(Radiographics. 2000;20:1649-1660.)
© RSNA, 2000
Role of Radionuclide Imaging in the Diagnosis of Postoperative Infection1
Christopher J. Palestro, MD ,
Charito Love, MD ,
Gene G. Tronco, MD and
Maria B. Tomas, MD
1 From the Division of Nuclear Medicine, Department of Radiology, Long Island Jewish Medical Center, 270-05 76th Ave, New Hyde Park, NY 11040. Recipient of a Certificate of Merit award for a scientific exhibit at the 1999 RSNA scientific assembly. Received April 5, 2000; revision requested April 28 and received June 23; accepted June 26. Address correspondence to C.J.P. (e-mail: palestro@lij.edu).
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Abstract
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Postoperative infections are a serious cause of morbidity and mortality and are difficult to diagnose. Signs and symptoms that are generally associated with infection may be masked by, or mistaken for, normal postoperative changes. Anatomic imaging modalities provide high-quality anatomic detail and are the procedures of choice in affected patients because of their availability, ease of performance, accuracy, and value in the selection of treatment options. However, radionuclide studies demonstrate physiologic processes, which often precede anatomic changes, and can help distinguish normal postoperative inflammation from infection. Radionuclide studies are also useful in identifying complicated orthopedic infections, in which the often extensive distortions produced by metallic hardware can confound the interpretation of anatomic images. Of the three agents (gallium-67 citrate, indium-111–labeled leukocytes, technetium-99m–labeled leukocytes) that are currently approved in the United States for imaging of infection, In-111–labeled leukocyte imaging is the procedure of choice for diagnosing postoperative infection. Gallium scintigraphy is best reserved for those situations in which leukocyte imaging is not available or there is concern that the suspected infection may not incite a neutrophil response. In general, the value of radionuclide imaging is maximized when used only in those patients for whom the results of anatomic imaging are negative, nondiagnostic, or at odds with the clinical impression.
Index Terms: Gallium, radioactive, **.1216,2 **.20 • Indium, radioactive, **.1216, **.20 • Leukocytes, **.1216, **.20 • Radionuclide imaging, **.1216, **.20 • Radionuclide imaging, comparative studies, **.1216, **.20 • Radionuclides, comparative studies, **.1216, **.20
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LEARNING OBJECTIVES
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After reading this article and taking the test, the reader will be able to:
- Identify the factors that affect gallium accumulation and labeled leukocyte uptake in the setting of infection.
- Describe the role of radionuclide imaging in the febrile postoperative patient.
- Discuss the principles and methods of interpreting combined leukocyte–bone marrow imaging.
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Introduction
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Infections are a significant cause of morbidity and mortality in postoperative patients. Surgical wound infections and pneumonia are the most commonly encountered postoperative infections. The patient's preoperative state and the nature of the surgery itself are important determinants of the risk of developing postoperative infections. Preoperative organ system dysfunction, obesity, advanced age, tobacco use, and preoperative colonization with methicillin-resistant Staphylococcus aureus are all associated with an increased prevalence of postoperative infection. Surgery-related factors including wound class, surgical site, duration of the procedure, perioperative complications, and the type and timing of preoperative antibiotic prophylaxis also affect the likelihood of postoperative infection (1–3).
The diagnosis of infection in the postoperative patient is difficult. Signs and symptoms generally associated with infection may be masked by, or misconstrued as, normal postoperative changes. Abscesses are especially difficult to diagnose clinically because the infection is contained within a wall of fibrin and collagen and physical examination findings may be minimal (4).
Consequently, imaging plays an important role in the identification of postoperative infection. Ultrasonography, computed tomography (CT), and magnetic resonance (MR) imaging provide high-quality anatomic information. CT is the prevailing standard of reference for the diagnosis of intraabdominal abscess and is typically the first imaging study performed in the postoperative patient (4,5). Nuclear medicine studies furnish salient physiologic information and are therefore complementary to the anatomic imaging modalities. In the United States, gallium-67, indium-111–labeled leukocytes, and technetium-99m–labeled leukocytes are the only approved radionuclide agents for imaging of infection and inflammation.
