Electron Accelerators and Medical Diagnostics

1
(Electron) Accelerators and Medical Diagnostics
Luca Serafini - INFN / Milano

• Medical Diagnostics imaging of biological
  tissues, micro-imaging of cells/proteins using
  radiation beams (IR to X-rays)

3 Examples of Advanced Medical Diagnostics
performed by means of Accelerators delivering
High (peak/average) Brightness Electron Beams

• IR spectro-microscopy _at_ DAFNE, Solar UV effect
  studies with UV beamline _at_ DAFNE, X-ray
  Absorption Spectroscopy on thin samples
• Radiological imaging with mono-chromatic tunable
  X-rays (10-500 keV) generated by Thomson
  scattering _at_ SPARC
• Proteine Cristallography with coherent X-rays
  generated by the X-FEL (SPARX)

2
X-Ray beam quality goes along with upgrade of
electron beams

• Since the invention of Crookes tubes (step!
  Roengten)

Up to modern (still under design) photo-LINACs
producing high brightness electron beams to drive
X-FELs (coherent X-ray beams) 1034 ph/s in 1
(mm.mrad)2 0.1 bandwidth 100 fs pulses
3
Linac Coherent Light Source _at_ SLAC X-Ray Free
Electron Laser
15 GeV e- beam using 1/3 of SLAC Linac
Courtesy of Max Cornacchia
4
X-ray sources over the last 100 years the story
of a marriage between electron beams and X-rays
5
Synchrotron radiation rules next generations
Thomson back-scattering of virtual
photonsvs.Bremsstrahlung on metallic targets
6
Brilliance of X-ray radiation sources
12.4
1.24
0.124
l (nm)
SASE-FELs will allow an unprecedented upgrade
in Source Brilliance
SPARX
TTF
Covering from the VUV to the 1 Å X-ray spectral
range new Research Frontiers
7
Design parameters Beam energy 510 MeV Max
number of bunches 120 Bunch spacing 2.7
ns Bunch current 40 mA Single
bunch luminosity 41030 cm?2 s?1
8
Av. Brilliance of SR from DAFNE compared to
existing facilities
DAFNE I 400 mA
9
Solar Ultraviolet Effect and UV beamline at
DAFNE-L

• Application ? investigation of the biological
• effects on human cell cultures (HeLa-x human
• skin fibroblast) of irradiation by UV B band
• i) dose and wavelength dependence
• ii) threshold effects
• iii) death neoplastic transformations.

Characteristics ? JobinYvon grating Monochromator
and mirrors in air i) UVB band (280-320 nm) ii)
resolution better than 0,3 iii) doses from 20
to 40 J/m2 .
10
IR spectromicroscopy
polline linfociti cellule ematiche biomasse virus

• SINBAD_at_10 microns

Transmission of 10 mm pinhole
March 18, 2004
BRUKER Equinox 55 BRUKER IRscope 1
Mid-IR
by A. Marcelli
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IR Spectromicroscopy

• Cancer cells investigation
• W. Kwiatek
• The Henryk Niewodniczanski Institute of Nuclear
  Physics

12
X-ray Absorption Near Edge Spectroscopy of low Z
elements (Mg, Al, P, S, Cl, K, Ca) and transition
metals (up to Cd)
The Soft X-ray beamline at DAFNE Fixed exit
monochromator with double Si(111) or Quartz(1010)
crystals Ion Chamber detectors for appling XAS in
transmission on thin samples Energy range from 1
up to 4 keV
Gianfelice Cinque
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From 3rd to 4th Generation..

• SASE-FELs (protein single shot imaging)
• Thomson Sources (compact 3rd generation sources
  aiming at advanced medical imaging inside
  hospitals)

All need High Brightness e- beams
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Brightness of Electron Beams isthe Key Issue
I peak current in fs to ps long electron
bunch ltIgt average current over 1 s enx rms
normalized transverse emittance
Quality Factor beam peak current density
normalized to the rms beam divergence angle
(linked to transverse beam coherence)
Brightness is crucial to maintain colliding or
copropagating (e-, hn) beams well overlapped
(enhancing coherence)
15
Brightness is crucial formany Applications
SASE FELs for coherent X-rays
Courtesy of D. Umstadter, Univ. of Michigan
Plasma Accelerators _at_ 100 GV/m
Relativistic Thomson Monochromatic X-Ray Sources
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Photo-Linacs (driven by RF Photo-Injectors) rule
over SR rings
LCLS (requested _at_ 15 GeV) 4.1015 enx eny1.5
mm SPARC ultimate goal (Ph. 2) 2.1015
I bunch peak current gt kA
ESRF (storage ring) lt 1014 enx 20 mm eny0.07
mm
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SPARC an Advanced Photo-Injector to drive a
SASE-FEL _at_ LNF/INFN
Co-funded by MIUR (2003-2006) and pursued by an
inter-institutional collaboration
INFN-ENEA-CNR-INFM-Univ.TorVergata-ST
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Two additional beam lines at SPARC for plasma
acceleration and monochromatic X-ray beams - the
Project PLASMON-X
100 fs synchr. TiSa multi-TW Laser System
1 J, 10 ps gaus
2 nC, 10 ps
1 J, 100 fs gaus
Compr.
20 mJ, 10 ps flat top
500 mJ
20 pC, 20 fs
en2 mm, s 50 mm
1 nC, 10 ps, en1 mm
en0.2 mm, s 10 mm
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Compact Sources of Monochromatic X-raysbased on
Relativistic Thomson back-scattering
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1 J Laser pulse interacting with 1 nC 10 ps
electron bunch _at_ 30 MeV w020 mm, s010 mm,
Z01.5 mm , b 6 mm
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Thomson Source frequency spectrum _at_ 20 keV
gng/5 xn2.236x,vxn2.236vx Ntot1,98107,Dw/w7,5

