What Does a Clinician Need from New Imaging Procedures?

  • Elena ZamagniEmail author


Bone disease is the most frequent feature of multiple myeloma (MM) and represents a marker of end-organ damage, used to establish the diagnosis and to dictate the immediate need of therapy. For this reason, imaging plays a significant role in the management of MM patients. Although conventional radiography has traditionally been the standard imaging modality, its low sensitivity in detecting osteolytic lesions and inability to evaluate response to therapy has called for the use of more sophisticated techniques, such as whole body low dose computed tomography (WBLDCT), whole body magnetic resonance imaging (WBMRI), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET/CT). In this chapter, the advantages, indications of use, and applications of the three different techniques in the management of patients with MM in different settings will be discussed. The European Myeloma Network (EMN) and the European Society for Medical Oncology (ESMO) guidelines have recommended whole body low-dose CT (WBLDCT) as the imaging modality of choice for the initial assessment of MM-related lytic bone lesions. MRI is the gold-standard imaging modality for detection of bone marrow involvement, while PET/CT provides valuable prognostic data and is to date the preferred technique in assessment of response to therapy. Standardization of most of the techniques is on-going.


Multiple myeloma Functional imaging techniques Minimal residual disease Staging Bone disease 


  1. 1.
    Terpos E, Berenson J, Raje N, Roodman GD. Management of bone disease in multiple myeloma. Expert Rev Hematol. 2014;7:113–25.CrossRefGoogle Scholar
  2. 2.
    Zamagni E, Cavo M. The role of imaging techniques in the management of multiple myeloma. Br J Haematol. 2012;159:499–513.PubMedGoogle Scholar
  3. 3.
    Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860–73.CrossRefGoogle Scholar
  4. 4.
    Siontis B, Kumar S, Dispenzieri A, et al. Positron emission tomography-computed tomography in the diagnostic evaluation of smoldering multiple myeloma: identification of patients needing therapy. Blood Cancer J. 2015;5:e364.CrossRefGoogle Scholar
  5. 5.
    Hillengass J, Moulopoulos LA, Delorme S, et al. Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the international myeloma working group. Blood Cancer J. 2017;7:e599.CrossRefGoogle Scholar
  6. 6.
    Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–48.CrossRefGoogle Scholar
  7. 7.
    Regelink JC, Minnema MC, Terpos E, et al. Comparison of modern and conventional imaging techniques in establishing multiple myeloma-related bone disease: a systematic review. Br J Haematol. 2013;162:50–61.CrossRefGoogle Scholar
  8. 8.
    Pianko MJ, Terpos E, Roodman GD, et al. Whole-body low-dose computed tomography and advanced imaging techniques for multiple myeloma bone disease. Clin Cancer Res. 2014;20:5888–97.CrossRefGoogle Scholar
  9. 9.
    Ippolito D, Besostri V, Bonaffini PA, et al. Diagnostic value of whole-body low-dose computed tomography (WBLDCT) in bone lesions detection in patients with multiple myeloma (MM). Eur J Radiol. 2013;82:2322–7.CrossRefGoogle Scholar
  10. 10.
    Hinge M, Andersen KT, Lund T, et al. Baseline bone involvement in multiple myeloma - a prospective comparison of conventional X-ray, low-dose computed tomography, and 18flourodeoxyglucose positron emission tomography in previously untreated patients. Haematologica. 2016;101(10):e415–8.CrossRefGoogle Scholar
  11. 11.
    Wolf MB, Murray F, Kilk K, et al. Sensitivity of whole-body CT and MRI versus projection radiography in the detection of osteolyses in patients with monoclonal plasma cell disease. Eur J Radiol. 2014;83(7):1222–30.CrossRefGoogle Scholar
  12. 12.
    Cretti F, Perugini G. Patient dose evaluation for the whole-body low-dose multidetector CT (WBLDMDCT) skeleton study in multiple myeloma. Radiol Med. 2016;121(2):93–105.CrossRefGoogle Scholar
  13. 13.
    Matsue K, Kobayashi H, Matsue Y. Prognostic significance of bone marrow abnormalities in the appendicular skeleton of patients with multiple myeloma. Blood Adv. 2018;2(9):1032–9.CrossRefGoogle Scholar
  14. 14.
