Diagnostic Performance of <sup>18</sup>F-FDG PET/CT in Infectious and Inflammatory Diseases according to Published Meta-Analyses

Treglia, Giorgio

doi:https://doi.org/10.1155/2019/3018349

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In Vivo Imaging of Inflammation and Infection 2019

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Review Article | Open Access

Volume 2019 | Article ID 3018349 | https://doi.org/10.1155/2019/3018349

Diagnostic Performance of ¹⁸F-FDG PET/CT in Infectious and Inflammatory Diseases according to Published Meta-Analyses

Giorgio Treglia^1,2,3

Guest Editor: Sarah Ohrndorf

Received20 Jan 2019

Revised04 Apr 2019

Accepted14 Jul 2019

Published25 Jul 2019

Abstract

Purpose. To date, several meta-analyses have reported data about the diagnostic performance of ¹⁸F-FDG PET/CT in infectious and inflammatory diseases. This article aims to summarize the published evidence-based data about the diagnostic performance of ¹⁸F-FDG PET/CT in this setting. Methods. A comprehensive computer literature search of meta-analyses published in PubMed/MEDLINE and Cochrane library database from January 2009 through December 2018 and regarding the diagnostic performance of ¹⁸F-FDG PET/CT in infectious and inflammatory diseases was carried out. This combination of key words was used: (i) “PET” OR “positron emission tomography” OR “FDG” OR “fluorodeoxyglucose” AND (ii) meta-analysis. Only records on inflammatory or infectious diseases were selected. Results. The diagnostic performance of ¹⁸F-FDG PET/CT in detecting inflammatory and infectious diseases has been summarized taking into account 36 meta-analyses published in the literature. Evidence-based data demonstrated good diagnostic performance of ¹⁸F-FDG PET/CT for several inflammatory and infectious diseases, in particular cardiovascular infectious and inflammatory diseases and some musculoskeletal infections. Conclusions. Evidence-based data about the diagnostic performance of ¹⁸F-FDG PET/CT in infectious and inflammatory diseases are increasing, with good diagnostic performance of this imaging method for some indications. More prospective multicenter studies and cost-effective analyses are warranted.

1. Introduction

Nuclear medicine techniques are noninvasive tools that can early detect pathophysiological changes in affected tissues in patients with inflammatory or infectious diseases. These changes usually occur before clinical onset of symptoms and before the development of anatomical changes detected by radiological techniques [1, 2]. Currently, hybrid imaging techniques as positron emission tomography/computed tomography (PET/CT) may provide functional and morphological information for early diagnosis of infectious and inflammatory diseases [1, 2].

Fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) is a radiolabelled glucose analogue taken up by cells via cell membrane glucose transporters and subsequently phosphorylated with hexokinase inside most cells [3]. The ability of ¹⁸F-FDG PET/CT to identify sites of inflammation and infection is mainly related to the glycolytic activity of the cells involved in the inflammatory response [3].

¹⁸F-FDG PET/CT has been proposed for imaging of infectious or inflammatory diseases (Figure 1) because it has been demonstrated that cells involved in infection and inflammation, especially neutrophils and the monocyte/macrophage family, are able to express high levels of glucose transporters and hexokinase activity [3–5].

Enough evidence in the literature already exists about the usefulness of ¹⁸F-FDG PET/CT in the diagnosis and management of several infectious and inflammatory diseases [5]. The aim of this article is to summarize the findings of meta-analyses published in the last ten years about the diagnostic performance of ¹⁸F-FDG PET/CT in this setting.

2. Methods

A comprehensive computer literature search of PubMed/MEDLINE and Cochrane library databases was conducted to find recent published meta-analyses on the diagnostic performance of ¹⁸F-FDG PET/CT for the diagnosis of infectious and inflammatory diseases.

A search algorithm based on the combination of the following terms was used: (i) “PET” OR “positron emission tomography” OR “FDG” OR “fluorodeoxyglucose” AND (ii) meta-analysis. The literature search was updated until December 31^st, 2018. No language restriction was used. Recent meta-analyses published in the last ten years and investigating the diagnostic performance of ¹⁸F-FDG PET/CT in infectious or inflammatory diseases were eligible for inclusion. Titles and abstracts of the retrieved articles were reviewed, applying the inclusion criteria mentioned above.

For each selected meta-analysis, information was collected about basic study characteristics (disease evaluated, authors, year of publication, number of original articles included, and number of patients included) and pooled diagnostic performance measures including 95% confidence interval values (95% CI).

Main findings of the selected meta-analyses were briefly described.

3. Results

From the comprehensive computer literature search from PubMed/MEDLINE and Cochrane databases, 36 meta-analyses were selected and retrieved in full-text version [6–41]. The characteristics of the selected articles are presented in Table 1 and summarized here below.

3.1. Fever of Unknown Origin (FUO)

Fever of unknown origin (FUO) is a very precise entity, as described in the literature. FUO is commonly defined as temperature ≥38.3°C on at least two occasions, duration of illness ≥3 weeks or multiple febrile episodes in ≥3 weeks, not immunocompromised patient, and uncertain diagnosis despite thorough history-taking, physical examination, and obligatory investigations [42]. The diagnosis in patients with FUO is a challenging medical problem; the causes of FUO may be infectious diseases, noninfectious inflammatory diseases, or tumours, and ¹⁸F-FDG PET/CT detecting foci of increased glucose metabolism may be used for revealing the source of fever [42]. Several meta-analyses have estimated the diagnostic performance of ¹⁸F-FDG PET/CT in the assessment of FUO unidentified by conventional workup [6–12].

Dong et al. firstly reported that the pooled sensitivity and specificity of ¹⁸F-FDG PET/CT for the detection of FUO were 98.2% (95% CI: 93.6–99.8) and 85.9% (95% CI: 75–93.4), respectively. Therefore, this method should be considered among the first diagnostic tools for patients with FUO in whom conventional diagnostics have been unsuccessful [6].

Hao et al. confirmed the high sensitivity of ¹⁸F-FDG PET/CT for the diagnosis of patients with FUO (pooled value: 85%; 95% CI: 81–88), but the possibility of false-positive results should be kept in mind [7].

Another meta-analysis demonstrated that abnormal ¹⁸F-FDG PET/CT findings are associated with a substantially increased final diagnostic rate in FUO (pooled odds ratio: 8.94; 95% CI: 4.18–19.12, ). Consequently, ¹⁸F-FDG PET/CT could be considered for inclusion in the first-line diagnostic workup of FUO. Further randomized prospective studies with standardized ¹⁸F-FDG PET/CT are warranted to confirm this first-line position [8].

Tateuchi et al. reported that ¹⁸F-FDG PET/CT can be useful in identifying the source of fever in patients with classic FUO (immunocompetent patients). The summary sensitivity, specificity, and diagnostic yield of this method were 86% (95% CI: 81–90), 52% (95% CI: 36–67), and 58% (95% CI: 51–64), respectively. The contribution of ¹⁸F-FDG PET/CT may be limited in clinical settings in which infectious and neoplastic causes are less common. Indirect comparisons of test performance suggested that ¹⁸F-FDG PET/CT outperformed standalone ¹⁸F-FDG PET, gallium-67 scintigraphy, and radiolabelled leukocyte scintigraphy in detecting causes of FUO. Studies using standardized diagnostic algorithms are needed to determine the optimal timing for testing and to assess the impact of tests on management decisions and patient-relevant outcomes [9].

Recently, Bharucha et al. reported an overall diagnostic contribution of 56% (95% CI: 50–61) of ¹⁸F-FDG PET/CT in all patients with FUO. In a subgroup analysis taking into account previous investigations, the diagnostic yield/added contribution of ¹⁸F-FDG PET/CT over CT was 32% (95% CI: 22–44). The pooled proportion of abnormal ¹⁸F-FDG PET/CT in patients with FUO was 69% (95% CI: 63–75); the higher proportion of abnormal scans was accounted for by a proportion of false-positive abnormal scans with no contribution to the final diagnosis, with an overall result of 9% (95% CI: 5–14). The authors concluded that there is insufficient evidence to support the value of ¹⁸F-FDG PET/CT in investigative algorithms of FUO [10].

