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DOI: 10.1148/rg.255045122
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RadioGraphics 2005;25:1357-1368
© RSNA, 2005

EDUCATION EXHIBIT

FDG PET of Infection and Inflammation1

Charito Love, MD, Maria B. Tomas, MD, Gene G. Tronco, MD and Christopher J. Palestro, MD

1 From the Division of Nuclear Medicine, Long Island Jewish Medical Center, 270–05 76th Ave, New Hyde Park, NY 11040. Presented as an education exhibit at the 2003 RSNA Annual Meeting. Received June 4, 2004; revision requested August 19 and received October 25; accepted November 9. All authors have no financial relationships to disclose. Address correspondence to C.L. (e-mail: love{at}lij.edu).


   Abstract
Top
 Abstract
LEARNING OBJECTIVES
 Introduction
 FDG Imaging
 Indications for FDG
 Conclusions
 References
 
Nuclear medicine plays an important role in the evaluation of infection and inflammation. Fluorine 18 fluorodeoxyglucose (FDG) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution tomography. In patients with acquired immunodeficiency syndrome, FDG positron emission tomography (PET) accurately helps localize foci of infection and is particularly useful for differentiating central nervous system lymphoma from toxoplasmosis. FDG PET can also help localize the source of fever of undetermined origin (FUO), thereby guiding additional testing. In the musculoskeletal system, FDG PET accurately helps diagnose spinal osteomyelitis, and in inflammatory conditions such as sarcoidosis and vasculitis, it appears to be useful for defining the extent of disease and monitoring response to treatment. FDG PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or a tumor. Nevertheless, this relatively new imaging technique promises to be helpful in the diagnosis of infection and inflammation. FDG PET will likely assume increasing importance in assessing FUO, spinal osteomyelitis, vasculitis, and sarcoidosis and may even become the radionuclide imaging procedure of choice in the evaluation of some or all of these pathologic conditions.

© RSNA, 2005


   LEARNING OBJECTIVES
Top
 Abstract
 LEARNING OBJECTIVES
Introduction
 FDG Imaging
 Indications for FDG
 Conclusions
 References
 
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   Introduction
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
FDG Imaging
 Indications for FDG
 Conclusions
 References
 
Nuclear medicine has an important role in assessing infection and inflammation. Although technetium 99m (99mTc) methylene diphosphonate imaging, gallium 67 (67Ga) citrate imaging, indium 111 (111In)–oxine autologous labeled leukocyte imaging, and 99mTc hexylmethylpropylene amineoxime autologous labeled leukocyte imaging are useful techniques, each of them has limitations. The radiotracer fluorine 18 (18F) fluorodeoxyglucose (FDG) is readily available and allows fast, sensitive high-resolution tomography. Thus, it is not surprising that the potential of this agent in detecting infection has attracted considerable interest.

In this article, we discuss and illustrate the role and limitations of FDG positron emission tomography (PET) in the assessment of infection and inflammation, including entities such as acquired immunodeficiency syndrome (AIDS), fever of undetermined origin (FUO), focal infection, musculoskeletal infections, sarcoidosis, and vasculitis.


   FDG Imaging
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
 FDG Imaging
Indications for FDG
 Conclusions
 References
 
FDG is transported into cells by glucose transporters and is phosphorylated by hexokinase enzyme to 18F-2'-FDG-6 phosphate but is not metabolized. The degree of cellular FDG uptake is related to the cellular metabolic rate and the number of glucose transporters (1–3). Increased FDG uptake in tumors is presumably due, at least in part, to an increased number of glucose transporters in malignant cells. A similar situation exists in inflammation (4,5): Activated inflammatory cells also demonstrate increased expression of glucose transporters. In addition, in inflammatory conditions, the affinity of glucose transporters for deoxyglucose is apparently increased by various cytokines and growth factors, a phenomenon that has not been observed in tumors (3,6). The role of FDG PET in a variety of malignancies has been extensively investigated and, in the course of these investigations, FDG uptake in nonmalignant inflammatory conditions has been observed (3,5). Although such uptake can produce false-positive results in patients with known or suspected malignancy, FDG represents another potentially useful radiotracer in the setting of infection and inflammation.

The areas of normal distribution of FDG include the brain, myocardium, and genitourinary tract. Activity in the bone marrow, stomach, and bowel is variable. Thymic uptake, especially in children, can also be observed. Hepatic and splenic uptake are generally low grade and diffuse (7–10); in the setting of infection, however, splenic uptake can be quite intense. The spleen, an integral part of the body’s immune system, performs multiple tasks, including clearance of encapsulated bacteria, production of inflammatory substances (eg, opsonins) and of immunoglobulin M and immunoglobulin G antibodies, and phagocytosis of infectious agents, in addition to serving as a reservoir of cellular elements, including leukocytes. Presumably, the increased splenic activity reflects increased glucose usage by this organ in the setting of infection. It is important to recognize that increased splenic activity does occur in patients with infection and should not automatically be equated with either splenic infection or tumor (Fig 1) (11).