In this article, we discuss and illustrate the role of gallium-67 imaging and labeled leukocyte imaging in the diagnosis of postoperative infections including pneumonia, abdominal abscess, vascular graft infection, and orthopedic hardware–related infection.
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Ga-67 Imaging
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Ga-67, a cyclotron-produced radionuclide, has been used for localizing infection for nearly 30 years. Although this radiotracer, with a half-life of 78 hours, emits a broad spectrum of gamma rays between 93 keV and 880 keV, the energy peaks that are most suitable for gamma camera imaging are 93 keV, 184 keV, 296 keV, and 388 keV. Between 10% and 25% of the administered dose is excreted through the kidneys within 24 hours after injection, after which time the principal excretory pathway is the colon. At 72 hours after injection, approximately 75% of the administered dose remains within the body, equally distributed among the soft tissues, liver, and bone or bone marrow. However, this normal distribution can vary considerably. Nasopharyngeal and lacrimal gland uptake can be prominent, even in the absence of any abnormality. Although usually faint and symmetric, breast uptake may be intense in pregnant and lactating women and in patients with renal failure or hypothalamic lesions. Normally healing surgical incisions may also demonstrate increased uptake of Ga-67. Large bowel uptake is variable and at times can confound study interpretation (Figs 1, 2) (6).
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Figure 1. Variations in normal distribution of gallium in four different patients. All four images were obtained 72 hours after injection. Gallium image in A demonstrates mild orbital activity with faint bowel uptake. Gallium image in B demonstrates breast uptake that is prominent but still normal. Gallium image in C demonstrates intense linear midline uptake extending from the lower thorax into the upper abdomen, a finding that represents a normally healing surgical incision. The superior mediastinal activity proved to be secondary to nodal involvement by Hodgkin disease. On a gallium image obtained in a child (D), bone marrow uptake is prominent with relatively less soft-tissue activity. Note the gastric uptake, another normal variant, in the left upper quadrant (arrows).
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Figure 2a. Variations in large bowel uptake of gallium. Gallium images obtained 72 hours after injection in four different patients (a-d) demonstrate large bowel activity that is highly variable both in distribution and intensity. None of these patients had colonic disease.
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Figure 2b. Variations in large bowel uptake of gallium. Gallium images obtained 72 hours after injection in four different patients (a-d) demonstrate large bowel activity that is highly variable both in distribution and intensity. None of these patients had colonic disease.
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Figure 2c. Variations in large bowel uptake of gallium. Gallium images obtained 72 hours after injection in four different patients (a-d) demonstrate large bowel activity that is highly variable both in distribution and intensity. None of these patients had colonic disease.
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Figure 2d. Variations in large bowel uptake of gallium. Gallium images obtained 72 hours after injection in four different patients (a-d) demonstrate large bowel activity that is highly variable both in distribution and intensity. None of these patients had colonic disease.
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There are several factors that govern the uptake of gallium in infection. About 90% of circulating gallium is in the plasma and is mostly protein-bound, principally to transferrin. Increased blood flow and vascular membrane permeability result in increased delivery and accumulation of plasma proteins, and hence of gallium, at inflammatory sites. To some degree, gallium is transported by means of leukocytes. Direct uptake by bacteria such as S aureus has been observed in vitro. Siderophores, low-molecular-weight chelates produced by bacteria, have a high affinity for gallium. It is believed that the siderophore-gallium complex is transported into the bacterium, where it remains until phagocytosis by macrophages occurs. Other plasma proteins also account for some gallium uptake in infection. In addition to transferrin, gallium also binds to lactoferrin, which is present in high concentrations in inflammatory foci. It is believed that gallium, delivered to the site of infection primarily as a gallium-transferrin complex, dissociates from the transferrin and forms a gallium-lactoferrin complex (7).