Conversely, in an updated meta-analysis on patients with FUO or inflammation of unknown origin (IUO), ¹⁸F-FDG PET/CT was demonstrated to be very helpful for recognizing and excluding diseases, directing further diagnostic decisions and avoiding unnecessary invasive examinations. The pooled sensitivity and specificity were 84% (95% CI: 79–89) and 63% (95% CI: 49–75), respectively. Based on these findings, the authors recommended ¹⁸F-FDG PET/CT among the first-line diagnostic tools for patients with FUO and IUO [11].

Lastly, it has been recently demonstrated that patients with negative ¹⁸F-FDG PET/CT results were significantly more likely to present with spontaneous fever regression than those with positive ¹⁸F-FDG PET/CT results (summary relative risk = 5.6 : 95% CI: 3.4–9.2; ) [12].

Overall, there is no agreement among the selected meta-analyses about the added value of ¹⁸F-FDG PET/CT in patients with FUO. The main drawback of the meta-analyses evaluating the diagnostic performance of ¹⁸F-FDG PET/CT for this specific indication is that they include articles without real FUO patients or with highly variable definitions of FUO; therefore, related meta-analyses could be not accurate in this regard [43].

Furthermore, the diagnostic yield of ¹⁸F-FDG PET/CT in patients with FUO should take into account not only the positive cases but also the true negative cases as patients with a negative ¹⁸F-FDG PET/CT are likely to have a favourable course [12]. Considering that 30–50% of patients with FUO will not have a final diagnosis and do well after prolonged follow-up without further treatment, the diagnostic yield of ¹⁸F-FDG PET/CT might be even higher compared to that reported in the selected meta-analyses [43].

3.2. Large Vessel Vasculitis (LVV)

Large vessel vasculitis (LVV) is defined as an inflammatory disease mainly affecting the large arteries, with two major variants, Takayasu arteritis (TA) and giant cell arteritis (GCA). GCA often coexists with polymyalgia rheumatica (PMR) in the same patient, since both belong to the same disease spectrum [44]. ¹⁸F-FDG PET/CT may demonstrate increased radiopharmaceutical uptake in the vascular wall of large vessels in patients with LVV; therefore, this method may be used for diagnosis, monitoring of disease activity, and evaluating disease progression in LVV [44–47], and several meta-analyses have assessed the role of this imaging method in this setting [13–19].

First meta-analyses including both ¹⁸F-FDG PET and PET/CT studies reported a valuable diagnostic performance of these methods in patients with GCA with a pooled sensitivity and specificity of 80% (95% CI: 63–91) and 89% (95% CI: 78–94), respectively [13], and a moderate value of these methods in assessing TA activity, with a pooled sensitivity and specificity of 70.1% (95% CI: 58.6–80) and 77.2% (95% CI: 64.2–87.3), respectively [14].

In a meta-analysis of Soussan et al. including both ¹⁸F-FDG PET and PET/CT studies, these imaging methods showed good performances in the diagnosis of LVV, with higher accuracy in GCA patients than in TA patients. A vascular uptake equal to or higher than the liver uptake appeared to be a good criterion for the diagnosis of vascular inflammation. ¹⁸F-FDG PET or PET/CT showed high sensitivity and specificity for the diagnosis of LVV in GCA patients in comparison to controls, with pooled values of 90% (95% CI: 79–93) and 98% (95% CI: 94–99), respectively. ¹⁸F-FDG PET or PET/CT had a pooled sensitivity of 87% (95% CI: 78–93) and specificity of 73% (95% CI: 63–81) for the assessment of disease activity in TA, with up to 84% of specificity in studies using National Institutes of Health criteria as the disease activity assessment scale [15].

Another meta-analysis by Lee et al. confirmed that ¹⁸F-FDG PET/CT has good diagnostic accuracy for LVV with a pooled sensitivity and specificity of 83.9 % (95% CI: 71.7–92.4) and 87.2% (95% CI: 72.6–95.7), respectively [16].

In a recent meta-analysis, the pooled sensitivity and specificity of ¹⁸F-FDG PET or PET/CT for detecting active disease in TA compared to clinical assessment were 81% (95% CI: 69–89) and 74% (95% CI: 55–86), respectively. Active disease by ¹⁸F-FDG PET or PET/CT was also associated with elevations of acute phase reactants, as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) [17]. Conversely, in another meta-analysis by Gomez et al. about the association between the CRP value and ¹⁸F-FDG PET or PET/CT vascular positivity in TA, CRP concentration only moderately reflected the ¹⁸F-FDG PET vascular positivity in TA, suggesting dissociated information [18]. More prospective studies are needed to assess the value of ¹⁸F-FDG PET/CT as an independent biomarker for subtle vascular wall inflammation detection in patients with TA [18].

Lastly, an updated meta-analysis confirmed that ¹⁸F-FDG PET or PET/CT has a good performance for the detection of active disease in patients with LVV with a pooled sensitivity and specificity of 88% (95% CI: 79–93) and 81% (95% CI: 64–91), respectively. Therefore, ¹⁸F-FDG PET/CT could be suggested as a surrogate biomarker for assessment of disease activity of LVV during or after immunosuppressive therapy, but further studies are warranted to determine if PET-based treatment of LVV can improve outcomes [19].

Several factors may significantly influence the arterial wall ¹⁸F-FDG uptake and must be taken into consideration for interpretation of ¹⁸F-FDG PET/CT in LVV [44]. Many PET interpretation criteria have been proposed; nevertheless, evidence supports the use of a visual ¹⁸F-FDG PET grading scale with vascular ¹⁸F-FDG uptake ≥ liver uptake as LVV positivity criterion [44]. Atherosclerotic vascular uptake may be a source of false positivity for LVV evaluation, despite a classical patchy uptake pattern. Taking these considerations into account, vascular inflammation in LVV on ¹⁸F-FDG PET classically appears as a smooth linear pattern [44].

Patients with suspected LVV often immediately receive high-dose glucocorticoids before ¹⁸F-FDG PET/CT, and this may reduce the intensity of arterial ¹⁸F-FDG uptake. The accuracy of ¹⁸F-FDG PET/CT can therefore vary in relation to the delay between the initiation of immunosuppressive therapy and ¹⁸F-FDG PET/CT [44].

For the precise evaluation of diagnostic accuracy of ¹⁸F-FDG PET/CT in patients with LVV, it should be taken into account that in some patients, ¹⁸F-FDG PET/CT may be the only modality allowing for the diagnosis of LVV, and therefore it cannot be compared to a gold standard [44].

Overall, based on the available evidence, ¹⁸F-FDG PET/CT has demonstrated high diagnostic performance for the detection of LVV. Further studies are needed to select the most clinically relevant and reproducible criteria for defining the presence of LVV with ¹⁸F-FDG PET/CT, as well as to test the clinical impact of ¹⁸F-FDG PET/CT on the management of patients with suspected LVV [44].

3.3. Infective Endocarditis (IE) and Cardiovascular Implantable Electronic Device (CIED) Infections

Infective endocarditis (IE) is a serious and potentially life-threatening condition. The current diagnosis of IE is based on the modified Duke criteria, which has approximately 80% sensitivity for the diagnosis of native valve endocarditis (NVE), with lower sensitivity for the diagnosis of prosthetic valve endocarditis (PVE) and culture-negative endocarditis [48, 49]. Noninvasive imaging modalities may improve diagnosis of infective endocarditis (IE) [48, 49]. In particular, ¹⁸F-FDG PET/CT is currently included as diagnostic tool in the diagnostic flow chart for IE [48–51], and some meta-analyses have evaluated the diagnostic performance of this method in patients with IE or CIED infections [20–24].

