Hybrid Magnetic Resonance Imaging and Positron Emission Tomography With Fluorodeoxyglucose to Diagnose Active Cardiac Sarcoidosis

Abstract

Objectives: The purpose of this study was to explore the diagnostic usefulness of hybrid cardiac magnetic resonance (CMR) and positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) for active cardiac sarcoidosis.

Background: Active cardiac sarcoidosis (aCS) is underdiagnosed and has a high mortality.

Methods: Patients with clinical suspicion of aCS underwent hybrid CMR/PET with late gadolinium enhancement (LGE) and FDG to assess the pattern of injury and disease activity, respectively. Patients were categorized visually as magnetic resonance (MR)+PET+ (characteristic LGE aligning exactly with increased FDG uptake), MR+PET- (characteristic LGE but no increased FDG), MR-PET- (neither characteristic LGE nor increased FDG), and MR-PET+ (increased FDG uptake in absence of characteristic LGE) and further characterized as aCS+ (MR+PET+) or aCS- (MR+PET-, MR-PET-, MR-PET+). FDG uptake was quantified using maximum target-to-normal-myocardium ratio and the net uptake rate (Ki) from dynamic Patlak analysis. Receiver-operating characteristic methods were used to identify imaging biomarkers for aCS. FDG PET was assessed using computed tomography/PET in 19 control subjects with healthy myocardium.

Results: A total of 25 patients (12 males; 54.9 ± 9.8 years of age) were recruited prospectively; 8 were MR+PET+, suggestive of aCS; 1 was MR+PET-, consistent with inactive cardiac sarcoidosis; and 8 were MR-PET-, with no imaging evidence of cardiac sarcoidosis. Eight patients were MR-PET+ (6 with global myocardial FDG uptake, 2 with focal-on-diffuse uptake); they demonstrated distinct Ki values and hyperintense maximum standardized uptake value compared with MR+PET+ patients. Similar hyperintense patterns of global (n = 9) and focal-on-diffuse (n = 2) FDG uptake were also observed in control patients, suggesting physiological myocardial uptake. Maximum target-to-normal-myocardium ratio values were higher in the aCS+ group (p < 0.001), demonstrating an area under the curve of 0.98 on receiver-operating characteristic analysis for the detection of aCS, with an optimal maximum target-to-normal myocardium ratio threshold of 1.2 (Youden index: 0.94).

Conclusions: CMR/PET imaging holds major promise for the diagnosis of aCS, providing incremental information about both the pattern of injury and disease activity in a single scan. (In Vivo Molecular Imaging [MRI] of Atherothrombotic Lesions; NCT01418313).

Keywords: (18)F-fluorodeoxyglucose; MR/PET; cardiac sarcoidosis.

Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1. MR+PET+ Patients With Imaging Evidence of aCS on Hybrid CMR/PET

Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) images on the left with hybrid 18F-fluorodeoxyglucose (FDG) CMR/positron emission tomography (PET) images on the right. (A) Subepicardial (near transmural) LGE in the basal anteroseptum extending in to the right ventricular free wall with increased FDG uptake localizing to exactly the same region on fused CMR/PET (maximum standardized uptake value = 3.4; maximum tissue-to-background ratio = 2.3; maximum target-to-normal myocardium ratio = 2.0). (B) Subepicardial LGE in the basal anterolateral wall with increased FDG uptake co-localizing to exactly that region on CMR/PET. (C) Patchy midwall LGE in the anterolateral wall with matched increased FDG uptake on CMR/PET. (D) Multifocal LGE in the lateral wall with matched increased FDG uptake on CMR/PET.

FIGURE 2. Patients Without Imaging Evidence of aCS on Hybrid CMR/PET

(A) MR+PET−. Transmural LGE inferolaterally in a patient with biopsy-proven sarcoidosis but with no evidence of increased FDG PET uptake in this region. This pattern suggests inactive cardiac sarcoidosis with residual myocardial scar. (B) MR−PET−. Normal appearances on LGE scan and no increased FDG uptake on hybrid CMR/PET. (C) MR−PET+ (generalized). No myocardial injury on LGE, but generalized hyperintense FDG uptake throughout entire myocardium (maximum standardized uptake value [SUVmax] = 20.6), indicating failed myocardial suppression. (D) MR−PET+ (focal-on-diffuse uptake). No myocardial injury on LGE, but intense focal-on-diffuse FDG uptake in inferolateral wall (SUVmax = 7.7). This was the only example in this study where target-to-normal myocardium ratio (TNMR) values did not agree with the visual categorization (TNMRmax = 1.4). aCS = active cardiac sarcoidosis; other abbreviations as in Figure 1.

FIGURE 3. Quantification of Myocardial FDG Uptake on Static CMR/PET Images

(A, B) Different methods for quantifying myocardial FDG uptake. (A) Maximum standardized uptake value (SUVmax) (maximal SUV in region of interest 1 [ROI1], drawn around characteristic LGE if present), maximum tissue-to-background ratio (TBRmax) (SUVmax in ROI1 corrected for blood pool uptake measured in ROI2) and TNMRmax (SUVmax in ROI1 corrected for background myocardial uptake in contralateral LGE-segment, ROI3). (B) Mean relaxation–time value (T2 mapping) in ROI1 on T2 parametric images. (C to F) Scattergrams of imaging parameters in MR+PET+ (aCS+); MR+PET−, MR−PET−, MR−PET+ (all aCS−) groups. (C) SUVmax, (D) TBRmax, (E) TNMRmax (focal-on-diffuse uptake represented by blue points). (F) Receiver-operating characteristic curves analysis to predict aCS+ patients using: TNMRmax (area under the curve = 0.98) and T2 mapping (area under the curve = 0.75). Abbreviations as in Figures 1 and 2.

FIGURE 4. Dynamic FDG PET Analysis for MR+PET+ and MR−PET+Subjects

(A) Myocardial FDG PET time–SUV curves, averaged over the MR+PET+ and MR PET+ subjects, including the 2 MR−PET+ cases with focal-on-diffuse FDG uptake (blue dots). (B) FDG net uptake rate (Ki), for MR+PET+ and MR−PET+ subject groups using quantitative Patlak analysis (focal-on-diffuse patients blue dots; p = 0.006 when removing them from statistical analysis). Abbreviations as in Figures 1 and 2.