Evaluation of a 3-hour indium-111 leukocyte image as a surrogate for a technetium-99m nanocolloid marrow scan in the diagnosis of orthopedic infection

OBJECTIVES: This is a retrospective study to evaluate a 3-hour In-111-labeled leukocyte image as a surrogate for a Tc-99m nanocolloid marrow scan in the investigation of suspected orthopedic infection using In-111 leukocyte scintigraphy. METHODS: Images from 51 patients who had received contemporaneous In-111-labeled leukocyte scintigraphy and Tc-99m nanocolloid marrow scintigraphy were reviewed. Initially, the 3-hour and 22-hour In-111-labeled leukocyte images were compared. Sites of abnormal uptake on the 22-hour image were correlated with the 3-hour image and were graded according to the level of concordance or discordance. One week later, the Tc-99m nanocolloid images and 22-hour In-111-labeled leukocyte images of the same patients were compared and graded for concordance or discordance. When discrepancies in grading arose between the observers, a consensus opinion was achieved after additional review of the images a week later. RESULTS: On inspection of the 22-hour In-111 leukocyte images, 93 sites of focal, potentially abnormal leukocyte accumulation were identified. When the grading system was reduced to simply "concordant" or "discordant," there was good agreement between the observers in the majority of cases, with kappa statistics 0.77 for Tc-99m nanocolloid versus 22-hour In-111-labeled leukocyte images and 0.78 for 3-hour versus 22-hour In-111-labeled leukocyte images. Using the comparison of the Tc-99m nanocolloid marrow scan and the 22-hour In-111-labeled leukocyte images to identify concordance or discordance as the "gold standard" for scintigraphic evaluation of suspected orthopedic infection, comparison of the 3-hour In-111-labeled leukocyte images with the 3-hour In-111-labeled leukocyte images gave a sensitivity of 77%, a specificity of 77%, and an accuracy of 77%. CONCLUSIONS: A 3-hour image is helpful using In-111-labeled leukocyte scintigraphy.     

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.     

Failure of indium-111 leukocyte scanning to detect nodal involvement with Mycobacterium avium-intracellulare infection in the acquired immunodeficiency syndrome

An In-111 leukocyte scan was used to evaluate fever of unknown origin in a patient with the AIDS rather than Ga-67. The scan was normal despite an impressively positive Ga-67 scan performed 48 hours later. In-111 should not be used to evaluate fever in patients with AIDS where mycrobacterium avium-intracellular infection is a diagnostic possibility.     

Importance of Tc-99m sulfur colloid liver-spleen scans performed before indium-111 labeled leukocyte imaging for localization of abdominal infection

INTRODUCTION: The localization of intraabdominal abscesses is a difficult imaging problem in nuclear medicine, especially when the location of the abscess is in the area of the liver and spleen. The need for performing Tc-99m sulfur colloid liver-spleen scans before injecting indium-111 leukocytes for improved lesion detection and characterization versus performing In-111 leukocyte scans alone has been questioned in the literature MATERIALS AND METHODS: We present 3 patients with intraabdominal abscesses in the liver-spleen area, in which liver-spleen scans were performed before In-111 leukocyte scans. The findings of all were correlated with computed tomography and interventional procedures. RESULTS: In all patients, the Tc-99m liver-spleen scan helped for accurate recognition of the location of the abscess, correlated with computed tomography findings, and were helpful for intervention and exclusion of the other sources of infection. CONCLUSION: Data from these 3 patients reinforces the need for Tc-99m sulfur colloid liver-spleen scans before performing In-111 WBC scans for better localization and interventional treatment of intraabdominal abscesses.     

Unsuspected extra-abdominal sites of infection: scintigraphic detection with indium-111-labeled leukocytes

Scintigraphy with indium-111-labeled leukocytes (In-111-WBC) was assessed in 128 patients with suspected abdominal-pelvic abscesses. Studies were positive in 37 of 41 patients with proved abscesses, in two of two with infected aortic grafts, and in 12 of 15 with other infections; studies were negative in 63 of 70 cases without infection. The sensitivity of leukocyte scintigraphy in this series was 88%, specificity 90%, and accuracy 89%. Sixteen percent of all patients studied with In-111-WBC scintigraphy had unexpected sites of infection outside the abdomen. Of the 58 patients with proved infection, 20 (34%) had alterations in diagnostic evaluations and therapeutic regimens due to such findings.     

