Indium-111-labeled white blood cells in the detection of osteomyelitis complicated by a pre-existing condition

Forty-six patients (23M, 23F) ranging in age from 19 to 79 yr with a clinical history of a nonunion fracture, surgery, diabetes or a soft-tissue infection were studied with [111In]oxine WBCs to detect osteomyelitis. There were 27 true-positive, nine true-negative, two false-positive and one false-negative. The false-positives and the false-negative occurred in patients with soft-tissue infections overlying the area of interest. All diagnoses were confirmed by intraoperative bone biopsies and cultures. Bone biopsy and scan were performed within 2 days of each other in 39 patients. The overall sensitivity was 97% (27/28), specificity, 82% (9/11) and the diagnostic accuracy, 92% (36/39). The remaining seven patients had negative [111In]WBC scans several months after positive bone biopsies and definite antibiotic treatment. This suggests that [In]WBC scans become negative after appropriate therapy is undertaken. Interobserver data was obtained from four nuclear physicians of varying experience blinded to clinical information. A high degree of agreement was found in over 90% of the cases. This study demonstrates the utility of [111In]WBC scans in the diagnosis and follow-up of complicated osteomyelitis and a high level of interobserver agreement in scan interpretation.     

Subacute and chronic bone infections: diagnosis using In-111, Ga-67 and Tc-99m MDP bone scintigraphy, and radiography

The usefulness of indium-111 white blood cell scintigraphy in the diagnosis of subacute or chronic bone infection was examined in 21 orthopedic patients. In-111 WBC imaging was compared with gallium-67 and technetium-99m methylene diphosphonate skeletal scintigraphy and bone radiography, all studies being performed within 1 week. In-111 WBC scintigraphy showed no definite advantage over Ga-67 scintigraphy in the identification of chronic bone infection. The two tests had the same sensitivity (80%) and similar specificity (In-111 WBC 75%, Ga-67 83%; difference not significant). Bone radiography had a sensitivity of 60% and a specificity of 67%. A negative Tc-99m MDP bone scintigram ruled out infection (sensitivity 100%), but because of low specificity (25%), final evaluation required performance of Ga-67 or In-111 WBC scintigraphy.     

In-111-labeled white blood cell uptake in noninfected closed fracture in humans: prospective study

Since indium-111 white blood cell (In-111 WBC) scintigraphy is often used to evaluate for osteomyelitis in bone fractures, it is important to know if noninfected fractures have In-111 WBC uptake. Twenty-seven noninfected closed fracture sites in 19 patients were prospectively evaluated with technetium-99m methylene diphosphonate bone scintigraphy and In-111 WBC scintigraphy. In-111 WBC uptake was present in 41% of the 27 sites. In the 11 positive sites, the In-111 WBC uptake was 1+ (definite but minimal) in 55%, 2+ (moderate) in 36%, and 3+ (marked) in 9%. The visual intensity of the radioactive uptake on In-111 WBC scintigrams relative to that on bone scintigrams was less in 82%, equal in 9%, and greater in 9%. The visual size of the area of uptake on In-111 WBC scintigrams and bone scintigrams was smaller in 36%, equal in 55%, and greater in 9%. Factors that may help distinction of In-111 WBC uptake due to fracture alone from infection associated with fracture are discussed.     

Correlation of 111indium WBC scintigraphy with ultrasound in the detection and assessment of inflammatory bowel disease

111Indium (111In) WBC scintigraphy is an accurate method of assessing the extent of inflammatory bowel disease. A prospective study was performed to determine the correlation of ultrasound scanning with 111In WBC scintigraphy in the assessment of inflammatory bowel disease. Eighty-three indium and ultrasound scans were performed in 57 patients. Forty-six patients had Crohn's disease and 11 patients had ulcerative colitis. The site extent of abnormality and the appearance of the bowel were recorded and compared to the findings on indium scintigraphy. Ultrasound detected 84% of indium-positive sites. If the rectum was excluded, sensitivity of detection rose to 91%. Three percent of indium-negative sites were positive on ultrasound.     

In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection: comparison with other imaging modalities

When infection of prosthetic orthopedic implants is suspected, optimal management requires accurate confirmation or exclusion of infection. The authors retrospectively studied 98 patients with possible infection who underwent scanning with indium-111-labeled white blood cells (WBCs) and subsequently underwent surgery within 14 days. At surgery, 50 patients had infections, as determined by means of culture or histologic results. The diagnostic accuracy of In-111 scanning was compared with that of plain radiography, arthrography, three-phase bone scanning, and various clinical and laboratory findings classically associated with infection. Positive findings on In-111 WBC scans and elevated erythrocyte sedimentation rates were found to be the most predictive variables in the diagnosis of septic prostheses (P less than or equal to .001 and P less than or equal to .002, respectively). Likelihood ratio analysis more clearly demonstrated the superiority of In-111 WBC scanning, with positive and negative scans yielding likelihood ratios of 5.0 and 0.16, respectively.     

