From Neutrino Oscillations to Curing Cancer

1
From Neutrino Oscillations to Curing Cancer

• Ken Peach
• John Adams Institute for Accelerator Science
• University of Oxford and Royal Holloway
  University of London
• Particle Therapy Cancer Research Institute
• (part of the James Martin 21st Century School,
  Oxford)
• Edinburgh
• 5th March 2009

2
Outline

• Introduction
• (Neutrino Oscillations what we know and dont
  know)
• The Neutrino Factory
• (Accelerators everywhere muons)
• The ns-FFAG Accelerator
• (the non-scaling Fixed-Field Alternating Gradient
  accelerator)
• EMMA
• Curing Cancer (with accelerators)
• Charged Particle Therapy (CPT)
• (proton and light-ion cancer treatment)
• PAMELA
• Summary

3
Note

• This is the third lecture in an occasional series
• Spring 1974
• Neutral Currents New Science or Nuisance?
• Before the Standard Model
• Spring 1987
• CP-violation, the Standard Model and the Number
  of Protons in the Universe
• Within the Standard Model
• Spring 2009
• From Neutrino Oscillations to Curing Cancer
• Beyond the Standard Model

4
The history and future of the neutrino

• 1930s Neutrino proposed
• 1940s ???
• 1950s electron neutrino observed, V-A proposed
• 1960s muon neutrino observed, V-A physics
  neutrino oscillations suggested
• 1970s neutral currents, DIS, structure functions
  solar neutrino deficit
• 1980s sin2qw, more structure functions, charm,
  ...
• 1990s more structure functions,sin2qw, more
  solar neutrino deficit atmospheric
  neutrino deficit
• 2000s Tau neutrino discovered,
• even more solar neutrinos accelerator
  oscillation measurements???
• 2010s neutrino factory ???? CP violation???

5
The history of the neutrino
Dear Radioactive Ladies and Gentlemen, 4th of
December 1930 As the bearer of these lines,
to whom I graciously ask you to listen, will
explain to you in more detail, how because of
the "wrong" statistics of the N and Li6 nuclei
and the continuous beta spectrum, I have hit
upon a desperate remedy to save the "exchange
theorem" of statistics and the law of
conservation of energy. Namely, the possibility
that there could exist in the nuclei
electrically neutral particles, that I wish to
call neutrons, which have spin 1/2 and obey the
exclusion principle and which further differ
from light quanta in that they do not travel with
the velocity of light. The mass of the neutrons
should be of the same order of magnitude as the
electron mass and in any event not larger than
0.01 proton masses. The continuous beta spectrum
would then become understandable by the
assumption that in beta decay a neutron is
emitted in addition to the electron such that
the sum of the energies of the neutron and the
electron is constant... I agree that my
remedy could seem incredible because one should
have seen those neutrons very earlier if they
really exist. But only the one who dares can win
and the difficult situation, due to the
continuous structure of the beta spectrum, is
lighted by a remark of my honoured predecessor,
Mr Debye, who told me recently in Bruxelles "Oh,
it's well better not to think to this at all,
like new taxes". From now on, every solution to
the issue must be discussed. Thus, dear
radioactive people, look and judge.
Unfortunately, I cannot appear in Tubingen
personally since I am indispensable here in
Zurich because of a ball on the night of 6/7
December. With my best regards to you, and also
to Mr Back. Your humble servant W. Pauli
6
The Standard Model of Particles and their
Interactions
Neither LHC nor Linear Collider will illuminate
the mystery of the neutrino!
7
The Standard Model

• The Parameters
• 6 quark masses
• mu , mc, mt
• md, ms, mb
• 3 lepton masses
• me, mm, mt
• 2 vector boson masses
• Mw, MZ
• (mg, mg0)
• 1 Higgs mass
• Mh
• 3 coupling constants
• GF, a, as
• 3 quark mixing angles
• q12, q23, q13
• 1 quark phase
• d

8
Why is the neutrino important?

1. It is ¼ of the matter part of the Standard
   Model
2. It is the only known neutral matter particle
3. It has only weak (and gravitational) interactions
4. It is the 2nd most abundant particle in the
   Universe
5. It is the only matter particle to oscillate
   in vacuum
6. It may explain the matter asymmetry of the
   Universe

9
Solar Neutrinos

• neutrinos are produced in the sun

• Of the 3 types of neutrino
• electron, muon, tau
• only electron neutrinos come from the sun

Can we detect them? YES! Do they all reach the
earth? Apparently NO!
10
SNO (Sudbury Neutrino Observatory)
11
What does SNO measure?

