Diagnostic Value of Bone SPECT/CT in Patients with Suspected Osteomyelitis

Objectives: The aim of our retrospective study was to evaluate the contribution of single photon emission computed tomography/computed tomography (SPECT/CT) to three phase bone scintigraphy/SPECT for the assessment of osteomyelitis (OM) and patient’s management. Methods: Eighty-five patients who were suspected as having OM were included in this study. Tc-99m MDP three phase bone scintigraphy and SPECT/CT were performed to the region of suspected OM. SPECT/CT findings were compared with the findings of planar images/SPECT. Both planar bone scan/SPECT and SPECT/CT findings were divided into two groups: With OM and without OM. In all patients, scintigraphic diagnosis was confirmed by clinical follow up, laboratory findings, microscopic-bacteriological examinations, radiological, surgical, and pathological findings. Results: SPECT/CT changed the diagnosis and treatment planning in 14/85 (16.5%) patients. SPECT/CT was significantly superior to planar scan/SPECT imaging for determining OM (kappa value was 0.626 for planar scan/SPECT, 0.929 for SPECT/CT). SPECT/CT was statistically more successful in detection of chronic OM, and useful in differentiating chronic OM from acute OM (kappa value was 0.541 for planar scan/SPECT, 0.944 for SPECT/CT). Conclusion: SPECT/CT increases accuracy of the diagnosis in the evaluation of OM when it is compared to three phase bone scintigraphy/SPECT. SPECT/CT can change the diagnosis and management of the patients.


Introduction
Osteomyelitis (OM) is a bone infection. Early diagnosis of OM is essential for a successful therapy and management of the complications. Determining whether the OM is acute or chronic is very important for deciding an appropriate antimicrobial and surgical treatment. The diagnosis of bone infection is still challenging. Clinical and laboratory parameters such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), microbiological examination are usually insufficient to make a correct diagnosis (1,2,3). The changes in plain radiography occur late and are non-specific. Computed tomography (CT) and magnetic resonance imaging (MRI) are able to show pathologic morphological changes in the bones and surrounding soft tissues. Although they are very sensitive, their specificity is moderate (3). Three-phase planar bone scintigraphy (3-phase PBS) is the first option among radionuclide techniques for detection of the OM since it is widely available, easy, and inexpensive. This technique has a high sensitivity, but its specificity is limited (1,2,3,4). PBS must be combined with single photon emission computed tomography (SPECT) to obtain high sensitivity and specificity however, their value is limited due to the poor accuracy in localizing the increased uptake (4,5). SPECT/ CT can improve the prognostic value of planar radionuclide techniques since it evaluates morphologic and functional information together (4,5). Use of SPECT/CT significantly increases the diagnostic accuracy of skeletal scintigraphy (6). Nowadays, SPECT/CT has been used frequently in orthopedic diseases (7,8,9,10). In this retrospectively study, we aimed to evaluate the contribution and superiority of SPECT/CT to 3-phase PBS/SPECT for assessment of OM and management of patients.

Patients
We retrospectively analyzed 85 patients who were suspected as having OM with clinical and laboratory findings and we performed the 3-phase PBS-SPECT/CT. The mean age of the patients was 50±32 years (range 18-82 years). There was clinical suspicion of bone infection (pain, swelling, erythema, heat, fever, wound etc.), and abnormal laboratory findings (increased number of white blood cells and neutrophils, ESR and CRP) during 10-90 days in the selected patients. Patients without follow up, patients with prostheses or metallic instrumentation causing artifacts on CT, patients who had an operation within 3 months and using antibiotic therapy for more than 7 days were excluded. The study group was consisted of 34 females and 51 males. There were systemic diseases in 22 patients (diabetes mellitus n=16, tuberculosis n=2, ankylosing spondylitis n=2, others=2). All patients had X-rays before radionuclide imaging and clinical follow up for at least 6 months. The patients' characteristics are summarized in Table 1. All patients gave their written informed consents for the 3-phase PBS and SPECT/CT study. Local Ethics Committee approved the present retrospective study (3739/0.01.2014).

