Advertisement

An update on the unparalleled impact of FDG-PET imaging on the day-to-day practice of medicine with emphasis on management of infectious/inflammatory disorders

  • Abass AlaviEmail author
  • Søren Hess
  • Thomas J. Werner
  • Poul Flemming Høilund-Carlsen
Editorial
Part of the following topical collections:
  1. Editorial

The concept of FDG-PET imaging was discussed for the first time among three investigators from the University of Pennsylvania, Abass Alavi, David Kuhl, and Martin Reivich, in the early 1970s [1]. These investigators had realized the potential for this novel radiolabeled compound in human research and clinical practice based on autoradiographic imaging studies using 14C-deoxyglucose in animals [1]. This initial discussion led to contacting chemists at the Brookhaven National Laboratory (BNL), which soon led to a joint effort to label deoxyglucose with 18F and determine its role by examining brain function in human beings. This investigation was led by Alfred Wolf and his colleagues at BNL and eventually, the compound was successfully synthesized and tested for toxicity before plans were made to image its distribution in human beings [2]. By mid-1976, an investigational new drug (IND) application was secured from the FDA for administering this radiotracer to normal human volunteers. Finally, in August 1976, the compound was shipped by a private plane to Philadelphia and successful images of the whole body by a conventional rectilinear scanner and tomographic images by a SPECT instrument were acquired by Abass Alavi at the University of Pennsylvania [3]. Soon thereafter, research protocols were drafted to determine the patterns of cerebral glucose metabolism with this compound in central nervous system disorders by Penn/BNL and UCLA investigators [4, 5]. The results from these early research studies conducted initially at these institutions and then later by a few other centers in the USA and Europe in the 1980s clearly demonstrated the great promise of FDG for both research and clinical applications.

In spite of the complexity and technical challenges that were faced by this demanding technology, over the past 4 decades, the role of this powerful imaging modality has been validated and well-established for assessing numerous disorders [6, 7]. Soon after its introduction, this approach was proven to be of great value in diagnosing Alzheimer’s disease with very high sensitivity and specificity which has remained unmatched by any other technique to date [8, 9, 10]. Other applications in the 1980s and 1990s included detection of seizure focus in temporal lobe epilepsy [11, 12, 13], vascular disorders [14], and a variety of neuropsychiatric diseases such as schizophrenia and manic depression [15, 16, 17, 18]. However, the major observation that was made from the early research studies in animal [19] and in human brain images with FDG was its critical role in detecting and characterizing malignant cells, particularly, brain tumors [20, 21]. These early research projects were carried out by investigators at BNL, Penn, and NIH. For the first time, the observation that was described by Warburg in the in vitro setting, where he was able to demonstrate high glycolytic activity of cancer cells compared with normal tissues, was verified by in vivo imaging with FDG [22, 23]. The latter further enhanced the potential for employing FDG-PET imaging to expand the horizons of this powerful methodology beyond central nervous system disorders.

In parallel with synthesis of FDG and testing its novel application in human diseases and disorders, efforts by Michael TerPogossian and colleagues at Washington University had resulted in designing and testing early PET instruments for imaging positron-based radiotracers [24]. The initial instruments provided images in a limited axial field of view and therefore were employed for assessing small organs such as the brain and the heart. By the early 1980s, efforts were made to assemble advanced instruments that could image the entire body with extended fields of view, which have been improved substantially over the past 3 decades [25].

Major advances that have been made in designing and building sophisticated PET instruments have further enhanced the impact of FDG-PET in many settings where imaging larger segments of the body along with structural data are essential for accurate diagnosis. In particular, the introductions of PET/CT in 2000 [26] and PET/MRI in 2008 [27] have substantially improved the performance of PET in disciplines such as radiation therapy and surgery. These instruments have allowed precise localization of FDG-positive targeted lesions.

The introduction of total-body PET imaging during the past year by investigators at UC Davis and Penn is expected to substantially enhance the role of this powerful modality even further [28]. This instrument allows imaging of the entire body within minutes and by administering substantially lower doses of FDG than the amounts currently being administered with limited field of view PET/CT scanners. Furthermore, total body imaging is going to allow for global disease assessment in serious diseases and disorders such as atherosclerosis, osteoporosis, vascular complications of many malignancies, and systemic inflammation including rheumatoid arthritis and psoriasis.

The synthesis of FDG, which was somewhat cumbersome and limited to academic institutions, was significantly simplified over the ensuing years and this has allowed rapid expansion of this technology to most advanced centers around the world. Since the 1990s, applications of FDG-PET have expanded to include imaging various malignancies and this has resulted in the acceptance of this technology by the oncologists for the diagnosis and treatment response following various therapeutic interventions [25]. By the mid-1990s, it was noted that FDG-PET imaging could potentially play a role in the detection of infection and aseptic inflammation due to a variety of disorders [29]. In the early 2000s, studies were reported describing FDG uptake in the atherosclerotic plaques in the aorta and other major arteries [30, 31]. Similarly, it was shown that clots in the venous system have substantial glycolytic activity and can be visualized by this technique [32, 33, 34]. In addition, detecting FDG uptake in the myocardium has been adopted for assessing myocardial viability before coronary artery bypass surgery [35, 36]. Therefore, over the past 2 decades, the domain for FDG-PET applications has expanded substantially and, in fact, the rate of expansion of this technology has exceeded that of any other modern imaging techniques in recent years [7]. Moreover, the molecular dimension and the ability to overlook major parts of the body in a single examination séance are going to change and improve our understanding of many diseases as exemplified by FDG-PET findings of significant vasculitis inside the body in what until now was considered a serious skin disease, namely psoriasis [37]. In addition, the superior sensitivity of PET and targeting at the molecular level opens for much earlier disease detection than with conventional structural imaging. A striking example of that is the detection of bone marrow instead of bone metastases by means of FDG-PET probably months or years before changes in the skeletal bone matrix become apparent by CT imaging, where they may persist even after active cancer cells are no longer present [38].

In contrast to CT and MRI, which were adopted without any hesitation, the medical community was reluctant to accept the validity of exploring PET as a viable modality for assessing any of the diseases and disorders enumerated above. In fact, early applications of PET were primarily supported by grants from the NIH, other government agencies, foundations, and institutional funding. It was not until 1998 when Medicare (US Government Insurance Agent) approved the use of this technology for characterizing lung nodules and for initial staging of non-small cell lung cancer (NSCLC). Fortunately, over the past decade, Medicare has expanded its coverage of PET for most malignancies and this has allowed rapid expansion of this technology particularly in the USA [39, 40]. In fact, without the latter initiative, PET would have never survived as a viable imaging technique. Unfortunately, clinical acceptance of FDG-PET as a very powerful method for assessing infection and inflammation has been somewhat slow and limited to centers where research funding has been secured from various agencies [41, 42, 43, 44, 45, 46, 47]. This is very disappointing since, based on reports that have appeared in the literature, FDG-PET imaging appears to be the most successful imaging approach for detection and characterization of many infectious and inflammatory disorders [7]. Efforts are being made to educate both the scientific and clinical communities about the unparalleled role of this technique in such domains.

