Actual dE/dx of heavy particles….

Applicazioni della fisica delle interazioni radiazione materia:

radioterapia e adroterapia

Actual dE/dx of heavy particles….

1/β²

Low β behaviour : z _eff

At β ~ 10

the electrons have the same velocity of the

projectile: energy transfer mechanism is no more efficient, reducing LET of stopping ions! zè z

This effect cause a sudden decrease of the dE/dx below the Bragg Peak

Z

= Z(1− exp

)

Z=4 Z=6 Z=10

Z=18 Z=92 Z=36

3

Range of charged particles

The energy loss of charge particles can be translated in a maximum range R (different from photons: attenuation)

E

= dE dx dx

0

∫

^dE dx ^∝

z

β

^ln

2 γ

β

m

c

I

^{+ ...}



  

  = z

f

( β ) = z

f

( E )

R ₌ dx

0 R

∫ ⁼ _z

_f ^dE

E

( E )

0 E₀₋mc²

∫ ^{= mc}

2

z

βd β f

( ₁₋ β

)

3 0 2

β₀

∫

The range R can be written as

dE ₌ mc

βd β 1− β

( )

3 2

Some useful scaling laws and behaviour can be obtained:

dE 1

1

Range ^{e + /e -} in ^Water

5

β decay electrons

RadioTherapy electrons

R ∝ E

Range and dose release:

different projectiles

the range & energy release by charge particles has very

attractive features

For thin layers or low density materials:

→ Few collisions, some with high energy transfer.

→ Energy loss distributions show large

fluctuations towards high losses: ”Landau tails”

For thick layers and high density materials:

→ Many collisions.

→ Central Limit Theorem → Gaussian shaped

energy ΔE deposited in a layer of finite thickness dx.

ΔE_m.p.» <ΔE>

e

DE e

δ electron

ΔEmost probable <ΔE>

DE

Energy loss fluctuations

7

Fluctuation in Energy Loss (straggling)

Energy losses of massive charged particles are a statistical

phenomenon and in each interaction different amounts of kinetic energy can be transferred to atomic electrons. The energy loss then has a distribution function. A possible parameterization is given by the Landau function:

1 1

( ) exp ( )

2 2

with

f e

E E

l l

p l

æ

ö

= ç è - + ÷ ø

D - D

=

δ -rays and energy straggling

• Energy loss distribution is not Gaussian around

mean (Landau dist.), because in some cases a lot of energy is transferred to a single electron: δ-rays.

• If the particle cross thick material than the energy distribution function gets Gaussian.

• If we assume that the particle looses ΔE in the Δx step in the material, the ΔE pdf is given by:

F(ΔE) = 1

2 πσ ^exp

ΔE − ΔE 2 σ



  

  ΔE = dE

dx Δx

σ

= 4 π ^z

^Ze

^N γ

⁽¹⁻ β

2 )Δx

The width of the gaussian

depends both on material and

projectile

Range fluctuations

The dE/dx is a stochastic process:

fluctuation of de/dx and range is

observed experimentally. The larger the dE/dx, the smaller the fluctuation

Mean range or CSDA range: Distance where I = I₀/2

Cosa succede a fine Range

Direzione del fascio di radiazioni nella materia

Posizione del tumore

11

Linear Energy Transfer (LET)

Linear energy transfer (LET) is a measure of the energy transferred to material as an ionizing particle travels through it. Typically, this measure is used to quantify the effects of ionizing radiation on biological specimens or electronic devices.

Linear energy transfer is closely related to stopping power .

Whereas stopping power, the energy loss per unit distance, focuses upon the energy loss of the particle, linear energy transfer focuses upon the energy transferred to the material surrounding the particle track, by means of secondary electrons

Since one is usually interested in energy transferred to the material in the vicinity of the particle track, one excludes secondary electrons with energies larger than a certain value Δ

Hence, linear energy transfer (also called "restricted linear electronic stopping

power") is defined by where refers to the energy loss due to electronic collisions

Linear Energy Transfer

• The LET is the rate at which energy is transferred to the medium and therefore the density of ionisation along the track of the radiation.