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  		Figure 1a.  Iatrogenic infection of surgical reinforcement mesh in a 50-year-old woman who had undergone repair of a ventral hernia 2 months earlier. (a) FDG PET scan shows intense radiotracer accumulation within the spleen, a finding that raised suspicion for tumor. However, additional work-up for malignancy was negative. (b) On a repeat FDG PET scan obtained 10 months later when the infection had resolved and the patient was in good health, the spleen is barely discernible.

 


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  		Figure 1b.  Iatrogenic infection of surgical reinforcement mesh in a 50-year-old woman who had undergone repair of a ventral hernia 2 months earlier. (a) FDG PET scan shows intense radiotracer accumulation within the spleen, a finding that raised suspicion for tumor. However, additional work-up for malignancy was negative. (b) On a repeat FDG PET scan obtained 10 months later when the infection had resolved and the patient was in good health, the spleen is barely discernible.

 
To minimize FDG uptake in normal tissues, patients are advised to fast for at least several hours prior to examination to reduce competition for glucose transporters. In the fasting state, for example, the myocardium, which "prefers" glucose, uses free fatty acids for metabolism and will accumulate less FDG. Because of avid FDG uptake by muscle tissues, limiting physical activity before injection can minimize striated muscle uptake of FDG (7). Administration of benzodiazepines 30–60 minutes before FDG injection can also diminish activity in muscle and brown adipose tissue (12). In the evaluation of the lower extremities, it is useful to have the patient remain at bed rest for at least 1 hour prior to injection.

The uptake of FDG is related to tissue metabolism in general; there is nothing specific about its uptake in inflammation. If the value of this radiotracer for imaging of inflammation and infection is to be maximized, appropriate indications for its use need to be developed.


   Indications for FDG
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
 FDG Imaging
 Indications for FDG
Conclusions
 References
 
Acquired Immuno-deficiency Syndrome
AIDS patients are vulnerable to a variety of opportunistic infections and tumors. For many years, gallium imaging has been the radionuclide study of choice for evaluating AIDS patients. FDG PET also accurately helps localize foci of infection, as well as tumor, in this population. In a study of 57 AIDS patients, O’Doherty et al (13) reported that FDG PET was 92% sensitive and 94% specific for localizing abnormalities that required treatment. However, they also noted that it was not possible to distinguish infection from tumor at FDG PET (Fig 2). FDG PET is especially valuable in the assessment of diseases affecting the central nervous system (CNS) in AIDS patients. Both toxoplasmosis and lymphoma are frequent CNS complications of AIDS, and it is not always possible to distinguish between the two at CT and magnetic resonance (MR) imaging. However, FDG PET is very useful in this setting (14). CNS lymphoma is highly metabolically active, whereas toxoplasmosis is not (Fig 3). Quantitative assessment has shown that the standardized uptake values of toxoplasmosis are significantly lower than those of lymphoma, with virtually no overlap between the uptake values of the two conditions (3).



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  		Figure 2a.  Fungal pneumonia in a 40-year-old man with AIDS and newly diagnosed anaplastic lymphoma. (a) Computed tomographic (CT) scan demonstrates a 6 x 3.5-cm thick-walled cavitary lesion in the posterior segment of the right lower lung. (b) FDG PET scan demonstrates intense, heterogeneous accumulation of radiotracer in the posterior aspect of the right lower lung, a finding that corresponds to the abnormality identified at CT and that could indicate lymphomatous involvement of the pulmonary parenchyma. The final diagnosis, however, was fungal pneumonia. It was not possible to distinguish lymphoma from infection on the basis of the FDG PET finding alone.

 


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  		Figure 2b.  Fungal pneumonia in a 40-year-old man with AIDS and newly diagnosed anaplastic lymphoma. (a) Computed tomographic (CT) scan demonstrates a 6 x 3.5-cm thick-walled cavitary lesion in the posterior segment of the right lower lung. (b) FDG PET scan demonstrates intense, heterogeneous accumulation of radiotracer in the posterior aspect of the right lower lung, a finding that corresponds to the abnormality identified at CT and that could indicate lymphomatous involvement of the pulmonary parenchyma. The final diagnosis, however, was fungal pneumonia. It was not possible to distinguish lymphoma from infection on the basis of the FDG PET finding alone.