    Zamagni E, Nanni C, Patriarca F, et al. A prospective comparison of 18F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance imaging and whole-body planar radiographs in the assessment of bone disease in newly diagnosed multiple myeloma. Haematologica. 2007;92:50–5.CrossRefGoogle Scholar
  15. 15.
    Zamagni E, Patriarca F, Nanni C, et al. Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood. 2011;118:5989–95.CrossRefGoogle Scholar
  16. 16.
    Bartel TB, Haessler J, Brown TL, et al. F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma. Blood. 2009;114:2068–76.CrossRefGoogle Scholar
  17. 17.
    Moreau P, Attal M, Caillot D, et al. Prospective evaluation of magnetic resonance imaging and [18F] Fluorodeoxyglucose positron emission tomography computed tomography at diagnosis and before maintenance therapy in symptomatic patients with multiple myeloma included in the IFM/DFCI 2009 trial: results of the IMAJEM study. J Clin Oncol. 2017;35:2911–8.CrossRefGoogle Scholar
  18. 18.
    Van Lammerem Venema D, Regelink JC, Ripaghen II, et al. 18F-fluoro-deoxyglucose positron emission tomography in assessment of myeloma-related bone disease: a systematic review. Cancer. 2012;118(8):1971–81.CrossRefGoogle Scholar
  19. 19.
    Lu YY, Chen JH, Lin WY, et al. FDG PET or PET/CT for detecting intramedullary and extramedullary lesions in multiple myeloma: a systematic review and meta-analysis. Clin Nucl Med. 2012;37(9):833–7.CrossRefGoogle Scholar
  20. 20.
    Cavo M, Terpos E, Nanni C, et al. Role of 18F-FDG positron emmission tomography/computed tomography in the diagnosis and management of multiple myeloma and other plasma cell dyscrasias: a consensus statement by the international myeloma working group. Lancet Oncol. 2017;18(4):e206–17.CrossRefGoogle Scholar
  21. 21.
    Dimopoulos MA, Hillengass J, Usmani S, et al. Role of magnetic resonance imaging in the management of patients with multiple myeloma: a consensus statement. J Clin Oncol. 2015;33:657–64.CrossRefGoogle Scholar
  22. 22.
    Koh DM, Collins DJ. Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol. 2007;188(6):1622–35.CrossRefGoogle Scholar
  23. 23.
    Walker R, Barlogie B, Haessler J, et al. Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol. 2007;25(9):1121–8.CrossRefGoogle Scholar
  24. 24.
    Baur-Melnyk A, Buhmann S, Becker C, et al. Whole-body MRI versus whole-body MDCT for staging of multiple myeloma. AJR Am J Roentgenol. 2008;190:1097–104.CrossRefGoogle Scholar
  25. 25.
    Ippolito D, Talei Franzesi C, Spiga S, et al. Diagnostic value of whole-body ultra-low dose computed tomography in comparison with spinal magnetic resonance imaging in the assessment of disease in multiple myeloma. Br J Haematol. 2017;177:395–403.CrossRefGoogle Scholar
  26. 26.
    Mai EK, Hielscher T, Kloth JK, et al. Association between magnetic resonance imaging patterns and baseline disease features in multiple myeloma: analyzing surrogates of tumour mass and biology. Eur Radiol. 2016;26(11):3939–48.CrossRefGoogle Scholar
  27. 27.
    Koutoulidis V, Fontara S, Terpos E, et al. Quantitative diffusion-weighted imaging of the bone marrow: an adjunct tool for the diagnosis of a diffuse MR imaging pattern in patients with multiple myeloma. Radiology. 2017;282(2):484–93.CrossRefGoogle Scholar
  28. 28.
    Terpos E, Kleber M, Engelhardt M, et al. European myeloma network guidelines for the management of multiple myeloma-related complications. Haematologica. 2015;100:1254–66.CrossRefGoogle Scholar
  29. 29.
    Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv52–61.CrossRefGoogle Scholar
  30. 30.
    Hillengass J, Fechtner K, Weber MA, et al. Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol. 2010;28:1606–10.CrossRefGoogle Scholar
  31. 31.
    Kastritis E, Moulopoulos LA, Terpos E, et al. The prognostic importance of the presence of more than one focal lesion in spine MRI of patients with asymptomatic (smoldering) multiple myeloma. Leukemia. 2014;28:2402–3.CrossRefGoogle Scholar
  32. 32.
    Merz M, Hielscher T, Wagner B, et al. Predictive value of longitudinal whole-body magnetic resonance imaging in patients with smoldering multiple myeloma. Leukemia. 2014;28(9):1902–8.CrossRefGoogle Scholar