A first meta-analysis published in 2016 demonstrated that the overall diagnostic performance of ¹⁸F-FDG PET/CT for the diagnosis of IE was not high due to the low sensitivity: pooled sensitivity and specificity were 61% (95% CI: 52–88) and 88% (95% CI: 80–93), respectively. However the diagnostic performance of ¹⁸F-FDG PET/CT increased in the subgroup of patients with PVE [20].

Mahmood et al. demonstrated that ¹⁸F-FDG PET/CT may be a useful adjunctive diagnostic tool in the evaluation of diagnostically challenging cases of IE, particularly in PVE. The pooled sensitivity and specificity of ¹⁸F-FDG PET/CT for diagnosis of IE were 76.8% (95% CI: 71.8–81.4) and 77.9% (95% CI: 71.9–83.2), respectively. Diagnostic accuracy was improved for PVE with pooled sensitivity of 80.5% (95% CI: 74.1–86) and pooled specificity of 73.1% (95% CI: 63.8–81.2). More recent studies published from 2015 to 2017 reported a higher pooled sensitivity of 81.3% (95% CI: 74.3–87) and specificity of 79% (95% CI: 71.2–85.5). The majority of the recent studies were prospective and used a specific protocol (i.e., a low-carbohydrate fat-allowed diet for at least 24 hours prior to imaging, a prolonged fasting prior to imaging, and/or an intravenous heparin bolus prior to ¹⁸F-FDG administration). ¹⁸F-FDG PET/CT also has the potential to detect clinically relevant extracardiac foci of infection, malignancy, and other sources of inflammation leading to more appropriate treatment regimens and surgical intervention. Additional extracardiac foci of infection were found on 17% of patients in this meta-analysis [21].

In another meta-analysis, Juneau et al. demonstrated that ¹⁸F-FDG PET/CT has a good diagnostic accuracy for the diagnosis of IE if adequate patient preparation for suppression of physiological myocardial ¹⁸F-FDG uptake was performed, including prolonged fasting at least 12 hours and/or heparin injection before ¹⁸F-FDG administration and/or high-fat carbohydrate-restricted protein-permitted diet. Pooled sensitivity of ¹⁸F-FDG PET/CT performed with adequate cardiac preparation for the diagnosis of IE was 81% (95% CI: 73–86) and pooled specificity was 85% (95% CI: 78–91). In the subgroup of patients with PVE, the pooled sensitivity was 85% (95% CI: 77–91) but specificity was 81% (95% CI: 72–88). Therefore, ¹⁸F-FDG PET/CT may be useful in the investigation of IE and should be considered in cases where the diagnosis is uncertain [22].

¹⁸F-FDG PET/CT may be helpful in the diagnosis of CIED infections, particularly in patients with the absence of localizing signs or definitive echocardiographic findings. In a recent meta-analysis, Mahmood et al. reported a pooled sensitivity and specificity of ¹⁸F-FDG PET/CT in the diagnosis of CIED infections of 85% (95% CI: 80–89) and 90% (95% CI: 84–94), respectively. ¹⁸F-FDG PET/CT demonstrated a higher sensitivity of 96% (95% CI: 86–99) and specificity of 97% (95% CI: 86–99) for diagnosis of pocket infections. Diagnostic accuracy for lead infections or CIED-IE was lower with pooled sensitivity of 76% (95% CI: 65–85) and specificity of 83% (95% CI: 72–90). In the subgroup of studies that described use of any myocardial suppression protocol, the pooled sensitivity was 92% (95% CI: 85–96) and the pooled specificity was 81% (95% CI: 71–89) [23].

Another recent meta-analysis confirmed the high diagnostic performance of ¹⁸F-FDG PET/CT for the diagnosis of CIED infections with a pooled sensitivity of 87% (95% CI: 82–91) and a pooled specificity of 94% (95% CI: 88–98). Pooled sensitivity and specificity for diagnosis of pocket/generator related CIED infections were 93% (95% CI: 84–98) and 98% (95% CI: 88–100), respectively. Pooled sensitivity and specificity for diagnosis of lead or IE-related CIED infection were 65% (95% CI: 53–76) and 88% (95% CI: 77–94), respectively [24].

Overall, ¹⁸F-FDG PET/CT demonstrated a good diagnostic performance in patients with IE and CIED infections with higher diagnostic accuracy if adequate patient preparation for suppression of physiological myocardial ¹⁸F-FDG uptake was performed.

3.4. Vascular Graft Infection (VGI)

Vascular graft infection (VGI), a serious complication in vascular surgery, has a high morbidity and mortality rate. The diagnosis is complicated by nonspecific symptoms and challenged by the variable accuracy of different imaging techniques [25, 52]. A recent meta-analysis demonstrated a good diagnostic performance of ¹⁸F-FDG PET/CT in patients with VGI with a pooled sensitivity and specificity of 95% (95% CI: 87–99) and 80% (95% CI: 69–89), respectively [25].

Another recent meta-analysis investigating the diagnostic accuracy of ¹⁸F-FDG PET/CT in VGI reported a pooled sensitivity and specificity for focal ¹⁸F-FDG uptake of 97% (95% CI: 89–99) and 89% (95% CI: 70–96), respectively [26].

One of the factors influencing the ¹⁸F-FDG uptake in patients with suspicious VGI is the time at which ¹⁸F-FDG PET/CT is performed after surgery. In fact, ¹⁸F-FDG uptake reaches its peak in the first few weeks after surgery and tends towards normal values around 4 weeks postoperatively, even if long-lasting physiologic activity has also been described. If ¹⁸F-FDG PET/CT is performed in cases of recently implanted grafts, increased ¹⁸F-FDG uptake can occur in uninfected grafts leading to false-positive ¹⁸F-FDG PET/CT findings for VGI [26].

False-negative ¹⁸F-FDG PET/CT findings in VGI may occur mainly because of the use of antibiotics prior to imaging, thus lowering the metabolic activity expected in infections and lowering the ¹⁸F-FDG uptake [26].

Variable interpretation criteria have been used to assess VGI by ¹⁸F-FDG PET/CT. The sensitivity and specificity of ¹⁸F-FDG PET/CT may therefore vary based on the criteria used [26]. A consensus about the parameters used for interpretation of the results would lead to better diagnostic accuracy, and this could be increased by performing the scan prior to antimicrobial treatment. Results from larger prospective studies are warranted [26].

3.5. Sarcoidosis

Sarcoidosis is a multisystem chronic inflammatory disease of unknown etiology characterized by widespread growth of noncaseating granulomas. The diagnosis of sarcoidosis is based on clinical and imaging presentation, histological confirmation, and the absence of alternative diseases. Imaging techniques may play a role in the diagnostic workup of patients with sarcoidosis to assess disease extent and activity and treatment response evaluation [53]. The role of ¹⁸F-FDG PET/CT in patients with sarcoidosis is well established [54, 55]. Based on evidence-based data, the recommendations for use of ¹⁸F-FDG PET/CT in patients with sarcoidosis could be the following: evaluation of inflammatory active disease in patients with persistent symptoms and negative serologic markers; assessment of inflammation in radiologic stage IV sarcoidosis with lung fibrosis; evaluation of inflammatory active extrathoracic sites of sarcoidosis or assessment of cardiac sarcoidosis (especially in patients with implanted pacemakers); identification of active sites for diagnostic biopsy not revealed by other methods; and evaluation of treatment response in refractory sarcoidosis [54].

The role of ¹⁸F-FDG PET/CT in cardiac sarcoidosis is currently under active investigation [56], and some meta-analyses have addressed the diagnostic performance of ¹⁸F-FDG PET/CT in this setting [27–29].

