Radiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online before print December 11, 2002, 10.1148/radiol.2262011939
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2262011939v1
226/2/391    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schiesser, M.
Right arrow Articles by von Schulthess, G. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schiesser, M.
Right arrow Articles by von Schulthess, G. K.
(Radiology 2003;226:391-398.)
© RSNA, 2003

Nuclear Medicine

Detection of Metallic Implant–associated Infections with FDG PET in Patients with Trauma: Correlation with Microbiologic Results1

Marc Schiesser, MD, Katrin D. M. Stumpe, MD, Otmar Trentz, MD, Thomas Kossmann, MD and Gustav K. von Schulthess, MD, PhD

1 From the Departments of Surgery, Division of Trauma Surgery (M.S., O.T.) and Medical Radiology, Division of Nuclear Medicine (K.D.M.S., G.K.v.S.), University Hospital, Rämistrasse 100, CH-8091 Zurich, Switzerland; and Department of Surgery, Division of Trauma Surgery, Monash University, Alfred Hospital, Melbourne, Australia (T.K.). From the 2001 RSNA scientific assembly. Received November 27, 2001; revision requested February 11, 2002; final revision received June 18; accepted June 27. Address correspondence to G.K.v.S. (e-mail: vonschulthess@dmr.usz.ch).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To prospectively evaluate the value of positron emission tomography (PET) with fluorine 18 fluorodeoxyglucose (FDG) in the detection of metallic implant–associated infections in patients with trauma.

MATERIALS AND METHODS: Twenty-nine partial-body FDG PET scans in 22 patients suspected of having metallic implant–associated infections were obtained prior to surgery. In two of the 22 patients, data were acquired with a combined PET-CT in-line system. Soft-tissue and bone infections were evaluated. PET scans were analyzed by two experienced nuclear medicine physicians first separately and then in consensus. Disease status was defined on the basis of the results of microbiologic evaluation of surgical specimens together with intraoperative findings. Sensitivities, specificities, accuracies, interobserver variability (determination of {kappa} values), and receiver operating characteristic curves were obtained.

RESULTS: Of 29 PET scans, 14 were true-positive, 14 were true-negative, and one was false-positive. Sensitivity, specificity, and accuracy were 100%, 93.3%, and 97%, respectively, for all PET data; 100%, 100%, and 100%, respectively, for the central skeleton; and 100%, 87.5%, and 95%, respectively, for the peripheral skeleton. The degree of overall interobserver concordance was high ({kappa} = 0.96).

CONCLUSION: FDG PET appears to be a sensitive and specific method for the detection of infectious foci due to metallic implants in patients with trauma.

© RSNA, 2003

Index terms: Bones, infection, 30.21, 30.453, 40.21, 40.453 • Computed tomography (CT), helical, 30.12115, 40.12115 • Dual-modality imaging, PET/CT • Metallic devices, 30.453, 40.453 • Positron emission tomography (PET), 30.12163, 30.12165, 40.12163, 40.12165


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
In contrast to acute osteomyelitis, the diagnosis of chronic or subacute osteomyelitis secondary to trauma or surgery is often difficult (1–3). The distinction between fracture instability and an implant-associated infection can hardly be achieved with the current imaging modalities, particularly in patients with nonunion fractures who had previously undergone surgery (4,5). Clinical signs and laboratory parameters are often uncharacteristic or even normal in the so-called low-grade infections (1). Furthermore, magnetic resonance (MR) imaging and computed tomography (CT) often display compromised image quality in patients with metallic implants. The distinction between soft-tissue and bone infection may not be possible (3,6–8). Therefore, the preoperative planning in patients suspected of having infections is difficult, and the choice of definitive surgical procedure often relies on intraoperative findings.

Several imaging modalities have been used in nuclear medicine to help diagnose osteomyelitis secondary to trauma. However, nonspecific tissue uptake of imaging agents and difficulty in distinguishing between osseous tissue and the surrounding soft-tissue infection due to limited spatial resolution restrict the usefulness of these methods (4,5,9). The current modalities are three-phase bone scanning, indium 111 (111In)-labeled leukocytes—often referred to as the standard of infection imaging (4,10)—gallium 67 scintigraphy (11), technetium 99m (99mTc) bone marrow scintigraphy (12), as well as those that use newer radiopharmaceuticals such as 99mTc-labeled monoclonal antibodies against granulocytic surface antigens and chemotactic peptides (13,14). In general, detection of infectious foci with white blood cell imaging is unsatisfactory in the central skeleton because of physiologic radiotracer accumulation in the hemopoietic bone marrow and frequent photopenic areas, especially in patients with chronic osteomyelitis (15–17). To improve sensitivity and specificity in the central skeleton in patients after trauma and surgery, a combination of colloid scintigraphy and white blood cell imaging has been used (18). However, the need for the two techniques exhibits several disadvantages. A single equally specific and sensitive technique would be welcome.

