1. Status and main challenges for detectors in Hadron Therapy European Radiation Detection and Imaging (ERDIT) Bernd Voss GSI Helmholtzzentrum für Schwerionenforschung GmbH
Literature sources:
Diamond Como
Diamond SFRS
Peter Forck
Maximum likelihood expectation maximization (MLEM)

2. What is Hadron Therapy about?
Guideline
What is Hadron Therapy about?
What are the methods & instruments offering particles for treatment during the evolution ‘State-of-the-art’  ‘Modern’  ‘Futuristic’ accelerators?
Which tasks do we have to perform and which questions do we have to answer in radio therapy (RT)?
Which requirements & challenges for detector systems result?
Are there already practical solutions?
ERDIT for Horizon2020, CERN

3. Hadron-Therapy Light Ions vs. Photons
IMRT
12C
Jäkel et al, Med Phys
Schardt et al, Rev Med Phys
Fragment tail
Ions…
Show inverse depth-dose profiles with a finite range and low lateral scattering at least in the plateau region
Allow superior tumor-dose conformality
Introduce increased sensibility to range uncertainties (wrong dosage) daily positioning for 30 days, intra- & inter-fractional target movement
ERDIT for Horizon2020, CERN

4. Hadron-Therapy Knowledge of base data is crucial
Depth-dose/range distributions Nuclear fragmentation cross-sections
Conversion of CT planning data (Hounsfield Units) into range of ions
Existing detector equipment for the base-data collection is mature
Relative ionization
Rietzel et al, Rad Onc 2,
Water equivalent path length
CT number
Depth in water (mm)
HU:
ERDIT for Horizon2020, CERN

5. ‘State-of-the-art’ Hadron Therapy facilities
‘Standard’ Accelerator structures
Cyclotron, Synchrotron, Synchro-cyclotron
Beam preparation
Heidelberg Ion Therapy:
Beam application
Beam transport
Mature detector equipment pick up, SEM, SCI, rest-gas monitors, IC, CG, MWPC
Under investigation: GEM-TPC, Diamond, Si
Basic research & Quality assurance
ERDIT for Horizon2020, CERN

6. ‘State-of-the-art’ beam delivery Minor Challenges
On-line monitoring of irradiation exhibits…
Local saturation
spoiling width determination for wire based gaseous systems in high-flux areas esp. for point-like (pencil) beams with high LET radiation (12C-RT)
Potential solution
Exploit robust amplification methods e.g. based on GEM technology First prototypes show feasibility
Potential improvements can be obtained in the high-flux areas of high-LET radiation (light-ion hadron therapy). Here local saturation is a hurdle for optimal width determination. The same limitation holds true for ultra-fast irradiations, here the dose-measurement may still be feasible by conventional methods (ionization) but measuring the position (esp if point-like) will be problematic. This issue may at least be overcome partially by exploiting other types of amplification (or abstain from using any) like GEM-based detectors which allow for a much higher local flux. For the latter measurements with prototypes have shown good results, 12C beam spatial distributions determined by film dosimetry and current integration were correctly reproduced.
ERDIT for Horizon2020, CERN

7. ‘Modern’ Accelerators LASER driven accelerator
E ≥1012V/cm
Relativistic e-
LASER PW250TW, Ti-Saphire, Neodynium-Glass, O(100m2) space req.
Pulse 700fs, 25/w10/s conventional p-cyclotron: 100MHz
Dose Rate (2 Gy/(min l)) ~10-3 Gy/pulse ~10-10 Gy/pulse
Spot point like O(10µm2), O(1021W cm-2)
Proton energy 10170MeV with exponential energy spectra (factor 2 still missing)
Targets thin foils (50nm-10µm Si,Ti,Hydro-Carbon), H2droplets
Limited mass to increase proton energy at given power at decreased divergence and to obtain (quasi) mono-chromatic beams!
In-vitro studies indicate no influence on the RBE
ERDIT for Horizon2020, CERN