Detection of occult infection following total joint arthroplasty using sequential technetium-99m HDP bone scintigraphy and indium-111 WBC imaging

Preoperative exclusion or confirmation of periprosthetic infection is essential for correct surgical management of patients with suspected infected joint prostheses. The sensitivity and specificity of [111In]WBC imaging in the diagnosis of infected total joint prostheses was examined in 28 patients and compared with sequential [99mTc]HDP/[111In]WBC scintigraphy and aspiration arthrography. The sensitivity of preoperative aspiration cultures was 12%, with a specificity of 81% and an accuracy of 58%. The sensitivity of [111In]WBC imaging alone was 100%, with a specificity of 50% and an accuracy of 65%. When correlated with the bone scintigraphy and read as sequential [99mTc]HDP/[111In]WBC imaging, the sensitivity was 88%, specificity 95%, and accuracy 93%. This study demonstrates that [111In]WBC imaging is an extremely sensitive imaging modality for the detection of occult infection of joint prostheses. It also demonstrates the necessity of correlating [111In]WBC images with [99mTc]HDP skeletal scintigraphy in the detection of occult periprosthetic infection.     

What is the role of bone scintigraphy in the diagnosis of infected joint prostheses?

AIM: To analyse the role played by bone scintigraphy in the diagnosis of infected joint prostheses. METHODS: The study included 77 patients, aged 32-77 years, in whom infection of a joint prosthesis (48 hip, 29 knee) was suspected. In all patients the following examinations were performed consecutively: a two-phase Tc methylene diphosphonate (Tc-MDP) bone scan, a Tc hexamethylproplyene amine oxime (Tc-HMPAO) labelled white blood cell (WBC) scan, and a Tc microcolloid bone marrow (BM) scan. The minimum interval between examinations was 48 h. The diagnoses were based on data obtained from bacteriological cultures. RESULTS: The bone scan was positive in all patients and 28 of them had an infection (sensitivity 100%, specificity 0%). The WBC scan was positive in 61 patients but only 27 had an infection. The WBC scan was negative in 16 patients, and the possibility of infection was discarded in 15 of these cases (sensitivity 96%, specificity 30%). The results of the bone marrow scan were not compatible with those of the WBC scan (suggestive of infection) in 27 patients: 26 of them had prosthesis infection. The results of both examinations were compatible in the other 34 patients and the possibility of infection was discarded in 33 of these patients (sensitivity 92.8%, specificity 98%). The addition of a BM scan to a WBC scan decreased the sensitivity from 96% to 92.8% but increased specificity from 30% to 98%. The addition of a bone scan to this dual combination did not alter the results. CONCLUSIONS: When infection of a prosthesis is suspected the diagnostic procedure should start with a WBC scan followed, if positive, by a BM scan. This procedure reduces the cost, the time required for a diagnosis, and the dose of radiation received by the patient.     

111 In-labeled leukocytes in the detection of prosthetic vascular graft infections

Making a clinical diagnosis of infection in prosthetic vascular grafts is difficult but when undiagnosed, this condition has a high mortality rate. Using Indium-111-labeled white-blood cells, 30 scans were performed in 21 patients suspected of having a prosthetic graft infection. The diagnosis of infected graft was confirmed by surgery in all cases, and lack of infection was established by resolution of symptoms with conservative therapy. Twenty-four hour scans of autologous Indium-111 leukocytes were obtained, and correlative CT studies were done in 11 cases. There were 13 infected grafts at surgery (purulent material present), and scans were positive in all (100% sensitivity); of 17 scans, there were 15 true negatives and two false positives (88% specificity). Using the criteria of gas or fluid around the graft, the sensitivity of CT was only 37% in a small subset of these patients. One-half of the cases in which infection was suspected clinically had no infection and had negative scans. Various types of grafts and graft materials were used, and there was no correlation with presence or absence of infection on the basis of the type of graft. Extragraft infection sites were found in five patients. In conclusion, use of Indium-111 leukocytes has been found to be an accurate and valuable diagnostic method for evaluation of suspected prosthetic vascular graft infection, and to have higher diagnostic accuracy than CT.     