In past years, fluorine 18 fluorodeoxyglucose (FDG) PET imaging has attracted interest as a means to diagnose infectious lesions. Findings from recent studies about the role of FDG PET in infection imaging showed an accumulation of FDG in various infectious and inflammatory processes (19–21). It is known that granulocytes and mononuclear cells, which are present in areas of ongoing infection, show an increased glycolytic activity during their so-called respiratory burst, while normal bone marrow exhibits nearly no glucose utilization (22,23). Unlike combined white blood cell imaging, FDG PET is highly accurate in the detection of chronic osteomyelitis in the central skeleton (24,25). Early results are very promising and indicate that metallic implants generate few image artifacts with FDG PET. This suggests that FDG PET may be useful for the distinction of sterile nonunion fractures and osseous infections in patients with metallic implants. The purpose of this investigation was to prospectively evaluate the value of FDG PET in the detection of metallic implant–associated infections in patients with trauma.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
Between June 1999 and May 2001, we prospectively performed 29 partial-body FDG PET examinations in 22 immunocompetent patients suspected of having metallic implant–associated infection prior to surgery. All of the patients were referred to us by the traumatology service at the Department of Surgery, University Hospital, Zurich. Two of the 29 partial-body FDG PET scans were acquired with a combined PET-CT in-line system. Seven patients underwent surgery twice during the study period. Patients with joint replacements such as shoulder, hip, or knee prostheses were not included in the study. The suspicion of an infection was based on clinical signs. All patients included in the study had pain at motion or rest for at least 6 weeks prior to imaging.

Six women and 16 men (age range, 18–86 years; mean age, 44.1 years) were included in the study. Informed consent was obtained from all patients, and the study was approved by the hospital ethics committee. Every patient had an osseous metallic implant close to the suspected infectious focus. The interval between the last surgical intervention and the time of PET scanning ranged between 6 weeks and 14 months and was not used as an exclusion criterion. None of the examined patients was receiving antibiotic treatment prior to or during the performance of FDG PET. None of the examined patients had an infection prior to the traumatic event. The patients underwent FDG PET at most 3 days prior to the revision surgery. In three patients, no operation was performed owing to negative FDG PET findings. These patients were evaluated further at clinical follow-up. No infection was assumed in patients who had no further clinical symptoms and normal infection parameters for more than 6 months.

PET Imaging Protocol
FDG PET studies were performed with a PET scanner (Advance; GE Medical Systems, Waukesha, Wis). The scanner acquires 35 two-dimensional sections of 4.25 mm thickness per increment, with a transverse field of view of 14.6 cm. Up to four increments were acquired. The patients were asked to fast for at least 4 hours prior to the study. Thirty to 40 minutes prior to emission scanning, the patients received an intravenous injection of 300–400 MBq of FDG, which was produced in-house by using a 17.8-MeV cyclotron (PET Trace 2000; GE Medical Systems, Uppsala, Sweden) and an automated FDG synthesis module (PET Tracer Synthesizer; GE Nuclear Interface, Muenster, Germany). Corrected and uncorrected transaxial images were acquired. Image reconstruction was performed with a multiplicative iterative reconstruction algorithm for improvement of image quality and reduction of computation time (26).

PET-CT Imaging Protocol
In two patients, imaging and data acquisition were performed with a PET-CT in-line system (Discovery LS; GE Medical Systems, Waukesha), which combines the ability to acquire CT images and PET data of the same patient in one session. PET (Advance NXi; GE Medical Systems, Milwaukee, Wis) and multisection helical CT (LightSpeed plus; GE Medical System, Milwaukee) scanners were integrated in this dedicated system. The axes of both systems were mechanically aligned to coincide perfectly. The offset between the CT and PET scanner–sensitive field of views along the table axis was 60 cm. The same table was used to acquire PET and CT images. Because of mechanical limitations of this prototype table version, the table excursion permitted scanning of only six contiguous PET sections covering 867 mm. However, this gave adequate coverage from the head to the pelvic floor in all patients. The PET and CT data sets were acquired at two independent computer consoles, which were connected by an interface to transfer CT data to the PET scanner. Both machines can be used independently or as a combined system. CT data were acquired first. For viewing the images, which came from the system in a coregistered manner, the PET and CT data sets were transferred to an independent personal computer workstation in a digital imaging and communications in medicine format. All viewing of coregistered images was performed with dedicated software (eNTEGRA; Elgems, Haifa, Israel).

