Http://@adams-institute.ac.uk British Accelerator Science & Radiation Oncology Consortium A new.

http://www.adams-institute.ac.uk [email protected]://www.basroc.org.uk

British Accelerator Science &

Radiation Oncology Consortium

A new accelerator for advanced research

andcancer therapy

Ken PeachJohn Adams Institute for Accelerator Science

University of Oxford and Royal Holloway University of London

RHUL22nd October 2008

Ken Peach John Adams Institute 22 X 08 2

Outline

• Introduction (Accelerators & Particle Physics)

• The Neutrino Factory(Why? The Muon Acceleration Challenge)

• The ns-FFAG Accelerator(non-scaling Fixed-Field Alternating Gradient)

EMMA

• Charged Particle Therapy (CPT)(proton and light-ion cancer treatment)

PAMELA

• Summary


Introduction

• There are more than 17,000 particle accelerators (> a few MeV) worldwide– Most are used in medicine

• Linacs, cyclotrons, some synchrotrons…

– Next most common in industry• Ion implantation etc

– Synchrotron Radiation Sources• Mostly synchrotrons, coming soon - linacs

– Neutron and radionuclide sources• Linacs, cyclotrons, synchrotrons, something weird

and– For particle physics!

• A few big synchrotrons (& colliders) – Often with Linacs at the front end

• And coming soon (maybe) the ILC


Classical Accelerator Types

Type Magnetic Field

RF Radius

Betatron Variable × Fixed

Cyclotron Fixed Variable

Synchrotron Variable Fixed

FFAG Fixed ~Fixed

Linear accelerators

(Linacs)×

+ assorted others – electrostatic, RFQs etc …

+ new ideas (laser-plasma for example) …


The Bleeding Edge?

• Medical accelerators– Mainly linacs and cyclotrons

• Research accelerators– Mainly synchrotrons

• Particle Physics applications– Better synchrotrons (LHC)– Better linacs (ILC)

• Why do we need anything new?

– Because life presents new challenges!


HiggsHiggsBosonBosonHiggsHiggsBoson?Boson?

For

ceF

o rce

Car

riers

Car

r iers

ZZ boson

WW boson

photon

ggluon

Generations of Generations of matter matter

-neutrino

tau

bbottom

ttop

III III

-neutrino

muon

sstrange

ccharm

II II

e

e-neutrino

eelectron

ddown

upu

I I

Lept

ons

Lept

ons

Qua

rks

Qua

rks

Particles and Forces

Each with its own

‘antiparticle’

© Brian Foster


The Standard ModelThe ParametersThe Parameters

• 6 quark masses– mu , mc, mt

– md, ms, mb

• 3 lepton masses– me, m, m

• 2 vector boson masses– Mw, MZ

• (m, mg=0)• 1 Higgs mass

– Mh

• 3 coupling constants– GF, , s

• 3 quark mixing angles– 12, 23, 13

• 1 quark phase–




Neutrino Factory

The “ultimate” neutrino facility


The Standard ModelThe ParametersThe Parameters

• 6 quark masses– mu , mc, mt

– md, ms, mb

• 3 lepton masses– me, m, m

• 2 vector boson masses– Mw, MZ

• (m, mg=0)• 1 Higgs mass

– Mh

• 3 coupling constants– GF, , s

• 3 quark mixing angles– 12, 23, 13

• 1 quark phase–

Neutrino sector

Neutrino masses identically 0!!!!


i

i

ii

ii

i

i

i

i

i

MNS

e

e

ccescscseccsss

scesssccecsssc

escscc

e

ecs

sc

ces

esc

cs

sc

U

1

1

1

1

1

231312231312231223131223

231312231312231223131223

1313121312

1212

1212

1313

1313

2323

2323

Neutrino Mixing

Parameters of neutrino oscillation

1 absolute mass scale

2 squared mass diffs

3 mixing angles

1 phase

2 Majorana phasesβα,

)esinθ always ( δ

θθθ

ΔmΔm

m

iδ13

132312

223

212

νe

, ,

,

221

232

231

2i

2j

2ji

ΔmΔmΔm

mmΔm

solarAtmospheric Majorana3G

cij=cosqij

sij=sinqij

O(1eV) masses

unknown ,,

unknown

0.032 sin

0.326 sin

eV10 0.35)(7.66

0.45sin

eV10 0.27)(2.38

232

132

0.040.05-12

2

25-221

0.160.09-23

2

2-3232

mSign

m

m

2

Fogli et al, 2008


a =22 GFneE = 7.6 10-5 E

Where is the electron density ; is the density (g/cm3) ; E is the neutrino energy (GeV)