8. ‘Futuristic’ Accelerators Dielectric Wall Accelerator
CT-guided rotational (200°) IMPT
Pulsed HF fields, p(200MeV) in 2m
(E,I,spot) variable pulse-to-pulse
Pulse length
On-line monitoring beam-application?
Lawrence Livermore
National Laboratory (LLNL)
ERDIT for Horizon2020, CERN
Y. -J. Chen et al. LLNL-CONF , 2009 8

9. ‘Modern’ beam delivery Major Challenges
DWA & PRIOR (???) still in a very early stage or just sketched
LASER based systems are set up; open questions:
Shielding the patient against beam contaminations (hard-X,e-,n)
Formation of irradiation-field from non-monochromatic beams
Dosimetry for exponential energy spectrum recently solved by conventional IC calibrated against FC
Measurements for (x,y,z) steering and control for ultra-fast (ns) irradiation techniques; how to do an intensity modulation & dose control particle therapy?
ERDIT for Horizon2020, CERN

10. Intermediate Summary …ongoing detector R&D
Besides ongoing attempts to optimize equipment for online monitoring of beam delivery & control (MWPC)
existing detector equipment for base-data collection and
state-of-the-art ion-beam application is mature
R&D endeavors concentrate on:
methods to reduce range uncertainties (anatomy, patient positioning, inter- and intra fractional motion of target volume)
attempting to obtain 3D in-vivo on-line dosimetry & tomography using available information emerging from the target volume
developing dedicated imaging detector systems
ERDIT for Horizon2020, CERN

11. Insight into target volume Interaction & products
Nucleons
& clusters
Projectile
Target
Projectile fragment
Target fragment
Fireball
Prompt g-rays
Fragmented ions
radioactive
nuclides
Time (s)
after collision
Particles
Prompt -rays
+-decay
for 1010 protons (170 MeV, ~2Gy): (3·109) n(9·108) p(1·107) a(2·105)
Aim: In-beam in-vivo single particle tomography & dosimetry
Exploit information on the target volume by emerging radiation
ERDIT for Horizon2020, CERN

12. Single particle (in-vivo) imaging
Single Particle Tomography
on-line / in-beam
‘off-line’
PET ß+emitter
SPECT
Prompt -rays
Interaction Vertex Imaging Light charged particles
Proton beams
Light ion beams
ICT Primaries
Range telescope
Passive collimation
Slit cameras
Single
slit
Multi
Electronic collimation
Compton camera
Silicon
Scintillator
CdZnTe = Scatterer
SCI,CZT = Absorber
in-beam
in-room
off-line
Mostly completely new methods (except PET)
Clinical applicable technical solutions not elaborated
Appropriate detectors not commercially available
Information obtained out of the irradiated volume itself by
HICT Heavy-Ion Computed Tomography (primary particles)
Penetrating primary particles probing the 3D density matrix (on-line)  (rest-) range telescope
Prompt- imager (SPECT, Compton Camera) Any free running system needs either a reduction of random coincidences or a slit system cutting also into the ‘good’ events.
PET imager Positron-Emission Tomography, mature technique, get rid of in-beam random coincidences/background which
SPECT Single Photon Emission Computed Tomography
SPI Secondary proton imaging (light charged particles)
ERDIT for Horizon2020, CERN

13. Positron Emission Tomography
Single Particle Tomography
on-line / in-beam
‘off-line’
PET ß+emitter
15O, 11C, ...
proton
projectile
neutron
16O
15O
Parodi et al, IEEE TNS 2005
nucleus of tissue
target fragment
β+ production is a by-product of the irradiation
in-beam
in-room
off-line
11C, 10C
15O, 11C, ...
target fragment
12C ion projectile
nucleus of tissue
16O
15O
neutrons
12C
11C
projectile fragment
Information obtained out of the irradiated volume itself by
HICT Heavy-Ion Computed Tomography (primary particles)
Penetrating primary particles probing the 3D density matrix (on-line)  (rest-) range telescope
Prompt- imager (SPECT, Compton Camera) Any free running system needs either a reduction of random coincidences or a slit system cutting also into the ‘good’ events.
PET imager Positron-Emission Tomography, mature technique, get rid of in-beam random coincidences/background which
SPECT Single Photon Emission Computed Tomography
SPI Secondary proton imaging (light charged particles)
Required devices: PET Camera
Parodi et al, IEEE TNS 2005
ERDIT for Horizon2020, CERN