• LET is expressed in terms of keV/µm or MeV/cm

Radiation LET keV/µm 1 MeV γ-rays

100 kV_p X-rays 20 keV β-particles 5 MeV neutrons 5 MeV α-particles 1 GeV muon

0.5 6 10 20 50 0.2

Table from: P. Dendy & B. Heaton, Physics for Diagnostic Radiology, 2^nd Edition

dX LET = - dE

dE = energy lost by radiation dX = length of track

Radiation that is easily

stopped has a high LET and vice versa

13

Linear Energy Transfer (II)

The linear energy transfer or restricted linear

electronic stopping power, L _Δ for charged particles, is defined as:

L

= dE

dx

dE

is the energy lost by a charged particle due to

electronic collisions in a step dx, minus the sum of the kinetic energies of all the electrons released in the step with kinetic energy in excess of Δ.

Generally is intended LET = L

, i.e. the ratio between

Exposure

Exposure is:

A quantity used to indicate the amount of

ionization in air produced by x- or gamma-ray radiation

The SI unit of exposure is the coulomb per kilogram (C/kg)

15

Absorbed Dose

The absorbed dose, D, is given by:

D = dE/dm

Where dE is the mean energy imparted to matter of mass dm

The unit of absorbed dose is is Gray (Gy)

1 Gray = 1 J kg

La radioterapia oncologica

La radioterapia consiste nell'uso medico di radiazioni per il trattamento del cancro per controllare le cellule maligne.

La radioterapia può essere utilizzata come trattamento curativo o coadiuvante:

- cura palliativa (dove la cura non è possibile e l'obiettivo è praticamente il sollievo sintomatico) - come trattamento terapeutico (dove la terapia

ha come obiettivo l’aumento della sopravvivenza e può essere curativo).

17

La radioterapia oncologica

Scopi

è

Fornire un'elevata dose di radiazione nell'area tumorale

è

Evitare tessuti sani e organi a rischio

Tipi di radiazione

è “Convenzionale”: fotoni e elettroni

è Adroterapia (“Particle Therapy”): protoni e ioni leggeri (Z<18)

External beam radiation:

e ^- Linac per produrre fotoni

19

Radioterapia esterna con fotoni

Medical Linear accelerator

Treatment (Straight Beam) Head

Power Supply Modulator

Electron Gun

Magnetron Klystron Or

Wave Guide system

Treatment (Bent Beam) Head Bending Magnet Accelerator Tube

A block diagram of typical medical Linear Accelerator

Electron Energy ~ 16-25 MeV

Bremms

e

g

21

La strategia base del trattamento

Anche:

Modulazione delle intensità

23

Hadrons for Radiotherapy

1946, R. Wilson: first proposal to use hadrons for radiotherapy

in 1946

First hadron therapy in the sixties in US (Protons)

1954 – Berkeley treats the first patient and begins extensive studies with various ions 1957 – first patient treated with protons in Europe at Uppsala

Fasci di energia diversa depositano energia a profondità

nel tessuto→

lungo la

direzione del fascio

25

The physics of Bragg Peak

dominated by

interaction with electrons

MCS, Energy loss fluctuations and nuclear interactions do affect the shape

Elastic nuclear scattering

180 MeV proton in water

Longitudinal profile: Transversel profile:

Φ(z) Φ(z,x)

Interdisciplinary aspects:

Physics and Biology

p on the Bragg peak when Rres ~ 0.2 mm E ~ 4 MeV

LET ~ 10 keV/μm

<d> ~ 4 nm

12C on the Bragg peak when R_res~ 1 mm E ~ 17 MeV/u LET ~ 140 kev/μm

<d> ~ 0.3 nm ²⁷

Effetto microscopico dei raggi X

5 μm

e- range = 15 mm X ray = 4 MeV

LET = ΔE/ Δx espresso in keV/μm = eV/nm

ΔE Δx

150 ionizzazioni/cell (Fcell ≈20-30 µm)

Effetto microscopico dei raggi X

ROS = reactive oxyg en species

d = 40 eV / LET_eV/nm≈ 200 nm

5 μm

e- range = 15 mm X ray = 4 MeV

LET = ΔE/ Δx espresso in keV/μm = eV/nm

ΔE Δx

LET elettrone 0.2 keV/μm

200 nm

(Cortesia U. Amaldi) ²⁹

Microscopic distribution of the hadronic ionizations

electron 0.3 keV/μm

d = 40 eV / LET_eV/nm= 130 nm

20 nm 2 nm

Protons are quantitatively Protons are

SPARSELY IONIZING

Microscopic distribution of the hadronic ionizations

res R Kin En.

