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Nuclear Medicine Imaging of Diabetic Foot Infections

  • Chiara Lauri
  • Luigi Uccioli
  • Alberto Signore
Chapter

Abstract

Diabetic foot infections represent a severe complication of long-standing diabetes. If not adequately recognized, the infection could spread from a foot ulcer to the bone, thus causing osteomyelitis (OM) that exposes the patients to the risk of amputation, bacteraemia/septicaemia and death. One of the most difficult aspects in the evaluation of a diabetic foot is to differentiate between OM, soft tissue infection (STI) and Charcot foot because these three conditions require very different therapeutic approaches. Despite the correct diagnosis could be achieved with the isolation of the pathogen from bone or soft tissues, it would be desirable to have non-invasive test able to diagnose and localize an infection with high accuracy. In this chapter, we examine the pros and cons of NM modalities in the approach at diabetic foot disorders.

Keywords

Diabetes Foot 99mTc-HMPAO-WBC SPECT/CT FDG PET/TC 

References

  1. 1.
    Ramsey SD, Newton K, Blough D, McCulloch DK, Sandhu N, Reiber GE, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care. 1999;22:382–7.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Reiberg GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg. 1998;176:5S–10S.CrossRefGoogle Scholar
  3. 3.
    Lavery LA, Armstrong DG, Wunderlich RP, Mohler MJ, Wendel CS, Lipsky BA. Risk factors for foot infections in individuals with diabetes. Diabetes Care. 2006;29(6):1288–93.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Prompers L, Huijberts M, Apelqvist J, Jude E, Piaggesi A, Bakker K, Edmonds M, Holstein P, Jirkovska A, Mauricio D, Ragnarson Tennvall G, Reike H, Spraul M, Uccioli L, Urbancic V, Van Acker K, van Baal J, van Merode F, Schaper N. High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study. Diabetologia. 2007;50(1):18–25. Epub 2006 Nov 9.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Lipsky BA. Osteomyelitis of the foot in diabetic patients. Clin Infect Dis. 1997;25(6):1318–26.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Lipsky BA, Aragón-Sánchez J, Diggle M, Embil J, Kono S, Lavery L, Senneville É, Urbančič-Rovan V, Van Asten S, International Working Group on the Diabetic Foot (IWGDF). IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes. Diabetes Metab Res Rev. 2016;32(Suppl 1):45–74.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Gierbolini R. Charcot’s foot: often overlooked complication of diabetes. J Am Acad Phys Assist. 1994;12:62–8.Google Scholar
  8. 8.
    García Morales E, Lázaro-Martínez JL, Aragón-Sánchez FJ, Cecilia-Matilla A, Beneit-Montesinos JV, González Jurado MA. Inter-observer reproducibility of probing to bone in the diagnosis of diabetic foot osteomyelitis. Diabet Med. 2011;28(10):1238–40.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Grayson ML, Gibbons GW, Balogh K, Levin E, Karchmer AW. Probing to bone in infected pedal ulcers: a clinical sign of underlying osteomyelitis in diabetic patients. JAMA. 1995;273(9):721–3.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Lavery LA, Armstrong DG, Peters EJ, Lipsky BA. Probe-to-bone test for diagnosing diabetic foot osteomyelitis: reliable or relic? Diabetes Care. 2007;30(2):270–4.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Palestro CJ, Love C. Nuclear medicine and diabetic foot infections. Semin Nucl Med. 2009;39(1):52–65.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Lauri C, AWJM G, Signore A. Leukocyte imaging of the diabetic foot. Curr Pharm Des. 2018;24(12):1270–6.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Israel O, Sconfienza LM, Lipsky BA. Diagnosing diabetic foot infection: the role of imaging and a proposed flow chart for assessment. Q J Nucl Med Mol Imaging. 2014;58(1):33–45. Epub 2013 Nov 14.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS, Senneville E, Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012;54(12):e132–73.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Palestro CJ, Caprioli R, Love C, Richardson HL, Kipper SL, Weiland FL, Tomas MB. Rapid diagnosis of pedal osteomyelitis in diabetics with a technetium-99m-labeled monoclonal antigranulocyte antibody. J Foot Ankle Surg. 2003;42(1):2–8.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Delcourt A, Huglo D, Prangere T, Benticha H, Devemy F, Tsirtsikoulou D, Lepeut M, Fontaine P, Steinling M. Comparison between Leukoscan (Sulesomab) and Gallium-67 for the diagnosis of osteomyelitis in the diabetic foot. Diabetes Metab. 