Distribution of leukocytes labeled with In-111 oxine in dogs with acute inflammatory lesions

The biodistributions of In-111 oxine (with and without leukocyte labeling) of Ga-67 citrate and of In-111 chloride were compared in 30 dogs with chemical and bacterial abscesses and acute joint inflammation. Serial blood samples were taken and tissues radioassayed at 24 hr. The concentration of In-111-oxine leukocytes in all three types of inflammatory lesion was invariably much higher than that of Ga-67 injected simultaneously. For bacterial abscesses, the mean abscess-to-muscle concentration ratio was 3,000 for labeled leukocytes and 72 for Ga-67. Aqueous buffered In-111 oxine sulfate solution appeared better for labeling leukocytes than In-111 oxine in ethanol. When In-111 oxine was not incubated with leukocytes before injection, or if the cells were poorly labeled or damaged, the abscess localization was often inferior to that of gallium. Localization of In-111 chloride also appeared inferior to that of gallium. No significant difference in distribution in the major organs or inflammatory lesions was demonstrable between labeled suspensions of "pure"neutrophils harvested by elutriation and "mixed"cell suspensions of leukocytes after erythrocyte sedimentation with hydroxyethyl starch. For both types of leukocyte suspension labeled with In-111 oxine, the average recovery of cell-bound activity in the circulating blood at 4 hr was 32% of the administered activity, inferior to that of DFP-32. It is concluded, therefore, that In-111 oxine is a more effective agent than Ga-67 for the detection of acute focal inflammatory lesions if leukocytes are properly labeled, but current techniques are unsatisfactory for the study of neutrophil kinetics.     

Osteomyelitis: diagnosis with In-111-labeled leukocytes

In a retrospective review, 485 patients with suspected osteomyelitis were studied. Of these, 453 patients were studied with both bone and indium-111 leukocyte scanning (173 sequentially and 280 simultaneously). The ability to determine that the infection was in bone rather than in adjacent soft tissue was greater with simultaneous bone scan and In-111 leukocyte studies than with sequential studies. The locations of suspected osteomyelitis were divided into central (containing active bone marrow), peripheral (hands and feet), and middle (between central and peripheral). Specificity remained high (about 90%) regardless of the location. Overall sensitivity was significantly lower in the central location than in the peripheral or middle location. Determination of whether the In-111 leukocyte activity was in bone or adjacent soft tissue was also more difficult when the infection was in the central location. For acute osteomyelitis, sensitivity was high regardless of the location. For chronic osteomyelitis, sensitivity was lower in the central location.     

Indium-111 leukocyte localization in infected prosthetic graft

Infective endocarditis can be difficult to prove, even in the face of strong clinical suspicion. A case in which standard methods of diagnosis failed to demonstrate endocarditis in a patient with recurrent Staphylococcus aureus bacteremia and porcine aortic valve is reported. An In-111 labelled leukocyte SPECT study demonstrated uptake in the aortic root and leaflets, and autopsy demonstrated vegetations on the leaflets. In-111 may prove useful in demonstrating endocarditis in patients with prosthetic valve infection.     

The complementary role of indium-111 labeled leukocyte imaging,ultrasonography and computed tomography in the evaluation of postoperative infection or abscess

We report our experiences with the combined use of indium-111 labeled leukocyte imaging (In-III WBC scan.), computed tomography (CT) and ultrasonography (US) for evaluation of suspected postoperative infection or abscess, and discuss the complementary roles of these modalities. Postoperative abscesses or infections were diagnosed in 9 of 20 patients. All patients were correctly diagnosed by In-111 WBC imaging and 4 patients could not be diagnosed by US because of bowel gas. One false-positive CT examination and another artifact on CT images due to respiratory movements were obtained. The three modalities were found to be complementary: CT and US were efficient imaging methods for diagnosis and treatment of abscess. In-111 WBC imaging could estimate the activity of inflammation.     

