen (β = −0.36, P = NS and β = −0.58, P = NS, respectively) Conclusions: In otherwise healthy individuals treated for hyperlipidemia, blood FDG activity is associated with artery wall activity. However, variation in blood activity may mask artery wall signal reflective of inflammation, which requires normalization. Blood-based TBR and subtraction do not sufficiently adjust for blood activity. Warranting further investigation, background reference tissues with cellular uptake such as the liver and spleen may better adjust for variation in blood activity to improve assessment of vascular activity.

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