Linh T. Tran1, L. Chartier1, D. A. Prokopovich2, D. Bolst1, S. Guatelli1, M.
Petasecca1, M. I. Reinhard2, M. L. F.Lerch1, N. Matsufuji3, Benjamin Clasie4,Chris Beltran5, V. L. Pereverlaylo6, and A. B. Rosenfeld1

1Centre for Medical Radiation Physics, University of Wollongong, NSW

2Australian Nuclear Science and Technology Organization, Australia

3Research Centre for Charge Particle Therapy, National Institute of Radiological Science, Japan
4Massachusetts General Hospital, MGH, Boston, USA
5Mayo Clinics, Rochester, Minnesota, USA
6SPA, BIT, Kiev, Ukrainedensely ionising

Relative dose

Relative dosesparsely ionising

mainly indirect DNA damage mainly direct DNA damage
irreparable DNA breaks

relative biologicalTumor
effectiveness:
RBEγ=1
RBEprotons= 1.1
Depth

IncreaseTumorof biologicaleffectivenessRBEcarbon= 2-4→ Radioresistant tumours!
Depth

HIMAC (Japan)
 Passive beam
 RBE values are derived
from in vitro
experimental data in conjunction with clinicalneutron experience and Microdosimetric Kinetic
Model - MKM).
 RBE estimation at HIMAC is independent ofthe tumor type

GSI (Germany)[1] O. Jäkel et al Technology in Cancer Research &Treatment, ISSN 1533-0346 ,Volume 2, Number 5,October (2003)[2] O. Steinsträter et al “Mapping of RBE-weighted doses
between HIMAC- and LEM-based treatment planningsystems”[3] N. Matsufuji et al Specification of Carbon ion dose atNIRS, JRS 2007.

 Scanning beam
 RBE values for planning were estimated using
Local Effect Model – LEM)
 RBE estimation are based on photon dose
response curves under the cell lines

Microdosimetry and Dose EquivalentMicrodosimetry◦ Lineal energy:

where E is the energy deposited in the cell and , <l>= average chord distribution◦ Microdosimetric spectra of a radiation field, (i.e. y2f(y) vs log(y))◦ Dose Equivalent : H= 𝐷 𝑄(𝑦)𝑦 2 f(y)d(log(y))

Image from Garret and Grisham, "Biochemistry"
Copyright 1995 by Sauders College Publishing

Biological Cell (um)Tissue Equivalent Proportional Counter Spherical SVin shape Tissueequivalency

5-10cm Large size of
assembly which reduces
spatial resolution andintroduces wall effects
 Can not measure anarray of cells.
High voltage appliedResearch strength of the University ofWollongong
Research to improve radiotherapy
treatment◦ New radiotherapy methodologies (e.g. use ofnanoparticles)◦ New QA instrumentation for X-ray radiotherapy,
brachytherapy, charged particle therapy

Development of detectors for radiation
protection in nuclear facilities, aviationand space missions

MOSkin, real time dosimetry

Magic Platein-vivo and realtime
Fluence verificationin RapidArc andIMRTTechnology
SOLUTIONS

Excellence inEDUCATIONANDRESEACHImage from www.visitsouthcoast.com.au

A/ProfProf Anatoly
Michael Lerch
Rozenfeld
Founder and Director

Karen FordAdmin Officerand PA

Dr Susanna
Guatelli

Dr GeorgeTakacs

Dr MitraSafavi-Naieni

Dr LinhTran

Dr IwanCornelius

Dr Yujin Qi

Prof PeterMetcalfe

Dr Elise Pogson

Dr Dean
CutajarDr MichaelWeaver

Dr Moeava
Tehei

Dr Marco
Petasecca

Dr Engbang LiDr
Alessandra
Malaroda

CMRP Proton and Heavy Ion Therapy Team

AnatolyDavid

LachlanJacinta
StuartSilicon Microdosimeter

Tissue Equivalent Proportional Counter

3mm4mm5-10cm Spherical SV  Large size ofin shape
assembly which
 Tissue
reduces
equivalency
spatial resolution
and introduces walleffects
 Can not measure
an array of cells.
High voltage
applied Can measure an arrayof cells
Micron sized SV Provide true
microscopic SV
 Compact size and low
voltage for operation
 High spatialresolution.

 Tissueequivalence need
to be considered &corrected whengenerate
microdosimetric
spectra .

