Image based in-vivo dosimetry: from PET to in-beam SPECT
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1 Image based in-vivo dosimetry: from PET to in-beam SPECT 2nd Workshop on Hadron Beam Therapy of Cancer Erice, Sicily, Italy May 25th, 2011 Fine Fiedler Institute of Radiation Physics Text optional: Institutsname Prof. Dr. Hans Mustermann Mitglied der Leibniz-Gemeinschaft
2 Outline The Dresden Proton beam facility In-vivo dosimetry In-beam PET in ion therapy Lessons learned from in-beam PET New developments towards a real-time in-vivo dosimetry
3 The proton project at OncoRay OncoRay National Center for Radiation Research in Oncology Unique proton therapy facility: Conventional proton therapy and Laser based proton accelerator 1 Proton cyclotron 2 Energy selection system 3 Transfer beamline 4 Therapy cave with isocentric gantry 5 PET/CT on rails 6 Research cave with cyclotron driven beamline 7 Beamline for laser accelerated protons Cyclotron Laser accelerator W. Enghardt et al., SPIE, Prague, 2011
4 The proton project at OncoRay W. Enghardt et al., SPIE, Prague, 2011
5 Radiotherapy with ion beams- Motivation Ions are superior to photons due to their physical and biological properties Ion beams can cause much more severe localized damage than photons In-vivo monitoring of the correct application is needed
6 Radiotherapy with ion beams- Motivation Ions are superior to photons due to their physical and biological properties Ion beams can cause much more severe localized damage than photons In-vivo monitoring of the correct application is needed Overdosagein the normal tissue applied dose planed dose Underdosage in the tumor
7 Radiotherapy with ion beams- Motivation Ions are superior to photons due to their physical and biological properties Ion beams can cause much more severe localized damage than photons In-vivo monitoring of the correct application is needed Ion dose distribution is extremely sensitive totheionrangein vivo Precision needs control
8 The physics Ion beam tissue interaction Interaction with electrons of tissue Dose deposition
9 The physics Ion beam tissue interaction Interaction with electrons of tissue Creation of positron emitters via nuclear reaction Nuclear reactions with tissue atoms Therapy beam 1 H 16 O * 15 O Dose deposition n γ (511 kev) e + e - 15 O BN γ (511 kev)
10 The physics Ion beam tissue interaction Interaction with electrons of tissue Creation of positron emitters via nuclear reaction Nuclear reactions with tissue atoms Formation of excited states of nuclei Therapy beam 1 H 16 O * 15 O Dose deposition n γ γ (511 kev) e + e - 15 O BN γ (511 kev)
11 The physics Ion beam tissue interaction Interaction with electrons of tissue Creation of positron emitters via nuclear reaction Nuclear reactions with tissue atoms Formation of excited states of nuclei Dose deposition γ (511 kev) O O * e + e - γ (511 kev) T 1/2 2 min 15 O γ Can be measured by means of (in-beam) PET Can be measured by means of in-beam SPECT
12 Radiotherapy with ion beams Clinical application Scientific and Technical Innovations The intensity-controlled raster scan method Biologically German optimized Heavy irradiation Ion planning Tumor Therapy Project Verification of the dose delivery with in beam positron emission tomography (PET) : Treatment of more than 440 patients with 12 C-beams Mostly head & neck Mostly applied protocol Ion source Heavy ion synchrotron Linear accelerator Ablenkmagnet 20 fractions, 2 (3) fields Schardt et al., Rev. Mod. Phys. 82, 2010
