Quantitative Analysis of Multimodal Skeletal SPECT/CT Reconstructions in Diagnosing Medication-related Osteonecrosis of the Jaw

Abstract

Aim Our goal was to assess visual and quantitative aspects of multimodal skeletal SPECT/CT reconstructions (recon) in differentiating necrotic and healthy bone of patients with suspected MRONJ.

Methods Prior to surgery, 20 patients with suspected MRONJ underwent SPECT/CT of the jaw 3–4 hours after injection of Tc-99m-DPD (622±112.4 MBq). SPECT/CT data were reconstructed using the multimodal xSPECT Bone and xSPECT Quant algorithms as well as the OSEM-algorithm FLASH 3D. For analysis, we divided the jaw into 12 separate regions. Both xSPECT Bone and FLASH 3D datasets were scored on a four-point scale (VIS xSPECT; VIS F3D), based on the intensity of localized tracer uptake. In F3D and xSPECT Quant datasets, local tracer uptake of each region was recorded as semi-quantitative uptake ratio (SQR F3D) or SUVs, respectively. ROC analysis was performed. Postoperative histologic results served as gold standard.

Results VIS F3D, VIS xSPECT and SQR F3D did not differ significantly in diagnostic accuracy (VIS xSPECT sensitivity=0.64; specificity=0.89). Of the quantitative parameters, SUVpeak yielded the best interobserver reproducibility. SUVpeak was 9.9±7.1 (95%CI: 7.84–11.95) in MRONJ regions, as opposed 3.6±1.8 (95% CI:3.36–3.88) elsewhere, with a cutpoint of 4.5 (sensitivity=0.83; specificity=0.80). Absolute quantitation significantly surpassed VIS and SQR (p<0.05) in accuracy and interobserver agreement (SUVpeak: κ=0.92; VIS xSPECT: κ=0.61; SQR F3D κ=0.66).

Conclusion Absolute quantitation proved significantly more accurate than visual and semi-quantitative assessment in diagnosing MRONJ, with higher interobserver agreement.

Zusammenfassung

Ziel Ziel unserer Studie war es, dass Potenzial der quantitativen Auswertung von multimodalen SPECT/CT-Rekonstruktionen (Recon) zum Nachweis von Kiefernekrosen bei Patienten mit vermuteter MRONJ zu untersuchen.

Methoden Präoperativ wurden 20 Patienten mit vermuteter MRONJ 3–4h nach Injektion von im Mittel 622±112,4MBq Tc-99m-DPD mittels SPECT/CT untersucht. Die Daten wurden sowohl mittels xSPECT Bone und xSPECT Quant als auch mittels des konventionellen OSEM-Algorithmus Flash3D (F3D) rekonstruiert. Zur Auswertung wurde der Kieferknochen in 12 Regionen unterteilt. Die xSPECT Bone und F3D Recon wurden hinsichtlich der Höhe des Uptakes mithilfe einer visuellen 4-Punkte-Skala (VIS xSPECT; VIS F3D) ausgewertet. Zusätzlich erfolgte eine VOI-basierte Bestimmung von semiquantitativen Ratios anhand der F3D Recon (SQR F3D) bzw. von SUVs anhand der xSPECT Quant Recon in den gleichen Regionen. Eine ROC-Analyse wurde durchgeführt. Das histologische Ergebnis diente als Goldstandard.

Ergebnisse VIS F3D, VIS xSPECT und SQR F3D zeigten keine signifikanten Unterschiede bei der Genauigkeit und Inter-Observer-Reliabilität (VIS F3D Sensitivität=0,62; Spezifität=0,88). Der SUV_peak lag in MRONJ-Regionen bei 9,9±7,1 (95%-KI 7,84–11,95) im Vergleich zu 3,6±1,8 (95%-KI 3,36–3,88) im übrigen Kiefer bei einem Cut-off-Wert von 4,5 (Sensitivität=0,83; Spezifität=0,80). Die Quantifizierung war dem VIS und dem SQR sowohl bei der Genauigkeit (p<0,05) als auch bei der Inter-Observer-Reliabilität (SUV_peak κ=0,92; VIS xSPECT κ=0,61; SQR F3D κ=0,66) überlegen.

Schlussfolgerung Die absolute Quantifizierung zeigt, bei höherer Inter-Observer-Reliabilität, im Vergleich zur visuellen und semiquantitativen Evaluation eine überlegene Genauigkeit beim Nachweis einer MRONJ.

