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www. ati.ac.atRadiation Physics
Radiation Physicsat ATI TUW and MedAustron
Lembit Sihver
TU Wien, AtominstitutUniv.Prof. of Medical Radiation Physics with Specialization in Ion Therapy
Head of Radiation Physics
EBG MedAustron GmbHHead of Applied Medical Physics Research
Content1. Major Research Areas Until Now… 2. Radiation Physics at Atominstitut, TU Wien3. Planned Main Research Projects at MedAustron
I. Studies of nuclear reactions, LET, lineal energy and dose distributions Measurements
MC particle and ion transport simulations
I. High LET radiation effects on DNA
II. Range verification using PET
4. Summary
Radiotherapy
Physics Modelling & Measurements for Beam Transport
& Treatment Planning System
Space DosimetryNuclear Power
Dose in the Atmosphere, ISS and Deep Space
Detector Development,Material Research,
Severe Nuclear Accidents, etc.
Short background
My main research areas through the years:
Radiobiology
DNA Damage
Particle and Ion Transport Simulations
Radiotherapy
Physics Modelling & Measurements for Beam Transport
& Treatment Planning System
Space DosimetryNuclear Power
Dose in the Atmosphere, ISS and Deep Space
Detector Development,Material Research,
Severe Nuclear Accidents, etc.
Short background
My main research areas through the years:
Radiobiology
DNA Damage
Particle and Ion Transport Simulations
Ion Beams in Radiotherapy
Responsible for developing models & codes for , dE/dx momentum, loss ‐> depth dose, energy, fluence, LET, dose‐averaged‐LET, track‐averaged‐LET distributions
Biological Dose = Physical Dose X RBE
Sihver & Kanai model
NIRS: National Institut for Radiological Sciences, Chiba, Japan
NIRS: 1991-1993First long-term non asian fellowship
Start of the construction of HIMAC: Heavy Ion Medical Accelerator in Chiba.
Sihver & Kanai model used in the TPS for cancer treatment from 1994 when HIMAC started to treat patients.
The model was also used in the other facilities in Japanand China, which followed HIMAC.
GSI: Gesellschaft für Schwerionenforschung
GSI: 1993-1994Visiting Scientist in the Biophysics Group lead byProf. Kraft
Prof. Kraft
GSI started carbon ion therapy 1997
Radiotherapy
Physics Modelling & Measurements for Beam Transport
& Treatment Planning System
Space DosimetryNuclear Power
Dose in the Atmosphere, ISS and Deep Space
Detector developmentMaterial Research, etc.
Short background
My main research areas through the years:
Radiobiology
DNA Damage
Particle and Ion Transport Simulations
Particle and Heavy Ion Transport code System
PHITS
All contents of PHITS (source files, binary, data libraries, graphic utility etc.) are fully integrated in one package
All contents of PHITS (source files, binary, data libraries, graphic utility etc.) are fully integrated in one package
All-in-one-Package
OECD/NEA Databank, RSICC (USA, Canada) and RIST (Japan)
Applications
Accelerator Design Radiation Therapy & Protection Space & Geoscience
CapabilityTransport and collision of nearly all particles over wide energy range
in 3D phase spacewith magnetic field & gravity
neutron, proton, meson, baryon electron, photon, heavy ions
10-4 eV to 1 TeV/u
Particle and Heavy Ion Transport code System
PHITS
All-in-one-Package
OECD/NEA Databank, RSICC (USA, Canada) and RIST (Japan)
Applications
Accelerator Design Radiation Therapy & Protection Space & Geoscience
Capability
in 3D phase spacewith magnetic field & gravity
neutron, proton, meson, baryon electron, photon, heavy ions
10-4 eV to 1 TeV/u
PHITS-shaped water phantom irradiated by 1 GeV proton
Event generator mode: all secondary particles are specified
IonizationSPAR or ATIMA
Neutron Proton, Pion(other hadrons) Nucleus e- / e+
QuantumMolecularDynamics(JQMD)
+Evaporation
(GEM)
Muon
EGS5
or
Atomic Data
Library(EEDL /ITS3.0 /
EPDL97)(~10GeV)
Photon
1 TeV 1 TeV/n
1 keV
10 MeV/n
1 TeV
1 keV 1 keV
Photo-Nuclear
JAM/QMD
+GEM
+JENDL
2 MeV
Low
←
En
ergy
→
H
igh
*Switching energies can be changed in input file of PHITS
Intra-nuclear cascade (JAM)+ Evaporation
(GEM)
Nuclear Data Library(JENDL-4.0)
20 MeV
10-5 eV
1 MeV
3.0 GeV
Intra-nuclear cascade (INCL4.6)+
Evaporation (GEM)
d
t
3He
Map of Models used in PHITS
Virtual Photo-Nuclear
JAM/JQMD
+GEM
200 MeV
EGS5
or
AtomicData
LibraryJENDL-4.0/ EPDL97
(~100GeV)
Physics models of PHITS and their switching energies*
Radiotherapy
Physics Modelling & Measurements for Beam Transport
& Treatment Planning System
Space DosimetryNuclear Power
Dose in the Atmosphere, ISS and Deep Space
Detector developmentMaterial Research, etc.