13 In-beam PET Physical background 11 C, 10 C Beam Therapy beam 1 H 16 O 15 O * n 11 C, 13 N, 15 O, 10 C γ (511 kev) ) e + e - 15 O BN γ (511 kev) W. Enghardt et al., Phys. Med. Biol. 37, 2127, 1992 J. Pawelke et al., IEEE T. Nucl. Sci. 44, 1492, 1997 W. Enghardt et al., Nucl. Instr. Meth. A 525, 284, 2004
14 In-beam PET Physical background 11 C, 10 C Beam Therapy beam 1 H 16 O 15 O * n 11 C, 13 N, 15 O, 10 C γ (511 kev) ) 15 O BN 12 C 6+ ions undergo nuclear reactions with tissue atoms A(r) D(r) Coulomb interaction between 12 C 6+ ions and electrons of the matter / tissue e + e - γ (511 kev) W. Enghardt et al., Phys. Med. Biol. 37, 2127, 1992 J. Pawelke et al., IEEE T. Nucl. Sci. 44, 1492, 1997 W. Enghardt et al., Nucl. Instr. Meth. A 525, 284, 2004
15 In-beam PET Physical background Dose distribution β + -activity measurement A(r) D(r) Dose distribution and β + -activity measurement are not directly comparable Predictionof β + -activityrequired
16 In-beam PET Clinical implementation Dose distribution γ Simulation Tomographic Reconstruction Prediction Measurement In-beam PET scanner at 12 C-therapy unitatgsi
17 In-beam PET Data evaluation Predicted β + -activity distribution Measured β + -activity distribution Requirements for data evaluation Superimposition of PET-Data and planning CT Display of all slices, frontal, sagittal and transversal Comparison between predicted and measured β + -distribution Prediction Comparison is done daily, normally 20 fractions Measurement F. Pönisch, FZD Report 378, 2003
18 In-beam PET Data 2.3 evaluation Results of in-beam PET clinical practice VI Comprehensive study 4fold dose, real patient plans, 6 experienced observers A range modification of 6 mm in water was applied in the shape of the frustum of a pyramid F. Fiedler et al., Phys. Med. Biol. 55, , 2010
19 In-beam PET Data 2.3 evaluation Results of in-beam PET clinical practice VI 6 observers, 81 patients, 3 cases possible 1458 studied cases Range verification by visual inspection: 4fold Dose, R = 6 mm, sensitivity = (92 ± 4) %, specifity= (96 ± 3) % Automatisation in progress F. Fiedler et al., Phys. Med. Biol. 55, 1989, 2010 A. Santiago, Master Thesis, TU Dresden, 2009
20 In-beam PET Data 2.3 evaluation Results of in-beam PET clinical practice Experience of 11 years : Monitoring of treatment of ~ 430 patients For 10 % of monitored treatments a modification is necessary Random errors like - Mispositioning - Patient- or organ movement - Density changes within the irradiated volume Systematic error - Range:R = R(HU)
21 In-beam PET Clinical results(i) Filling of cavities β + -activity prediction β + -activity measurement Beam Filling of cavity Reduced range Estimation of difference in dose required
22 In-beam PET Clinical 2.3 Results results(i) of in-beam PET clinical practice I W. Enghardt et al., Radioth. Oncol, 73, S96-98, 2004, K. Parodi, FZD Report 415, 2004
23 In-beam PET Clinical 2.3 Results results(i) of in-beam PET clinical practice I planning CT Dose difference modified CT Maximum deviation D = -214 mgy (D max = Gy) W. Enghardt et al., Radioth. Oncol, 73, S96-98, 2004, K. Parodi, FZD Report 415, 2004
24 In-beam PET Clinical 2.3 Results results(i) of in-beam PET clinical practice I β + -activity prediction β + -activity measurement Filling of cavity Reduced range 3 days later, after medicaments prescribtion
25 In-beam PET Clinical results(ii) Anatomical changes in the irradiated volume Fraction 5 Fraction 7
26 In-beam PET Clinical results(iii) Patient mispositioning Beam