d_av

- 260 mm 200 MeV d=90 nm

- 75mm 100 MeV d=50 nm

- 4 mm 20 MeV d=15 nm

- 0.2 mm 4 MeV d=4 nm

20 nm

keV/μm 0.45 0.55 2.5 10

2 nm

- 260 mm 4800 MeV

d=4 nm

- 100 mm 2800 MeV

d=3 nm

- 42 mm 1800 MeV

d= 2 nm

- 1 mm 200 MeV d=0.3 nm

keV/μm 10 14 20 140

SSB

DSB

31

d=130 nm

Protons: 1. more favorable dose      2.  same  ‘indirect effects’

30 cm

Beam of 200 MeV protons X-rays beam

d=50 nm

d= 15 nm d=90 nm

d=130 nm

Carbon ions: 1. more favorable dose      2.  ‘direct effects’

30 cm

Beam of 200 MeV protons X-rays beam

Carbon ions are DENSELY IONIZING (higher biological effectiveness)

Beam of 4800 MeV carbon ions

d= 4 nm

d= 2 nm

d= 0.3 nm

Courtesy U.Amaldi ³³

Modulazione della profondità e capacita’

di conformazione

muovendo il fascio in X,Y e

variandone l’energia (profondità raggiunta) tutto il bersaglio puo’ essere efficacemente irradiato

35

Conformazione: il concetto di Spread Out Bragg Peak (SOBP)

Size of the tumor region

PTV = Planned Treatement Volume

This plot is in physical dose for a

constant biogical effectiveness

37

Riconsiderando gli esempi precedenti

Hadrontherapy IMRT

39

Passive

delivery Active

delivery

Treatment Delivery

Magneti deflettono lateralmente il fascio incidente di energia variabile allo scopo di irraggiare tutto il bersaglio che è suddiviso in volumi cubici(voxel) raggruppati in sezioni longitudinali (slices, la cui posizione dipende dall’energia)

Il concetto di raster scanning (scanning attivo)

41

In maggior dettaglio:

43

Non e’ conveniente utilizzare ioni piu’ pesanti del Carbonio: producono troppi frammenti nucleari che vanno piu’ lontano di quello che serve

Ione (nucleo di Carbonio): 6 protoni + 6 neutroni

Range di energia utile:

Protoni: 50 - 250 MeV

12

C: 60 - 400 MeV/u

Ciclotroni o Sincrotroni

soprattutto Sincrotroni

45

Particle therapy con nuclei (ioni): il caso del carbonio

Profilo di dose conforme in profondità

È facilmente assorbibile dai tessuti biologici

VANTAGGI

Elevata efficacia biologica “a fine corsa”

Possibilità verifica in-beam mediante PET

Tecnologie di produzione costose (>100 milioni di €)

SVANTAGGI

Frammentazione nucleare

Attuamente la terapia con ioni carbonio è effettuata a

•

48 clinical centers in operation

Under construction: 25 proton/4 heavy ion centers Only in USA 27 new centers expected by 2017

~2014: 137179 treated patients: 118195 with p, mainly in USA, 53532

15736 with

C,

+ 46,000 in the past 5 years≈ 10,000 patients per year

Charged Particle Therapy in the world

47

Picco di Bragg e interazioni nucleari

Carbon Ion Therapy

Bragg peak in a water phantom 400 MeV/A C beam:

The importance of fragmentation

16

O 284.1 MeV/u

49

28

SI 575.4 MeV/u

56

Fe 963 MeV/u

51

Straggling dependence on mass

Multiple scattering: gaussian approximation

Due to MS the charged particles wiggles along its path Δx through the material. The deflection angle is approximately gaussian

f ( ϑ ) = 1

2 πϑ

^{exp −}

ϑ

2 ϑ



  

  ϑ

= 13.6MeV β ^{cp z}

Δx

X

1+ 0.038ln Δx X



  

 



  

 

X

is the same of photons: 7/9 of the mean free path for pair production by a high-energy photon.

θ

is smaller for heavy and/or energetic particles. Electrons of MeV kinetic energy suffers a lot of multiple scattering

53

12C @ 299.94 MeV/u

K. Parodi et al Journal of Radiation Research, 2013, 54, i91–i96

Measured lateral distributions with corresponding MC simulations (normalized to the Entrance

channel Near to

Bragg peak

Ion Therapy: the lateral scattering

New ion beams for therapy

Beam size at the Isocenter

MC simulation of the CNAO beamline

55

Gli ioni di ⁴He sembrerebbero quindi convenienti rispetto ai protoni per via del minor spread laterale

Imaging diagnostico.