In the meta-analysis of Youssef et al., the pooled sensitivity and specificity of ¹⁸F-FDG PET or PET/CT for diagnosis of cardiac sarcoidosis were 89% (95% CI: 79–96) and 78% (95% CI: 68–86), respectively [27].

Tang et al. demonstrated that the diagnostic accuracy of ¹⁸F-FDG PET/CT for cardiac sarcoidosis depends on adequate suppression of physiological cardiac glucose uptake. Overall, ¹⁸F-FDG PET/CT had a pooled sensitivity of 75% (95% CI: 69–80) and a pooled specificity of 81% (95% CI: 76–85) for the diagnosis of cardiac sarcoidosis. This modest diagnostic accuracy was attributed to the inclusion of studies in which a short fasting duration before scanning likely influenced its sensitivity. Excluding studies without adequate myocardial suppression resulted in a pooled sensitivity of 81% (95% CI: 76–86) and a pooled specificity of 82% (95% CI: 77–86). Fasting for at least 12 hours before scanning or a high-fat low-carbohydrate diet given at 3 to 6 hours before imaging or heparin infusion before imaging has shown to improve the diagnostic accuracy of ¹⁸F-FDG PET/CT in cardiac sarcoidosis [28].

Lastly, an updated meta-analysis on the diagnostic performance of ¹⁸F-FDG PET or PET/CT in cardiac sarcoidosis demonstrated a pooled sensitivity and specificity of 84% (95% CI: 71–91) and 83% (95% CI: 74–89), respectively. The presence of combined myocardial perfusion imaging improved the diagnostic accuracy of ¹⁸F-FDG PET/CT for diagnosis of cardiac sarcoidosis. Nevertheless, further large multicenter studies in this setting are needed [29].

3.6. Musculoskeletal Infections

Musculoskeletal infections are a serious problem in healthcare. Establishing the correct diagnosis is often difficult and may have a huge impact on daily life. Treatment of a musculoskeletal infection often requires a long time and/or costly procedures which can be avoided if musculoskeletal infection is excluded [57]. On the other hand, timely identification and precise localization of musculoskeletal infections by imaging techniques are critical for early initiation of treatment and can have a significant impact on patient outcome. In this setting, nuclear medicine and radiological imaging are complementary techniques [57]. In particular, several meta-analyses have investigated the diagnostic performance of ¹⁸F-FDG PET/CT in patients with suspicious musculoskeletal infections [30–38].

Wang et al. calculated the diagnostic performance of ¹⁸F-FDG PET or PET/CT in patients with suspicious osteomyelitis reporting a high pooled sensitivity and specificity in this setting: pooled values were 92.3% (95% CI: 86.7–96.1) and 92% (95% CI: 87–95.6), respectively [30].

A first meta-analysis focused on the diagnostic performance of ¹⁸F-FDG PET or PET/CT in osteomyelitis related to diabetic foot reported a pooled sensitivity and specificity of 74% (95% CI: 60–85) and 91% (95% CI: 85–96), respectively [31]. An updated meta-analysis on the same topic demonstrated a pooled sensitivity of 89% (95% CI: 68–97) and a pooled specificity of 92% (95% CI: 85–96) [32].

Jin et al. calculated the diagnostic performance of ¹⁸F-FDG PET or PET/CT in detecting prosthetic infection after arthroplasty. They found a pooled sensitivity and specificity of 86% (95% CI: 82–90) and 86% (95% CI: 83–89), respectively. The pooled sensitivity of ¹⁸F-FDG PET or PET/CT in demonstrating hip and knee prosthetic infection was 88% (95% CI: 83–92) and 72% (95% CI: 58–84), respectively. The pooled specificity of ¹⁸F-FDG PET or PET/CT in demonstrating hip and knee prosthetic infection was 88% (95% CI: 84–91) and 80% (95% CI: 71–88), respectively [33].

A meta-analysis focused on periprosthetic hip infection confirmed the good diagnostic accuracy of ¹⁸F-FDG PET or PET/CT in this setting with pooled sensitivity and specificity of 86% (95% CI: 80–90) and 93% (95% CI: 90–95), respectively, using increased ¹⁸F-FDG uptake in the bone-prosthesis interface as the criterion for infection for the index test [34].

A meta-analysis focused on periprosthetic knee infection demonstrated a not optimal diagnostic accuracy of ¹⁸F-FDG PET or PET/CT in this setting with pooled sensitivity and specificity of 70% (95% CI: 56–81) and 84% (95% CI: 76–90) [35].

Some factors influencing the diagnostic performance of ¹⁸F-FDG PET/CT in patients with osteomyelitis should be underlined: first of all, several interpretation criteria of ¹⁸F-FDG PET have been used in the literature, by using visual and/or semiquantitative criteria, leading to different diagnostic accuracy values [30–35]. Furthermore, continuous physiologic ¹⁸F-FDG activity around the prostheses may be the cause of false-positive ¹⁸F-FDG PET/CT findings for periprosthetic infection [33–35].

¹⁸F-FDG PET or PET/CT has an excellent diagnostic performance in detecting infectious spondylodiscitis [58]. A first meta-analysis on ¹⁸F-FDG PET or PET/CT in patients with suspicious spondylodiscitis reported a pooled sensitivity and specificity of 97% (95% CI: 83–100) and 88% (95% CI: 74–95), respectively [36]. In this setting, the diagnostic performance of ¹⁸F-FDG PET or PET/CT was higher compared with magnetic resonance imaging (MRI). Considering studies comparing ¹⁸F-FDG PET or PET/CT and MRI, pooled sensitivity and specificity of ¹⁸F-FDG PET or PET/CT were 96% (95% CI: 84–99) and 90% (95% CI: 79–96), whereas the pooled sensitivity and specificity of MRI were 76% (95% CI: 65–84) and 62% (95% CI: 45–77) [37]. Another recent meta-analysis confirmed the better diagnostic accuracy of ¹⁸F-FDG PET or PET/CT compared to MRI for the detection of spondylodiscitis: for ¹⁸F-FDG PET or PET/CT, pooled sensitivity and specificity were 95% (95% CI: 87–98) and 88% (95% CI: 73–95), respectively; and for MRI, pooled sensitivity and specificity were 85% (95% CI: 65–95) and 66% (95% CI: 48–80), respectively [38].

Overall, based on the available evidence, ¹⁸F-FDG PET/CT has demonstrated a good diagnostic performance for the detection of musculoskeletal infections.

3.7. Inflammatory Rheumatic Diseases

Molecular imaging methods, including ¹⁸F-FDG PET/CT, have been proposed for a better assessment of inflammatory rheumatic diseases [59]. ¹⁸F-FDG uptake in the shoulders or hips was often reported in PMR (pooled prevalence: 76%), especially in periarticular sites (pooled prevalence: 84%). Furthermore, interspinous ¹⁸F-FDG uptake, demonstrating interspinous bursitis, is common in PMR (pooled prevalence: 67%). However, these findings are not very specific for PMR [39].

Patients with rheumatoid arthritis (RA) may also have interspinous ¹⁸F-FDG uptake (pooled prevalence: 34%) or articular ¹⁸F-FDG uptake in shoulders or hips (pooled prevalence: 66%) or in other articular regions (pooled prevalence: 78%). Articular ¹⁸F-FDG uptake is not specific for PMR or RA as it is common in other connective tissue diseases (pooled prevalence: 70%). Overall, ¹⁸F-FDG PET/CT is helpful in diagnostic research, but the interpretation of ¹⁸F-FDG uptake at each site is not characteristic of a specific inflammatory rheumatic disease [39].