 


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  		Figure 3a.  (a, b) Toxoplasmosis in an AIDS patient. (a) Contrast material–enhanced T1-weighted MR image shows an enhancing lesion in the right frontal operculum. (b) On an FDG PET scan, the lesion is hypometabolic. The final diagnosis was toxoplasmosis. (c, d) CNS lymphoma in a different AIDS patient. (c) Contrast-enhanced T1-weighted MR image reveals an enhancing mass in the splenium of the corpus callosum. (d) On an FDG PET scan, the lesion is hypermetabolic. The lesion subsequently proved to be lymphoma.

 


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  		Figure 3b.  (a, b) Toxoplasmosis in an AIDS patient. (a) Contrast material–enhanced T1-weighted MR image shows an enhancing lesion in the right frontal operculum. (b) On an FDG PET scan, the lesion is hypometabolic. The final diagnosis was toxoplasmosis. (c, d) CNS lymphoma in a different AIDS patient. (c) Contrast-enhanced T1-weighted MR image reveals an enhancing mass in the splenium of the corpus callosum. (d) On an FDG PET scan, the lesion is hypermetabolic. The lesion subsequently proved to be lymphoma.

 


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  		Figure 3c.  (a, b) Toxoplasmosis in an AIDS patient. (a) Contrast material–enhanced T1-weighted MR image shows an enhancing lesion in the right frontal operculum. (b) On an FDG PET scan, the lesion is hypometabolic. The final diagnosis was toxoplasmosis. (c, d) CNS lymphoma in a different AIDS patient. (c) Contrast-enhanced T1-weighted MR image reveals an enhancing mass in the splenium of the corpus callosum. (d) On an FDG PET scan, the lesion is hypermetabolic. The lesion subsequently proved to be lymphoma.

 


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  		Figure 3d.  (a, b) Toxoplasmosis in an AIDS patient. (a) Contrast material–enhanced T1-weighted MR image shows an enhancing lesion in the right frontal operculum. (b) On an FDG PET scan, the lesion is hypometabolic. The final diagnosis was toxoplasmosis. (c, d) CNS lymphoma in a different AIDS patient. (c) Contrast-enhanced T1-weighted MR image reveals an enhancing mass in the splenium of the corpus callosum. (d) On an FDG PET scan, the lesion is hypermetabolic. The lesion subsequently proved to be lymphoma.

 
Fever of Undetermined Origin
FUO is an illness of at least 3 weeks duration, with several episodes of fever exceeding 38.3°C and no diagnosis after an appropriate inpatient or outpatient evaluation. There are numerous causes of FUO, with infection accounting for about 20%–30% of cases and neoplasms for about 15%–25%. Other causes include collagen vascular disease, granulomatous diseases, pulmonary emboli, cerebrovascular accidents, and drug fever. Identifying the source of an FUO is often difficult, and radionuclide studies are an important part of the diagnostic evaluation of this entity. At the present time, there is no consensus on the optimal radionuclide approach to FUO (15). Labeled leukocyte imaging is more sensitive early in the course of an illness, whereas gallium imaging is more sensitive later on, and the selection of the procedure is sometimes governed by the duration of the illness. Because the causes of FUO are so diverse, some individuals prefer the sensitive but nonspecific gallium for the initial radionuclide study. Unfortunately, if one begins with gallium imaging, it is necessary to wait a minimum of 7–10 days before performing a labeled leukocyte study. If labeled leukocyte imaging is performed first, one can immediately proceed to gallium imaging if necessary. Regardless of which study is performed first, however, it may take several days before both procedures are completed.

In contrast, the use of FDG poses no such problems. Like gallium, FDG is not specific but is sensitive and therefore ideally suited to the evaluation of an entity with diverse causes (Figs 4, 5). Furthermore, the short half-life of 18F does not delay the performance of any additional radionuclide studies that might be contemplated. Indeed, there are several studies that support the use of FDG PET in patients with FUO (16–19). Blockmans et al (16) studied the contribution of FDG PET in 58 cases of FUO and found that it provided helpful information in 41% of cases. Forty of the 58 patients also underwent gallium imaging. In this subgroup, FDG PET was helpful in 35% of cases, whereas gallium imaging was helpful in 25%. The authors concluded that FDG PET compares favorably with gallium imaging and, because it can be performed rapidly, could replace gallium scintigraphy as a radionuclide study for the evaluation of patients with FUO. Using a coincidence detection system, Meller et al (17) prospectively evaluated the use of FDG PET in 20 patients with FUO. They reported that FDG was 84% sensitive and 86% specific for identifying the source of the FUO. In a subgroup of 18 patients who also underwent gallium imaging, FDG was more sensitive (81%) and more specific (86%) than gallium (67% and 78%, respectively). Recently, Bleeker-Rovers et al (18) evaluated 35 patients with FUO and reported that FDG PET was clinically helpful in 37% of cases, with a sensitivity and specificity of 93% and 90%, respectively, a positive predictive value of 87%, and a negative predictive value (NPV) of 95%.