Il caso della TAC (CT)

Consider a flux I

of γ‘s crossing a material. Any photons of the beam can interact or cross unperturbed the slab. The amount of the photon

flux that interact in a thickness dx is given by:

The attenuation coefficient μ [cm

] is the probability of interaction per unit length and depends on energy an the material. Often is used normalized to density: μ/ρ [cm

/g].

Comparing with the

dI(x) = −I(x) µ ^dx

57

Si misura

l’attenuazione di un fascio di raggi X che attraversa il corpo da tante direzioni diverse (facendo una rotazione del fascio)

L’attenuazione è tanto

maggiore quanto maggiore è la densita degli elettroni

della materia attraversata (quanti eletttroni ci sono per unità di volume)

Si misura

l’attenuazione di un fascio di raggi X che attraversa il corpo da tante direzioni diverse (facendo una rotazione del fascio)

L’attenuazione è tanto

maggiore quanto maggiore è la densita degli elettroni

della materia attraversata

59

Si misura

l’attenuazione di un fascio di raggi X che attraversa il corpo da tante direzioni diverse (facendo una rotazione del fascio)

L’attenuazione è tanto

maggiore quanto maggiore è la densita degli elettroni

della materia attraversata (quanti eletttroni ci sono per unità di volume)

Si misura

l’attenuazione di un fascio di raggi X che attraversa il corpo da tante direzioni diverse (facendo una rotazione del fascio)

L’attenuazione è tanto

maggiore quanto maggiore è la densita degli elettroni

della materia attraversata

61

Si misura

l’attenuazione di un fascio di raggi X che attraversa il corpo da tante direzioni diverse (facendo una rotazione del fascio)

L’attenuazione è tanto

maggiore quanto maggiore è la densita degli elettroni

della materia attraversata (quanti eletttroni ci sono per unità di volume)

Si misura

l’attenuazione di un fascio di raggi X che attraversa il corpo da tante direzioni diverse (facendo una rotazione del fascio)

L’attenuazione è tanto

maggiore quanto maggiore è la densita degli elettroni

della materia attraversata

63

Si misura

l’attenuazione di un fascio di raggi X che attraversa il corpo da tante direzioni diverse (facendo una rotazione del fascio)

L’attenuazione è tanto

maggiore quanto maggiore è la densita degli elettroni

della materia attraversata (quanti eletttroni ci sono per unità di volume)

Da queste misure di attenuazione in varie direzioni si ricostruisce l’immagine.

C’è una teoria matematica alla base di questa operazione:

Trasformata di Radon

Tutto viene ripetuto per diverse

“fette” del corpo considerato

Hounsfield Units

65

The CT scan contains integer values “Hounsfield Unit”

reflecting the X-ray attenuation coefficient μ

HU

= 1000 (μ

-μ

) / μ

typically -1000 ≤ HU ≤ 3500

Nuclear reactions: elastic and non-elastic

In general there are two kind of nuclear reactions: elastic and non-elastic.

• Elastic interactions are those that do not change the internal

structure of the projectile/target and do not produce new particles.

Their effect is to transfer part of the projectile energy to the target (lab system), or equivalently to deflect in opposite directions target and projectile in the centre-of-mass system (CMS) with no change in their energy. There is no threshold for elastic interactions

• Non-elastic reactions are those where new particles are produced and/or the internal structure of the projectile/target is changed (eg exciting a nucleus). A specific non-elastic reactions has usually an energy threshold below which the reaction cannot occur (the

exception being neutron capture)

67

Hadron-Nucleon Cross Section

Total and elastic cross section for p-

and p-n scattering, together with experimental data

Models for Nucleus-Nucleus

interactions can be built

starting from nucleon-

Target nucleus description (density, Fermi motion, etc)

Preequilibrium stage

with current exciton configuration and excitation energy

(all non-nucleons emitted/decayed + all nucleons below 30-100 MeV) Glauber-Gribov cascade with formation zone

Generalized IntraNuclear cascade

Evaporation/Fragmentation/Fission model γ de-excitation

t (s) 10^-23

10^-22

10^-20

10^-16

Simplified scheme of Nuclear Interactions

69

From one to many

At energies below a few GeV hA interactions can be described by a single primary collision hN (elastic or non- elastic), followed by reinteraction of the secondary particles (INC). At higher energies, the Glauber calculus predicts explicit multiple primary collisions

