Medical Applications of Accelerators

Hywel Owen

School of Physics and Astronomy, University of Manchester

&

Cockcroft Institute for Accelerator Science and Technology

IOP PAB Annual Meeting, 10th April 2014

Radiotherapy Statistics for UK

• ‘Radiotherapy Services in England 2012’, DoH

– 130,000 treatments, most common age around 60 yrs

– 2.5 million attendances

– More than half of attendances are breast/prostate

• X-rays

– 265 linacs in clinical use

– Almost all machines IMRT-enabled, 50% IGRT (Image-Guided)

– Each machine does >7000 ‘attendances’

– 147 more linacs required due to increasing demand

• Protons

– 1 centre (Clatterbridge)

• Cancer care

– 40% curative treatments utilise radiotherapy

– 16% cured by radiotherapy alone

Protons vs X-Rays

IMRT

Clatterbridge Centre for Oncology

5µ+1µ foils

PMMA

0

50

100

150

200

250

300

0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0 20.0 22.0 24.0 26.0 28.0 30.0

Range (mm eye tissue)

No

.

62 MeV Scanditronix Cyclotron

UK Proton Therapy Centres - Update

• Timeline:

– Pre-qualification questionnaire and technical specification issued:

– Competitive dialogue underway now – bidders being narrowed

– Manufacturer chosen/ contract placed end 2014 this is when we know what kind of machine it will be

– First patients 2018

• Specification:

– 2 centres

– 230/330 MeV protons only, spot scanning

– 2 Gy/min/litre

– 1500 patients (750/centre), 3 or 4 treatment rooms per centre

Paediatric Indications

Chordoma/Chondrosarcoma 15

Rhabdomyosarcoma Orbit 5

Parameningeal & Head & Neck 15

Pelvis 10

Osteosarcoma 3

Ewings 9

PPNET (Extra-osseous Ewing's) 5

Ependymoma 25

Low Grade Glioma 5

Optic Pathway Glioma 12

Craniphayngioma 15

Medulloblastoma (PNET) 70

Hodgkins 5

Retinoblastoma 5

Meningioma 3

Intracranial Germinoma 10

Nasopharynx (Head & Neck) 15

Difficult Cases (Esthesioneuroblastoma/Neuroblastoma/Liver) 5

Very Young Age (Extra Cases) 20

Paediatric TOTAL 252

Adult Indications

Choroidal melanoma 100

Ocular / Orbital 25

Chordoma Base of Skull 60

Chondrosarcoma Base of Skull 30

Para-spinal / Spinal Sarcoma Including

Chordoma 180

Meningioma 100

Acoustic Neuroma 100

Craniospinal NOS (Pineal) 10

Head & Neck & Paranasal Sinuses 300

PNET (medullo/intracranial) 30

Difficult Cases 300

Adult TOTAL 1235

TOTAL 1487

Christie Site

UCLH Site

04/04/13 Simon Jolly, University College London 7

Crucifor

m

Building

Rosenhei

m

Building

Macmillan

Cancer

Centre

Jeremy

Bentham

Pub

Spearmin

t Rhino

Odeon

Site

• Provides UK patients with

optimum access to the

service, with limited travel

times by car or public

transport

• Both sites at the centre of

regional public transport links

• Ensures as many patients as

possible will be able to return

home during their treatment

Benefits for patients: Geography

Private Proton Therapy in the UK?

• ProTom-based (330 MeV compact synchrotron) centre proposed for Moorgate 2012

– Single room, synchrotron-based

– Seems to have disappeared

– ProTom have just announced single-room centre for MGH

• Advanced Oncotherapy

– Number of press releases over the summer

– Caused much interest within NHS

– 3/4/7 private centres in the UK?

– No hard information

– Tie-in with BMI Healthcare and/or Spire

– Definitely linac-based, use of TERA/ADAM/CERN 3 GHz structures

Moorgate Private Proton Therapy Centre?

• Private treatment

• CareCapital/Advanced Proton Solutions Holdings Limited

• ProTom Radiance 330 MeV synchrotron

• Gantry interesting

• Single gantry, robotic rotating couch

UK Research Activities and Expertise for Radiotherapy

• Manchester – FFAG design, gantry design, Monte Carlo, computational methods, Si dosimetry, novel detectors.