Short background
My main research areas through the years:
Radiobiology
DNA Damage
Particle and Ion Transport Simulations
Personal dosimetry(EuCPD)
Phantom experiments(e.g. MATROSHKA)
Area monitoring(DOSIS-3D)
Radiation Measurements at the ISS
WPL for TU Wien, Austria: PI: G. Reitz, DLR, GermanyL. Sihver WPL for simulations and analysis:
L. Sihver
DOSIS-3D: 3D Radiation Map of the whole ISS
DOSIS-3D: Inside the Columbus module of ISS
Launch: 29. January 2004
MATROSHKA 1 Experiment
Docking: 31. January 2004EVA: 26. February 2004Exposure time outside: 539 days
MTR-1 / MTR-2A / MTR-2B
MTR-2 KIBO
MATROSHKA: From “Russia to Japan” Effective dose equivalent rates [mSv/day]MTR-1 MTR-2A MTR-2B
ICRP 1991ICRP 2007
0.690 +/ -330.722 +/- 35
0.549 +/- 270.552 +/- 26
0.566 +/- 290.566 +/- 27
Compare with average natural background radiation on Earth: 2.4 mSv/year
WPL for Austria for MTR-3, which will be launched 2018:L. Sihver
The aim of OrionDOS is to measure the spatial distribution of the radiation environment inside the Orion capsule during the mission.
TL for Austria for OrionDOS for ORION Exploration Mission 1 (EM-1), 2018 (25-day unmanned flight around the moon): L. Sihver
OrionDOS for ORION EM-1
Chalmers
MATROSHKA-R and “Protective Curtain” Altea, Alteino, SilEeyProject lead: V. A. Shurshakov Project leads: M. Casolino and L. Narici
Institute of Biomedical Problems (Russia) l'Università di Roma Tor Vergata (Italy)
Simulations of many experiments inside and outside ISS
The Alteino detector (AST) on board theISS
DNA Dosimeter Tissue-equivalent dosimeter for mixed radiation fields, e.g. in space
Short DNAQuencher(TAMRA)
When there is a breakage on the DNA, the fluorescence light is emitted and can bemeasured with a fluorometer
Fluorescencemodulator (6-FAM)
ggggg Fluorescence Resonance Energy Transfer (FRET)
