Internal tissue references for 18Fluorodeoxyglucose vascular inflammation imaging: Implications for cardiovascular risk stratification and clinical trials

PLoS One. 2017 Nov 13;12(11):e0187995. doi: 10.1371/journal.pone.0187995. eCollection 2017.

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.

MeSH terms

  • Aged
  • Atherosclerosis / diagnostic imaging
  • Clinical Trials as Topic*
  • Female
  • Fluorodeoxyglucose F18 / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Multimodal Imaging
  • Positron-Emission Tomography
  • Prospective Studies
  • Radiopharmaceuticals / administration & dosage*
  • Tomography, X-Ray Computed
  • Vasculitis / diagnostic imaging*

Substances

  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18

Grants and funding

The research is funded by the National Institutes of Health intramural research program. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.