• Liverpool – diagnostic instrumentation, neutron instrumentation, FFAG design

• Lancaster – high-gradient RF cavities

• National Physical Laboratory – dosimetry standards for protons

• Clatterbridge – new nozzle design, backgrounds

• UCL/UCLH – dosimetry, neutron instrumentation, novel imaging

• Oxford – radiobiology, throughput/computation

• RHUL – Beam tracking/background estimation

• Imperial – FFAGs, FFAG gantries, laser-plasma protons and manipulation, radiobiology

• Huddersfield – FFAG design, beam tracking/space charge

• STFC RAL – laser proton acceleration, laser isotope production, FFAG design

• STFC DL – conventional magnet design

Delivering protons

Multi-room vs single room

installations;

Depends on cost and size of

source 3 mins

1 mins

0 mins 3 mins

1 mins

0 mins

2 mins 2 mins

Wait time per beam v No. of rooms Fractions per day v No. of rooms

Current Trends

• Industry is focused on cutting costs

– Mature commercial solutions exist

– Would like to make protons available to less-developed countries

• Emerging trends

– Fast spot scanning is replacing double-scattering passive delivery

– Increasing adoption of superconducting technology – SC cyclotrons, gantries

– Increased offering of single-room solutions

– X-band technology for acceleration

– Ability to deliver higher energies for imaging; 350 MeV

Recent Activities

• EUCARD2 Applications of Accelerators – networking funding

– Gantry workshop (Jan 2014)

– Accelerator-driven systems (April 2014)

– Accelerator-based neutron sources (April 2014)

• National Physical Laboratory

– Dosimetry workshop (Mar 2014)

• CERN Medical Intitiative

– Drawing together CERN with European laboratories to progress research in important medical areas

UK Research Activities and Interests in Radiotherapy

• Manchester – FFAG design, gantry design, Monte Carlo, computational methods, Si dosimetry.

• Liverpool – diagnostic instrumentation, neutron instrumentation

• Lancaster – high-gradient RF cavities

• Clatterbridge – new nozzle design, backgrounds

• UCL/UCLH – dosimetry, neutron instrumentation

• Oxford – radiobiology, throughput/computation

• RHUL – Beam tracking/background estimation

• Imperial – FFAG gantries, laser-plasma protons and manipulation, radiobiology

• Huddersfield – FFAG design, beam tracking/space charge

• STFC RAL – laser proton acceleration, laser isotope production, FFAG design

• STFC DL – conventional magnet design

Current Challenges

• Image guidance is a fundamental issue

– Range uncertainty much more important for protons/carbon than for x-rays

– Improved imaging – secondary particle imaging

– Gating, adaptive treatments

• Planning and dose estimation

– Want dose estimates less susceptible to artefacts; Monte Carlo

– Want treatment plans robust to patient changes

• Radiobiology

– Systematic experiments needed to improve data, even for protons

– Effect of particle type

– Effect on specific tissue types

• Improved technology

– More compact carbon accelerators – carbon-11 facility?

– Higher-energy, economic proton sources

– Compact gantries, including faster layer switching

– Fast switching

Using Xeon Phi as a validation platform

• Xeon Phi – ‘a cluster on a card’

• Unlike GPUs these are CPUs using shared memory

• No re-write of GEANT4 needed

• Each thread can access the same memory space – 512 x 512 x 512 image fits!

• GEANT4.10 MT implemented on Xeon Phi – (2 cards in each box)

• Now hooking the cards together

• Advantage: speed & cost & size & power

1x Xeon Phi 7120p card

61 cores

244 threads

1 hour

10^7 particles for validation

work in progress, Manchester Christie

The problem of range uncertainty

• At the moment, range uncertainty and patient motion is basically handled by ‘blurring out’ the protons using repainting

– Gets rid of some of the advantages protons give over x-rays

• Improved imaging is biggest priority for UK clinicians in proton therapy

04/04/13 Simon Jolly, University College London 15

Imaging & Motion

• Why accept standards inferior to those of photons?

• Need higher resolution imaging to match proton precision: biggest challenge for UK indication list.

• Link with robust and adaptive planning development.

• Several challenges: – Usefulness of CBCT; incorporation with

gantries; dose issues with adaptive re-planning.

– In-room MR; other dose-free/low-dose methods; ultrasound too little used; registration methods to combine imaging modalities.

– Motion monitoring (particularly with scanned beams); relation to UK-funded indications (cf. lung, pancreas); but have long-term view of indications; technology limitation for fast energy change when range tracking.

• Proton radiography has much promise but is under developed.