Due to the relativistic length contraction and the uncertainty

The projectile is hitting a “bag” of protons and

neutrons representing the nucleus. The products of this interaction can in turn hit other neutrons and protons and so on. The most energetic particles, p,n, γ’s (and a few light fragments) are emitted in this

phase

… INC, a bit like snooker…

71

The projectile is hitting a “bag” of protons and

neutrons representing the nucleus. The products of this interaction can in turn hit other neutrons and protons and so on. The most energetic particles, p,n, γ’s (and a few light fragments) are emitted in this

phase

… INC, a bit like snooker…

The projectile is hitting a “bag” of protons and

neutrons representing the nucleus. The products of this interaction can in turn hit other neutrons and protons and so on. The most energetic particles, p,n, γ’s (and a few light fragments) are emitted in this

phase

… INC, a bit like snooker…

…it is in this phase that if energy is enough extra “balls” (new particles) are produced (contrary to snooker). The target

“balls” are anyway protons and neutrons, so further

collisions will mostly knock out p’s and n’s

Evaporation:

After many collisions and possibly particle emissions, the residual nucleus is left in a highly excited “equilibrated” state. De-excitation can be described by statistical models which resemble the

evaporation of “droplets”, actually low energy particles (p, n, d, t,

3He, alphas…) from a “boiling”soup characterized by a “nuclear

temperature”

Evaporation:

After many collisions and possibly particle emissions, the residual nucleus is left in a highly excited “equilibrated” state. De-excitation can be described by statistical models which resemble the

evaporation of “droplets”, actually low energy particles (p, n, d, t, 3He, alphas…) from a “boiling”soup characterized by a “nuclear temperature”

75

Evaporation:

After many collisions and possibly particle emissions, the residual nucleus is left in a highly excited “equilibrated” state. De-excitation can be described by statistical models which resemble the

evaporation of “droplets”, actually low energy particles (p, n, d, t, 3He, alphas…) from a “boiling”soup characterized by a “nuclear temperature”

The process is terminated when all available energy is spent ➜ the leftover nucleus, possibly radioactive, is now “cold”, with typical

recoil energies ~ MeV. For heavy nuclei the excitation energy can be

large enough to allow breaking into two major chunks (fission). Since

only neutrons have no barrier to overcome, neutron emission is

Evaporation:

After many collisions and possibly particle emissions, the residual nucleus is left in a highly excited “equilibrated” state. De-excitation can be described by statistical models which resemble the

evaporation of “droplets”, actually low energy particles (p, n, d, t, 3He, alphas…) from a “boiling”soup characterized by a “nuclear temperature”

The process is terminated when all available energy is spent ➜ the leftover nucleus, possibly radioactive, is now “cold”, with typical

recoil energies ~ MeV. For heavy nuclei the excitation energy can be large enough to allow breaking into two major chunks (fission). Since only neutrons have no barrier to overcome, neutron emission is

strongly favoured.

77

The abrasion-ablation paradigm

• Fragments from quasi-projectile have V

~V

and narrow emission angle. Longer range then beam

• The other fragments have wider angular distribution but lower energy. Usually light particles (p,d,He)

b

v

time Quasi-projectile decay Quasi-target fragments

Nuclear reactions: what really matters?

q Proton therapy

Ø Reaction cross sections (beam attenuation) +++

Ø Elastic cross sections +

Ø Particle (p,n,α..) emission + (mostly for background, ++

radiobiology)

Ø Positron emitter production + (data available)

q Therapy with ions

:

ü Reaction cross sections (beam attenuation) +++

ü Fragment (α included) production +++

ü Particle emission, p +++, others + ü Positron emitter production +++

q Conventional therapy

v (γ,x) (particularly (γ,n)) + (mostly for background) ₇₉

Biological effects

The biological effect of a given dose depends on the type of radiation, the target tissue, the fraction of an organ exposed and other factors.

In radiobiology, the ‘relative biological effectiveness’

(RBE) of a radiation type is defined as the ratio of the dose

of a standard radiation, frequently

Co γ rays, to the dose

of the radiation in question that gives the same biological

effect.

Efficacia Biologica Relativa (RBE)

• RBE: rapporto tra la dose di una radiazione di riferimento (D

) e la dose della radiazione in esame (D

) necessarie per ottenere lo stesso livello dell’effetto biologico considerato

0

. . .