2005;31(2):125–33.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Harwood SJ, Valdivia S, Hung GL, Quenzer RW. Use of Sulesomab, a radiolabeled antibody fragment, to detect osteomyelitis in diabetic patients with foot ulcers by leukoscintigraphy. Clin Infect Dis. 1999;28(6):1200–5.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Dinh MT, Abad CL, Safdar N. Diagnostic accuracy of the physical examination and imaging tests for osteomyelitis underlying diabetic foot ulcers: meta-analysis. Clin Infect Dis. 2008;47:519–27.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Capriotti G, Chianelli M, Signore A. Nuclear medicine imaging of diabetic foot infection: results of meta-analysis. Nucl Med Commun. 2006;27:757–64.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Teh J, Berendt T, Lipsky BA. Rational imaging. Investigating suspected bone infection in the diabetic foot. BMJ. 2009;339:b4690.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Signore A, Lauri C, Galli F. Radiolabelled probes targeting infection and inflammation for personalized medicine. Curr Pharm Des. 2014;20(14):2338–45.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Roca M, de Vries EF, Jamar F, Israel O, Signore A. Guidelines for the labelling of leucocytes with 111In-oxine. Inflammation/infection taskgroup of the European association of nuclear medicine. Eur J Nucl Med Mol Imaging. 2010;37:835–41.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Signore A, Jamar F, Israel O, Buscombe J, Martin-Comin J, Lazzeri E. Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline. Eur J Nucl Med Mol Imaging. 2018;45(10):1816–31.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Jamar F, Buscombe J, Chiti A, Christian PE, Delbeke D, Donohoe KJ, Israel O, Martin-Comin J, Signore A. EANM/SNMMI guideline for 18F-FDG use in inflammation and infection. J Nucl Med. 2013;54(4):647–58.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Glaudemans AWJM, Jutte PC, Cataldo MA, Cassar-Pullicino V, Gheysens O, Borens O, Trampuz A, Wörtler K, Petrosillo N, Winkler H, Signore A, Sconfienza LM. Consensus document for the diagnosis of peripheral bone infection in adults: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement). Eur J Nucl Med Mol Imaging. 2019;46(4):957–70.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Signore A, Sconfienza LM, Borens O, Glaudemans AWJM, Cassar-Pullicino V, Trampuz A, Winkler H, Gheysens O, Vanhoenacker FMHM, Petrosillo N, Jutte PC. Consensus document for the diagnosis of prosthetic joint infections: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement). Eur J Nucl Med Mol Imaging. 2019;46(4):971–88.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Lauri C, Tamminga M, Glaudemans AWJM, Juárez Orozco LE, Erba PA, Jutte PC, Lipsky BA, IJzerman MJ, Signore A, Slart RHJA. Detection of osteomyelitis in the diabetic foot by imaging techniques: a systematic review and meta-analysis comparing MRI, white blood cell scintigraphy, and FDG-PET. Diabetes Care. 2017;40(8):1111–20.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Maurer AH, Millmond SH, Knight LC, et al. Infection in diabetic osteoarthropathy: use of indium-labeled leukocytes for diagnosis. Radiology. 1986;161(1):221–5.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Keenan AM, Tindel NL, Alavi A. Diagnosis of pedal osteomyelitis in diabetic patients using current scintigraphic techniques. Arch Intern Med. 1989;149(10):2262–6.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Johnson JE, Kennedy EJ, Shereff MJ, Patel NC, Collier BD. Prospective study of bone, indium-111-labeled white blood cell, and gallium-67 scanning for the evaluation of osteomyelitis in the diabetic foot. Foot Ankle Int. 1996;17(1):10–6.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Newman LG, Waller J, Palestro CJ, et al. Leukocyte scanning with 111In is superior to magnetic resonance imaging in diagnosis of clinically unsuspected osteomyelitis in diabetic foot ulcers. Diabetes Care. 1992;15(11):1527–30.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Unal SN, Birinci H, Baktiroğlu S, Cantez S. Comparison of Tc- 99m methylene diphosphonate, Tc-99m human immune globulin, and Tc-99m-labeled white blood cell scintigraphy in the diabetic foot. Clin Nucl Med. 2001;26(12):1016–21.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Erdman WA, Buethe J, Bhore R, et al. Indexing severity of diabetic foot infection with 99mTc-WBC SPECT/CT hybrid imaging. Diabetes Care. 2012;35(9):1826–31.