Schlüsselwörter

MRONJ - Quantitative SPECT/CT - Multimodale SPECT-Rekonstruktion - Multimodale SPECT/CT

Keywords

MRONJ - Quantitative SPECT/CT - Multimodal SPECT reconstruction - Multimodale SPECT/CT

Publication History

Received: 10 December 2020

Accepted after revision: 07 June 2021

Article published online:
11 August 2021

• References

• 1 Marx RE, Sawatari Y, Fortin M. et al. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 2005; 63: 1567-1575 DOI: 10.1016/j.joms.2005.07.010. (PMID: 16243172)
• 2 Ruggiero SL, Mehrotra B, Rosenberg TJ. et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004; 62: 527-534
• 3 Pichardo SE, Kuijpers SC, van Merkesteyn JP. Bisphosphonate-related osteonecrosis of the jaws: Cohort study of surgical treatment results in seventy-four stage II/III patients. J Craniomaxillofac Surg 2016; 44: 1216-1220 DOI: 10.1016/j.jcms.2016.06.016. (PMID: 27421170)
• 4 Fleisch H, Russell RG, Francis MD. Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 1969; 165: 1262-1264 DOI: 10.1126/science.165.3899.1262. (PMID: 5803538)
• 5 Mucke T, Krestan CR, Mitchell DA. et al. Bisphosphonate and Medication-Related Osteonecrosis of the Jaw: A Review. Semin Musculoskelet Radiol 2016; 20: 305-314 DOI: 10.1055/s-0036-1592367. (PMID: 27741546)
• 6 Matsushita Y, Hayashida S, Morishita K. et al. Denosumab-associated osteonecrosis of the jaw affects osteoclast formation and differentiation: Pathological features of two cases. Mol Clin Oncol 2016; 4: 191-194 DOI: 10.3892/mco.2015.696. (PMID: 26893859)
• 7 Sivolella S, Lumachi F, Stellini E. et al. Denosumab and anti-angiogenetic drug-related osteonecrosis of the jaw: an uncommon but potentially severe disease. Anticancer Res 2013; 33: 1793-1797 (PMID: 23645723)
• 8 Hallmer F, Bjornland T, Nicklasson A. et al. Osteonecrosis of the jaw in patients treated with oral and intravenous bisphosphonates: experience in Sweden. Oral Surg Oral Med Oral Pathol Oral Radiol 2014; 118: 202-208 DOI: 10.1016/j.oooo.2014.05.006. (PMID: 25047929)
• 9 Qi WX, Tang LN, He AN. et al. Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials. Int J Clin Oncol 2014; 19: 403-410 DOI: 10.1007/s10147-013-0561-6. (PMID: 23605142)
• 10 Ruggiero S, Gralow J, Marx RE. et al. Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in patients with cancer. J Oncol Pract 2006; 2: 7-14 DOI: 10.1200/JOP.2006.2.1.7. (PMID: 20871729)
• 11 Rugani P, Acham S, Kirnbauer B. et al. Stage-related treatment concept of medication-related osteonecrosis of the jaw-a case series. Clin Oral Investig 2015; 19: 1329-1338 DOI: 10.1007/s00784-014-1384-1. (PMID: 25511385)
• 12 Treister NS, Friedland B, Woo SB. Use of cone-beam computerized tomography for evaluation of bisphosphonate-associated osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109: 753-764 DOI: 10.1016/j.tripleo.2009.12.005. (PMID: 20303301)
• 13 Stockmann P, Hinkmann FM, Lell MM. et al. Panoramic radiograph, computed tomography or magnetic resonance imaging. Which imaging technique should be preferred in bisphosphonate-associated osteonecrosis of the jaw? A prospective clinical study. Clin Oral Investig 2010; 14: 311-317 DOI: 10.1007/s00784-009-0293-1. (PMID: 19513765)
• 14 Nomayr A, Romer W, Strobel D. et al. Anatomical accuracy of hybrid SPECT/spiral CT in the lower spine. Nuclear medicine communications 2006; 27: 521-528 DOI: 10.1097/00006231-200606000-00008. (PMID: 16710107)
• 15 Romer W, Nomayr A, Uder M. et al. SPECT-guided CT for evaluating foci of increased bone metabolism classified as indeterminate on SPECT in cancer patients. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2006; 47: 1102-1106
• 16 Van den Wyngaert T, Huizing MT, Fossion E. et al. Prognostic value of bone scintigraphy in cancer patients with osteonecrosis of the jaw. Clinical nuclear medicine 2011; 36: 17-20 DOI: 10.1097/RLU.0b013e3181feeb72. (PMID: 21157201)