14. Positron Emission Tomography …some Hardware
In-beam: GSI Darmstadt
Off-line: MGH Boston, HIT Heidelberg
more…
• HIMAC, Chiba
• NCC, Kashiwa
• HIBMC, Hyogo
• MDACC, Houston
• Univ. of Florida
In-vivo range measurements
In-vivo dosimetry & real-time image guidance
Ongoing developments (TOF-PET, PET+CT) reduce unfavorable in-beam random coincidences/background (by 20-30%)
Mature technology
in case of 12C in-beam randoms totally prevent of using this data slot
Tagging the events with an in-beam detector (TOF-PET)
Courtesy W. Enghardt / OncoRay
ERDIT for Horizon2020, CERN

15. Prompt -ray imaging Required devices: Hodoscope (x,y,t)
Single Particle Tomography
on-line / in-beam
SPECT
Prompt -rays
Ray (IPN Lyon)
Passive collimation
Slit camera
Single
slit
Multi
Electronic collimation
Compton camera
Silicon
Scintillator
CZT
SCI,CZT
Ray (IPN Lyon)
Required devices:
Hodoscope (x,y,t)
Scatterer (x,y,E)
Absorber (x,y,z,E,t)
Information obtained out of the irradiated volume itself by
HICT Heavy-Ion Computed Tomography (primary particles)
Penetrating primary particles probing the 3D density matrix (on-line)  (rest-) range telescope
Prompt- imager (SPECT, Compton Camera) Any free running system needs either a reduction of random coincidences or a slit system cutting also into the ‘good’ events.
PET imager Positron-Emission Tomography, mature technique, get rid of in-beam random coincidences/background which
SPECT Single Photon Emission Computed Tomography
SPI Secondary proton imaging (light charged particles)
ERDIT for Horizon2020, CERN

16. Prompt -ray imaging Technique
Proton treatment plan
-rays MC simulation
Nucleons
and clusters
Prompt g-rays
Primary ions
blue FLUKA
red Data
12C(75/95 AMeV) on PMMA
BP position
P R E L I M I N A R Y
Prieels et al (IBA) Dauvergne et al (IPNL Lyon)
A. Ferrari and FLUKA collaboration
ERDIT for Horizon2020, CERN

17. Prompt -ray imaging …some Hardware
single slit
22Na
CZT-strip+LYSO-block Detector
54x54x20 mm3
multi slit
20x20x5 mm3
Scintillating-fibre Hodoscope
2x128 (1x1mm2)
Timing ASIC
T. Kormoll, et al.,
NIM A626 (2011) 114,
IEEE NSS-MIC, 2011, pp. 3484
Le Foulher et al IPN Lyon
Krimmer, De Rydt
IPN Lyon
s-1
ERDIT for Horizon2020, CERN

18. Interaction-Vertex imaging (secondary protons)
Single Particle Tomography
on-line / in-beam
Interaction Vertex Imaging Light charged particles
Proton beams
Light ion beams
Dauvergne et al 2009
Required devices:
Hodoscope (x,y,t)
Trackers (x,y,z,E,t)
in coincidence
Information obtained out of the irradiated volume itself by
HICT Heavy-Ion Computed Tomography (primary particles)
Penetrating primary particles probing the 3D density matrix (on-line)  (rest-) range telescope
Prompt- imager (SPECT, Compton Camera) Any free running system needs either a reduction of random coincidences or a slit system cutting also into the ‘good’ events.
PET imager Positron-Emission Tomography, mature technique, get rid of in-beam random coincidences/background which
SPECT Single Photon Emission Computed Tomography
SPI Secondary proton imaging (light charged particles)
AQUA Project: G4 simulations
ERDIT for Horizon2020, CERN