3.8. Inflammatory Bowel Diseases

¹⁸F-FDG PET/CT may also be used to image areas of active inflammation, such as those occurring in patients with active inflammatory bowel disease (IBD) as Crohn's disease and ulcerative colitis [60]. In this setting, ¹⁸F-FDG PET or PET/CT showed a good accuracy with a pooled sensitivity and specificity of 85% (95% CI: 81–88) and 87% (95% CI 84–90), respectively [40]. These findings were confirmed by another meta-analysis including prospective studies only [41]. Nevertheless, more prospective studies evaluating the role of ¹⁸F-FDG PET/CT for this indication are needed. Specific challenges for the use of ¹⁸F-FDG PET/CT in IBD are the physiological ¹⁸F-FDG uptake in the bowel and the movement of the bowel that may influence a correct coregistration of ¹⁸F-FDG PET and CT images [40].

4. Discussion

Overall, this article demonstrates that there is increasing evidence about the diagnostic performance of ¹⁸F-FDG PET/CT in infectious and inflammatory diseases, with good diagnostic accuracy values for some indications (Table 1). Awareness of the results described in this review has the potential to affect patient care by providing supportive evidence for more effective use of ¹⁸F-FDG PET/CT in the diagnosis of some infectious or inflammatory diseases. ¹⁸F-FDG PET/CT may potentially be useful to direct therapeutic strategies improving patient outcome, but prospective outcome studies are needed in this setting. In fact, diagnostic accuracy of a test is not a measure of clinical effectiveness, and good diagnostic performance does not necessarily result in improved patient outcomes. Other factors beyond the diagnostic performance should influence the choice of an imaging modality in patients with infectious and inflammatory diseases (i.e., availability, radiation dose, safety, examination time, legal, organization and economic aspects, and cost-effectiveness).

Some limitations of the included meta-analyses should be underlined because they could limit definitive conclusions on the diagnostic performance of ¹⁸F-FDG PET/CT in infectious and inflammatory diseases. First of all, in some meta-analyses, a limited number of published articles (some of them with small sample size) were included reducing the statistical power of the analysis (Table 1).

In several meta-analyses, a considerable heterogeneity of diagnostic performance of ¹⁸F-FDG PET/CT among studies was found. Heterogeneity may represent a potential source of bias in a meta-analysis. This heterogeneity is likely to arise through baseline differences among the patients in the included studies, diversity in methodological aspects between different studies, and different study quality [61]. The diversity of the interpretation criteria used for ¹⁸F-FDG PET/CT may also have contributed to the heterogeneity among studies.

About the study design, only some articles included in each meta-analysis were prospective studies, influencing the overall quality of the meta-analysis and causing heterogeneity. Many of the included studies are small, single-centre, retrospective series limiting their applicability to a broader setting. In most of the included studies, the ¹⁸F-FDG PET/CT results were available to the clinicians caring for patients which may have influenced their decision making. Moreover, interpretation of imaging was often not blinded to the clinical scenario, which may have influenced reporting of ¹⁸F-FDG PET/CT results.

The lack of a reliable “gold standard” for the diagnosis of infection and inflammation could be another limitation of the described meta-analyses. The studies included in the meta-analyses used multiple and imperfect reference standards and were deemed likely to have produced biased results because of differential verification and incorporation of the ¹⁸F-FDG PET/CT result in the reference standard. Differential verification and incorporation bias are likely to lead to overestimation of test performance, and thus the summary estimates should be interpreted with caution [61].

Also, publication bias is a major concern in all meta-analyses as studies reporting significant findings are more likely to be published than those reporting nonsignificant results [61].

Some current indications of ¹⁸F-FDG PET/CT in infectious and inflammation were not evaluated by meta-analyses. In particular, septicemia and/or bacteremia of unknown origin is an important current field of use of ¹⁸F-FDG PET/CT [62–67]; furthermore, the diagnostic performance of ¹⁸F-FDG PET/CT for infections caused by specific pathogens (i.e., fungal infections, mycobacteriosis, etc.) [68, 69] needs also to be evaluated through a meta-analytic approach.

Large multicenter prospective studies and in particular more cost-effective analyses comparing ¹⁸F-FDG PET/CT with other imaging modalities in infectious and inflammatory diseases are warranted. To this regard, cost-effective analyses on ¹⁸F-FDG PET/CT in patients with FUO and bacteremia are already available, demonstrating that ¹⁸F-FDG PET/CT appears to be a cost-effective imaging technique in these settings by avoiding unnecessary investigations and reducing the duration of hospitalization [70–73].

By using ¹⁸F-FDG PET/CT, it is difficult to distinguish sterile inflammation from inflammation caused by infection. Even though radiolabelled leukocytes are routinely used in clinical practice for this purpose, new radiopharmaceuticals including imaging agents targeting bacteria are currently investigated [74, 75]. A recent evidence-based review highlighted the availability of many promising PET radiopharmaceuticals for bacterial imaging despite some bias related to animal selection and index test, but few have been translated to human subjects. Results showed a lack of standardized infection models and experimental settings [75]. PET/CT using autologous leukocytes radiolabelled with ¹⁸F-FDG demonstrated a good diagnostic accuracy for the diagnosis of infectious diseases, but larger studies are needed [76].

Furthermore, radiopharmaceuticals beyond ¹⁸F-FDG have been developed for evaluating inflammatory diseases, in particular to define new strategies for imaging immune cells as well as tissue modifications induced by the inflammatory process [77].

The role of ¹⁸F-FDG PET/CT for assessing treatment response in infectious or inflammatory diseases is also promising [78]. However, there are currently no recommended imaging modalities to objectively evaluate the effectiveness of treatment. Therapeutic effectiveness is currently gauged by the patient's subjective clinical response [78].

Hybrid PET/MRI systems, combining functional information with high soft tissue contrast provided by MRI, are now available for clinical use. Although the role of ¹⁸F-FDG PET/MRI in infectious and inflammatory diseases is promising, these areas of clinical investigation are still in the early phase, and more evidence-based data are needed in this setting [79].

Conflicts of Interest

The author declares no conflicts of interest.

