Original Article
Scan-rescan measurement repeatability of 18F-FDG PET/MR imaging of vascular inflammation

https://doi.org/10.1007/s12350-021-02627-5Get rights and content

Abstract

Non-invasive positron emission tomography (PET) of vascular inflammation and atherosclerotic plaque by identifying increased uptake of 18F-fluordeoxyglucose (18F-FDG) is a powerful tool for monitoring disease activity, progression, and its response to therapy. 18F-FDG PET/computed tomography (PET/CT) of the aorta and carotid arteries has become widely used to assess changes in inflammation in clinical trials. However, the recent advent of hybrid PET/magnetic resonance (PET/MR) scanners has advantages for vascular imaging due to the reduction in radiation exposure and improved soft tissue contrast of MR compared to CT. Important for research and clinical use is an understanding of the scan-rescan repeatability of the PET measurement. While this has been studied for PET/CT, no data is currently available for vascular PET/MR imaging. In this study, we determined the scan-rescan measurement repeatability of 18F-FDG PET/MR in the aorta and carotid arteries was less than 5%, comparable to similar findings for 18F-FDG PET/CT.

Introduction

Vascular inflammation is a hallmark of atherosclerosis. Atherosclerosis begins with lipid accumulation in the vessel wall of larger arteries including the aorta, carotid, peripheral and coronary arteries. As the plaque develops, recruitment of monocytes to the vessel wall and subsequent macrophage accumulation signal an inflammatory process that eventually destabilizes the plaque and increases the risk of rupture, thrombus formation and downstream ischemic events.1 The accumulation of macrophages in the vessel wall can be detected using positron emission tomography (PET) imaging of the radio-labeled glucose analog 18F-fluorodeoxyglucose (18F-FDG) owing to the preferential uptake of glucose by macrophages in the vessel wall compared to neighboring tissues.2, 3, 4, 5, 6

Non-invasive imaging of inflammation in the atherosclerotic plaque is a powerful tool for monitoring disease activity, predicting progression of this chronic disease, and assessing response to therapy in research and clinical settings.7,8 Combined with computed tomography (CT), 18F-FDG PET/CT imaging has become an established technique for non-invasive imaging of vascular inflammation. Importantly, the scan-rescan repeatability of 18F-FDG PET/CT imaging of vascular inflammation has been measured in the aorta, carotid and peripheral arteries.9, 10, 11, 12 A measurement repeatability of 5% 9 is sufficient to allow PET measurements to be used as an end point in many clinical trials,13, 14, 15, 16 including one study that showed short term changes in arterial inflammation measured by 18F-FDG PET can predict structural progression of carotid plaque.17 Importantly, increased vascular 18F-FDG uptake has been associated with a predilection for future cardiovascular events.18,19

Currently, most PET imaging is performed concurrently with CT, the latter providing attenuation information for PET image reconstruction as well as co-registered anatomical information to complement interpretation of the low-resolution PET data. However, PET/CT of vascular inflammation has two key limitations. Firstly, CT adds to the radiation exposure of the imaging test. Despite advances in low-radiation CT imaging, PET/CT is regarded with caution for longitudinal imaging. Secondly, soft tissue contrast of CT imaging that can be used for evaluating plaque size and contents is generally poor and requires higher radiation contrast-enhanced protocols to distinguish plaques with a soft lipid core and to separate vessel wall from lumen. Despite the excellent depiction of vascular calcification on CT imaging, especially for coronary calcium scoring, PET/CT imaging is limited in the additional information that can be garnered about the plaque.

Recently, combined PET and magnetic resonance (MR) systems have become available. MR has a number of advantages over CT for vascular inflammation imaging.20 First, MR is a radiation-free modality that can be used to obtain attenuation and anatomical information. This reduces the overall radiation dose of the test to a point where repeat studies for either clinical follow up or translational investigations, including studies in younger patients at an early disease stage, become feasible. Second, MR has excellent soft tissue contrast, and is able to distinguish lumen from wall, lipid core, the presence of intra-plaque hemorrhage and ulceration of the fibrous cap, as well as physiological changes such as micro-vessel permeability with gadolinium-based contrast-enhanced techniques.21, 22, 23, 24 Consequently, MR in the carotid arteries has become a well-established technique for assessing plaque vulnerability.25 The addition of vascular inflammation to the repertoire using hybrid PET/MR represents a significant advance for imaging of atherosclerosis that a number of studies have begun to explore.20,26, 27, 28, 29 PET/MR is also truly simultaneous, whereas PET and CT, while in the same gantry, are acquired sequentially. This may have additional advantages for monitoring dynamic processes including motion and perfusion while also measuring dynamic PET tracer uptake.

