MRI-guided Radiotherapy Seeing what to treat!

Transcription

1 MRI-guided Radiotherapy Seeing what to treat! Cornelis (Nico) van den Berg MR physicist, Associate Professor Department of Radiotherapy, Centre of Image Sciences UMC Utrecht, The Netherlands.

2 Contents Brief intro in radiotherapy State-of-the art radiotherapy and its shortcomings Why MRI in radiotherapy? Combining an MRI and a linear accelerator New therapeutic possibilities with MRI-guided RT

3 External beam radiotherapy After WWII: Cobalt Sources From 1970s, linear accelerators First treatment with cobalt unit, 1953 Borgo Val Sugana, Source: ESTRO 30 th anniversary book From mid 1980, computer controlled Linacs Source: Elekta website

4 Radiaton physics behind dose deposition Dose deposition by secondary electron cascade Source: slideshare: Amus Sygenus, Aarhus hospital

5 Effect of ionizing radiation on cells Radiation causes damage in the DNA Direct damage by double strand breakage Through creation of oxygen radicals. The damage cannot repaired -> cells die at cell division Tumor cell divide faster than normal cells The body naturally eliminates the damaged cells -> tumor shrinks

6 The balance between therapeutic effect and toxicity The higher the dose to the tumour -> the higher the therapeutic effect However, normal healthy cells are also affected -> toxicity Two important factors than can increase therapeutic effect and lower toxicity 1. Focusing the radiation to the target and minimize dose to healthy tissue 2. Apply radiation in multiple fractions of limited dose (~ 2 Gray) -> exploit higher ability of healthy tissue to repair.

7 2D Simulation in the old days.. Target Localization and set up of the radiation field A x-ray machine mimicking the MeV radiation machine was used to localize the target with respect to bony anatomy Radiation field was defined and through light transferred to patient This process is called the simulation process in radiotherapy

8 Dose planning in the old days.. Minimum info Patient outline Target location Dose was modulated by entry angles and lead wedges. Dose calculated by integrating along beam path

9 Starting in later nineties: A revolution due to CT imaging, inverse planning, beam shaping. CT Linac Computerized Inverse planning Portal Imaging Device MLC

10 State of the art simulation workflow CT imaging Delineation Dose definition Image guided 30x radiation Beam shaping Dosis evaluation Computerized dose planning Courtesy: Bram van Asselen, UMCUtrecht

11 Image guided dose delivery Cone beam CT Patient anatomy aligned to radiation beam by registration of daily CBCT to planning CT Provides translation and rotation of patient table

12 Technology advancement -> better quality treatment? We can design based on 3D CT image very conformal 3D dose coverage to tumor for a given patient Radiotherapy: 50% of the patients now receive radiotherapy As adjuvant therapy combined with chemo or surgery As primary treatment

13 However, we should not be satisfied!! There is still considerable uncertainty in the process Consequence: we irradiate a lot of healthy tissue We have to limit the dose to tumor to mitigate toxicity Tumor Clinical target volume Motion target volume CT of pancreas with delineated tumor

14 Delivery Simulation ( once ) Where are the uncertainties? CT imaging Tumor delineation, the weakest link in search for accuracy Manual delineation Treatment planning Njeh et al, Med Phys 2008 Much to be gained by addressing position/motion uncertainties during dose delivery Treatment = 'mimicking of simulation' Baumann (1-40 et times) al, Nature. Rev. 2016

15 1. Addressing delineation uncertainty by adopting MRI in the simulation workflow. Exploiting the superior soft tissue contrast of MRI to perform better target definition ->Seeing more CT MRI

16 2. Address delivery uncertainties: MRI- Linac Integrating MRI and a Linac provides soft tissue contrast during treatment delivery -> see tumor during therapy + Lagendijk and Bakker, MRI guided radiotherapy - A MRI based linear accelerator Radiotherapy and Oncology Volume 56, Supplement 1, September 2000, 220