PET Image Evaluation
Image analysis was consistently performed by using a movie mode at a digital viewing system (Extended Viewing Station; GE Medical Systems, Waukesha).

The PET scans were analyzed by two board-certified nuclear medicine physicians (K.D.M.S, G.K.v.S.) with extended experience, first separately and then in consensus according to the following procedure: The readers were blinded to the results of other imaging studies and the final diagnosis. However, at the referring surgeon’s request, they were often aware of the possible site of the infectious focus. The readers were specifically asked to differentiate osseous from soft-tissue uptake. Images were analyzed as follows: First, physiologic FDG uptake, such as can occur into muscles, was identified and excluded from further analysis. Second, the lesions deemed to be pathologic were classified according to the following semiquantitative four-point grading scale: 0, FDG uptake as in the background; 1, low FDG uptake, comparable to uptake in inactive muscles and fat; 2, moderate FDG uptake clearly noticeable and distinctly higher than uptake into inactive muscles and fat; 3, high FDG uptake but distinctly lower than that noted in normal cerebral cortex; and 4, very high FDG uptake, comparable to normal cerebral cortex. This grading scale was adapted from Stumpe et al (21).

In this study, a receiver operating characteristic analysis in which the aforementioned grading scale was used showed that classification of grade 3 and 4 lesions as infectious foci yields the best discrimination between infected and noninfected lesions. To make sure that the infectious focus was not an artifact associated with misregistration between emission and transmission scans, the emission-only scans were evaluated as well. Only if the lesions were also clearly visible on these scans, the lesion was called infected. From these data, sensitivities, specificities, and accuracies were calculated for each observer for all data and for the central and the peripheral skeleton.

The clinical value of FDG PET information on the preoperative planning was retrospectively and independently analyzed by two experienced surgeons (M.S., T.K.) who performed the surgery. They classified the value of PET scans into two subgroups: relevant information (affecting therapeutic plan) and not relevant information (no further information).

Standard of Reference
The final diagnosis was made on the basis of results of the microbiologic evaluation of the surgical specimens and the intraoperative findings. The following categories were differentiated: osteomyelitis, soft-tissue infection, nonunion fracture, osseous necrosis, and no infection. In three cases in which no microbiologic samples were available, clinical follow-up for more than 6 months served as the standard of reference.

Statistical Evaluation
The ability to differentiate infection from noninfectious processes was determined for each reader separately by calculating the areas under the receiver operating characteristic curves (27). The interobserver agreement between the grading of the two readers was determined with a {kappa} statistic ({kappa} > 0.75 represents excellent agreement; {kappa} < 0.40, poor agreement; and {kappa} between 0.40 and 0.75, fair to good agreement) for all data and for the central and the peripheral skeleton.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Microbiologic evaluation was performed after 26 of 29 PET scans were obtained (Table 1). Of the 29 cases of trauma with clinically suspicious metallic implant–associated infection, 15 showed no infection according to the intraoperative findings and the microbiologic evaluation of the surgical specimen (n = 12) or the clinical follow-up (n = 3). Among these cases, there were six cases with sterile nonunion fractures and one case with an osseous necrosis. The duration of symptoms ranged between 6 and 60 weeks (Table 1). Clinically, all eight patients with bone infection presented with pain; two patients had an additional fistula, two had elevated white blood cell count and erythrocyte sedimentation rate, and in one patient no fracture consolidation had occurred (Table 1).


View this table:
[in this window]
[in a new window]

  		TABLE 1. Summary of Patient Characteristics and Diagnoses

 
In 14 of 29 cases, the bacteriologic culture was positive. According to intraoperative findings, there were six cases of soft-tissue infection and eight cases of osteomyelitis.

All osseous or soft-tissue infections were classified as infection at FDG PET and therefore were true-positive. None of the transmission-corrected scans showed prominent activity at the sites where the uncorrected scans showed little activity. There were no false-negative findings in this study (Table 1). Sensitivity was 100%. In the group of patients without apparent infection, 14 of 15 infections were classified as true-negative at FDG PET. There was one false-positive finding in a patient who had been surgically treated for osteomyelitis only 6 weeks prior to the FDG PET examination. In this case, FDG accumulation represented postoperative changes. Overall specificity was 93.3%. Sensitivities, specificities, and accuracies were calculated for all data and for the two subsets of patients who were suspected of having an infection in the central and the peripheral skeleton. The accuracy was 100% and 95%, respectively (Table 2).


