Advanced Silicon detectors for Micro-and Mini- dosimetry in particle - PowerPoint PPT Presentation

Advanced Silicon detectors for Micro-and Mini- dosimetry in particle therapy Anatoly B. Rozenfeld Space Science School , 4-8 September, 2018 , University of Bergen, Norway,

Acknowledgement of Contributors Centre for Medical Radiation Physics , University Of Wollongong Dr Linh Tran, Dr Marco Petasecca, Dr Susanna Guatelli, A/ Prof Michael Lerch, Dr Jeremy Davis, Dr Brad Oborn, Prof Peter Metcalfe CMRP PhD students: Lachlan Chartier, David Bolst, Matthew Newall, Aaron Merchant, Emily Debrot, James Vohradsky, Trent Causer and many others POWH: Dr Michael Jackson, MD ANSTO : Dr Dale Prokopovich, Dr Mark Reinhard, Prof David Cohen, SINTEF : Dr Angela Kok, Dr Marco Povoli and 3DMiMiC team SPA BIT Ukraine , Dr V.Perevertaylo HIT facilities in Japan : Prof N.Matsufuji , Prof T. Yamaya (NIRS), Prof T.Kanai, (GUMC) Institute of Radiooncology, HZDR at OncoRay, Dresden : Dr A.L.Hoffman and team MGH F Burr Proton Therapy Center and Harvard Medical School Ben Clasie, PhD , Jay Flanz, PhD, Nicolas Depauw, PhD. Hanne Kooy, PhD, Harald Paganetti, PhD ,

Content Concept Microdosimetry and MKM • Benefit of particle therapy • 3D Microdosimetric detector :fabrication • Silicon-Tissue conversion • RBE in particle therapy: MicroPlus 3D probe results • Other applications in hadron therapy • Mini-dosimetry in particle therapy • Conclusion and future work • 3 Document title

Meet the CMRP team Prof Anatoly Dr Marco A/ Prof Dr George Dr Iwan Prof Peter Dr Dean Rozenfeld Petasecca Michael Lerch Takacs Cornelius Metcalfe Cutajar Founder and Director Karen Ford Dr Peter Dr Jeremy Dr Alessandra Dr Nan Dr Susanna Dr Engbang Li Admin Officer Dr Yujin Qi Lazarakis Li Davis Malaroda Guatelli and PA Dr Linh Tran Dr Moeava Tehei Dr Brad Oborn

Human missions in space Long journeys aboard the ISS occur more frequently Human missions to Mars are envisaged in the future ISS The amount of radiation received by astronauts depends on several factors including orbital inclination, altitude, position in the solar cycle, and mission duration . The average altitude of space shuttle orbits is 170 Nautical Miles corresponding to 9 milliRad/ day 9 Document title

Space Radiation Environment This figure illustrates the rise and fall of fluxes Integral proton fluences for several of solar energetic particles during an SPE . major SPEs over the last four solar cycles 10 Document title

Mixed radiation field: Aviation and Space environment Doses are affected by…  Altitude,  Latitude and  Long journeys aboard the ISS occur more frequently. Human missions to Mars  Solar activity are envisaged in the future  Protect astronauts from harmful effects of space radiation is crucial  Dosimetry for radiation protection in high energy mixed radiation fields is a challenging task TEPC Bubble detector 11 Document title Dosimeters for spacecraft crew

Bragg Peak (BP) William Henry Bragg William Lawrence Bragg • 1895: the first recorded surgical use of the Roentgen ray in Australia • 1905: ‘brought to light a fact, which we believe to have been hitherto unobserved. It is, that the a particle is a more efficient ionizer towards the extreme end of its course.’ • 1915: father and son won Nobel Prize Bethe Formula

Proton therapy history In 1946 Harvard physicist Robert Wilson (1914-2000)  suggested * : ◦ Protons can be used clinically ◦ Accelerators are available ◦ Maximum radiation dose can be placed into the tumor ◦ Proton therapy provides sparing of normal tissues ◦ Modulator wheels can spread narrow Bragg peak First human patient treated in 1954 at the Lawrence Berkeley Laboratory (LBL) with proton therapy

First Human Treatment • Cornelius Tobias was a pioneer for hadron beams and was part of first human patient treatment in 1954 at the Lawrence Berkeley Laboratory (LBL) with proton therapy Cornelius Tobias • Continued investigation for treatment using alpha and heavier ions Tobias’ most famous work was his in 1957 using Berkley’s newly constructed Heavy Ion Linear investigation of bright streaks, reported by the crew of Apollo-11. He irradiated himself Accelerator (HILAC) (below) with alphas and neutrons and experienced the light himself

Advantages of Heavy Ion Therapy  Secondary nuclear Courtesy of M. Scholz Cell damage due to Cell damage due to direct fragments indirect DNA damage DNA damage, irreparable  Secondary neutrons DNA breaks