Pravda Si tracker/calorimeter

Lincoln/Liverpool/Birmingham

Non-Invasive Beam Monitor for Medical Applications

• Aim: Non-destructive measurement of beam tails;

• Idea: Use LHCb Velo detector to correlate between halo signal and beam current;

• Study halo – dose relationship.

Proof-of-principle: G. Casse, et al., Liverpool

Issues: dimensioning of air dryer and chiller to prevent

detector from creating ice during cool down; detector

remote positioning system (transverse and

longitudinal), reduction of noise, system integration

(purpose-built rack, etc.) – realized in close partnership

with and strong support from STFC, full design

presented at IBIC, article in PRST-AB in prep. Courtesy Liverpool Uni

Technical drawings of the Scanditronix MC-60 PF Cyclotron unit at Clatterbridge Cancer Centre (CCC), Wirral, UK. Technical drawings of the Scanditronix MC-60 PF Cyclotron unit at Clatterbridge Cancer Centre (CCC), Wirral, UK.

Ion max. kinetic energy [MeV] 62.0

Ion type p

Magnetic field avg. min [T] 1.05

Magnetic field avg. max. [T] 1.75

Magnetic field max. hill [T] 2.13

RF frequency [MHz] 26.7

RF period [ns] 37.5

RF beam acceptance [deg] 13

Scanditronix MC-60

PF cyclotron at

CCC.

Scanditronix MC-60

PF cyclotron at

CCC.

Clatterbridge MC-60 PF Cyclotron

T. Cybulski, C.P. Welsch, Proc. BIW (2012)

PBT Research

• UCL/NPL are using one of the SuperNEMO calorimeter modules for protons: first beam tests at Clatterbridge encouraging

Courtesy Simon Jolly, UCL

FFAGs

• PAMELA design study successfully completed

• Utilised semi-scaling approach

– Tune stabilised with higher-order field components

• Next version 330 MeV protons only – proton CT

Injection 70 MeV (cyclotron)

Extraction 330 MeV

RF Cycle Rate 1 kHz

RF Frequency Sweep 10-50 MHz (approx.)

Acceleration Time ~0.4 ms

Harmonic Number ~10

Bunch Structure Single Bunch

Bunch Charge 0.04 – 1.2 pC

Charge Stability ~10%

Average Extracted Current ~0.2 nA

Average Dose Rate 2 Gy-litre/min

Extracted Emittance 2 mm x 2mrad

Extracted Energy Spread <0.5%

Acceleration Voltage 100-200 kV/turn

Courtesy of S. Tygier

Laser-accelerated protons

• LIBRA: EPSRC Basic technology

grant (approx £5m)

• Intended to develop target technology

for laser-induced beams of protons,

ions, x-rays and neutrons

• Birmingham role in applications group:

beam dosimetry working with NPL

Laser

High power

pulsed Laser

Patient on horizontal

treatment couch capable of

3600 rotation & elevation Mirror

Target

laser power >

1020 W/cm2

E > 1012 Vm-1

Acceleration modes

Target Normal Sheath Acceleration

Ion energy a I0.5

Radiation Pressure Acceleration

Ion energy a I

Gantries provided by mirror reflection of laser?

Courtesy S. Green, UHB

Gabor lenses (J. Pozimski, Imperial)

Superconducting Gantries Magne. c'rigidity'(2)'

Ex: Heidelberg:

Carbon, 425 MeV/u (30 cm penetration depth), B*r = 6.57 T*m

Present (normal) dipole: B = 1.8 T, r = 3.65 m

If superconducting dipole: B = 3.3 T, r = 2 m

! 29

After D. Robin

Accelerators and Gantries PARTNER school, CERN F. Kircher March 5 2012

32

From the previous situation and requirements, it was decided to study the effect

of using superconducting magnets in a ‘Heidelberg-like’ gantry.