References

A. Signore, K. L. Anzola, S. Auletta et al., “Current status of molecular imaging in inflammatory and autoimmune disorders,” Current Pharmaceutical Design, vol. 24, no. 7, pp. 743–753, 2018.
View at: Publisher Site | Google Scholar
M. Sollini, C. Lauri, R. Boni, E. Lazzeri, P. A. Erba, and A. Signore, “Current status of molecular imaging in infections,” Current Pharmaceutical Design, vol. 24, no. 7, pp. 754–771, 2018.
View at: Publisher Site | Google Scholar
F. Jamar, J. Buscombe, A. Chiti et al., “EANM/SNMMI guideline for ¹⁸F-FDG use in inflammation and infection,” Journal of Nuclear Medicine, vol. 54, no. 4, pp. 647–658, 2013.
View at: Publisher Site | Google Scholar
S. Hess, A. Alavi, and S. Basu, “PET-based personalized management of infectious and inflammatory disorders,” PET Clinics, vol. 11, no. 3, pp. 351–361, 2016.
View at: Publisher Site | Google Scholar
A. W. Glaudemans, E. F. de Vries, F. Galli, R. A. Dierckx, R. H. Slart, and A. Signore, “The use of ¹⁸F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases,” Clinical and Developmental Immunology, vol. 2013, Article ID 623036, 14 pages, 2013.
View at: Publisher Site | Google Scholar
M.-j. Dong, K. Zhao, Z.-f. Liu, G.-l. Wang, S.-y. Yang, and G.-j. Zhou, “A meta-analysis of the value of fluorodeoxyglucose-PET/PET-CT in the evaluation of fever of unknown origin,” European Journal of Radiology, vol. 80, no. 3, pp. 834–844, 2011.
View at: Publisher Site | Google Scholar
R. Hao, L. Yuan, Y. Kan, C. Li, and J. Yang, “Diagnostic performance of ¹⁸F-FDG PET/CT in patients with fever of unknown origin,” Nuclear Medicine Communications, vol. 34, no. 7, pp. 682–688, 2013.
View at: Publisher Site | Google Scholar
F. L. Besson, P. Chaumet-Riffaud, M. Playe et al., “Contribution of ¹⁸F-FDG PET in the diagnostic assessment of fever of unknown origin (FUO): a stratification-based meta-analysis,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 43, no. 10, pp. 1887–1895, 2016.
View at: Publisher Site | Google Scholar
M. Takeuchi, I. J. Dahabreh, T. Nihashi, M. Iwata, G. M. Varghese, and T. Terasawa, “Nuclear imaging for classic fever of unknown origin: meta-analysis,” Journal of Nuclear Medicine, vol. 57, no. 12, pp. 1913–1919, 2016.
View at: Publisher Site | Google Scholar
T. Bharucha, A. Rutherford, S. Skeoch et al., “Diagnostic yield of FDG-PET/CT in fever of unknown origin: a systematic review, meta-analysis, and Delphi exercise,” Clinical Radiology, vol. 72, no. 9, pp. 764–771, 2017.
View at: Publisher Site | Google Scholar
Y. Kan, W. Wang, J. Liu, J. Yang, and Z. Wang, “Contribution of ¹⁸F-FDG PET/CT in a case-mix of fever of unknown origin and inflammation of unknown origin: a meta-analysis,” Acta Radiologica, vol. 60, no. 6, pp. 716–725, 2018.
View at: Publisher Site | Google Scholar
M. Takeuchi, T. Nihashi, A. Gafter-Gvili et al., “Association of ¹⁸F-FDG PET or PET/CT results with spontaneous remission in classic fever of unknown origin: a systematic review and meta-analysis,” Medicine, vol. 97, no. 43, Article ID e12909, 2018.
View at: Publisher Site | Google Scholar
F. L. Besson, J.-J. Parienti, B. Bienvenu et al., “Diagnostic performance of ¹⁸F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 38, no. 9, pp. 1764–1772, 2011.
View at: Publisher Site | Google Scholar
Y. Cheng, N. Lv, Z. Wang, B. Chen, and A. Dang, “18-FDG-PET in assessing disease activity in Takayasu arteritis: a meta-analysis,” Clinical and Experimental Rheumatology, vol. 31, no. 75, pp. S22–S27, 2013.
View at: Google Scholar
M. Soussan, P. Nicolas, C. Schramm et al., “Management of large-vessel vasculitis with FDG-PET,” Medicine, vol. 94, no. 14, Article ID e622, 2015.
View at: Publisher Site | Google Scholar
Y. H. Lee, S. J. Choi, J. D. Ji, and G. G. Song, “Diagnostic accuracy of ¹⁸F-FDG PET or PET/CT for large vessel vasculitis,” Zeitschrift für Rheumatologie, vol. 75, no. 9, pp. 924–931, 2016.
View at: Publisher Site | Google Scholar
L. Barra, T. Kanji, J. Malette, and C. Pagnoux, “Imaging modalities for the diagnosis and disease activity assessment of Takayasu’s arteritis: a systematic review and meta-analysis,” Autoimmunity Reviews, vol. 17, no. 2, pp. 175–187, 2018.
View at: Publisher Site | Google Scholar
L. Gomez, P. Chaumet-Riffaud, N. Noel et al., “Effect of CRP value on ¹⁸F-FDG PET vascular positivity in Takayasu arteritis: a systematic review and per-patient based meta-analysis,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 45, no. 4, pp. 575–581, 2018.
View at: Publisher Site | Google Scholar
S.-W. Lee, S.-J. Kim, Y. Seo, S. Y. Jeong, B.-C. Ahn, and J. Lee, “F-18 FDG PET for assessment of disease activity of large vessel vasculitis: a systematic review and meta-analysis,” Journal of Nuclear Cardiology, vol. 26, no. 1, pp. 59–67, 2018.
View at: Publisher Site | Google Scholar
J. Yan, C. Zhang, Y. Niu et al., “The role of ¹⁸F-FDG PET/CT in infectious endocarditis: a systematic review and meta- analysis,” International Journal of Clinical Pharmacology and Therapeutics, vol. 54, no. 5, pp. 337–342, 2016.
View at: Publisher Site | Google Scholar
M. Mahmood, A. T. Kendi, S. Ajmal et al., “Meta-analysis of ¹⁸F-FDG PET/CT in the diagnosis of infective endocarditis,” Journal of Nuclear Cardiology, vol. 26, no. 3, pp. 922–935, 2017.
View at: Publisher Site | Google Scholar
D. Juneau, M. Golfam, S. Hazra et al., “Molecular Imaging for the diagnosis of infective endocarditis: a systematic literature review and meta-analysis,” International Journal of Cardiology, vol. 253, pp. 183–188, 2018.
View at: Publisher Site | Google Scholar
M. Mahmood, A. T. Kendi, S. Farid et al., “Role of ¹⁸F-FDG PET/CT in the diagnosis of cardiovascular implantable electronic device infections: a meta-analysis,” Journal of Nuclear Cardiology, vol. 26, no. 3, pp. 958–970, 2017.
View at: Publisher Site | Google Scholar
D. Juneau, M. Golfam, S. Hazra et al., “Positron emission tomography and single-photon emission computed tomography imaging in the diagnosis of cardiac implantable electronic device infection: a systematic review and meta-analysis,” Circulation: Cardiovascular Imaging, vol. 10, no. 4, 2017.
View at: Publisher Site | Google Scholar
E. I. Reinders Folmer, G. C. I. Von Meijenfeldt, M. J. Van der Laan et al., “Diagnostic imaging in vascular graft infection: a systematic review and meta-analysis,” European Journal of Vascular and Endovascular Surgery, vol. 56, no. 5, pp. 719–729, 2018.
View at: Publisher Site | Google Scholar
D. Rojoa, N. Kontopodis, S. A. Antoniou, C. V. Ioannou, and G. A. Antoniou, “¹⁸F-FDG PET in the diagnosis of vascular prosthetic graft infection: a diagnostic test accuracy meta-analysis,” European Journal of Vascular and Endovascular Surgery, vol. 57, no. 2, pp. 292–301, 2019.
View at: Publisher Site | Google Scholar
G. Youssef, E. Leung, I. Mylonas et al., “The use of ¹⁸F-FDG PET in the diagnosis of cardiac sarcoidosis: a systematic review and metaanalysis including the Ontario experience,” Journal of Nuclear Medicine, vol. 53, no. 2, pp. 241–248, 2012.
View at: Publisher Site | Google Scholar