eP

ELm

ELm

ELmsssccc 4442313122312

213

221

231

232 sinsinsinsin8

ELmccsc 4

2223

212

212

213

221sin4

EaL

ELm

ELm

ELm sssc 4

213444

223

213

213 21sinsincos8

221

231

232

231

2213211

mas

E

Lmssc 422

23213

213

213sin4

ELm

ELm

ELmsssccsssc 4442313122312231312

213

221

231

232 sinsincoscos8

ELmsssccsssccsc 4

21323122312

223

213

212

223

212

212

213

221sincos24

Why is it hard to measure the parameters?

(Richter: hep-ph/0008222)

aa

cij=cosij, sij=sinij


What to Measure?

Neutrinos

e disappearance

e appearance

e appearance

disappearance

e appearance

appearance

… and the corresponding antineutrino interactions

Note: the beam requirements for these experiments are:

high intensity known flux

known spectrum known composition (preferably no background)


CP-violation

FNAL Feasibality Study 1


A Neutrino Factory is …

… an accelerator complex designed to produce >1020 muon decays per year directed at a detector thousands of km away

Muon Acceleration

… need to accelerate muons very quickly

[@5 GeV, ~0.1msec]


Neutrino Factory cost drivers

• High Power proton drivers – MW power, ns pulses

• RLA or FFAG?– Which is cheaper?

• RF – 30% of the cost?

• Cooling– How much? (20% of the

cost?)

BNL Feasibality Study 2




The non-scaling FFAG Accelerator

Fixed-Field Alternating Gradient


Fixed Field Alternating Gradient accelerators

• Fixed-Field (like a cyclotron)

– Rapid acceleration possible– Rapid cycling possible

• Alternating Gradient (like a synchrotron)

– Focussing!!!!• Small(er) magnets/beam pipe/vacuum system

• … and large acceptance

• The best of both worlds!– So why is the world not full of FFAGs?

Type Magnetic Field RF Radius

FFAG Fixed ~Fixed


Early FFAGs (1955-1960)

• MURA built several electron FFAGs in the 1950s

20 to 400 keV machine

Chandrasekhar Bohr

Radial sector Spiral sector

Large complicated magnets• c.f. Cyclotron – large simple magnets

• c.f. Synchrotron – small simple magnets


Newer FFAG’s (post-2000)

• The Japanese have built two “proof of principle” proton FFAGs

500 keV proton FFAG @ KEK 150 MeV proton FFAG @ KEK


… but …

• Why?… the magnets are LARGE LARGE and COMPLICATEDCOMPLICATED

• Why does k have to be so large?1. Larger k means stronger focussing

2. k > 0 means horizontal focussing– This means that the average field increases with radius

3. The momentum compaction 1/(k+1)– Large momentum bite small orbit excursion p

pRR

Orbit excursion ~ 0.9m

+ k

r

rBB

00

where k >> 1

1 krp


Scaling and non-scaling FFAGs

k

r

rBB

00

where k >> 1

1 krp

k

r

rBB

00

where k = 1

LinearLinear magnets!

i.e. quadrupoles

Invented in 1999


Simpler Magnets

… the magnets are LARGE LARGE and COMPLICATEDCOMPLICATED

B0 x B1

B0

x

to magnets that are SMALL SMALL and SIMPLESIMPLE


The ns-FFAG

• Should combine the advantages of FFAGs – Fixed Field

• Fast cycling (limited essentially by RF)• Simpler, cheaper power supplies• No eddy-currents• High intensity (pulsed, ~continuous)• Low beam losses• Easier maintenance and operation• Lower stresses

– Strong Focussing• Magnetic ring• Variable energy extraction• Higher energies (than cyclotrons)• Different ion species possible

• with relative ease of construction


… so … where is the catch?

• Variable tune!