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  		Figure 4a.  Metastatic renal cell carcinoma in an 81-year-old woman who presented with persistent fevers and no localizing signs. (a) FDG PET scan demonstrates a hypermetabolic focus in the mediastinum. (b) CT scan reveals mediastinal lymphadenopathy. Biopsy results confirmed mediastinal lymph node involvement by metastatic renal cell carcinoma.

 


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  		Figure 4b.  Metastatic renal cell carcinoma in an 81-year-old woman who presented with persistent fevers and no localizing signs. (a) FDG PET scan demonstrates a hypermetabolic focus in the mediastinum. (b) CT scan reveals mediastinal lymphadenopathy. Biopsy results confirmed mediastinal lymph node involvement by metastatic renal cell carcinoma.

 


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  		Figure 5.  Infected bypass graft. Axial (left) and coronal (right) FDG PET scans demonstrate intense radiotracer activity in an infected left femoral artery bypass graft.

 
Infective endocarditis can also be the source of an FUO. The diagnosis is usually made by combining clinical and laboratory data, along with the echocardiographic identification of valvular vegetations. Occasionally, however, vegetations are not infected. Furthermore, small vegetations in patients with prosthetic heart valves are obscured by the intense echoes produced by the prosthesis and may escape detection. Although the diagnosis of infective endocarditis with a variety of radionuclide imaging techniques has been reported, the clinical value of these techniques has never been established. A recent pilot study suggests that, in spite of the normal myocardial FDG uptake, FDG PET accurately helps identify sites of infective endocarditis and is a promising supplement to conventional echocardiography (Fig 6) (20).



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  		Figure 6a.  Infective endocarditis in a patient who had undergone mitral valve replacement. FDG PET was performed because of persistent bacteremia. (a) Axial (left) and coronal (right) FDG PET scans show a focus of increased intracardiac activity. Results of echocardiography confirmed the presence of valvular vegetations and a mitral annular abscess. (b) 111In-labeled leukocyte image is unremarkable.

 


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  		Figure 6b.  Infective endocarditis in a patient who had undergone mitral valve replacement. FDG PET was performed because of persistent bacteremia. (a) Axial (left) and coronal (right) FDG PET scans show a focus of increased intracardiac activity. Results of echocardiography confirmed the presence of valvular vegetations and a mitral annular abscess. (b) 111In-labeled leukocyte image is unremarkable.

 
Only about one-half of all FUOs are caused by infection or tumor. Other entities such as vasculitis, thromboembolic disease (Fig 7 ), childhood sarcoidosis, and chronic granulomatous disease, all of which can manifest as an FUO, are associated with increased FDG uptake (3).



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  		Figure 7a.  Pulmonary embolism with pulmonary infarction in a 31-year-old woman who had been successfully treated for endometritis. The patient presented with persistent fevers but no localizing signs or symptoms. (a) Anterior (left) and posterior (right) 111In-labeled leukocyte images are normal. FDG PET was performed in an effort to identify the source of the patient’s fevers. (b) Axial (left) and coronal (right) FDG PET scans show evidence of a left-sided pleural effusion and a hypermetabolic pleura-based focus in the left lower lung. CT pulmonary angiography was performed because malignancy was thought to be clinically unlikely and because of the propensity of FDG to accumulate in thromboembolic disease. (c, d) CT pulmonary angiograms show left lower lobe pulmonary emboli (arrowhead in c) and a nonenhancing wedge-shaped lesion in the periphery of the left lower lung (d) corresponding to the hypermetabolic focus seen at FDG PET. The final diagnosis was pulmonary embolism with pulmonary infarction. This case illustrates the importance of sensitivity when evaluating patients with FUO. The labeled leukocyte study correctly excluded infection as the source of the patient’s fever but provided no additional information about the nature or location of the source of the fever. FDG, although not providing a specific diagnosis, did help localize the source of the FUO, facilitating the diagnosis with subsequent studies.

 


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  		Figure 7b.  Pulmonary embolism with pulmonary infarction in a 31-year-old woman who had been successfully treated for endometritis. The patient presented with persistent fevers but no localizing signs or symptoms. (a) Anterior (left) and posterior (right) 111In-labeled leukocyte images are normal. FDG PET was performed in an effort to identify the source of the patient’s fevers. (b) Axial (left) and coronal (right) FDG PET scans show evidence of a left-sided pleural effusion and a hypermetabolic pleura-based focus in the left lower lung. CT pulmonary angiography was performed because malignancy was thought to be clinically unlikely and because of the propensity of FDG to accumulate in thromboembolic disease. (c, d) CT pulmonary angiograms show left lower lobe pulmonary emboli (arrowhead in c) and a nonenhancing wedge-shaped lesion in the periphery of the left lower lung (d) corresponding to the hypermetabolic focus seen at FDG PET. The final diagnosis was pulmonary embolism with pulmonary infarction. This case illustrates the importance of sensitivity when evaluating patients with FUO. The labeled leukocyte study correctly excluded infection as the source of the patient’s fever but provided no additional information about the nature or location of the source of the fever. FDG, although not providing a specific diagnosis, did help localize the source of the FUO, facilitating the diagnosis with subsequent studies.