27 In-beam PET Clinical results(iv) Prediction Measurement The detection of systematic range deviations The accuracy of the physical beam model used for treatment planning 1998 Since 1999 Rel. water equiv. path 1,2 1,1 2,5 2 1,5 1 0,5 Range:R = R(HU) Table 08/98 Table 08/ Soft tissue Hounsfield unit Prediction Measurement 1,0 0, E. Rietzel et al., Radiat Oncol 2, 2007 M. Krämer et al., Radiother. Oncol. 73, S80, 2004
28 Different modalities of particle therapy PET 1 st field 0.66 Gy 2 nd field 0.37 Gy Shakirinet al., Phys. Med. Biol. 56, 1281, 2011
29 Different modalities of particle therapy PET 1 st field 0.66 Gy 2 nd field 0.37 Gy? Shakirinet al., Phys. Med. Biol. 56, 1281, 2011
30 In-beam PET forotherionsthan 12 C In-beam PET applicable for a large variety of light therapy relevant ions K. Parodi et al., IEEE T. Nucl. Sci. 52, 778, 2005 F. Fiedler et al., IEEE T. Nucl. Sci. 53, 2252, 2006 F. Sommerer et al., Phys. Med. Biol. 54, 3979, 2009 M. Priegnitz et al., Phys. Med. Member Biol., of53, the Helmholtz 4443, Association 2008
31 In-beam PET for hard photons Small double head ELBE 2 BGO-block detectors 8 8 crystals; 2 2 PMT ELBE Dipole magnet 2 linear moving PET detectors Target To beamdump e - Phantom Bremsstrahlung T. Kluge et al., Phys. Med. Biol. 52, N467, 2007 D. Kunath et al., IEEE T. Nucl. Sci., 56, 57, 2009
32 In-beam PET 3.4 Looking beyond: In-beam PET hard ELBE photon beams PMMA; E e- = 33 MeV; t irr = 90 min E e- 30 MeV 34 MeV 37 MeV 40 MeV 1 cm Aktivity Dose Aktivity Dose In-beam PET has the potential for an in-situ und in-vivo Monitoring of dose application for irradiation with high-energy photons T. Kluge et al., Phys. Med. Biol. 52 N467, 2007, D. Kunath et al., IEEE T. Nucl. Sci., 56, 57, 2009
33 Lessons learned from 2.3 Results in-beam of in-beam PET limited PET angle clinical practice VI Geometries and reconstruction results GSI - Configuration 12 x 8 16 x 6 48 x 4 P. Crespo et al., Phys. Med. Biol. 51, 2143, 2006
34 Lessons learned from in-beam PET Metabolism Feasibility to solve the inverse problem: A(r) spatial distribution of activity A(r) = T D(r) D(r) spatial distribution of dose T transition matrix For inorganic phantoms: K. Parodi, T. Bortfeld, Phys. Med. Biol. 51, 2006 Limited angle artefacts (in-beam PET) D < 0.9 D max K. Parodi, T. Bortfeld: Phys. Med. Biol. D 51 > (2006) 0.9 D1991 max Quantification of metabolic washout rate of β + -radioactivity impossible - individual - tissue dependent - dose dependent - fraction dependent - disturbed by the tumour T 1/2 /s = f T 1/2 /s = f F. Fiedler et al., Acta Oncol. 47, 1077, 2008
35 Ion therapy-dosimetry-state oftheart- In-beam PET Dose distribution γ Simulation Tomographic Reconstruction Prediction Measurement In-beam PET scanner at 12 C-therapy unitatgsi : Evaluation of more than 440 patients A procedure for the verification Of the irradiation field position Of the particle range Simultaneous with the therapeutic irradiation In-beam PET is clinically proven.
36 Ion therapy- Dosimetry Ongoing Research? In-beam PET scanner at 12 C-therapy unitatgsi
37 Ion therapy-dosimetry-state oftheart- In-beam PET In-beam PET scanner at 12 C-therapy unitatgsi Projects: 4D In-beam PET Kristin Laube New concept for activity prediction from treatment plan Marlen Priegnitz Automatic evaluation of in-beam PET data Stephan Helmbrecht Integration of in-room PET into an irradiation facility Daniela Kunath Time-of-flight PET Heide Rohling
38 4D In-beam PET Position Time Amplitude of motion Reconstruction with without correction for motion 4D 3D x / mm Amplitude of motion WP PhD project of Kristin Laube y / mm