Two phases:

▪ Preliminary study done for the Etoile project (2006 - 2008)

- Irfu (SACM, SIS), Ganil, IPNL, Etoile

- All gantry aspects included (optics, SC magnet, rotative system)

- Technical feasibily, cost, planning

- - Need to build a prototype

Gantry NC (Heidelberg) SC (Etoile)

Weight (t) 600 210

Length (m) 18 13.5

Radius (m) 7 4

Accelerators and Gantries PARTNER school, CERN F. Kircher March 5 2012

Preliminary'study'done'at'Saclay'(1)'

No practical advantage for

250 MeV protons

Advantageous for 350 MeV

protons and for ions

NIRS (Japan) 3.0 T for 430 MeV/u 200 t total 13 m x 5.5 m

Courtesy Y. Iwata (NIRS)

FFAG Gantries – needs a demonstrator

Carbon Ek=400 MeV/u Br = 6.35 Tm ( q= Bl/Br ) Warm iron magnets: B=1.6 T then r ~ 4.0 m Superconducting magnets B=3.2 T then r ~ 2.0 m

4.1

m

8.6 m

20.8

courtesy D. Trbojevic

LEIR for radiobiology studies

D. Abler et al., Journal of Radiation Research, 2013, 54, i162–i167

BNCT - UHB

• 1.7 MeV reaction threshold

• Solid or liquid lithium target

• Example: 3 MeV proton ‘dynamitron’ (electrostatic machine)

• Useful flux of neutrons requires large currents

– 10^12 n/s requires 1 mA

– Liquid targets, complex cooling

• Arrangement of neutron moderator/absorber modifies spectrum to peak at optimum energy for BNCT, 4 eV to 40 keV

– Boron Neutron Capture Therapy

courtesy S. Green, UHB

511511511511511(2)Gammas

(keV)

190017301200960630Positron

(keV)

275d2m10m20.5m110minHalf-Life

Ge-68O-15N-13C-11F-18Nuclide

PET Radionuclides

Isotope production

• Three main areas:

• Conventional short-lived isotopes:

– F18, C11, N13

– Hospital-based

– Commercial solutions widespread

– Compact low-cost accelerators

• Tc99m

– Reactor-based production fragile

– A number of accelerator methods exist

• Alpha-emitters, Ra223, At211, Bi213

– Several methods and opportunities exist

– CERN MEDICIS

Tc-99m in the UK

• UK has no domestic creation of Mo99 or Tc99m

• Dependent on overseas suppliers, mainly Canada/Belgium

• NHS working group set up to recommend alternatives

• Report later on this year

Using an Accelerator

1. Cyclotron 100Mo(p,2n)99mTc

– E.g. TRIUMF, 99.54% enrichment, TR-19 (15.5-17 MeV), 1.5-3h

– Co-production with other isotopes, multiple cyclotrons

2. Photonuclear 100Mo(g,n)99Mo

– E.g. Saskatchewan/CLS/PIPE,

– Demonstrated, near to market – few regional centres

3. Photofission 238U(g,f)

– E.g. TRIUMF/ARIEL

– Higher waste stream, licensing issues?

– Large UK expertise in electron linacs and high power targets

– Single UK facility?

4. Neutron Capture 98Mo(n,g)99Mo, Subcritical Fission

– E.g. SHINE, CERN/Buono/Rubbia large linac/spallation, small accelerator-Be/Li target, or IBA ADONIS (NIMA 493, 163 (2002), resonance enhancement possible, subcritical system?

– Single large European accelerator could have high capacity, but security of supply?

– Single European facility?

NRC INMS Proof-of-concept

(Ottawa)

Courtesy M. de Jong, CLS

100Mo target (CLS)

www.lightsource.ca

Isotope Linac and Target Assembly

Compact cyclotrons/FFAGs for conventional isotopes?

• Lower energy allows higher current

• E.g. Ionetix Isotron:

– 12.5 MeV/~6 T/35 kW

• Cryogen-free magnets

– Cryocooler tech, quite demanding

– 1.5 W at 4.2 K

– Still difficulty with fault recovery

2 October 2012

TA Antaya

13N SOLUTION in a compact Sc cyclotron

• Despite significant advantages over alternatives in SPECT and PET, 13N has had two

main limits to adoption:

• Half-life is only 10 minutes so you have to make it where you will use it

• However, few medical facilities have on-site cyclotrons due to size and cost

• Ultra-compact high field superconducting cyclotron system to provide superior blood

flow imaging by enabling PET imaging agent 13N availability directly in a clinical setting

19

Isotron'PET

Imaging

Suite!

2 October 2012

TA Antaya

Isotron N13 Demo Cyclotron- First beam 2 June 2012

21

2 October 2012

TA Antaya

Isotron scale?

About the same pole size as the 1932 Cyclotron but 160 times

higher final proton energy

23

Courtesy T. Antaya, Ionetix

Siemens Oniac

• ‘Magnet free’

• Single stage only, perhaps up to 10 MV

• 5-stage Greinacher cascade, H- n , stripped to H+ at centre

• Demonstrator installed at RAL – results to come!

