Bloodpool SPECT as part of bone SPECT/CT in painful total knee arthroplasty (TKA): validation and potential biomarker of prosthesis biomechanics

  • Jolien Verschueren
  • Adrien Albert
  • Laurens Carp
  • Sarah Ceyssens
  • Ivan Huyghe
  • Sigrid Stroobants
  • Frédéric Paycha
  • Gopinath Gnanasegaran
  • Tim Van den WyngaertEmail author
Original Article



To compare bloodpool SPECT with planar imaging in bone SPECT/CT of painful total knee arthroplasty (TKA) with respect to inter-rater agreement, confidence, prosthesis outcome, and biomechanical functioning.


Retrospective study of bloodpool SPECT and planar control images. Four raters used the validated Bruderholz scheme and a 5-point scale to grade uptake. Inter-rater agreement and overall confidence scores were calculated. Variable cluster analysis was performed to identify patterns of uptake, and associations between patterns and prosthesis outcome and biomechanical functioning were examined.


In all, 55 knees in 43 patients were analyzed (median follow-up 17 months; revision rate 21.8%). SPECT significantly improved inter-rater agreement in 24% of regions (all P < 0.05) and overall confidence by 20% (P < 0.001). Regional uptake cluster analysis showed improved antero-posterior separation with SPECT, and distinct patterns associated with prosthesis survival in lateral femoral (P = 0.041) and medial tibial (P < 0.001) regions. The prognostic value of SPECT outperformed planar imaging for tibial (P < 0.001), patellar (P = 0.009), and synovial (P = 0.040) assessment. Internal femoral malrotation resulted in increased uptake in posteromedial (P = 0.042) and anterolateral (P = 0.016) femoral, and lateral patellar (P = 0.011) regions. Internal tibial malrotation increased uptake in posterolateral (P = 0.026) and posteromedial tibial (P = 0.005), and medial patellar regions (P = 0.004). Bloodpool SPECT improved the prognostic value of late-phase SPECT/CT for the assessment of the medial tibial region.


Bloodpool SPECT outperforms planar assessment of painful TKAs and the identification of distinct uptake patterns make it a potentially clinically relevant biomarker of prosthesis survival and biomechanical functioning.


SPECT/CT SPECT Bloodpool Bone scintigraphy Total knee arthroplasty 



This study was funded by the Department of Nuclear Medicine of the Antwerp University Hospital.

Compliance with ethical standards

Ethical approval

All procedures were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Conflict of interest

The authors report no conflict of interests.