Gastrointestinal tract radionuclide activity on In-111 labeled leukocyte imaging: clinical significance in patients with fever of unknown origin

To determine the frequency and clinical significance of indium-111 labeled leukocyte activity in the gastrointestinal (GI) tract of patients with fever of unknown origin, we reviewed 312 leukocyte studies involving 271 patients. Radionuclide activity was noted in the bowel in 59 cases. Of these, only 27 were due to the infection or inflammatory disease that caused the patient's fever. The 32 false-positive results were due primarily to swallowed leukocytes or bleeding. In two cases, no explanation was found for the activity in the GI tract. We conclude that bowel activity on In-111 labeled leukocyte scans in patients with fever of unknown origin often does not correlate with the true cause of the patient's fever.     

Indium-111 chloride imaging with ununited fractures

Twenty patients with ununited fractures and a suspicion of infection had In-111 chloride imaging. Surgically obtained cultures were positive for infection in 12 and negative in eight patients. In-111 chloride images were positive in all 12 patients with infection but also were positive in six of the patients with negative cultures. It is not possible to differentiate infected from noninfected ununited fractures by In-111 chloride imaging.     

Role of in-111 labeled leukocyte scintigraphy in the diagnosis of intracerebral lesions

The differential diagnosis of intracerebral enhancing lesions on contrast computed tomography includes tumors, abscesses, and cerebrovascular accidents. Particularly important is the differentiation between tumor and abscess. While In-111 labeled leukocyte imaging is an accurate test for identification of foci of infection in general, the role of this procedure in the evaluation of the intracranial lesion is not well established. We undertook a retrospective review of 16 patients with contrast enhancing intracerebral lesions identified on computed tomography, who were also studied with labeled leukocyte imaging. Final diagnoses were: abscess (n = 2), primary brain tumor (n = 6), metastasis (n = 4), dermoid cyst (n = 1), and cerebral infarct (n = 3). There were two positive labeled leukocyte studies; both were cerebral abscesses. No labeled leukocyte activity was identified in any of the tumors or infarcts. We conclude that In-111 labeled leukocyte imaging is an accurate method of differentiating infectious from noninfectious causes of intracerebral lesions identified on computed tomography.     

Abdominal patterns of indium-111 labeled leukocyte imaging

In-111 oxine WBC abdominal scanning is now a widely accepted technique for the detection of abdominal infectious processes. High sensitivity and specificity are achieved. In-111 labeled leukocyte accumulation, however, does not always suggest the diagnosis of abscess. Higher specificity could be obtained by the knowledge of the In-111 leukocyte distribution pattern in the abdomen in other pathologic states like inflammation of abdominal wounds, stoma; surgical complication without abscess formation; inflammatory or ischemic bowel disease; or swallowing leukocytes which subsequently are visualized in the intestinal lumen. One hundred fifty-two consecutive WBC scans performed over 18 months were reviewed and classified according to their pattern of uptake: 96 cases showed no abdominal uptake, and 56 had accumulation of leukocytes in the abdomen. Twenty-eight of these patients had proven abdominal abscess, and the remaining 26 were positive due to other causes. This report briefly discusses the distribution pattern of In-111 labeled leukocytes in the latter patients and compares the results obtained using different diagnostic criteria.     

"Halo" sign on indium-111 leukocyte scan in gangrenous cholecystitis

A 56-year-old man with a long history of Crohn's disease was evaluated by In-111 labeled leukocyte scanning. A "halo" of leukocyte activity was seen around the gallbladder fossa. A gangrenous gallbladder was removed at surgery.     

Nonvisualization of sterile surgical incisions with indium-111 labeled leukocytes

The localization of In-111 labeled leukocytes (WBCs) in recent surgical incisions was studied in 18 patients. In-111 WBC images correlated well with culture results and clinical findings. No accumulation of In-111 WBCs was detected at the site of noninfected incisions in nine patients. In-111 WBCs did accumulate at incision sites in nine patients with infected surgical incisions. These results indicate that In-111 WBC study can accurately distinguish between normal healing and infection of recent surgical incisions.     

