Combined simultaneous FDG-PET/MRI with T1 and T2 mapping as an imaging biomarker for the diagnosis and prognosis of suspected cardiac sarcoidosis

Abstract

Purpose: To evaluate the diagnostic and prognostic significance of combined cardiac ¹⁸F-fluorodeoxyglucose (FDG) PET/MRI with T1/T2 mapping in the evaluation of suspected cardiac sarcoidosis.

Methods: Patients with suspected cardiac sarcoidosis were prospectively enrolled for cardiac ¹⁸F-FDG PET/MRI, including late gadolinium enhancement (LGE) and T1/T2 mapping with calculation of extracellular volume (ECV). The final diagnosis of cardiac sarcoidosis was established using modified JMHW guidelines. Major adverse cardiac events (MACE) were assessed as a composite of cardiovascular death, ventricular tachyarrhythmia, bradyarrhythmia, cardiac transplantation or heart failure. Statistical analysis included Cox proportional hazard models.

Results: Forty-two patients (53 ± 13 years, 67% male) were evaluated, 13 (31%) with a final diagnosis of cardiac sarcoidosis. Among patients with cardiac sarcoidosis, 100% of patients had at least one abnormality on PET/MRI: FDG uptake in 69%, LGE in 100%, elevated T1 and ECV in 100%, and elevated T2 in 46%. FDG uptake co-localized with LGE in 69% of patients with cardiac sarcoidosis compared to 24% of those without, p = 0.014. Diagnostic specificity for cardiac sarcoidosis was highest for FDG uptake (69%), elevated T2 (79%), and FDG uptake co-localizing with LGE (76%). Diagnostic sensitivity was highest for LGE, elevated T1 and ECV (100%). After median follow-up duration of 634 days, 13 patients experienced MACE. All patients who experienced MACE had LGE, elevated T1 and elevated ECV. FDG uptake (HR 14.7, p = 0.002), elevated T2 (HR 9.0, p = 0.002) and native T1 (HR 1.1 per 10 ms increase, p = 0.044) were significant predictors of MACE even after adjusting for left ventricular ejection fraction and immune suppression treatment. The presence of FDG uptake co-localizing with LGE had the highest diagnostic performance overall (AUC 0.73) and was the best predictor of MACE based on model goodness of fit (HR 14.9, p = 0.001).

Conclusions: Combined cardiac FDG-PET/MRI with T1/T2 mapping provides complementary diagnostic information and predicts MACE in patients with suspected cardiac sarcoidosis.

Keywords: CMR; Cardiac MRI; Cardiac sarcoidosis; FDG PET; PET/MRI; Sarcoidosis.

Fig. 1

Combined 18F-FDG PET/MRI images in a 67-year-old male with cardiac and extra-cardiac sarcoidosis. Mid-ventricular short-axis native T1 map (A), native T2 map (B), late gadolinium-enhanced (LGE) image (C), and fused 18F-FDG PET and LGE image (D) demonstrate high T1 (green arrow), high T2 (black arrow), mid-wall LGE (red arrow) and co-localizing focal FDG uptake (white arrow) at the mid-anterior wall. There was extra-cardiac FDG uptake in mediastinal and hilar lymph nodes (not shown). The study was positive on both PET and MRI, likely reflecting active cardiac sarcoidosis with myocardial inflammation

Fig. 2

Combined 18F-FDG PET/MRI images in a 72-year-old male with cardiac and extra-cardiac sarcoidosis. Basal short-axis native T1 map (A), native T2 map (B), late gadolinium-enhanced (LGE) image (C), and fused 18F-FDG PET and LGE image (D) demonstrate slightly elevated native T1 (green arrow) and corresponding mid-wall LGE (red arrow) at the basal inferolateral wall. There was no corresponding elevation of native T2 or focal FDG uptake (white arrow). There was extra-cardiac FDG uptake in mediastinal and hilar lymph nodes (not shown) and in the lung parenchyma (blue arrow) in keeping with extra-cardiac sarcoidosis. With respect to the heart, the study was negative on PET and positive on MRI, likely reflecting chronic, burnt-out cardiac sarcoidosis

Fig. 3

Bar charts for PET and MRI findings by patient group. CMV (A), focal FDG uptake (B), LGE presence (C) and co-localized FDG uptake and LGE presence (D)

Fig. 4

Kaplan–Meier survival probability curves for the primary end-point of major adverse cardiac events (MACE) demonstrate that patients with late gadolinium enhancement (LGE), focal FDG uptake, and co-localized focal FDG uptake and LGE have worse event-free survival compared to patients without those findings. The number of patients at risk is shown at the bottom of the figures. Annualized event rates were higher in patients with LGE, focal FDG uptake, and co-localized focal FDG uptake and LGE