Real-time monitoring of ion rangespeople.na.infn.it/.../Erice2011/TalkContributions/Letang.pdf · 2011-05-25 · Real-time monitoring of ion ranges J.M. Létang on behalf of IPNL

Real-time monitoring of ion ranges

J.M. Létangon behalf of IPNL and CREATIS groups (Lyon, France)

2nd Workshop on Hadron Beam Therapy of CancerErice, Sicily, Italy

May 20, 2011 - May 27, 2011

• Two facilities for C-ion facilities will be available in 2015-16● Caen (Archade, IBA-C400 cyclotron): fundamental research● Lyon (ETOILE center): clinical facility and translational research

PRRHRhône-Alpes Research Program in Hadrontherapy

6. Simulations for the treatment plan / dose deposition D. Sarrut, N. Freud

Medical

Mathematics

Physics

Radiobiology

Dosimetry

Imaging

Technology

1. Medical Project (evaluation) J. Balosso, P. Pommier

2. Medico-economical simulations P. Pommier

3. In silico modelling of treatments B. Ribba

4. Basic data acquisition, online control D. Dauvergne

5. Hadronbiology, radiobiological effects of carbon ions C. Rodriquez, M. Beuve and N. Foray

7. Movement and deformation of tumours B. Shariat, D. Sarrut

8. Technological developements (gantry) collab. CEA, M. Bajard

Research topics of PRRH(coordinators: Prof. J-M. Moreau, Prof. J. Remillieux)

Outline of the talk

1. Context of the research

2. Rationale of real-time monitoring

3. Preliminary development (TOF)

4. Measurements

5. Simulations and Physics models

6. Camera designs

7. Reconstruction issues

8. TPS issues

Rationale of real-time monitoring

With Ion-Beam Therapy:

1. The dose is more conformational to the tumor

2. but uncertainties exist

● stoichiometric calibration (~3% in ion range)

● patient motion intra and inter fractions

► Need for a feedback loop to stop treatment if deviations occur

Ion range vs Dose

In-situ 1-D Camera is sufficient for real-time ion range monitoring of each beam spot (information in the plane normal to the beam can be integrated).

Dose calculations are not necessary for real-time monitoring, it is an off-line issue.

511 keV γ-rays vs prompt photons

Statistical photons Giant Dipole Resonance Nucleon-nucleon Bremsstrahlung

12C 310 MeV/u in water

Le Foulher 2010

What is the best particle to monitor treatment?

► β+ emitters cannot be used because of time constraints

► several 2ndary particles (γ, n, p...) are instantly emitted and correlated to the Bragg peak

► Choice may depend on the incident particle type (p, C-ion...)

Choice for real-time monitoring

Outline of the talk




4. Measurements


6. Camera designs


8. TPS issues

Many 2ndary particles (esp. for C-ion beam) out of the patient

► Background rejection welcome (e.g. neutrons)

► Need of a beam tagging device for TOF measures

► Knowledge of the transversal position of each ion would ease 1D reconstruction

Development of an Hodoscope

Preliminary development

• 1mm2 square fibers (2 planes H+V x 32 fibers): spatial resolution• Light transmission: optic fibers• coupled to flat panel PM : Hamamatsu H8500 64 channels

Timing resolution: 350 ps rmsFluence capability of fibers: >1012 ions/cm2

Scintillating fibers hodoscope (1st proto)

Fluence(1012 ions / cm2)

Threshold(mV)

Efficiency (%)

0.7 30 95

230 65

15 90

4

15 85

No gain in efficiency when:● decreasing the threshold● increasing the HT

To Do:– Measurement of the

maximum count rate– Development of a

hodoscope coupled to a MCP-PMT

4020 60 Charge (pC)

charge spectrum at the flat-panel output with a beam of 12C ions at 75 MeV/u

Scintillating fibers hodoscope (1st proto)

Ageing:> 1 year on clinical condition

Outline of the talk




4. Measurements


6. Camera designs


8. TPS issues

Several sets of C-ion experiments have been carried out

● Low energy [GANIL]: ✗ 13C-ion @ 73 MeV/u✗ 12C-ion @ 95 MeV/u

● High energy [GSI]: ✗ 12C de 292 MeV/u✗ 12C de 310 MeV/u

Prompt-γ experiments

Prompt-γ experiments: Setup

Setup● Collimated scintillators @ 90°● Target on a translation table

GANIL TOF measurements with BaF2 13/3

3

Prompt-γ experiments: 2-D TOF spectrum

● Broad prompt-γ spectrum● Time and energy window for better background removal

12C at 95 MeV/u

Longitudinal Position (mm)

Num

ber

o f g

amm

a /

ion

No selectionTime of flight (2-4 ns)

