An easy and practical guide for imaging infection/inflammation by [18F]FDG PET/CT

Aim The aim of this mini-review was to summarize the role of positron emission tomography/computed tomography (PET/CT) with 18Fluorine-fluorodeoxyglucose ([18F]FDG) in inflammatory and infective processes, based on the published scientific evidence. Methods We analysed clinical indications, patient preparation, image acquisition protocols, image interpretation, pitfalls and how to make the report of cardio-vascular diseases, musculoskeletal diseases and other inflammatory and infective systemic diseases. Results of this analysis are shown in practical tables, easy to understand for daily routine consultation. Conclusions Despite [18F]FDG is currently used in several inflammatory and infective diseases, standardized interpretation criteria are still needed in most cases. It is, therefore, foreseen the execution of multicentre clinical studies that, by adopting the same acquisition and interpretation criteria, may contribute to the standardization of this imaging modality.


Introduction
The diagnosis of an infection by means of imaging modalities mainly relies on the possibility to exclude aseptic inflammation due to degenerative process, or autoimmune/allergic reactions or simply irritative causes. Several radiological and Nuclear Medicine procedures are, therefore, involved, in the search of which modality is more accurate in which clinical setting.
From the Nuclear Medicine point-of-view, this challenge to differentiate an infection from a sterile inflammation, has led to the production of hundreds of different radiopharmaceuticals that have open new ways to the possibility to specifically image the underlying process from a molecular point of view [1,2].
Radiolabelled antibiotics [3,4] or glucose derived sugars [5][6][7][8] have shown the potential to image bacteria, and, on the other hand, radiolabelled cytokines [9] or monoclonal antibodies [10] open the possibility to image different white blood cell subsets for histopathological characterization in vivo of the inflammatory/infective process.
Despite this enthusiastic output of new radiopharmaceuticals, the scintigraphy with radiolabelled white blood cells (WBCs), developed in early 1970 [11,12], remains the Nuclear Medicine modality of choice for routine and accurate diagnosis of infection. Over the years, we learned that this technique strictly relies on the application of precise labelling modalities, image acquisition protocol and interpretation criteria that have been published as guidelines by the European Association of Nuclear Medicine (EANM) [13][14][15][16][17][18]. 1 3 In the last two decades, given the increasing availability and application of positron emission tomography/computed tomography (PET/CT) with 18 Fluorine-fluorodeoxyglucose ([ 18 F]FDG) in several clinical contexts, infection and inflammation have also been extensively studied [19].
The great sensitivity of [ 18 F]FDG, together with the high quality of images provided by new generation tomographs, suggest the use of this modality for both diagnostic and follow-up purposes [19].
Nevertheless, well-standardized interpretation criteria, as it has been done for radiolabelled WBC scintigraphy, still do not exist for many infective or inflammatory disorders, thus resulting in different approaches adopted by each centre, and, most important, in a wide variability of reported accuracies of this modality that do not allow to make a direct comparison of different studies.
Nonetheless, the proposed interpretation criteria for [ 18 F] FDG PET/CT imaging in many clinical indications still need to be universally validated.

Purpose
This mini-review aims at providing an overview on the state of art of [ 18 F]FDG PET/CT imaging in musculoskeletal infections, cardiovascular infections and inflammations, and systemic inflammatory and infective diseases with particular emphasis on image acquisition protocols and interpretation criteria.

Methods
In this mini-review, we summarize the available procedural recommendations for [ 18  quently observed pitfalls and artefacts that need to be considered for a correct interpretation of the scan. -Final report: describes how to report the exam (in addition to demographic data and technical information of the scan, type of tomograph, body weight and administered dose) with a focus on essential parts of the report. Time between injection and image acquisition should always be included in the report since it could be particularly useful for both long-term follow-up and therapy evaluation studies when SUV max are compared.

Results
Results are summarized in easy to read tables, aiming at proving a useful tool in daily practice (Tables 1, 2, 3, and 4). It emerges that standardized protocols for patient preparation, image acquisition and interpretation criteria exist only for very limited clinical indications in the field of infection and inflammation and, in particular, for infective endocarditis, cardiac implantable devices infections, left ventricular assist device-associated infections, cardiac sarcoidosis, large vessel vasculitis and spondylodiscitis. For all other clinical indications, the recommendations for patient preparation and the acquisition protocols, commonly adopted for oncologic studies, are currently applied. As far as image interpretation is concerned, several criteria have been proposed for vascular graft infections, osteomyelitis, diabetic foot infections,   Qualitative analysis Description of lymph nodes (lambda sign), pulmonary, pleural, lacrimal and a salivary glands, brain, musculoskeletal and brain involvement; For assessing myocardial involvement, see Table 1 Semi-quantitative analysis prosthetic joint infections, and systemic infections/inflammations, but they still need to be validated in larger multicentre studies being the reported diagnostic accuracy of single centre studies, extremely variable and generally lower than the diagnostic accuracy of WBC scintigraphy [20,27].

Conclusions
In summary, this article and the following, published in this journal, provide a useful tool for identifying several patterns of [ 18 F]FDG uptake able to discriminate between an infection and a sterile inflammation aiming at increasing the specificity and the accuracy of this radiopharmaceutical. This may have a great clinical impact on the management of each specific disease, may help to smooth the wide heterogeneity that is still evident in literature and will lay the basis for future comparative studies. The definition of disease-specific acquisition protocols is warranted to increase the specificity and accuracy of this imaging modality. Moreover, it is mandatory, that the definition of precise and standardized interpretation criteria for [ 18 F]FDG PET/CT imaging in different infective or inflammatory disorders need to be adopted and shared by several institutions and validated in large, possibly multicentre, studies.

Declarations
Conflicts of interest Alberto Signore, Chiara Lauri and Massimiliano Casali have nothing to declare.

Compliance with Ethics Guidelines
This article does not contain any studies with human or animal subjects performed by any of the authors.
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