Radiotherapy

Proton and Carbon Ion therapy
Fast Neutron Therapy
BNCT

Radiation protection

Separate varying LET
components
Measure dose due to 10B
neutron capture and total
doseRadiation Research: March
1999, Vol. 151, No. 3, pp. 235243.

Third generation-VAl10µm-V-Vp+n+p+n+p+

SiO2nSOI
SOI devices - large area 4x5 mm2
segmented microdosimeters withseparated cylindrical 2D planar SVs(10 µm in diameter), Fabricated on 10 µm thick n-SOI anddemonstrated a 100% yield of working
SVs
Charge sharing between SVs which isleading to excessive deposition of low
energy events. [J. Livingstone et al2012]

Figure 1. Top and side-on schematic of asensitive volume

Area of whole chip : 3.6 x 4.1mm2; 4320 cells

oddeven

Etched regionAl contacta) Array of sensitive volumesb) Cross-section image of SV

5.5MeVHe2+Purpose: Study the charge collection
properties of the SVs in 3D mesabridge microdosimeter.

Beam focal diameter: 1𝜇m

Ion

Energy (MeV)

Entrance LET in Si(keV/μm)

Range in Si (μm)

1H

2.0

26.09

47.69

4He

5.5

133.4

28.02

[] R. Siegele, D. Cohem, and N. Dytlewski, ―The ANSTO high energy heavy ion microprobe, Nucl. Instrum. Methods
Phys. Res. B, vol. 158, pp. 31–38, 1999.

3rd generation
microdosimeter

3D Mesa-Bridgemicrodosimeter

Energy spectrum and median energy map showing the spatial distribution of energy
deposited by 5.5 MeV He+ ions in the SVs of the odd and even arrays. The detector
was at -10 V

By Geant4 simulations

 Geant4 handles:◦ Complex geometries and materials◦ Particle tracking◦ Physics processes◦ Detector response◦ User interface◦ Visualisation of the experimental set-up◦ Variance reduction techniques◦ Analysis tools

Geant4 20th Anniversary Symposium & 19th Collaboration
Meeting, September 29th - October 4th, 2014 Okinawa, Japan

Katsuya Amako, Koichi Murakami, Takashi Sasaki



CMRP is a Member of the Geant4 Collaboration
since 2002



Validation of physics models

Development of Geant4 advanced examples◦ Brachytherapy◦ Radioprotection◦ Human phantom

2nd Geant4 School andMonte Carlo Workshop,CMRP, UOW, April 2013

Member of the Geant4 Low Energy Group, Geant4DNA and Geant4 Advanced examples groupGeant4 user support

Organiser of Geant4 schoolsDosimetry(macroscopic scale)Absorbed dose
Linear energy transfer(LET)/Stopping power

Microdosimetry(cellular scale)Specific energy
distributions
Lineal energy distributions

Nanodosimetry(DNA scale)
Spatial distribution ofinteractions on a nanometre
scale to estimate biological
25effectivenessSlides adapted fromMarc Marc Verderi, LLR – Ecole Polytechnique, France
Sebastien Incerti, CENBG, Bordeaux, FranceEM physics
“standard” processes valid from ~ 1 keV to ~PeV“low energy” valid from 250 eV to ~PeV

Down to eV for Geant4-DNA in liquid water

optical photons

Weak interaction physics
decay of subatomic particlesradioactive decay of nuclei

Hadronic physics
pure strong interaction physics valid from 0 to ~TeVelectro- and gamma-nuclear valid from 10 MeV to ~TeVParameterized or “fast simulation” physics
27Standard : Complete set of processes
covering charged particles and gammas.
◦ Energy range 1 keV - ~PeV

Low Energy : More precise description at
low energy for e+, e-, g, charged hadrons
incident particle.
◦ More atomic shell structure detail◦ Some processes valid down to hundreds of eV◦ Down to eV scale for Geant4-DNA◦ Two alternative flavours:

Based on Livermore Evaluated data Libraries

Penenope MC code models

Atomic de-excitation◦ Fluorescence and Auger electrons

K. Amako, S. Guatelli, et al, "Validation of Geant4
electromagnetic physics versus the NIST
databases", IEEE Trans. on Nucl. Sci., vol. 52 (4),2005, pp. 910-918.
28