Tune ~ c

Must crossresonances


Beam Acceleration

• Resonance is a coherentcoherent effect– Can fast acceleration circumvent the

resonances?• If the momentum changes by a large

amount during a single turns, is it possible to leap-frog over the resonance?

– Small variation of the path length with momentum (small momentum compaction)

• Fixed radio-frequency cavities?

10MeV

20MeV

|df/f|~0.1%

0.1ns

Plots for EMMA


Does it work?

• We do not know!– There is no “no-go” theorem

• Need for a “proof of principle” demonstrator– EMMA

• Electron Model for Many Applications– Originally Electron Model for Muon Acceleration

• Funding obtained in the UK to design and build a EMMA – the world’s first non-scaling FFAG accelerator!


Objectives of the CONFORM Project

1. Show the non-Scaling Fixed-Field Alternating Gradient Accelerators work

• Build an Electron Model (EMMA)• Design a prototype Charged Particle

Therapy machine based on ns-FFAGs• Protons and carbon ions

2. Develop applications of ns-FFAGs


EMMA Parameters

42 identical straight length 394.481 mm

Long drift 210.000 mm

F Quad 58.782 mm

Short drift 50.000 mm

D Quad 75.699 mm


Location of EMMA

Daresb

ury

Daresb

ury


EMMA at the ERLP@Daresbury

After Neil Bliss

ERLP Parameters


EMMA: Lattice & Magnets

B0 x B1

B0

xMagnet linear slide

After Neil Bliss


Diagnostics, injection & extraction

After Rob Edgecock


Status of EMMA

• Funded! (~£6M)– Started 1st April 2007

• Lattice - fixed

• Component design - ongoing– Prototype quads being measured now

• Final design - complete Jan 08

• Construction - complete Jul 09

• Beam studies - until Sep 10– At least …

After Tkeichiro Yokoi


CONFORM




PAMELA

Charged Particle Therapy (CPT)

BASROC & CONFORM


Incidence of Cancer in the UK

• 12.5% probability, all types (except skin cancer) by 65– Rises to more than 1/3rd for whole-life– Around half are associated with specific risks– Statistically, some will be close to sensitive tissue

• and difficult to treat surgically or chemically

Source: Cancer Research UK


An important statisticAn important statistic

“ Radiotherapy remains a mainstay in the treatment of cancer. Comparison of the contribution towards cure by the major cancer treatment modalities shows that of those cured, 49% are cured by surgery, 40% by radiotherapy and 11% by chemotherapy”.

RCR document BFCO(03)3, (2003).

Chemotherapy provides by far the smallest contribution towards cancer cure yet is much more expensive than radiotherapy and generates a disproportionately large research and media interest.

Roger Dale, Hammersmith Hospital and Imperial College


What is RBE?RBE = Relative Biological Effectiveness.

A measure of the biological “potency” of a particular type of radiation relative to that of a reference radiation.

Reference radiation (conventional x-rays) has RBE = 1

For a given biological end-point:

Proton RBEs: ~ 1.1

Neutron RBEs: 3 - 5

Carbon ion RBEs: 3 - 5

radiationealternativwithrequiredDose

radiationreferencewithrequiredDoseRBE

Roger Dale, Hammersmith Hospital and Imperial College


The concept and definition of RBE are both straightforward. Unfortunately….

Even for a particular type of radiation, RBE is not fixed.

Its value depends on:

a) The size of the dose used at each treatment

b) The chosen biological end-point

c) The nature of the irradiated tissueRoger Dale, Hammersmith Hospital and Imperial College


Development of Cancer RadiotherapyDevelopment of Cancer Radiotherapy

• 1895 : Konrad Rontgen’s X-1895 : Konrad Rontgen’s X-raysrays

• 1898 - Marie Curie’s Radium1898 - Marie Curie’s Radium• Radium and x-ray machines Radium and x-ray machines

used to treat cancerused to treat cancer• Most current radiotherapy Most current radiotherapy

uses High energy X-ray uses High energy X-ray beams from linear beams from linear accelerators or ‘linacs’accelerators or ‘linacs’

• These X-ray beams pass These X-ray beams pass through entire thickness of through entire thickness of bodybody Modern Linac


