Value of a 24-hour image (four-phase bone scan) in assessing osteomyelitis in patients with peripheral vascular disease

The delayed images of the four-phase 99mTc phosphonate bone scan are compared with the delayed images of the three-phase study in patients with diabetes mellitus and/or peripheral vascular disease and suspected osteomyelitis. Three-phase bone imaging includes an immediate postinjection radionuclide angiogram, a blood-pool image, and delayed static images to 7 hr. The four-phase study adds a 24-hr static image. The scan is positive for osteomyelitis if images show progressively increasing lesion to background activity ratios over time. The results of analyzing 21 three- and four-phase bone scans in 17 patients were correlated with clinical course, cultures, and/or x-rays, gallium scans, and CT scans. The accuracy of four-phase bone imaging for diagnosing osteomyelitis was 85%; for three phase, 80%. Sensitivity for four phase was 80%; specificity was 87%. Sensitivity for three phase was 100%; specificity was 73%. Since overall accuracy of the four-phase study is slightly better than three phase, in these patients with diabetes mellitus and/or peripheral vascular disease, the addition of a 24-hr image, creating a four-phase bone scan, is recommended.     

Acute osteomyelitis in children: combined Tc-99m and Ga-67 imaging

This retrospective study was done to determine the value of combined bone (technetium-99m methylene-diphosphonate) and gallium-67 citrate imaging in selected children with complicated clinical situations. Thirty-one children were evaluated for suspected osteomyelitis by bone scan followed within 4 days by a gallium scan. These 31 children represented a subpopulation in whom the Tc-99m scan is known to be potentially unreliable in diagnosing acute osteomyelitis. Eight children had acute osteomyelitis by strict criteria, while 23 did not. The bone scan successfully identified five of the eight with osteomyelitis but was positive in ten of the other 23. The gallium scan correctly identified all eight with osteomyelitis but was positive in seven of the other 23. The gallium scan was significantly less specific when the suspected lesion was in the extremities compared with central locations; causes of false-positive gallium scans included fracture and juvenile rheumatoid arthritis. Combined gallium and bone scanning increased accuracy of the scintigraphic diagnosis of acute osteomyelitis. Both tests may, however, be abnormal in conditions other than osteomyelitis. These findings emphasize the importance of correlating all imaging studies in detection of osteomyelitis.     

Chronic osteomyelitis: bone and gallium scan patterns associated with active disease

Bone and gallium scans are used to assess osteomyelitis patients with prior bone disease. To refine the criteria for interpreting these scans, the data from 136 consecutive patients with clinically suspected osteomyelitis were reviewed. Active osteomyelitis was diagnosed with surgery or biopsy and culture in 49 patients, excluded with the same criteria in 16, and excluded by clinical follow-up for at least 6 months in 71. Five different scintigraphic patterns were found. The true-positive and false-positive ratios, the likelihood ratios, and posterior probabilities for active osteomyelitis in each pattern were calculated. Only one pattern (gallium uptake exceeding bone-seeking radiopharmaceutical uptake) was indicative of active disease. Other patterns slightly raised or decreased the probability of disease. The extent of these changes varies directly with the prior probability of disease, determined from patient-specific factors (e.g., clinical data, laboratory data, findings on plain films) known best by the referring clinician.     

Vertebral osteomyelitis: assessment using MR

Thirty-seven patients who were clinically suspected of having vertebral osteomyelitis were prospectively evaluated with magnetic resonance (MR), radiography, and radionuclide studies. These findings were correlated with the final clinical, microbiologic, or histologic diagnoses. Based on the results of these latter studies, 23 patients were believed to have osteomyelitis. MR examinations consisted of at least a sagittal image (TE = 30 msec, TR = 0.5 sec) and an image obtained at TE = 120 msec, TR = 2-3 sec. All patients underwent radiographic and MR examinations, 36 underwent technetium 99m-HDP bone scanning, and 20 patients underwent gallium 67 scanning. Nineteen patients underwent both bone and gallium scanning. The imaging studies were reviewed independently by investigators blinded to the final diagnoses. MR had a sensitivity of 96%, specificity of 92%, and accuracy of 94%. Combined gallium and bone scan studies (19 cases) had a sensitivity of 90%, specificity of 100%, and accuracy of 94%. Bone scans alone had a sensitivity of 90%, specificity of 78%, and accuracy of 86%. Plain radiographs had a sensitivity of 82%, specificity of 57%, and accuracy of 73%. The MR appearance of vertebral osteomyelitis in this study was characteristic, and MR was as accurate and sensitive as radionuclide scanning in the detection of osteomyelitis.     