Main Models

High Energy
Quark/gluon
dominating behavior

Intermediate Energy
Nucleon dominating
behaviorl

String Models:E > 20 GeV
Quark Gluon
String,Fritiofl

Intra-Nuclear
Cascade Models: 170 MeV - 20Binary, GeV
Bertini
Precompound

Low Energy
Nucleus dominating
behaviorlFission /evaporation E < 170 MeV
Capture at rest
Radioactive decay

Partial Hadronic Model Inventory
At restabsorption, ,, K, anti-p

Photo-nuclear, electro-nuclear
Electro-nuclear dissociation

Radioactivedecay

QMD (ion-ion)High precision
neutronEvaporation
Fermi breakup
Multifragment
Photon Evap

Wilson Abrasion
Precompound

Quark Gluon string

Binary cascade
Fritiof string
Bertini-style cascade

1 MeV 10 MeV 100 MeV 1 GeV 10 GeV 100 GeV 1TeV12

Measure energy deposition in Si cylinder modelling microdosimeterin 290 MeV/u 12C radiation field

Find size of water cylinder that matches the energy deposition in Si◦ Described in (S. Guatelli et al IEEE Trans on Nuc. Sci, 55, 3407-3413(2008); P.Bradley at al Med.Phys. )◦ Correction factor =0.53CMRP collaboration with NIRS, Japan(Prof. Matsufuji et al)

http://www.nirs.go.jp/ENG/research/charged_particle/index.shtml

290MeV/u 12C SOBP Irradiation
Experiment in PMMA phantom

3D Mesabridge MD
connected topreamplifier
and electronics

Purpose: observe detector response with therapeutic
12C beam, determine RBE in PMMA, and measure
biological dose distribution.
Passive beam delivery: lead scatterer, ridge filter andcollimators produce a 10x10 cm2 field, 6cm SOBP,
290MeV/uDose-mean lineal energy deposition and microdosimetric spectra
obtained along the SOBP

y0=150keV/um

αo= 0.13 Gy-1; β= 0.05 Gy-2 ;rd = 0.42 µm is radius of subcellular domain in MK model
Where D10,R = 5Gy is 10%
survival of 200 kVp X rays for
HSG cells

290MeV/u 12C SOBP Irradiation
Experiment in Movable Water phantom
Low noise electronics probe “MIcroPlus”
and microdosimeter in water-proof sheath

A new system was developed
whereby a microdosimetercan be moved sub-mm
incrementdepthsandundergo motion similar tothat of organs.

XY-stage with water tank andMicroPlus probeSpherical bolus made from PE

Aim: Observe response to a clinical scanning proton beam, tomeasure 𝑦𝐷 depth distribution, investigate effect of motion on
microdosimetric spectra
Fields: 130MeV pencil beam (𝜎 = 11mm) and clinical patient plan(spinal)

Left: Moveable water phantom with Bridge
Microdosimeter in front of PBS nozzle.

Right: Patient
Asteroid TPS

planshownin

Temporal lung motion
pattern used to movedetector during irradiation

yD when moving and stationary, 10mm Down Stream
and 15mm Up Stream from isocentre
Treatment plan showing movement(arrow) and stationary (x) locations

This work presented the first high spatial resolution RBE10 derivationin 12C ion therapeutic beam line
◦ SOI microdosimeter◦ The RBE10 values are in good agreement with values obtained using a TEPC, with an
exception at the distal part of the SOBP. This is due to TEPC measurements being
carried out in water which lacks the C atoms that comprise PMMA.

Significant difference observed between the stationary
microdosimetric spectra at distal part of the SOBP and the casewhere the detector mimicked lung motion.
◦ Microdosimetric spectra and dose mean lineal energy obtained out-of-field in proton
beam scanning allow the determination of neutron dose equivalent and thecomparison with passive treatment delivery.







The Centre for Medical Radiation Physics has developed a new
microdosimeter probe, with measurement threshold as low as~ 0.3 keV/µm.
The motion can lead to changes in the microdosimetric
spectrum and consequently the RBE.

The microdosimeter has the ability of measuring neutrons
dose outside of the treatment field.
Silicon microdosimeters can be used for BNCTNIRS, Japan
Prof. Naruhiro Matsufuji
 MGH, Boston, USA
Dr. Benjamin Clasie Mayo Clinic, USA
Dr. Chris BeltranDr. Mark Reinhard
Dr. Dale Prokopovich

Dr. Angela Kok
Dr. Marco Povoli
SPA, BIT, Ukraine
Dr. Vladimir Perevertaylo