Imaging is typically performed 48–72 hours after injection. The large bowel excretes gallium, and the presence of colonic activity can confound image interpretation. Single photon emission CT or delayed imaging can facilitate the differentiation of physiologic bowel uptake from true abnormalities (Fig 3). However, the value of routine use of laxatives is questionable (8,9).
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Figure 3a. Psoas abscess in a 21-year-old woman who presented with left hip pain. The patient had a history of a left femoral fracture requiring surgical intervention. Results of MR imaging performed at another institution were normal, and the patient was referred to the nuclear medicine department for evaluation of suspected osteomyelitis. (a) Anterior gallium image obtained 48 hours after injection demonstrates left lower quadrant activity (arrow), a finding that could easily be misinterpreted as normal bowel activity. (b) Coronal (top) and transverse (bottom) single photon emission CT scans clearly demonstrate that the activity lies outside the bowel (cf Fig 19).
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Figure 3b. Psoas abscess in a 21-year-old woman who presented with left hip pain. The patient had a history of a left femoral fracture requiring surgical intervention. Results of MR imaging performed at another institution were normal, and the patient was referred to the nuclear medicine department for evaluation of suspected osteomyelitis. (a) Anterior gallium image obtained 48 hours after injection demonstrates left lower quadrant activity (arrow), a finding that could easily be misinterpreted as normal bowel activity. (b) Coronal (top) and transverse (bottom) single photon emission CT scans clearly demonstrate that the activity lies outside the bowel (cf Fig 19).
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Labeled Leukocyte Imaging
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Technique
Labeled leukocyte scintigraphy is often used in the evaluation of postoperative fever. Approximately 40 mL of whole blood is drawn into a syringe containing an anticoagulant. The syringe is allowed to stand upright for 1–2 hours to permit the sedimentation of erythrocytes. This is facilitated by the addition of hydroxyethyl starch. The leukocytes are subsequently separated from platelets with centrifugation and collect at the bottom of the tube, forming a pellet. This pellet, which consists of a mixed population of leukocytes, is then labeled with either In-111 oxine or Tc-99m exametazine oxine. The entire procedure takes approximately 3 hours.
Uptake of labeled cells depends on intact chemotaxis, the number and type of cells labeled, and the principal cellular component of a given inflammatory response. Leukocyte labeling is now a routine procedure, and when performed according to standard methodology, it allows preservation of the chemotactic response. It is generally agreed that a total white blood cell count of at least 2,000/mm3 is necessary to obtain a satisfactory study. In most clinical settings, the majority of labeled cells are neutrophils; thus, the procedure is most useful for identifying neutrophil-mediated inflammatory processes. The technique is less sensitive for detecting inflammatory processes in which the cellular response is other than neutrophilic. The normal biodistribution of In-111–labeled leukocytes is limited to the liver, spleen, and bone marrow (Fig 4). Tc-99m–labeled leukocytes also accumulate in the reticuloendothelial system as well as in the genitourinary tract, large bowel, blood pool, and, occasionally, the gallbladder. In-111–labeled leukocyte imaging is advantageous in that, unlike gallium or Tc-99m–labeled leukocytes, activity is not generally present in the normal gastrointestinal or genitourinary tract. Although Tc-99m–labeled leukocyte imaging provides better resolution, delayed imaging may be necessary to detect abscesses. For these reasons, In-111–labeled leukocyte imaging is the preferred method for detecting infection in the postoperative patient (10).
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Figure 4. Normal distribution of In-111-labeled leukocytes. Anterior (left) and posterior (right) labeled leukocyte images obtained about 24 hours after injection demonstrate activity that is confined to the liver, spleen, and bone marrow.
