Imaging techniques for in-vivo treatment verification

Transcription

1 Imaging techniques for in-vivo treatment verification Katia Parodi, Ph.D. Heidelberg Ion Therapy Centre, Heidelberg, Germany Previously: Massachusetts General Hospital and Harvard Medical School, USA, and Research Center Dresden-Rossendorf, Germany Hadron Therapy Workshop 2011 Erice, Italy, May 25 th, 2011 Massachusetts General Hospital and Harvard Medical School HIT Betriebs GmbH am Universitätsklinikum Heidelberg mit beschränkter Haftung

2 The physical advantages of ion beams The finite range with the characteristic Bragg-peak Photons Bragg-Peak Protons 12 C-ions Peak-region Plateau-region Depth in water (cm)

3 Treatment uncertainties in ion beam therapy TPS dose calculation errors Inhomogeneities, metallic implants Conversion HU in ion range CT artifacts Difference TP / delivery Daily setup variations Internal organ motion Anatomical / physiological changes Daily practice of compromising dose conformality for safe delivery After Enghardt 2005

4 Accounting for uncertainties in the clinical practice Current approach: Opposed fields, overshooting Desirable approach: Different beam angles and no overshooting? In-vivo verification A. Trofimov et al, MGH Protons

5 Positron-Emission-Tomography (PET) Imaging of b + -activity 1) b + -decay A(Z,N) A(Z-1,N+1) + e + + n e 2) Moderation of e + in medium (typically few mm in tissue) 3) Annihilation into 2 opposite g-rays (511 kev each) 4) Coincident detection and processing Detector g b + -emitter e + e - Coincidence processor Image reconstruction 180 E g = 511 kev g

6 PET imaging for verification of ion therapy In-situ, non-invasive detection of b + -activity Injected to the patient via irradiation using primary b + -radioactive ions like 19 Ne (T 1/2 17s), 11 C (T 1/2 20 min) and 10 C (T 1/2 19 s) Low dose exposure prior to therapy with stable beam (pioneered in 70s at LBL, USA) or prior to irradiation with same radioactive beam (planned at HIMAC, Japan) LBL, USA Not (yet?) in clinical routine use HIMAC, Japan 11 C 19 Ne from 20 Ne Llacer et al, Nucl. Sci. Appl. 3 (1998)111; Kitagawa et al, Rev. Sci. Instrum 77 (2006)

7 PET imaging for verification of ion therapy In-situ, non-invasive detection of b + -activity Formed as by-product of irradiation in nuclear fragmentation reactions ( 11 C [T 1/2 20 min], 15 O [T 1/2 2 min], ) 12 C (A) (D) 12 C ions in PMMA 11 C, 10 C n f 0 g-emission g-emission ( prompt ) annihilation 15 O, 11 C,... A(r) D(r) Dose-guidance from PET surrogate by comparing measured b + -activity with expectation as done at GSI 11 C 11 B+ e + + n e T 1/2 E g = 511 kev e + e - <~180 Annihilation g-rays Schardt et al, Rev Mod Phys 2010; Parodi et al, IEEE TNS 2005; Enghardt, Parodi Nucl Instrum Meth A 2004

8 In-beam PET for scanned 12 C therapy at GSI > 400 patients For every fraction (typically 20 1Gy) Planned dose Once g MC calculated b + -Activity g Beam on (noise) Beam off (PET signal) Time in s Verification of Beam range Lateral position In case of deviation Timely reaction Measured b + -Activity Enghardt, Parodi Nucl Instrum Meth A 2004; Parodi et al Nucl Instrum Meth A 2005

9 In-beam PET for scanned 12 C therapy at GSI Extraction of ion range in-vivo Validation of the physical beam model of treatment planning 1998 Since 1999 Prediction Measurement 1. Precision measurements: Range of 12 C-Ions in tissue (D. Schardt et al. GSI) 2. Modification: R = R(HU) (E. Rietzel et al. GSI) Prediction Measurement

10 Indirect PET-guided dose quantification Indirect estimation of 12 C dose deviation from in-beam PET b + -activity: prediction b + -activity: measurem. Fast Dose PET recalculation Original-CT Original-CT Modified CT Modified CT Hypothesis on the reason for the deviation from the treatment plan Interactive CT manipulation Original-CT Modified CT New CT CT after PET findings Parodi Ph.D. Thesis, 2004; Enghardt, Parodi et al, Radiother Oncol, 2004

11 PET monitoring of proton therapy? Proton 12 C In-beam phantom (PMMA) experiments at GSI (A) (D) 12 C ions g-emission g-emission 11 C, 10 C (Projectile fragmentation only for Z>1) 15 O, 11 C,... A p ~ 3 A12 C at same range and dose (but ~10 2 lower than in nuclear medicine PET for typical therapuetic ion doses) (A) (D) 15 O, 11 C,... protons Parodi et al PMB 2002, Parodi et al IEEE TNS 2005