39 4D In-beam PET Comparison static vs moving target Static reference 4D-in-beam PET 3D-in-beam PET β + -activity distribution in the static irradiation for the same applied dose Profile along the spread out bragg peak Motion corrected β + -acti-vity distribution; compara- ble to the reference Width of lateral 80-20% fall-off region Width of 80%-plateau Maximal difference to static reference Static Reference Blurred β + -activity distribution measurement 4D-inbeam PET 3D-inbeam PET 7.7 mm 8.0 mm 17.6 mm 36.4 mm 36.3 mm 29.7 mm PhD project of Kristin Laube
40 Ion therapy-dosimetry-state oftheart- In-beam PET In-beam PET scanner at 12 C-therapy unitatgsi Projects: 4D in-beam PET Kristin Laube New concept for activity prediction from treatment plan Marlen Priegnitz Automatic evaluation of in-beam PET data Stephan Helmbrecht Integration of in-room PET into an irradiation facility Daniela Kunath Time-of-flight PET Heide Rohling
41 New concepts for simulation Measurements in pure targets PhD project of Marlen Priegnitz
42 New concepts for simulation Measurements in pure targets Water - H 2 0 Graphite - C PMMA - (C 5 H 8 O 2 ) n PE - (CH 2 ) n PhD project of Marlen Priegnitz
43 New concepts for simulation Measurements in pure targets Water - H 2 0 Graphite - C PE - (CH 2 ) n Database Combination of data according to stoichiometry of the irradiated system Next step: Tests with patient data PhD project of Marlen Priegnitz
44 New concepts for simulation Measurements in pure targets Water - H 2 0 Graphite - C PE - (CH 2 ) n Database Combination of data according to stoichiometry of the irradiated system Next step: Tests with patient data PhD project of Marlen Priegnitz
45 Ion therapy-dosimetry-state oftheart- In-beam PET In-beam PET scanner at 12 C-therapy unitatgsi Projects: 4 D in-beam PET Kristin Laube New concept for activity prediction from treatment plan Marlen Priegnitz Automatic evaluation of in-beam PET data Stephan Helmbrecht Integration of in-room PET into an irradiation facility Daniela Kunath Time-of-flight PET Heide Rohling
46 Automatic evaluation of in-beam PET data WP 5 PhD project of Stephan Helmbrecht
47 Automatic evaluation of in-beam PET data Beam direction range as planned range enhanced range decreased PhD project of Stephan Helmbrecht
48 Automatic evaluation of in-beam PET data A Receiver Operating Characteristics is used to demonstrate the performance of a classifier Sensitivity if there is something you should see it TP / (TP + FN) Specificity if you see something it should be there TN / (TN + FP) PhD project of Stephan Helmbrecht
49 Automatic evaluation of in-beam PET data PhD project of Stephan Helmbrecht
50 Automatic evaluation of in-beam PET data Beam direction range as planned range enhanced range decreased PhD project of Stephan Helmbrecht
51 Automatic evaluation of in-beam PET data Stephan Helmbrecht: Development of a 3D routine for the automatic evaluation of in-beam PET data for the ion therapy Erice 2011
52 Ion therapy-dosimetry-state oftheart- In-beam PET In-beam PET scanner at 12 C-therapy unitatgsi Projects: 4D PET Kristin Laube New concept for activity prediction from treatment plan Marlen Priegnitz Automatic evaluation of in-beam PET data Stephan Helmbrecht Integration of in-room PET into an irradiation facility Daniela Kunath Time-of-flight PET Heide Rohling
53 Integration of in-room PET into an irradiation facility The Dresden proton irradatiation facility Wolfgang Enghardt, Stephan Helmbrecht, Daniela Kunath et al.