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Pitfalls
Assessment of the postoperative patient, especially in the immediate postsurgical phase, is challenging, and if the value of radionuclide imaging is to be maximized, certain pitfalls must be recognized. Labeled leukocytes do not accumulate in normally healing surgical wounds, so that the presence of such activity is indicative of infection. There are, however, certain exceptions. Wounds that heal by secondary intention ("granulating wounds") can manifest as areas of intense activity on leukocyte images even in the absence of infection. Examples include "ostomies" (eg, colostomy, tracheostomy) (Fig 5) and skin grafts. Up to about 4 hours after injection, diffuse pulmonary uptake of labeled leukocytes is a normal physiologic event. By 24 hours, such uptake is abnormal and is usually related to a clinically obvious condition such as pneumonia or adult respiratory distress syndrome. Occasionally, diffuse lung activity is observed in a severely septic patient with no respiratory tract abnormalities. This uptake is probably secondary to cytokine release at the site of infection with subsequent activation of granulocytes and the pulmonary vascular endothelium (Fig 6) (11). In-111–labeled leukocyte uptake in the bowel is abnormal because leukocytes do not accumulate in the normal colon. In the hospitalized patient, a frequent cause of such activity is antibiotic-associated (pseudomembranous) colitis (Fig 7). Other possible causes include ischemic colitis, inflammatory bowel disease, and gastrointestinal bleeding. Finally, because leukocytes are a blood component, they will accumulate at sites of active bleeding as long as they are within the circulation. Focal uptake, especially when superficial in location, requires careful clinical correlation. Vascular access lines, dialysis catheters, and even lumbar punctures can all yield false-positive results in the absence of appropriate clinical history (Fig 8).
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Figure 5. Normal postoperative accumulation of labeled leukocytes. Anterior labeled leukocyte image obtained about 24 hours after injection shows activity at the sites of a tracheostomy (top arrow) and gastrostomy (bottom arrow). Note also the uptake of labeled cells in the right lung, a finding that represents pneumonia.
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Figure 6. Diffuse bilateral pulmonary uptake of labeled leukocytes in a septic patient with no respiratory distress. Repeat sputum cultures and chest radiographs were all negative. Anterior (left) and posterior (right) labeled leukocyte images obtained about 24 hours after injection show increased uptake in the lungs. This uptake is probably related to the release of cytokines, which cause activation of leukocytes and the pulmonary vascular endothelium.
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Figure 7. Antibiotic-associated (pseudomembranous) colitis in a patient who had been treated with multiple antibiotics. Anterior abdominal labeled leukocyte image obtained about 24 hours after injection demonstrates accumulation throughout the colon. Although the cause of this finding is variable, the most likely diagnosis in patients receiving antibiotics is pseudomembranous colitis.
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Figure 8. Increased uptake due to bleeding in a patient who underwent femoral puncture for hemodialysis a few hours after reinjection of labeled leukocytes. Anterior pelvic image obtained about 24 hours after injection shows intense activity in the left groin (arrow) that is due to bleeding rather than infection.
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Anatomic versus Radionuclide Imaging
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Because of its high sensitivity and its capacity to allow rapid whole-body assessment, radionuclide imaging has historically been the initial procedure performed in evaluation for infection. Over the past two decades, however, important changes have occurred. Rapid assessment of the entire body is no longer the exclusive domain of nuclear medicine. State-of-the-art CT allows imaging of the thorax and abdomen in minutes and is comparable to radionuclide imaging in terms of sensitivity. Equally important is the evolution of the treatment of postoperative infections. At one time, many of these infections were surgically drained. Despite its limited anatomic resolution, radionuclide imaging was often sufficient to allow the surgeon to proceed with any necessary intervention. Today, many postoperative infections are drained percutaneously with CT guidance. These procedures require far more anatomic detail than that provided by radionuclide images. Consequently, the majority of patients—even those who undergo diagnostic radionuclide studies—must undergo anatomic imaging (Fig 9). In terms of present-day, cost-effective health care, a more reasonable approach is to start the work-up of the febrile postoperative patient with anatomic imaging, the role of nuclear medicine in this population being complementary. Reserving radionuclide imaging for specific situations can maximize its value.