View this table:
[in this window]
[in a new window]

  		TABLE 2. ROC Curve Analysis

 
The interobserver variability in the PET readings was very low, differing in five cases by at most one grade (Table 1). Considering all cases, the area under the receiver operating characteristic curve was 0.98 for reader 1 and 0.96 for reader 2 (Table 2). FDG PET was able to permit the distinction between soft-tissue infection and osteomyelitis despite the presence of metallic implants. Examples are shown in Figures 1 and 2.



View larger version (94K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1a. Images in a 64-year-old man 8 months after osteosynthesis and muscle flap coverage of a grade 3 open fracture of the left tibia. (a) Coronal FDG PET scan of the distal lower limb shows increased FDG uptake in the course of the muscle flap and osseous activity in the region of one of the distal screws (arrowheads). (b) Anteroposterior conventional radiograph of the distal lower limb shows osteopenia and a suspicious loosened plate (arrowheads) in the distal left tibia. In addition, complete dislocation of one screw is seen. (c) Contrast-enhanced T1-weighted coronal MR image shows multiple artifacts in the left tibia and the surrounding soft tissues (arrows).

 


View larger version (79K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1b. Images in a 64-year-old man 8 months after osteosynthesis and muscle flap coverage of a grade 3 open fracture of the left tibia. (a) Coronal FDG PET scan of the distal lower limb shows increased FDG uptake in the course of the muscle flap and osseous activity in the region of one of the distal screws (arrowheads). (b) Anteroposterior conventional radiograph of the distal lower limb shows osteopenia and a suspicious loosened plate (arrowheads) in the distal left tibia. In addition, complete dislocation of one screw is seen. (c) Contrast-enhanced T1-weighted coronal MR image shows multiple artifacts in the left tibia and the surrounding soft tissues (arrows).

 


View larger version (85K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1c. Images in a 64-year-old man 8 months after osteosynthesis and muscle flap coverage of a grade 3 open fracture of the left tibia. (a) Coronal FDG PET scan of the distal lower limb shows increased FDG uptake in the course of the muscle flap and osseous activity in the region of one of the distal screws (arrowheads). (b) Anteroposterior conventional radiograph of the distal lower limb shows osteopenia and a suspicious loosened plate (arrowheads) in the distal left tibia. In addition, complete dislocation of one screw is seen. (c) Contrast-enhanced T1-weighted coronal MR image shows multiple artifacts in the left tibia and the surrounding soft tissues (arrows).

 


View larger version (59K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2a. Images in a 44-year-old man with a titanium implant in the left tibia after a grade 2 open fracture. (a) Anteroposterior conventional radiograph shows central osteopenia of the distal third of the tibia. (b) Anteroposterior projection of an image obtained at antigranulocyte monoclonal antibody scintigraphy of the feet 6 hours after injection shows activity at the medial side of the left calf (arrows). Compared with PET, in monoclonal antibody scintigraphy, focus localization and differentiation between soft tissue and bone was more difficult. (c) Coronal and (d) transverse PET sections demonstrate intense FDG uptake in the soft tissue (black arrowheads) medial to the osteosynthetic plate of the left calf, as well as linear increased intramedullary uptake (white arrowheads) in the distal left tibia, which corresponds to soft-tissue infection with tibial osteomyelitis.

 


View larger version (130K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2b. Images in a 44-year-old man with a titanium implant in the left tibia after a grade 2 open fracture. (a) Anteroposterior conventional radiograph shows central osteopenia of the distal third of the tibia. (b) Anteroposterior projection of an image obtained at antigranulocyte monoclonal antibody scintigraphy of the feet 6 hours after injection shows activity at the medial side of the left calf (arrows). Compared with PET, in monoclonal antibody scintigraphy, focus localization and differentiation between soft tissue and bone was more difficult. (c) Coronal and (d) transverse PET sections demonstrate intense FDG uptake in the soft tissue (black arrowheads) medial to the osteosynthetic plate of the left calf, as well as linear increased intramedullary uptake (white arrowheads) in the distal left tibia, which corresponds to soft-tissue infection with tibial osteomyelitis.

 


View larger version (71K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2c. Images in a 44-year-old man with a titanium implant in the left tibia after a grade 2 open fracture. (a) Anteroposterior conventional radiograph shows central osteopenia of the distal third of the tibia. (b) Anteroposterior projection of an image obtained at antigranulocyte monoclonal antibody scintigraphy of the feet 6 hours after injection shows activity at the medial side of the left calf (arrows). Compared with PET, in monoclonal antibody scintigraphy, focus localization and differentiation between soft tissue and bone was more difficult. (c) Coronal and (d) transverse PET sections demonstrate intense FDG uptake in the soft tissue (black arrowheads) medial to the osteosynthetic plate of the left calf, as well as linear increased intramedullary uptake (white arrowheads) in the distal left tibia, which corresponds to soft-tissue infection with tibial osteomyelitis.