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Przybylski MM, Holloway S, Vyce SD, Obando A. Diagnosing osteomyelitis in the diabetic foot: a pilot study to examine the sensitivity and specificity of Tc(99m) white blood cell-labelled single photon emission computed tomography/computed tomography. Int Wound J. 2016;13(3):382–9.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Blume PA, Dey HM, Daley LJ, Arrighi JA, Soufer R, Gorecki GA. Diagnosis of pedal osteomyelitis with Tc-99m HMPAO labeled leukocytes. J Foot Ankle Surg. 1997;36(2):120–6.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Van der Wall H, Lunz D, Stanton F, Bruce W. Prognostic value of 99m Tc leukocyte scintigraphy in diabetic pedal osteomyelitis. Foot Ankle Int. 2001;22(9):720–4.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Schauwecker DS, Park HM, Burt RW, Mock BH, Wellman HN. Combined bone scintigraphy and indium-111 leukocyte scans in neuropathic foot disease. J Nucl Med. 1988;29(10):1651–5.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Sanlı Y, Ozkan ZG, Unal SN, Türkmen C, Kılıçoğlu O. The additional value of Tc 99m HMPAO white blood cell SPECT in the evaluation of bone and soft tissue infections. Mol Imaging Radionucl Ther. 2011;20(1):7–13.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Devillers A, Moisan A, Hennion F, Garin E, Poirier JY, Bourguet P. Contribution of technetium-99m hexamethylpropylene amine oxime labelled leucocyte scintigraphy to the diagnosis of diabetic foot infection. Eur J Nucl Med. 1998;25(2):132–8.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Heiba SI, Kolker D, Mocherla B, et al. The optimized evaluation of diabetic foot infection by dual isotope SPECT/CT imaging protocol. J Foot Ankle Surg. 2010;49(6):529–36.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Heiba S, Kolker D, Ong L, et al. Dual-isotope SPECT/CT impact on hospitalized patients with suspected diabetic foot infection: saving limbs, lives, and resources. Nucl Med Commun. 2013;34(9):877–84.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Ertugrul MB, Baktiroglu S, Salman S, et al. The diagnosis of osteomyelitis of the foot in diabetes: microbiological examination vs. magnetic resonance imaging and labelled leucocyte scanning. Diabet Med. 2006;23(6):649–53.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Larcos G, Brown ML, Sutton RT. Diagnosis of osteomyelitis of the foot in diabetic patients: value of 111In-leukocyte scintigraphy. AJR Am J Roentgenol. 1991;157(3):527–31.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Glaudemans AW, de Vries EF, Vermeulen LE, Slart RH, Dierckx RA, Signore A. A large retrospective single-centre study to define the best image acquisition protocols and interpretation criteria for white blood cell scintigraphy with (99)mTc-HMPAO-labelled leucocytes in musculoskeletal infections. Eur J Nucl Med Mol Imaging. 2013;40:1760–9.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Erba PA, Glaudemans AW, Veltman NC, Sollini M, Pacilio M, Galli F, et al. Image acquisition and interpretation criteria for 99mTc-HMPAO-labelled white blood cell scintigraphy: results of a multicenter study. Eur J Nucl Med Mol Imaging. 2014;41:615–23.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Familiari D, Glaudemans AW, Vitale V, Prosperi D, Bagni O, Lenza A, Cavallini M, Scopinaro F, Signore A. Can sequential 18F-FDG PET/CT replace WBC imaging in the diabetic foot? J Nucl Med. 2011;52(7):1012–9.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Filippi L, Uccioli L, Giurato L, Schillaci O. Diabetic foot infection: usefulness of SPECT/CT for 99mTc-HMPAO-labeled leukocyte imaging. J Nucl Med. 2009;50:1042–6.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Palestro CJ, Mehta HH, Patel M, et al. Marrow versus infection in the Charcot joint: indium-111 leukocyte and technetium-99m sulphur colloid scintigraphy. J Nucl Med. 1998;39(2):346–50.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Palestro CJ, Roumanas P, Swyer AJ, Kim CK, Goldsmith SJ. Diagnosis of musculoskeletal infection using combined in-111 labeled leukocyte and Tc-99m SC marrow imaging. Clin Nucl Med. 1992;17(4):269–73.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Tomas MB, Patel M, Marwin SE, Palestro CJ. The diabetic foot. Br J Radiol. 2000;73(868):443–50.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Vouillarmet J, Morelec I, Thivolet C. Assessing diabetic foot osteomyelitis remission with white blood cell SPECT/CT imaging. Diabet Med. 2014;31(9):1093–9.