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Figure 9a. Abscess in a 10-year-old girl who was referred to the nuclear medicine department for evaluation of possible right hip osteomyelitis. (a) Anterior and posterior labeled leukocyte images of the abdomen obtained about 24 hours after injection demonstrate intense uptake in the right flank extending from the liver to the pelvis. (b) CT scan obtained a day later demonstrates a large, presumably appendiceal abscess that was subsequently drained. Despite the finding in a, diagnosis and drainage could easily have been accomplished with CT alone. In fact, if the initial clinical impression had been appendicitis rather than osteomyelitis, the patient would never have been referred to the nuclear medicine department. (Reproduced, with permission, from reference 10.)
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Figure 9b. Abscess in a 10-year-old girl who was referred to the nuclear medicine department for evaluation of possible right hip osteomyelitis. (a) Anterior and posterior labeled leukocyte images of the abdomen obtained about 24 hours after injection demonstrate intense uptake in the right flank extending from the liver to the pelvis. (b) CT scan obtained a day later demonstrates a large, presumably appendiceal abscess that was subsequently drained. Despite the finding in a, diagnosis and drainage could easily have been accomplished with CT alone. In fact, if the initial clinical impression had been appendicitis rather than osteomyelitis, the patient would never have been referred to the nuclear medicine department. (Reproduced, with permission, from reference 10.)
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Types of Postoperative Infection
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Pneumonia
Pneumonia occurs in up to 50% of postoperative patients (12). Although the diagnosis is usually made with chest radiography, radionuclide imaging can at times prove useful (Fig 10).
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Figure 10a. Pneumonia in a 32-year-old woman who was undergoing hemodialysis. Results of blood cultures were positive. (a) Chest radiograph obtained at the time of admission is negative. (b) Anterior (left) and posterior (right) labeled leukocyte images obtained 24 hours later demonstrate no graft infection, but intense uptake is seen in the right midlung. (c) Chest radiograph obtained 24 hours after b demonstrates a corresponding area of consolidation. (Reproduced, with permission, from reference 10.)
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Figure 10b. Pneumonia in a 32-year-old woman who was undergoing hemodialysis. Results of blood cultures were positive. (a) Chest radiograph obtained at the time of admission is negative. (b) Anterior (left) and posterior (right) labeled leukocyte images obtained 24 hours later demonstrate no graft infection, but intense uptake is seen in the right midlung. (c) Chest radiograph obtained 24 hours after b demonstrates a corresponding area of consolidation. (Reproduced, with permission, from reference 10.)
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Figure 10c. Pneumonia in a 32-year-old woman who was undergoing hemodialysis. Results of blood cultures were positive. (a) Chest radiograph obtained at the time of admission is negative. (b) Anterior (left) and posterior (right) labeled leukocyte images obtained 24 hours later demonstrate no graft infection, but intense uptake is seen in the right midlung. (c) Chest radiograph obtained 24 hours after b demonstrates a corresponding area of consolidation. (Reproduced, with permission, from reference 10.)
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Abdominal Abscess
The accuracy of CT in diagnosing intraabdominal abscess in unselected patients has been reported to be over 95% (13,14). Associated soft-tissue inflammation and anatomic distortions produced by peritonitis or trauma may hinder the distinction of normal postoperative changes from infection (14). Nuclear medicine procedures demonstrate physiologic processes, which often precede anatomic changes, and can help distinguish normal postoperative inflammation from infection (Figs 11, 12).
