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Recent Developments of Ion Sources for Life Science Studies at HIMAC

This article discusses the needs and requirements for ion sources in life science research, with a focus on the recent developments at HIMAC NIRS. It covers topics such as dose distribution, biological effectiveness, and approaches to life science studies using ion beams.

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Recent Developments of Ion Sources for Life Science Studies at HIMAC

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  1. Recent Developments of Ion Sources for Life Science Studies at HIMAC NIRS HIMAC Contents: 1. Needs - life science research 2. Status of life science studies at HIMAC 3. Requirements for ion sources 4. Experimental Results of 18 GHz NIRS-HEC 5. Wide spread of heavy-ion radiotherapy facilities A. Kitagawa, A.G. Drentje, T. Fujita, M. Muramatsu, NIRS, Chiba, Japan K. Fukushima, N. Shiraishi, T. Suzuki, K. Takahashi, W. Takasugi, AEC, Chiba, Japan S. Biri, R. Racz, ATOMKI, Debrecen, Hungary Y. Kato, Osaka Univ., Osaka, Japan T. Uchida, Y. Yoshida, Toyo Univ., Kawagoe, Japan

  2. 1. Needs – life science research

  3. Linear energy transfer 1. Needs – life science research Particles’ energy is slowly decreasing through the interaction High dose distribution near the stopping position Particles’ movement in a straight line Heavy ion Low dose distribution at high energy region • Biological effectiveness depends on micro distribution of dose, etc… Secondary electrons or radicals affect DNA in cells Ionization density (keV/mm3) photons Photons’ amount and energy are steadily decreasing Low dose distribution, and a few photons penetrate deep High dose distribution due to amount of photons

  4. Biological effectiveness 1. Needs – life science research Mitosis Ｓｉ Gap2 4 Interphase Ｈ Ｃ Gap1 S 3 RBE, OER 2 1 RBE OER 0 1 10 100 1000 10000 LET(keV/mm) M.R.Raju:Heavy Particle Radiotherpy (1980) LET dependence of Relative Biological Effectiveness (RBE), and Oxygen Enhancement Ratio (OER)

  5. Exporsures of heavy ions 1. Needs – life science research

  6. 1. Needs – life science research Approaches to life science studies • Micro-beam experiment • To investigate microscopic processes in cells • A low-energy single ion irradiation • An accuracy of sub-micrometers • Relativistic high-energy heavy-ion beams • To observe macroscopic phenomena • Under the situations similar to space environment or radiotherapy

  7. 1. Needs – life science research Facilities in physics research BEVALAC at LBL AGS at BNL E.A. Blakely, et al., Adv. Radiat. Biol. 11, 295 (1984).Biological and Medical Research with Accelerated Heavy Ions at the Bevalac, LBL-11220, UC-48 (1980). G. Kraft, Advances in hadrontherapy, p.385, Elsevier, Amsterdam-Lausanne-NewYork–Oxford-Shanno-Tokyo (1997). B.M. Sutherland, et al., Proc Natl. Acad. Sci. USA 97(1), 103 (2000). M.E. Vazquez, et al., Adv. Space Res. 25, 2041 (2000). SiS at GSI HIRFL at IMP

  8. Heavy Ion Medical Accelerator in Chiba (HIMAC) 1. Needs – life science research Ion species: H – Xe (He – Si for clinical) Treatment room: 3 (4 port) Experiment room: 4 (6 port) Size: 60 x 120 m Construction cost: 32.6GJPY (Building 14.6GJPY) (machine 18.0GJPY) *GJPY ~10MUS$

  9. 2. Status of life science studies at HIMAC

  10. Framework of experiments 2. Status of life science studies at HIMAC Call for proposals All proposals! NIRS researchers follow the same process Twice every year Submit proposals PAC evaluates all proposals PAC When accepted Scheduling of beam time Announcement of beam time ½ year schedule

  11. Number of proposals 2. Status of life science studies at HIMAC Beam time ~ 5000 hours / year

  12. Statistics in 2012 – 2014 Typical topics of life science studies Risk study in space Modeling and its verification of tumor control Response of normal tissues by mammals,fishes, bacterias,… Investigating of the pathway of DNA damage/repair Observation of the bystander effec etc… 2. Status of life science studies at HIMAC

  13. Endpoint of experiments 2. Status of life science studies at HIMAC Courtesy of Y. Furusawa, N. Nakajima, NIRS.

  14. 3. Requirements for ion sources

  15. 3. Requirements for ion sources Statistics of biology experiments *The above were the scheduled time. The failure rate is 0.2%~0.3% every year.