SF r SF

RX

D E D

B R

÷÷

ø çç ö

è

= æ

SF_XR

SF _p

D0

p D XR

SF RBE SF

÷ =

÷ ø ö çç

è

=æ

81

Uso di diverse qualità di radiazione.

Il concetto di RBE

Efficacia Radiobiologica (numero puro)

Il danno biologico è proporzionale al prodotto:

RBE * Energia deposta

Raggi X RBE = 1 Protoni RBE ~ 1.1 12-C RBE ~ 3-4

Attenzione:

Da indagare!!!

RBE vs LET

83

fare un SOBP uniforme nel

caso di RBE variabile...

Treatment Planning in hadrontherapy

(Effective) Dose Optimization

Imaging:

CT scan

and/or PET-CT)

Electron density

Intensity, position and energies to be delivered

to patient

Radiobiology:

RBE parameters OER (not yet…)

Treatment Planning System

Nuclear Physics:

Dose vs Depth

hadrone/nucleus scattering:

fragments etc.

Radiotherapist:

identification of Target Volume and of Organs at Risk

85

Inverse planning per scansione attiva

2 2

2

= [ D

- D

] + [ D

- D

]

C å å

Input:

• Hounsfield numbers (dalla CT) dei voxels in cui è suddiviso l’intero volume anatomico

• Identificazione da parte del clinico del volume da trattare e la dose da somministrare e degli organ-at-risk (OAR) e la dose

massima

Si può scrivere la funzione-costo da minimizzare e come esempio si

può usare la seguente:

Treatment Planning System

TPS is directly related to scanning modality and RBE evaluation model

Need to include management of moving organs and integration of in-room imaging

(TPS used at CNAO) ⁸⁷

The Hyogo ‘dual’ Centre

carbon

proton

29 m linac

Hyogo Dual Center

HIT - Heidelberg

Ion- Sources

LINAC

Synchrotron

Treatment halls by Siemens Medical

High Energy Beam Transport Line

Quality Assurance

Gantry

First patient: end 2009 So far about 2.000 patients

89

CNAO - Pavia

Il sincrotrone del CNAO

91

Design compatto

Dose delivery system

93

inizio terapia clinica a fine Ottobre 2014

ProtonTerapia di Trento

1 fixed line room for research irradiations Two scanning-only 360°gantries Energies at isocentre from 70 to 226 MeV 2D imaging in one gantry room Ct on rail being installed in the second gantry room

95

Rivelatori per Radio e Adroterapia

Peakfinder water column

Rivelatori per Radio e Adroterapia

Integral Depth Dose Distributions (mono-en. pencil beams)

121 MeV/u

97

Depth Dose Distributions (mono-en. pencil beams)

«Peakfinder»

Rivelatori per Radio e Adroterapia

Integral Depth Dose Distributions (mono-en. pencil beams)

121 MeV/u

Depth Dose Distributions (mono-en. pencil beams)

121 MeV/u

«Peakfinder»

99

101

Nozzle and monitor system

z

E₀<E₁<…<E_n

Isocentro

x E⁰E¹ Eⁿ

Scanning magnets

Disegno - Realizzazione - Test - Utilizzo clinico

E

Slice

Sistema di distribuzione e

monitoraggio on-line del fascio

101

Le incertezze: il problema del range

Delegates were asked what they considered as the main obstacle to proton therapy becoming

mainstream:

• 35 % unproven clinical advantage of lower integral dose

•19 % never become a mainstream treatment option

• 33 % range uncertainties AAPM, August 2012

Incertezze sul Range

Different density → different range

P Andreo, Phys Med Biol, 2009

– Energy uncertainty

– Heterogeneity density effect

– Patient positioning

– Moving target

– CT scan calibration

– CT artefacts

– Anatomical changes

– RBE changes

Charged Particle therapy Photon therapy

103

How to mitigate uncertainties?

