Clinical significance of additional lateral imaging in diagnosis of prosthesis infection by combined Tc-99m labeled leukocyte/bone marrow scintigraphy

Document Type : Original Article


1 Nuclear Medicine Department, Faculty of Medicine, Mersin University, Mersin, Turkey

2 Physical Therapy and Rehabilitation Department, Fırat University, Elazığ, Turkey

3 Department of Orthopedics, Fırat University, Elazığ, Turkey

4 Department of Pathology, Fırat University, Elazığ, Turkey


Introduction: Recently the most accurate diagnostic method in the diagnosis of prosthesis infection is the combination of Tc-99m labeled leukocyte/bone marrow imaging. However the diagnostic efficiency of the test is influenced because of its low spatial resolution. Recently SPECT/CT imaging is implicated in this test with efficient additional diagnostic improvement. In the departments without capability of SPECT/CT lateral imaging may provide important clinical information. The aim of this study was to analyze the additional diagnostic information provided by additional lateral spot images to the diagnostic accuracy of combined Tc-99m labeled leukocyte/bone marrow imaging in diagnosis of prosthesis infection.
Methods: Retrospective evaluation of 11 patients (9 F, 2 M; 61±8,6 years old)  with pre-diagnosis of prosthesis infection (4 patients with right knee, 3 left, 2 bilateral, 2 right hip) by two experienced Nuclear Medicine physicians were included into the study. The age of the prosthesis were 7,8±15,3 months by the time of imaging. The imaging was performed from the region of interest at the first, second and fourth hour of injection of approximately 5 mCi (185 MBq) labeled leukocyte imaging and one hour after injection of 5 mCi (185 MBq) Tc-99m nanocolloid in anteroposterior and in additional lateral position. The diagnosis of prosthesis infection was decided in case of increased activity accumulation in leukocyte imaging higher than in bone marrow imaging. The final diagnosis was decided by additional aspiration biopsy (n=1), culture results (n=3), revision arthroplasty (n=1) or according to follow up results (n=6)(sedimentation, CRP) in 3,4±3,4 months follow up.
Results:The labeling efficiency of the patients was in an acceptable range (33-67%) in leukocyte labeling. The diagnosis of prosthesis infection was decided in two patients according to scintigraphy results and these two patients were documented to have prosthesis infection (revision arthroplasty and biopsy results).  One patient was decided to have prosthesis infection despite negativity of scintigraphy (false negative) due to persistently high sedimentation, CRP levels in follow up despite proper antibiotic treatment. One patient was diagnosed as negative due to demonstration of anterior cellulites rather than prosthesis infection in the lateral images. The diagnostic sensitivity, specificity, accuracy, negative and positive predictive value of the test were 60%, 87.5%, 81%, 60%, 87.5%, respectively for anteroposterior imaging only with additional lateral imaging the rates were increased to 60%, 100%, 91%, 89% and 89%, respectively.
Conclusion: Lateral imaging increases the diagnostic accuracy of the combined Tc-99m labeled leukocyte/bone marrow scintigraphy compared to anteroposterior imaging only and might be implemented in combined imaging protocol in case of non-availability of SPECT/CT imaging.


