Quantification of FDG uptake in patients with a suspicion of prosthetic valve endocarditis: Part of the problem or part of the solution?
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Diagnostic Criteria for FDG-PET in Patients with a Suspicion of PVE
During the past 5 years, FDG-PET imaging has demonstrated its incremental value over echocardiography for the detection of prosthetic valve endocarditis (PVE).1,2 The results of these studies lead to the inclusion of the presence of an abnormal signal in the valvular region on FDG-PET imaging as a major criterion for the diagnosis of PVE in the recently published guidelines of the European Society of Cardiology.3 An important remaining issue for the interpretation of FDG-PET in patients with a suspicion of PVE is the lack of established diagnostic criteria to define what should be considered as an abnormal signal. The quantification of FDG uptake in valves might represent an interesting criterion among others for the analysis of PET images. In this issue of JNC, Scholtens et al.4 describe the range of values that have been identified in valves with FDG-PET in the existing literature. Interestingly, they found the values measured in valves of patients with definite or rejected PVE to be highly variable between centers. This work questions the significance of the intensity of valvular FDG uptake for the diagnostic of PVE.
Standardization of PET Protocols in Patients with PVE
There may be several explanations for this important variability in values measured in the valves. First, PET acquisition protocols differed between centers. Consequently, Scholtens et al.4 suggest to implement PET reconstruction protocols recommended by the European Association of Nuclear Medicine Research Ltd. (EARL) accreditation that have been developed for multi-centric studies in oncology5 for the imaging of patients with a suspicion of PVE. EARL protocols require to reconstruct image with large voxels and high level of smoothing in order to obtain comparable values in centers with different generations of PET systems. These protocols are, however, not appropriate for the imaging of patients with PVE because the focal and often weak FDG signal in valves will tend to be diluted in background signal owing to important partial volume effects on images at low spatial resolution.6 A reasonable alternative would be to agree on dedicated PET protocols for the imaging of patients with a suspicion of PVE that offer a compromise between image quality and the need for standardization of PET acquisitions, in a similar way to what has already been proposed for the imaging of atherosclerosis that present similar constraints.7 Second, valves are subjected to important cardiac and respiratory motion. Signal quantification would certainly benefit from the development of dual cardiac and respiratory gating and motion correction of PET acquisitions. Third, a consensus needs to be reached on the methodology applied for the quantification of the FDG signal in valves. In most clinical studies, two main metrics have been described so far: maximal SUV in the valvular region, and prosthesis to background ratio (PBR), which is usually calculated by dividing the maximal SUV measured on three adjacent slices centered on the valve with the mean SUV of blood measured in the right atrium. The two values included in PBR are similarly affected by variations in the activity of FDG injected to patients, the delay between injection and acquisition and PET acquisition parameters. PBR, as ratio between two values, is therefore less susceptible than SUV to be affected by these approximations and seems therefore the most robust metrics to compare the intensity of FDG uptake in valves between different centers. Forth, high FDG uptake in the myocardium can lead to overestimation of valvular SUV measured in the valvular region because of FDG signal spreading from the myocardium and local increase in image noise. For these reasons, patients with a suspicion of PVE scheduled for PET imaging should be prepared with a high fat, low carb diet before the imaging that allows in most patients for the suppression of FDG uptake in the myocardium.8 Taken together, the implementation of these recommendations will support a more reliable and robust quantification of FDG uptake in valves.
Intrinsic Limitations of Signal Quantification in PVE
One important challenge that cannot be overcome by improving acquisition protocols is that PVE can cause a large variety of valvular or peri-valvular lesions that have different intensities of FDG uptake: the intensity of FDG uptake in a vegetation is lower than in pre-suppurative tissue owing to the difference in the number of activated leucocytes present in each lesion.9 The intensity of FDG uptake in valve can also vary according to the germ involved in PVE and to the duration of antibiotherapy before imaging. Hence, the identification of diagnostic criteria for PVE requires the comparison of a large number of FDG-PET studies to take into account the multiple clinical, biological and imaging characteristics that can influence the aspects and intensity of FDG uptake on PET. In regards to the relative small number of patients with PVE recruited in each center, the identification of relevant diagnostic criteria corresponding to the different clinical presentations of IE would certainly gain from building up large multi-centric registries of patients with PVE imaged with FDG-PET. In this context, the definition of common PET acquisition protocol and metrics in patients imaged for PVE would represent an important first step in order to have reliable and comparable measurements of valvular FDG uptake between centers.
Integrating Clinical, Biology and Imaging for the Diagnostic of PVE
In summary, efforts should be directed towards defining common PET acquisition protocols and metrics for the evaluation of patients with a suspicion of PVE. This should facilitate the comparison of measurements originating from different imaging centers and support the implementation of multi-centric registries in this field. The grading of FDG uptake in valves as intense, moderate, mild or absent might be a more appropriate methodology for the analysis of PET images than a simple classification as positive or negative. The set-up of multi-centric registries would help for the identification of the most relevant thresholds corresponding to each level of valvular FDG uptake and relate these different levels to the probability of PVE in patients. In a similar way to what already exists for the analysis of echocardiography in the Duke classification, the precise quantification of valvular FDG uptake could be the groundwork for the definition of major and minor criteria of PVE using PET in combination with the analysis of the pattern and location of FDG uptake in valvular regions.
F. Hyafil, F. Rouzet and D. Le Guludec have nothing to disclose.
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