– PET

– Prompt γ imaging

– Charged particles

– …

Bea m

511 keV

proto n

• Controlled patient positioning

• Motion effect mitigation

• Moving target control

• Well known CT scan

• Artefact removing algorithms

• Adaptive RT

• Margins

Monitoring on-line con i secondari

Beam

511 keV

511 keV

prompt

proton

neutron I fasci di p,

C generano una grande quantità di secondari:

prompt gs (diseccitazione nucleare), PET- gs, neutroni e frammenti carichi Rivelatori esterni al paziente possono essere utilizzati come monitor del trattamento

Baseline: attività indotta β⁺

• Isotopi tipici:

10C (20 s)

tempo di dimezzamento breve rispetto ai radionuclidi utilizzati per la diagnostica medica (ore)

• Bassa attività: tempi di acquisizione di qualche minuto. Difficoltà nel feedback

• Wash-out metabolico degli emettitori β⁺ : importante misurare in vivo

105

Correlation between β ⁺ activity and dose

Projectiles & target

fragmentation Target fragmentation

Gli isotopi nucleari rilevanti

107

Dose

Monte Carlo

β

-activity

β

-activity Dose

Irradiat ion

Evaluation and reaction

W. Enghardt et al.: Radiother. Oncol. 73 (2004) S96

In-Vivo range measurement with PET:

workflow and potential

Positron Emission Tomography in vivo

Primo tentativo di in-beam PET: GSI, con ~400 pazienti 109

Inorganic crystals

511 keV photons

Looking for coincidence of hit crystal in opposite cameras

Le alternative

Si può correlare la distribuzione del punto di emissione dei fotoni con la posizione del piucco di Bragg

secondari carichi a grande angolo possono essere facilmente tracciati e correlati con la posizione del picco di Bragg

Il caso dei Prompt Photons

• Nuclear De-excitation photons are quite copiously produced by proton and

C beams.

• The emission region stretches along all the beam path but has been shown to ends near the Bragg peak for both beams.

• Experimentally: there is a huge background due to neutrons &

uncorrelated gamma produced by neutrons. This background is beam, energy and site specific

111

Emissione a «righe» + fondo continuo

Range di energia utile: ~2-10 MeV

Τest Beams: γ’s

@GANIL

• 73 AMeV carbon beam

• g peak correlated with BP

• MC one order of magnitude off

but it’s improving fast ⁾

• Neutrons background (TOF rejection ?)

BP position

The slit camera

• Optimized on proton beam

• Optimized for range measurement

beam

J Smeets et al. Phys. Med. Biol. 57 (2012) 3371

113

Knife-edge-slit camera by IBA

Courtesy of J. Smeets

Νew approach: charged particles

Charged particles have several nice features as

• The detection efficiency is almost one

• Can be easily back-tracked to the emission point->

can be correlated to the beam profile & BP

proton beam

BUT…

• They are not so many as photons

• Energy threshold to escape

~ 100 MeV

• They suffer multiple

scattering inside the patient -> worsen the back-pointing

resolution

First Exp. Test at large angle with ¹² C ions

PMMA Beam

LYSO Crystals PMT StartCounter 2

PMTs+Scint.

//

x

y z

DC

VETO StartCounter 1

PMTs+Scint.

Charged secondary produced at 90

by

12

C 220 MeV/u at GSI

Beam radiography

Beam Beam

L. Piersanti et al. 2014 Phys. Med. Biol. 59 1857

Bragg

Beam radiography

dN_ch

60^o

( )

INnovative Solutions for In-beam DosimEtry in Hadrontherapy

Funds: PRIN + Centro Fermi + INFN (RM1-TO-MI-PI)

q

Dual signal operation

q

integrated in treatment room

q

Provide in-beam feedback on beam range

q

Challenge: fusion of charged and PET information

The Project @

β

activity

HEADS

proton emission

Tracker + Calorimeter = DOSE PROFILER

117

✤

Detectors to measure the 511 keV back-to-back photons in order to reconstruct the β

activity map.

✤

Two planar panels: 10 cm x 20 cm wide => 2 x 4 detection modules;

✤

1-2 mm resolution expected along the beam path

Each module = pixelated LSO matrix 16 x 16 pixels, 3 mm x 3 mm crystals (pitch 3.1mm)

The INSIDE PET System

LSO CALO

⊡ 3 x 3 mm² MAPMT 64 ch

6 UV PLANES Fiber ⊡ 0.5 mm Fiber readout

SiPM ⊡ 1 mm

The INSIDE charge Profiler

Tracker: back-tracking of secondary protons to the beam line

Calo: select higher energy protons to minimize MS in the patient.

Reconstruction: deconvolution of absorption inside the patient from the emission shape

Calibration: BP position vs Emission shape parameters

119

Planes composed of 2

orthogonally oriented layers of plastic scintillating fibres (squared 500 µm)

SiPMs readout (1 mm²)

LSO CALO

⊡ 3 x 3 mm² MAPMT 64 ch Fiber readout

SiPM ⊡ 1 mm

The INSIDE charge Profiler

Tracker: back-tracking of secondary protons to the beam line

Calo: select higher energy protons to minimize MS in the patient.

Reconstruction: deconvolution of absorption inside the patient from the emission shape

Calibration: BP position vs Emission

Planes composed of 2

orthogonally oriented layers of plastic scintillating fibres (squared 500 µm)

SiPMs readout (1 mm²) Traccia ricostruita in proiezione X-Z

121

Teste PET Dose Profiler

(tracciatore carichi)

La tomografia a Protoni

Idea: from Computed Tomography using X rays to Proton Computed Tomography (pCT): protons and photons have different interaction with matter and pCT could exploit directly proton info directly for dose calculation

( ) _{ò ( )}

ò ⁼

out

E

E L

e S E

K dE r

d

h r

E_in is the incident proton energy and E_out is the proton energy after traversing through the object, S(E) is the proton stopping power, and K is a constant.

BUT the exact path L in the pCT in unknown due to Multiple

Coulomb Scattering and only initial and final information can be

measured for each proton

La tomografia a Protoni: vantaggi potenziali

Posizionamento del Paziente:

pCT potrebbe garantire una accuratezza migliore, soprattutto in futuri trattamenti con ipofrazionamento

Calcolo della Dose:

pCT permetrebbe di utilizzare direttamente la risposta dei protoni per il calcolo della dose

123

proton based imaging system (pCT)

Conventional X ray tomographies taken before the proton treatment session and in a different setup. Precision improvement if positioning and treatment could be done in one go

Treatment planning is defined using X-CT but protons and photons interact differently with matter. Direct measure of the stopping power maps with same particles used to irradiate

1 100 10⁴

X-Ray Absorption Coefficient

Bone Muscle H2O Fat

µ

[1/cm] ¹⁰

100

Stopping Power for Protons

Bone Muscle H2O

dE/dl Fat

[MeV/cm]

Proton CT:

• replaces X-ray absorption with proton energy loss

• reconstruct mass density (r)

distribution instead of electron

distribution

PARAMETER VALUE Proton beam kinetic

energy ~300 MeV

Proton beam rate 1 MHz

Spatial resolution < 1 mm

Electronic density

resolution <1%

Detector radiation

hardness >1000 Gy

Dose per scan < 5 cGy

P₁ P₂ P₃ P₄

z y x

• Single particle proton tracking: silicon strip detectors → MLP

• Residual energy measurement: crystal calorimeter → energy loss

A set of single event information can be processed by appropriate reconstruction algorithms (FBP, ART) to produce tomographic images.

No particular request on track or calo system…

PCT principle and setup

Prima – RDH Collaboration 125

Silicon strip tracker.

High resistivity n-type Float Zone Silicon 200^µm thick - Single side microstrip Squared size 5.25 x 5.25 cm²

256 strips, AC coupled – width: 60^µm,

Proof of principle at 60 MeV LNS p beam

pCT reconstruction after patient

positioning for treatment and Treatment Planning System recalculation with pCT data need massive CPU power –> real challenge of pCT on the fly

GPU technology needed (INFN-RIDOS-

FRED)

x100^µm

x100µm

Vanzi E. et al., Nucl. Instr. and Meth. A 730 (2013)

Reconstruction of PMMA phantom with Filtered Back Projection as seed for

Algebraic Reconstruction Technique. Using Modified

Radon Transform:

+¥

òò

¥ -

- +

= X x y F s xsen y dxdy s

p( ,

q

q

q

X(x,y) p(s,θ)

q s

Test Trento October 2016

Calorimeter and two traker planes

The main aim was to integrate the tracker-calorimeter system and to take

a radiography of an anthropomorphic phantom (by courtesy of Centro

Protonterapia)

Test Trento October 2016

129

Front radiography using residual energy and

stopping power integral map:

− "

#_$%

#_&'(

[ *

+ ,

. ]

12

Test Trento October 2016

Front radiography using residual energy and

stopping power integral map:

− "

#_$%

#_&'(

[ *

+ ,

. ]

12

5 mm diameter

metal thoot insertion

Metallic spine prostheses

proton radiography at LANL

using 800 MeV protons

of course a wonderful resolution at this energy

But this is not achievable with normal therapeutic beams!

(p with E

~250 MeV)

131

END

Per ulteriori informazioni e approfondimenti contattare:

giuseppe.battistoni@mi.infn.it silvia.muraro@mi.infn.it