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.

Bone scintigraphy with technetium-99m-labeled diphosphonates is one of the most frequently performed of all radionuclide procedures. Radionuclide bone imaging is not specific, but its excellent sensitivity makes it useful in screening for many pathologic conditions. Moreover, some conditions that are not clearly depicted on anatomic images can be diagnosed with bone scintigraphy. Bone metastases usually appear as multiple foci of increased activity, although they occasionally manifest as areas of decreased uptake. Traumatic processes can often be detected, even when radiographic findings are negative. Most fractures are scintigraphically detectable within 24 hours, although in elderly patients with osteopenia, further imaging at a later time is sometimes indicated. Athletic individuals are prone to musculoskeletal trauma, and radionuclide bone imaging is useful for identifying pathologic conditions such as plantar fasciitis, stress fractures, "shin splints," and spondylolysis, for which radiographs may be nondiagnostic. A combination of focal hyperperfusion, focal hyperemia, and focally increased bone uptake is virtually diagnostic for osteomyelitis in patients with nonviolated bone. Bone scintigraphy is also useful for evaluating disease extent in Paget disease and for localizing avascular necrosis in patients with negative radiographs. Radionuclide bone imaging will likely remain a popular and important imaging modality for years to come.

Some complications of joint replacement surgery are easily diagnosed; however, differentiating infection from aseptic loosening is difficult because these entities are remarkably similar at clinical and histopathologic examination. Clinical signs and symptoms, laboratory tests, radiography, and joint aspiration are insensitive, nonspecific, or both. Cross-sectional imaging modalities are hampered by artifacts produced by the prosthetic devices themselves. Radionuclide imaging is not affected by the presence of metallic hardware and is therefore useful for evaluating the painful prosthesis. Bone scintigraphy is useful as a screening test, despite an accuracy of only 50%-70%, because normal results essentially exclude a prosthetic complication. The addition of gallium-67, a nonspecific inflammation-imaging agent, improves the accuracy of bone scintigraphy to 70%-80%. The accuracy of combined leukocyte-marrow imaging, 90%, is the highest among available radionuclide studies. Its success is due to the fact that leukocyte imaging is most sensitive for detection of neutrophil-mediated inflammation (ie, infection). The success of leukocyte-marrow imaging is tempered by the limitations of in vitro labeling. In vivo labeling has been investigated, and a murine monoclonal antigranulocyte antibody appears promising. Some investigations have focused on fluorodeoxyglucose imaging. Although this method is sensitive, specificity is a concern.

Prosthetic joint replacement surgery is performed with increasing frequency. Overall the incidence of prosthetic joint infection (PJI) and subsequently prosthesis revision failure is estimated to be between 1 and 3%. Differentiating infection from aseptic mechanical loosening, which is the most common cause of prosthetic failure, is especially important because of different types of therapeutic management. Despite a thorough patient history, physical examination, multiple diagnostic tests and complex algorithms, differentiating PJI from aseptic loosening remains challenging. Among imaging modalities, radiographs are neither sensitive nor specific and cross-sectional imaging techniques, such as computed tomography and magnetic resonance imaging, are limited by hardware-induced artefacts. Radionuclide imaging reflects functional rather than anatomical changes and is not hampered by the presence of a metallic joint prosthesis. As a result scintigraphy is currently the modality of choice in the investigation of suspected PJI. Unfortunately, there is no true consensus about the gold standard technique since there are several drawbacks and limitations inherent to each modality. Bone scintigraphy (BS) is sensitive for identifying the failed joint replacement, but cannot differentiate between infection and aseptic loosening. Combined bone/gallium scintigraphy (BS/GS) offers modest improvement over BS alone for diagnosing PJI. However, due to a number of drawbacks, BS/GS has generally been superseded by other techniques but it still may have a role in neutropenic patients. Radiolabelled leucocyte scintigraphy remains the gold standard technique for diagnosing neutrophil-mediated processes. It seems to be that combined in vitro labelled leucocyte/bone marrow scintigraphy (LS/BMS), with an accuracy of about 90%, is currently the imaging modality of choice for diagnosing PJI. There are, however, significant limitations using in vitro labelled leucocytes and considerable effort has been devoted to developing alternative radiotracers, such as radiolabelled HIGs, liposomes, antigranulocyte antibodies and fragments, as well as more investigational tracers such as radiolabelled antibiotics, antimicrobial peptides, bacteriophages and thymidine kinase. On the other hand, positron emission tomography (PET) is still growing in the field of PJI imaging with radiotracers such as (18)F-fluorodeoxyglucose (FDG), (18)F-FDG white blood cells and (18)F-fluoride. But unfortunately this superb tomographic technique will only receive full acceptance when specific PET uptake patterns can be successfully developed. The emergence of hybrid modality imaging using integrated single photon emission computed tomography (SPECT) and PET with computed tomography (SPECT/CT and PET/CT) may also have a contributing role for more accurate assessment of joint replacement complications, especially combined with new radiotracers such as (68)Ga and (64)Cu. Finally, in searching for infection-specific tracers, currently there is no such diagnostic agent available.

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The use of labeled leukocyte (white blood cell [WBC]) studies in the diagnosis of osteomyelitis can be problematic. A combined study consisting of WBC imaging and complementary bone marrow imaging performed with technetium 99m (99mTc) sulfur colloid is approximately 90% accurate and is especially useful for diagnosing osteomyelitis in situations involving altered marrow distribution. There are limitations and pitfalls associated with a combined study. If there is no labeled WBC activity in the region of interest, marrow imaging is not useful. The sulfur colloid image becomes photopenic within about 1 week after the onset of infection, so that the study should be interpreted cautiously in the acute setting. Labeled WBC accumulation in lymph nodes can also confound image interpretation, although nodal activity can usually be recognized because it is typically round, discrete, multifocal, linear in distribution, and often bilateral. Furthermore, 99mTc-sulfur colloid that is improperly prepared or is more than about 2 hours old degrades image quality, potentially causing erroneous conclusions. Nevertheless, WBC-marrow imaging is a very accurate technique for diagnosing osteomyelitis. Knowledge of the criteria for image interpretation and of the aforementioned limitations and pitfalls, combined with careful attention to imaging technique, will maximize the value of this study.

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SummaryDespite significant advances in the understanding of its pathogenesis, infection remains a major cause of patient morbidity and mortality. While the presence of infection may be suggested by signs and symptoms, imaging tests are often used to localize or confirm its presence. There are two principal imaging test types: morphological and functional. Morphological tests include radiographs, computed tomography (CT), magnetic resonance imaging, and sonongraphy. These procedures detect anatomic, or structural, alterations produced by microbial invasion and host response. Functional imaging tests reflect the physiological changes that are part of this process. Prototypical functional tests are radionuclide procedures such as bone, gallium, labelled leukocyte and fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging. In-line functional/morphological tomographic imaging systems, PET/CT and single photon emission tomography (SPECT)/CT, have revolutionized diagnostic imaging. These devices consist of a functional imaging device (PET or SPECT) joined together with a CT scanner. The patient undergoes both tests sequentially without leaving the examination table. Images from each study can be viewed separately and as fused images, providing precisely localized anatomic and functional information. It must be noted, however, that none of the current morphological or functional tests, either alone or in combination, are specific for infection and the goal of finding such an imaging test remains elusive.