R. Tang, J. T.-Y. Wang, L. Wang et al., “Impact of patient preparation on the diagnostic performance of ¹⁸F-FDG PET in cardiac sarcoidosis,” Clinical Nuclear Medicine, vol. 41, no. 7, pp. e327–e339, 2016.
View at: Publisher Site | Google Scholar
S.-J. Kim, K. Pak, and K. Kim, “Diagnostic performance of F-18 FDG PET for detection of cardiac sarcoidosis; a systematic review and meta-analysis,” Journal of Nuclear Cardiology, 2019.
View at: Publisher Site | Google Scholar
G.-l. Wang, K. Zhao, Z.-f. Liu, M.-j. Dong, and S.-y. Yang, “A meta-analysis of fluorodeoxyglucose-positron emission tomography versus scintigraphy in the evaluation of suspected osteomyelitis,” Nuclear Medicine Communications, vol. 32, no. 12, pp. 1134–1142, 2011.
View at: Publisher Site | Google Scholar
G. Treglia, R. Sadeghi, S. Annunziata et al., “Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography for the diagnosis of osteomyelitis related to diabetic foot: a systematic review and a meta-analysis,” The Foot, vol. 23, no. 4, pp. 140–148, 2013.
View at: Publisher Site | Google Scholar
C. Lauri, M. Tamminga, A. W. J. M. Glaudemans et al., “Detection of osteomyelitis in the diabetic foot by imaging techniques: a systematic review and meta-analysis comparing MRI, white blood cell scintigraphy, and FDG-PET,” Diabetes Care, vol. 40, no. 8, pp. 1111–1120, 2017.
View at: Publisher Site | Google Scholar
H. Jin, L. Yuan, C. Li, Y. Kan, R. Hao, and J. Yang, “Diagnostic performance of FDG PET or PET/CT in prosthetic infection after arthroplasty: a meta-analysis,” Quarterly Journal of Nuclear Medicine and Molecular Imaging, vol. 58, no. 1, pp. 85–93, 2014.
View at: Google Scholar
S. J. Verberne, P. G. Raijmakers, and O. P. P. Temmerman, “The accuracy of imaging techniques in the assessment of periprosthetic hip infection,” Journal of Bone and Joint Surgery, vol. 98, no. 19, pp. 1638–1645, 2016.
View at: Publisher Site | Google Scholar
S. J. Verberne, R. J. A. Sonnega, O. P. P. Temmerman, and P. G. Raijmakers, “What is the accuracy of nuclear imaging in the assessment of periprosthetic knee infection? a meta-analysis,” Clinical Orthopaedics and Related Research, vol. 475, no. 5, pp. 1395–1410, 2017.
View at: Publisher Site | Google Scholar
M. L. Prodromou, P. D. Ziakas, L. S. Poulou, P. Karsaliakos, L. Thanos, and E. Mylonakis, “FDG PET is a robust tool for the diagnosis of spondylodiscitis,” Clinical Nuclear Medicine, vol. 39, no. 4, pp. 330–335, 2014.
View at: Publisher Site | Google Scholar
Y. Yin, X. Liu, X. Yang, J. Guo, Q. Wang, and L. Chen, “Diagnostic value of FDG-PET versus magnetic resonance imaging for detecting spondylitis: a systematic review and meta-analysis,” Spine Journal, vol. 18, no. 12, pp. 2323–2332, 2018.
View at: Publisher Site | Google Scholar
S. J. Kim, K. Pak, K. Kim, and J. S. Lee, “Comparing the diagnostic accuracies of F-18 FDG PET and MRI for the detection of spondylodiscitis: a meta-analysis,” Spine, 2018.
View at: Publisher Site | Google Scholar
L. Descamps, L. Olagne, C. Merlin, F. Cachin, M. Soubrier, and S. Mathieu, “Utility of PET/CT in the diagnosis of inflammatory rheumatic diseases: a systematic review and meta-analysis,” Annals of the Rheumatic Diseases, vol. 77, no. 11, p. e81, 2018.
View at: Publisher Site | Google Scholar
G. Treglia, N. Quartuccio, R. Sadeghi et al., “Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography in patients with chronic inflammatory bowel disease: a systematic review and a meta-analysis,” Journal of Crohn’s and Colitis, vol. 7, no. 5, pp. 345–354, 2013.
View at: Publisher Site | Google Scholar
J. Zhang, L.-F. Li, Y.-J. Zhu et al., “Diagnostic performance of ¹⁸F-FDG-PET versus scintigraphy in patients with inflammatory bowel disease,” Nuclear Medicine Communications, vol. 35, no. 12, pp. 1233–1246, 2014.
View at: Publisher Site | Google Scholar
I. J. E. Kouijzer, C. M. Mulders-Manders, C. P. Bleeker-Rovers, and W. J. G. Oyen, “Fever of unknown origin: the value of FDG-PET/CT,” Seminars in Nuclear Medicine, vol. 48, no. 2, pp. 100–107, 2018.
View at: Publisher Site | Google Scholar
I. J. E. Kouijzer, J. W. M. van der Meer, W. J. G. Oyen, and C. P. Bleeker-Rovers, “Diagnostic yield of FDG-PET/CT in fever of unknown origin: a systematic review, meta-analysis, and Delphi exercise,” Clinical Radiology, vol. 73, no. 6, pp. 588-589, 2018.
View at: Publisher Site | Google Scholar
R. H. J. A. Slart, Writing group, Reviewer group et al., “FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 45, no. 7, pp. 1250–1269, 2018.
View at: Publisher Site | Google Scholar
G. Treglia, M. V. Mattoli, L. Leccisotti, G. Ferraccioli, and A. Giordano, “Usefulness of whole-body fluorine-18-fluorodeoxyglucose positron emission tomography in patients with large-vessel vasculitis: a systematic review,” Clinical Rheumatology, vol. 30, no. 10, pp. 1265–1275, 2011.
View at: Publisher Site | Google Scholar
G. Treglia, A. Versari, L. Giovanella, N. Pipitone, and C. Salvarani, “Is ¹⁸F-FDG PET a ‘potentially hazardous’ or an effective tool in evaluating patients with large-vessel vasculitis?” Clinical and Experimental Rheumatology, vol. 31, no. 75, p. S93, 2013.
View at: Google Scholar
C. Dejaco, S. Ramiro, C. Duftner et al., “EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice,” Annals of the Rheumatic Diseases, vol. 77, no. 5, pp. 636–643, 2018.
View at: Publisher Site | Google Scholar
P. A. Erba, P. Lancellotti, I. Vilacosta et al., “Recommendations on nuclear and multimodality imaging in IE and CIED infections,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 45, no. 10, pp. 1795–1815, 2018.
View at: Publisher Site | Google Scholar
A. Gomes, A. W. J. M. Glaudemans, D. J. Touw et al., “Diagnostic value of imaging in infective endocarditis: a systematic review,” Lancet Infectious Diseases, vol. 17, no. 1, pp. e1–e14, 2017.
View at: Publisher Site | Google Scholar
G. Treglia and F. Bertagna, “Factors influencing the sensitivity of ¹⁸F-FDG PET/CT in the detection of infective endocarditis,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 40, no. 7, pp. 1112-1113, 2013.
View at: Publisher Site | Google Scholar
C. Caldarella, L. Leccisotti, G. Treglia, and A. Giordano, “Which is the optimal acquisition time for FDG PET/CT imaging in patients with infective endocarditis?” Journal of Nuclear Cardiology, vol. 20, no. 2, pp. 307–309, 2013.
View at: Publisher Site | Google Scholar
G. Treglia, F. Maggi, L. Bonomo, and A. Giordano, “Usefulness of fluorine-18 fluorodeoxyglucose PET/computed tomography in diagnosis of aortitis and treatment response evaluation in a patient with aortic prosthesis,” Journal of Cardiovascular Medicine, vol. 12, no. 11, pp. 814–816, 2011.
View at: Publisher Site | Google Scholar
A. R. Larici, A. W. Glaudemans, A. Del Ciello, R. H. Slart, L. Calandriello, and O. Gheysens, “Radiological and nuclear medicine imaging of sarcoidosis,” Q J Nucl Med Mol Imaging, vol. 62, no. 1, pp. 14–33, 2018.
View at: Publisher Site | Google Scholar
G. Treglia, S. Annunziata, D. Sobic-Saranovic, F. Bertagna, C. Caldarella, and L. Giovanella, “The role of ¹⁸F-FDG-PET and PET/CT in patients with sarcoidosis,” Academic Radiology, vol. 21, no. 5, pp. 675–684, 2014.
View at: Publisher Site | Google Scholar