Excitations Source
Excitations Source
γ, e-, p, ion
Y. Matuo, ….L. Sihver, and N. Yasuda, Radiatt Environ. Biophy. (submitted).
Assumptions:1. No. broken molecules is proportional to dose2. PFRET is not a function of dose
www. ati.ac.at
NuclearChemistry
RadiationChemistry
X-raxPhysics
Radiation Radiation Protectionin Space and on Earth
Archaeomeryand
Environmental Analysis
L. Sihver C. Streli S. Ismail K. Poljanc A. Musilek J.H. Sterba J. Welch M. Rauwolf J . Prost M. Puchalska H. Rohling A. Hirtl K.P Brabcova A. Turyanskaya H. Böck I. Pradler
Medical Radiation Physics
MedAustron
YES!WE CARE
Technicians andProj. Engineers
+ project workers, BSc & MSc and PhD students
Material Characterisation
MethodDevelopement
TUW – Radiation PhysicsHead – Lembit Sihver
Professors, Assistants, Lectures and Project Staff
Emeritus and Assignedat MedAustron
P. Wobrauschek
Experiments
RadiationPhysics
Radiobiology
Radiation Chemistry
Simulations
Nucleus-Nucleus Inelastic Cross Sections
Total reaction (σ)Differential (dσ/dE)Double Differential (d2σ/dEdΩ)
•
Treatment Planning System (TPS)
We need to follow the primary particles and the produced secondary particles from start/ejection energy down to total stopping.
In each voxel we need to know:
1. The total energy deposition.2. How much energy leaves the
voxel to other places inside the patient.
1. How much energy escapes the patient.
We are developing the cross section part of the RayStation carbon ion TPS!
New mixed radiation field inside the patient´s body!
New mixed radiation field inside the patient´s body!
projectile
target
projectile fragments
target fragments
For the therapy we have to know all interaction events,i.e. particles (all generations) fluences vs. energies, and angles.
Interaction of the radiation withthe material in the beam line, incl. tissue and organs in the body... Target Fragments Projectile fragments
… lower charges … lower charges than target than primaries
… high LETs … mixed LETs … short ranges … long ranges
Nuclear reactions
I. Pshenichnov
Carbon ion therapy: 120 - 400 MeV/u
Caused by projectile fragments
High-energy carbon beam stopping in water
Projectile
FragmentsHow do we calc. thecollision distance d ?
Where will the reaction occur ?
Target
Transport Calculations of Nucleus in Matter
Projectile
Fragments
Target
Collision distance D–ln(r)
D = –––––Σt
r: random numberΣt: total macroscopic cross sections = σR ρA [1/length]ρA = density of atoms in the target [1/volume]
Transport Calculations of Nucleus in Matter
Fragment spectrum
Beam
Si and Si Strip Detector Array
50 mm x 50 mm x 500 μm thStrip width 1 mm
CsI(Tl) Array thicknesses of 4.5, 6.5, 8,
10, 10, 12, 15 mm
Beam
Front View
Large Volume
of Scintillator
Covering Large Solid Angle of ~3.6 Sr(+/- 35 º horizontal and vertical)
Energy Measurements and Particle ID for Fragments Si (ΔE) – CsI(Tl) E Counter Telescope
Angular Measurements e.g. Si Strip Detectors (x and y)
Large Solid-Angle Counter telescope Ideal setup for measurements of
σR, multiplicities and momentumdistributions
Simultaneous measurements of σR, dσ/dE, and d2σ/dEdΩ!!
ReactionTarget
Beam Counter
Setup of σR, dσ/dE and d2σ/dEdΩ measurements for ion beams
Side View
This Setup allows Precise Measurements of σR based on Transmission Method by ΔE - E
Counter Telescope covering large solid angle of 3.6 Sr (+/- 35 º H. & V.). Reconstruction of Energy and Particle Identification of Pile-up Events
(Multi-hit Analysis).
Reaction Target
Detector Array
Pile-up EventsDetectors hit by more than 1 fragments at the same time.
Multi-hit Analysis
Array of relatively thin scintillators allow fragments stop at different detectors.
Longer-range fragmentcan be measured as a single event
using the latter part of detector array.
Reconstruction of shorter-range fragment’s PID and E by subtracting
information of longer-range fragment.
Multi-hit AnalysisImportant for determining dσ/dE
Setup of σR, dσ/dE and d2σ/dEdΩ measurements for ion beams
+
CsI(Tl) scintillators withlight guides and PMTs
NaI detector
Si detectors
Experimental Setup for Simultaneous Measurements of σR and dσ/dE has been tested at HIMAC 2015 - 2016
L. Sihver and Takechi, Cross section measurements for improvement ofTPS for ion beam therapy”. 55th Annual Conference of the PTCOG, Prague, Czech Republic, May 22-28, 2016.
Ion beam tracks Uniform dose distribution
Non-uniform dose distributions
Ion Track StructureRelative Biological Effectiveness (RBE) depends on the ion track structure (and many other things)– LET is not enough!