E. Testa et al., Appl. Phys. Lett. 93, 093506 (2008)

beam

Prompt-γ experiments: Feasibility studyPrompt-γ emission depth scans

12C at 95 MeV/u

Longitudinal Position (mm)

Num

ber

o f g

amm

a /

ion

No selectionTime of flight (2-4 ns)

E. Testa et al., Appl. Phys. Lett. 93, 093506 (2008)

beam

Prompt-γ experiments: Feasibility studyPrompt-γ emission depth scans

1st evidence with C-ion of correlation between prompt-γ emission and ion range

prompt-γ yield = 0.3 per C-ion (Edep

>2MeV)

Pulse Shape Discrimination – BC501

Prompt-γ experiments: Neutron study

GANIL

BC

501

BaF

2

Neutron uncorrelated in time and position with C-ions

No apparent range verification with n

18/33

Prompt-γ experiments: Neutron study

Outline of the talk




4. Measurements


6. Camera designs


8. TPS issues

GANIL – 13C@73 MeV/u (PMMA target)

Prompt-γ counting rate: simulations overestimate by a factor of ~ 12with Binary Cascade (BIC) nuclear collision model

F. Le Foulher IEEE TNS 2010


E>2 MeV

Prompt-γ simulations: Early comparisons

Monte Carlo toolbox Geant4 v9.1


Prompt-γ counting rate: simulations overestimate by a factor of ~ 12with Binary Cascade (BIC) nuclear collision model

F. Le Foulher IEEE TNS 2010


E>2 MeV

Prompt-γ simulations: Early comparisons

Monte Carlo toolbox Geant4 v9.1

A complete tuning (identification free parameters) of Geant4 nuclear models for hadrontherapy domain is required

3 stages:

Nuclear CollisionBinary Cascade, QMD, Bertini Cascade

EquilibrationPrecompound Model, Preequilibrium Model

DeexcitationMultifragmentation, Evaporation, Fermi Break-Up, PhotonEvaporation

Prompt-γ simulations: Geant4 nuclear model

QMD tuning is a complicated problem• Multiparameter• Some parameters have some degrees of freedom

(within physical constraints)• Not always easy to predict the influence of modifications

(dose, β+ emitters, other 2ndary particles...)• Not much documented• Ultimate check (Photon Yield in the Detector) is CPU demanding

2 'free' parameters have been identified for prompt-γ yield:● Cluster size● Particle wavepacket width

Prompt-γ simulations: QMD nuclear collision

G. Dedes unpublished 2011

● QMD cluster size has a straightforward influence:✗ Lower maximum distance ✗ Smaller clusters ✗ Smaller nuclei ✗ Lower excitation Energy ✗ Lower yields

● but there are some physical limits due to nucleons size and the impact on light fragment yield will have to be investigated

Prompt-γ simulations: QMD cluster size



Clear improvements but not sufficientG. Dedes unpublished 2011

Shape is better reproduced by QMD 2fm

As expected, increase in lighter fragments with decreasing clustering maximum distance



2ndary fragment distributions

Lighter fragments have lower excitation energies and produce less photons:

Prompt-γ spectrum change



Lighter fragments have lower excitation energies and produce less photons:

Prompt-γ spectrum change



Geant4 nuclear models are indeed tunable for the hadrontherapy domain. Further investigations are needed (HP neutrons, De-Excitation Handler, Photon Evaporation...)

Outline of the talk




4. Measurements


6. Camera designs


8. TPS issues

Collimated prompt-γ camera

M. Testa REBS 2010

Components:- Hodoscope: ion tagging (time and position) with scintillating fibres

(delayed stop signal)- Collimation: vertical slits (W)- Detectors: LYSO (start signal) - TOF: γ-n discrimination (resolution: 1ns)

Polychromatic prompt-γ spectrum (exponential fit)

Line segment prompt-γ source(to simulate the prompt-γ emission points along the ion range)

The collimator geometry is a trade-off between detection efficiency and spatial resolution (S=T=3mm)

Simulation set-up

M. Testa REBS 2010

Collimated prompt-γ camera: design

Q/2

22 mm

25 mm

28 mm

d

Q/2

M. Testa REBS 2010

Collimated prompt-γ camera: spatial resolution

3 detection profiles (shift 3mm) 11 detection profiles (shift 1mm)

Quantitative evaluation of the spatial resolution:

fit erf, error function (inflection point)

Spatial resolution RCam: minimum detectable shift in source edge displacement

Spatial resolution driven by the collimator (around 2mm for a 3mm slit)and by the number of detectors for a given FOV (detection solid angle)

