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High resolution FDG-microPET of carotid atherosclerosis: plaque components underlying enhanced FDG uptake

  • Jin Liu
  • William S. Kerwin
  • James H. Caldwell
  • Marina S. Ferguson
  • Daniel S. Hippe
  • Adam M. Alessio
  • Vanesa Martinez-Malo
  • Kristi Pimentel
  • Robert S. Miyaoka
  • Ted R. Kohler
  • Thomas S. Hatsukami
  • Chun Yuan
Original Paper

Abstract

This study sought to discover which atherosclerotic plaque components co-localize with enhanced [18F]-fluorodeoxyglucose (FDG) uptake in carotid positron emission tomography (PET) images. Although in vivo PET currently lacks the resolution, high-resolution ex vivo FDG-microPET with histology validation of excised carotid plaque might accomplish this goal. Thirteen patients were injected with FDG before carotid endarterectomy. After excision, the plaque specimens were scanned by microPET and magnetic resonance imaging, and then serially sectioned for histological analysis. Two analyses were performed using generalized linear mixed models: (1) a PET-driven analysis which sampled high and low FDG uptake areas from PET images to identify their components in matched histology specimens; and (2) a histology-driven analysis where specific plaque components were selected and matched to corresponding PET images. In the PET-driven analysis, regions of high FDG uptake were more likely to contain inflammatory cells (p < 0.001) and neovasculature (p = 0.008) than regions of low FDG uptake. In the histology-driven analysis, regions with inflammatory cells (p = 0.001) and regions with loose extracellular matrix (p = 0.001) were associated with enhanced FDG uptake. Furthermore, areas of complex inflammatory cell infiltrate (co-localized macrophages, lymphocytes and foam cells) had the highest FDG uptake among inflammatory subgroups (p < 0.001). In conclusion, in carotid plaque, regions of inflammatory cell infiltrate, particularly complex one, co-localized with enhanced FDG uptake in high-resolution FDG-microPET images. Loose extracellular matrix and areas containing neovasculature also produced FDG signal. This study points to the potential ability of FDG-PET to detect the cellular components of the vulnerable plaque.

Keywords

Atherosclerosis FDG MicroPET Vulnerable plaque Carotid plaque Inflammation 

Notes

Acknowledgments

The authors thank Dr. Jie Sun for his valuable discussions of pathology, and Zach Miller for his help on the manuscript. This study was funded by National Heart, Lung, and Blood Institute (Grant Number R21HL106061). This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington.

Compliance with ethical standards

Conflict of interest

Dr. Kerwin is an employee of Presage Biosciences. Mr. Hippe has received grants from GE Healthcare. Dr. Alessio has received research support from GE Healthcare. Dr. Hatsukami has received grants from Philips Healthcare. Dr. Yuan holds grants from the NIH and Philips Healthcare. He also serves as a Member of Radiology Advisory Network, Philips. All other authors have reported that they have no relationships to disclose.

Ethical standard

All human and animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

All persons gave their informed consent prior to their inclusion in the study.

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Jin Liu
    • 1
  • William S. Kerwin
    • 2
  • James H. Caldwell
    • 2
  • Marina S. Ferguson
    • 2
  • Daniel S. Hippe
    • 2
  • Adam M. Alessio
    • 2
  • Vanesa Martinez-Malo
    • 2
  • Kristi Pimentel
    • 2
  • Robert S. Miyaoka
    • 2
  • Ted R. Kohler
    • 3
    • 4
  • Thomas S. Hatsukami
    • 4
  • Chun Yuan
    • 1
    • 2
  1. 1.Department of BioengineeringUniversity of WashingtonSeattleUSA
  2. 2.Department of RadiologyUniversity of WashingtonSeattleUSA
  3. 3.Department of SurgerySeattle VA Puget Sound Health Care SystemSeattleUSA
  4. 4.Department of SurgeryUniversity of WashingtonSeattleUSA

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