hadron imaging and x-ray dosimetry systems in clinical radiotherapy · 2019-05-15 · hadron...

Hadron Imaging and X-ray dosimetry systems in clinical radiotherapy

Mara BruzziUniversity of Florence, Dept. of Physics and Astronomy and INFN Firenze, Italy

[email protected]

M. Bruzzi, Scuola di Specializzazione in Fisica Medica, Milano , May 10, 20191

Outline


1. Motivation

2. Radiotherapy Irradiation Facilities

3. X-ray dosimetry systems in clinical radiotherapy

❑ epitaxial silicon

❑ polycrystalline diamond

4. Proton Imaging in Proton Therapy

❑ proton Computed Tomography – pCT

5. Conclusions

2

RadiotherapyA technological solution to a biological problem

Radioterapy with external beamsRadiation beams with high energy (X, γ,electrons, protons, ions) produced byradionuclides or particle accelerators

BrachytherapySealed radioactive sources introduced in the body

Methabolic radiotherapyNon-sealed radioactive sources vehicolatedwithin the body

3M. Bruzzi, Scuola di Specializzazione in Fisica Medica, Milano , May 10, 2019

•immobilization techniques allow forpositioning patient during the treatment withalways increasing accuracy,

•accelerators equipped with beam modifyingdevices able to get dose distributions closelyshaped on the target volume.

State-of-art Radiotherapy Machines

Procedures have been consistently upgraded in recent years, dueto continuously developing technologies.

Advanced, highly accurate imaging and dose verifications systems must match with increased accuracy of irradiation techniques .


M. Bruzzi, Physics and Astronomy Dept. Univ. of Florence– Physicist, materials science and detector development

C. Civinini, Physicist, INFN Sezione di Firenze- Physicist, pCT tracker development

M. Scaringella, INFN Florence Tecnologo- Electronic Engineer

M. Intravaia, PhD Student, Pegaso Univ. of Pisa/Florence/Siena- Electronic Engineer

C. Talamonti, Biomedical, Experimental and Clinical Science Dept. Univ. of Florence– Medical Physicists

The Florence Research Group

5

LINAC radiotherapy facility• LINAC ( Linear Accelerator ) by means of high

frequency ( ~ 3 GHz ) electromagnetic wavesaccelerates charged particles at high energy along a linear path


X-raysirradiation



Intensity Modulated Radiation Therapy (IMRT) consists in using a fewradiation beams, generally from 2 to 9, produced by the same linearaccelerator and directed towards the tumor from different angles, in order toconcentrate the dose released on the volume of the tumor.

Intensity Modulated Radiation Therapy (IMRT)

7


Flat Dose Map Modulated Intensity Dose Map

To spare at best surrounding healthy tissues the dose released to the tumor needs to be shaped along an

irregular field to be best conformed to the tumorvolume

8

Multi Leaf Collimators (MLC)The dose conformation is obtainedusing Multileaf Collimators with setsof mobile lamellas in W mountedexternally on the LINAC head

9



Example: IMRT irradiation in step and shoot modality, the total dose is released asa sum of nine segments. Each segment corresponds to a particular arrangement ofthe MLC lamellas (left). Beam is off during their movement.

10

Total dose is obtained as the sum of the dose released by each segment (right).


VMAT (Volumetric Modulated Arc Therapy)

❑ Able to focus more accurately at tumor tissues, ensuring greater preservation ofhealthy ones.

❑ Modulating not only the amplitude and velocity of the MLC, but also rotationspeed of the Gantry and Linac dose-rate.

❑ continuous rotation of the accelerator head during irradiation for maximumfocusing of radiation on tumor tissues, which are thus affected by all possibleangles.

❑ significantly reducing duration of treatments compared to IMRT: about 5-7minutes compared to traditional times which are around 20 minutes persession.

❑ useful when treatment focus must be maximum to preserve nearby organs:tumors of the head / neck, as larynx, pharynx and oral cavity; tumors of thepelvis, as prostate and rectum; tumors of the lung and breast.

11

Hadrontherapy

Hadrontherapy is the treatment of tumors by heavy charged particles, such

as protons (proton-therapy) or ions.

Sviluppo di un sistema di imaging

tomografico con protoni per adroterapia

Firenze, 4 Ottobre 2018

2

➢ X-rays, often used in clinical radiotherapy, release their energy gradually during

their propagation.

➢ Protons release most of their energy in the Bragg peak.

Accurate dose distribution planning


Outline


1. Motivation







5. Conclusions

13


Highly accurate imaging and dose verifications systems must match with

increased accuracy of the irradiation techniques . In IMRT / VMAT, the way to

perform dose distribution verifications is still a matter of discussion within the

scientific community. Detector requirements:

• Response independent of energy - often Charged Particle Equilibrium (CPE)

lacks (a phenomenon associated with the range of secondary particles and hence

dependent on the beam energy, composition and density of the medium );

• small volume and high sensitivity - to get enough spatial resolution;

• response independent of dose rate, continuously changing during VMAT;

• Real time invivo detectors - european community require dose delivery to be

verified experimentally directly during irradiation (Article 56 of COUNCIL-

DIRECTIVE-2013/59/EURATOM).