G. Treglia, S. Taralli, and A. Giordano, “Emerging role of whole-body ¹⁸F-fluorodeoxyglucose positron emission tomography as a marker of disease activity in patients with sarcoidosis: a systematic review,” Sarcoidosis Vasculitis and Diffuse Lung Diseses, vol. 28, no. 2, pp. 87–94, 2011.
View at: Google Scholar
R. H. J. A. Slart, A. W. J. M. Glaudemans, P. Lancellotti et al., “A joint procedural position statement on imaging in cardiac sarcoidosis: from the cardiovascular and inflammation & infection committees of the European association of nuclear medicine, the European association of cardiovascular imaging, and the American society of nuclear cardiology,” Journal of Nuclear Cardiology, vol. 25, no. 1, pp. 298–319, 2018.
View at: Publisher Site | Google Scholar
A. W. Glaudemans, N. Prandini, M. Di Girolamo et al., “Hybrid imaging of musculoskeletal infections,” Quarterly Journal of Nuclear Medicine and Molecular Imaging, vol. 62, no. 1, pp. 3–13, 2018.
View at: Google Scholar
G. Treglia, C. Focacci, C. Caldarella et al., “The role of nuclear medicine in the diagnosis of spondylodiscitis,” European Review for Medical and Pharmacological Sciences, vol. 16, no. 2, pp. 20–25, 2012.
View at: Google Scholar
F. Jamar, A. Versari, F. Galli, F. Lecouvet, and A. Signore, “Molecular imaging of inflammatory arthritis and related disorders,” Seminars in Nuclear Medicine, vol. 48, no. 3, pp. 277–290, 2018.
View at: Publisher Site | Google Scholar
O. Catalano, F. Maccioni, C. Lauri, S. Auletta, R. Dierckx, and A. Signore, “Hybrid imaging in Crohn’s disease: from SPECT/CT to PET/MR and new image interpretation criteria,” Quarterly Journal of Nuclear Medicine and Molecular Imaging, vol. 62, no. 1, pp. 40–55, 2018.
View at: Publisher Site | Google Scholar
R. Sadeghi and G. Treglia, “Systematic reviews and meta-analyses of diagnostic studies: a practical guideline,” Clinical and Translational Imaging, vol. 5, no. 2, pp. 83–87, 2017.
View at: Publisher Site | Google Scholar
M. B. Brøndserud, C. Pedersen, F. S. Rosenvinge, P. F. Høilund-Carlsen, and S. Hess, “Clinical value of FDG-PET/CT in bacteremia of unknown origin with catalase-negative gram-positive cocci or Staphylococcus aureus,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 46, no. 6, pp. 1351–1358, 2019.
View at: Publisher Site | Google Scholar
J. Colombo, L. Elzi, G. Treglia, and A. Perren, “Light in the dark: ¹⁸F-FDG PET/CT in Staphylococcus aureus bacteremia of unknown origin,” Intensive Care Medicine, vol. 44, no. 4, pp. 488-489, 2018.
View at: Publisher Site | Google Scholar
D. Mandry, A. Tatopoulos, E. Chevalier-Mathias et al., “¹⁸F-fluorodeoxyglucose positron emission tomography combined with whole-body computed tomographic angiography in critically ill patients with suspected severe sepsis with no definite diagnosis,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 41, no. 10, pp. 1924–1930, 2014.
View at: Publisher Site | Google Scholar
J.-R. Tseng, K.-Y. Chen, M.-H. Lee, C.-T. Huang, Y.-H. Wen, and T.-C. Yen, “Potential usefulness of FDG PET/CT in patients with sepsis of unknown origin,” PLoS One, vol. 8, no. 6, Article ID e66132, 2013.
View at: Publisher Site | Google Scholar
A. Tewari, S. Padma, and P. Sundaram, “The diagnostic role of 18-fluorodeoxyglucocose-positron emission tomography/computed tomography in occult bacteremia searching underlying primary disease,” Annals of Indian Academy of Neurology, vol. 15, no. 4, pp. 336–338, 2012.
View at: Publisher Site | Google Scholar
S. Kluge, S. Braune, A. Nierhaus et al., “Diagnostic value of positron emission tomography combined with computed tomography for evaluating patients with septic shock of unknown origin,” Journal of Critical Care, vol. 27, no. 3, pp. 316.e1–7, 2012.
View at: Publisher Site | Google Scholar
B. Leroy-Freschini, G. Treglia, X. Argemi et al., “¹⁸F-FDG PET/CT for invasive fungal infection in immunocompromised patients,” QJM: An International Journal of Medicine, vol. 111, no. 9, pp. 613–622, 2018.
View at: Publisher Site | Google Scholar
G. Treglia, S. Taralli, M. L. Calcagni, F. Maggi, A. Giordano, and L. Bonomo, “Is there a role for fluorine 18 fluorodeoxyglucose-positron emission tomography and positron emission tomography/computed tomography in evaluating patients with mycobacteriosis? a systematic review,” Journal of Computer Assisted Tomography, vol. 35, no. 3, pp. 387–393, 2011.
View at: Publisher Site | Google Scholar
I. J. Kouijzer, F. J. Vos, C. P. Bleeker-Rovers, and W. J. Oyen, “Clinical application of FDG-PET/CT in metastatic infections,” Quarterly Journal of Nuclear Medicine and Molecular Imaging, vol. 61, no. 2, pp. 232–246, 2017.
View at: Publisher Site | Google Scholar
H. Balink, S. S. Tan, N. J. G. M. Veeger et al., “¹⁸F-FDG PET/CT in inflammation of unknown origin: a cost-effectiveness pilot-study,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 42, no. 9, pp. 1408–1413, 2015.
View at: Publisher Site | Google Scholar
E. M. Becerra Nakayo, A. M. García Vicente, A. M. Soriano Castrejón et al., “Análisis de costo-efectividad en el diagnóstico de fiebre de origen desconocido y el papel de la ¹⁸F-FDG PET-TC: propuesta de algoritmo diagnóstico,” Revista Española de Medicina Nuclear e Imagen Molecular, vol. 31, no. 4, pp. 178–186, 2012.
View at: Publisher Site | Google Scholar
F. J. Vos, C. P. Bleeker-Rovers, B. J. Kullberg, E. M. M. Adang, and W. J. G. Oyen, “Cost-effectiveness of routine ¹⁸F-FDG PET/CT in high-risk patients with gram-positive bacteremia,” Journal of Nuclear Medicine, vol. 52, no. 11, pp. 1673–1678, 2011.
View at: Publisher Site | Google Scholar
T. Ebenhan, E. Lazzeri, and O. Gheysens, “Imaging of bacteria: is there any hope for the future based on past experience?” Current Pharmaceutical Design, vol. 24, no. 7, pp. 772–786, 2018.
View at: Publisher Site | Google Scholar
S. Auletta, M. Varani, R. Horvat, F. Galli, A. Signore, and S. Hess, “PET radiopharmaceuticals for specific bacteria imaging: a systematic review,” Journal of Clinical Medicine, vol. 8, no. 2, p. 197, 2019.
View at: Publisher Site | Google Scholar
M. Meyer, N. Testart, M. Jreige et al., “Diagnostic performance of PET or PET/CT using ¹⁸F-FDG labeled white blood cells in infectious diseases: a systematic review and a bivariate meta-analysis,” Diagnostics, vol. 9, no. 2, p. 60, 2019.
View at: Publisher Site | Google Scholar
M. Pacilio, C. Lauri, D. Prosperi, A. Petitti, and A. Signore, “New SPECT and PET radiopharmaceuticals for imaging inflammatory diseases: a narrative review,” Seminars in Nuclear Medicine, vol. 48, no. 3, pp. 261–276, 2018.
View at: Publisher Site | Google Scholar
M. M. Sathekge, A. O. Ankrah, I. Lawal, and M. Vorster, “Monitoring response to therapy,” Seminars in Nuclear Medicine, vol. 48, no. 2, pp. 166–181, 2018.
View at: Publisher Site | Google Scholar
M. Sollini, R. Berchiolli, M. Kirienko et al., “PET/MRI in infection and inflammation,” Seminars in Nuclear Medicine, vol. 48, no. 3, pp. 225–241, 2018.
View at: Publisher Site | Google Scholar

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Copyright © 2019 Giorgio Treglia. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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