Mechanistic understanding  Chromosomal aberration will be fatal, especially if clustered.  Energy deposition to the chromosomal size (~ μ m) is the keystone.  Spatial energy deposition in μ m scale is highly dependent on the incident radiation … Microdosimetry 16 Courtesy of Prof N.Matsufuji Courtesy of Dr Scholz (GSI)

Definition Microdosimetry quantifies: the spatial and temporal energy deposition by ionizing • radiation in irradiated material at a scale where the energy deposition is stochastic in nature i.e. microdosimetry quantifies the spatial and temporal • probability distribution of energy deposition by ionizing radiation in a irradiated volume

Stochastic nature of ionization events Determinist Stochastic At microscopic scale ic Interactions between radiation and • a medium occur in discrete events These events occur stochastically • around a track At macroscopic scale: The number of these events allows • to treat the energy deposition in a 1 µm volume as a deterministic quantity

Temporal considerations time (s) Temporal evolution of concentration of radical species from a 4 keV electron track Courtesy of Dr Marco Zaider

Track structure of ionizing radiation Track structures in 100 nm water

Microdosimetry vs. (traditional) dosimetry Dosimetry Microdosimetry is a deterministic quantity stochastic quantity measures average energy deposition per probability distribution of energy unit mass distribution is expressed as where <E> is the average energy f( z ) is the probability distribution of deposition of the specific energy z deposited in the mass m

Cell damage by Gamma and Heavy Ions radiation sparsely ionising densely ionising protons 1 MeV/u 12 C ions 1 MeV/u in water in water Images by M Kraemer, M. Scholz et al. GSI, Germany Immunoflourescence image Rad. Res. (2001) p398 of the repair protein mainly indirect DNA damage mainly direct DNA damage irreparable DNA breaks relative biological effectiveness: RBE γ =1 Increase of biological effectiveness RBE protons = 1.1 RBE carbon = 2-4 → Radioresistant tumours!

Microdosimetry :Specific energy Energy imparted ε : is the energy imparted within a site • Predictions on the energy imparted can be made based on a probability distributions of energy transfers. Specific energy z: is defined as the ratio of the imparted energy ε and the site’s mass • m: • Lineal energy y: is defined as a ratio of the imparted energy and mean chord length Energy per unit mass vs mass for constant dose D. Reducing of the target is changing deterministic deposition of energy to stochastic. Each radiation type has own signature . Each type of radiation has their own signature of a single event spectra

Proportional Counters – TEPC TEPC - Measurable Quantities • E t Absorbed dose – E g Mean Quality factor – Dose equivalent – Microdosimetric averages – Diameter of Tissue Site   ∆ X   ρ = ρ t Density of   ∆ g t X Tissue Site   g (1000 kg.m -3 ) Density Diameter of of Gas Gas Cavity Tsuda et. al. Phys. Med. Biol., 55, 5089-5101, 2010

Microdosimetric spectra Average quality � = ∫ ∞ factor: 𝑹 𝑹 𝒛 𝒆 𝒛 𝒆𝒛 𝟏 H=QD • Dose distributions yd(y) as a function of Dose Equivalent energy (bottom) and site size (top)

Local Effect Model (LEM) :cell damage by ions Low LET d(r) Sparsely ionisation S = exp [ - αD - βD 2 ] Linear Quadratic Model High LET • LEM is based on corresponding biological d C (r) effect for X rays • The difference in biological effectiveness between Densely ionisation photons and charged particles is due to track structure. Courtesy Gustavo Russo, (INFN, Torino )

Microdosimetric Kinetic Model ~1 μ m ~10 μ m 𝑨 +MKM TDRA 𝑀 ~ 𝐵𝑨 + 𝐶𝑨 2 S=exp(-L) � 𝑄𝑄𝑄𝑄𝑄𝑄𝑄𝑄 0, 𝑀 Linear Quadratic Model S(D) = exp [ - αD - βD 2 ] Single lesion in any domain leads Hawkins, Rad. Res. (2003) to cell death Kase et al ., Rad. Res. (2006) 27 Courtesy of Prof N.Matsufuji

Microdosimetric Kinetic Model (MKM) Hawkins et al. 1994, 2003 10% survival D 10,R D 10 Radiobiological Effectiveness (RBE): 𝑆𝐶𝐹 10 Biological dose = RBE × D 𝑌−𝑠𝑆𝑠𝑠 = 𝐸𝑄𝑄𝐸 𝑢𝑢𝑢𝑢 𝑕𝑄𝑕𝐸𝑄 10% 𝑑𝐸𝑑𝑑 𝑄𝑡𝑡𝑕𝑄𝑕𝑢𝑑 | 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝑬 𝟐𝟏 , 𝒚 = 𝑬 𝟐𝟏 , 𝒋𝒋𝒋𝒋

Bridge MD Version 2 Figure 1. Top and side-on schematic of a sensitive volume Area of whole chip : 3.6 x 4.1mm 2 ; 4320 cells IEEE Trans on Nucl. Sci., 62(6):3027-3033 , 2015

3D Silicon Microdosimeters-Mushrooms (SEM images) Full 3D (air-trenched) Planar n+ 3D p+ (poly-trenched)