Main Subjects

  1. Lewis SS, Cox GM, Stout JE. Clinical utility of indium 111-labeled white blood cell scintigraphy for evaluation of suspected infection. Open Forum Infect Dis. 2014 Sep 17;1(2):ofu089. 
  2. Becker W, Meller J.The role of nuclear medicine in infection and inflammation. Lancet Infect Dis. 2001 Dec;1(5):326-33.
  3. Datz FL, Thorne DA. Effect of chronicity of infection on the sensitivity of the In-111-labeled leukocyte scan. AJR Am J Roentgenol. 1986 Oct;147(4):809-12.
  4. Granados U, Fuster D, Soriano A, García S, Bori G, Martínez JC, Mayoral M, Perlaza P, Tomás X, Pons F. Screening with angiographic images prior to (99m)Tc-HMPAO labelled leukocyte scintigraphy in the diagnosis of periprosthetic infection. Rev Esp Med Nucl Imagen Mol. 2015 Jul-Aug;34(4):219-24.
  5. Palestro CJ. Radionuclide imaging of osteomyelitis. Semin Nucl Med. 2015 Jan;45(1):32-46.
  6. Chacko TK, Zhuang H, Nakhoda KZ, Moussavian B, Alavi A. Applications of fluorodeoxyglucose positron emission tomography in the diagnosis of infection. Nucl Med Commun. 2003 Jun;24(6):615-24.
  7. Van Acker F, Nuyts J, Maes A, Vanquickenborne B, Stuyck J, Bellemans J, Vleugels S, Bormans G, Mortelmans L. FDG-PET, 99mtc-HMPAO white blood cell SPET and bone scintigraphy in the evaluation of painful total knee arthroplasties. Eur J Nucl Med. 2001 Oct;28(10):1496-504.
  8. Filippi L, Schillaci O. Usefulness of hybrid SPECT/CT in 99mTc-HMPAO-labeled leukocyte scintigraphy for bone and joint infections. J Nucl Med. 2006 Dec;47(12):1908-13.
  9. Zhuang H, Duarte PS, Pourdehnad M, Maes A, Van Acker F, Shnier D, Garino JP, Fitzgerald RH, Alavi A. The promising role of 18F-FDG PET in detecting infected lower limb prosthesis implants. J Nucl Med. 2001 Jan;42(1):44-8.
  10. García-Barrecheguren E, Rodríguez Fraile M, Toledo Santana G, Valentí Nín JR, Richter Echevarría JA. FDG-PET: a new diagnostic approach in hip prosthetic replacement. Rev Esp Med Nucl. 2007 Jul-Aug;26(4):208-20.
  11. Love C, Marwin SE, Tomas MB, Krauss ES, Tronco GG, Bhargava KK, Nichols KJ, Palestro CJ. Diagnosing infection in the failed joint replacement: a comparison of coincidence detection 18F-FDG and 111In-labeled leukocyte/99mTc-sulfur colloid marrow imaging. J Nucl Med. 2004 Nov;45(11):1864-71.
  12. Palestro CJ. Nuclear medicine and the failed joint replacement: Past, present, and future. World J Radiol. 2014 Jul 28;6(7):446-58.
  13. Palestro CJ, Love C, Miller TT. Infection and musculoskeletal conditions: Imaging of musculoskeletal infections. Best Pract Res Clin Rheumatol. 2006 Dec;20(6):1197-218.
  14. Tomas X, Bori G, Garcia S, Garcia-Diez AI, Pomes J, Soriano A, Ríos J, Almela M, Mensa J, Gallart X, Martinez JC, Riba J. Accuracy of CT-guided joint aspiration in patients with suspected infection status post-total hip arthroplasty. Skeletal Radiol. 2011 Jan;40(1):57-64.
  15. McInerney DP, Hyde ID. Technetium 99Tcm pyrophosphate scanning in the assessment of the painful hip prosthesis. Clin Radiol. 1978 Sep;29(5):513-7.
  16. Williams F, McCall IW, Park WM, O'Connor BT, Morris V. Gallium-67 scanning in the painful total hip replacement. Clin Radiol. 1981 Jul;32(4):431-9.
  17. Hofmann AA, Wyatt RW, Daniels AU, Armstrong L, Alazraki N, Taylor A Jr. Bone scans after total knee arthroplasty in asymptomatic patients. Cemented versus cementless. Clin Orthop Relat Res. 1990 Feb;(251):183-8.
  18. Palestro CJ, Swyer AJ, Kim CK, Goldsmith SJ. Infected knee prosthesis: diagnosis with In-111 leukocyte, Tc-99m sulfur colloid, and Tc-99m MDP imaging. Radiology. 1991 Jun;179(3):645-8.