Sequential technetium-99m sulfur colloid/indium-111 white blood cell imaging in macroglobulinemia of Waldenstrom

Technetium-99m sulfur colloid (SC) and indium-111 labeled leukocyte (In-111 WBC) scintigraphy was performed on a 77-year-old female patient to rule out a left periprosthetic infection. Anterior Tc-99m SC and In-111 WBC images of the pelvis and femurs revealed no abnormal deposition of radiotracer about the Austin-Moore prosthesis. Absent radiotracer uptake, however, was demonstrated within the left hemipelvis. A left iliac bone marrow aspirate and biopsy revealed a lymphoplasmacytic infiltrate consistent with Waldenstrom's macroglobulinemia.     

Uptake of In-111 labeled leukocytes by lymphocele. A cause of false-positive vascular graft infection.

In-111 labeled leukocyte scintigraphy is a sensitive test for the diagnosis of prosthetic vascular graft infections. However, several causes of false-positive results have been reported. The authors describe a case of uninfected lymphocele around a synthetic vascular graft in a patient who showed an infected graft on In-111 labeled leukocyte scintigraphy.     

Tc-99m HMPAO-labeled leukocytes for hematopoietic marrow imaging. Comparison with In-111 chloride.

The current study was initiated to define whether Tc-99m leukocyte imaging, compared to In-111 chloride imaging, could provide additional information on the hematopoietic activity of the bone marrow in diffuse hematologic disorders. A total of 11 patients with hematologic disorders were studied both with Tc-99m leukocytes and In-111 chloride. One patient with myelofibrosis showed disparate tracer distribution in the bone marrow between the two; Tc-99m leukocyte uptake in the central marrow was highly decreased, whereas In-111 chloride showed expanded marrow. The disparate results of granuloid hypoplasia and erythroid hyperplasia obtained by bone marrow biopsy and aspiration in this patient were thought to give an explanation for the radionuclide findings. The remaining 10 patients showed similar tracer distribution in the marrow, and the observation of hematopoietic cellularity confirmed by bone marrow biopsy and aspiration correlated well with the radionuclide findings. These results demonstrate that Tc-99m leukocytes may be a potential imaging agent for evaluating hematopoietic activity in the bone marrow, in particular granulopoietic activity.     

Effect of chronicity of infection on the sensitivity of the In-111-labeled leukocyte scan

This study was undertaken to determine the effect of chronicity of infection on the sensitivity of In-111-labeled leukocyte scanning. A total of 332 scans on 290 patients were reviewed retrospectively. The diagnosis of infection was based on culture results and other laboratory data, autopsy findings, radiographic studies, and clinical course. Duration of infection at the time of scanning was determined by the date of onset of fever and symptoms, elevation of white cell count, positive cultures, and abnormal findings on radiographic studies. Sensitivity of leukocyte scanning was 90% for 69 patients who had infections for 0-14 days and 86% for 86 who had infections for 15 days or longer. This difference is not statistically significant.     

Indium-111 labeled purified granulocytes in the diagnosis of synthetic vascular graft infection

Indium-111 labeled leukocytes have been shown to be useful in the diagnosis of synthetic vascular graft infection. To minimize the potential effects of labeled red blood cells and platelets on image interpretation, the authors prepared purified autologous granulocytes (PG) from 84 ml of blood using Volex enhanced gravity sedimentation and Ficoll-Hypaque double density centrifugation. The labeling efficiency of PG with In-111 tropolone was 90 +/- 9% (mean +/- SD). Imaging was performed 18-24 hours following injection of approximately 445 microcuries of In-111 PG in 26 patients with suspected infection of vascular grafts that had been implanted 12 days to 12 years prior to the study. In ten patients with proven graft infection, seven had positive In-111 PG scans. Ten of 11 patients without infection had negative scans. In five patients with clinically equivocal findings, scan results were positive in one, negative in one, and equivocal in three. A false-positive scan occurred in a patient with an uninfected inflammatory pseudoaneurysm of an aortic graft. These results confirm an earlier report that In-111 PG imaging is a useful technique in the diagnosis of synthetic vascular graft infection.