 


View larger version (112K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2d. Images in a 44-year-old man with a titanium implant in the left tibia after a grade 2 open fracture. (a) Anteroposterior conventional radiograph shows central osteopenia of the distal third of the tibia. (b) Anteroposterior projection of an image obtained at antigranulocyte monoclonal antibody scintigraphy of the feet 6 hours after injection shows activity at the medial side of the left calf (arrows). Compared with PET, in monoclonal antibody scintigraphy, focus localization and differentiation between soft tissue and bone was more difficult. (c) Coronal and (d) transverse PET sections demonstrate intense FDG uptake in the soft tissue (black arrowheads) medial to the osteosynthetic plate of the left calf, as well as linear increased intramedullary uptake (white arrowheads) in the distal left tibia, which corresponds to soft-tissue infection with tibial osteomyelitis.

 
Since preoperative planning is dependent on multiple variables, it is difficult to define the influence of FDG PET findings on the clinical decision-making process. However, by analyzing the clinical influence retrospectively, the surgeons found that PET provided relevant information in 18 of 29 cases. In six of the patients in whom osteomyelitis was correctly diagnosed, PET led to the removal of osteosynthetic material and partial bone resection. Three of the 18 patients suspected of having an osseous infection were treated without surgical intervention, since FDG PET findings were negative. Findings from the 6-month follow-up revealed no clinical signs of infection in these patients. Furthermore, in seven of 18 patients, exclusion of osseous infection allowed direct osteosynthetic material implantation or exchange of loose implants. Finally, in two of 18 patients, revision surgery for soft tissues alone was performed, as PET helped to exclude osseous infection. In 11 cases, the surgeons determined that no relevant information was obtained with PET.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
In traumatology, osteomyelitis is a rare but serious complication following fracture stabilization with metallic implants. Recently, findings from studies about the role of FDG PET in the diagnosis of chronic osteomyelitis in the peripheral and the central skeleton provided a high degree of accuracy. Guhlmann et al (24) evaluated the role of FDG PET in the diagnosis of chronic osteomyelitis by using histopathologic findings as a standard of reference. These authors reported an overall sensitivity of 100% and a specificity of 92% in 31 patients. In concordance with these results, findings from this study demonstrate a high accuracy of FDG PET in the diagnosis of metallic implant–associated infections in patients with trauma. Lesions in the peripheral and central skeleton were correctly identified with an overall sensitivity of 100% and a specificity of 93%. Furthermore, FDG PET displayed adequate anatomic information and resolution in distinguishing between soft-tissue and bone infection, despite the presence of metallic material. These findings are comparable to the results of de Winter et al (25), who analyzed the use of FDG PET in the diagnosis of chronic musculoskeletal infections in 60 patients. In that study, 34 patients had metallic implants at the time of scanning. The overall sensitivity and specificity was 100% and 88%, respectively. Microbiologic confirmation was obtained in only 18 of 60 patients. In this study, only patients with osteosynthetic implants that were placed because of trauma were evaluated, and microbiologic and/or surgical evidence was available in almost all patients (26 of 29 cases).

The pooled data of all 29 cases yielded adequate CIs (eg, for the accuracy of 97%, the CI was between 82% and 100%). However, the sample size for the two subgroups (central and peripheral skeleton) was small.

The distinction between soft-tissue and bone infection was possible in all cases of PET imaging. There was only one false-positive finding in the soft tissues (classified as grade 3 uptake by both readers) in a patient 6 weeks after surgery. However, in eight patients who also had PET scans 6–8 weeks after surgery, the PET scans were true-negative. In our study, no implant-associated artificial FDG accumulation due to patient motion between emission and transmission scanning was noted. While other authors who evaluated nontraumatologic metallic implants have found false-positive results due to sterile inflammation occurring with prosthetic loosening (25), we did not experience this problem in our series. Most likely this is owing to the different sizes (more slender), materials (titanium, which has a relatively low photon absorption), and methods (frequent external fixation) used in traumatology. Furthermore, distinction between physiologic muscular activity and pathologic FDG uptake did not pose a problem. This is likely owing to the fact that overuse of muscles leads to FDG activity in the entire muscle, while muscular soft-tissue infection is more circumscribed and typically does not affect the entire muscle.