Three-phase PBS
After a bolus injection of the 740 MBq technetium-99m methylene diphosphonate (Tc-99m MDP) (Monrol, Eczacıbaşı, Turkey), perfusion images were obtained immediately by acquiring blood flow images, 1 frame for 60 sec, at 64x64 matrix. Blood pool images were acquired after perfusion (anterior-posterior position, 256x256 matrix, 500,000-750,000 counts). Whole body and static images were obtained 3 hours after the injection (whole body scan 8 cm/min, static images 500,000-750,000 counts). The images were acquired with a dual head gamma camera, equipped with a low energy, high resolution, large-field-ofview parallel-hole collimator (Millennium Hawkeye 4, GE Medical Systems, Milwaukee, WI).

SPECT/CT
After the 3-phase PBS, SPECT/CT was performed on the region of suspected OM in all patients, firstly, CT scan

Image interpretation
Images were interpreted by two qualified nuclear medicine specialists who were blinded to all clinical and radiological details of the patients (p<0.005). But they had information about the suspicious infection area due to the dynamic study. Each nuclear medicine specialist independently looked at the first 3-phase PBS and SPECT images together using a linear grey scale display. The uptake of perfusion, blood pool and delayed phase were compared with the opposite side. Then, SPECT/CT fusion images were read at the same time using color display. On the basis of the findings on the 3-phase PBS/SPECT and SPECT/CT, patients were divided into two groups: with OM, without OM (no OM). Without OM: Normal radiotracer uptake on perfusion-blood pool phase, normal, slightly or mild increased radiotracer uptake in the delayed phase with no abnormal morphologic changes or detection of osteoarthritis-degenerative-traumaticpostoperative changes, osteonecrosis, heterotopic ossification on CT were described as no OM. With OM: Intense or mild diffuse or focal increased radiotracer uptake at the lesion site in all three phases in 3-phase PBS was defined OM. Detection of periosteal reaction, small focus of gas or foreign bodies, soft tissue abscesses and edema on CT with scintigraphic findings were considered as acute OM (AOM). Bone destruction, sequestration, involucra, fistulous tract on CT associated with the radiotracer uptake were interpreted as chronic OM (COM).

Final Diagnosis
All patients were followed up in our hospital for 6 months. The final diagnosis was verified by microbiologic examination in 39 patients, by radiology and scintigraphic techniques in 31 patients (CT=8, MRI=17, gallium=6), and by surgery and histopathologic findings in 15 patients. We could not use the same gold standard, because there were not microbiologic-histopathologic results in all patients.

Statistical Analysis
Kappa test was used to compare 3-phase PBS/SPECT and SPECT/CT. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of each method were calculated.    Table 2 Table 4.

Three
Sensitivity, specificity, PPV, NPV and accuracy of each method were calculated. The results are showed in the