  16. Necessary intensities Standard irradiation region at BIOC 1.8 x 109 pps carbon beams Diameter: 10 cm Thickness of SOBP: 6 cm Dose rate: 3 Gy/min. 2.5 x 108 pps iron beams Thickness: mono energy Dose rate: 5 Gy/min. 3. Requirements for ion sources Depth dose distributions Fe

  17. 3. Requirements for ion sources Kei2 NIRS-ECR NIRS- HEC NIRS-PIG MEXP PH1 PH2 SB2 SB1 E BIOC C F B A G : Ion source : Linac : Treatment room : Synchrotron : Experiment room Block diagram of HIMAC beam courses

  18. Daily schedule 3. Requirements for ion sources Night Day Night Treatment Treatment Treatment • Weekdays(daytime) • Treatment 9AM-7PM ~10h • Weekdays(night) • Experiment 9PM-7AM ~10h • Monday • Maintenance / Treatment • Weekends • Experiment ~24h • Sunday • Shutdown / Experiment • Requirements • No exposure to the atmosphere • Easy operation / Good reproducibility • 2-hours interval • Accelerator switch the beam within 1 hour.

  19. 3. Requirements for ion sources Additional requirements • Stability • The short-term stability is not so sensitive because the fine structure of the beam pulse will almost disappear during the acceleration in the synchrotron. • The long-term stability and reproducibility after restarting are more important. Because of some biology experiments compare the dependence on the dose rate. • Switching time between different ion species • The switching time at an ion source is too long for the two-hours interval at HIMAC • Two ion sources have been setup for each ion productions, then they are switched at the intervals. • Every ion sources are prepared during their off time. • Easy operation and maintenance • Since a daily accelerator operator is not a specialist of ion sources, the automatic setup system is important.

  20. 3. Requirements for ion sources Daily operation • Solutions to keep the good stability, reproducibility and to reduce the switching time • Don’t expose to the atmosphere. • Save the optimized conditions of all devices to the control system. • Consider a hysteresis of produced ions.

  21. Hysteresis of exchange ion species 3. Requirements for ion sources Pressure (Pa) Beam current (emA) 250 10-3 Case 1 C Ne C 200 10-4 150 100 10-5 50 10-6 0 0 2 4 6 8 Time (hour) Case 2 C O C Vacuum pressure Beam current Daily carbon operation (Vacuum evacuation during one night) Operation of other ion species, O, Ne… (Vacuum evacuation during one night) • Carbon operation • Set the previous parameter • Measure the transient time to the stable operation Procedure of the switching of ion species Carbon beam currents after the switching from oxygen and neon beam by Kei2.

  22. 4. Experimental Results of 18 GHz NIRS-HEC

  23. Features Max. 60kV extraction voltage (A high voltage power supply on the source potential safely applies the extraction voltage between the plasma electrode and the extraction electrode independent of the source potential. ) Room temperature coils Vertical beam extraction Designed for production of ions with charge-to-mass ratio of 1/7 Long lifetime with the minimum maintenance under dirty conditions Good reproducibility for easy operation 4. Experimental Results of 18 GHz NIRS-HEC Waveguide Biased disk Gas inlet MIVOC container Mirror magnet 500l/sTMP Plasma chamber Extraction electrode (movable) Sextupole permanent magnet High voltage platform Insulator 500l/sTMP Acceleration gap (Insulator) Einzel lens Gate valve Slit Triplet Q Analyzer magnet 1m Faraday Cup & Slit 18GHz NIRS-HEC ECRIS NIRS-HEC is operating mainly for basic experiments since 1996.

  24. 4. Experimental Results of 18 GHz NIRS-HEC Output currents of NIRS-HEC (1)

  25. 4. Experimental Results of 18 GHz NIRS-HEC Schematic diagram of the gas-flow control A Vapor Pressure C B Adequate Range Room Temperature Case C Peltier cooler Metal Ions from Volatile Compound (MIVOC) method • Merits of MIVOC • The material consumption rate is very low. • The equipment is small and easy. • The ion species can be changed without exposing the vacuum chamber to atmosphere. Block diagram of the cooling MIVOC system W. Takasugi, et al., Rev. Sci. Instrum. 81, 02A329 (2010). The drawback of MIVOC, large contamination of carbons, is able to be neglected in our situation.