Finally, FDG-PET is the most quantitative imaging technique for assessing disease activity in medicine, and as such, it contributes enormously to determine the course of disease and the effectiveness of various interventions [48]. Particularly, its ability to provide a single value as evidence for global disease activity is essential for overall assessment of multiple benign and malignant disorders [49]. Previously, the mentioned limited fields of view was a hindrance to such overall assessments, but with the extended fields of modern scanners, their higher sensitivity and correspondingly shorter image acquisition times, not to mention the advent of the total-body PET scanner [28], the concept of providing a global disease score (GDS) representing the extension and severity of disease in part of (D) or in the total body has come into reach as illustrated in Fig. 1 in a HIV/TB-positive patient. Until recently, to provide such scores have often been too time-consuming for application in the daily routine since it requires careful segmentation of all disease areas and lesions in the body, which implies great observer experience and, in particular, when it comes to small lesions, correction for partial volume effect. However, with the rapid introduction of artificial intelligence-based systems for quantitative, observer-independent processing of PET images in seconds or a few minutes, overall disease assessment will become a major target for future clinical research and implementation [49].
Fig. 1

Baseline (a, b) and follow-up (c, d) maximum intensity projection (MIP) PET images of an HIV/TB-positive patient. The lung lesion decreased in size and disease activity following 2 months of antiretroviral therapy (black arrows). Coincident with response to treatment in the lung lesion, an increased lymph node reaction was observed on FDG-PET scan (red arrows). The FDG-avid lung inflammatory site was segmented semi-automatically using an adaptive contrast-oriented thresholding system (ROVER; ABBX, Radeberg, Germany). The values for metabolic tumor volume (MTV), SUVmean, partial volume corrected SUVmean (pvcSUVmean), SUVmax, total lesion glycolysis (TLG), and partial volume corrected total lesion glycolysis (pvcTLG) at the baseline and the follow-up are noted in the table. (These images are courtesy of Professor Mboyo-Di-Tamba Vangu, University of the Witwatersrand, Johannesburg)

In this review, we will describe in great detail the role of FDG in a variety of infectious and inflammatory disorders.

Early in the history of FDG-PET imaging, occasional reports of false-positive findings due to infection or inflammation in patients with malignant tumors were a nuisance to oncologists who had to realize that FDG was not a cancer-specific tracer [50]. It has now been established that this is because cells involved in the inflammatory response (e.g., neutrophils, macrophages, and activated leukocytes) similar to malignant cells often express high levels of glucose transporters. In addition, circulating cytokines seem to increase the affinity of these glucose transporters for FDG [51, 52]. Tahara et al. reported on the first cases using FDG directly for imaging infection with increased accumulation in abdominal abscesses in humans [53], and since then, there has been a growing interest in using PET and PET/CT for the study of infectious and inflammatory diseases [29, 54, 55]. Generally speaking, the use of FDG and PET in infectious and inflammatory diseases can be divided into systemic whole-body diseases and focused, organ- or symptom-specific diagnostics.

In the former category falls one of the most well-established indications, namely fever of unknown origin (FUO), a heterogeneous group of diseases with a multitude of differential diagnoses, i.e., infectious, malignant, or inflammatory diseases all with an element of hypermetabolism. Patients often present with unspecific symptoms and few diagnostic clues, and it may be challenging to reach an etiologic diagnosis [56, 57]. Whole-body FDG-PET/CT is sensitive in guiding the clinician towards more specific investigations and provides clinically helpful and important information towards reaching a diagnosis in overall 50–60% of patients (i.e., 42–92% of cases depending on how the authors define “helpful”), substantially better than any other diagnostic procedure [58, 59]. Also, one must remember that the underlying studies usually include patients without a firm diagnosis after a multitude of other diagnostic procedures, i.e., often the most difficult patients.

Another challenging whole-body ailment is bacteremia of unknown origin; early studies found clinically relevant findings in up to half of patients with bacteremia of unknown origin or suspected metastatic spread with high positive and negative predictive values [60, 61] and established FDG-PET/CT to be cost-effective due to significantly lower relapse rates and mortality [62, 63]. More recent studies have corroborated these initial findings in heterogeneous settings of bacteremia of unknown origin with PET leading to change in clinical management in half of the patients, also after prolonged febrile periods in patients heavily pretreated with antibiotics [64]. FDG-PET/CT has also been shown to have a direct therapeutic consequence in one-third of critically ill septicemic patients with unknown etiology [65], and high sensitivity and significant clinical impact in 53–75% of immunocompromised patients with febrile neutropenia [66, 67]. Another entity with potential metastatic infection is infective endocarditis (IE), especially prosthetic valve endocarditis; focal FDG uptake in the valve area may be indicative of endocarditis, often an incidental finding in FUO or equivocal cases, but imaging the heart is difficult without prolonged fasting due to the physiologic myocardial uptake of FDG; thus, FDG-PET may better contribute in infective endocarditis by detecting clinically occult metastatic infectious foci, as an adjunct to echocardiography in equivocal cases, or in suspected cardiac device infection [68, 69, 70, 71].

Looking at more specific indications, FDG-PET/CT is second to none in chronic osteomyelitis; a meta-analysis pooling data from 23 studies found FDG-PET had the highest accuracy in diagnosing and excluding chronic osteomyelitis, with a sensitivity of 96% and a specificity of 91%, compared with 78% and 84% with combined bone and leucocyte scintigraphy, and 84% and 60% with MRI [72]. Similarly, with spondylodiscitis, a meta-analysis found sensitivity and specificity of 97% and 88%, respectively [73], and a recent study established that FDG-PET/CT is especially adept in the early phase with sensitivity of 96% compared with 50% with MRI within the first 2 weeks after symptom debut [74]. Although it only represents 2–4% of osteomyelitis cases, structural imaging may be insufficient in spondylodiscitis, because morphologic changes are often nonspecific and discrimination between infection and degenerative changes is challenging. Although the specificity of FDG-PET may be lower in the initial postoperative period due to unspecific inflammation [75], excellent results are achievable in patients with suspected spinal infection related to metallic implants, i.e., overall sensitivity, specificity, and accuracy in the range of 94–100%, 87–93%, and 91–97%, respectively, with corresponding results for patients with metallic implants: 91%, 71%, and 83%, respectively—in one study, FDG-PET was found to increase the physician’s confidence, which added significantly to the clinical decision-making process and treatment strategy in two-thirds of patients [76, 77].

FDG-PET has also been employed in the diagnosis of prosthetic joint infections. Although still controversial, several meta-analyses as well as prospective comparisons have demonstrated more robust results with FDG-PET (i.e., pooled sensitivity and specificity of 70–95% and 84–93%, respectively) compared with combinations of white blood cell scintigraphy and bone marrow scintigraphy (i.e., pooled sensitivity and specificity of 33–80% and 93–96%, respectively) [47, 78, 79, 80, 81].

Finally, several studies have pointed to FDG-PET as a useful modality in the diagnostic challenging diabetic foot. One study reported lower sensitivity but higher specificity and accuracy with FDG-PET than with MRI [82], while another found both higher sensitivity and accuracy with FDG-PET, concluding that this method was able to reliably differentiate Charcot’s neuroarthropathy from osteomyelitis [45]. A recent prospective study found that FDG-PET/CT imaging of the diabetic foot had a sensitivity, specificity, and accuracy of 100%, 92%, and 95%, respectively, in the diagnosis of osteomyelitis [83].