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Figure 11a. Abscess in a 52-year-old woman with left groin pain who had undergone percutaneous femoral angiography. CT performed 5 days after angiography demonstrated normal findings. Because of unrelenting hip pain and an elevated erythrocyte sedimentation rate, a labeled leukocyte study was performed 10 days later. (a) Anterior (left) and left lateral (right) labeled leukocyte images of the pelvis obtained about 24 hours after injection demonstrate intense uptake in the left lower quadrant of the abdomen and extending into the proximal thigh. (b) Repeat CT scan obtained with administration of contrast material helps confirm a large left psoas abscess.
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Figure 11b. Abscess in a 52-year-old woman with left groin pain who had undergone percutaneous femoral angiography. CT performed 5 days after angiography demonstrated normal findings. Because of unrelenting hip pain and an elevated erythrocyte sedimentation rate, a labeled leukocyte study was performed 10 days later. (a) Anterior (left) and left lateral (right) labeled leukocyte images of the pelvis obtained about 24 hours after injection demonstrate intense uptake in the left lower quadrant of the abdomen and extending into the proximal thigh. (b) Repeat CT scan obtained with administration of contrast material helps confirm a large left psoas abscess.
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Figure 12a. Postsurgical abscess in a 52-year-old man with spiking fevers who had undergone appendectomy. (a) CT scan of the abdominopelvic region obtained 5 days after surgery demonstrates only postoperative changes. (b, c) Planar (b) and transverse and coronal tomographic (c) labeled leukocyte images of the pelvis obtained about 24 hours after injection demonstrate abnormal uptake in both the surgical bed (arrowhead) and superficially at the incision site (arrow). Subsequently, pus began draining through the incision. The patient improved with intravenous antibiotic therapy.
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Figure 12b. Postsurgical abscess in a 52-year-old man with spiking fevers who had undergone appendectomy. (a) CT scan of the abdominopelvic region obtained 5 days after surgery demonstrates only postoperative changes. (b, c) Planar (b) and transverse and coronal tomographic (c) labeled leukocyte images of the pelvis obtained about 24 hours after injection demonstrate abnormal uptake in both the surgical bed (arrowhead) and superficially at the incision site (arrow). Subsequently, pus began draining through the incision. The patient improved with intravenous antibiotic therapy.
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Figure 12c. Postsurgical abscess in a 52-year-old man with spiking fevers who had undergone appendectomy. (a) CT scan of the abdominopelvic region obtained 5 days after surgery demonstrates only postoperative changes. (b, c) Planar (b) and transverse and coronal tomographic (c) labeled leukocyte images of the pelvis obtained about 24 hours after injection demonstrate abnormal uptake in both the surgical bed (arrowhead) and superficially at the incision site (arrow). Subsequently, pus began draining through the incision. The patient improved with intravenous antibiotic therapy.
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Vascular Graft Infection
Medical progress has made the use of prosthetics a popular option in almost every part of the body. Unfortunately, any foreign substance is a nidus for infection. The reported frequency of synthetic vascular graft infection is less than 5% (15), but delay in establishing the diagnosis is an important factor in the high morbidity and mortality rates associated with this condition. CT is often the first imaging test performed to evaluate suspected graft infections. Interestingly, labeled leukocyte imaging has demonstrated very good results in detecting occult graft infection when anatomic modalities have failed (Fig 13) (15). Labeled leukocyte imaging is uniquely successful in the detection of infected hemodialysis grafts (Fig 14) (16).
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Figure 13a. Vascular graft infection in a 74-year-old man with a left femoral bypass graft who presented with septicemia. The patient had undergone subtotal colectomy 4 weeks earlier. (a) CT scan depicts only a skin defect extending to the ventral surface of the graft (arrow). The usefulness of CT was limited by metallic hardware in both hips. (b) Anterior labeled leukocyte image obtained about 24 hours after injection demonstrates intense uptake (arrow) representing an infected vascular graft.