Chronic osteomyelitis: the relative roles of scintigrams, plain radiographs, and transmission computed tomography

We evaluated the relative contribution of transmission computed tomograms (CT), plain radiographs, and bone/gallium scans in the diagnosis of 27 patients with suspected active chronic osteomyelitis. All patients were imaged with all modalities and had surgical proof of the presence or absence of disease. At surgery, osteomyelitis was shown to be active in 20 patients, 15 of whom had sequestra, and inactive in the remaining seven. CT depicted all 15 sequestra, but was falsely positive in three patients, all of whom had bone remodeling only and had negative bone/gallium scintiscans. Plain radiographs had a limited value; they detected sequestra, which was the only findings to indicate the presence of active disease, in 5 patients out of the 15 with surgical proof thereof. The authors conclude that, considering the shortcoming of other modalities with regard to depicting sequestra, scintigraphy is helpful in confirming the presence or absence of active disease and therefore in preventing unnecessary surgery.     

The role of bone scan and radiography in the diagnostic evaluation of suspected pedal osteomyelitis

The authors reviewed the three-phase bone scans and radiographs of 24 patients with suspected pedal osteomyelitis who also had histologic confirmation of the diagnosis. Twenty patients had a pedal ulcer, cellulitis, or necrosis. Sensitivity and specificity of bone scanning were 70% and 43% respectively. Sensitivity and specificity of radiography were 70% and 50% respectively. The non-invasive diagnosis of pedal osteomyelitis remains problematic due to the poor specificity of bone scans and radiographs.     

Diagnosis of osteomyelitis of the foot in diabetic patients: value of 111In-leukocyte scintigraphy

The noninvasive diagnosis of osteomyelitis of the foot in diabetic patients with currently available radiologic and radionuclide imaging techniques is often difficult. Recently, 111In-labeled leukocyte scintigraphy has been proposed as an attractive alternative. Accordingly, we retrospectively reviewed 51 111In-labeled leukocyte scans, 49 technetium-99m bone scans, and 49 plain radiographs obtained in 51 adults with diabetes in whom osteomyelitis of the foot was suspected. The sensitivity and specificity of these techniques were evaluated in all patients, as well as in a subgroup of 11 patients with neuroarthropathy. Results with 111In-labeled leukocyte scans were also examined in subsets of patients with soft-tissue ulcers (n = 35) and those receiving antibiotics during investigation (n = 20). Confirmation or exclusion of osteomyelitis was made surgically in 28 patients and clinically in 23. Fourteen patients had osteomyelitis. Bone scans were most sensitive (93%) but least specific (43%); plain radiographs were most specific (83%) but least sensitive (43%). 111In-labeled leukocyte scans were both sensitive (79%) and specific (78%), and remained useful in patients with neuroarthropathy, soft-tissue ulcers, and antibiotic treatment. Poor spatial resolution contributed to the false-negative and false-positive 111In-labeled leukocyte scans, suggesting that this technique should not be interpreted independent of other tests. 111In-labeled leukocyte scans are a valuable diagnostic tool for the diagnosis of pedal osteomyelitis in diabetic patients.     

Usefulness of hybrid SPECT/CT in 99mTc-HMPAO-labeled leukocyte scintigraphy for bone and joint infections.