Corporate TechnologyCorporate TechnologyCorporate Technologyp gy

Challenges to the business of nuclear medicine related to availability of radioisotopes were Challenges to the business of nuclear medicine related to availability of radioisotopes were Challenges to the business of nuclear medicine related to availability of radioisotopes were

identified assessed and a vision for the future business approach was developed identified, assessed and a vision for the future business approach was developed. identified, assessed and a vision for the future business approach was developed.

h l di i b i 3 ill S C 200 300 d d j if l lThe nuclear medicine business rests on 3 pillars SPECT: 200 – 300 doses per day are necessary to justify local The nuclear medicine business rests on 3 pillars SPECT: 200 300 doses per day are necessary to justify local

• Equipment for the production of radiopharmaceuticals radioisotope production• Equipment for the production of radiopharmaceuticals radioisotope productionq p p p

S l f di h i l• Supply of radiopharmaceuticalsSupply of radiopharmaceuticals

• PET & SPECT imaging• PET & SPECT imagingg g

Th h ll l d di h i lThe top challenges related to radiopharmaceuticalsThe top challenges related to radiopharmaceuticals

• Currently: expensive large and unreliable accelerators• Currently: expensive, large and unreliable acceleratorsy p g

U il bili f di h i l d l bl• Unavailability of radiopharmaceuticals due to supply problemsUnavailability of radiopharmaceuticals due to supply problems

• A relatively stagnant portfolio of radiopharmaceuticals due high • A relatively stagnant portfolio of radiopharmaceuticals due high y g p p g

development cost an long release cycles at the same time: development cost an long release cycles, at the same time: p g y

relatively low specificity of the available tracersrelatively low specificity of the available tracersL l SPECT di i t d ti i l fit bl ith

y p y

f i i i iLocal SPECT radioisotope production is only profitable with a

• The return of investment is limitedLocal SPECT radioisotope production is only profitable with a

bi d PET d SPECT di i D l hiThe return of investment is limited

combined PET and SPECT radioisotope set-up Dual use machine• Clinical side: low reimbursement rates growing prices for

combined PET and SPECT radioisotope set up Dual use machine• Clinical side: low reimbursement rates, growing prices for g g p

radiopharmaceuticals and equipmentradiopharmaceuticals and equipmentEnabling technology by CT T P HTC

p q pEnabling technology by CT T-P HTC

• Providers of radiopharmaceuticals: high running cost growing g gy y

ONIAC l hi h l l i lProviders of radiopharmaceuticals: high running cost, growing

• ONIAC, a novel compact high voltage electrostatic acceleratorcost for up front investment (e g quality assurance)

ONIAC, a novel compact high voltage electrostatic acceleratorcost for up front investment (e.g. quality assurance)

Req irements for f t re offerings in n clear medicineRequirements for future offerings in nuclear medicineq g

• PET radioisotope production unit: Customer price starting at 500k€• PET radioisotope production unit: Customer price starting at 500k€

Automated flexible rapid radiotracer chemistry module including • Automated flexible rapid radiotracer chemistry module including p y g

t t d lit t l t d i tautomated quality control to reduce running costq y g

• SPECT detector program with focus on resolution and sensitivity• SPECT detector program with focus on resolution and sensitivity

G t il bilit f di h ti l i l th • Guarantee availability of radiopharmaceuticals: regional rather y p g

th l b l lthan global supplythan global supply

PET: 30 – 50 doses per day are necessary to justify local Radioisotope PET: 30 – 50 doses per day are necessary to justify local Radioisotope

productionproduction

P tPartnersPartners

• Sector lead H IM• Sector lead H IM

H lth CTO / St t• Healthcare CTO / StrategyHealthcare CTO / Strategy

• Business Unit H IM MI• Business Unit H IM MI

M BiT h C 11 (t th ith CT T MHM MME)• MoBiTech C-11 program (together with CT T MHM MME)MoBiTech C 11 program (together with CT T MHM MME)

• Member of the healthcare “detector board” CdTe• Member of the healthcare detector board CdTe

Corporate TechnologyCorporate Technologyp gy

Conclusions

• Lots of relevant activities in UK

• Previous focus around EMMA/PAMELA

• Now focus around new proton centres? – Test beamlines available

– Many technologies can be tried out

• Interest in bringing applications community together

• ‘Applications of Particle Accelerators in Europe’ – UK hosted meeting,

September?