X-ray therapy began within months of Roentgen’s discovery


Present status of cancer in society Present status of cancer in society

• Cancer arises in 40% of populationCancer arises in 40% of population• Most forms increase with age and Most forms increase with age and prevalence expected to increaseprevalence expected to increase

• Therapy has Therapy has side effects (mild to severe, side effects (mild to severe, and sometimes permanent)and sometimes permanent)……there can ……there can be no complacencybe no complacency

• Molecular approaches have produced Molecular approaches have produced limited gains so farlimited gains so far

• Earlier diagnosis is increasingly possibleEarlier diagnosis is increasingly possible


Curing Cancer with X-rays

Dose

Linac

Linac

Linac

Linac

Linac

Linac

Linac

Linac

Linac

Linac

Linac


Radiotherapy linacs


Intensity Modulated Radiation Therapy (IMRT)


Bragg peak

Plateau

Carbon Ion Beam ProfileThe Bragg Peak


Can we do better?

Dose

Proton

Proto

n

The Bragg Peak


Is it better?


100

60

10

X-rays

With Protons

Medulloblastoma in a child


(from Gillies McKenna)

“When proton therapy facilities become available it will become malpractice not to use them for

children.”

Herman Suit, M.D., D.Phil.

Chair, Radiation Medicine

Massachusetts General Hospital


A Proton Therapy Centre


A rotating gantry


The Clatterbridge Centre for Oncology

• Established 1989 – First hospital based

proton therapy – >1400 patients with

ocular melanoma– First example of 3D

computer treatment planning in UK;

• eye gaze direction used to obtain best approach angle to eye.

• Unsung success story of British Oncology!

After Bleddyn Jones


Can we do even better?

Dose

Carbon


The ‘spread-out’ Bragg Peak –plateau effect

[SOBP]

65MeV 140meV200MeV

5 10 cmDepth

Dose (%)

Effective Range varies with proton Energy

X-rays

protonsThe Spread-Out Bragg Peak


Cancer of the Kidney Stage I: TIa N0 M0 80GyE / 16fr. /4wks

Cancer of the Kidney Stage I: TIa N0 M0 80GyE / 16fr. /4wks

1 year1 year2 years2 years

3 years3 years5 years5 years

Does it work?

From Japan


Prostate Cancer Results

Loma Linde

Clinical usesClinical uses

Inoperable brain tumoursHead and neck tumoursProstate tumoursParaspinal tumoursThoracic tumours (some)In addition

– Radiobiology programme– Cell line and animal irradiations

From Alex Elliott

Intracranial TumourIntracranial Tumour

17 month old child

From Alex Elliott

Rectal carcinomaRectal carcinoma

Protons reduce radiation toxicity and dysfunctionFrom Alex Elliott


Japan: Tsukuba UniversityJapan: Tsukuba UniversityNew Proton Medical Research Centre, 2001New Proton Medical Research Centre, 2001


C-ion Dose Distribution in Lung cancer: Chiba, Japan


Liver cancerLiver cancer

• Primary liver Primary liver cancer treated cancer treated by carbon by carbon ions ions

• 5 year follow 5 year follow up in cured up in cured patientpatient


Expected and achievable benefitsExpected and achievable benefits

• Reduce fear of cancer treatment, improved Reduce fear of cancer treatment, improved patient experience,patient experience,

• Dose Dose increaseincrease to cancer : 1% increase in to cancer : 1% increase in cancer control per unit increase in dose cancer control per unit increase in dose …..i.e. 15 Gy extra …..i.e. 15 Gy extra 15% extra control.15% extra control.

• Dose Dose reductionreduction to organs e.g. lung, brain, to organs e.g. lung, brain, eye, spine, bowel, bone: leading to reduced eye, spine, bowel, bone: leading to reduced or absence of many side effectsor absence of many side effects

• Chemotherapy better toleratedChemotherapy better tolerated• Better quality of life, ability to contribute to Better quality of life, ability to contribute to

society etc.society etc.


World & UK Position World & UK Position

• USA 12 centres, Germany 6, Japan 8.USA 12 centres, Germany 6, Japan 8.