White blood cell scanning with (99m)Tc-hexamethylpropylene amine oxime (HMPAO) has proven highly sensitive and specific in the diagnosis and follow-up of patients with suspected osteomyelitis. The aim of this prospective study was to evaluate the usefulness of SPECT and transmission CT performed simultaneously using a hybrid imaging device for the functional anatomic mapping of bone and joint infections. METHODS: (99m)Tc-HMPAO scintigraphy was performed on 28 consecutive patients: 15 with suspected bone infection (group 1) and 13 with suspected orthopedic implant infection (group 2). Planar scans were acquired 30 min, 4 h, and 24 h after injection. SPECT/CT was obtained 6 h after tracer injection, using a dual-head gamma-camera coupled with a low-power x-ray tube. In all patients, scintigraphic results were matched with the results of surgery or cultures and of clinical follow-up. RESULTS: (99m)Tc-HMPAO scintigraphy was true-positive for infection in 18 of 28 patients (for a total of 21 sites of uptake) and true-negative in 10 of 28 subjects. SPECT/CT provided an accurate anatomic localization of all positive foci. With regard to the final diagnosis, SPECT/CT added a significant clinical contribution in 10 of 28 patients (35.7%). In fact, SPECT/CT differentiated soft-tissue from bone involvement both in patients with osteomyelitis and in patients with orthopedic implants, allowed correct diagnosis of osteomyelitis in patients with structural alterations after trauma, and identified synovial infection without prosthesis involvement in patients with a knee implant. CONCLUSION: Our results indicate that SPECT/CT performed using a hybrid device can improve imaging with (99m)Tc-HMPAO-labeled leukocytes in patients with suspected osteomyelitis by providing accurate anatomic localization and precise definition of the extent of infection.     

Radionuclide imaging of musculoskeletal infection: conventional agents

The diagnosis of musculoskeletal infection can be clinically challenging, and radionuclide imaging is often performed as part of the diagnostic workup. Conventional studies include bone scan, gallium imaging, and labeled leukocyte imaging. No single test is equally efficacious in all situations, and thus the procedure(s) performed should be optimized for the individual patient. Three-phase bone imaging, readily available and relatively inexpensive, is very accurate in unviolated bone. In the setting of underlying osseous abnormalities, however, the specificity of the test decreases. Four-phase bone, sequential bone/gallium, and labeled leukocyte imaging all have been used in an effort to enhance specificity. Labeled leukocyte imaging is the radionuclide procedure of choice for diagnosing so-called complicating osteomyelitis such as infected joint prostheses, diabetic pedal osteomyelitis, and infection of the neuropathic joint. To maximize the accuracy of the study, complementary bone marrow imaging often must be performed. Labeled leukocyte imaging is of limited value in spinal osteomyelitis, however, because this entity often presents as a nonspecific photopenic defect on white cell studies. The conventional radionuclide study for evaluating spinal osteomyelitis is gallium imaging, which should be performed regardless of the findings on a contemporaneous bone scan. The reasons for this are as follows: Gallium improves the specificity of the bone scan; gallium detects accompanying soft tissue infection, whereas the bone scan does not, and gallium may be more sensitive than the bone scan in elderly patients.     

Comparison of Tc-99m methylene diphosphonate, Tc-99m human immune globulin, and Tc-99m-labeled white blood cell scintigraphy in the diabetic foot.

PURPOSE: The aims of this prospective study were to evaluate the contribution of Tc-99m methylene diphosphonate (MDP), Tc-99m human immune globulin (HIG), and Tc-99m white blood cell (WBC) to the diagnosis of osteomyelitis in the diabetic foot and to evaluate the surgical or medical therapy with Tc-99m HIG and Tc-99m WBC scans. METHODS: Twenty patients (15 men, 5 women) with suspected pedal osteomyelitis were included in the study. All patients had type II diabetics. Three- and four-phase bone scintigraphy (3P-MDP, 4P-MDP), early (e) and late (l) HIG, and WBC scans were completed within 1 week in all patients. The lesion-to-background ratios were calculated for early and late images of the feet for all scans and named as the indices. Eight weeks after the end of medical or surgical therapy, Tc-99m HIG and Tc-99m WBC scans were repeated in 10 patients. The difference in indices between 3P-MDP and 4P-MDP for osteomyelitis and indices for osteomyelitis, cellulitis, and inflammation in Tc-99m HIG and Tc-99m WBC in early and late scans were tested for significance. RESULTS: In 20 patients, 53 lesions were investigated. Among these 53 lesions were 25 sites of proved osteomyelitis, 6 sites of cellulitis, and 22 sites of inflammation confirmed by radiography, microbiologic culture, and clinical evaluation. 4P-MDP was more specific than 3P-MDP for detecting osteomyelitis (50% and 67%, respectively). There was also a significant difference between the mean indices of 3P-MDP and 4P-MDP (P < 0.000). The index values were increased in 4P-MDP scans. There was no significant difference between the indices of early and late Tc-99m HIG scans for inflammation, cellulitis, and osteomyelitis. Early and late Tc-99m WBC scans did not show a significant difference in differentiating osteomyelitis. However, Tc-99m WBC scans could differentiate aseptic inflammation from infection (P < 0.031) in early and late scans. There was a significant difference of index values between pre- and post-treatment Tc-99m HIG and Tc-99m WBC scans. The best combination of scans for detecting osteomyelitis was 4P-MDP with WBC scans, with an accuracy rate of 92%. CONCLUSIONS: These results show that four-phase bone scintigraphy with early Tc-99m WBC scanning is preferred for detecting osteomyelitis of the diabetic foot. To evaluate the response to therapy, Tc-99m WBC scans are the preferred method, but if this is not available, Tc-99m HIG scanning can be used.     