α-particles, 2 MeV Fe-ions, 1 GeV/u
Light vs. Heavy Ions at the same LET (140 keV/mm)
LET∞: Transferred energy within a certain distance SAMEy: Transferred energy within a certain volume DIFFERENT
Timepix3 can give the dE/dx in Si for each particle.Spatial resolution for vertically incident tracks is better than 50 µm -> information about energy spread.
Hybrid Pixel Detectors
Measurements with the Timepix3 detector at HIMAC
Timepix3 in Space
Also used by NASA at the ISS and on EFT-1 on Dec. 5, 2014
Etching and AFM analysis conditions
- Etching: 7 N NaOH 70 °C, 0.5hrB=0.974 µm (ave)
- AFM: - Tapping mode- Scan size : 25 μm x 25 μm - Resolution: 1024 x 1024 - Scan rate: 1.5 Hz- Scan image: 100 images
- PitFit: Manual analysis
Dose contribution from target fragments from 160 MeV proton beam in CR-39 (C12H18O6)*.
Measurements performed in the BIO Room at HIMAC
Dose from secondary particles measured by optical microscopy is ≈ 60 % lower than that measured by AFM, since AFM can measure short tracks in PNTDs after substantially less bulk etch.
Measurements of target fragmentation using e.g. PNTD
Optical Microscopy AFM (15 µm etch) (1 µm etch)
ThMeasurements of target fragmentation using e.g. PNTD
AFM analysis has a distinct advantage over optical microscopy analysis for measuring the LET of such tracks.
The same technique can be used to measure dose from n!
Absorbed dose contribution from target fragments is only ≈ 1% of the primary proton dose, but:
Target fragments -> ≈ 20 % additional dose equivalent to that ofthe primary proton beam!!
This contribution is not measured by conventional ionization chambers and is usually not accounted for in treatment planning!!
*S. Kodaira, T. Konishi, H. Kitamura, M. Kurano, H. Kawashima, Y. Uchihori, T. Nishio, N. Yasuda, K. Ogura, L. Sihver and E.R. Benton, NIM B 349, 163-168 (2015).
Characterization of the TLD/OSLD for available proton and carbon beams.
Measurements of dose and LET distributions (from primary and secondary particles) from available primary proton and carbon beams in an anthropomorphic phantom undergoing a typical radiotherapy.
Comparison of measurements with MC simulations and RayStation TPS.
In the future extend the measurements to helium and oygen beams, when these beams will be available.
PTV
Bilski et al. 2016 (doi:10.1016/j.radmeas.2016.02.029) Puchalska et al. 2014 (doi:10.1007/s00411-014-0560-7)
3D dose distributionDetector characterization
Measurements of dose and LET distributions using PNTD & TLD/OSLD
supercoiled, pBR322
(E. coli cloning vector with 4361 base pair)
plasmid DNA
gamma 60Coprotonsheavy ions
direct action
H2O
indirect action
nnn
nnn
nnn
K. Pachnerová Brabcová, L. Sihver, O. Ploc, M. Davídková, L. Pinsky and Y. Uchihori, 12th Int. Workshop on Radiation Damage to DNA, Prague, Czech Republic, June 2-7, 2012.
K. Pachnerová Brabcová, V. Štěpán, L. Sihver, S. Incerti and M. Davídková, MICROS 2013 16th International Sympoisum on Microdosimetry, Treviso, Italy, October 20-25, 2013.
K. Pachnerova Brabcova, L. Sihver, N. Yasuda, Y. Matuo and T. Murakami, the NIRS 2013 Annual Report of the Research Project with Heavy Ions at NIRS-HIMAC, NIRS, 2014.
K. Pachnerová Brabcová, L. Sihver, V. Štěpán and M. Davídková, XXXVIth Days of Radiation Protection, Slovakia, November 10-14, 2014.
K. Pachnerová Brabcova, L. Sihver, N. Yasuda, Y. Matsuo V. Štěpán and M. Davídková. Radiat. Environ. Biophys. 53, 705-712, 2014.