Discussion
The diagnosis of OM is challenging. The localization of the infection site and determination of acute or COM are important for planning the treatment. The treatment of OM is multidisciplinary. It is very important to take the appropriate antimicrobial treatment and to choose the patients for surgery. Untreated or insufficiently treated bone infection leads to destruction and recurrence of diseases. Three-phase PBS is widely used for evaluation of the suspected OM (1,2,3,4). SPECT/CT has become an increasingly important diagnostic modality in addition to 3-phase PBS in orthopedic diseases (7,8,9,10). In this study, we investigated the contribution and superiority of SPECT/CT to 3-phase PBS/SPECT in the patients who were suspected as having OM and underwent 3-phase PBS. Three-phase PBS in the diagnosis of OM has high sensitivity, but its specificity is limited (1,2,3). SPECT/CT increases sensitivity and specificity in diagnosis of OM (4,5,7,8). We found that SPECT/CT was a more sensitive and specific method in comparison to PBS/SPECT for diagnosing OM (sensitivity 88.3% versus 100%; specificity 75.6% versus 95.4%). SPECT/CT improved specificity rather than sensitivity. Analysis of the kappa values showed that SPECT/CT was significantly better than PBS/SPECT in the diagnosis of OM. Horger et al. (7) found that sensitivity was 78% for PBS/SPECT and SPECT/CT. But specificity of SPECT/CT was higher than PBS/SPECT. It was 50% for PBS/ SPECT and 86% for SPECT/CT. In our experiment, sensitivity was similar with this study, but specificity was significantly higher for both techniques. In our study, the number of patients who had a history of fracture and several bone surgery was more than in the study of Horger et al. (7). In our study, SPECT/CT showed actual anatomical localization of radiotracer uptake and allowed true localization, extension, and activation of infection. Actual anatomic localization was particularly useful for differentiating soft tissue and bone infection. Morphologic changes on CT also helped to make a correct diagnosis.   This patient had had surgery five months before the scan. Both techniques failed to differentiate postoperative changes from infection. Three-phase PBS could be interpreted as false positive in this period, because bone surgery leads to increase in bone turnover and osteoblastic activity. Accurate differentiation of AOM from COM is very important for patient management. Increased radiotracer uptake is found on all three phases of 3-phase PBS in both AOM and reactive COM. As AOM is treated with antimicrobial therapy, surgery with antimicrobial therapy may be needed in COM (11). SPECT/CT is important in differentiating AOM from reactive COM. In our experience, SPECT/CT correctly classified COM in 8 of 36 patients who were interpreted as AOM on 3-phase PBS (Figure 1). We saw that SPECT/CT was particularly useful for the diagnosis of post-traumatic and post-operative OM in the patients with reactive COM.
SPECT/CT improved the image quality, resolution and identified minimal increased activity. SPECT/CT might easily evaluate the small multiple osseous structure in hand-wrist, and foot-ankle (12,13). SPECT/CT confirmed final diagnosis in 40 out of 41 patients with suspected lesions in their hands and feet ( Figure 2). It is sometimes difficult to identify an infection focus in the appendicular skeleton such as skull, vertebra or pelvis with 3-phase PBS, because of compact bone structure and superposition of bones (14). In our study, there were three patients with suspected OM of skull after operation. OM sites could be diagnosed accurately in these patients by SPECT/CT ( Figure 3). Bolouri et al. (15) performed bone SPECT/CT to evaluate patients who were suspected as having OM on the jaw. They found that SPECT/CT slightly improved the specificity of 3-phase PBS. Damle    Fusion images show that radiotracer uptake around the trochanter major is associated with the bone structures within soft tissue (arrows). The findings of SPECT/computed tomography (CT) are described as heterotopic ossification and soft tissue infection. This diagnosis is confirmed by CT and pathology 4). The therapy of those patients completely changed. Linke et al. (8) reported that bone SPECT/CT findings led to change in the diagnosis of one third of patients with pain in the extremities (17). The highest rate of diagnostic alteration was found 60% among patients who were suspected as having OM (8).

Study Limitations
There were three limitations in our study. The main limitation was the retrospective design of the study. Despite the fact that the nuclear medicine specialists did not know the clinical and radiological results of the patients, they had information about the region of suspected OM due to perfusion and blood pool images.
The second limitation was that there was lack of standard gold reference for the final diagnosis of OM. All patients did not have microbiologic and histopathologic examinations. We had to compare the 3-phase PBS and SPECT/CT results with different references. Because of this reason, there was no standardization in the final diagnosis.
The third limitation in our study was that poor image quality due to low dose CT. Even though low dose CT was enough for anatomic localization of radiotracer uptake; the morphologic evaluation of particularly small and compact bone structures in the foot, hand, mandibula, and spine was difficult.

Conclusion
Three-phase PBS combined with SPECT/CT is an useful tool in diagnosis of OM. We think that SPECT/CT has more diagnostic accuracy than 3-phase PBS/SPECT in differentiation of reactive COM and AOM. Especially SPECT/CT is superior in postoperative and posttraumatic OM. SPECT/CT is very successful in the evaluation of skull, vertebra, pelvis, spine, hand, and foot than PBS. We recommend that SPECT/CT should be used in selected patients.

Ethics
Ethics Committee Approval: This retrospective study was approved by the Ethics Committee of the Ankara Numune Training and Research Hospital (3739/0.01.2014).
Informed Consent: All patients gave their written informed consents.