Vascular graft infection is a rare but serious complication carrying high mortality and morbidity with a substantial risk of limb loss or death [84, 85]. It is often difficult to distinguish morphologically between graft infection, non-infected hematoma, and lymphocele. While CT has low sensitivity in low-grade infections, FDG-PET may lack specificity. In the first hybrid PET/CT study, Keidar et al. found excellent sensitivity and specificity of 93% and 91%, respectively [86]. Whereas subsequent studies generally confirmed the high sensitivity, specificities varied considerably, i.e., two recent meta-analyses found pooled sensitivities and specificities of 95–97% and 80–89%, respectively, with confidence intervals for specificities ranging from 69–96%. Even so, FDG-PET/CT generally performs much better than CT with several studies finding both sensitivities and specificities in the 55–65% range only [85, 87]. However, several caveats pertain to the available FDG-PET literature, e.g., patient populations are generally a heterogeneous mix of acute and chronic, low-grade infections, various graft types, and most are heavily pretreated with antibiotics. Also, methodologies are generally suboptimal with regard to a reference standard and a lack of consensus on interpretation strategy.

Due to the nonspecific nature of FDG, more infection-specific tracers are desirable. A multitude of alternative candidates has been assessed preclinically, including several different isotopes (e.g., 64Cu, 68Ga, and 124I). Although results have been promising and scientifically interesting, a recent systematic review established a significant lack of standardization in the preclinical settings and that only few have been translated into humans and with disappointing results [88].

Besides mere diagnosis, the use of FDG-PET/CT for response evaluations of treatments for infectious diseases has also been explored, albeit to a much lesser extent than in malignant diseases, e.g., spondylodiscitis [89], vascular graft infections [90, 91], and tuberculosis [92]; results have been promising, but further and larger prospective studies are warranted in this setting.

Non-infectious inflammation is also FDG-avid by mechanisms similar to those of infectious diseases, i.e., higher glucose transporter expression in inflammatory cells and increased affinity of the glucose transporters for FDG under the influence of circulating cytokines [46, 93]. Most validated clinically is vasculitis characterized by inflammation and necrosis of the vessel wall, most commonly affects large- and medium-sized arteries, e.g., giant cell arteritis (GCA) and Takayasu’s arteritis [94]. In GCA, biopsy of the temporal artery remains the reference standard, but false-negative results are seen in as many as 40% of patients [93]. Furthermore, a significant proportion of patients have extra-cranial disease manifestations, and thus, imaging remains important to help locate suitable biopsy sites and assess disease extent and response to treatment. Evidence on FDG-PET in GCA is mounting, and recent systematic reviews have found sensitivities and specificities of 80–90% and 89–98% [95, 96], respectively, in GCA, and 70–87% and 73–84%, respectively, in Takayasu’s arteritis [96, 97, 98]. Earlier studies underlined problems with visualizing the smaller arteries in the head-and-neck including the temporal artery because of its small caliber and proximity to physiologic uptake in the adjacent brain, but a recent study found high diagnostic accuracy for GCA using a dichotomous assessment of FDG uptake in cranial arteries [99]. A well-known pitfall is glucocorticoid treatment known to hamper FDG uptake and leading to false-negative scans, but another recent study found remaining high sensitivity within the first 3 days of high-dose glucocorticoids, whereas sensitivity was significantly reduced after 10-day treatment [100]. Polymyalgia rheumatica is a systemic disease entity characterized by soft tissue inflammation, synovitis, and bursitis, and is often associated with large-vessel vasculitis. As with GCA, available imaging has been sparse, but in recent years, several reports have proposed several well-defined anatomical areas related to bursae and axial joints where increased FDG uptake is associated with polymyalgia rheumatica [101, 102, 103].

Reports on FDG uptake in sarcoidosis emerged in the early 1990s, and whole-body FDG-PET is a sensitive marker of sarcoidosis activity [104, 105]. Although not the modality of choice in the initial diagnostic workup due to its inability to differentiate benign granulomatous disease from lymphoma, a systematic review identified nine studies with a total of 379 patients and reported great potential in several areas, e.g., assessing disease activity and thus aiding the monitoring of treatment response as early as 6 weeks following initiation of therapy, and for staging and detection of sites that are clinically occult [106]. Also, FDG may have a role in cardiac sarcoidosis, but the same caveats as with infective endocarditis apply, i.e., patient preparation is pivotal to suppress physiologic uptake in the myocardium [107, 108].

Several other inflammatory diseases have been suggested and investigated using FDG-PET with potential, but evidence is still equivocal. These include inflammatory bowel disease where physiologic FDG uptake may complicate matters, but two meta-analyses found overall sensitivity and specificity of 84–85% and 86–87%, respectively [109, 110]. A possible application is a differentiation between inflammatory and fibrostenotic strictures with obvious advantages for treatment planning and avoiding invasive surgical procedures [111]. All of this could be of special significance in pediatric inflammatory bowel disease [112]. Also, FDG has been suggested to detect and assess inflammatory joint disorders [113], also for monitoring treatment response because morphologic assessment of synovial thickening is difficult [114], but important with the effective but expensive new biological drugs that may present serious side effects [115]. Finally, FDG has been proposed in venous thromboembolism (VTE) as commonly used diagnostic imaging techniques do not address some of the important aspects of this disease [32]: VTE may present in the entire venous vasculature, but routine imaging only assesses lower extremity veins and pulmonary arteries; an underlying disease like cancer is often a key factor in the development of VTE, but patients are not examined routinely to disclose this; and differentiating acute from chronic VTE is impossible by routine imaging, but has profound influence on treatment strategy. A recent systematic review has summarized the potential within all of the mentioned domains, but the literature is still too sparse for firm conclusions [116].

The enormous impact of FDG-PET imaging on many disciplines of medicine competes with any other major development to date. The increasing number of newer applications of FDG for assessing diseases beyond cancer has significantly improved patient care far beyond any other imaging technique over the past decades. As it becomes more and more evident that contrast agents designed for CT and MRI are associated with serious side effects, it is conceivable that FDG will be used in place of these radiologic contrast agents in the future. In addition, the introduction of FDG has resulted in the survival of PET as an imaging modality and made PET as the most powerful imaging technique to assess disease processes at the molecular level. Furthermore, the survival of PET as such a powerful modality has resulted in the development of new radiotracers that are revolutionizing our ability to assess many diseases and disorders at the molecular level. These advances are going to be essential for characterizing the underlying causes of numerous maladies and developing potential approaches for therapeutic interventions. As such, it may be appropriate to portray the introduction of FDG-PET to medicine as compared with that of X-ray by Roentgen in 1895 (Fig. 2).
Fig. 2

Introduction of X-ray to medicine by Röntgen in 1895 (left) has had a substantial impact on the day-to-day practice of medicine. Similarly, imaging with FDG (right) has been another major step forward by enhancing the role of medical imaging and this has led to an unparalleled impact on both research and patient care