Indium-111 chloride imaging in the detection of infected prostheses

Thirty-three patients with painful joint prostheses and a suspicion of infection were imaged with [111In]chloride. A final diagnosis was established by culture in 19. Of these, 12 were categorized as true positives and three as true negatives. There were two false-positive studies, occurring in patients with knee prostheses. In both, the culture was obtained by aspiration. Two false negatives were in patients with hip prostheses, one of whom had been on long-term antibiotic suppressive therapy. The sensitivity was 86%, specificity 60%, and accuracy 79%. Seventeen of the proven cases had bone imaging prior to [111In]chloride imaging. All 17 static images were positive and were not helpful in differentiating loosening from infection. Using increased uptake on the blood-pool image as a criteria for infection, the sensitivity was 89%, but the specificity was 0. Adding flow studies made little difference in interpreting the blood-pool images. This study shows that [111In]chloride accurate in evaluating infection in prosthesis than bone imaging.     

White blood cell scintigraphy with monoclonal antibodies in the study of the infected endoprosthesis.

Forty-three patients with suspected infection of a hip or a knee prosthesis were studied with white blood cell scintigraphy (WBC), using technetium-99m (n = 37) or iodine-123 (n = 6) labelled monoclonal mouse antibody (MoAb). Previously, all patients had undergone skeletal scintigraphy, which was performed as a three-phase study in 33 cases. The final diagnosis was established by open surgery, histology and culture in 37 cases, by puncture and culture in 3 cases, and by clinical follow-up of at least 6 months in 3 cases. Eighteen prostheses were infected, 25 uninfected. The delayed phase of skeletal scintigraphy had a sensitivity of 92%, a specificity of 24% and an accuracy of 48% in the detection of infection. The perfusion and blood pool activity of the three-phase bone scan had a sensitivity of 67%, a specificity of 71% and an accuracy of 70%. The diagnostic value of WBC was sensitivity 89%, specificity 84% and accuracy 86%. WBC with 99m-Tc-MoAb is easy to perform and always available. Its diagnostic accuracy is similar to conventional WBC scintigraphy with either indium-111 or technetium-99m.     

White blood cell scintigraphy with monoclonal antibodies in the study of the infected endoprosthesis

Forty-three patients with suspected infection of a hip or a knee prosthesis were studied with white blood cell scintigraphy (WBC), using technetium-99m (n = 37) or iodine-123 (n = 6) labelled monoclonal mouse antibody (MoAb). Previously, all patients had undergone skeletal scintigraphy, which was performed as a three-phase study in 33 cases. The final diagnosis was established by open surgery, histology and culture in 37 cases, by puncture and culture in 3 cases, and by clinical follow-up of at least 6 months in 3 cases. Eighteen prostheses were infected, 25 uninfected. The delayed phase of skeletal scintigraphy had a sensitivity of 92%, a specificity of 24% and an accuracy of 48% in the detection of infection. The perfusion and blood pool activity of the three-phase bone scan had a sensitivity of 67%, a specificity of 71% and an accuracy of 70%. The diagnostic value of WBC was sensitivity 89%, specificity 84% and accuracy 86%. WBC with ^99m-Tc-MoAb is easy to perform and always available. Its diagnostic accuracy is similar to conventional WBC scintigraphy with either indium-111 or technetium-99m. Offprint requests to: J. Sciuk     

Clinical evaluation of indium-111-labeled leukocyte imaging in bone infection

In-111-oxine-labeled leukocyte imaging was performed on twenty-one patients suspected of having bone infection. Nine of eleven cases (82%) were diagnosed as having active infection as demonstrated by abnormal accumulation of In-111-labeled leukocytes at the site of infection. There are two false negative (18%) cases. Two cases without active infection showed abnormal uptake. Four cases revealed cold defects on the scintigraphy. Marked uptake of radiotracer was noted not only in the case of acute osteomyelitis with acute septicaemia but also in the case with persistent chronic active osteomyelitis. It was observed that for precise evaluation of the test results it was equally important to compare the imaging findings with physical signs and laboratory investigations. It is concluded that In-111-oxine-labeled leukocyte imaging is a useful tool for the evaluation of the progression of bone infection.     

SPECT/CT using 67Ga and 111In-labeled leukocyte scintigraphy for diagnosis of infection.