• 3 Separate measurements of the Solar Neutrino
  Flux
• Neutral Current (NC) interaction
• nx d ? p n nx ? measures TOTAL flux
• Charged Current (CC) interaction
• ne d ? p p e- ?measures electron
  neutrino flux
• Elastic Scattering (ES)
• nx e- ? nx e- ?measures electron neutrino
  flux 15 of the non-electron flux
• If neutrinos do NOT oscillate, then all should
  measure same flux

12
SNO
Wark
13
So Neutrinos what do we know?

• Both electron and muon neutrinos apparently
  vanish between creation and detection
• The effect is large
• Neutrino oscillation is the most likely
  explanation
• How can we be sure?
• What are the parameters?
• Important for
• Particle physics
• neutrinos are a major component of the Standard
  Model
• Cosmology
• neutrinos are the second most abundant particle
  in the Universe
• Could explain the matter-antimatter asymmetry of
  the Universe

14
Neutrino Oscillations (2-flavour)

• 2 flavour eigenstates na,nb, 2 mass eigenstates
  n1,n2

• After a finite time, the neutrino flavour
  balance has changed
• Some wrong flavour component has been
  introduced.
• Note
• 1. If the masses are the same there is no
  oscillation
• 2. If a mass is zero, that neutrino decouples
  from oscillation
• 3. The oscillation is a beating phenomenon
• In the lab frame, the propagation is
• Oscillation depends upon
• Dm2ijm2i-m2j

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What is a neutrino oscillation?
Only possible if neutrino have mass!
ne
nx
16
Neutrino Oscillation Measurements
Probability that a nb appears as a function of
L from a na produced at L0
Signal
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3 flavour oscillation

• Neutrinos are created as flavour eigenstates
• electron ne , muon nm , tau nt
• but these are not the mass eigenstates
• n1 , n2 , n3
• The flavour eigenstates are a mix of the mass
  eigenstates

U is the Maki-Nakagawa-Sakata Matrix
Prog.Theor.Phys.28 870 (1962).
18
Neutrino Mixing 3 flavour
Atmospheric
Solar
Majorana
cij cosqij sij sinqij
Matter-antimatter asymmetry
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Why is it hard to measure the parameters?
a 2?2 GFneEn 7.6 10-5 r E Where is the
electron density r is the density (g/cm3) E
is the neutrino energy (GeV)

• (Richter hep-ph/0008222)

cijcosqij, sijsinqij
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Latest global fits
Schwetz et al, arXiv/0808.2016
21
Mass Hierarchy Phase

• What we know

and what we dont know
Normal hierarchy
Inverted hierarchy
or the phase angle d
22
Neutrino Factory

• The ultimate neutrino facility

23
What to Measure?

• Neutrinos
• ne disappearance
• ne ? nm appearance
• ne ? nt appearance
• nm disappearance
• nm ? ne appearance
• nm ? nt 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)
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CP-violation
FNAL Feasibality Study 1
25
A Neutrino Factory is
an accelerator complex designed to produce
gt1020 muon decays per year directed at a detector
thousands of km away
need to accelerate muons very quickly _at_5 GeV,
tm0.1msec
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The non-scaling FFAG Accelerator

• Fixed-Field Alternating Gradient

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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)
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Fixed Field Alternating Gradient accelerators
Type Magnetic Field RF Radius
FFAG Fixed ? Fixed

• 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?

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Early FFAGs (1955-1960)

• MURA built several electron FFAGs in the 1950s

Radial sector
Spiral sector

• Large complicated magnets
• c.f. Cyclotron large simple magnets
• c.f. Synchrotron small simple magnets

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Newer FFAGs (post-2000)

• The Japanese have built two proof of principle
  proton FFAGs

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but
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Scaling and non-scaling FFAGs
Invented in 1999
Linear magnets! i.e. quadrupoles
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Simpler Magnets
to magnets that are SMALL and SIMPLE
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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

35
so where is the catch?

• Variable tune!

Must cross resonances
Tune wb/wc
36
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 worlds first non-scaling FFAG
  accelerator!

37
Objectives of the CONFORM Project

• 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
• Develop applications of ns-FFAGs

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Location of EMMA
Daresbury
39
EMMA
ALICE
Diagnostics Beamline
IOT Rack
RF Distribution
After Rob Edgecock
40
EMMA at the ALICE_at_Daresbury
After Neil Bliss
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Status of EMMA

• Funded! (6M)
• Started 1st April 2007
• Lattice - fixed
• Component design - completed
• Final design - completed Jan 08
• Construction - Autumn 09
• Beam studies - until Sep 10
• At least

After Tkeichiro Yokoi
42
Charged Particle Therapy (CPT)
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Incidence of Cancer in the UK
Source Cancer Research 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

44
An 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
45
Development of Cancer Radiotherapy

• 1895 Konrad Rontgens X-rays
• 1898 - Marie Curies Radium
• Radium and x-ray machines used to treat cancer
• Most current radiotherapy uses High energy X-ray
  beams from linear accelerators or linacs
• These X-ray beams pass through entire thickness
  of body