Imaging of primary sternal osteomyelitis in a patient with Crohn's disease

A 41-year-old man with known Crohn's disease presented with chest pain and fever. Plain film and CT of the chest were normal, but bone scan and gallium scans showed intense sternal uptake. Surgery revealed staphylococcal osteomyelitis of the sternum. Following appropriate antibiotic treatment, the patient's symptoms resolved and follow-up gallium scans became normal. This is the first report of the association of sternal osteomyelitis and Crohn's disease, although other sites have been described. Sternal osteomyelitis has a high morbidity and the index of suspicion for this condition must be high even in the face of initially negative imaging.     

The value of quantitative gallium-67 single-photon emission tomography in the clinical management of malignant external otitis

Malignant external otitis (MEO) is a severe infectious disorder usually caused by Pseudomonas aeruginosa, which most frequently affects diabetic patients. Due to its rarity, the diagnosis of MEO is often not made promptly. Extension into deeper structures or chronic osteomyelitis may occur without signs of infection on local clinical examination. Of the imaging techniques, magnetic resonance imaging provides a fairly adequate picture of the spread of the disease, but, as with computed tomography (CT) scanning and bone scintigraphy, the images remain unchanged for a long time after disease regression. The objective of this study was to establish whether quantitative gallium-67 single-photon emission tomography (SPET) represents an accurate method for the assessment of infection and, moreover, for the monitoring of therapeutic effect. Eight patients (five males, three females) with the clinical diagnosis of MEO were studied. In three patients antibiotic treatment was prolonged for several weeks because visual analysis of gallium scintigraphy still showed slightly increased uptake in the affected area on the first follow-up scan. In one patient, it was decided to stop antibiotic treatment despite a slight increase in uptake on the second follow-up scan. Lesion to non-lesion (L/NL) ratios obtained from ⁶⁷Ga SPET images at initial diagnosis and during follow-up were assessed in correlation with clinical and biochemical data and with the results of CT scans. In addition to a raised erythrocyte sedimentation rate (ESR), all patients showed increased uptake on the affected side, with L/NL ratios ranging from 1.4 to 3.6 at the time of diagnosis. CT scans failed to demonstrate abnormalities in four patients. Including four scans demonstrating slightly increased uptake in the affected area, L/NL ratios after 6–8 weeks of antibiotic treatment were 1.0±0.1. Despite a persistently elevated ESR in the majority of patients, none of them demonstrated local recurrence or complications during follow-up. In all patients, leucocyte count was within the normal range throughout the course. No relation was found between the slightly increased uptake on the follow-up scans and surgical treatment. It is concluded that in addition to the visual analysis of ⁶⁷Ga SPET imaging, L/NL ratios should be calculated for a more accurate assessment of disease activity in MEO. Despite visually slightly increased uptake, L/NL ratios of 1.0±0.1 during follow-up are highly indicative of complete recovery, regardless of ESR values or leucocytosis. CT scans are of little value for diagnosis or for monitoring of therapeutic effect. Received 13 August and in revised form 15 August 1997     

Tc-99m HMPAO labeled leukocytes superior to bone scan in the detection of osteomyelitis in children.