17 1 MRI for improved target definition (and OARs)

18 Oesphageal cancer CT vs MR CT MR (T2W) 1.3 x 1.3 x 3 mm x 0.7 x 3 mm 3

19 Verduijn et al, IJROBP, 2009 MRI has superior soft tissue contrast T2N2b hypopharynx tumor, CE-CT T1w MRI Gd

20 Verduijn et al, IJROBP, 2009 Registration CT-MRI facilitates overlay of MRI delineation to CT. T2N2b hypopharynx tumor, CE-CT T1w MRI Gd

21 MRI's superior soft tissue contrast: cervix GTV primary tumor bladder CTV nodes (path.lymph nodes) GTV pathological lymph nodes (left) CTV primary (cervix, corpus uteri) rectum GTV pathological lymph nodes (right) T2-weighted

22 Tumor-background contrast: versatile MR contrast Pancreas CT MRI T2w MRI Diffusion Weighted MRI T1w

23 Functional imaging for prostate cancer Diffusion weighted imaging b=0 s/mm 2 b=1000 s/mm 2 ADC Diffusion MRI provides information about water mobility In tumor mobility restricted By making scans with strong diffusion encoding gradients -> we can make MRI sensitive to microscopic motion of free water molecules in tissue.

24 MR-CT Radiotherapy simulation workflow 1. Imaging 2. Planning 3. Treatment Electron density for dose planning Image fusion Delineation of tumor and organs at risk Matteo Maspero, UMCUtrecht

25 State-of-the-art simulation workflow 1. Imaging 2. Planning 3. Treatment Prostate = x 35 times Linac Linac Image fusion Delineation Plan & Dose Reference Images Position Verification IT news

26 Setup adaptation MRI: scan in treatment position At Treatment (Linac) MR-RT simulator: - Wide bore to allow scan in treatment position - Positioning lasers to record patient position Flat table top instead of Concave MR diagnostic table top

27 2 MRI guided RT

28 Delivery Simulation ( once ) Current RT workflow: where to improve? CT imaging Tumor delineation, the weakest link in search Manual delineationfor accuracy Treatment planning Njeh et al, Med Phys 2008 Much to be gained by Treatment = 'mimicking of simulation' addressing (1-40 position/motion times) uncertainties during dose delivery Baumann et al, Nature. Rev. 2016

29 Different anatomical conditions between radiation fractions for cervix cancer patients.. Patient 1 Patient 2 Day to Day motion Ellen Kerckhof, Bas Raaymakers, UMCU, NL Tumor Clinical Target volume Total target volume due to motion uncertainties

30 2. Address delivery uncertainties: MRI- Linac Integrating MRI and a Linac provides soft tissue contrast during treatment delivery -> see tumor during therapy + Lagendijk and Bakker, MRI guided radiotherapy - A MRI based linear accelerator Radiotherapy and Oncology Volume 56, Supplement 1, September 2000, 220

31 2:) MR guided RT addresses delivery uncertainties Conventional RT MRI-guided RT with a MRI-Linac brachy2 brachy2 move patient to suit a fixed treatment plan adjust treatment plan to suit the daily patient situation Courtesy: R Tijssen, UMCU

32 MRI-guided radiotherapy: seeing what to treat 1. Make MRI and delineate relevant structures 2. Make a conformal new plan based on anatomy at time of treatment 3. Allows smaller margins -> less toxicity. Image acquisition and VOI delineation Online treatment planning Delivery

33 Radiotherapy Department UMCU Development MR linac invention Design/ principles 1 st prototype 2 nd prototype 3 rd prototype in collaboration Elekta and Philips 2015 (pre)clinical

34 MRI system

35 Technical feasibility of a hybrid MRI-accelerator RF waves db/dt B 0 1. Effect static magnetic field of MRI on accelerator 2. Beam transmission through MRI system 3. Dose deposition in 1.5 T magnetic field 4. RF interference Schematic design