Beam rms angle qm5 mrad
gng/5 xnx, vxn5vx Ntot8,4 107,Dw/w6,8
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Thomson Source frequency spectrum_at_ 500 keV
(a)Beam rms angle qm1 mrad Ntot8,5107
Dw/w7,9 (b) Beam rms angle 0.7ltqmlt1.4 mrad
Ntot1.06 108 Dw/w11
(a)iris (b) hollow
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Non-invasive Coronaric Angiography
Dynamic IVCAG (Intravenous Coronary
Arteriography) using monochromatic X-rays
produced by Synchrotron Radiation and
monochromators was clinically tested at KEK-AR
and Tsukuba University, obtaining clear dynamic
images (33 shots/s) of the coronary artery, with
37 keV X-rays , 1011 photons/s generated by an
undulator at the AR ring (intravenous contrast
agent applied instead of invasive artery cateter
insertion).
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Mammography with Mono-chromatic X-Rays
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MaMBO Experiment Mammography
Monochromatic Beam Outlook
Main aim conducting test experiments on phantoms
with the PLASMON-X Mono-chromatic X-ray beam _at_ 20
keV, in order to avoid absorption of low energy
photons in the tissue (dose without informations)
as well as the scattering of the high energy
photons (image contrast degradation) in the
spectrum of a typical X-ray tube for mammography
Request 1011 ph/s with 10 frequency spread
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Projects world-wide on Thomson Sources for
Mono-chromatic X-rays
Sumitomo-Festa (S-band, medical) Univ. of Tokyo
- NERL (S-band, medical) NIRS - Univ. of Tokyo -
KEK (X-band, medical) SLAC (X-band,
medical) Brookhaven ATF (S-band, by-product in
laser acceleration) Livermore (S-band, material
studies, nuclear weapons)
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Sumitomo - Festa Collab. (Tokyo)
Measured spatial profile of the scattered X-rays
(The electron beam is in the plane of the laser
polarization)
X
Y
70mm
Energy 14 MeV Bunch charge
0.5 nC Focused beam size 100 mm(rms)
The lines represent the results of the
theoretic analysis
X-ray energy 4.6keV(peak)
Pulse length (calc.) 3ps(rms),
Intensity 1.5x105/pulse
Intensity fluctuation 10
Pulse energy 85mJ/pulse Pulse
length 100fs(rms) Focused beam
size 108mm_at_0o-collision
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X-band advanced protoype
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COFIN Proposal for a 2 year RD program on
Compact X-band Thomson Sources subm. to MIUR
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What is a SASE-FEL Radiation Source? a Bright
Electron Beam propagating through an Undulator
Spontaneous Radiation peaked at lr _at_
lu / 2g2(1 K2) g 2.103 Beam rms
divergence s _at_ 1/g _at_ 100 mrad (Thomson
Backscattering of undulator virtual photons) I
r _at_ N e N e number of electrons per
bunch (_at_ 109)
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Interaction of e- with Spontaneous Radiation
causes Microbunching and SELF-AMPLIFICATION of
Spontaneous Emission (SASE)
In the SASE mode the Intensity I ph _at_ N ea
a gt 4/3 N e number of electrons (_at_
109) Amplification gives extraordinary High
Photon Flux (diffraction limited beam) Beam rms
divergence s _at_ l / 2pse _at_ few mrad
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This Ultra-Bright Coherent Radiation opens up
new Research Frontiers in several fields

• Atomic physics
• Plasma and warm dense matter
• Femtosecond chemistry
• Life science
• Single Biological molecules and clusters
• Imaging / holography
• Micro and nano lithography

X-rays are the ideal probe for determining the
structure of matter on the atomic and molecular
scale Science with Soft X-Rays, Nevill Smith,
Physics Today, January 2001
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Biology and Protein Crystallography

• WATER WINDOW (280-530 eV) is of extreme
  interest for BIOLOGY see Review ( Neutze, R., et
  al., Potential for biomolecular imaging with
  femtosecond X-ray pulses. Nature, 2000. 406 p.
  752-757 ) where many Applications are summarized
• CHROMOSOMES
• MALARIA INFECTED ERYTROCYTES
• CALCIFIED TISSUES
• MUSCLES
• LIPID MEMBRANES
• POLYMERS

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Single Shot Protein Crystallography with Single
100 fs X-Ray pulses
No Need to make Crystalline Proteins ! Most
Proteins cannot be made crystalline In vivo
imaging possible
R.Neutze, R.Wouts D. van der Spoul,, E. Weckert,
J. Hajdu Nature 406, 752, (2000)
Full ionization of the whole protein molecule,
Coulomb explosion on a time scale of 50-100
fs FEL pulse must be faster to bring information
to detector!
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Conclusions

• DAFNE is an ideal example of how a machine
  designed and operated to provide a cutting edge
  beam with very challenging performances
  (ultra-high luminosity) for basic research could
  generate (as a fringe benefit) a broad-band
  spin-off on medical/biological applications with
  frontier innovative research studies
• The combined SPARC PLASMON-X projects will
  generate a mono-chromatic tunable soft and hard
  X-ray beam within 2007, available to experiments
  in the advanced medical diagnostics field (MaMBO,
  etc.) serious chance to become a key european
  test facility
• Vigorous RD should be pursued (and funded!
  funding agencies solicited) on the design and
  tests of compact hospital-based Thomson Sources,
  in order to perform a first prototype
  commissioning, followed by the launch of mass
  production within this decade