• 17 Assaf AT, Zrnc TA, Remus CC. et al. Intraindividual comparison of preoperative (99m)Tc-MDP SPECT/CT and intraoperative and histopathological findings in patients with bisphosphonate- or denosumab-related osteonecrosis of the jaw. J Craniomaxillofac Surg 2015; 43: 1461-1469 DOI: 10.1016/j.jcms.2015.06.025. (PMID: 26232916)
• 18 Beck M, Sanders JC, Ritt P. et al. Longitudinal analysis of bone metabolism using SPECT/CT and (99m)Tc-diphosphono-propanedicarboxylic acid: comparison of visual and quantitative analysis. EJNMMI research 2016; 6: 60 DOI: 10.1186/s13550-016-0217-4. (PMID: 27464623)
• 19 Vija H. Introduction to xSPECT Technology: Evolving Multi-modal SPECT to Become Context-based and Quantitative. Siemens Medical Solutions USA Inc Molecular Imaging.. 2013
• 20 Ruggiero SL, Dodson TB, Assael LA. et al. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaw – 2009 update. Aust Endod J 2009; 35: 119-130 DOI: 10.1111/j.1747-4477.2009.00213.x. (PMID: 19961450)
• 21 Youden WJ. Index for rating diagnostic tests. Cancer 1950; 3: 32-35 DOI: 10.1002/1097-0142(1950)3:1<32::aid-cncr2820030106>3.0.co;2-3. (PMID: 15405679)
• 22 Cohen J. A coefficient of agreement for nominal scales. Educational and Psychosocial Measurement 1960; 20: 37-46
• 23 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33: 159-174 (PMID: 843571)
• 24 Dore F, Filippi L, Biasotto M. et al. Bone scintigraphy and SPECT/CT of bisphosphonate-induced osteonecrosis of the jaw. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2009; 50: 30-35 DOI: 10.2967/jnumed.107.048785.
• 25 Lapa C, Linz C, Bluemel C. et al. Three-phase bone scintigraphy for imaging osteoradionecrosis of the jaw. Clinical nuclear medicine 2014; 39: 21-25 DOI: 10.1097/RLU.0000000000000296. (PMID: 24300350)
• 26 Bolouri C, Merwald M, Huellner MW. et al. Performance of orthopantomography, planar scintigraphy, CT alone and SPECT/CT in patients with suspected osteomyelitis of the jaw. European journal of nuclear medicine and molecular imaging 2013; 40: 411-417 DOI: 10.1007/s00259-012-2285-7. (PMID: 23151914)
• 27 Ogura I, Sasaki Y, Sue M. et al. Tc-99m hydroxymethylene diphosphonate scintigraphy, computed tomography, and magnetic resonance imaging of osteonecrosis in the mandible: Osteoradionecrosis versus medication-related osteonecrosis of the jaw. Imaging Sci Dent 2019; 49: 53-58 DOI: 10.5624/isd.2019.49.1.53. (PMID: 30941288)
• 28 Watanabe S, Nakajima K, Kinuya S. )Symposium: Imaging modalities for drug-related osteonecrosis of the jaw (5), utility of bone scintigraphy and (18)F-FDG PET/CT in early detection and risk assessment of medication-related osteonecrosis of the jaw (secondary publication. Jpn Dent Sci Rev 2019; 55: 76-79 DOI: 10.1016/j.jdsr.2018.12.002. (PMID: 30956739)
• 29 Ogura I, Kobayashi E, Nakahara K. et al. Quantitative SPECT/CT imaging for medication-related osteonecrosis of the jaw: a preliminary study using volume-based parameters, comparison with chronic osteomyelitis. Annals of nuclear medicine 2019; 33: 776-782 DOI: 10.1007/s12149-019-01390-5. (PMID: 31342316)
• 30 Suh MS, Lee WW, Kim YK. et al. Maximum Standardized Uptake Value of (99m)Tc Hydroxymethylene Diphosphonate SPECT/CT for the Evaluation of Temporomandibular Joint Disorder. Radiology 2016; 280: 890-896 DOI: 10.1148/radiol.2016152294. (PMID: 27035060)
• 31 Ritt P, Kuwert T. Quantitative SPECT/CT. Recent Results Cancer Res 2013; 187: 313-330 DOI: 10.1007/978-3-642-10853-2_10. (PMID: 32594399)
• 32 Duncan I, Ingold N. The clinical value of xSPECT/CT Bone versus SPECT/CT. A prospective comparison of 200 scans. Eur J Hybrid Imaging 2018; 2: 4 DOI: 10.1186/s41824-017-0024-9. (PMID: 29782595)
• 33 Delcroix O, Robin P, Gouillou M. et al. A new SPECT/CT reconstruction algorithm: reliability and accuracy in clinical routine for non-oncologic bone diseases. EJNMMI research 2018; 8: 14 DOI: 10.1186/s13550-018-0367-7. (PMID: 29435671)