Predominantly morphologic modalities such as CT and MR imaging provide excellent anatomic detail. However, their application is often limited in the detection of complicating osteomyelitis due to increased local bone remodelling, lesion repair hyperemia and edema, or implant-associated artifacts (Fig 1) (2,28,29).

99mTc bone marrow and 111In-labeled leukocyte scintigraphy have been the methods of choice for posttraumatic infection imaging (4). The results of 99mTc-labeled monoclonal antibodies against granulocytic surface antigens are comparable to those obtained with 111In-labeled leukocytes but show an even stronger accumulation in normal hematopoietic bone marrow (13,14). For this reason, the sensitivities for the detection of chronic osteomyelitis in the central skeleton with these methods have only attained the range of 53%–76% (15–18), compared with a sensitivity of 100% for FDG PET in this study.

FDG PET has several advantages over the other nuclear techniques. First, FDG accumulates in the lesion within 30–60 minutes, whereas other infection-specific nuclear medicine modalities require imaging for more than 24 hours because of slow accumulation kinetics of the radiotracer. This is advantageous both for the patient and for the surgeon, for the latter, particularly when urgent decisions have to be made. Second, FDG PET has a distinctly higher spatial resolution than the single photon-based methods and is inherently tomographic. This permits a much better distinction between osseous and soft-tissue infection. This distinction is relevant for the surgeon, as the operative approach differs greatly when osteomyelitis is present. Third, FDG is less expensive than the leukocyte-based labeling techniques, except for 99mTc monoclonal antibody scintigraphy. Fourth, FDG accumulates only where granulocytes and macrophages are actively fighting an infection, and in particular, when there is no physiologic accumulation in the hematopoietic bone marrow of the central skeleton.

FDG PET seems to be an excellent imaging modality in patients with osteosynthetic metallic implants and trauma, who are suspected of having infections. The value of PET in patients with trauma was examined prospectively in relation to histologic findings, whereas the evaluation of the clinical value of PET was retrospective. The study design has its limitation: The surgeon was not prospectively asked how he would proceed prior to PET scanning and then again after PET scanning. The reason for this is the limited experience in infection imaging with FDG PET in patients with trauma.

The decision to perform an operation or treatment depended on several pieces of information. However, by retrospectively assessing the treatment plan, the surgeons at least were able to estimate whether the PET study added something to their assessment of a case. This provides an initial idea of whether PET contributes something in this setting or provides only redundant information. In almost two-thirds of the patients, PET increased the confidence of the surgeons to treat or not to treat and how to treat.

A general limitation of FDG PET is that despite a relatively high spatial resolution, the anatomic information available with PET images is very limited. To improve this, recently integrated PET-CT in-line systems have been introduced that provide "hardware" coregistered PET and CT images, with CT providing a precise anatomic reference map. The additional precision of the location of FDG activity obtained with such combined systems may further enhance the use of PET in the setting discussed here. A case in point is shown in Figure 3.



View larger version (53K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3a. Images in a 75-year old woman 2 years after lumbar decompression and spondylodesis of the lumbar spine, who was suspected of having a low-grade infection. (a) Sagittal coregistered PET-CT scan shows activity (arrow) in the region of the L1-2 intervertebral disk level. (b) Transverse combined PET-CT scan shows increased FDG uptake in the region of the right cranial screw (arrowheads) in the L1 vertebral body. Bone destruction is noted on the CT scan. (c) Transverse combined PET-CT scan shows FDG accumulation cranial to the infected right-sided screw in b (arrowheads).

 


View larger version (40K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3b. Images in a 75-year old woman 2 years after lumbar decompression and spondylodesis of the lumbar spine, who was suspected of having a low-grade infection. (a) Sagittal coregistered PET-CT scan shows activity (arrow) in the region of the L1-2 intervertebral disk level. (b) Transverse combined PET-CT scan shows increased FDG uptake in the region of the right cranial screw (arrowheads) in the L1 vertebral body. Bone destruction is noted on the CT scan. (c) Transverse combined PET-CT scan shows FDG accumulation cranial to the infected right-sided screw in b (arrowheads).

 


View larger version (46K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3c. Images in a 75-year old woman 2 years after lumbar decompression and spondylodesis of the lumbar spine, who was suspected of having a low-grade infection. (a) Sagittal coregistered PET-CT scan shows activity (arrow) in the region of the L1-2 intervertebral disk level. (b) Transverse combined PET-CT scan shows increased FDG uptake in the region of the right cranial screw (arrowheads) in the L1 vertebral body. Bone destruction is noted on the CT scan. (c) Transverse combined PET-CT scan shows FDG accumulation cranial to the infected right-sided screw in b (arrowheads).