36 B o static magnetic field MRI Static magnetic field affects Linac Behaviour of magnetron that accelerates electrons altered

37 Exploit principle of active B 0 field shielding to minimize stray field Current direction Inner Windings Bp ou t Outer shielding Windings Bc out + = B0 out =Bp out -Bc out =0 0 T area B0=Bp in -Bc in cross section through magnet 0 T area Courtesy Bas Raaymakers, UMCUtrecht

38 Magnetic field MRI

39 Magnetic coupling solved by modified active shielding Zero-field zone on outside of magnet (position of Linac gun) Achieved by shift and change in #turns of shielding coils Johan Overweg et al. Proc. Int. Soc, Mag. Res. 2009

40 Design requires transmission through the cryostat 150 mm Gap between central coils increased to ~ 150 mm Possible without compromising homogeneity Cryostat with reduced and uniform gamma attenuation Standard MR/RT design

41 Split gradient coil Actively shielded coil system Central gap width 200 mm Courtesy Johan Overweg Prototype gradient coil (Futura, Heerhugowaard, NL)

42 Dose deposition in magnetic field Electron trajectory is changed by the Lorentz force Therefore the local dose deposit will change hν e hν B 0 Pacific Northwest national laboratory Lorentz Force: ԦF = qԧv B

43 Dose deposition in a magnetic field The Electron Return Effect (ERE) B = 0 B = 1.5 T γ γ e- γ γ e- γ γ e- e- e- e-

44 ERE at tissue-lung transitions simulation geometry -ray, 6 MV 4 x 4 cm 2 water ρ = 1 lung ρ = 0.25 water ρ = 1

45 Relative Dose (%) ERE at tissue-lung transitions Dose distribution and in-depth dose profiles T T Depth (cm ) Dose (%)

46 Relative Dose (%) ERE at tissue-lung transitions Dose distribution and in-depth dose profiles T 1.5 T Depth (cm ) Dose (%)

47 larynx IMRT treatment plan at 1.5 Tesla treatment 6 beams setup

48 Arb. Units larynx IMRT treatment plan at 1.5 Tesla single beam dose distribution showing ERE B 1 1 air gap Distance (cm)

49 larynx IMRT treatment plan at 1.5 Tesla optimized dose distribution Gy

50 Volume % larynx IMRT treatment plan at 1.5 Tesla DVH for optimized dose distribution and comparison to B = 0 T 100 PTV myelum Dose (Gy) Courtesy: Alexander Raaijmakers, UMCutrecht Dashed lines: B = 0 T Solid lines: B = 1.5 T

51 Volume % larynx IMRT treatment plan at 1.5 T with 5 beams DVH for optimized dose distribution and comparison to B = 0 T 100 PTV myelum Dose (Gy) Courtesy: Alexander Raaijmakers, UMCutrecht Dashed lines: B = 0 T Solid lines: B = 1.5 T

52 Radiotherapy Department UMCU Development MR linac invention design 1 st prototype 2 nd prototype 3 rd prototype 2015 (pre)clinical in collaboration Elekta and Philips

53 1.5 T MRI accelerator: prototype 1 Simultaneous beam on and MRI Artist impression First prototype MRI accelerator 1.5 T diagnostic MRI quality No impact of beam on MRI (image quality)

54 Second prototype MRI linac: rotating gantry with linac integrated with MR system. Cooling equipment Power supplies & electronics MLC & accelerator waveguide Slipring RF waveguides Modulator

55 Magnet prototype at Philips Helsinki

56 Third pre-clinical prototype MRI accelerator Key specifications Atlantic: 1.5 T MRI 7 MV linac Cylindrical geometry 70 cm Bore diameter Radiation perpendicular to B- field JJW Lagendijk et al. Semin Radiat Oncol 24: JJW Lagendijk and Bakker, MRI guided radiotherapy - An MRI based linear accelerator Radiother Oncol. 56, S1, 2000, 220