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Figure 13b. Vascular graft infection in a 74-year-old man with a left femoral bypass graft who presented with septicemia. The patient had undergone subtotal colectomy 4 weeks earlier. (a) CT scan depicts only a skin defect extending to the ventral surface of the graft (arrow). The usefulness of CT was limited by metallic hardware in both hips. (b) Anterior labeled leukocyte image obtained about 24 hours after injection demonstrates intense uptake (arrow) representing an infected vascular graft.
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Hemodialysis graft infection. Labeled leukocyte images obtained about 24 hours after injection show intense uptake in the upper extremity representing an infected arteriovenous hemodialysis graft.
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Orthopedic Hardware–related Infection
Postsurgical anatomic distortion and the metallic prostheses themselves can hinder the interpretation of high-resolution anatomic studies. Nuclear medicine techniques, notably combined leukocyte–bone marrow imaging, are especially useful in these situations. Although leukocytes do not usually accumulate at sites of increased bone mineral turnover in the absence of infection, they do accumulate in the bone marrow. The implantation of orthopedic hardware can alter the normal distribution of hematopoietically active marrow, making it difficult to distinguish uptake of labeled leukocytes in infection from uptake in marrow. This problem can be overcome by performing complementary bone marrow scintigraphy with Tc-99m sulfur colloid. Both labeled leukocytes and sulfur colloid accumulate in the marrow, whereas only leukocytes accumulate in infection. Hence, images on which the distribution of the two radiotracers is the same indicate that the leukocyte uptake involves the marrow (Fig 15). Activity on the leukocyte image without corresponding activity on the bone marrow image indicates that the leukocyte uptake is due to infection (Fig 16). The accuracy of this dual radiotracer technique exceeds 90% (17).
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Figure 15a. Increased bone marrow uptake in an 86-year-old woman who was referred for evaluation of possible osteomyelitis. The patient had sustained right lower extremity fractures 1 month earlier. (a) Radiograph reveals multiple fractures of the right tibia and fibula. An internal fixation device is seen in the tibia. (b) Labeled leukocyte image obtained about 24 hours after injection (left) shows intense uptake in the right tibia, a finding that could easily be misinterpreted as osteomyelitis. However, this same uptake pattern is also present on a bone marrow scan (right), which indicates that the labeled leukocyte uptake represents marrow (albeit atypical in location) rather than infection. Thus, when taken together, the two images are negative for infection.
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Figure 15b. Increased bone marrow uptake in an 86-year-old woman who was referred for evaluation of possible osteomyelitis. The patient had sustained right lower extremity fractures 1 month earlier. (a) Radiograph reveals multiple fractures of the right tibia and fibula. An internal fixation device is seen in the tibia. (b) Labeled leukocyte image obtained about 24 hours after injection (left) shows intense uptake in the right tibia, a finding that could easily be misinterpreted as osteomyelitis. However, this same uptake pattern is also present on a bone marrow scan (right), which indicates that the labeled leukocyte uptake represents marrow (albeit atypical in location) rather than infection. Thus, when taken together, the two images are negative for infection.
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Figure 16. Increased uptake due to infection in an 84-year-old man with an infected right hip prosthesis. Labeled leukocyte image obtained about 24 hours after injection (left) appears negative for infection of the right hip (arrow). However, a bone marrow scan (right) clearly demonstrates the absence of uptake in the right hip (arrow). Thus, when taken together, the two images are positive for infection. Intensity of uptake is not a reliable criterion for determining whether infection is present.
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Newer Imaging Agents
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Leukocytes are components of inflammation, which explains the value of labeled leukocyte imaging in the diagnosis of infection. The major disadvantage of this imaging method is the need for in vitro labeling of cells.
This has led to the investigation of in vivo leukocyte labeling. One in vivo technique makes use of a peptide, P483, a derivative of platelet factor 4. When P483 is complexed with heparin, the resulting compound, P483H, is leukocyte-avid. Preliminary results suggest that imaging with this agent is comparable to in vitro–labeled leukocyte imaging (Fig 17) (18).