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Alavi A, Reivich M. Guest editorial: the conception of FDG-PET imaging. Semin Nucl Med. 2002;32:2–5.  https://doi.org/10.1053/snuc.2002.29269.CrossRefPubMedGoogle Scholar
  2. 2.
    Ido T, Wan C-N, Casella V, Fowler JS, Wolf AP, Reivich M, et al. Labeled 2-deoxy-D-glucose analogs. 18F-labeled 2-deoxy-2-fluoro-D-glucose, 2-deoxy-2-fluoro-D-mannose and 14C-2-deoxy-2-fluoro-D-glucose. J Label Compd Radiopharm. 1978;14:175–83.  https://doi.org/10.1002/jlcr.2580140204.CrossRefGoogle Scholar
  3. 3.
    Hess S, Hoilund-Carlsen PF, Alavi A. Historic images in nuclear medicine: 1976: the first issue of clinical nuclear medicine and the first human FDG study. Clin Nucl Med. 2014;39:701–3.  https://doi.org/10.1097/rlu.0000000000000487.CrossRefPubMedGoogle Scholar
  4. 4.
    Alavi A, Reivich M, Greenberg J, Hand P, Rosenquist A, Rintelmann W, et al. Mapping of functional activity in brain with 18F-fluoro-deoxyglucose. Semin Nucl Med. 1981;11:24–31.CrossRefGoogle Scholar
  5. 5.
    Alavi A, Hirsch LJ. Studies of central nervous system disorders with single photon emission computed tomography and positron emission tomography: evolution over the past 2 decades. Semin Nucl Med. 1991;21:58–81.CrossRefGoogle Scholar
  6. 6.
    Basu S, Alavi A. Unparalleled contribution of 18F-FDG PET to medicine over 3 decades. J Nucl Med. 2008;49:17N–21N 37N.CrossRefGoogle Scholar
  7. 7.
    Hess S, Blomberg BA, Zhu HJ, Hoilund-Carlsen PF, Alavi A. The pivotal role of FDG-PET/CT in modern medicine. Acad Radiol. 2014;21:232–49.  https://doi.org/10.1016/j.acra.2013.11.002.CrossRefPubMedGoogle Scholar
  8. 8.
    Khosravi M, Newberg A, Alavi A. Cognitive impairment and dementias. Semin Nucl Med. 2018;48:498–512.  https://doi.org/10.1053/j.semnuclmed.2018.07.005.CrossRefPubMedGoogle Scholar
  9. 9.
    Khosravi M, Peter J, Wintering NA, Serruya M, Shamchi SP, Werner TJ, et al. 18F-FDG is a superior indicator of cognitive performance compared to 18F-florbetapir in Alzheimer’s disease and mild cognitive impairment evaluation: a global quantitative analysis. J Alzheimers Dis. 2019.  https://doi.org/10.3233/jad-190220.CrossRefGoogle Scholar
  10. 10.
    Hoilund-Carlsen PF, Barrio JR, Gjedde A, Werner TJ, Alavi A. Circular inference in dementia diagnostics. J Alzheimers Dis. 2018;63:69–73.  https://doi.org/10.3233/jad-180050.CrossRefPubMedGoogle Scholar
  11. 11.
    Meyer PT, Cortes-Blanco A, Pourdehnad M, Levy-Reis I, Desiderio L, Jang S, et al. Inter-modality comparisons of seizure focus lateralization in complex partial seizures. Eur J Nucl Med. 2001;28:1529–40.  https://doi.org/10.1007/s002590100602.CrossRefPubMedGoogle Scholar
  12. 12.
    Wolf RL, Alsop DC, Levy-Reis I, Meyer PT, Maldjian JA, Gonzalez-Atavales J, et al. Detection of mesial temporal lobe hypoperfusion in patients with temporal lobe epilepsy by use of arterial spin labeled perfusion MR imaging. AJNR Am J Neuroradiol. 2001;22:1334–41.PubMedGoogle Scholar
  13. 13.
    Peter J, Houshmand S, Werner TJ, Rubello D, Alavi A. Novel assessment of global metabolism by 18F-FDG-PET for localizing affected lobe in temporal lobe epilepsy. Nucl Med Commun. 2016;37:882–7.  https://doi.org/10.1097/mnm.0000000000000526.CrossRefPubMedGoogle Scholar
  14. 14.
    Moghbel M, Al-Zaghal A, Werner TJ, Constantinescu CM, Hoilund-Carlsen PF, Alavi A. The role of PET in evaluating atherosclerosis: a critical review. Semin Nucl Med. 2018;48:488–97.  https://doi.org/10.1053/j.semnuclmed.2018.07.001.CrossRefPubMedGoogle Scholar
  15. 15.
    Kumar A, Newberg A, Alavi A, Berlin J, Smith R, Reivich M. Regional cerebral glucose metabolism in late-life depression and Alzheimer disease: a preliminary positron emission tomography study. Proc Natl Acad Sci U S A. 1993;90:7019–23.CrossRefGoogle Scholar
  16. 16.
    Gur RE, Resnick SM, Alavi A, Gur RC, Caroff S, Dann R, et al. Regional brain function in schizophrenia. I. A positron emission tomography study. Arch Gen Psychiatry. 1987;44:119–25.  https://doi.org/10.1001/archpsyc.1987.01800140021003. CrossRefPubMedGoogle Scholar
  17. 17.
    Gur RE, Resnick SM, Gur RC, Alavi A, Caroff S, Kushner M, et al. Regional brain function in schizophrenia. II. Repeated evaluation with positron emission tomography. Arch Gen Psychiatry. 1987;44:126–9.  https://doi.org/10.1001/archpsyc.1987.01800140028004. CrossRefPubMedGoogle Scholar
  18. 18.
    Resnick SM, Gur RE, Alavi A, Gur RC, Reivich M. Positron emission tomography and subcortical glucose metabolism in schizophrenia. Psychiatry Res. 1988;24:1–11.CrossRefGoogle Scholar
  19. 19.
    Som P, Atkins HL, Bandoypadhyay D, Fowler JS, MacGregor RR, Matsui K, et al. A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection. J Nucl Med. 1980;21:670–5.PubMedGoogle Scholar
  20. 20.
    Alavi JB, Alavi A, Chawluk J, Kushner M, Powe J, Hickey W, et al. Positron emission tomography in patients with glioma. A predictor of prognosis. Cancer. 1988;62:1074–8.CrossRefGoogle Scholar
  21. 21.
    Patronas NJ, Di Chiro G, Kufta C, Bairamian D, Kornblith PL, Simon R, et al. Prediction of survival in glioma patients by means of positron emission tomography. J Neurosurg. 1985;62:816–22.  https://doi.org/10.3171/jns.1985.62.6.0816.CrossRefPubMedGoogle Scholar
  22. 22.
    Warburg O. On the origin of cancer cells. Science (New York, NY). 1956;123:309–14.CrossRefGoogle Scholar
  23. 23.
    Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8:519–30.CrossRefGoogle Scholar
  24. 24.
    Ter-Pogossian MM, Phelps ME, Hoffman EJ, Mullani NA. A positron-emission transaxial tomograph for nuclear imaging (PETT). Radiology. 1975;114:89–98.  https://doi.org/10.1148/114.1.89.CrossRefPubMedGoogle Scholar
  25. 25.
    Hustinx R, Benard F, Alavi A. Whole-body FDG-PET imaging in the management of patients with cancer. Semin Nucl Med. 2002;32:35–46.  https://doi.org/10.1053/snuc.2002.29272.CrossRefPubMedGoogle Scholar
  26. 26.