 


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  		Figure 7c.  Pulmonary embolism with pulmonary infarction in a 31-year-old woman who had been successfully treated for endometritis. The patient presented with persistent fevers but no localizing signs or symptoms. (a) Anterior (left) and posterior (right) 111In-labeled leukocyte images are normal. FDG PET was performed in an effort to identify the source of the patient’s fevers. (b) Axial (left) and coronal (right) FDG PET scans show evidence of a left-sided pleural effusion and a hypermetabolic pleura-based focus in the left lower lung. CT pulmonary angiography was performed because malignancy was thought to be clinically unlikely and because of the propensity of FDG to accumulate in thromboembolic disease. (c, d) CT pulmonary angiograms show left lower lobe pulmonary emboli (arrowhead in c) and a nonenhancing wedge-shaped lesion in the periphery of the left lower lung (d) corresponding to the hypermetabolic focus seen at FDG PET. The final diagnosis was pulmonary embolism with pulmonary infarction. This case illustrates the importance of sensitivity when evaluating patients with FUO. The labeled leukocyte study correctly excluded infection as the source of the patient’s fever but provided no additional information about the nature or location of the source of the fever. FDG, although not providing a specific diagnosis, did help localize the source of the FUO, facilitating the diagnosis with subsequent studies.

 


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  		Figure 7d.  Pulmonary embolism with pulmonary infarction in a 31-year-old woman who had been successfully treated for endometritis. The patient presented with persistent fevers but no localizing signs or symptoms. (a) Anterior (left) and posterior (right) 111In-labeled leukocyte images are normal. FDG PET was performed in an effort to identify the source of the patient’s fevers. (b) Axial (left) and coronal (right) FDG PET scans show evidence of a left-sided pleural effusion and a hypermetabolic pleura-based focus in the left lower lung. CT pulmonary angiography was performed because malignancy was thought to be clinically unlikely and because of the propensity of FDG to accumulate in thromboembolic disease. (c, d) CT pulmonary angiograms show left lower lobe pulmonary emboli (arrowhead in c) and a nonenhancing wedge-shaped lesion in the periphery of the left lower lung (d) corresponding to the hypermetabolic focus seen at FDG PET. The final diagnosis was pulmonary embolism with pulmonary infarction. This case illustrates the importance of sensitivity when evaluating patients with FUO. The labeled leukocyte study correctly excluded infection as the source of the patient’s fever but provided no additional information about the nature or location of the source of the fever. FDG, although not providing a specific diagnosis, did help localize the source of the FUO, facilitating the diagnosis with subsequent studies.

 
In summary, in patients with FUO, FDG PET helps identify the organ or tissue where the source of the fever is likely to be found, thereby guiding additional, appropriate testing. Equally important is the high NPV of this modality: Negative FDG PET findings make it very unlikely that a morphologic origin of the fever will be identified.

Focal Infection
Although sensitivity may be more important than specificity in the evaluation of patients with FUO, specificity assumes considerably more importance in the evaluation of focal infection. In patients with suspected focal infection who are referred for radionuclide studies, a discrete abnormality has frequently been detected but not precisely characterized with anatomic imaging. Often, these patients are suspected of harboring a postoperative infection or have a history of tumor, and the radionuclide study is relied upon to help differentiate infection from postoperative changes or tumor (21). The limitations of FDG in differentiating infection from tumor are obvious (Figs 2 , 8). Although the role of FDG in the evaluation of postoperative infection has not been extensively studied, persistent FDG uptake in uninfected surgical incisions has been observed (Figs 9, 10). In patients with tumors, it is generally suggested that at least several weeks be allowed to elapse between surgery and FDG PET to minimize the likelihood of false-positive results secondary to postoperative changes (22). Data indicate that in patients with suspected focal infection, FDG PET has a sensitivity comparable to that of 111In-labeled autologous leukocyte imaging but is considerably less specific. False-positive results have been associated with tumor and postoperative changes (23,24).



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  		Figure 8a.  Metastatic involvement in a patient with a history of colon cancer and fever. (a) CT scan shows a destructive soft-tissue mass involving the sacrum. (b) FDG PET scan shows the mass to be hypermetabolic but does not help differentiate infection from tumor. The final diagnosis was metastatic colon carcinoma.