12 Offline PET/CT for scattered p therapy at MGH Proton Irradiation min elapsed Offline PET/CT Only long-lived isotopes ( 11 C: T 1/2 20 min 15 O: T 1/2 2 min) Full ring tomograph CT for co-registration Passive beam delivery at MGH Boston MGH Radiology

13 Offline PET/CT for scattered p therapy at MGH Clinical case of clival chordoma Field 1: 0.87 Gy, DT 1 ~ 26 min Field 2: 0.87 Gy, DT 2 ~ 16 min TPS MC dose MC Phys. PET MC + washout PET PET/CT Meas. Field 2 Field 1 mgy mgy Bq/ml Bq/ml Range monitoring: possible in well co-registered low perfused tissues Challenges: washout, S/N, and (extra-cranial sites) motion, registration Parodi et al Int J Rad Oncol Biol Phys 2007

14 Offline PET/CT clinical experience at MGH # of patients Dose / field [GyE] head eye 1 10 C-spine T-spine L-spine sacrum prostate 2 2 TOTAL Parodi et al, IJROBP 68, 2007; Knopf, Parodi et al, PMB 54, 2009; Knopf, Parodi et al, IJROBP 72, 2011

15 Direct PET-guided dose quantification Mathematical formalism towards dose deconvolution in proton therapy Convolution with filter functions (cross-section dependent) Planned dose Filter-PET MC-PET (offline PET/CT scan) 11 C activity + washout b + -activity + washout Deconvolution would enable direct dose quantification from measured PET images, but issue of statistical noise, washout, motion Need for improved imaging strategies Parodi and Bortfeld PMB 2006; Parodi et al AAPM 2006; Attanasi, Parodi IEEE 2009

16 Towards better imaging strategies Short delay DT improves S/N, reduces washout Short scan time t meas minimizes motion artifacts and maximizes patient throughput But optimal solution depends on Development and integration efforts Patient throughput in treatment room Beam macro- and micro-structure Single g-rf time correlation experiments at GSI Random correction failure due to prompt (sub-ns) radiation correlated with RF (problem even worse for cyclotron) Dedicated data acquisition needed (Enghardt, Crespo, Parodi, Pawelke, patented) Beam on (noise) Beam off (PET signal) Time in s Worldwide active research on novel dedicated in-beam PET scanners Shakirin, Parodi PMB 2011; Parodi et al IJROB 2008; Parodi et al NIMA 2005

17 Novel PET systems for in-room imaging Dual-head scanner mounted on rotating gantry in Kashiwa, Japan Distance between two opposing detector heads of cm Icentric rotating of deg. Position resolution of mm FWHM Detection area of mm 2 Planning dose Reference activity daily activity - Planar imaging starting immediately after end of irradiation (cyclotron) - A(r) D(r): Daily measurement compared to reference activity (reproducibility check) - > 50 patients of H&N, Liver, Lung, Prostate and Brain from 2007/10 Similar finding as for GSI (e.g., detection of anatomical changes) Courtesy of T. Nishio NCC Kashiwa, Nishio et al IJROBP 2010

18 Closeby PET/CT at HIT Heidelberg Newly installed PET/CT next to the treatment rooms PET/CT Tx room Tx room Tx room Biograph mct Combs,, Parodi MIRANDA clinical study; Visualization / Analysis tools within BMBF project DOTMOBI

19 Establishment of clinical workflow at HIT Adaptation of MC to handle facility-, patient- and plan-specific information for automated dose calculation Sommerer et al, Rad Oncol 2010 supported by EU-project PARTNER Extension / validation of MC for calculation of b + -emitter yields GUI for automated simulation data management, visualization, data exploration and analysis Merging MC utilities for patient calculations of dose and PET Unholtz,. Parodi, DGBMT 2010; Bauer,., Parodi, PTCOG 2011

20 Establishment of clinical workflow at HIT Implementation realized via SimInterface (Software developement within the BMBF DOTMOBI project) Unholtz,. Parodi, DGBMT 2010; Bauer,., Parodi, PTCOG 2011

21 Towards 4D PET-guided in-vivo verification 12 C ion tracking experiment with time-resolved in-beam PET at GSI Dipole magnets Dynamic wedge Motion sensor Absorber Dipole magnets Static absorber Moving target (PMMA) Motion sensor Dynamic wedge Moving target (PMMA) Wedges 12 C beam PET Target Moving platform Static absorber Planned delivery of homogeneous extended dose Irradiation to static (ref.) and moving (~3cm in 1.5s) target Correlation of dynamic PET acquisition with motion Planned dose Parodi et al Med Phys 2009, in collaboration with GSI (Bert), FZD (Enghardt), SAG (Rietzel), patent pending