    Beyer T, Townsend DW, Brun T, Kinahan PE, Charron M, Roddy R, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med. 2000;41:1369–79.PubMedGoogle Scholar
  27. 27.
    Antoch G, Bockisch A. Combined PET/MRI: a new dimension in whole-body oncology imaging? Eur J Nucl Med Mol Imaging. 2009;36(Suppl 1):S113–20.  https://doi.org/10.1007/s00259-008-0951-6. CrossRefPubMedGoogle Scholar
  28. 28.
    Badawi RD, Shi H, Hu P, Chen S, Xu T, Price PM, et al. First human imaging studies with the EXPLORER Total-Body PET Scanner. J Nucl Med. 2019;60:299–303.  https://doi.org/10.2967/jnumed.119.226498.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Zhuang H, Alavi A. 18-fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation. Semin Nucl Med. 2002;32:47–59.  https://doi.org/10.1053/snuc.2002.29278.CrossRefPubMedGoogle Scholar
  30. 30.
    Yun M, Yeh D, Araujo LI, Jang S, Newberg A, Alavi A. F-18 FDG uptake in the large arteries: a new observation. Clin Nucl Med. 2001;26:314–9.CrossRefGoogle Scholar
  31. 31.
    Yun M, Jang S, Cucchiara A, Newberg AB, Alavi A. 18F FDG uptake in the large arteries: a correlation study with the atherogenic risk factors. Semin Nucl Med. 2002;32:70–6.  https://doi.org/10.1053/snuc.2002.29279.CrossRefPubMedGoogle Scholar
  32. 32.
    Hess S, Madsen PH, Basu S, Hoilund-Carlsen PF, Alavi A. Potential role of FDG PET/CT imaging for assessing venous thromboembolic disorders. Clin Nucl Med. 2012;37:1170–2.  https://doi.org/10.1097/RLU.0b013e318279bf73.CrossRefPubMedGoogle Scholar
  33. 33.
    Sydow BD, Srinivas SM, Newberg A, Alavi A. Deep venous thrombosis on F-18 FDG PET/CT imaging. Clin Nucl Med. 2006;31:403–4.  https://doi.org/10.1097/01.rlu.0000222950.98284.94.CrossRefPubMedGoogle Scholar
  34. 34.
    Sharma P, Kumar R, Singh H, Jeph S, Patnecha M, Reddy RM, et al. Imaging thrombus in cancer patients with FDG PET-CT. Jpn J Radiol. 2012;30:95–104.  https://doi.org/10.1007/s11604-011-0016-9.CrossRefPubMedGoogle Scholar
  35. 35.
    Schelbert HR, Henze E, Phelps ME, Kuhl DE. Assessment of regional myocardial ischemia by positron-emission computed tomography. Am Heart J. 1982;103:588–97.CrossRefGoogle Scholar
  36. 36.
    Schelbert HR, Schwaiger M. Positron emission tomography in human myocardial ischemia. Herz. 1987;12:22–40.PubMedGoogle Scholar
  37. 37.
    Mehta NN, Yu Y, Saboury B, Foroughi N, Krishnamoorthy P, Raper A, et al. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT): a pilot study. Arch Dermatol. 2011;147:1031–9.  https://doi.org/10.1001/archdermatol.2011.119.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Hoilund-Carlsen PF, Hess S, Werner TJ, Alavi A. Cancer metastasizes to the bone marrow and not to the bone: time for a paradigm shift! Eur J Nucl Med Mol Imaging. 2018;45:893–7.  https://doi.org/10.1007/s00259-018-3959-6.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Coleman RE, Hillner BE, Shields AF, Duan F, Merlino DA, Hanna LG, et al. PET and PET/CT reports: observations from the National Oncologic PET Registry. J Nucl Med. 2010;51:158–63.  https://doi.org/10.2967/jnumed.109.066399.CrossRefPubMedGoogle Scholar
  40. 40.
    Siegel BA. Cassen Lecture: what have we learned from the National Oncologic PET Registry? J Nucl Med. 2014;55:9n–15n.CrossRefGoogle Scholar
  41. 41.
    Zhuang H, Duarte PS, Pourdehnad M, Maes A, Van Acker F, Shnier D, et al. The promising role of 18F-FDG PET in detecting infected lower limb prosthesis implants. J Nucl Med. 2001;42:44–8.PubMedGoogle Scholar
  42. 42.
    Hochhold J, Yang H, Zhuang H, Alavi A. Application of 18F-fluorodeoxyglucose and PET in evaluation of the diabetic foot. PET Clin. 2006;1:123–30.  https://doi.org/10.1016/j.cpet.2006.03.001.CrossRefPubMedGoogle Scholar
  43. 43.
    Kumar R, Basu S, Torigian D, Anand V, Zhuang H, Alavi A. Role of modern imaging techniques for diagnosis of infection in the era of 18F-fluorodeoxyglucose positron emission tomography. Clin Microbiol Rev. 2008;21:209–24.  https://doi.org/10.1128/cmr.00025-07.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Basu S, Zhuang H, Alavi A. FDG PET and PET/CT Imaging in complicated diabetic foot. PET Clin. 2012;7:151–60.  https://doi.org/10.1016/j.cpet.2012.01.003.CrossRefPubMedGoogle Scholar
  45. 45.
    Basu S, Chryssikos T, Houseni M, Scot Malay D, Shah J, Zhuang H, et al. Potential role of FDG PET in the setting of diabetic neuro-osteoarthropathy: can it differentiate uncomplicated Charcot’s neuroarthropathy from osteomyelitis and soft-tissue infection? Nucl Med Commun. 2007;28:465–72.  https://doi.org/10.1097/MNM.0b013e328174447f.CrossRefPubMedGoogle Scholar
  46. 46.
    Basu S, Chryssikos T, Moghadam-Kia S, Zhuang H, Torigian DA, Alavi A. Positron emission tomography as a diagnostic tool in infection: present role and future possibilities. Semin Nucl Med. 2009;39:36–51.  https://doi.org/10.1053/j.semnuclmed.2008.08.004.CrossRefPubMedGoogle Scholar
  47. 47.
    Basu S, Kwee TC, Saboury B, Garino JP, Nelson CL, Zhuang H, et al. FDG PET for diagnosing infection in hip and knee prostheses: prospective study in 221 prostheses and subgroup comparison with combined (111)in-labeled leukocyte/(99m)Tc-sulfur colloid bone marrow imaging in 88 prostheses. Clin Nucl Med. 2014;39:609–15.  https://doi.org/10.1097/rlu.0000000000000464. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Houshmand S, Salavati A, Hess S, Werner TJ, Alavi A, Zaidi H. An update on novel quantitative techniques in the context of evolving whole-body PET imaging. PET Clin. 2015;10:45–58.  https://doi.org/10.1016/j.cpet.2014.09.004.CrossRefPubMedGoogle Scholar
  49. 49.
    Hoilund-Carlsen PF, Edenbrandt L, Alavi A. Global disease score (GDS) is the name of the game! Eur J Nucl Med Mol Imaging. 2019;46:1768–72.  https://doi.org/10.1007/s00259-019-04383-8.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Larson SM. Cancer or inflammation? A Holy Grail for nuclear medicine. J Nucl Med. 1994;35:1653–5.PubMedGoogle Scholar
  51. 51.
    Yamada S, Kubota K, Kubota R, Ido T, Tamahashi N. High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med. 1995;36:1301–6.PubMedGoogle Scholar