( )DetCollCam RRfuR ,=

M. Testa REBS 2010

Collimated prompt-γ camera: spatial resolution

On-going work of F. Roellinghoff (PhD@CPO with IBA) of collimated and slit cameras

● Measured prompt-γ yields:

● ~ 2×10-7 γ ion-1 (1 detector, field of view ~ 3 mm)

● ~ 1 to 2×10-7 γ ion-1 · msr-1 · mm-1

● Typical carbon treatment : ● ~ 2×107 ions per energy slice (average)● ~ 4 γ for 1 slice in 1 detector 3mm x 5cm

● Multi-detector ● 25 crystals at a same FOV (depth)

→ size equivalent to GSI-PET

● Yield per energy slice:

● Along ion range ~ 100 counts / FOV

● Beyond ion range ~ 30 counts / FOV

→ resolution on Bragg peak position ~ 3 - 4 mm (MC simulations)

Pencil beam scanning

Collimated prompt-γ camera: clinical conditions

2ble scattering Compton camera: setup

M.-H. Richard TNS 2011

Compton cone completely defined by● 2 scattering + ● 1 partial absorption events

Fragmentation point reconstruction:

simple line-cone intersection

● incident C-ion: hodoscope● hypothesis: no straggling

M.-H. Richard TNS 2011

2ble scattering Compton camera: MC simulations

● TOF for (n + scattered-γ) background rejection:

no shielding

● Si-scatterer to limit Doppler broadening

● Point source (broad spectrum)

Prompt-γ energy spectrum

2ble scattering Compton camera: FWHM

True events

Edep

< 2MeV

e- escape from the 1st scatterer (MIP)

FWHM 6mm

FWHM 30mm

Bad events

2ble scattering Compton camera: FWHM

True events

Edep

< 2MeV

e- escape from the 1st scatterer (MIP)

FWHM 6mm

FWHM 30mm

Bad events

Spatial resolution (6mm) acceptable but low detection efficiency (10-5)

Scatterer stack Compton camera: setup

F. Roellinghoff NIMA 2011

Based on MC simulations: from all events in the absorber, 75% correspond to total absorption in a 1in LYSO for a typical prompt-γ spectrum

● most single scattering events are reconstructible● higher detection efficiency for the same scatterer equivalent Si-thickness


Scatterer stack Compton camera: simulations

● 10 Silicon strip detector (2mm thickness)● 1in LYSO absorber● Point source (broad spectrum) at 10cm from the 1st scatterer● Line-cone reconstruction


Scatterer stack Compton camera: PSF

Spatial resolution (8.3mm) still acceptable and higher (x25) detection efficiency (2.5x10-4)

Scatterer stack Compton camera: Proton beam

Detection Efficiency

FWHM

scatterer limitscatterer limit

FWHM and DE deteriorate when the lateral position of emission

point along the ion range is away from the camera center

Study the influence of the fragmentation point lateral position(Compton camera centered in front of Bragg peak)

160MeV proton beam upon a water phantom (9x9x20 cm3)

Scatterer stack Compton camera: p@160MeV

Reconstructed pointsEmission points

Comparison of γ profiles

Reconstructed profile:

PSF(pos)

*[D

E(pos) x prompt-γ_profile]

Scatterer stack Compton camera: p@160MeV

Reconstructed pointsEmission points

Comparison of γ profiles

Reconstructed profile:

PSF(pos)

*[D

E(pos) x prompt-γ_profile]

More advanced Compton reconstruction techniques are required

Angular Resolution Measure

Scatterer stack CC by-product: SPECT imaging

M.-H. Richard unpublished 2011

Reconstruction algorithm necessary (no hodoscope)

Detection efficiency:● 0.05% @ 300keV● 0.1% @ 511keV● 0.09% @ 1MeV

Proton Vertex Imaging for C-ion beams

Idea:Use 2ndary protons to monitor the C-ion range

Is the proton Statistics high enough for ion-range monitoring?

P. Henriquet PhD 2011

Secondary proton detection

[GANIL]

Experimental detection rate :2.41 x 10-5 proton/12C/msr

Simulated detection rate (Geant4) :2.51 x 10-5 proton/12C/msr

Proton Vertex Imaging: Measurements


Good agreement (~4%)

20 °

10 cm Tracker

p12C

Proton Vertex Imaging: 1st simulated setup


● C-ion@200MeV/u● 10cm PMMA target● Si-tracker @ +/-20° Trade-off between proton straggling (minimum at 0°) / reconstruction uncertainty (minimum at 90°)

Incident 12C(beam hodoscope)

Reconstructed vertex Segment S (of lenght d)

Single mode

Coincidence mode

Reconstruction modes:

● Single (with hodoscope)● Coincidence

Proton Vertex Imaging: 1st simulated setup


Single

Coincidence

Depth (mm)