 
In conclusion, our data suggest that FDG PET is an excellent method for the detection of metallic osteosynthetic implant–associated infection in patients with trauma in both the central and the peripheral skeleton. Differentiation between osteomyelitis and an infectious involvement of the adjacent soft tissue may be a better possibility with FDG PET than with CT or MR imaging alone because of better lesion-to-background contrast and because of artifacts due to metallic implants arising with these techniques. In the future, anatomometabolic fusion images with PET and CT combined into a single scanner will allow even more precise anatomic localization of the infectious focus. To assess the definitive clinical influence of FDG PET in this setting, prospective studies in which surgical strategy is evaluated, including combined PET-CT scanning and larger patient populations, are needed.


   ACKNOWLEDGMENTS
 
The authors gratefully acknowledge the help by Dr Burkhardt Seifert in performing the statistical evaluation of the data.


   FOOTNOTES
 
Abbreviation: FDG = fluorodeoxyglucose

Author contributions: Guarantors of integrity of entire study, M.S., K.D.M.S., G.K.v.S., T.K.; study concepts, all authors; study design, M.S., K.D.M.S.; literature research, M.S., K.D.M.S.; clinical studies, M.S., K.D.M.S., T.K., G.K.v.S.; data acquisition, M.S., K.D.M.S., T.K.; data analysis/interpretation, M.S., K.D.M.S., T.K., G.K.v.S.; statistical analysis, M.S., K.D.M.S., G.K.v.S.; manuscript preparation, editing, and final version approval, M.S., K.D.M.S., G.K.v.S.; manuscript definition of intellectual content, M.S., K.D.M.S., O.T., T.K.; manuscript revision/review, K.D.M.S., G.K.v.S., O.T., T.K.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 