  52. 52.
    Sugawara Y, Gutowski TD, Fisher SJ, Brown RS, Wahl RL. Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, L-methionine, 67Ga-citrate, and 125I-HSA. Eur J Nucl Med. 1999;26:333–41.CrossRefGoogle Scholar
  53. 53.
    Tahara T, Ichiya Y, Kuwabara Y, Otsuka M, Miyake Y, Gunasekera R, et al. High [18F]-fluorodeoxyglucose uptake in abdominal abscesses: a PET study. J Comput Assist Tomogr. 1989;13:829–31.CrossRefGoogle Scholar
  54. 54.
    Hess S, Alavi A, Basu S. PET-based personalized management of infectious and inflammatory disorders. PET Clin. 2016;11:351–61.  https://doi.org/10.1016/j.cpet.2016.02.008.CrossRefPubMedGoogle Scholar
  55. 55.
    Zhuang H, Yu JQ, Alavi A. Applications of fluorodeoxyglucose-PET imaging in the detection of infection and inflammation and other benign disorders. Radiol Clin N Am. 2005;43:121–34.  https://doi.org/10.1016/j.rcl.2004.07.005.CrossRefPubMedGoogle Scholar
  56. 56.
    Knockaert DC, Vanderschueren S, Blockmans D. Fever of unknown origin in adults: 40 years on. J Intern Med. 2003;253:263–75.CrossRefGoogle Scholar
  57. 57.
    Al-Zaghal A, Raynor WY, Seraj SM, Werner TJ, Alavi A. FDG-PET imaging to detect and characterize underlying causes of fever of unknown origin: an unavoidable path for the foreseeable future. Eur J Nucl Med Mol Imaging. 2019;46:2–7.  https://doi.org/10.1007/s00259-018-4164-3.CrossRefPubMedGoogle Scholar
  58. 58.
    Israel O, Keidar Z. PET/CT imaging in infectious conditions. Ann N Y Acad Sci. 2011;1228:150–66.  https://doi.org/10.1111/j.1749-6632.2011.06026.x.CrossRefPubMedGoogle Scholar
  59. 59.
    Hess SHS, Pedersen KT, Basu S, Høilund-Carlsen PF. FDG-PET/CT in infectious and inflammatory diseases. PET Clin. 2014;9:497–519.CrossRefGoogle Scholar
  60. 60.
    Bleeker-Rovers CP, Vos FJ, Wanten GJ, van der Meer JW, Corstens FH, Kullberg BJ, et al. 18F-FDG PET in detecting metastatic infectious disease. J Nucl Med. 2005;46:2014–9.PubMedGoogle Scholar
  61. 61.
    Hess S, Vind SH, Skarphedinsson S, Pedersen C, Kolmos HJ, Gerke O, et al. Clinical value of PET/CT in bacteraemia of unknown origin. Results from an observational pilot study. Eur J Nucl Med Mol Imaging. 2010;37:S468.  https://doi.org/10.1007/s00259-010-1559-1.CrossRefGoogle Scholar
  62. 62.
    Vos FJ, Bleeker-Rovers CP, Kullberg BJ, Adang EM, Oyen WJ. Cost-effectiveness of routine (18)F-FDG PET/CT in high-risk patients with gram-positive bacteremia. J Nucl Med. 2011;52:1673–8.  https://doi.org/10.2967/jnumed.111.089714. CrossRefPubMedGoogle Scholar
  63. 63.
    Vos FJ, Bleeker-Rovers CP, Sturm PD, Krabbe PF, van Dijk AP, Cuijpers ML, et al. 18F-FDG PET/CT for detection of metastatic infection in gram-positive bacteremia. J Nucl Med. 2010;51:1234–40.  https://doi.org/10.2967/jnumed.109.072371. CrossRefPubMedGoogle Scholar
  64. 64.
    Brondserud MB, Pedersen C, Rosenvinge FS, Hoilund-Carlsen PF, Hess S. Clinical value of FDG-PET/CT in bacteremia of unknown origin with catalase-negative gram-positive cocci or Staphylococcus aureus. Eur J Nucl Med Mol Imaging. 2019;46:1351–8.  https://doi.org/10.1007/s00259-019-04289-5.CrossRefPubMedGoogle Scholar
  65. 65.
    Kluge S, Braune S, Nierhaus A, Wichmann D, Derlin T, Mester J, et al. Diagnostic value of positron emission tomography combined with computed tomography for evaluating patients with septic shock of unknown origin. J Crit Care. 2012;27:316 e1–7.  https://doi.org/10.1016/j.jcrc.2011.10.004.CrossRefGoogle Scholar
  66. 66.
    Guy SD, Tramontana AR, Worth LJ, Lau E, Hicks RJ, Seymour JF, et al. Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients. Eur J Nucl Med Mol Imaging. 2012;39:1348–55.  https://doi.org/10.1007/s00259-012-2143-7.CrossRefPubMedGoogle Scholar
  67. 67.
    Gafter-Gvili A, Paul M, Bernstine H, Vidal L, Ram R, Raanani P, et al. The role of (1)(8)F-FDG PET/CT for the diagnosis of infections in patients with hematological malignancies and persistent febrile neutropenia. Leuk Res. 2013;37:1057–62.  https://doi.org/10.1016/j.leukres.2013.06.025.CrossRefPubMedGoogle Scholar
  68. 68.
    Rewers KISA, Thomassen A, Hess S. The role of 18F-FDG-PET/CT in infectious endocarditis and cardiac device infection. Curr Mol Imaging. 2014;3.Google Scholar
  69. 69.
    Scholtens AM, Budde RPJ, Lam M, Verberne HJ. FDG PET/CT in prosthetic heart valve endocarditis: there is no need to wait. J Nucl Cardiol. 2017;24:1540–1.  https://doi.org/10.1007/s12350-017-0938-4. CrossRefPubMedGoogle Scholar
  70. 70.
    Scholtens AM, Swart LE, Verberne HJ, Tanis W, Lam MG, Budde RP. Confounders in FDG-PET/CT imaging of suspected prosthetic valve endocarditis. J Am Coll Cardiol Img. 2016;9:1462–5.  https://doi.org/10.1016/j.jcmg.2016.01.024.CrossRefGoogle Scholar
  71. 71.
    Millar BC, Prendergast BD, Alavi A, Moore JE. (18)FDG-positron emission tomography (PET) has a role to play in the diagnosis and therapy of infective endocarditis and cardiac device infection. Int J Cardiol. 2013;167:1724–36.  https://doi.org/10.1016/j.ijcard.2012.12.005.CrossRefPubMedGoogle Scholar
  72. 72.
    Termaat MF, Raijmakers PG, Scholten HJ, Bakker FC, Patka P, Haarman HJ. The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-analysis. J Bone Joint Surg Am. 2005;87:2464–71.  https://doi.org/10.2106/jbjs.d.02691. CrossRefPubMedGoogle Scholar
  73. 73.
    Prodromou ML, Ziakas PD, Poulou LS, Karsaliakos P, Thanos L, Mylonakis E. FDG PET is a robust tool for the diagnosis of spondylodiscitis: a meta-analysis of diagnostic data. Clin Nucl Med. 2014.  https://doi.org/10.1097/rlu.0000000000000336.CrossRefGoogle Scholar
  74. 74.
    Smids C, Kouijzer IJ, Vos FJ, Sprong T, Hosman AJ, de Rooy JW, et al. A comparison of the diagnostic value of MRI and (18)F-FDG-PET/CT in suspected spondylodiscitis. Infection. 2017;45:41–9.  https://doi.org/10.1007/s15010-016-0914-y.CrossRefPubMedGoogle Scholar
  75. 75.