  26. 4. Experimental Results of 18 GHz NIRS-HEC Output currents of NIRS-HEC (2) • To improve intensities • Two frequency technique is suitable and very effective in our situation. • Necessary operation conditions • To supply enough power for both microwaves. • To precisely adjust the additional frequency. The best frequency depends on operation parameters; magnetic configuration, vacuum pressure, and so on. • Advantages • Effective for any kinds of ion species • Coexistent with almost other techniques • No modification of existing structure

  27. 4. Experimental Results of 18 GHz NIRS-HEC Synthesizer Power feedback Splitter Phase shifter Signal generator (18.0GHz fixed) 700W TWT 700W TWT 1500W Klystron Magic T 3kW dummy Circulator Power monitor Power monitor D. Coupler ECRIS 1200W max 17.1 ~ 18.5 GHz 1500W max 18.0 GHz Two-Frequency Heating Technique

  28. Typical Spectrum of Xe 4. Experimental Results of 18 GHz NIRS-HEC 132Xe21+ Obtained results When an additional microwave is added in the above situation, the plasma stability is improved at larger microwave power obtained by the mixture

  29. 5. Wide spread of heavy-ion radiotherapy facilities

  30. Present facilities in Japan Wide spread of heavy-ion radiotherapy facilities GHMC Gunma (2010) HIBMC Hyogo (2001) HIMAC Chiba (1994) SAGA-HIMAT Saga (2013) iROCK Kanagawa (2015) Heavy ion Heavy ion (under construction) Proton (including shutdown) Proton (under construction) • Operation facilities: • Period Patients • total (in 2014) • HIMAC (1994 – 2015.3) 9021 (794*) • HIBMC (2005 – 2014.12) 2146 (241) • GHMC (2010 – 2014.12) 1486 (501) • Saga (2013 – 2014.12) 547 (503) • -HIMAT • sum 13020 (2039) • *from Apr. to Mar. • Under construction: • iROCK (plan 2015 – ) • construction cost • machine 7500 MJPY • building 3800 MJPY • 11300 MJPY *~10M US$ • Other plans: • Osaka, Yamagata, Okinawa, …

  31. Charged particle radiotherapy worldwide Wide spread of heavy-ion radiotherapy facilities Marburg (2015) Heidelberg (2009- ) Wiener Neustat (2016) Chiba (1994- ) Hyogo (2005- ) Gunma (2010- ) Saga (2013- ) Kanagawa (2015) Pavia (2012- ) Wuwei (2015) Lanzhou Lanzhou (2016~?) Clinical research has been carried out at the physics institute at present. Soul (2017~?) Heavy ion Heavy ion (under construction) Shanghai (2014- ) Proton Proton (under construction)

  32. Wide spread of heavy-ion radiotherapy facilities ECRIS dedicated for carton ion radiotherapy GHMC KeiGM1 T. Ohno, et al., Cancers 3, 4046 (2011). M. Muramatsu, et al., Rev. Sci. Instrum. 76, 113304 (2005).

  33. Wide spread of heavy-ion radiotherapy facilities Charge-to-mass ratio: about 1/3 (margin is 10%) Target ion species: He ~ Ne (if possible ~ Si) Magnet: …………….. same as previous Kei-series Microwave: Development of Kei3 See M. Muramatsu et al., MonPE33 M. Muramatsu, et al., ECRIS2012, Sydney, September 2012, p.49 (2012). This will be not sufficient for ion species heavier than Si, like Fe.

  34. Typical Spectrum of Fe by NIRS-HEC Wide spread of heavy-ion radiotherapy facilities Fe15+ q/m~1/4 Fe16+ O3+ O5+ C2+ Fe13+ Fe12+ Fe17+ Fe11+ Fe10+ Fe9+ • Operation parameters • optimized 56Ni17+ at after-grow • tmw =50ms • f1=18.00GHz, P1=700W • f2=17.87GHz, P2=600W • Binj=1.21T, Bext=0.77T • Vext=31kV, dext=20mm • TNi=13C • SO2=0.030cc/min atom • Pinj=2.5 x 10-5Pa • It’s estimated that this intensity realizes, • a few Gy/min at Bragg peak • with a diameter 20 mm.

  35. Summary • Status of biology experiments There are still many continuous needs for medical researches and various biology experiments with relativistic high-energy ion beams.; • About 70 users used about 1000 hours beam per year. • The mean time for one user was about 2 hours. • A rich variety of ion species from hydrogen to xenon ions is expected by users. • Developments of ion sources • MIVOC technique is suitable for biology experiments. • Two frequency heating technique is effective for highly charged ions. • The switching interval time is a problem even at HIMAC.

  36. NIRS HIMAC Thank you for your visit in Chiba, 2013, and wish a successfull ICIS’15

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