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(Electron) Accelerators and Medical Diagnostics

(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).

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(Electron) Accelerators and Medical Diagnostics

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  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 @ DAFNE, Solar UV effect studies with UV beamline @ DAFNE, X-ray Absorption Spectroscopy on thin samples • Radiological imaging with mono-chromatic tunable X-rays (10-500 keV) generated by Thomson scattering @ SPARC • Proteine Cristallography with coherent X-rays generated by the X-FEL (SPARX) Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  2. DC 106 photons/s in 1 (mm.mrad)2 0.1 % bandwidth 10-50 keV electrons 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 Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  3. SLAC Linac Undulator Hall Two Chicanes for bunchcompression FFTB Tunnel Near Hall Far Hall Linac Coherent Light Source @ SLAC X-Ray Free Electron Laser 15 GeV e- beam using 1/3 of SLAC Linac Courtesy of Max Cornacchia Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  4. X-ray sources over the last 100 years: the story of a marriage between electron beams and X-rays Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  5. Dipole in storage ring Dq=1/g Wiggler Undulator Dq=1/Nw Dq @ mrad Free electron laser Dq= lr/4ps Dq @ mrad • Brilliance (10 orders of magn. > 3rd generation SR sources) • Transverse Coherence (diffraction limited) Pulse time structure < 100fs • Spontaneous Radiationpeaked at lr@ lu / 2g2(1 + K2) lu = 2 cm g= 3.104 (15 GeV)lr =1 Å, 12 keV Synchrotron radiation rules next generations:Thomson back-scattering of virtual photonsvs.Bremsstrahlung on metallic targets Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  6. PLASMON-X Compact Thomson Sources extend SR to hard X-ray range allowing Advanced Radiological Imaging inside Hospitals 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 Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  7. Design parameters Beam energy : 510 MeV Max number of bunches : 120 Bunch spacing : 2.7 ns Bunch current : 40 mA Single bunch luminosity : 4·1030 cm2 s1 Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  8. Av. Brilliance of SR from DAFNE compared to existing facilities DAFNE I = 400 mA Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  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 . Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  10. polline linfociti cellule ematiche biomasse virus IR spectromicroscopy Transmission of 10 mm pinhole March 18, 2004 SINBAD@10 microns BRUKER Equinox 55 BRUKER IRscope 1 Mid-IR by A. Marcelli

  11. IR Spectromicroscopy • Cancer cells investigation • W. Kwiatek • The Henryk Niewodniczański 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 Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  13. 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 Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  14. x’ s’low s’=s/b s s’high b z x seq Brightness of Electron Beams isthe Key Issue I = peak current in fs to ps long electron bunch <I> = 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…) Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  15. Brightness is crucial formany Applications SASE FEL’s for coherent X-rays Courtesy of D. Umstadter, Univ. of Michigan Plasma Accelerators @ 100 GV/m Relativistic Thomson Monochromatic X-Ray Sources Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  16. hn RF Laser Driven Photo-Injectors: a break-through in High Brightness e- beams hn Photo-Linacs (driven by RF Photo-Injectors) rule over SR rings LCLS (requested @ 15 GeV) 4.1015 enx =eny=1.5 mm SPARC ultimate goal (Ph. 2) 2.1015 I = bunch peak current > kA ESRF (storage ring) < 1014 enx =20 mm eny=0.07 mm Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  17. SPARC: an Advanced Photo-Injector to drive a SASE-FEL @ LNF/INFN Co-funded by MIUR (2003-2006) and pursued by an inter-institutional collaboration INFN-ENEA-CNR-INFM-Univ.TorVergata-ST Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  18. Two additional beam lines at SPARC for plasma acceleration and monochromatic X-ray beams - the Project PLASMON-X 100 fs synchr. Ti:Sa multi-TW Laser System 1 J, 10 ps gaus 2 nC, 10 ps* Compr. 1 J, 100 fs gaus 20 mJ, 10 ps flat top 500 mJ 20 pC, 20 fs$ *en=2 mm, s =50 mm 1 nC, 10 ps, en=1 mm $en=0.2 mm, s =10 mm Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  19. lX@ llas / 4g2((1-cosY)/2) llas = 0.8 mm g=80 (40 MeV) lX =0.32 Å, 37 keV Blue-sky effect Thomson scattering if hn << m0c2 (no e- recoil) Spontaneous Synchrotron Radiation emitted by electrons oscillating in the intense laser field Laser Synchrotron Radiation Source Compact Sources of Monochromatic X-raysbased on Relativistic Thomson back-scattering Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  20. 1 J Laser pulse interacting with 1 nC 10 ps electron bunch @ 30 MeV w0=20 mm, s0=10 mm, Z0=1.5 mm , b*= 6 mm Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  21. Thomson Source frequency spectrum @ 20 keV gn=g/5 xn=2.236x,vxn=2.236vx Ntot=1,98107,Dw/w=7,5% Beam rms angle qm=5 mrad gn=g/5 xn=x, vxn=5vx Ntot=8,4 107,Dw/w=6,8% Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  22. Thomson Source frequency spectrum@ 500 keV (a)Beam rms angle qm=1 mrad Ntot=8,5107Dw/w=7,9% (b) Beam rms angle 0.7<qm<1.4 mrad Ntot=1.06 108Dw/w=11% (a)iris(b) hollow Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  23. Mono-chromatic X-rays allow to perform mass screening of coronaric artery deaseses, responsible for a large fraction of mortatility in western countries Our aim: develop Compact Systems compatible for operation in hospitals 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). Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  24. Mammography with Mono-chromatic X-Rays Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  25. MaMBO Experiment: Mammography Monochromatic Beam Outlook Main aim: conducting test experiments on phantoms with the PLASMON-X Mono-chromatic X-ray beam @ 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 Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  26. 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) Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  27. 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@0o-collision Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  28. X-band advanced protoype Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  29. COFIN Proposal for a 2 year R&D program on Compact X-band Thomson Sources subm. to MIUR Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  30. What is a SASE-FEL Radiation Source? a Bright Electron Beam propagating through an Undulator Spontaneous Radiation: peaked at lr@ lu / 2g2(1 + K2) ; g≥ 2.103 Beam rms divergence s’@ 1/g@ 100 mrad (Thomson Backscattering of undulator virtual photons) I r@ N e ; N e number of electrons per bunch (@ 109) Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  31. Interaction of e- with Spontaneous Radiation causes Microbunching and SELF-AMPLIFICATION of Spontaneous Emission (SASE) In the SASE mode the Intensity: I ph@ N eaa > 4/3 ; N e number of electrons (@ 109) Amplification gives extraordinary High Photon Flux (diffraction limited beam) Beam rms divergence s’@l / 2pse@ few mrad Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  32. 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 Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  33. 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 Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  34. 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! Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

  35. 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 R&D 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 Workshop on“Particle Accelerators and Detectors: from Physics to Medicine”

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