Dosimetry Challenges

14


State-of-art commercial dosimetric devices used in clinicalradiotherapy

IC (AIR) SILICON DIAMOND

[g/cm3] 1.29x10-3 2.33 3.52

Ei [eV] 34.00 3.60 16.20

S [nC/Gymm3] 0.038 647.22 217.28

Area [mm2] 25.00 0.64 3.80

thickness [mm] 5.00 0.03 0.001

volume [mm3] 125 0.019 0.0038

Array OCTAVIUS

PTW

MAPCHECK

SunNuclear

-

Detector 729 PTW SunPoint®

Diode Detector

microDiamond

type 60019 PTW

Reference

15


16

Advantages:- High sensitivity (about 18000 times higher than air filled IC with same activevolume).- Well developed manufacture technology.- high spatial resolution.- work in null bias mode ( in-vivo applications possible ).

Drawbacks:- Sensitivity decrease with accumulated dose due to increase of concentrationof recombination centers (recalibrations needed).- Dose rate dependency due to centers saturation at high dose rates.- Energy dependence, since Si is not "water equivalent" (Z=14).

The Silicon Choice


18

19

iSi ERG /=

G,: carrier generation rate:

R,: dose rate;

Si: Si density;

Ei: mean ionization energy.

s: sensitivity

(per unit volume of active region)

Q: released charge;

D: delivered dose;

q: elementary charge

3637

mmGy

nC

E

q

R

qG

D

Qs

i

Si

====

Ei vs Egap constant for many

semiconductors under general

conditions. In silicon

Ei≈3.6eV/pair.

a) "null bias" (to minimize leackage current).

b) DC coupling.

c) Sampling time and reset fixed by digital electronics

(usually T10ms).

d) Only integrated charge is measured.

Working Principle

0 2 4 6 8 10 12 140

100

200

300

400

500

n-type

p-type

Sensitiv

ity [nC

/Gy]

Dose [KGy]

G.Rikner et al.Phys. Med. Biol. 28, 1983, 1261-1267

Decrease in sensitivity S during device lifetime in past-times

- Frequent Calibration needed. - Usually Si devices pre-irradiated up to 10kGy


20

The Florence Radiation Hardening Choice: Epitaxial Si

• 4” p-type MCz wafer

• Epitaxial layers with 50mm thickness grown by ITME Warsaw Poland

• Manufacturing of the device carried out by ITC-IRST Trento (now FBK)

Constant active volume during irradiation: epitaxial layer thickness andguard ring distance from active area thinner than minimum diffusion lengthreached during device lifetime will provide constant sensitivity.

High quality crystalline epitaxial Si of 50mm thickness is now commerciallyavailable on large scale at very low costs

Sensitivity of silicon is quite high, and the subsequent reduction in signalstrength is of no concern.


21

Radiation hardening: thin p-type Epitaxial Si


22

Pixel: 2x2mmPitch: 3mmDetector size: 6.3x6.3cm2

Matrix: 21x21pixels

M. Bruzzi, Scuola di Specializzazione in Fisica Medica, Milano , May 10, 2019 23

Nine modules to cover an area of about 2020 cm2. System complexity: ~4k channels

2D Dosimeter Module and Array Geometry

24

The Diamond Choice

◼ it is almost water equivalentit doesn’t perturb the radiation field → small fields the energy is absorbed as in the water → no correction factors

◼ high radiation hardness → long term stability◼ high density → high sensitivity → small dimensions◼ non toxic◼ it can be used as TL dosimeter (off-line) or for on-line applications

☺

◼ high defect density - priming effects – instability of the signal◼ high voltage required◼ high production costs


No large area array available yet


25

26

Single crystal diamond dosimeter

Layout device produced by Università di Roma Tor Vergata


The Florence Choice: polycrystalline Diamond

◼ difficult to selectstones with proper

dosimetric response

Natural diamond

Single crystal CVD (Chemically VapourDeposited) diamond

Polycrystalline CVD diamond

◼ zero/low voltage to reduce polarization effects*

◼ grown on HPHT diamond◼ not available in large areas

❑ ability to produce largearea wafers of 3-5”

☺

*M. Bruzzi et al., Diamond & Related Materials 20 (2011) 84–92


27

28

Chemical Vapour Deposited polycrystalline Diamond

50 mm 200mm Courtesy of Element Six

After polishing andMaterial removal

- Columnar growth –increased quality at

growth side


28

Problem: priming and instability effects due to defects in pCVD


29


TO GET STABLE SIGNAL

Idea : back to back schottky barriersand low/null bias

defects in the bulk are notcontributing to the currentresponse and signal is thus onlydue to the charge collected atinterfaces.

Trapping–detrapping mechanismsin the bulk, which are believed togive the main contribution topriming and signal instability aretherefore now negligible.