There are a number of key differences between PET/CT and PET/MR systems 30 that can potentially affect the measurement of activity, both its quantitative accuracy and its reliability, including detector type, configuration and sensitivity, and the method and implementation of the attenuation measurement,31,32 including the attenuation correction of the MR transmit and receive hardware that is present within the detection range of the PET detectors. In this study, we sought to establish for the first time the scan-rescan measurement repeatability of 18F-FDG PET/MR imaging of vascular inflammation in the aorta and carotid arteries in a group of patients undergoing this imaging to evaluate vascular inflammation. Moreover, this data was used to determine the group sizes required to detect a range of changes in measured PET signal following an intervention in the setting of a clinical trial. Finally, we aimed to compare the group sizes for studies with matched pairs to those for studies involving two independent groups.

Section snippets

Patients

With approval of the Institutional Review Board at the Icahn School of Medicine at Mount Sinai (GCO 01-1032), patients undergoing 18F-FDG PET/MR imaging in a pilot study of vascular inflammation and atopic dermatitis in our institution33 were enrolled for repeat imaging. All patients gave written informed consent. Patients were recruited for two 18F-FDG PET/MR scans within 14 days. Exclusion criteria included contraindications for MRI (pace-maker, non-compliant metal implants, pregnancy or

Results

Ten patients (Table 1) were scanned 9 ± 3 days apart, with an average dose of 265 ± 33 MBq (18F-FDG).

Elevated vascular inflammation was evident on 18F-FDG-PET images. Fused PET/MR images allowed localization of the increased uptake to the vessel wall in both the aorta and carotid arteries. Comparison of scan 1 and scan 2 showed similar patterns of uptake indicating that imaging has a high degree of repeatability over the 2 weeks between scans (Figure 1).

Image analysis was successful in all

Discussion

This study has shown that 18F-FDG PET/MR measurements of vascular inflammation have a high degree of repeatability. The 95% confidence interval for the difference between two measurements of TBRmean was 0.17, and the measurement repeatability for TBRmean was 4.3%. The repeatability of 18F-FDG PET/MR measurements was comparable to previous studies using 18F-FDG PET/CT,9, 10, 11, 12 indicating that the choice of PET/MR or PET/CT system does not impact the reliability of measurements of TBR and,

New Knowledge Gained

This study outlines the repeatability of 18F-FDG PET measurements in the vasculature using the hybrid PET/MR platform and confirms the equivalence of PET/CT and PET/MR platforms. The results can be used as a direct reference for vascular inflammation measurements using PET/MR but also provide relevant reference material on the reliability of quantitative and longitudinal PET measurements in a wide range of applications using this imaging platform. The measurements have also been used to present

Conclusion

The scan-rescan measurement repeatability of 18F-FDG PET/MR imaging of vascular inflammation in the aorta and carotid arteries is high. This study found a measurement repeatability of less than 5% for TBRmean values. Measurement repeatability was comparable to similar studies using PET/CT indicating that the choice of PET/MR or PET/CT system does not impact the reliability of measurements of TBR in vascular imaging of the carotid arties and aorta.

Acknowledgements

This work was supported by NIH Grant R01 HL071021

References (42)

  • SabaL et al.

    Imaging biomarkers of vulnerable carotid plaques for stroke risk prediction and their potential clinical implications

    Lancet Neurol

    (2019)
  • SilveraSS et al.

    Multimodality imaging of atherosclerotic plaque activity and composition using FDG-PET/CT and MRI in carotid and femoral arteries

    Atherosclerosis

    (2009)
  • CatanaC

    Principles of simultaneous PET/MR imaging

    Magn Reson Imaging Clin N Am

    (2017)
  • UngarB et al.

    A preliminary 18F-FDG-PET/MRI study shows increased vascular inflammation in moderate-to-severe atopic dermatitis

    J Allergy Clin Immunol Pract

    (2020)
  • FinnAV et al.

    Concept of vulnerable/unstable plaque

    Arterioscler Thromb Vasc Biol

    (2010)
  • RuddJHF et al.

    Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography

    Circulation

    (2002)
  • DaviesJR et al.

    Identification of culprit lesions after transient ischemic attack by combined 18F fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging

    Stroke

    (2005)
  • DunphyMPS et al.

    Association of vascular 18F-FDG uptake with vascular calcification

    J Nucl Med Off Publ Soc Nucl Med

    (2005)
  • Niccoli AsabellaA et al.

    Higher reliability of 18F-FDG target background ratio compared to standardized uptake value in vulnerable carotid plaque detection: a pilot study

    Ann Nucl Med

    (2014)
  • OgawaM et al.

    Application of 18F-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilization of vulnerable atherosclerotic plaques

    J Nucl Med Off Publ Soc Nucl Med

    (2006)
  • RuddJHF et al.

    Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations

    J Nucl Med Off Publ Soc Nucl Med

    (2008)
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