The present study evaluated the role of SPECT/CT as an adjunct to (67)Ga (GS) or (111)In-labeled white blood cell (WBC) scintigraphy for diagnosis or localization of infection. METHODS: Eighty-two patients (56 male and 26 female; mean age, 62 y) assessed for known or suspected infectious processes underwent 88 SPECT/CT studies. Forty-seven patients underwent GS SPECT/CT (13 with fever of unknown origin, 21 with suspected osteomyelitis, and 13 with suspected soft-tissue infection), and 35 patients underwent WBC SPECT/CT (24 with suspected vascular graft infection, and 11 with suspected osteomyelitis). Ninety-eight suggestive sites were identified (52 on GS and 46 on WBC). Additional information provided by SPECT/CT for diagnosis or localization of infection, as compared with planar and SPECT scintigraphy, was recorded. The SPECT/CT contribution was analyzed on a patient and site basis and was compared for the 2 tracers and clinical indications. RESULTS: SPECT/CT provided additional information for infection diagnosis and localization in 39 (48%) of 82 patients and in 47 (48%) of 98 sites. SPECT/CT defined the extent of infection in 35 patients (43%) in 43 sites (44%) and excluded infection in 4 suggestive sites defined as physiologic bowel uptake on GS. SPECT/CT was incorrect in 2 suggestive sites (1 GS and 1 WBC). The contribution of SPECT/CT was significantly higher for WBC than for GS (P < 0.05)--in 63% versus 36% of patients, respectively, and in 61% versus 36% of sites, respectively. CONCLUSION: SPECT/CT made an incremental contribution to GS and WBC in 48% of patients with suspected infections, by improving diagnosis, localization, and definition of extent of disease. SPECT/CT has an important role mainly with highly specific, low-background infection-seeking tracers such as WBC.     

Chronic bacterial osteomyelitis: prospective comparison of <Superscript>18</Superscript>F-FDG imaging with a dual-head coincidence camera and <Superscript>111</Superscript>In-labelled autologous leucocyte scintigraphy

Indium-111-labelled white blood cells ((111)In-WBCs) are currently considered the tracer of choice in the diagnostic work-up of suspected active chronic osteomyelitis (COM). Previous studies in a limited number of patients, performed with dedicated PET systems, have shown that [(18)F]2'-deoxy-2-fluoro- D-glucose (FDG) imaging may offer at least similar diagnostic accuracy. The aim of this prospective study was to compare FDG imaging with a dual-head coincidence camera (DHCC) and (111)In-WBC imaging in patients with suspected COM. Thirty consecutive non-diabetic patients with possible COM underwent combined skeletal scintigraphy (30/30 patients), (111)In-WBC imaging (28/30 patients) and FDG-PET with a DHCC (30/30 patients). During diagnostic work-up, COM was proven in 11/36 regions of suspected skeletal infection and subsequently excluded in 25/36 regions. In addition, soft tissue infection was present in five patients and septic arthritis in three. (111)In-WBC imaging in 28 patients was true positive in 2/11 regions with proven COM and true negative in 21/23 regions without further evidence of COM. False-positive results occurred in two regions and false-negative results in nine regions suspected for COM. Most of the false-negative results (7/9) occurred in the central skeleton. If the analysis was restricted to the 18 regions with available histology ( n=17) or culture ( n=1), (111)In-WBC imaging was true positive in 2/18 regions, true negative in 8/18 regions, false negative in 7/18 regions and false positive in 1/18 regions. FDG-DHCC imaging was true positive in 11/11 regions with proven COM and true negative in 23/25 regions without further evidence of COM. False-positive results occurred in two regions. If the analysis was restricted to the 19 regions with available histology ( n=18) or culture ( n=1), FDG-DHCC imaging was true positive in 9/9 regions with proven COM and true negative in 10/10 regions without further evidence of COM. It is concluded that FDG-DHCC imaging is superior to (111)In-WBC scintigraphy in the diagnosis of COM in the central skeleton and therefore should be considered the method of choice for this indication. This seems to hold true for peripheral lesions as well, but in our series the number of cases with proven infection was too small to permit a final conclusion.     

Comparison of 67Ga-citrate, 111In-bleomycin and 99mTc-citrate in the evaluation of pulmonary lesions

A total of 128 patients were examined using three tumor localizing agents, 99mTc-citrate, 111In-bleomycin and 67Ga-citrate. All these patients had clinical symptoms of pulmonary disease and chest x-rays. Twenty-two patients were excluded from the original number. From the 106 remaining patients, 14 were benign cases and 92 malignant. A scan with a gamma-camera was performed 3 to 4 h following an intravenous injection of 15 mCi of 99mTc-citrate. Upon completion of this examination, the patient was given 2.5 mCi of 67Ga-citrate and 72 h later, scans were obtained using a 5in. rectilinear scanner. Fifteen days later 2.5 mCi of 111In-bleomycin was given and a similar examination to that of gallium was performed. In evaluating benign lesions, 99mTc-citrate gave no false positive results, while 111In-bleomycin gave 5% and 67Ga-citrate 20%. In the case of malignant lesions, 67Ga-citrate gave 79% true positive diagnosis, 111In-bleomycin 65% and 99Tc-citrate (of 57 evaluated patients) 46%.     