Seven children (aged 7 to 16 years) with confirmed osteomyelitis underwent imaging with Tc-99m HMPAO labeled leukocytes and with Tc-99m diphosphonates. The patients were scanned at 1/2 hour and at 3 hours. The scans were evaluated visually, and the lesion-to-normal bone ratios were quantitated. All the lesions on leukocyte scans and six out of seven lesions in bone scans were readily detectable 1/2 hour after injection of the radiopharmaceutical, but 3 hours is the better imaging time. In quantitative analysis, the lesion-to-normal bone ratio increased with leukocytes significantly higher than with the bone scans (P less than 0.05). When the scintigraphic findings were compared with surgical and radiologic results, the leukocyte images detected and localized lesions better than the bone scans. According to these preliminary results, Tc-99m HMPAO labeled leukocytes seem to offer a rapid and accurate method for detecting bone infections.     

Improvement of bone scintigraphy by quantitative evaluation compared with X-ray studies and iliac crest biopsy in malignant disease

Bone marrow biopsy of the iliac crest was performed on 268 patients (124; 144). Of these patients 206 had haematological systemic disorders (HSD) or carcinoma and suspected bone involvement, which was confirmed by biopsy on 66 patients.Bone biopsy was performed not longer than 3 weeks after X-ray examination and bone scintigraphy which, combined, had already raised the suspicion of skeletal involvement in 55% of the 66 patients with skeletal involvement diagnosed by biopsy. Additional quantitative evaluation of the bone scans using bone to soft tissue ratios was able to increase the overall accuracy to 67% in that group.Additional quantitative assessment of the scan yielded considerably more effective bone scintigraphy, particularly in cases with visually normal patterns. Available equipment should therefore be used in scintigraphic bone imaging on a routine basis.It was shown that the various methods of examination, i.e. X-ray, biopsy and scintigraphy with both visual and quantitative evaluation provide their own individual values for the final diagnosis. Therefore, if one of the methods shows a negative result, bone involvement is not excluded and the others should be used for confirmation.     

Bone scanning in the diagnosis of acute osteomyelitis

Fifty-nine patients with suspected osteomyelitis were referred to the Nuclear Medicine Service for bone scanning during a twelve month period. The bone scan correctly identified abnormal sites in 18 of 19 patients with osteomyelitis (sensitivity of 95%) while the radiograph detected only 6 of 19 (sensitivity of 32%). In this clinical setting, the bone scans and radiographs had specificities of 92% and 89% respectively. Technetium-99m phosphate radiopharmaceuticals are superior to the previously used isotopes of fluorine and strontium in that they are readily available, can be imaged with conventional instruments, and allow high quality scans to be completed within 4 h. Routine bone scanning should be performed in patients presenting with suspected osteomyelitis and normal radiographs. The scan can be helpful in confirming or excluding the clinical suspicion and can lead to a more rapid institution of appropriate treatment.     

Diagnosis of osteomyelitis by MR imaging

Bone scans are highly sensitive for the diagnosis of acute osteomyelitis, but the difficulty of separating bone-marrow processes from soft-tissue disease limits the specificity and accuracy. A diagnostic technique capable of distinguishing bone-marrow processes from soft-tissue disease would improve the diagnostic accuracy of osteomyelitis. To evaluate the use of MR in the diagnosis of osteomyelitis, MR examinations were performed in 35 patients with suspected acute osteomyelitis. Twelve of these were proved to have osteomyelitis either by surgery (nine patients) or by clinical follow-up (three patients). In the other 23, osteomyelitis was excluded by surgery (12 patients) or by the clinical course (11 patients). Evidence of osteomyelitis on MR consisted of abnormalities of the bone marrow with decreased signal intensity on the T1-weighted images and increased signal intensity on the T2-weighted or short-T1 inversion recovery (STIR) images. MR and bone scintigraphy were interpreted by two radiologists who were given no clinical information other than to rule out osteomyelitis. The sensitivities of MR and static bone scan were 100% for bone-marrow abnormality. Because bone-marrow abnormality in osteomyelitis associated with healing fractures was incorrectly diagnosed by MR (one case) and bone scintigraphy (two cases), the sensitivities of MR and scintigraphy for the diagnosis of osteomyelitis were 92% and 82%, respectively. The specificities of MR and scintigraphy were 96% and 65%, respectively (p less than .05). The overall accuracy for the diagnosis of osteomyelitis was 94% for MR and 71% for bone scan (p less than .05). Because of its ability to separate soft-tissue disease from underlying bone marrow, MR may be used to evaluate patients with positive bone scintigraphy to improve the specificity and accuracy of diagnosis for osteomyelitis.     