57 First clinic treatment on 1.5 T MR-Linac: First in Man Patient population Patients with bone metastases treated with palliative intention Treatment 8 Gy in a single fraction 3 or 5 field IMRT Goal: Demonstrate technical accuracy and safety in the clinical setting Online workflow MRI Deformable registration Delineations deformedct Independent Calc PV Pre-Treatment CT AutoPlanning OK Raaymakers et al. PMB. 2017;62(23):41-50 Courtesy Bas Raaymakers, UMCUtrecht

58 Clinical MRI-guided RT has become reality at UMC Utrecht stereotactic treatment of positive lymph nodes May 2017: First patient treatments in clinical study setting on 1.5 T MR-Linac June 2018: 1.5 T Elekta Unity system receives CE Mark August 2018: First regular clinical treatments on 1.5 T Elekta Unity in Utrecht

59 MRI-guided radiotherapy: seeing what to treat 0.35T MRIdian Viewray 1 1.5T Unity Elekta 2 3 Cobalt-60 sources/linac 0.35 T superconducting MRI Siemens MRI back-end Treated first patient in February 2014 February 2017: FDA clearance for Linac 7 MeV Linac 1.5 T superconducting MRI Philips MRI back-end Treated first patient in May 2017 June 2018 CE clearance August 2018: Start clinical treatment 1 The ViewRay system: magnetic resonance-guided and controlled radiotherapy. Mutic S, Dempsey JF. Semin Radiat Oncol The magnetic resonance imaging-linac system. Lagendijk JJ, Raaymakers BW, van Vulpen M. Semin Radiat Oncol Jul;24(3):207-9

60 1.5 T MR-Linac has diagnostic image quality 1.5T Ingenia 1.5T MR-Linac Courtesy: M. Philippens, (UMCU), Eveline Alberts (Philips)

61 3 Use cases for MRIguided RT

62 MRI integration in MRgRT workflow 1 week per treatment session MR-sim contour plan pre-beam MRI contour beam on MRI plan Courtesy: R Tijssen, UMCU

63 Hypo fractionated Radiotherapy of prostate with MRI-Linac anatomical Diffusion With MRI-guided RT allows designing a radiation plan based on the actual anatomy ADC Reduce uncertainties Exploit this to lower the amount of fractions Soft tissue and functional contrast allows localization of tumor in prostate Dose boost to tumor Dose

64 Lymp nodes: Room for improvement. Presence of positive lymph node is a strong negative prognostic factor in many cancers Lymph nodes are located (on CT) based on anatomical boundaries Large target volumes Dose to OAR Toxicity (e.g edema) PTV We can treat lymph nodes with MRIguided RT much better than currently occurs in radiotherapy. Courtesy Van Heijst et al., UMCUtrecht

65 2D T2 TSE Marielle Phillipens Tristan van Heijst

66 Stereotactic treatment of lymph nodes on MRL With MR-Linac we can re-localize the positive nodes and stereotactically sterilize it. axillary Lymph nodes on T2-FFE sequence T. Van Heijst, UMCU

67 4 Ongoing technological developments for MRIguided RT

68 Real time dose adaption The goal we are working towards.. Patient-ID: name: F. Ictitious real-time MR-Linac tracking tumor-site: kidney Tracking is ON Real-time imaging Motion history Beam s eye view Beam is ON Accumulated Dose offsets FH: RL: AP: resp: 1.0mm 0.5mm 0.2mm 3.2mm Courtesy Rob Tijssen, UMCUtrecht

69 Real time dose adaption: Latency and imaging speed Latency: difference between time stamp of imaging and beam adaptation For a 2D imaging case with standard Fourier reconstruction: MRI acquisition + reconstruction adds about ms latency. motion analysis + multi-leaf collimator control about ms What happens if we go for the 3D imaging case? Courtesy B.Stemkens, UMCUtrecht