54 Ion therapy-dosimetry-state oftheart- In-beam PET In-beam PET scanner at 12 C-therapy unitatgsi Projects: 4D PET Kristin Laube New concept for activity prediction from treatment plan Marlen Priegnitz Automatic evaluation of in-beam PET data Stephan Helmbrecht Integration of in-room PET into irradiation facility Daniela Kunath Time-of-flight PET Heide Rohling
55 Time-of-flight PET Time resolution worse than 0.2 ns(fwhm) Integration of TOF in iterative algorithms Shakirinet al., Proc.IEEE NSS MIC, Honolulu, USA, , 2007 Time resolution better than 0.2 ns(fwhm) DirectTOF method: reconstructionin real time Crespo et al., Phys. Med. Biol. 52, 6795, 2007
56 Time-of-flight PET OS-EM, no TOF OS-EM, TOF 1.2 ns DirektTOF 0.2 ns DirektTOF 0.1ns WP 2
57 Ion therapy-dosimetry-state oftheart- In-beam PET In-beam PET scanner at 12 C-therapy unitatgsi Non-invasive 3-dimensional In-situ and in-vivo Clinically proven Projects: 4D PET Kristin Laube New concept for simulation Marlen Priegnitz Automatic evaluation of in-beam PET data Stephan Helmbrecht Integration of in-room PET into an irradiation facility Daniela Kunath Time-of-flight PET Heide Rohling Semiquantitative No direct dosimetry No real time capability Low signal to noise ratio
58 Ion therapy Dosimetry Future In-beam SPECT Therapy beam 1 H 16 O 15 O * n γ γ (511 kev) e + e - 15 O BN γ (511 kev)
59 Principle of a Compton camera Compton Scatter Formula Scattering of the γ Absorption of the γ
60 Ion therapy Dosimetry Future In-beam SPECT Projects: Simulation ofinteractionoftherapybeam with tissue Andreas Müller Simulation of interaction of gammas with different detector configurations Heide Rohling Reconstruction for Compton Cameras Sebastian Schöne Assembly of the prototype Thomas Kormoll, Christian Golnik
61 Simulation of interaction of therapy beam with tissue Real patient plan brain tumor primary protons calculated about 10-4 of real primary fluence (60 Gy) 2 fields (15,16 energies): - 1 st MeV 15 energies - 2 nd MeV 16 energies WP 3 Calculated by the planning tool... result in gammas in 4π... approximately gammas / Gy... need cones for reconstruction... efficiency of scanner of 0.1 %... solid angle of 10 %... we detect gammas sufficient for imaging way we want to go Calculated by Geant4 Diploma / PhD project of Andreas Müller
62 Ion therapy Dosimetry Future In-beam SPECT Projects: Simulation of interaction of therapy beam with tissue Andreas Müller Simulation of interaction of gammas with different detector configurations Heide Rohling Reconstruction for Compton Cameras Sebastian Schöne Assembly of the prototype Thomas Kormoll, Christian Golnik
63 Simulation of different detector configurations cm³ LSO cm³ CZT 4 cm % Isotropically emitted, V 100 cm³, d = 10 cm No interaction Preliminary Optimize Detector, Geometry, Compton scattering L 1, φ 1, L 2, φ 2 Multiple scattering Pair production PhD project of Heide Rohling
64 Simulation of different detector configurations cm³ LSO cm³ CZT 2 cm 2 cm % Isotropically emitted, V 100 cm³, d = 10 cm No interaction Preliminary Optimize Detector, Geometry, Compton scattering L 1, φ 1, L 2, φ 2 Multiple scattering Pair production PhD project of Heide Rohling
65 Ion therapy Dosimetry Future In-beam SPECT Projects: Simulation of interaction of therapy beam with tissue Andreas Müller Simulation of interaction of gammas with different detector configurations Heide Rohling Reconstruction for Compton Cameras Sebastian Schöne Assembly of the prototype Thomas Kormoll, Christian Golnik
66 Reconstruction for Compton Cameras? Source distribution Increasing number of iterations Measurement Data Increasing complexity of SM Rekonstruktion Reconstruction: find image b with maximum similarity to the unknown study objectbfrom the datad Image SM: b d SM System Matrix PhD project of Sebastian Schöne
67 Ion therapy in-vivo dosimetry In-beam SPECT Event Event Backprojection of a measurement 22 Na point center 2 cm camera distance 2000 Events Known energy PhD project of Sebastian Schöne
68 Ion therapy Dosimetry Future In-beam SPECT Projects: Simulation of interaction of therapy beam with tissue Andreas Müller Simulation of interaction of gammas with different detector configurations Heide Rohling Reconstruction for Compton Cameras Sebastian Schöne Assemblyoftheprototype Thomas Kormoll, Christian Golnik
69 Assembly of the prototype PhD project of Thomas Kormoll VME based system & C++ class library (libcvme) FPGA controlled trigger logic Versatile VME module control interface Multi-threaded data taking and analysis system
70 Assembly of the prototype LSO detector CZT detector E/E (662 kev) = 2.2 % PhD project of Thomas Kormoll Kormoll et al., Nucl. Instr. Meth. A , 114, 2011
71 In-beam SPECT Thank you In-beam PET
72 The people
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