Radiation Physics at ATI TUW and MedAustron - … · Radiation Physics www. ati.ac.at Radiation...

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

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





Detector developmentMaterial Research, etc.

Short background


Radiobiology

DNA Damage


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





Detector developmentMaterial Research, etc.

Short background


Radiobiology

DNA Damage


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


direct action

H2O

indirect action

nnn

nnn

nnn


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


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


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!


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!

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