70 Image acquisition speed: 1D, 2D, 3D How fast can we image with conventional techniques? Pulse sequence: cartesian T1-SPGR, one readout line per RF pulse TR = ~3ms 1D navigator 1RF pulse + 1 readout 2D image FOV = 350 x 350 mm 2 Res = 2 x 2 mm 2 Matrix = 175 x 175 T_acq = 3 x 175 3D image FOV = 350 x 350 x 270 mm 3 Res = 2 x 2 x 2 mm 3 Matrix = 175 x 175 x 135 T_acq = 3 x 175 x 135 => 3 ms => 525 ms => 708 s Courtesy: R Tijssen, UMCU

71 Image acquisition speed: 1D, 2D, 3D How fast can we image with conventional techniques? Pulse sequence: cartesian T1-SPGR, one readout line per RF pulse TR = ~3ms 1D navigator 1RF pulse + 1 readout 2D image FOV = 350 x 350 mm 2 Res = 2 x 2 mm 2 Matrix = 175 x 175 T_acq = 3 x 175 3D image FOV = 350 x 350 x 270 mm 3 Res = 2 x 2 x 2 mm 3 Matrix = 175 x 175 x 135 T_acq = 3 x 175 x 135 => 3 ms => 525 ms => 11.8 min Courtesy: R Tijssen, UMCU

72 73 Accelerating 3D acquisitions No undersampling 2x undersampled PI recon We can speed up MRI acquisitions by sub Nyquist undersampling Results in aliasing artifacts unless we apply parallel imaging 1,2 (PI) exploiting multi-element receive arrays Combining PI with Compressed Sensing 3 (CS) allows even higher acceleration 1. Pruesman et al, MRM 1999, 2. Sodickson et al, MRM 1997, 3. Lustig et al. MRM 2007

73 Towards fast, low latency 3D cine MRI 64-element coil array 1. Development of a radiolucent, high channel receiver array for MRI-Linac To further advance 3D image acquisition 2. Application of advanced reconstruction methods 1 Low latency reconstruction of undersampled data Zijlema et al. # 1737 ISMRM Zhu et al. Image reconstruction by domain-transform manifold learning, Nature 2018 With participation of Federico d Agata, University of Turin

74 Integrating MRI in RT treatment cycles Evaluate therapy efficacy by systematic response monitoring MR-Sim -> Better targeting due to superior contrast MRI driven by MR-Sim and MRI-Linac MRI-guidance: Designing a daily new plan based the observed patient anatomy

75 The goal we are working towards: curative organ preserving radiotherapy treatment Example: Esophageal cancer: Preoperative CRT surgery Path CR 29% 1. Can we increase complete response rate (pcr) rate? 2. Can we identify pcr prior to surgery?

76 Characterizing and adapting to the daily tumor status with MRI-guided RT Geometrical response Functional (Diffusion) response Before RT Day 0 Day 10 Day 20 b During RT e ΔADC = 48% After RT h Courtesy: Gert Meijer Peter van Rossum DWI (b=800) ΔADC = 44% ADC map

77 Online MR guidance facilitates tumour and OAR visualization Cone beam CT T2W MRI-Linac With online MR guidance we see tumor and risk organs Courtesy Gert Meijer

78 MRI guided RT: Better sight on what to treat! MRI simulation: Better target definition and characterization MRI guided Radiotherapy Brings MRI to treatment table -> seeing what to treat. Design radiation plan on actual anatomy Real time beam adaptation. MR based response assessment Evaluating and optimizing treatment efficacy Incorporate in therapy management. MRI in RT reduces uncertainties increase of therapeutic effect with equal/ lower toxicity!! Interventional radiotherapy/surgery without a knife

79 Center of Image Sciences. UMC Utrecht Developing new MRI_guided therapies MRI linac (3x) MRI brachytherapy (1x) MRI HIFU (1x) MRI Holmium Radioembolisation (1x) MRI guided protons (in silico)

80 Acknowledgements UMCUtrecht Federico d Agata, Caterina Guiot, University of Turin