  33. 33.
    Kyle R, Larson DR, Therneau TM, et al. Long-term follow-up of monoclonal Gammopathy of undetermined significance. N Engl J Med. 2018;378(3):241–9.CrossRefGoogle Scholar
  34. 34.
    Kastritis E, Terpos E, Moulopoulos L, et al. Extensive bone marrow infiltration and abnormal free light chain ratio identifies patients with asymptomatic myeloma at high risk for progression to symptomatic disease. Leukemia. 2013;27:947–53.CrossRefGoogle Scholar
  35. 35.
    Zamagni E, Nanni C, Gay F, et al. 18F-FDG PET/CT FOCAL, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease. Leukemia. 2015;30(2):417–22.CrossRefGoogle Scholar
  36. 36.
    Usmani SZ, Mitchell A, Waheed S, et al. Prognostic implications of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3. Blood. 2013;121(10):1819–23.CrossRefGoogle Scholar
  37. 37.
    Rasche L, Chavan SS, Stephens OW, et al. Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing. Nat Commun. 2017;8(1):268.CrossRefGoogle Scholar
  38. 38.
    Kumar S, Paiva B, Anderson KC, et al. International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328–46.CrossRefGoogle Scholar
  39. 39.
    Paiva B, Puig N, Cedena MT, et al. Impact of next generation flow minimal residual disease monitoring in multiple myeloma: results from the PETHEMA/GEM2012 trial. Blood. 2015;125(20):3059–68.CrossRefGoogle Scholar
  40. 40.
    Davies FE, Rosenthal A, Rasche L, et al. Treatment to suppression of focal lesions on positron emission tomography-computed tomography is a therapeutic goal in newly diagnosed multiple myeloma. Haematologica. 2018;103(6):1047–53.CrossRefGoogle Scholar
  41. 41.
    Caldarella C, Treglia G, Isgrò MA, et al. The role of fluorine-18-fluorodeoxyglucose positron emission tomography in evaluating the response to treatment in patients with multiple myeloma. Int J Mol Imaging. 2012;2012:175803.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Zamagni E, Nanni C, Mancuso K, et al. PET/CT improves the definition of complete response and allows to detect otherwise unidentifiable skeletal progression in multiple myeloma. Clin Cancer Res. 2015;21:4384–90.CrossRefGoogle Scholar
  43. 43.
    Rasche L, Angtuaco E, MCDonald JE, et al. Low expression of Hexokinase-2 is associated with false-negative FDG-positron emission tomography in multiple myeloma. Blood. 2017;130(1):30–4.CrossRefGoogle Scholar
  44. 44.
    Pandit-Taskar N. Functional imaging methods for assessment of minimal residual disease in multiple myeloma: current status and novel immunoPET based methods. Semin Hematol. 2018;55:22–32.CrossRefGoogle Scholar
  45. 45.
    Nanni C, Versari A, Chauvie S, et al. Interpretation criteria for FDG PET/CT in multiple myeloma (IMPeTUs): final results. IMPeTUs (Italian myeloma criteria for PET USe). Eur J Nucl Med Mol Imaging. 2018;45(5):712–9.CrossRefGoogle Scholar
  46. 46.
    Hillengass J, Ayyaz S, Kilk K, et al. Changes in magnetic resonance imaging before and after autologous stem cell transplantation correlate with response and survival in multiple myeloma. Haematologica. 2012;97(11):1757–60.CrossRefGoogle Scholar
  47. 47.
    Hillengass J, Merz M, Delorme S. Minimal residual disease in multiple myeloma: use of magnetic resonance imaging. Semin Hematol. 2018;55:19–21.CrossRefGoogle Scholar
  48. 48.
    Pawlyn C, Fowkes L, Otero S, et al. Frequency, distribution and clinical management of incidental findings and extramedullary plasmacytomas in whole body diffusion weighted magnetic resonance imaging in patients with multiple myeloma. Haematologica. 2016;101(4):e142–4.CrossRefGoogle Scholar
  49. 49.
    Bourillon C, Rahmouni A, Lin C, et al. Intravoxel incoherent motion diffusion-weighted imaging of multiple myeloma lesions: correlation with whole-body dynamic contrast agent-enhanced MR imaging. Radiology. 2015;277(3):773–83.CrossRefGoogle Scholar
  50. 50.
    Lacognata C, Crimì F, Guolo A, et al. Diffusion-weighted whole-body MRI for evaluation of early response in multiple myeloma. Clin Radiol. 2017;72:850–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.“Seràgnoli” Institute of Hematology, Bologna University School of MedicineBolognaItaly

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