Detection of subacute infectious foci with indium-111-labeled autologous leukocytes and indium-111-labeled human nonspecific immunoglobulin G: a prospective comparative study

In 35 patients suspected of an infectious focus, the outcome of scintigraphy with 111In-labeled autologous leukocytes (WBC) and 111In-labeled human nonspecific immunoglobulin G (IgG) was evaluated in a prospective comparative study. Clinical, roentgenologic and microbiologic findings were considered to be proof of the presence of infection or inflammation. In this group of patients with mainly subacute infections, 111In-IgG scintigraphy performed significantly better than 111In-WBC scintigraphy, especially in infections of the locomotor system, but also in various soft-tissue infections. Both techniques showed disappointing results in patients with disseminated yersinia infection and in some patients with tuberculosis. Overall sensitivity and specificity was 74% and 100% for 111In-IgG scintigraphy and 52% and 78% for 111In-WBC scintigraphy, respectively.     

Doppler ultrasound scanning in the detection of renal artery stenosis in hypertensive patients.

The diagnostic accuracy of Doppler ultrasound in the detection of renal arterial disease has been assessed in a prospective study of 61 hypertensive patients. The findings of Doppler ultrasound were compared with the results of renal angiography. In 15 patients (24.5%) no accurate Doppler signs could be obtained and the Doppler ultrasound examination was considered a technical failure. Of the remaining 46 patients, 24 had renal artery stenosis. Nine of the stenoses were not detected by Doppler ultrasound and in three patients a false positive diagnosis of renal artery stenosis was made. The sensitivity of Doppler ultrasound was 62.5%, the specificity 86.4% and the overall diagnostic accuracy was 73.9%. By comparing the 15 patients in whom Doppler ultrasound failed with the 46 in whom it was successful, age appeared to be higher and creatinine clearance lower in the failure group. By comparing the 34 patients with true positive and true negative results with the 12 patients with false results, no significant differences were found. In a multivariate analysis, higher age showed a significant relation to failure of Doppler ultrasound. Doppler ultrasound has limited value in the screening of hypertensive patients for renal artery stenosis.     

Detection of acute osteomyelitis with indium-111 labeled white blood cells in a patient with sickle cell disease

A young patient with sickle cell disease (SCD) and multiple hospitalizations for crisis was admitted because of suspected osteomyelitis. Initial laboratory work, radiographs, and bone images were not contributory. An In-111 white blood cell (WBC) study demonstrated two areas of increased radionuclide uptake consistent with osteomyelitis. One of these had associated soft tissue infection. No other areas of active osteomyelitis were visualized, in spite of the presence of several additional infection sites. Imaging with In-111 WBC is probably not justified for routine diagnosis of acute osteomyelitis in areas free of previous disease, where conventional bone images are highly efficient. In-111 WBC imaging, however, may be helpful in detecting osteomyelitis in selected patients with SCD in whom Tc-99m bone images and radiographs are usually abnormal and difficult to interpret due to previous bone infarcts. Localization of the infection focus is very important in choosing the aspiration site for bacteriologic studies. A negative study, however, should be interpreted cautiously.     

Postoperative bone marrow alterations: potential pitfalls in the diagnosis of osteomyelitis with In-111-labeled leukocyte scintigraphy.

Scintigraphy was used after injection of technetium-99m methylene diphosphonate (MDP) and indium-111-labeled white blood cells (WBCs) to assess for the presence of osteomyelitis in 97 patients who had undergone prior surgical procedures. Thirty-four patients with abnormal In-111-labeled WBC patterns underwent restudy with Tc-99m albumin colloid (AC). Scintigraphic findings were considered positive for osteomyelitis whenever localization of In-111-labeled WBCs exceeded Tc-99m AC activity in extent or focal intensity (discordant pattern). Ten of 12 patients with culture-proved osteomyelitis had discordant patterns; two had false-negative (concordant) patterns. The cases of 20 of 22 patients without infection who were considered to have osteomyelitis on the basis of patterns of In-111-labeled WBCs and Tc-99m MDP were reclassified correctly on the basis of concordant patterns of In-111-labeled WBCs and Tc-99m AC. Radiocolloid images improved the overall scintigraphic specificity for osteomyelitis from 59% without bone marrow imaging to 92%; sensitivity decreased from 94% to 88%.