  1. Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med 1997; 336:999-1007.[Free Full Text]
  2. Elgazzar AH, Abdel Dayem HM, Clark JD, Maxon HR. Multimodality imaging of osteomyelitis. Eur J Nucl Med 1995; 22:1043-1063.[CrossRef][Medline]
  3. Crim JR, Seeger LL. Imaging evaluation of osteomyelitis. Crit Rev Diagn Imaging 1994; 35:201-256.[Medline]
  4. Schauwecker DS. The scintigraphic diagnosis of osteomyelitis. AJR Am J Roentgenol 1992; 158:9-18.[Abstract/Free Full Text]
  5. Palestro CJ, Swyer AJ, Kim CK, Goldsmith SJ. Infected knee prosthesis: diagnosis with In-111 leukocyte, Tc-99m sulfur colloid, and Tc-99m MDP imaging. Radiology 1991; 179:645-648.[Abstract/Free Full Text]
  6. Hodler J, Steinert H, Zanetti M, et al. Radiographically negative stress related bone injury: MR imaging versus two-phase bone scintigraphy. Acta Radiol 1998; 39:416-420.[Medline]
  7. Morrison WB, Schweitzer ME, Bock GW, et al. Diagnosis of osteomyelitis: utility of fat-suppressed contrast-enhanced MR imaging. Radiology 1993; 189:251-257.[Abstract/Free Full Text]
  8. Williamson MR, Quenzer RW, Rosenberg RD, et al. Osteomyelitis: sensitivity of 0.064 T MRI, three-phase bone scanning and indium scanning with biopsy proof. Magn Reson Imaging 1991; 9:945-948.[CrossRef][Medline]
  9. McAfee JG. What is the best method for imaging focal infections? J Nucl Med 1990; 31:413-416.[Free Full Text]
  10. Schauwecker DS. Osteomyelitis: diagnosis with In-111-labeled leukocytes. Radiology 1989; 171:141-146.[Abstract/Free Full Text]
  11. Palestro CJ. The current role of gallium imaging in infection. Semin Nucl Med 1994; 24:128-141.[CrossRef][Medline]
  12. Seabold JE, Forstrom LA, Schauwecker DS, et al. Procedure guideline for indium-111-leukocyte scintigraphy for suspected infection/inflammation: Society of Nuclear Medicine. J Nucl Med 1997; 38:997-1001.[Free Full Text]
  13. Becker W, Goldenberg DM, Wolf F. The use of monoclonal antibodies and antibody fragments in the imaging of infectious lesions. Semin Nucl Med 1994; 24:142-153.[CrossRef][Medline]
  14. Reuland P, Winker KH, Heuchert T, et al. Detection of infection in postoperative orthopedic patients with technetium-99m-labeled monoclonal antibodies against granulocytes. J Nucl Med 1991; 32:2209-2214.[Abstract/Free Full Text]
  15. Jacobson AF, Gilles CP, Cerqueira MD. Photopenic defects in marrow-containing skeleton on indium-111 leucocyte scintigraphy: prevalence at sites suspected of osteomyelitis and as an incidental finding. Eur J Nucl Med 1992; 19:858-864.[CrossRef][Medline]
  16. Datz FL, Thorne DA. Cause and significance of cold bone defects on indium-111-labeled leukocyte imaging. J Nucl Med 1987; 28:820-823.[Abstract/Free Full Text]
  17. Even Sapir E, Martin RH. Degenerative disc disease: a cause for diagnostic dilemma on In-111 WBC studies in suspected osteomyelitis. Clin Nucl Med 1994; 19:388-392.[CrossRef][Medline]
  18. Palestro CJ, Torres MA. Radionuclide imaging in orthopedic infections. Semin Nucl Med 1997; 27:334-345.[CrossRef][Medline]
  19. Tahara T, Ichiya Y, Kuwabara Y, et al. High [18F]-fluorodeoxyglucose uptake in abdominal abscesses: a PET study. J Comput Assist Tomogr 1989; 13:829-831.[Medline]
  20. Yamada S, Kubota K, Kubota R, Ido T, Tamahashi N. High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med 1995; 36:1301-1306.[Abstract/Free Full Text]
  21. Stumpe KD, Dazzi H, Schaffner A, von Schulthess GK. Infection imaging using whole-body FDG-PET. Eur J Nucl Med 2000; 27:822-832.[CrossRef][Medline]
  22. Babior BM. The respiratory burst of phagocytes. J Clin Invest 1984; 73:599-601.
  23. Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 1992; 33:1972-1980.[Abstract/Free Full Text]
  24. Guhlmann A, Brecht Krauss D, Suger G, et al. Fluorine-18-FDG PET and technetium-99m antigranulocyte antibody scintigraphy in chronic osteomyelitis. J Nucl Med 1998; 39:2145-2152.[Abstract/Free Full Text]
  25. de Winter F, van de Wiele C, Vogelaers D, de Smet K, Verdonk R, Dierckx RA. Fluorine-18 fluorodeoxyglucose-position emission tomography: a highly accurate imaging modality for the diagnosis of chronic musculoskeletal infections. J Bone Joint Surg Am 2001; 83:651-660.[Abstract/Free Full Text]
  26. Schmidlin P. Improved iterative image reconstruction using variable projection binning and abbreviated convolution. Eur J Nucl Med 1994; 21:930-936.[Medline]
  27. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982; 143:29-36.[Abstract/Free Full Text]
  28. Ma LD, Frassica FJ, Bluemke DA, Fishman EK. CT and MRI evaluation of musculoskeletal infection. Crit Rev Diagn Imaging 1997; 38:535-568.[Medline]
  29. Unger E, Moldofsky P, Gatenby R, Hartz W, Broder G. Diagnosis of osteomyelitis by MR imaging. AJR Am J Roentgenol 1988; 150:605-610.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 RadiologyHome page
G. K. von Schulthess, H. C. Steinert, and T. F. Hany
Integrated PET/CT: Current Applications and Future Directions
Radiology, February 1, 2006; 238(2): 405 - 422.
[Abstract] [Full Text] [PDF]

Home page
 JBJSHome page
M.F. Termaat, P.G.H.M. Raijmakers, H.J. Scholten, F.C. Bakker, P. Patka, and H.J.T.M. Haarman
The Accuracy of Diagnostic Imaging for the Assessment of Chronic Osteomyelitis: A Systematic Review and Meta-Analysis
J. Bone Joint Surg. Am., November 1, 2005; 87(11): 2464 - 2471.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
K. D. M. Stumpe, H. P. Notzli, M. Zanetti, E. M. Kamel, T. F. Hany, G. W. Gorres, G. K. von Schulthess, and J. Hodler
FDG PET for Differentiation of Infection and Aseptic Loosening in Total Hip Replacements: Comparison with Conventional Radiography and Three-Phase Bone Scintigraphy
Radiology, May 1, 2004; 231(2): 333 - 341.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
R. L. Wahl
Why Nearly All PET of Abdominal and Pelvic Cancers Will Be Performed as PET/CT
J. Nucl. Med., January 1, 2004; 45(90010): 82S - 95.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2262011939v1
226/2/391    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schiesser, M.
Right arrow Articles by von Schulthess, G. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schiesser, M.
Right arrow Articles by von Schulthess, G. K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
RADIOLOGY RADIOGRAPHICS RSNA JOURNALS ONLINE