title: A large retrospective single-centre study to define the best image acquisition protocols and interpretation criteria for white blood cell scintigraphy with ⁹⁹mTc-HMPAO-labelled leucocytes in musculoskeletal infections.
abstract: OBJECTIVE
  The diagnosis of infection is often based on clinical, pathological and microbiological results. However, these investigations lack specificity. White blood cell (WBC) scintigraphy is considered the gold standard nuclear imaging technique for diagnosing infections in bone and soft tissues (except spondylodiscitis). However, image acquisition and interpretation criteria differ amongst centres throughout the world, leading to differences in reported results. The aim of this study was to identify the most accurate WBC scintigraphy acquisition and interpretation protocols for diagnosis of bone and soft tissue infections.
  
  
  METHODS
  Included in this retrospective study were 297 patients with suspected bone or soft tissue infection who underwent WBC scintigraphy with (99m)Tc-HMPAO-labelled leucocytes between 2009 and 2012. Sensitivity, specificity, accuracy, and positive and negative predictive values of WBC scintigraphy were determined for two different dual time point acquisition protocols (fixed-time acquisition and time decay-corrected acquisition) and five image interpretation methods (visual and semiquantitative with four different reference regions of interest). Final diagnosis was based on pathological and microbiological reports, and when these were not available, on clinical follow-up of at least 6 months.
  
  
  RESULTS
  The best acquisition protocol was 4 h and 20 - 24 h dual time-point acquisition with time decay-corrected acquisition. When using this acquisition protocol, visual qualitative interpretation led to a sensitivity of 85.1 %, a specificity of 97.1 %, a diagnostic accuracy of 94.5 %, a positive predictive value of 88.8 % and a negative predictive value of 95.9 %. For semiquantitative analysis, the best results were found when lesion-to-reference ratios were calculated with the contralateral side as the reference tissue, except for osteomyelitis and infected osteosynthesis, for which the contralateral bone marrow was found to be the best reference tissue. Results of the semiquantitative analyses per se were not better than for visual analysis. In the optimal analysis protocol, scans are first visually evaluated, and if this gives equivocal results, semiquantitative analysis is performed. This strategy resulted in an improved sensitivity of 97.9 %, a specificity of 91.8 % and a diagnostic accuracy of 93.1 %.
  
  
  CONCLUSIONS
  WBC scintigraphy for bone and soft-tissue infection is best performed using a dual acquisition protocol at 4 h and at 20-24 h after injection, in which the acquisition time of the scans is corrected for decay. In most patients, visual analysis is sufficient and leads to high diagnostic accuracy. When interpretation by visual analysis is inconclusive, semiquantitative analysis adds accuracy. Based on our results, we propose a flow chart for analysing WBC scintigraphy in musculoskeletal infections.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700, Groningen, RB, The Netherlands, a.w.j.m.glaudemans@umcg.nl.
authors.forename: Andor W J M
authors.initials: AW
authors.lastname: Glaudemans
authors.forename: Erik F J
authors.initials: EF
authors.lastname: de Vries
authors.forename: Liliane E M
authors.initials: LE
authors.lastname: Vermeulen
authors.forename: Riemer H J A
authors.initials: RH
authors.lastname: Slart
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Alberto
authors.initials: A
authors.lastname: Signore
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001850:Bone Diseases, Infectious / Q000000981:diagnostic imaging*; D002648:Child; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007962:Leukocytes / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D019275:Radiopharmaceuticals; D012189:Retrospective Studies; D018461:Soft Tissue Infections / Q000000981:diagnostic imaging*; D019690:Technetium Tc 99m Exametazime; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime