Medical Applications of Particle Physics:Medical Applications of Particle Physics:pp ypp yfrom the First Radiography to Hadrontherapyfrom the First Radiography to Hadrontherapy

Saverio BracciniSaverio Braccini

Albert Einstein Albert Einstein Center for Fundamental PhysicsCenter for Fundamental PhysicsLHEPLHEP –– Laboratory for High Energy PhysicsLaboratory for High Energy PhysicsLHEP LHEP Laboratory for High Energy PhysicsLaboratory for High Energy Physics

University of Bern, SwitzerlandUniversity of Bern, Switzerland

Rome - 15-18.03.10 - SB - 1/8 1saverio.braccini@cern.chsaverio.braccini@cern.ch

OutlineOutline

1.1. Introduction: a historical overviewIntroduction: a historical overview1.1. Introduction: a historical overviewIntroduction: a historical overviewoo Physics and medicine: two paths, many crossroadsPhysics and medicine: two paths, many crossroadsoo The first radiography and the concept of doseThe first radiography and the concept of dose

22 M d di l di iM d di l di i2.2. Modern medical diagnosticsModern medical diagnostics3.3. Particle accelerators for medicineParticle accelerators for medicine44 Conventional radiation therapyConventional radiation therapy4.4. Conventional radiation therapyConventional radiation therapy5.5. Basic principles of hadrontherpyBasic principles of hadrontherpy6.6. Present and future of hadrontherapyPresent and future of hadrontherapy7.7. A tour in a hadrontherapy centreA tour in a hadrontherapy centre8.8. Specific topics in hadrontherapySpecific topics in hadrontherapy

Rome - 15-18.03.10 - SB - 1/8 2

Fundamental research in particle physics and modern medicineFundamental research in particle physics and modern medicineFundamental research in particle physics and modern medicineFundamental research in particle physics and modern medicine

Two paths, many crossroadsTwo paths, many crossroads

Rome - 15-18.03.10 - SB - 1/8 3

The starting point The starting point

•• November 1895 : discovery of X raysNovember 1895 : discovery of X rays

Wilhelm Conrad RöntgenWilhelm Conrad Röntgen

•• December 1895 : first radiographyDecember 1895 : first radiography

Rome - 15-18.03.10 - SB - 1/8 4

…the real first medical radiography……the real first medical radiography…

Important points:Important points:

•• XX--rays penetrate matterrays penetrate matterXX rays penetrate matterrays penetrate matter

•• XX--rays are differently absorbed by bone and rays are differently absorbed by bone and muscle tissuesmuscle tissues

E ti 15 i tE ti 15 i t•• Exposure time 15 minutesExposure time 15 minutes

•• Exposure nowadays for a hand radiography:Exposure nowadays for a hand radiography:

•• 1/25 to 1/50 second1/25 to 1/50 second1/25 to 1/50 second1/25 to 1/50 second

•• Dose: about <0.1 mSv (natural Dose: about <0.1 mSv (natural background 1background 1--2 mSv/year)2 mSv/year)

Radiography of the hand of Radiography of the hand of

CuriositiesCuriosities

•• Roentgen convinced his wife to participate Roentgen convinced his wife to participate in an experimentin an experiment

Roentgent’s wife BerthaRoentgent’s wife Bertha •• Bertha was horrified and saw in the image a Bertha was horrified and saw in the image a premonition of deathpremonition of death

Rome - 15-18.03.10 - SB - 1/8 5

Basic unitsBasic units•• The The physical dosephysical dose absorbed by matter is measured in Grayabsorbed by matter is measured in Gray

•• 1 Gy = 1 J / 1 Kg1 Gy = 1 J / 1 Kg

•• Used in radiation therapyUsed in radiation therapy•• Used in radiation therapyUsed in radiation therapy

•• In radioprotection the In radioprotection the dose equivalent dose equivalent is measured in Sievertis measured in Sievert

•• Dose Equivalent = (Physical dose) x Wr Dose Equivalent = (Physical dose) x Wr

•• Wr takes into account the biological effects of specific radiationWr takes into account the biological effects of specific radiation

Rome - 15-18.03.10 - SB - 1/8 6

Basic unitsBasic units

•• In radioprotection the In radioprotection the effective doseeffective dose is defined asis defined as

•• Effective dose = (Physical dose) x Wr x Wt Effective dose = (Physical dose) x Wr x Wt

•• Wt takes into account the sensitivity to radiation of different organs for Wt takes into account the sensitivity to radiation of different organs for stochastic effectsstochastic effects

Rome - 15-18.03.10 - SB - 1/8 7

Dose equivalent and effective doseDose equivalent and effective dose

•• Wr is a multiplicative factor to take into account the “biological effectiveness” Wr is a multiplicative factor to take into account the “biological effectiveness” of radiationof radiation

•• Wt has a different meaningWt has a different meaning

•• Σ Wt = 1Σ Wt = 1

•• If the dose is “full body” If the dose is “full body” dose equivalent = effective dosedose equivalent = effective dose

•• If the irradiation is not homogeneous (ex. The dose is given only to one If the irradiation is not homogeneous (ex. The dose is given only to one ) th ff ti d t th d i l t i t th f ll) th ff ti d t th d i l t i t th f llorgan) the effective dose represents the dose equivalent given to the full organ) the effective dose represents the dose equivalent given to the full

body which produces the same risk. body which produces the same risk.

•• Risk for stochastic effects:Risk for stochastic effects:Annual limit for radio exposed workers

Risk for stochastic effects:Risk for stochastic effects:

Rome - 15-18.03.10 - SB - 1/8 8

Stochastic and deterministic effects of radiationStochastic and deterministic effects of radiation

•• The cancer induction risk factor is estimated at 4% SvThe cancer induction risk factor is estimated at 4% Sv--1 for a population of 1 for a population of workers and at 5 % Svworkers and at 5 % Sv--1 for the general population (children included!)1 for the general population (children included!)

•• The threshold dose of deterministic effects is situated at 0.5 Gy.The threshold dose of deterministic effects is situated at 0.5 Gy.

•• Deterministic effects:Deterministic effects:

•• The aim of radiation therapy is to cure i.e. to produce deterministic effectsThe aim of radiation therapy is to cure i.e. to produce deterministic effects

•• The doses are therefore large (of the order of 60The doses are therefore large (of the order of 60--80 Gy) and there are no limits 80 Gy) and there are no limits g (g ( y)y)for patients coming form laws on radiation protectionfor patients coming form laws on radiation protection

Rome - 15-18.03.10 - SB - 1/8 9

XX--rays: what we know today…rays: what we know today…

XX--ray tube : accelerated electrons ray tube : accelerated electrons yyinteract and radiate photonsinteract and radiate photons

==

XX--ray productionray production

XX ray energy spectrumray energy spectrum

Rome - 15-18.03.10 - SB - 1/8 10

XX--ray energy spectrumray energy spectrum

Production of X and Production of X and γγ “quanta” “quanta”

atom

ionization

Physicists:Physicists:

keV → X quantakeV → X quanta

M VM V ttionization MeV → MeV → γγ quantaquanta

Medical doctors:Medical doctors:nucleus

Medical doctors:Medical doctors:

They are all X rays!They are all X rays!

3 MeVquantum

heavy nucleus

electron acceleratedto 10 MeV

nucleus

scattered electron7 MeV

electromagneticfield drawn

by the electron

Rome - 15-18.03.10 - SB - 1/8 11

The physical processThe physical process

Rome - 15-18.03.10 - SB - 1/8 12

Photons interact with matterPhotons interact with matterXX--rays interact with matter (material Z) rays interact with matter (material Z) through different mechanisms:through different mechanisms:

•• PhotoPhoto--electric effectelectric effect

•• Compton effectCompton effect ProbabilityProbabilityCompton effectCompton effect

•• Electron Positron pair productionElectron Positron pair production

(Threshold : 2 x 511 keV)(Threshold : 2 x 511 keV)

yy

( )( )

What happens to a photon beam ?What happens to a photon beam ?

II00 I = II = I00 ee--μμss μμ attenuation coefficientattenuation coefficientDepends on:Depends on:pp

•• The material (z)The material (z)

•• The densityThe density

Rome - 15-18.03.10 - SB - 1/8 13

ss •• The energy of the photonsThe energy of the photons

The attenuation coefficientThe attenuation coefficient

Why water?Why water?Water is the main component of tissuesWater is the main component of tissues

“Water equivalent” a very used concept in“Water equivalent” a very used concept in

Rome - 15-18.03.10 - SB - 1/8 14

Water equivalent a very used concept in Water equivalent a very used concept in medical applicationsmedical applications

Water and other materialsWater and other materials

Rome - 15-18.03.10 - SB - 1/8 15

Let’s get back to RoentgenLet’s get back to Roentgen

Many XMany X--rays stop in the tissuesrays stop in the tissues

Dose to the patient!Dose to the patient!

Rome - 15-18.03.10 - SB - 1/8 16

The beginning of modern physics andThe beginning of modern physics andmedical physicsmedical physics

An accelerator of 1897An accelerator of 18971895 1895 –– starting date of four starting date of four magnificent years in magnificent years in experimental physicsexperimental physics

18951895

experimental physicsexperimental physics

discovery of X raysdiscovery of X raysWilhelm Conrad Wilhelm Conrad RöntgenRöntgen

Rome - 15-18.03.10 - SB - 1/8 17

J.J. Thomson and the electronJ.J. Thomson and the electron

The beginning of modern physics andThe beginning of modern physics andmedical physicsmedical physics

Henri Becquerel Henri Becquerel (1852(1852--1908)1908)

1896:1896:

Discovery of naturalDiscovery of natural

radioactivityradioactivity

18981898Thesis of Mme. Curie – 1904

18981898

Discovery of radiumDiscovery of radiumα, β, γ in magnetic field

Rome - 15-18.03.10 - SB - 1/8 18

MariaMariaSkSkłodowska Curiełodowska Curie

(1867 (1867 –– 1934)1934)

About one hundred years agoAbout one hundred years agoPierre CuriePierre Curie(1859 (1859 –– 1906)1906)

First applications in cancer therapyFirst applications in cancer therapy

Basic conceptBasic conceptLocal control Local control of the tumourof the tumour

1908 : first attempts of skin cancer 1908 : first attempts of skin cancer radiation therapy in France radiation therapy in France (“(“CuriethérapieCuriethérapie”)”)

Rome - 15-18.03.10 - SB - 1/8 19

(( pp ))

A big step forward…A big step forward…

…in physics and in…in physics and in

•• Medical diagnostics Medical diagnostics

•• Cancer radiation therapyCancer radiation therapyCancer radiation therapyCancer radiation therapy

due to the development of threedue to the development of threeM. S. Livingston and E. LawrenceM. S. Livingston and E. Lawrence

with the 25 inches cyclotronwith the 25 inches cyclotron

due to the development of three due to the development of three fundamental toolsfundamental tools

•• Particle acceleratorsParticle accelerators

P i l dP i l d•• Particle detectorsParticle detectors

•• ComputersComputers

Rome - 15-18.03.10 - SB - 1/8 20

GeigerGeiger--MMüller counter built byüller counter built byE. Fermi and his group in RomeE. Fermi and his group in Rome

1930: invention of the cyclotron1930: invention of the cyclotron1930: the beginning of 1930: the beginning of four other magnificent four other magnificent

yearsyears

Spiral trajectory of an Spiral trajectory of an accelerated nucleusaccelerated nucleus

Ernest Lawrence Ernest Lawrence

(1901 (1901 –– 1958)1958)

Modern cyclotronModern cyclotron A copy is on display at A copy is on display at CERN MicrocosmCERN Microcosm

Rome - 15-18.03.10 - SB - 1/8 21

CERN MicrocosmCERN Microcosm

The invention of the cyclotronThe invention of the cyclotron

•• Magnet of 9 inches = 22.8 cm Magnet of 9 inches = 22.8 cm

•• Magnetic field of 15 000 gauss = 1.5 TMagnetic field of 15 000 gauss = 1.5 Tg gg g

Rome - 15-18.03.10 - SB - 1/8 22

E. O. Lawrence and M. S. Livingston, Physical Review, 38 (1931) 834.

The Lawrence brothersThe Lawrence brothers

Rome - 15-18.03.10 - SB - 1/8 23

Ernst Lawrence and his brother John Lawrence   at the control panel of the 60‐inch (152 cm) cyclotron shortly. 

The Lawrence brothersThe Lawrence brothers

John Lawrence, brother of John Lawrence, brother of Ernest, was a medical doctorErnest, was a medical doctor

They were both working in They were both working in BerkleyBerkley

First use of artificially produced First use of artificially produced isotopes for medical diagnostics isotopes for medical diagnostics p gp gand therapyand therapy

Beginning of nuclear medicineBeginning of nuclear medicineBeginning of nuclear medicineBeginning of nuclear medicine

An interdisciplinary An interdisciplinary environment helps environment helps

innovation!innovation!

Rome - 15-18.03.10 - SB - 1/8 24

Discovery of the neutronDiscovery of the neutron

19321932

James ChadwickJames Chadwick

(1891 (1891 –– 1974)1974)

Neutrons are used today toNeutrons are used today to

Student of Student of

Ernest RutherfordErnest Rutherford

•• Produce isotopes for medical diagnostics Produce isotopes for medical diagnostics and therapyand therapy

•• Cure some kind of cancer Cure some kind of cancer

Rome - 15-18.03.10 - SB - 1/8 25

Ernest RutherfordErnest Rutherford

Matter and antimatter...Matter and antimatter...

Rome - 15-18.03.10 - SB - 1/8 26

1932 1932 –– discovery of antimatter: the positrondiscovery of antimatter: the positron

Slowed-down

ti lparticleCLOUD

CHAMBER

Positive fast particle

Lead layer

Carl D. Anderson Carl D. Anderson -- CaltechCaltech

pcoming from below

Rome - 15-18.03.10 - SB - 1/8 27

The positron is at the basis of Positron Emission Tomography (PET)The positron is at the basis of Positron Emission Tomography (PET)

Discovery of the effectiveness of slow neutronsDiscovery of the effectiveness of slow neutrons

O. D’Agostino E. Segrè E. Amaldi F. Rasetti E. FermiO. D’Agostino E. Segrè E. Amaldi F. Rasetti E. FermiO. D Agostino E. Segrè E. Amaldi F. Rasetti E. FermiO. D Agostino E. Segrè E. Amaldi F. Rasetti E. Fermi

19341934First radioisotope of IodineFirst radioisotope of Iodine

Rome - 15-18.03.10 - SB - 1/8 28

among fifty new artificial speciesamong fifty new artificial species

Also for physicists, patents are important!Also for physicists, patents are important!

Rome - 15-18.03.10 - SB - 1/8 29

Istituto Superiore di Sanità Istituto Superiore di Sanità -- 19341934

“Il tubo”“Il tubo”

Rome - 15-18.03.10 - SB - 1/8 30

“Il tubo” “Il tubo” –– 1 MeV Cockcroft1 MeV Cockcroft--Walton ion accelerator Walton ion accelerator --1938193819381938

Rome - 15-18.03.10 - SB - 1/8 31

Fermi and the use of radio isotopes in medicineFermi and the use of radio isotopes in medicine

Rome - 15-18.03.10 - SB - 1/8 32

Four other crucial years: the synchrotronFour other crucial years: the synchrotron

19441944

principle of phase stabilityprinciple of phase stabilityVertical magnetic

field principle of phase stabilityprinciple of phase stability

Circular trajectory of the Circular trajectory of the particles accelerated in a particles accelerated in a

field

1 GeV electron synchrotron1 GeV electron synchrotron

Frascati Frascati -- INFN INFN -- 19591959

“synchrotron”“synchrotron”

Veksler visits McMillanVeksler visits McMillan

Rome - 15-18.03.10 - SB - 1/8 33

1959 1959 -- BerkeleyBerkeley

RadioRadio--frequency linacs for protons and ionsfrequency linacs for protons and ions

Linear accelerator (linac)Linear accelerator (linac)

200 MHzλ= 1.5 m

L AlvarezL Alvarez100 MeV linac on display 100 MeV linac on display L. AlvarezL. Alvarez

1946 1946 –– Drift Tube LinacDrift Tube Linacat CERN Microcosmat CERN Microcosm

Rome - 15-18.03.10 - SB - 1/8 34

The electron linacThe electron linac

Sigurd VarianSigurd Varian William W. HansenWilliam W. Hansen

Russell VarianRussell Varian

19391939

Invention of the klystronInvention of the klystron

~ 1 m~ 1 m

Invention of the klystronInvention of the klystron1947 1947

first linac for electronsfirst linac for electrons4 5 M V d 3 GH4 5 M V d 3 GH

The electron linac is used today in The electron linac is used today in hospital based conventional radiation hospital based conventional radiation

Rome - 15-18.03.10 - SB - 1/8 35

4.5 MeV and 3 GHz4.5 MeV and 3 GHzpptherapy facilitiestherapy facilities

The beginning of CERN 50 years agoThe beginning of CERN 50 years ago

1952: Pierre Auger Edoardo Amaldi1952: Pierre Auger Edoardo Amaldi

Secretary GeneralSecretary General

19521952--5454

Isidor RabiIsidor Rabi

UNESCO talk in 1950UNESCO talk in 1950

19521952--5454

at the meeting that created the provisional CERNat the meeting that created the provisional CERN

Rome - 15-18.03.10 - SB - 1/8 36

At CERN we have linacs and strongAt CERN we have linacs and strong--focusing synchrotronsfocusing synchrotronsLLarge

HadronCollider

(7+7) TeV8.5 km8.5 km

(7 7) TeV

In 1952 the “strongIn 1952 the “strong--focusing” methodfocusing” methodThe PS in 1959The PS in 1959 gg gg

invented at BNL (USA)invented at BNL (USA)

was chosen for the CERN PSwas chosen for the CERN PS

Rome - 15-18.03.10 - SB - 1/8 37

Accelerators running in the worldAccelerators running in the world

~120High Energy acc (E >1GeV)NUMBER IN USE (*)NUMBER IN USE (*)CATEGORY OF ACCELERATORSCATEGORY OF ACCELERATORS

>100>100~200~200

Synchrotron radiation sourcesSynchrotron radiation sourcesMedical radioisotope productionMedical radioisotope production

120High Energy acc. (E >1GeV)

~1000Research acc. included biomedical research

> 7500> 7500Radiotherapy acceleratorsRadiotherapy accelerators 90009000

>7000Ion implanters, surface modification

~1500Acc. for industrial processing and research

> 17500> 17500TOTALTOTAL

(*) W. Maciszewski and W. Scharf: Int. J. of Radiation Oncology, 2004

Ab t h lf d f biAb t h lf d f bi di l li tidi l li tiRome - 15-18.03.10 - SB - 1/8 38

•• About half are used for bioAbout half are used for bio--medical applicationsmedical applications

Particle detectorsParticle detectors

Th th “ ” f ti l h i i tTh th “ ” f ti l h i i tThey are the “eyes” of particle physicistsThey are the “eyes” of particle physicists

A very impressive development in the last 100 yearsA very impressive development in the last 100 years

–– From the Geiger counter to ATLAS and CMS at CERN!From the Geiger counter to ATLAS and CMS at CERN!

Crucial in many medical applicationsCrucial in many medical applicationsCrucial in many medical applicationsCrucial in many medical applications

Rome - 15-18.03.10 - SB - 1/8 39

One example: the multiwire proportional chamberOne example: the multiwire proportional chamber

Georges Charpak, CERN Georges Charpak, CERN physicist since 1959,physicist since 1959,

Nober prize 1992Nober prize 1992

•• Invented in 1968, launched the era of fully electronic particle detectionInvented in 1968, launched the era of fully electronic particle detection

Nober prize 1992Nober prize 1992

, y p, y p•• Used for biological research and could eventually replace photographic recording Used for biological research and could eventually replace photographic recording in applied radioin applied radio--biologybiology•• The increased recording speeds translate into faster scanning and lower body The increased recording speeds translate into faster scanning and lower body

Rome - 15-18.03.10 - SB - 1/8 40

doses in medical diagnostic tools based on radiation or particle beamsdoses in medical diagnostic tools based on radiation or particle beams

Radiography and imaging with radiationsRadiography and imaging with radiations

General features:General features:

Sensitivity of the detector = less dose to the patientSensitivity of the detector = less dose to the patient

Granularity of the detector = better image definitionGranularity of the detector = better image definitionGranularity of the detector = better image definitionGranularity of the detector = better image definition

Speed of the detector = detection of movementsSpeed of the detector = detection of movements

Rome - 15-18.03.10 - SB - 1/8 41

End of part IEnd of part I

Rome - 15-18.03.10 - SB - 1/8 42