 


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  		Figure 8b.  Metastatic involvement in a patient with a history of colon cancer and fever. (a) CT scan shows a destructive soft-tissue mass involving the sacrum. (b) FDG PET scan shows the mass to be hypermetabolic but does not help differentiate infection from tumor. The final diagnosis was metastatic colon carcinoma.

 


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  		Figure 9.  FDG PET scan obtained in a patient who had undergone abdominal surgery 2 months earlier demonstrates a linear area of intense radiotracer activity (arrowheads) representing a normally healed surgical incision.

 


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  		Figure 10.  FDG PET scans obtained in a patient who had undergone total right knee replacement 3 months earlier show intense radiotracer activity along the lateral margin of the asymptomatic, uninfected replacement. More extensive investigation is needed to clarify the role of FDG PET in the evaluation of postoperative infection.

 
Osteomyelitis
Radionuclide imaging techniques play an important role in the diagnosis of osteomyelitis. In the absence of underlying bone abnormalities, three-phase bone scintigraphy is both sensitive and specific for osteomyelitis (25). However, in the setting of previous trauma, orthopedic hardware, or a neuropathic joint, bone scintigraphy is less useful. In these situations, dual radiotracer studies are often used: sequential bone-gallium, combined leukocyte-bone or, in most situations, combined leukocyte–bone marrow imaging (26). However, these dual radiotracer studies have important limitations. The need for additional imaging adds to the complexity and cost of the study and is an inconvenience to patients, many of whom are elderly and debilitated. In labeled leukocyte imaging, the in vitro labeling process is labor intensive, not always available, and requires direct contact with blood products. Thus, investigators continue to search for suitable alternatives. One agent that has generated considerable interest is FDG. Baseline FDG uptake by normal cortical bone is quite low (27). Bone marrow uptake is variable and can be slightly to moderately more intense than that of bone (28). In osteomyelitis, the presence of inflammatory cells (eg, neutrophils, lymphocytes, macrophages) with heightened metabolic activity results in increased FDG uptake (27,29). Several studies have shown that FDG is useful in diagnosing osteomyelitis (27,29–31). However, increased osseous FDG activity has also been observed in inflammatory arthritis, in acute fractures, and in normally healing bone up to 4 months after surgery (32,33). These observations are not surprising: The healing process is associated with many of the same cellular components that are present in inflammation (34). Because FDG accumulates in the bone marrow, it is likely that some of this increased uptake, in the absence of infection, may also be related to localized hypercellular marrow. This phenomenon has in fact been observed in patients with failed lower extremity joint prostheses (35).

It is important to recall that not all radiotracers perform equally well in all situations. For example, although labeled leukocyte imaging is the radionuclide study of choice for diagnosing prosthetic joint infection and identifying pedal osteomyelitis in diabetic patients, it is of little use in spinal osteomyelitis (26). Thus, although initial reports about the value of FDG in diagnosing osteomyelitis have generally been encouraging, extensive investigations focusing on specific indications are needed to accurately define the role of FDG in the evaluation of musculoskeletal infection.

Prosthetic Joint Infection
More than 400,000 hip and knee arthroplasties are performed annually in the United States (36). Differentiating infection from aseptic loosening, the most common cause of joint arthroplasty failure, is extremely important because the management of these two conditions differs markedly. The diagnosis of infection has significant implications, both clinically and economically, in terms of prolonged antibiotic treatment, a longer hospital stay, and a second operation. The failure to diagnose infection also has serious ramifications. Persistence of infection will almost assuredly lead to failure of a revision arthroplasty, continuing periprosthetic osteolysis, and the need for a second surgical procedure, which may be more difficult and extensive than the first. Bone marrow imaging with a combination of 111In-labeled leukocytes and 99mTc sulfur colloid has an accuracy of more than 90% and is the preferred radionuclide procedure for diagnosing prosthetic joint replacement infection (37,38).

The role of FDG PET in the evaluation of painful lower extremity joint prostheses has been extensively investigated (35,39–43). Although initial reports suggested that FDG PET could accurately help identify an infected joint prosthesis, recent studies are less encouraging. FDG PET does not appear to be capable of helping distinguish an infected joint prosthesis (Fig 11a) from an aseptically loosened prosthesis (Fig 11b) (35,43). This is not surprising when one considers that inflammation, often intense, is present in both aseptic loosening and infection. Thus, both conditions will be characterized by increased periprosthetic FDG uptake (35,43).