  19. Basu S, Kwee TC, Saboury B, Garino JP, Nelson CL, Zhuang H, Parsons M, Chen W, Kumar R, Salavati A, Werner TJ, Alavi A. FDG PET for diagnosing infection in hip and knee prostheses: prospective study in 221 prostheses and subgroup comparison with combined (111)In-labeled leukocyte/(99m)Tc-sulfur colloid bone marrow imaging in 88 prostheses. Clin Nucl Med. 2014 Jul;39(7):609-15.
  20. Love C, Marwin SE, Tomas MB, Krauss ES, Tronco GG, Bhargava KK, Nichols KJ, Palestro CJ. Diagnosing infection in the failed joint replacement: a comparison of coincidence detection 18F-FDG and 111In-labeled leukocyte/99mTc-sulfur colloid marrow imaging. J Nucl Med. 2004 Nov;45(11):1864-71.
  21. Stumpe KD, Nötzli HP, Zanetti M, Kamel EM, Hany TF, Görres GW, von Schulthess GK, Hodler J. FDG PET for differentiation of infection and aseptic loosening in total hip replacements: comparison with conventional radiography and three-phase bone scintigraphy. Radiology. 2004 May;231(2):333-41.
  22. van der Bruggen W, Bleeker-Rovers CP, Boerman OC, Gotthardt M, Oyen WJ. PET and SPECT in osteomyelitis and prosthetic bone and joint infections: a systematic review. Semin Nucl Med. 2010 Jan;40(1):3-15.
  23. Kim HO, Na SJ, Oh SJ, Jung BS, Lee SH, Chang JS, Bin SI, Ryu JS. Usefulness of adding SPECT/CT to 99mTc-hexamethylpropylene amine oxime (HMPAO)-labeled leukocyte imaging for diagnosing prosthetic joint infections. J Comput Assist Tomogr. 2014 Mar-Apr;38(2):313-9.
  24. Filippi L, Schillaci O. Usefulness of hybrid SPECT/CT in 99mTc-HMPAO-labeled leukocyte scintigraphy for bone and joint infections. J Nucl Med. 2006 Dec;47(12):1908-13.
  25.  Bar-Shalom R, Yefremov N, Guralnik L, Keidar Z, Engel A, Nitecki S, Israel O. SPECT/CT using 67Ga and 111In-labeled leukocyte scintigraphy for diagnosis of infection. J Nucl Med. 2006 Apr;47(4):587-94.
  26. Graute V, Feist M, Lehner S, Haug A, Müller PE, Bartenstein P, Hacker M. Detection of low-grade prosthetic joint infections using 99mTc-antigranulocyte SPECT/CT: initial clinical results. Eur J Nucl Med Mol Imaging. 2010 Aug;37(9):1751-9. 
  27. Fink B. Revision of late periprosthetic infections of total hip endoprostheses: pros and cons of different concepts. Int J Med Sci. 2009 Sep 4;6(5):287-95.
  28. Erba PA, Glaudemans AW, Veltman NC, Sollini M, Pacilio M, Galli F, Dierckx RA, Signore A. Image acquisition and interpretation criteria for 99mTc-HMPAO-labelled white blood cell scintigraphy: results of a multicentre study. Eur J Nucl Med Mol Imaging. 2014 Apr;41(4):615-23.
  29. Pelosi E, Baiocco C, Pennone M, Migliaretti G, Varetto T, Maiello A, Bellò M, Bisi G. 99mTc-HMPAO-leukocyte scintigraphy in patients with symptomatic total hip or knee arthroplasty: improved diagnostic accuracy by means of semiquantitative evaluation. J Nucl Med. 2004 Mar;45(3):438-44.
  30. Van Dyke D, Price D, Shkurkin C, Yano Y, Anger HO. Differences in distribution of erythropoietic and reticuloendothelial marrow in hematologic disease. Blood. 1967 Sep;30(3):364-74.
  31. Kanegaye JT, Vance CW, Parisi M, Miller JH, Mahour GH, Chan LS, Schonfeld N. Failure of technetium-99m hexamethylpropylene amine oxime leukocyte scintigraphy in the evaluation of children with suspected appendicitis. Pediatr Emerg Care. 1995 Oct;11(5):285-90.
  32. Ostovar A, Assadi M, Vahdat K, Nabipour I, Javadi H, Eftekhari M, Assadi M. A pooled analysis of diagnostic value of (99m)Tc-ubiquicidin (UBI) scintigraphy in detection of an infectious process. Clin Nucl Med. 2013 Jun;38(6):413-6.