  1. 1.
    Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007;89(4):780–5.Google Scholar
  2. 2.
    Dalury DF, Pomeroy DL, Gorab RS, Adams MJ. Why are total knee arthroplasties being revised? J Arthroplast. 2013;28(8 Suppl):120–1.CrossRefGoogle Scholar
  3. 3.
    Seil R, Pape D. Causes of failure and etiology of painful primary total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2011;19(9):1418–32.CrossRefGoogle Scholar
  4. 4.
    Lim HA, Song EK, Seon JK, et al. Causes of aseptic persistent pain after total knee arthroplasty. Clin Orthop Surg. 2017;9(1):50–6.CrossRefGoogle Scholar
  5. 5.
    Hirschmann MT, Konala P, Iranpour F, Kerner A, Rasch H, Friederich NF. Clinical value of SPECT/CT for evaluation of patients with painful knees after total knee arthroplasty—a new dimension of diagnostics? BMC Musculoskelet Disord. 2011;12:36.CrossRefGoogle Scholar
  6. 6.
    Mandalia V, Eyres K, Schranz P, et al. Evaluation of patients with a painful total knee replacement. J Bone Joint Surg Br. 2008;90(3):265–71.CrossRefGoogle Scholar
  7. 7.
    Park CN, White PB, Meftah M, Ranawat AS, Ranawat CS. Diagnostic algorithm for residual pain after total knee arthroplasty. Orthopedics. 2016;39:e246–52.CrossRefGoogle Scholar
  8. 8.
    Fogelman I, Gnanasegaran G, Van der Wall H. Radionuclide and hybrid bone imaging. Berlin and Heidelberg: Springer; 2013.Google Scholar
  9. 9.
    Hirschmann MT, Amsler F, Rasch H. Clinical value of SPECT/CT in the painful total knee arthroplasty (TKA): a prospective study in a consecutive series of 100 TKA. Eur J Nucl Med Mol Imaging. 2015;42(12):1869–82.CrossRefGoogle Scholar
  10. 10.
    Awengen R, Rasch H, Amsler F, Hirschmann MT. Symptomatic versus asymptomatic knees after bilateral total knee arthroplasty: what is the difference in SPECT/CT? Eur J Nucl Med Mol Imaging. 2016;43(4):762–72.CrossRefGoogle Scholar
  11. 11.
    van der Bruggen W, Hirschmann MT, Strobel K, Kapen WU, Kuwert T, Gnanasegaran G, et al. SPECT/CT in the postoperative painful knee. Semin Nucl Med. 2018;48(5):439–53.CrossRefGoogle Scholar
  12. 12.
    Hirschmann MT, Iranpour F, Konala P, Kerner A, Rasch H, Cobb JP, et al. A novel standardized algorithm for evaluating patients with painful total knee arthroplasty using combined single photon emission tomography and conventional computerized tomography. Knee Surg Sports Traumatol Arthrosc. 2010;18(7):939–44.CrossRefGoogle Scholar
  13. 13.
    Van den Wyngaert T, Palli SR, Imhoff RJ, Hirschmann MT. Cost-effectiveness of bone SPECT/CT in painful total knee arthroplasty. J Nucl Med. 2018;59(11):1742–50.CrossRefGoogle Scholar
  14. 14.
    Van den Wyngaert T, Strobel K, Kampen WU, Kuwert T, van der Bruggen W, Mohan HK, et al. The EANM practice guidelines for bone scintigraphy. Eur J Nucl Med Mol Imaging. 2016;43(9):1723–38.CrossRefGoogle Scholar
  15. 15.
    Pietsch M, Djahani O, Hofmann S. There is an optimal rotational alignment in total knee replacement: femoral rotation does matter. In: Hirschmann MT, Becker R, editors. The unhappy total knee replacement: a comprehensive review and management guide. Switzerland: Springer; 2015. p. 29–38.CrossRefGoogle Scholar
  16. 16.
    Pujol N, Berhouet J, Boisrenoult P, Beaufils P. There is an optimal rotational alignment in total knee replacement: tibial rotation does matter. In: Hirschmann MT, Becker R, editors. The unhappy total knee replacement: a comprehensive review and management guide. Switzerland: Springer; 2015. p. 39–45.CrossRefGoogle Scholar
  17. 17.
    Gwet KL. Computing inter-rater reliability and its variance in the presence of high agreement. Br J Math Stat Psychol. 2008;61(Pt 1):29–48.CrossRefGoogle Scholar
  18. 18.
    Gwet KL. Testing the difference of correlated agreement coefficients for statistical significance. Educ Psychol Meas. 2016;76(4):609–37.CrossRefGoogle Scholar
  19. 19.
    Rabe-Hesketh S, Skrondal A. Multilevel and longitudinal modeling using Stata. 3rd ed. College Station, TX: Stata Press; 2012.Google Scholar
  20. 20.
    Anderberg M. Cluster analysis for applications. New York: Academic Press; 1973.Google Scholar
  21. 21.
