Whole-Body Dynamic Contrast- Enhanced (DCE) MR Imaging in patients with myeloma

Transcription

1 Whole-Body Dynamic Contrast- Enhanced (DCE) MR Imaging in patients with myeloma Alain Rahmouni, Department of Medical Imaging, Mondor Academic Hospital : Centre Hospitalo-Universitaire Henri Mondor-Assistance Publique-Hôpitaux de Paris et Université Paris Est-Créteil,

2 Imaging MM? Diffuse and multifocal disease W-B Increased angiogenesis Impact on prognosis and response to treatment Rationale : Extract functional parameters on a W-B scale Prognostic impact?

3 Plan Whole-Body MR imaging Biological aspects DCE MR imaging DCE WB MR imaging PET imaging

4 MRI in Myeloma Standard MRI direct, high contrast visualization of bone marrow: best imaging technique (T1&FatsatT2) Durie/Salmon PLUS 2006 T1WI T2WI 61y female patient? Durie/Salmon 1975 Rahmouni et al. AJR 1993, Baur-Melnyk A et al. EJR 2005

5 Plan Whole-Body MR imaging Biological aspects DCE MR imaging DCE WB MR imaging PET imaging

6 Myeloma, biological aspects 1. Myeloma cells produce angiogenic cytokines (VEGF ) inducing bone marrow neovascularization Vacca A et al. Blood 1999; Parameters of angiogenesis on bone marrow biopsy : Microvessel density (MVD) and total vascular area Higher in MM patients than controls (p < 0.001) Higher in nonresponders than complete responders (p <0.001) Bhatti SS et al. Am J Hematol 2006;81: MVD density: independent prognostic factor

7 Angiogenesis in Myeloma Control Patient Microvessel density (MVD): anti-cd34 immunostain

8 Plan Whole-Body MR imaging Biological aspects DCE MR imaging DCE MR imaging PET imaging

9 Dynamic Contrast Enhanced DCE-MR Imaging Repeated imaging to track the entrance of diffusible paramagnetic contrast agents into tissue over time (reflecting angiogenesis) DCE parameters are related to flow, blood volume and capillary permeability

10 DCE-MR Imaging Infiltration grade /MVD/disease activity (serum markers) Low infiltration high infiltration Treatment response ** But only a single segment! 2D turboflash sequence single or 11 slices before after Norsas-Garcia S et al. J Magn Reson Imaging Rahmouni A et al. Radiology 2003.

11 Lecouvet FE et al. Br J Haematol 1999; 106:35-39.

12 Plan Whole-Body MR imaging Biological aspects DCE MR imaging DCE WB MR imaging PET imaging

13 Protocol design Cover most of the bone marrow space Where? Which planes to take? How many stations in total? WB temporal resolution (per repetition)? Factor of acceleration-parallel imaging? Resolution, number of slices Sequence, 2D vs. 3D? How long the duration? When to inject?

14 DCE WB MR Imaging Cover most of the bone marrow space Where? Which planes? How many stations in total? WB temporal resolution (per repetition)? Factor of acceleration-parallel imaging? Resolution, number of slices Sequence, 2D vs. 3D? How long the duration? When to inject?

15 DCE WB MR Imaging

16 WB 5-stations DCE-MRI

17 DCE WB MR Imaging

18 WB DCE-MRI sequences Goal < 1min 3D GRE fat sat VIBE with high spatial and temporal resolution GRAPPA parallel acquisition with acceleration factor 2 TR/TE 3/1.3 ms, angle de bascule de 20 to get heavy T1-weighted images 256 x 192 matrix (voxel: 2 x 2.6 x 3 mm sagittal and 2 x 2.6 x 5 mm coronal)

19 DCE WB MR Imaging Signal Emax (%) Emax Timing Time

20 DCE WB MR Imaging Injection Each sagittal station: 24 slices in 7 seconds (3mm/slice) Each coronal station: 40 slices in 9 seconds (5mm/slice) 152 slices/60 seconds

21 T1 SE T2 TSE FS Example: 64 ans / baseline 2ème 4ème 7ème 5ème 6ème 3ème 1ère répétition

22 Feasibility study: 21 patients with plasma cell disorders, 14 MM (66%) Bone marrow and focal lesion enhancement successfully evaluated

23 Without Diffuse infiltration With Diffuse infiltration Before Gd After Gd 1st repetition Before Gd After Gd 1st repetition

24 DCE WB MR Imaging for treatment evaluation 30 patients, prospective study Multiple myeloma Systemic therapy Assess post-treatment bone marrow changes and, Correlate with clinical response (based on international uniform criteria) Durie BGM et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20:

25 Timeline Baseline WB DCE-MRI 1 n = 30 Induction chemotherapy Pre-ASCT WB DCE-MRI 2 n = 30 High-dose therapy + ASCT Post-ASCT WB DCE-MRI 3 n = 20 ASCT: autologous stem cell transplantation

26 Bone marrow enhancement (BME) Stations I, II, IV, V 2 ROIs per station averaged Emax (%) of each station Maximal value among the 4 stations BMEmax (%) of each exam

27 Focal lesion enhancement (FLE) 1 ROI per lesion 5 target lesions per exam FLEmax (%) and FLEmax Timing of all target lesions

28 Female patient, 64y, before and after induction chemotherapy Responder Rehaussem ent (% ) Tem ps (m in) Timing of FLEmax (early) Rehaussem ent (% ) Tem ps (m in) Timing of FLEmax (late)

29 MR vs. clinical response Post-ASCT evaluation: concordant 65 (%) *4 good responders (uniform criteria) but poor responders on WB DCE-MRI relapsed

30 Female patient, 63y, good responder after ASCT on clinial and biological criteria but not WB DCE MRI M-protein IgA: from 37 g/l to 0g/L CR (uniform criteria) BMEmax < 97% Early-enhancing focal lesions (+) 2 months later After Gd 1st repetition After Gd 1st repetition

31 WB DCE-MRI can be used to assess treatment response in patients with MM (superior to T1/T2WI) Particular usefulness for patients with oligosecretory or nonsecretory disease

32 Consensus statement MRI Dimopoulos et al, JCO 2015 Smoldering or asymptomatic myeloma: MRI indicated for >5mm focal lesion Is there a role for low-dose CT?

33

34

35

36 DCE WB-MRI in Myeloma 35 y/o man, non-secretory MM post autologous stem cell transplant in 2005 Newly-onset low back pain in Nov. 2006

37 Diffuse marrow infiltration + hepatic nodules (incidental findings)

38 DCE WB-MRI in Myeloma Potentials for evaluation of disease activity Same patient: after chemotherapy, before allogeneic stem cell transplant

39 Whole-spine MR (3 stations) T1, T2FS and T1FS+Gd difficult to know if the tiny lesion is active

40 Dynamic MR demonstrates its activity (another adjacent lesion only a central spot is active, other portions progressive enhancement).

41 3D-VIBE 0 3D-VIBE 1 3D-VIBE 6

42 57y/o woman, MM with right sacral mass. Bone marrow transplant 2 years ago Follow-up exam, clinically mild right shoulder pain

43 T1 SE T1 Gd 2ème répétition 1ère 4ème 7ème 2ème 3ème 6ème 5ème répétition

44 55y/o man, ASCT 2007 Ig 50 3 g/lgood response WB DCE MRI

45

46 3D-VIBE 2

47 3D-VIBE 0 3D-VIBE 1 All focal lesions appeared active on DCE-MRI!!

48 october Patient had back pain

49 Marked progression in the entire imaged marrow space with massive left pleural effusion

50 3D-VIBE 2

51 3D-VIBE 0 3D-VIBE 3

52 64y female new patient with stage 3 (Durie/Salmon) IgG Kappa MM, baseline WB-DCE MRI example of diffuse & focal infiltration

53 Diffuse infiltration Baseline, monoclonal peak at 20g/L After 3 cycles of chemotherapy, monoclonal peak decreased to 8g/L VIBE0 VIBE1 VIBE0 VIBE1

54 Right sacral mass Baseline, monoclonal peak at 20g/L After 3 cycles of chemotherapy, monoclonal peak decreased to 8g/L VIBE0 VIBE1 VIBE1

55 60y/o man, MM after 4 cycles Incidental findings

56

57

58 80y/o man with stage I MM and chronic hepatitis C Incidental findings

59

60 VIBE 0 VIBE 1 VIBE 3 VIBE 6 Last MRI of liver (décembre 06) negative!!

61 52y/o woman, MGUS Incidental findings

62 In favor of hemangiomas, no MR evidence of myeloma marrow infiltration, but.

63 Plan Whole-Body MR imaging Biological aspects DCE MR imaging DCE WB MR imaging PET imaging

64 A B C D E * 11 C-ACT 18 F-FDG 11 C-ACT PET/CT 18 F-FDG PET/CT WB-DCE-MRI Courtesy Dr Lin, Taiwan

65 Conclusion WB MRI should be used for myeloma staging but also plasmocytoma and MGUS On going WB DCE MRI evaluation for prognostic value As other hematologic malignancies, functional imaging is necessary for patient evaluation