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  		Figure 11a.  (a) Infected left hip prosthesis. FDG PET scan shows increased periprosthetic radiotracer activity at the bone-prosthesis interface along the lateral aspect of the femoral component of the prosthesis. (b) Aseptically loosened left hip prosthesis. FDG PET scan demonstrates uptake similar to that seen in a along the lateral margin of the prosthesis. Bone-prosthesis interface activity at FDG PET, once thought to be specific for infection, is probably related to osteolysis, which is present in both infection and loosening.

 


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  		Figure 11b.  (a) Infected left hip prosthesis. FDG PET scan shows increased periprosthetic radiotracer activity at the bone-prosthesis interface along the lateral aspect of the femoral component of the prosthesis. (b) Aseptically loosened left hip prosthesis. FDG PET scan demonstrates uptake similar to that seen in a along the lateral margin of the prosthesis. Bone-prosthesis interface activity at FDG PET, once thought to be specific for infection, is probably related to osteolysis, which is present in both infection and loosening.

 
Spinal Osteomyelitis
Spinal osteomyelitis accounts for less than 10% of all cases of osteomyelitis and has a predilection for the elderly. It may result from bacteremia or from direct inoculation of bacteria into the spine. Although spinal osteomyelitis is usually confined to the vertebral body and intervertebral disk, the posterior elements may be involved in up to 20% of cases. The majority of patients have prolonged symptomatology prior to diagnosis, and laboratory tests are of limited value. MR imaging, with an accuracy of 90%, is the diagnostic imaging procedure of choice for spinal osteomyelitis (44). MR imaging permits early diagnosis of infection and provides direct visualization of the spinal cord, subarachnoid space, extradural soft tissues, and spinal column without the use of intrathecal contrast material. On the other hand, MR imaging is sensitive to motion degradation, so that patients with movement disorders may not be suitable candidates, and certain metallic implants are contraindications for this modality. MR imaging cannot always help distinguish osteomyelitis from severe degenerative arthritis; in such cases, scintigraphy provides important information. The current radionuclide imaging method of choice for diagnosing spinal osteomyelitis is combined bone-gallium imaging, with results comparable to those of MR imaging having been reported (26). In addition to enhancing the specificity of the bone scan, gallium is useful for detecting the abscesses that often accompany spinal osteomyelitis. There are data that indicate that gallium single photon emission CT (SPECT) is comparable to combined bone-gallium imaging for diagnosing this entity (45). Regardless of whether gallium imaging is performed alone or in combination with bone scintigraphy, the study is time consuming and requires that the patient make multiple visits to the nuclear medicine department. Although most of the series reported to date are small, FDG PET appears to be useful in diagnosing spinal osteomyelitis, with high sensitivities and specificities and an accuracy comparable to that of gallium imaging having been reported (Fig 12) (27,28,46–48).



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  		Figure 12a.  Spinal osteomyelitis. (a) FDG PET scan shows intense radiotracer accumulation in the lower lumbar spine. (b) Coronal image from a gallium SPECT study shows a similar abnormality.

 


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  		Figure 12b.  Spinal osteomyelitis. (a) FDG PET scan shows intense radiotracer accumulation in the lower lumbar spine. (b) Coronal image from a gallium SPECT study shows a similar abnormality.

 
Foot Infections in Diabetes
Diabetes mellitus affects about 5% of the U.S. population (49). Each year, more than 10% of diabetic patients are hospitalized for foot complications from the disease, which are the principal cause of morbidity, disability, and mortality in this population. The most commonly encountered complication in the diabetic forefoot is the mal perforans ulcer, which accounts for more than 90% of all cases of diabetic pedal osteomyelitis. The radionuclide study of choice for diagnosing diabetic pedal osteomyelitis is the labeled leukocyte study, with an accuracy of about 80% (50).

In the mid- and hindfoot, the most commonly encountered complication of diabetes is the neuropathic (Charcot) joint. Although the neuropathic joint does not usually become infected, it is difficult to determine if superimposed infection is present or to differentiate between a rapidly progressive neuropathic joint and osteomyelitis. Combined leukocyte–bone marrow scintigraphy is the radionuclide procedure of choice for determining whether the neuropathic joint is infected (51). At the present time, there is little information available on the role of FDG PET in the evaluation of foot infections in diabetes.

Miscellaneous Conditions
Sarcoidosis is a chronic inflammatory condition of unknown cause. Assessment of disease activity largely determines the type of therapy to be instituted. Brudin et al (52) found that the degree of FDG uptake correlates well with disease activity and that FDG PET could be used for monitoring response to treatment. FDG PET has even helped detect sarcoidosis in transplanted lungs (3). FDG uptake patterns in sarcoidosis are not specific and can be misinterpreted as malignancy. Thus, although FDG PET is not useful for initial diagnosis, it will probably be useful for evaluating the extent of active disease and monitoring response to therapy in patients with known sarcoidosis (Fig 13).