    Huellner MW, Strobel K. Clinical applications of SPECT/CT in imaging the extremities. Eur J Nucl Med Mol Imaging. 2014;41(Suppl 1):S50–8.CrossRefGoogle Scholar
  22. 22.
    Mohan HK, Strobel K, van der Bruggen W, Gnanasegaran G, Kampen WU, Kuwert T, et al. The role of hybrid bone SPECT/CT imaging in the work-up of the limping patient: a symptom-based and joint-oriented review. Eur J Hybrid Imaging. 2018;2(1):8.CrossRefGoogle Scholar
  23. 23.
    Lu SJ, Ul Hassan F, Vijayanathan S, Gnanasegaran G. Radionuclide bone SPECT/CT in the evaluation of knee pain: comparing two-phase bone scintigraphy, SPECT and SPECT/CT. Br J Radiol. 2018;91(1090):20180168.Google Scholar
  24. 24.
    Mandegaran R, Agrawal K, Vijayanathan S, Gnanasegaran G. The value of 99mTc-MDP bone SPECT/CT in evaluation of patients with painful knee prosthesis. Nucl Med Commun. 2018;39(5):397–404.CrossRefGoogle Scholar
  25. 25.
    Dordevic M, Hirschmann MT, Rechsteiner J, Falkowski A, Testa E, Hirschmann A. Do chondral lesions of the knee correlate with bone tracer uptake by using SPECT/CT? Radiology. 2016;278(1):223–31.CrossRefGoogle Scholar
  26. 26.
    Hirschmann A, Hirschmann MT. Chronic knee pain: clinical value of MRI versus SPECT/CT. Semin Musculoskelet Radiol. 2016;20(1):3–11.CrossRefGoogle Scholar
  27. 27.
    Hirschmann MT, Schon S, Afifi FK, Amsler F, Rasch H, Friederich NF, et al. Assessment of loading history of compartments in the knee using bone SPECT/CT: a study combining alignment and 99mTc-HDP tracer uptake/distribution patterns. J Orthop Res. 2013;31(2):268–74.CrossRefGoogle Scholar
  28. 28.
    Aydogan F, Akbay E, Cevik C, Kalender E. Blood-pool SPECT in addition to bone SPECT in the viability assessment in mandibular reconstruction. Eur Rev Med Pharmacol Sci. 2014;18(4):587–92.Google Scholar
  29. 29.
    Donell S. Patellar maltracking in primary total knee arthroplasty. Effort Open Rev. 2018;3:106–13.CrossRefGoogle Scholar
  30. 30.
    Berger RA, Crossett LS, Jacobs JJ, Rubash HE. Malrotation causing patellofemoral complications after total knee arthroplasty. Clin Orthop Relat Res. 1998;356:144–53.CrossRefGoogle Scholar
  31. 31.
    Kuriyama S, Ishikawa M, Furu M, Ito H, Matsuda S. Malrotated tibial component increases medial collateral ligament tension in total knee arthroplasty. J Orthop Res. 2014;32(12):1658–66.CrossRefGoogle Scholar
  32. 32.
    Lee TQ, Morris G, Csintalan RP. The influence of tibial and femoral rotation on patellofemoral contact area and pressure. J Orthop Sports Phys Ther. 2003;33(11):686–93.CrossRefGoogle Scholar
  33. 33.
    Slevin O, Schmid FA, Schiapparelli FF, Rasch H, Amsler F, Hirschmann MT. Increased in vivo patellofemoral loading after total knee arthroplasty in resurfaced patellae. Knee Surg Sports Traumatol Arthrosc. 2018;26(6):1805–10.CrossRefGoogle Scholar
  34. 34.
    Stumpe KD, Romero J, Ziegler O, Kamel EM, von Schulthess GK, Strobel K, et al. The value of FDG-PET in patients with painful total knee arthroplasty. Eur J Nucl Med Mol Imaging. 2006;33(10):1218–25.CrossRefGoogle Scholar
  35. 35.
    Saltybaeva N, Jafari ME, Hupfer M, Kalender WA. Estimates of effective dose for CT scans of the lower extremities. Radiology. 2014;273(1):153–9.CrossRefGoogle Scholar
  36. 36.
    Kricun ME. Red–yellow marrow conversion: its effect on the location of some solitary bone lesions. Skelet Radiol. 1985;14(1):10–9.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jolien Verschueren
    • 1
  • Adrien Albert
    • 2
  • Laurens Carp
    • 2
    • 3
  • Sarah Ceyssens
    • 2
    • 3
  • Ivan Huyghe
    • 2
    • 3
  • Sigrid Stroobants
    • 2
    • 3
  • Frédéric Paycha
    • 4
  • Gopinath Gnanasegaran
    • 5
  • Tim Van den Wyngaert
    • 2
    • 3
    Email author
  1. 1.Department of Nuclear Medicine and Molecular ImagingUniversity Hospital LeuvenLeuvenBelgium
  2. 2.Department of Nuclear MedicineAntwerp University HospitalEdegemBelgium
  3. 3.Faculty of Medicine and Health SciencesUniversity of AntwerpWilrijkBelgium
  4. 4.Department of Nuclear Medicine, Hôpital LariboisièreAssistance Publique-Hôpitaux de ParisParisFrance
  5. 5.Department of Nuclear MedicineRoyal Free London NHS Foundation TrustLondonUK

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