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Figure 17. Arteriovenous dialysis graft infection in a 70-year-old woman. Peptide image of the left forearm obtained about 90 minutes after injection (left) demonstrates excellent resolution. A corresponding labeled leukocyte image (right) was obtained about 24 hours after injection. Both images demonstrate uptake in the infected graft.
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It is also possible to label leukocytes with antigranulocyte antibodies. Use of a murine monoclonal immunoglobulin M antibody, which binds to CD-15 receptors on leukocytes, is currently under investigation (Fig 18) (19). Use of a murine monoclonal antibody fragment, which binds to normal cross-reactive antigen-90 present on granulocytes, has been the subject of extensive clinical trials. The advantages of imaging with an antibody fragment rather than with a whole antibody include rapid clearance, which permits earlier imaging, and a lower prevalence of human antimurine antibody formation (20). None of these agents is currently available for routine use in the United States.
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Figure 18a. Diverticulitis in a 75-year-old woman who was referred to the nuclear medicine department because of persistent hip pain. The patient had recently undergone left hip replacement surgery. A monoclonal antibody study was performed to rule out infection. (a) Anterior (left) and posterior (right) antibody images obtained about 24 hours after injection demonstrate intense uptake within the pelvic midline (arrow), despite the fact that the left hip prosthesis was normal. (b) Subsequent CT scan reveals diverticulitis.
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Figure 18b. Diverticulitis in a 75-year-old woman who was referred to the nuclear medicine department because of persistent hip pain. The patient had recently undergone left hip replacement surgery. A monoclonal antibody study was performed to rule out infection. (a) Anterior (left) and posterior (right) antibody images obtained about 24 hours after injection demonstrate intense uptake within the pelvic midline (arrow), despite the fact that the left hip prosthesis was normal. (b) Subsequent CT scan reveals diverticulitis.
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Regardless of how the cells are labeled, the success of a leukocyte study depends on the migration of labeled cells, predominantly neutrophils, to the focus of infection. Infections that do not incite a neutrophilic response or in which the neutrophilic response has waned may go undetected (10). Consequently, although labeled leukocyte imaging may be the preferred radionuclide method for evaluating the postoperative patient, gallium imaging should not be totally discarded (Fig 19).
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Figure 19a. Psoas abscess in the same patient as in (a) Labeled leukocyte image obtained about 24 hours after injection (left) demonstrates normal findings, whereas abnormal activity is seen in the left lower quadrant on a gallium image (right) (arrow). (b) Transverse and coronal tomographic gallium images more clearly demonstrate the abnormality (arrows). (c) CT scan reveals a left psoas abscess.
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Figure 19b. Psoas abscess in the same patient as in (a) Labeled leukocyte image obtained about 24 hours after injection (left) demonstrates normal findings, whereas abnormal activity is seen in the left lower quadrant on a gallium image (right) (arrow). (b) Transverse and coronal tomographic gallium images more clearly demonstrate the abnormality (arrows). (c) CT scan reveals a left psoas abscess.
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View larger version (111K):
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Figure 19c. Psoas abscess in the same patient as in (a) Labeled leukocyte image obtained about 24 hours after injection (left) demonstrates normal findings, whereas abnormal activity is seen in the left lower quadrant on a gallium image (right) (arrow). (b) Transverse and coronal tomographic gallium images more clearly demonstrate the abnormality (arrows). (c) CT scan reveals a left psoas abscess.
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Conclusions
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Because of their availability, ease of performance, accuracy, and importance in patient treatment, anatomic imaging modalities are the procedures of choice in the febrile postoperative patient. Radionuclide imaging is best reserved for those patients in whom anatomic imaging is negative, nondiagnostic, or at odds with the clinical impression.
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Footnotes
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**. indicates multiple body systems. 
See the commentary by Sarkar
following this article.
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References
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Abstract
LEARNING OBJECTIVES