19. Interaction-Vertex imaging Technique
Prompt g-rays
Nucleons (protons)
Primary ions
Single proton
Double proton
Courtesy of E. Testa
ERDIT for Horizon2020, CERN

20. Interaction-Vertex imaging …some Hardware
‘PRR30’ 2x SCI Stack (r,E)
48x3mm plastic
15cm WEPL ( MeV)
WLS fibres MPPC SiPM >106 s-1
CMOS
Hodoscope
2x2cm planes 10°
PMMA
GEM tracker
30x30cm2 2D-strips ~106 s-1 rad.hard
GANIL (95 AMeV) & HIT ( AMeV)
Courtesy of
TERA
ERDIT for Horizon2020, CERN

21. Interaction-Vertex imaging …some Results
10 cm
secondary protons
__ primary protons
1.5 m
target
GEM
PRR30
1010 s-1
~5×105 s-1
GEM-spatial  400m    6mrad Angular resolution  ~0.3% (0.04 sr) Solid angle
reconstructed vertices
Large-angles beam diagnostics is feasible at an acquisition rate of 106 tracks/s
Courtesy of
TERA
ERDIT for Horizon2020, CERN

22. Primary-Ion Radiography / Tomography
Single Particle Tomography
on-line / in-beam
ICT Primaries
Range telescope
Prompt g-rays
Nucleons (protons)
Primary ions
Traversing particles
Bragg peak position depends on the traversed materials
Required devices:
IC Range Telescope (r(Ei))
(Trackers (x,y)i,e)
Information obtained out of the irradiated volume itself by
HICT Heavy-Ion Computed Tomography (primary particles)
Penetrating primary particles probing the 3D density matrix (on-line)  (rest-) range telescope
Prompt- imager (SPECT, Compton Camera) Any free running system needs either a reduction of random coincidences or a slit system cutting also into the ‘good’ events.
PET imager Positron-Emission Tomography, mature technique, get rid of in-beam random coincidences/background which
SPECT Single Photon Emission Computed Tomography
SPI Secondary proton imaging (light charged particles)
For transmission ion-imaging prior to or in-between RT
ERDIT for Horizon2020, CERN

23. Primary-Ion Radiography / Tomography
Water equivalent thickness
12C ions Radiography X-rays
Water equivalent path length
Tomography
1x1mm2
3x0.6mm2
61x ICs & PMMA slabs (300x300x3)mm3
Rinaldi et al 2012 (
Electrometer
Transmission ion imaging prior to or in-between RT is feasible
ERDIT for Horizon2020, CERN

24. P R E L I M I N A R Y P R E L I M I N A R Y
12C Ion Tomography
3D ART Reconstruction
P R E L I M I N A R Y
P R E L I M I N A R Y
Rinaldi, Gianoli et al 2012
Rinaldi, Gianoli et al 2012
ERDIT for Horizon2020, CERN

25. Several ‘modern’ beam production scenarios under investigation
Summary
Several ‘modern’ beam production scenarios under investigation
LASER driven accelerators are not table-top like so far Dosimetry by IC with FC calibration successfull
DWA & 4.5 GeV Proton Camera are far from being reality
Detectors for Beam Control & Treatment Steering are mature
Imaging setups to gain inside in on-line dosimetry are required
Most detector systems exist on a prototype/proof-of-principle base, larger scales are needed
Several ‘new’ detector materials are under investigation (CdZnTe,LaBr,LYSO,..)
Imaging results are promising for PET, prompt gamma, secondary proton, primary-ion tomography
Serious applications as standard medical device still pending
ERDIT for Horizon2020, CERN

26. from whom I borrowed some of the information shown.
Acknowledgement
Special thanks to:
Ilaria Rinaldi (Heidelberg University Hospital, Heidelberg) Katia Parodi (Ludwig-Maximilians University, Munich) Wolfgang Enghardt (OncoRay, Dresden)
from whom I borrowed some of the information shown.
ERDIT for Horizon2020, CERN