Bone scanning in the diagnosis of acute osteomyelitis

Fifty-nine patients with suspected osteomyelitis were referred to the Nuclear Medicine Service for bone scanning during a twelve month period. The bone scan correctly identified abnormal sites in 18 of 19 patients with osteomyelitis (sensitivity of 95%) while the radiograph detected only 6 of 19 (sensitivity of 32%). In this clinical setting, the bone scans and radiographs had specificities of 92% and 89% respectively. Technetium-99m phosphate radiopharmaceuticals are superior to the previously used isotopes of fluorine and strontium in that they are readily available, can be imaged with conventional instruments, and allow high quality scans to be completed within 4 h. Routine bone scanning should be performed in patients presenting with suspected osteomyelitis and normal radiographs. The scan can be helpful in confirming or excluding the clinical suspicion and can lead to a more rapid institution of appropriate treatment.     

Diagnosis of osteomyelitis in the presence of soft-tissue infection and radiologic evidence of osseous abnormalities: value of leukocyte scintigraphy

To evaluate the usefulness of 111In-leukocyte scintigraphy for identifying osteomyelitis in the presence of soft-tissue infection, we prospectively studied 45 bone sites adjacent to soft-tissue infection in patients with abnormal findings on radiographs and 99mTc bone scans that were suggestive of osteomyelitis. 111In-leukocyte scans were analyzed in terms of the intensity of abnormal uptake and its location relative to bone. The diagnosis of osteomyelitis was established from results of percutaneous bone biopsy culture (n = 35), histologic examination of surgical specimens (n = 8), and clinical follow-up (n = 2). Osteomyelitis was present at 22 sites, including 16 of 18 sites with increased leukocyte uptake in bone, resulting in a sensitivity of 73%, specificity of 91%, and positive predictive value of 89% for this finding. Osteomyelitis was present at four of 17 sites with predominantly soft-tissue localization of leukocyte activity in the region of bone, none of seven sites with normal leukocyte scans, and two of three sites with diminished leukocyte uptake in bone. Although not helpful in distinguishing infectious from noninfectious bone abnormalities, 3- and especially 24-hr bone scans viewed in conjunction with leukocyte studies provided important correlation to aid in estimating the location of focal abnormal leukocyte uptake. The finding of soft-tissue infection with increased uptake of labeled leukocytes that extends to involve adjacent bone strongly suggests concurrent osteomyelitis. When the presence of abnormal leukocyte uptake in bone is uncertain, additional imaging and possibly biopsy may be required to establish or exclude the diagnosis of osteomyelitis.     

Radio-isotope bone scanning in suspected osteomyelitis in children

The usefulness of radio-isotope bone scanning in suspected osteomyelitis has been widely acclaimed. Fourteen children had rectilinear bone scans performed three hours after injection of Tc99m methylene diphosphonate. A diagnostic accuracy of 56% was achieved, which is lower than in other series. The reasons for this are discussed and the value of bone scanning in the evaluation of osteomyelitis is questioned.     

Radio-isotope bone scanning in suspected osteomyelitis in children

The usefulness of radio-isotope bone scanning in suspected osteomyelitis has been widely acclaimed. Fourteen children had rectilinear bone scans performed three hours after injection of Tc99m methylene diphosphonate. A diagnostic accuracy of 56% was achieved, which is lower than in other series. The reasons for this are discussed and the value of bone scanning in the evaluation of osteomyelitis is questioned.