    De Winter F, Gemmel F, Van De Wiele C, Poffijn B, Uyttendaele D, Dierckx R. 18-Fluorine fluorodeoxyglucose positron emission tomography for the diagnosis of infection in the postoperative spine. Spine. 2003;28:1314–9.  https://doi.org/10.1097/01.brs.0000065483.07790.34. CrossRefPubMedGoogle Scholar
  76. 76.
    Schiesser M, Stumpe KD, Trentz O, Kossmann T, Von Schulthess GK. Detection of metallic implant-associated infections with FDG PET in patients with trauma: correlation with microbiologic results. Radiology. 2003;226:391–8.  https://doi.org/10.1148/radiol.2262011939.CrossRefPubMedGoogle Scholar
  77. 77.
    Hartmann A, Eid K, Dora C, Trentz O, von Schulthess GK, Stumpe KD. Diagnostic value of 18F-FDG PET/CT in trauma patients with suspected chronic osteomyelitis. Eur J Nucl Med Mol Imaging. 2007;34:704–14.  https://doi.org/10.1007/s00259-006-0290-4.CrossRefPubMedGoogle Scholar
  78. 78.
    Kwee TC, Kwee RM, Alavi A. FDG-PET for diagnosing prosthetic joint infection: systematic review and metaanalysis. Eur J Nucl Med Mol Imaging. 2008;35:2122–32.  https://doi.org/10.1007/s00259-008-0887-x.CrossRefPubMedGoogle Scholar
  79. 79.
    Jin H, Yuan L, Li C, Kan Y, Hao R, Yang J. Diagnostic performance of FDG PET or PET/CT in prosthetic infection after arthroplasty: a meta-analysis. Q J Nucl Med Mol Imaging. 2014;58:85–93.PubMedGoogle Scholar
  80. 80.
    Verberne SJ, Raijmakers PG, Temmerman OP. The accuracy of imaging techniques in the assessment of periprosthetic hip infection: a systematic review and meta-analysis. J Bone Joint Surg Am. 2016;98:1638–45.  https://doi.org/10.2106/jbjs.15.00898. CrossRefPubMedGoogle Scholar
  81. 81.
    Verberne SJ, Sonnega RJ, Temmerman OP, Raijmakers PG. What is the accuracy of nuclear imaging in the assessment of periprosthetic knee infection? A meta-analysis. Clin Orthop Relat Res. 2017;475:1395–410.  https://doi.org/10.1007/s11999-016-5218-0.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Nawaz A, Torigian DA, Siegelman ES, Basu S, Chryssikos T, Alavi A. Diagnostic performance of FDG-PET, MRI, and plain film radiography (PFR) for the diagnosis of osteomyelitis in the diabetic foot. Mol Imaging Biol. 2010;12:335–42.  https://doi.org/10.1007/s11307-009-0268-2. CrossRefPubMedGoogle Scholar
  83. 83.
    Kagna O, Srour S, Melamed E, Militianu D, Keidar Z. FDG PET/CT imaging in the diagnosis of osteomyelitis in the diabetic foot. Eur J Nucl Med Mol Imaging. 2012;39:1545–50.  https://doi.org/10.1007/s00259-012-2183-z.CrossRefPubMedGoogle Scholar
  84. 84.
    Rojoa D, Kontopodis N, Antoniou SA, Ioannou CV, Antoniou GA. 18F-FDG PET in the diagnosis of vascular prosthetic graft infection: a diagnostic test accuracy meta-analysis. Eur J Vasc Endovasc Surg. 2019;57:292–301.  https://doi.org/10.1016/j.ejvs.2018.08.040.CrossRefPubMedGoogle Scholar
  85. 85.
    Reinders Folmer EI, Von Meijenfeldt GCI, Van der Laan MJ, Glaudemans A, Slart R, Saleem BR, et al. Diagnostic imaging in vascular graft infection: a systematic review and meta-analysis. Eur J Vasc Endovasc Surg. 2018;56:719–29.  https://doi.org/10.1016/j.ejvs.2018.07.010. CrossRefPubMedGoogle Scholar
  86. 86.
    Keidar Z, Engel A, Hoffman A, Israel O, Nitecki S. Prosthetic vascular graft infection: the role of 18F-FDG PET/CT. J Nucl Med. 2007;48:1230–6.  https://doi.org/10.2967/jnumed.107.040253. CrossRefPubMedGoogle Scholar
  87. 87.
    Bruggink JL, Glaudemans AW, Saleem BR, Meerwaldt R, Alkefaji H, Prins TR, et al. Accuracy of FDG-PET-CT in the diagnostic work-up of vascular prosthetic graft infection. Eur J Vasc Endovasc Surg. 2010;40:348–54.  https://doi.org/10.1016/j.ejvs.2010.05.016. CrossRefPubMedGoogle Scholar
  88. 88.
    Auletta S, Varani M, Horvat R, Galli F, Signore A, Hess S. PET radiopharmaceuticals for specific bacteria imaging: a systematic review. J Clin Med. 2019;8.  https://doi.org/10.3390/jcm8020197.CrossRefGoogle Scholar
  89. 89.
    Nanni C, Boriani L, Salvadori C, Zamparini E, Rorato G, Ambrosini V, et al. FDG PET/CT is useful for the interim evaluation of response to therapy in patients affected by haematogenous spondylodiscitis. Eur J Nucl Med Mol Imaging. 2012;39:1538–44.  https://doi.org/10.1007/s00259-012-2179-8.CrossRefPubMedGoogle Scholar
  90. 90.
    Husmann L, Ledergerber B, Anagnostopoulos A, Stolzmann P, Sah BR, Burger IA, et al. The role of FDG PET/CT in therapy control of aortic graft infection. Eur J Nucl Med Mol Imaging. 2018;45:1987–97.  https://doi.org/10.1007/s00259-018-4069-1.CrossRefPubMedGoogle Scholar
  91. 91.
    Husmann L, Sah BR, Scherrer A, Burger IA, Stolzmann P, Weber R, et al. (1)(8)F-FDG PET/CT for therapy control in vascular graft infections: a first feasibility study. J Nucl Med. 2015;56:1024–9.  https://doi.org/10.2967/jnumed.115.156265. CrossRefPubMedGoogle Scholar
  92. 92.
    Sjölander H, Strømsnes T, Gerke O, Hess SJC, Imaging T. Value of FDG-PET/CT for treatment response in tuberculosis: a systematic review and meta-analysis. 2018;6:19–29.  https://doi.org/10.1007/s40336-017-0259-2.CrossRefGoogle Scholar
  93. 93.
    Basu S, Zhuang H, Torigian DA, Rosenbaum J, Chen W, Alavi A. Functional imaging of inflammatory diseases using nuclear medicine techniques. Semin Nucl Med. 2009;39:124–45.  https://doi.org/10.1053/j.semnuclmed.2008.10.006.CrossRefPubMedGoogle Scholar
  94. 94.
    Zerizer I, Tan K, Khan S, Barwick T, Marzola MC, Rubello D, et al. Role of FDG-PET and PET/CT in the diagnosis and management of vasculitis. Eur J Radiol. 2010;73:504–9.  https://doi.org/10.1016/j.ejrad.2010.01.021.CrossRefPubMedGoogle Scholar
  95. 95.
    Besson FL, Parienti JJ, Bienvenu B, Prior JO, Costo S, Bouvard G, et al. Diagnostic performance of (1)(8)F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2011;38:1764–72.  https://doi.org/10.1007/s00259-011-1830-0.CrossRefPubMedGoogle Scholar
  96. 96.
    Soussan M, Nicolas P, Schramm C, Katsahian S, Pop G, Fain O, et al. Management of large-vessel vasculitis with FDG-PET: a systematic literature review and meta-analysis. Medicine (Baltimore). 2015;94:e622.  https://doi.org/10.1097/md.0000000000000622.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Cheng Y, Lv N, Wang Z, Chen B, Dang A. 18-FDG-PET in assessing disease activity in Takayasu arteritis: a meta-analysis. Clin Exp Rheumatol. 2013;31:S22–7.PubMedGoogle Scholar