C-ion@200MeV/u10cm PMMA target

Statistics:106 primary C-ion

Single coincidence: higher statistics and better ion range discrimination

Depth-vertex profiles

Proton Vertex Imaging: "Clinical" setup


Target:● 3mm cranium bone● 25cm sphere (cervical tissue)

2 Detector pairs:● Pixellated Si-planes (10x10cm2)● +/-20° angle @ 30 & 35 cm

12C-ion beam:● 100 to 300MeV/u● 106 primary particles

(NB: about 107 C-ion / energy slice for 1GyE in a 120cm3 tumor volume)



Depth (mm)

Reconstructed vertices

Generated vertices

Depth-Vertex profiles

Reconstructed vertex profile drop is correlated to ion range [150 - 300MeV/u]



Depth (mm)

Reconstructed vertices

Generated vertices

Depth-Vertex profiles

Reconstructed vertex profile drop is correlated to ion range [150 - 300MeV/u]

Proton vertex imaging is a promising technique. Further investigations are needed

Outline of the talk




4. Measurements


6. Camera designs


8. TPS issues

3D Compton reconstruction

Analytical inversion formula Iterative List-mode Maximum Likelihood Expectation-Maximization

(LM-MLEM)

Status:● Line-cone reconstruction simple but limited● Hodoscope must be available (pb for SPECT)

2 research themes are investigated:

Analytical 3D Compton reconstruction

V. Maxim Inverse Problems 2009

Compton projection Pf definition:

V. Maxim Inverse Problems 2009

Inversion formula:


Fourier transform of the 2D Radon transformof the Compton projections

Exact Analytical inverse Compton transform exists!

Bessel function

Scattering probability


● Point γ source● Broad spectrum● 1.3 x 105 events

NB axial = plane normal to the beam

Real detector(energy and spatial resolutions)

Ideal detector (Δx=ΔE=0): projections truncation artefacts

Axial slicesTransverse slices

Application to the proposed scatterer-stack Compton camera

No axial resolution with the scatterer-stack Compton camera setup

FWHM = 6mm(transverse)


● Point γ source● Broad spectrum● 1.3 x 105 events

NB axial = plane normal to the beam

Real detector(energy and spatial resolutions)

Ideal detector (Δx=ΔE=0): projections truncation artefacts

Axial slicesTransverse slices

Application to the proposed scatterer-stack Compton camera

No axial resolution with the scatterer-stack Compton camera setup

FWHM = 6mm(transverse)

Limited applicability with one single CC(use as initialisation of an iterative reconstruction)

Outline of the talk




4. Measurements


6. Camera designs


8. TPS issues

TPS: Prior computation of detector response

The real-time monitoring (feedback loop) should be carried at the detector level

The detector signature must be pre-computed from the optimized DICOM RT-plan

Simple distance measures must be developped to trigger the feedback loop

Robustness issues must be taken into account

TPS needs:● a flexible optimization inverse planning SW● to optimize at the same time entry channels & fluences w.r.t.

● the prescribed dose,● plan uncertainties,● the way the ion range will be monitored

Development of a Genetic Algorithm-based TPS

Genetic Algorithm-based TPS

F. Smekens PhD 2011

OAR PTV

C-shape model

3000 beams after10000 generations

50 initial beams

● Continuous coding (angles and target points)

● Variable length (nr of beams)

128x128x107 voxels (1mm)


F. Smekens PhD 2011

Application to CT data

200 beams (random pos+ang)

3000 beams (14000 generations)128x128x107 voxels (1mm)


F. Smekens PhD 2011

Application to CT data

To do: include robustness and monitoring issues

Conclusions

Collaborators: IPNL: M. Bajard, M. Chevallier, D. Dauvergne, G. Dedes, S. Deng,

P. Henriquet, J. Krimmer, F. Le Foulher, C. Ray, M.-H. Richard, E. Testa, M. Testa

CREATIS: N. Freud, X. Locajono, V. Maxim, R. Prost, F. Roellinghoff, F. Smekens

Research program supports:● PRRH ETOILE (CPER 2007-2013)● GDR MI2B (CNRS-IN2P3)● Project ANR Gamhadron (2010-2013)● FP7 Collaboration project ENVISION (2010-2013)● FP7 ITN project ENTERVISION (2011-2014)

Real-time monitoring of ion-range seems accessible, several solutions are being investigated, but many developments are still required before translating to clinic.

Documents

Real-time monitoring of ion rangespeople.na.infn.it/.../Erice2011/TalkContributions/Letang.pdf · 2011-05-25 · Real-time monitoring of ion ranges J.M. Létang on behalf of IPNL