Lack of Clinical Utility of Labeled White Blood Cell Scintigraphy in Patients with Fever of Unknown Origin

Background Labeled white blood cell scintigraphy (WBCS) has been used for over 40 years to localize an infection source in patients with fever of unknown origin (FUO). It continues to be in widespread use for such patients in modern times, despite the tremendous advances in modern radiological imaging and laboratory medicine. Methods We critically evaluated the clinical contribution of WBCS performed in 132 patients with FUO at 7 hospitals from mid-2015 to the end of 2019. For each patient, all radiographic and laboratory results, and all electronic clinical notes, were carefully evaluated as many days prior to and following the scan as necessary to arrive at a final diagnosis. Results Although 50 WBCS (38%) showed positive findings, the majority of these were false positive (FP). Of the 19 true positive (TP) scans, most were already known or about to become known by tests already ordered at the time of the scan. Only 2 TP scans (1.5%) contributed to the final diagnosis, and these did so only indirectly. FP scans led to 7 unnecessary procedures. Conclusions In FUO patients for whom an infection source is not discovered following an appropriate radiographic and laboratory workup, WBCS is not a useful procedure.

The Role of a Virtual Noncalcium Dual-Energy CT Application in the Detection of Bone Marrow Edema in Peripheral Osteomyelitis

Purpose: To determine the sensitivity and specificity of dual-energy CT (DECT) virtual noncalcium images (VNCa) with bone and soft tissue reconstructions in the diagnosis of osteomyelitis. Materials & Methods: Between December 1, 2014 to December 1, 2020, 91 patients who had 99 DECT performed for a clinical indication of osteomyelitis with corresponding MRI, triphasic bone scan and/or white blood cell scintigraphy with CT/SPECT performed either 2 weeks before or 1 month after the DECT were retrospectively identified. The presence or absence of osteomyelitis was established using a second imaging test, bone biopsy or surgery. Two radiologists interpreted VNCa images alone and with bone and soft tissue reconstructions for osteomyelitis. Fleiss k statistics was used to assess inter-level agreement. Results: Osteomyelitis was present in 26 cases (26.2%), of which 4 cases (4%) had co-existing septic arthritis. DECT was performed at the following sites: ankle/foot (n = 59), calf (n = 12), knee (n = 3), thigh (n = 7), hip (n = 9), pelvis (n = 6), wrist/hand (n = 1), and shoulder (n = 2). Sensitivity with VNCa images alone was 53.8% and 73.1% and specificity was 84.9% and 71.2%. Sensitivity with VNCa images and bone and soft tissue reconstructions was 80.8% and 80.8% and specificity was 80.8% and 72.6%. Interobserver agreement was 76.7% (76 of 99 cases), for VNCa images alone (k = .487), and 66.7% (66 of 99 patients) for bone and soft tissue reconstructions with VNCa images together (k = .390). Conclusion: When VNCa images were combined with bone and soft tissue reconstructions, there is improved sensitivity in the diagnosis of osteomyelitis.

Comparison of White Blood Cell Scintigraphy, FDG PET/CT and MRI in Suspected Diabetic Foot Infection: Results of a Large Retrospective Multicenter Study

Diabetic foot infections (DFIs) represent one of the most frequent and disabling morbidities of longstanding diabetes; therefore, early diagnosis is mandatory. The aim of this multicenter retrospective study was to compare the diagnostic accuracy of white blood cell scintigraphy (WBC), 18F-fluorodeoxyglucose positron emission tomography/computed tomography ((18F) FDG PET/CT), and Magnetic Resonance Imaging (MRI) in patients with suspected DFI. Images and clinical data from 251 patients enrolled by five centers were collected in order to calculate the sensitivity, specificity, and accuracy of WBC, FDG, and MRI in diagnosing osteomyelitis (OM), soft-tissue infection (STI), and Charcot osteoarthropathy. In OM, WBC acquired following the European Society of Nuclear Medicine (EANM) guidelines was more specific and accurate than MRI (91.9% vs. 70.7%, p < 0.0001 and 86.2% vs. 67.1%, p = 0.003, respectively). In STI, both FDG and WBC achieved a significantly higher specificity than MRI (97.9% and 95.7% vs. 83.6%, p = 0.04 and p = 0.018, respectively). In Charcot, both MRI and WBC demonstrated a significantly higher specificity and accuracy than FDG (88.2% and 89.3% vs. 62.5%, p = 0.0009; 80.3% and 87.9% vs. 62.1%, p < 0.02, respectively). Moreover, in Charcot, WBC was more specific than MRI (89.3% vs. 88.2% p < 0.0001). Given the limitations of a retrospective study, WBC using EANM guidelines was shown to be the most reliable imaging modality to differentiate between OM, STI, and Charcot in patients with suspected DFI.

Leukocyte Imaging of the Diabetic Foot

Background: Diagnosing diabetic foot infection is often difficult, despite several available diagnostic methods. Amongst these, several imaging modalities exist to evaluate the diabetic foot in case of a suspected osteomyelitis. Nuclear Medicine, in particular, offers a variety of radiopharmaceuticals and techniques. Nowadays the gold standard radionuclide procedure, when an osteomyelitis is suspected, is represented by the use of radiolabelled leukocytes with either 99mTc-HMPAO or 111In-oxine. Methods: : In this review, we describe the correct acquisition and interpretation of white blood cell scintigraphy and we provide an overview of the existing literature data of the use of this technique in the infected diabetic foot. If images are correctly acquired, displayed and interpreted, this modality reaches very high diagnostic accuracy (>95%) in detecting osteomyelitis and it allows the differential diagnosis with a soft tissue infection or inflammation. Single-photon emission computed tomography/computed tomography (SPECT/CT) in addition to planar images is mandatory to determine the extent and exact location of the infective process in both fore foot and midhint foot. With the addition of bone marrow scintigraphy using radiolabelled nanocolloids, radiolabelled white blood cell scintigraphy is also able to differentiate between Charcot neuroarthropathy and osteomyelitis, which is a challenge in the evaluation of diabetic foot. Radiolabelled anti-granulocyte monoclonal antibodies and their fragments can also be used instead of white blood cells although there is a limited experience on their usefulness in diabetic foot infection.