Modern Linac
46
X-ray therapy began within months of Roentgens
discovery
47
Curing Cancer with X-rays
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Intensity Modulated Radiation Therapy (IMRT)
49
The Bragg Peak
Bragg peak
Plateau
50
Can we do better?
The Bragg Peak
51
Is it better?
52
Medulloblastoma in a child
With Protons
With X-rays
100 60 10
When proton therapy facilities become available
it will become malpractice not to use them for
children with cancer. Herman Suit, M.D.,
D.Phil., Chair, Radiation Medicine, Massachusetts
General Hospital
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Prostate Cancer Results
Loma Linde
54
A Proton Therapy Centre
55
A rotating gantry
56
The Clatterbridge Centre for Oncology

• Established 1989
• First hospital based proton therapy
• gt1400 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
57
Can we do even better?
58
Does it work?
Cancer of the Kidney Stage I TIa N0 M0 80GyE /
16fr. /4wks
???
From Japan
59
Japan Tsukuba UniversityNew Proton Medical
Research Centre, 2001
60
Spot Scanning
Proton pencil beam
Target
Patient
Pedroni et al, Med Phys. 2237-53, 1995
61
Clinical uses

• Mostly eye cancers
• Relatively rare primary cancers
• skull base or spine
• difficult to cure with x-rays
• Far fewer for common cancers
• Lung
• Oesophagus
• Breast
• Kidney
• Liver
• Pancreas
• Prostate

From Alex Elliott
62
BBC 7th November 2008
63
PAMELA

• Particle Accelerator for MEdicaL Application

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CPT What remains to be done?

• CPT has moved from laboratory to hospital
• Where it belongs
• But there is still much to do
• Improved accelerator technology
• Improved patient experience, better control
• Improved beam delivery instrumentation
• Better control, reduced errors, lower dose to
  healthy tissue
• Improved understanding of the evidence
• Better treatment planning, domains of
  applicability
• Improved treatment regimes
• Finding the best way of delivering the lethal
  dose to the tumour
• Improved understanding of mechanisms
• Better treatment planning, more effective
  outcomes
• Improve - patient experience
• - increase effectiveness
• - decrease cost

65
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

66
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
• gt100 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.

67
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

68
Clinical Requirements
69
Challenges

• The non-relativistic, non-scaling Fixed-Field
  Alternating Gradient Accelerator (nrns-FFAG) is a
  new type of accelerator
• Dense lattice
• Challenging magnets, RF, injections and
  extraction
• Resonance crossing
• Stability
• EMMA will demonstrate the ns-FFAG
• PAMELA will demonstrate the nrns-FFAG

70
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
• Lattice cell defined at end of 2008
• Work through the design in 2009
• Incorporate the lessons from EMMA
• Produce a conceptual design in 2010

71
PAMELA

• Particle Accelerator for MEdical Applications

Part of the CONFORM Project Design
PAMELA Oxford-Imperial-RAL-Daresbury
Protons or carbon ions
Protons or carbon ions
72
PAMELA
73
Summary

• After 30 years, there is clear evidence that the
  Standard Model is incomplete
• Neutrino Oscillations require New Physics
• Uncovering this New Physics will require New
  Technologies
• Including perhaps a Neutrino Factory
• These New Technologies might also help address
  Old Problems
• Better treatment of some cancers

74
Medical advances may seem like wizardry. But
pull back the curtain, and sitting at the lever
is a high-energy physicist, a combinational
chemist or an engineer. Magnetic resonance
imaging is an excellent example. Perhaps the last
century's greatest advance in diagnosis, MRI is
the product of atomic, nuclear and high-energy
physics, quantum chemistry, computer science,
cryogenics, solid state physics and applied
medicine.

• Harold Varmus, Nobel Laureate in Medicine,
  Washington Post, 2000

75
Backup slides
76
Cost of CPT

• (numbers approximate)
• Capital cost (4 rooms) 100M
• Running costs per annum 15M
• Capital charges (20 years) 100M
• Total cost 500M
• Cost/year 25M
• Patient throughput
• 30min/patient, 12 hr/day, 5 days/week
• 25000 patient sessions/year
• 35 fractions/patient
• 700 patients/year
• 36,000 per patient

20 fraction/patient 3 patients/hour 1800
patients/year 14,000 per patient
- reduced cost of other care
77
How many centres?

• 2005 289k new cases
• 1390 under 15
• Estimates suggest that 1 proton centre is
  required per 10 million population
• 1/3rd that number of carbon centres
• UK population 60M
• Implies 8 proton centres
• 1 each in Scotland, Wales and N.I, SW and N of
  England, 3 in Midlands and SE
• 2 carbon centres
• Capacity for 10,000 patients/year 300M