  98. 98.
    Barra L, Kanji T, Malette J, Pagnoux C. Imaging modalities for the diagnosis and disease activity assessment of Takayasu’s arteritis: a systematic review and meta-analysis. Autoimmun Rev. 2018;17:175–87.  https://doi.org/10.1016/j.autrev.2017.11.021.CrossRefPubMedGoogle Scholar
  99. 99.
    Nielsen BD, Hansen IT, Kramer S, Haraldsen A, Hjorthaug K, Bogsrud TV, et al. Simple dichotomous assessment of cranial artery inflammation by conventional 18F-FDG PET/CT shows high accuracy for the diagnosis of giant cell arteritis: a case-control study. Eur J Nucl Med Mol Imaging. 2019;46:184–93.  https://doi.org/10.1007/s00259-018-4106-0.CrossRefPubMedGoogle Scholar
  100. 100.
    Nielsen BD, Gormsen LC, Hansen IT, Keller KK, Therkildsen P, Hauge EM. Three days of high-dose glucocorticoid treatment attenuates large-vessel 18F-FDG uptake in large-vessel giant cell arteritis but with a limited impact on diagnostic accuracy. Eur J Nucl Med Mol Imaging. 2018;45:1119–28.  https://doi.org/10.1007/s00259-018-4021-4.CrossRefPubMedGoogle Scholar
  101. 101.
    Maestri Brittain J, Gormsen LC, von Benzon E, Andersen KF. Concomitant polymyalgia rheumatica and large-vessel vasculitis visualized on (18)F-FDG PET/CT. Diagnostics (Basel, Switzerland). 2018;8.  https://doi.org/10.3390/diagnostics8020027. CrossRefGoogle Scholar
  102. 102.
    Sondag M, Guillot X, Verhoeven F, Blagosklonov O, Prati C, Boulahdour H, et al. Utility of 18F-fluoro-dexoxyglucose positron emission tomography for the diagnosis of polymyalgia rheumatica: a controlled study. Rheumatology (Oxford, England). 2016;55:1452–7.  https://doi.org/10.1093/rheumatology/kew202. CrossRefGoogle Scholar
  103. 103.
    Rehak Z, Sprlakova-Pukova A, Kazda T, Fojtik Z, Vargova L, Nemec P. (18)F-FDG PET/CT in polymyalgia rheumatica-a pictorial review. Br J Radiol. 2017;90:20170198.  https://doi.org/10.1259/bjr.20170198.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Alavi A, Buchpiguel CA, Loessner A. Is there a role for FDG PET imaging in the management of patients with sarcoidosis? J Nucl Med. 1994;35:1650–2.PubMedGoogle Scholar
  105. 105.
    Kwee TC, Torigian DA, Alavi A. Nononcological applications of positron emission tomography for evaluation of the thorax. J Thorac Imaging. 2013;28:25–39.  https://doi.org/10.1097/RTI.0b013e31827882a9.CrossRefPubMedGoogle Scholar
  106. 106.
    Treglia G, Annunziata S, Sobic-Saranovic D, Bertagna F, Caldarella C, Giovanella L. The role of 18F-FDG-PET and PET/CT in patients with sarcoidosis: an updated evidence-based review. Acad Radiol. 2014;21:675–84.  https://doi.org/10.1016/j.acra.2014.01.008. CrossRefPubMedGoogle Scholar
  107. 107.
    Kim SJ, Pak K, Kim K. Diagnostic performance of F-18 FDG PET for detection of cardiac sarcoidosis; a systematic review and meta-analysis. J Nucl Cardiol. 2019.  https://doi.org/10.1007/s12350-018-01582-y.
  108. 108.
    Tang R, Wang JT, Wang L, Le K, Huang Y, Hickey AJ, et al. Impact of patient preparation on the diagnostic performance of 18F-FDG PET in cardiac sarcoidosis: a systematic review and meta-analysis. Clin Nucl Med. 2016;41:e327–39.  https://doi.org/10.1097/rlu.0000000000001063.CrossRefPubMedGoogle Scholar
  109. 109.
    Treglia G, Quartuccio N, Sadeghi R, Farchione A, Caldarella C, Bertagna F, 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. J Crohn’s Colitis. 2013;7:345–54.  https://doi.org/10.1016/j.crohns.2012.08.005.CrossRefGoogle Scholar
  110. 110.
    Zhang J, Li LF, Zhu YJ, Qiu H, Xu Q, Yang J, et al. Diagnostic performance of 18F-FDG-PET versus scintigraphy in patients with inflammatory bowel disease: a meta-analysis of prospective literature. Nucl Med Commun. 2014;35:1233–46.  https://doi.org/10.1097/mnm.0000000000000202.CrossRefPubMedGoogle Scholar
  111. 111.
    Lenze F, Wessling J, Bremer J, Ullerich H, Spieker T, Weckesser M, et al. Detection and differentiation of inflammatory versus fibromatous Crohn’s disease strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and transabdominal ultrasound versus endoscopic/histologic evaluation. Inflamm Bowel Dis. 2012;18:2252–60.  https://doi.org/10.1002/ibd.22930.CrossRefPubMedGoogle Scholar
  112. 112.
    Malham MHS, Nielse RG, Husby S, Høilund-Carlsen PF. PET/CT in the diagnosis of inflammatory bowel disease in pediatric patients: a review. Am J Nucl Med Mol Imaging. 2014.Google Scholar
  113. 113.
    Carey K, Saboury B, Basu S, Brothers A, Ogdie A, Werner T, et al. Evolving role of FDG PET imaging in assessing joint disorders: a systematic review. Eur J Nucl Med Mol Imaging. 2011;38:1939–55.  https://doi.org/10.1007/s00259-011-1863-4.CrossRefPubMedGoogle Scholar
  114. 114.
    Sarma M, Vijayant V, Basu S. (18)F-FDG-PET assessment of early treatment response of articular and extra-articular foci in newly diagnosed rheumatoid arthritis. Hell J Nucl Med. 2012;15:70–1.PubMedGoogle Scholar
  115. 115.
    Elzinga EH, van der Laken CJ, Comans EF, Boellaard R, Hoekstra OS, Dijkmans BA, et al. 18F-FDG PET as a tool to predict the clinical outcome of infliximab treatment of rheumatoid arthritis: an explorative study. J Nucl Med. 2011;52:77–80.  https://doi.org/10.2967/jnumed.110.076711. CrossRefPubMedGoogle Scholar
  116. 116.
    Hess S, Frary EC, Gerke O, Werner T, Alavi A, Høilund-Carlsen PFJC, et al. FDG-PET/CT in venous thromboembolism. 2018;6:369–78.  https://doi.org/10.1007/s40336-018-0296-5.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of RadiologyHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Radiology and Nuclear MedicineHospital of Southwest JutlandEsbjergDenmark
  3. 3.Department of Clinical Research, Faculty of Health SciencesUniversity of Southern DenmarkOdenseDenmark
  4. 4.Department of Nuclear MedicineOdense University HospitalOdenseDenmark

Personalised recommendations