22 Proof-of-principle of 4D in-beam PET motion motion Static reference Static reference 3D PET (motion uncorrected) 4D co-registered PET 3D PET (motion uncorrected) 4D co-registered PET Ongoing / planned investigations Experiments at GSI / HIT to compare inbeam vs offline PET for monitoring of motion-mitigated ion beam delivery (gating, tracking, ) Explore benefits from advanced internal motion sensors (ultrasound-based) Extrapolation to clinical cases Parodi et al Med Phys 2009; collaboration HIT/GSI/FZD/Siemens/Mediri funded by EU Project ENVISION

23 12 C or p Real-time prompt gamma imaging (Z>1) Protons in water n f 0 g-emission ( prompt ) annihilation Experimentally verified correlation between 90 angled prompt g profiles and p / 12 C ions ion range Carbon ions in PMMA Promise of real time in-vivo range verification insensitive to washout Challenge of efficient detector solution (Anger or Compton camera) => Next talks! Testa et al, Applied Physics Letters 93 (2008)

24 Pre- (intra-?) treatment ion-based imaging Imaging residual range of high energy transmitted ion beams for - Validation of CT-range calibration curve - Assessment of range variations in motion cycle - Low dose verification of patient position at the treatment site Pioneered since the 60 s, but no routine clinical application yet Issue of high energies required and Coulomb scattering (esp. for protons) Several groups are now working on small scale systems based on (single) ion tracking and residual range measurement via range telescopes or thick energy detectors Proton radiograph of a phantom measured with in-house developed prototype at PSI Major efforts towards tomographic imaging to eventually replace X-ray CT for treatment planning Schneider et al 1990s, (Paul Scherrer Institute, Switzerland)

25 Towards ion radiography / tomography at HIT Stack of ionization chambers (Voss et al, GSI) with new electronics Scanning in steps of 5 12 C pencil-beam 400 MeV/u 3.5 mm Gaussian FWHM 5 x 10 6 pps PMMA phantom D=160 mm tissue equivalent rods d=28mm Multi-channel electrometer electronics highly integrated Simple 2D back-projected reconstruction Proof-of-principle 12 C Heavy Ion Tomography Rinaldi Ph.D. research at HIT/DKFZ (in collaboration with B. Voss, GSI); Voss et al GSI Report 2010, in press

26 Post-treatment magnetic resonance imaging Radiation induces fatty tissue replacement of vertebral bone marrow Pre-Tx MRI Planned dose Post-Tx MRI (1 month) Investigations on using this signal as range indicator of TOTAL dose delivery (not for single fraction) for population-based assessment Krejcarek et al IJROBP 2007

27 The time scales of in-vivo imaging techniques for in-vivo range verification DT Irradiation Time Long after therapy (DT days - weeks ) Magnetic Resonance Imaging (MRI) Sum of Fxs Long after treatment (DT ~ min) Offline PET(/CT) Shortly after treatment (DT ~ 2 10 min) In-room or nearby PET(/CT) In-beam delayed (DT ms - min) Positron-Emission-Tomography (PET) In-beam real-time (DT << ms) Prompt gamma, emitted particles Selected Fx Each or selected Fx Each Fx Each Fx Pre-treatment (-DT ~ min) Radioactive ion (RI) beams Ion radiography / tomography First or each fraction (Fx)

28 Conclusion Full clinical exploitation of ion therapy promises requires In-vivo imaging of surrogate signal, e.g., from escaping secondary radiation or physiological changes correlated to range / dose Reliable computational tools for accurate modeling of the surrogate signal in relation to the range / dose deposition PET is a mature imaging technique for in-vivo treatment verification, however technological / methodological improvements desirable In-beam PET would be the method of choice but requires dedicated, expensive instrumentation: industrial partners? Alternative or complementary (time scales!) techniques based on emitted / transmitted radiation or MRI under development / investigation

29 Outlook Synergy between imaging for (real-time?) verification of - Patient / tumour position (image-guided-radiotherapy) - Range / dose delivery (towards dose-guided radiotherapy) Ion gantry Motion sensor (ions, novel X- rays?) X-ray source Transmission (ions, novel X-rays?) X-ray imager Prompt g PET R&D in modeling, detector development, exp. validation, clinical integration, depending on beam production / delivery (beam time structure, background radiation, )

30 Acknowledgements The MC-modeling and in-vivo imaging research group at HIT: J. Bauer, C. Kurz, A. Mairani (now CNAO), I. Rinaldi, F. Sommerer, D. Unholtz The colleagues at HIT, Universitätsklinikum Heidelberg and DKFZ: J. Debus, S. Combs, T. Haberer, O. Jäkel and Medical Physics Group J. Engelke, M. Martisikova Collaborators / former colleagues: A. Ferrari, F. Cerutti, CERN Geneva D. Schardt, C. Bert, B. Voss, GSI Darmstadt T. Bortfeld, H. Paganetti, MGH Boston W. Enghardt, F. Fiedler, K. Laube, HZDR Dresden F. Attanasi, INFN Pisa Funding: FP7 EU Project PARTNER FP7 EU Project ENVISION BMBF Project DOT-MOBI HIT Start of clinical operation on 15 th November 2009 To date: > 400 patients treated Thank you for your attention