K. Pachnerová Brabcová, V. Štěpán, M. Karamitros, M. Karabín, P. Dostálek, S. Incerti, M. Davídková, and L. Sihver, Rad. Prot. Dos. 1-5, 2015.
K. Pachnerova Brabcová, L. Sihver, Humans in space Symposium, Prague, Czech Republic, June 29 - July 3. 2015.
K. Pachnerová Brabcová, L. Sihver, V. Štěpán, M. Davídková: XXXVII Days of Radiation Protection, Mikulov, Czech Republic, 9-13 November, 2015.
Correlation of radiation, radical production and DNA Damage
OH eaq‐ H H2 H2O2 H3O+ ...
supercoiled, pBR322
plasmid DNA
gamma 60Coprotonsheavy ions
direct action
H2O
indirect action
nnn
nnn
nnn
Correlation of radiation, radical production and DNA Damage
MethodsAGE and AFMEnzymatic treatmentHPLC coupled with fluorescent detector
OH eaq‐ H H2 H2O2 H3O+ ...
supercoiled, pBR322
plasmid DNA
coumarin‐3‐carboxylic acid
radical scavengers
glycyl glycine
dimethyl sulfoxide
gamma 60Coprotonsheavy ions
linear
fragments
direct action
SSB
DSB
SSBDSB
circle
SSB
SSB
H2O
indirect action
oxidative bases
Nth
Fpg
more SSB, DSB
nnn
nnn
SSBDSB
nnn
7‐OH‐C3CA
Correlation of radiation, radical production and DNA Damage
Plasmid in solution:
Great simplified model of DNA in the cell, only without repair processes primary DNA damage
Solutions with controlled level of hydroxyl radical (scavengers)
Application of enzymes (Fpg and Nth) involved in reparation process of base damages(purines – Fpg, pyrimidines – Nth)
Electrophoresis: detection of separated plasmid forms
Unfortunately, we not not see short DNA fragments!
Correlation of radiation, radical production and DNA Damage
Agarose gel electrophoresis
AFM images to see short fragments Optimization of DNA concentration All plasmid forms and fragments
can be seen AFM by Bruker – tapping mode
Imaging with Atomic Force Microscope (AFM)
Image segmentation - isolation of pixels which describe DNA molecule
Fragmentation of plasmid DNAinduced by gamma radiation
(c)
(b)
(e)(a)(d)
(a) Heavy ion beam
(b) Ionization chamber
(c) Irradiation area (10 cmΦ)
(d) Binary filter (PMMA)
(e) Sample quartz cells
Production of a Fluorescence Probe in Ion-beam Radiolysis of Aqueous Coumarin-3-carboxylic Acid Solution….”,T. Maeyama, .. L. Sihver,.. Katsumura, Rad. Phys. Chem. 80, 1352-1357 (2011).
Measurements of Radicals Yields at HIMAC
Range uncertainties
The advantage of using charged particles for radiotherapy is that they stop at a certain depth…
Range uncertainties
… the disadvantage of using charged particles for radiotherapy is that we don´t always know where!…
Range uncertainties In-vivo dosimetry motivation
“Forgiving” Not “forgiving”
Establish a software package for range monitoring of ion-beam therapyusing PET at MedAustron.
Adjustment, implementation, or development of all modelling and analysing steps, incl.the decay of the β+- emitters and the washout, required for the range varication using off-line PET.
Setup and improve the PET simulation based on treatment plans.
Measure the production yields of β+- emitting nuclides with PET using activated targets.
Model the production of β+- emitters resulting from 4He beams.
Range Verification using PET at EBG MedAustron
Philips Gemini TF Big Bore PET/CT
Summary – Planned Research at MedAustron1. Studies of nuclear reactions, LET & lineal energy distributions,
and dose distributions Measurements MC particle and ion transport simulations Needed for TPS, transport simulations, radiation dosimetry and
shielding in space, and better understanding of nuclear physics.2. High LET radiation effects on DNA
Complex DNA damage is a precursor of genomic instability and carcinogenesis and a simple/reliable endpoint to measure biological radiation damage.
3. Range Verification using PET Protons & carbon ions have sharp Bragg Peaks #
Range verification needed!