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Lazaga F, Van Asten SA, Nichols A, et al. Hybrid imaging with 99mTc-WBC SPECT/CT to monitor the effect of therapy in diabetic foot osteomyelitis. Int Wound J. 2016;13(6):1158–60.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Dominguez-Gadea L, Martin-Curto LM, de la Calle H, Crespo A. Diabetic foot infections: scintigraphic evaluation with 99mTc labelled anti-granulocyte antibodies. Nucl Med Commun. 1993;14(3):212–8.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Palestro CJ, Caprioli R, Love C, et al. Rapid diagnosis of pedal osteomyelitis in diabetics with a technetium-99m-labeled monoclonal antigranulocyte antibody. J Foot Ankle Surg. 2003;42(1):2–8.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Delcourt A, Huglo D, Prangere T, et al. Comparison between Leukoscan (Sulesomab) and Gallium-67 for the diagnosis of osteomyelitis in the diabetic foot. Diabetes Metab. 2005;31(2):125–33.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Basu S, Chryssikos T, Moghadam-Kia S, Zhuang H, Torigian DA, Alavi A. Positron emission tomography as a diagnostic tool in infection: present role and future possibilities. Semin Nucl Med. 2009;39:36–51.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Treglia G, Sadeghi R, Annunziata S, Zakavi SR, Caldarella C, Muoio B, Bertagna F, Ceriani L, Giovanella L. Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography for the diagnosis of osteomyelitis related to diabetic foot: a systematic review and a meta-analysis. Foot (Edinb). 2013;23(4):140–8.CrossRefGoogle Scholar
  58. 58.
    Nawaz A, Torigian DA, Siegelman ES, Basu S, Chryssikos T, Alavi A. Diagnostic performance of FDG-PET, MRI, and plain film radiography (PFR) for the diagnosis of osteomyelitis in the diabetic foot. Mol Imaging Biol. 2010;12(3):335–42.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Kagna O, Srour S, Melamed E, Militianu D, Keidar Z. FDG PET/CT imaging in the diagnosis of osteomyelitis in the diabetic foot. Eur J Nucl Med Mol Imaging. 2012;39(10):1545–50.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Schwegler B, Stumpe KD, Weishaupt D, Strobel K, Spinas GA, von Schulthess GK, et al. Unsuspected osteomyelitis is frequent in persistent diabetic foot ulcer and better diagnosed by MRI than by 18F-FDG PET or 99mTc-MOAB. J Intern Med. 2008;263:99–106.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Keidar Z, Militianu D, Melamed E, Bar-Shalom R, Israel O. The diabetic foot: initial experience with 18F-FDG PET/CT. J Nucl Med. 2005;46(3):444–9. PubMed PMID: 15750157.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Basu S, Chryssikos T, Houseni M, Scot Malay D, Shah J, Zhuang H, Alavi A. Potential role of FDG PET in the setting of diabetic neuro-osteoarthropathy: can it differentiate uncomplicated Charcot's neuroarthropathy from osteomyelitis and soft-tissue infection? Nucl Med Commun. 2007;28(6):465–72.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Shagos GS, Shanmugasundaram P, Varma AK, Padma S, Sarma M. 18-F flourodeoxy glucose positron emission tomography-computed tomography imaging: a viable alternative to three phase bone scan in evaluating diabetic foot complications? Indian J Nucl Med. 2015;30(2):97–103.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Ruotolo V, Di Pietro B, Giurato L, et al. A new natural history of Charcot foot: clinical evolution and final outcome of stage 0 Charcot neuroarthropathy in a tertiary referral diabetic foot clinic. Clin Nucl Med. 2013;38(7):506–9.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Glaudemans AW, Uçkay I, Lipsky BA. Challenges in diagnosing infection in the diabetic foot. Diabet Med. 2015;32(6):748–59.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Yang H, Zhuang H, Rubello D, Alavi A. Mild-to-moderate hyperglycaemia will not decrease sensitivity of 18F-FDG PET imaging in the detection of pedal osteomyelitis in diabetic patients. Nucl Med Commun. 2016;37:259–62.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Glaudemans AW, Prandini N, DI Girolamo M, Argento G, Lauri C, Lazzeri E, Muto M, Sconfienza LM, Signore A. Hybrid imaging of musculoskeletal infections. Q J Nucl Med Mol Imaging. 2018;62(1):3–13.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Chiara Lauri
    • 1
  • Luigi Uccioli
    • 2
  • Alberto Signore
    • 1
  1. 1.Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine“Sapienza” University of RomeRomeItaly
  2. 2.Diabetic Foot Unit, Department Systems MedicineUniversity of Rome Tor VergataRomeItaly

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