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  		Figure 13.  Active sarcoidosis. Axial (left) and coronal (right) FDG PET scans show intense radiotracer activity in the mediastinum. In patients with sarcoidosis, FDG PET can be used to monitor disease activity and response to therapy.

 
Vasculitis is characterized by inflammation and necrosis of blood vessel walls. The diagnosis of vasculitis is complicated by a lack of specific signs and symptoms. Imaging is often used to confirm a suspected diagnosis in the absence of histologic proof, as well as to identify sites for biopsy (53). FDG uptake in giant cell arteritis, Takayasu arteritis, aortitis, and unspecified large vessel vasculitis has been described (Fig 14). Blockmans et al (54) observed abnormal vascular FDG uptake in 19 (76%) of 25 patients with proved temporal arteritis or polymyalgia rheumatica. Thoracic artery uptake had a positive predictive value of 93% and an NPV of 80%. Meller et al (55) compared the use of FDG PET with that of MR imaging in 15 patients with vasculitis and found that the radionuclide study, which helped identify more areas of involvement than did MR imaging, was effective in the diagnosis and follow-up of patients with aortitis. FDG PET appears to have great potential in the diagnosis and treatment of patients with aortitis.



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  		Figure 14.  Vasculitis. FDG PET scan shows increased radiotracer activity in the major arteries of the thorax, abdomen, and pelvis. (Case courtesy of W. J. G. Oyen, MD, PhD, Department of Nuclear Medicine, University Medical Center, Nijmegen, The Netherlands.)

 
Although few data are available on the role of combined PET-CT in the assessment of infection and inflammation, this modality will undoubtedly prove to be useful. Combined PET-CT may prove to be especially useful for evaluating the musculoskeletal system to determine whether the infection involves bone, soft tissue, or both, in cases in which radionuclide imaging alone is inadequate (Fig 15).



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  		Figure 15a.  Osteomyelitis in an 80-year-old woman who had undergone insertion of spinal hardware 6 months earlier. (a) Axial CT scan demonstrates osteopenia and destruction of the L4 vertebral body. (b) Axial FDG PET scan demonstrates increased activity in the lower lumbar spine. PET-CT was performed owing to increasing back pain. (c) Axial coregistered PET-CT scan helps confirm that the abnormal FDG accumulation seen in b involves the bone. (Case courtesy of K. D. Stumpe, MD, Division of Nuclear Medicine, University Hospital, Zurich, Switzerland.)

 


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  		Figure 15b.  Osteomyelitis in an 80-year-old woman who had undergone insertion of spinal hardware 6 months earlier. (a) Axial CT scan demonstrates osteopenia and destruction of the L4 vertebral body. (b) Axial FDG PET scan demonstrates increased activity in the lower lumbar spine. PET-CT was performed owing to increasing back pain. (c) Axial coregistered PET-CT scan helps confirm that the abnormal FDG accumulation seen in b involves the bone. (Case courtesy of K. D. Stumpe, MD, Division of Nuclear Medicine, University Hospital, Zurich, Switzerland.)

 


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  		Figure 15c.  Osteomyelitis in an 80-year-old woman who had undergone insertion of spinal hardware 6 months earlier. (a) Axial CT scan demonstrates osteopenia and destruction of the L4 vertebral body. (b) Axial FDG PET scan demonstrates increased activity in the lower lumbar spine. PET-CT was performed owing to increasing back pain. (c) Axial coregistered PET-CT scan helps confirm that the abnormal FDG accumulation seen in b involves the bone. (Case courtesy of K. D. Stumpe, MD, Division of Nuclear Medicine, University Hospital, Zurich, Switzerland.)

 

   Conclusions
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
 FDG Imaging
 Indications for FDG
 Conclusions
References
 
Although it is nascent and its role is still evolving, FDG PET is a promising modality in the diagnosis of infection and inflammation. FDG PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or a tumor. However, it will likely assume increasing importance in assessing FUO, spinal osteomyelitis, vasculitis, and sarcoidosis, perhaps even becoming the radionuclide procedure of choice in the evaluation of some or all of these entities.


   Footnotes
 

Abbreviations: AIDS = acquired immunodeficiency syndrome, CNS = central nervous system, FDG = fluorodeoxyglucose, FUO = fever of undetermined origin, NPV = negative predictive value

Editor’s Note.—In keeping with the highest standards of professional integrity and ethics, RSNA requires that authors of continuing medical education articles fully disclose to their readers that they will discuss the unlabeled use of a commercial product, device, or pharmaceutical that has not been approved for such purpose by the FDA. All the authors have submitted such a disclosure statement for this article.


   References
Top
 Abstract
 LEARNING OBJECTIVES
 Introduction
 FDG Imaging
 Indications for FDG
 Conclusions
 References
 

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