• Italy, Switzerland, Sweden, France all Italy, Switzerland, Sweden, France all have facilities with plans for expansion have facilities with plans for expansion and large new centresand large new centres

• Cancer Reform Strategy (2007): Cancer Reform Strategy (2007): arrangements for patients to be sent arrangements for patients to be sent abroad: 12 in first year, Perhaps up to abroad: 12 in first year, Perhaps up to 400. Explore business case for UK 400. Explore business case for UK Centre(s)Centre(s)


Spot Scanning

Target

Magnetic scanner

‘Range shifter’ plate

Patient

Proton pencil beam

Pedroni et al, Med Phys. 22:37-53, 1995


Why use Carbon?

0

1

2

3

4

5

6

7

8

9

10

0 2 4 6 8 10 12 14

Depth in water [cm]]

effe

ctiv

e do

se [

rela

tive

units

]

photons

protons

biol. eff. dose: Carbon ions

Tumor

Daniela Schulz-Ertner, Heiddelberg


CPT facilities operating & planned


Hadron Therapy in Chiba (Japan)

Borrowed from Rob Edgecock


The requirements

• There are obvious potential benefits from proton/light ion therapy– Need to maximise the benefits

• Requirements– Rapid variable energy extraction– Rapid variable transverse spot scanning– Variable ion species– Accurate dose measurements

• Flux control


PAMELA Objectives

• Produce the conceptual design for a combined proton/carbon/light ion cancer therapy facility– 250 MeV protons, 400 MeV/u Carbon

• Preliminary performance parameters– >100 Hz cycle rate and one turn ejection– Dose rate of 2 to 10 Gy/minute.

• (1Gy ~ 2 x 1010 protons)

– Voxel size from 4x4x4 mm3 to 10x10x10 mm3

– Up to 100 pulses/voxel• With a typical tumour volume of 250 cm3 & voxel-

volume 0.064 cm3 (4x4x4), there are 4,000 elements, which with 10 to 100 pulses for each voxel needs 40k to 400k pulses in around 300 seconds, or a cycle rate of 133 Hz to 1.3 kHz.


Accelerator Technology?

• 4 possible technologies– Cyclotrons

• Fixed energy extraction, difficult for Carbon at full energy (equivalent to 1.2 GeV/c protons)

– Synchrotrons• Flexible, but difficult to meet the pulse

requirements; slow extraction difficult; normal conducting machine (stability?)

– (ns) FFAG• Flexible, rapid cycling (fixed field), variable

energy … but … unproven technology

– Laser-Plasma Ion accelerators• Far in the future …


Synchrotron Cyclotron FFAG

Intensity (>100nA) Low Plenty Plenty

1-16nA >100nA

Maintenance Hard Normal Normal

Extraction eff Good Poor Good?

Operation Not easy Easy Easy

Ions Yes No Yes

Variable energy Yes No Yes

Multi-extraction Possible No Yes

After Y.Mori KEK/Kyoto

Advantages of FFAG in Charged Particle Therapy


Challenges

• The non-relativistic, non-scaling Fixed-Field Alternating Gradient Accelerator (nrns-FFAG) is a new type of accelerator– Very dense lattice– Challenging magnets, RF, injections

and extraction– Resonance crossing– Stability

• EMMA will demonstrate the ns-FFAG• PAMELA will demonstrate the nrns-FFAG


Status

• Studies underway using a test lattice– Magnets – probably combined function

superconducting magnets– RF – a number of schemes are being

considered– Injection and extraction – will constrain the

lattice parameters

• Aim– Design a new lattice with a cell that can be

engineered by end of 2008– Work through the design in 2009– Incorporate the lessons from EMMA– Produce a conceptual design in 2010


PAMELA

Particle Accelerator for MEdical Applications

Fixed Field Alternating Gradient Accelerator

Protons or carbon ions

Protons or carbon ions


PAMELA


Superconducting FFAG Gantries

Fixed field of 3.7T Transports 150-400 MeV/u

Length ~15m

D Trbojevic/BNL


BASROC


Summary

• Non-scaling FFAG accelerators are:– New– Untried– Interesting for

• Neutrino physics• Cancer therapy

– And other applications » Spallation neutron sources, muon sources» Accelerator driven reactors, nuclear waste disposal

• We will know in ~3 years if they work– Let us hope that they do … they could be

very useful devices …

Http://@adams-institute.ac.uk British Accelerator Science & Radiation Oncology Consortium A new.

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