30

The Polycrystalline pixel diamond dosimeter prototype of Florence

b)

- Material- Up to three polycrystalline diamond films 2.5x2.5cm2 active area each, 300mm thick; - Premium Detector Grade Element Six, UK

- Contacts • Schottky Barriers produced @ University of Florence•12 x 12 matrix, pixel size: 1.8x1.8 mm2 → 288 pixels in total

- Read Out Electronics •four 64 channels 20 bit current-input analog to digital converter chips able of measuring currents from fAs to mAs; 160ms-1s integration time (50ms)•custom printed circuit board;•semi-rigid silver-polymer pin-contacts produced by us connecting each pixel of the 144 matrix connecting vias on PCB .

-Measurement•Low voltage to get fast and reproducible signals;•Device can be moved in x-y directions to cover a wider radiation field area.


31

pCVD Diamond test under linac

LINAC @ Radioterapia AOUC Firenze

1 pCVD on PCB 2 pCVD in PMMA /front

/rear


32

Linearity with dose

14th IPRD, 3 - 6 October 2016 Siena, Italy A. Bartoli et al.


Repeatability

Dose rate dependence

∆=0.9832 ± 0.0015

𝑆 =𝑑𝑄

𝑑𝐷~24

𝑛𝐶

𝐺𝑦

Performance under conventional and IMRT radiotherapy beam

Current response of all pixels in a

conventional X-ray beam (Vapp = 1V)

Dose-rate 50 Mu/min

✓negligible dark current → high S/N ✓negligible polarization effects → stable

response , fast dynamics

Current response of one pixel under

an IMRT beam in step and shoot

modality

Bartoli et al. 2017 JINST 12 C03052


34

2.5x2.5cm2 pCVD Diamond prototype IMRT map 14x10cm2

measured by shifting the diamond dosimeter

IMRT breast cancer map asmeasured by the pCVD Diamond .

IMRT breast cancer map as calculated by the TPS (treatment planning system)

(GT = gantry target direction; LL = lateral-lateral direction) Grid spacing 3 mm.

First IMRT map with Diamond Device


35

Time structure of VMAT

delivery as measured by

one pixel of the pCVD

diamond dosimeter

VMAT Experimental Test

- lung cancer treatment fraction- 2 polycrystalline diamond dosimeters - Active area: 5.0x2.5cm2

- moved ±2.0cm in the y-direction to cover field


36

Calculated vs measured VMAT maps

➢ VMAT lung cancer treatment ➢ 2 polycrystalline diamond dosimeter 2.5x2.5cm2 moved in xy directions to cover 6x5cm2 area

VMAT map as calculated by the TPS (Treatment Planning System)

VMAT map as measured by thepCVD Diamond .

90% pixels with Y index< 1

(3mm, 3% criteria)

Bartoli et al. 2017 JINST 12 C0305237



What Next ? The Florence Choice: CsPbBr3

38


Present project in Florence aims at developing a new dosimetric system for in vivo dosimetry, exploiting flexible geometry, real-time measurement, wireless read-out.

microcrystalline CsPbBr3 film deposited on alumina substrate carrying two parallel gold contacts

In CsPbBr3, mean energy to create an electron-hole pair: ECsPbBr3 = 5.3 eV. Considering CsPbBr3 = 4.55 g/cm3 → sCsPbBr3 = 860 nC/ Gymm3

Higher sensitivity than silicon:

TPS treatment plan Relative dose verification TPS treatment plan, Si Mapcheck and CsPbBr3.

39

Outline


1. Motivation







5. Conclusions

40

Proton Therapy Challenges: proton Computed Tomography - pCT

A treatment plan needs the patient’s Relative (to water)Stopping Power (RSP) maps.

RSP maps are currently extracted from x-ray CTs, introducingerrors in the Bragg peak positioning up to a few millimetres.

The direct measurement of the proton RSP maps, usingprotons themselves for tomographies, can potentially reduceinaccuracies in tumor irradiation.B. Schaffner and E. Pedroni Phys. Med. Biol. 43 (1998) 1579–1592

41

𝑆(𝐸)𝑅 =𝑆(𝐸)

𝑆(𝐸)𝑤𝑎𝑡𝑒𝑟𝑆 𝐸 = −

𝑑𝐸

𝑑𝑙


A proton CT apparatus

Prima – RDH – IRPT Collaboration

M. Bruzzi1,2, C. Civinini2, M.Intravaia3,2, N. Randazzo4, M. Rovituso4,

M. Scaringella2, V. Sipala5,6, F. Tommasino4,7

1Physics and Astronomy Department, University of Florence, Florence, Italy 2INFN - Florence, Florence, Italy

3Information Engineering and Mathematical Sciences Department, University of Siena, Italy4INFN - Catania, Catania, Italy

5INFN - TIFPA, Trento, Italy6INFN - Laboratori Nazionali del Sud, Catania, Italy7Chemistry and Pharmacy Department, University of Sassari, Sassari, Italy8Physics Department, University of Trento, Trento, Italy

M. Bruzzi, Scuola di Specializzazione in Fisica Medica, Milano , May 10, 2019 42

The pCT system➢ Measurement of the trajectory of

each proton. Tracker

➢ Measurement of the residual energy

of each proton.Calorimeter

➢ Most Likely Path reconstruction.

➢ Tomographic reconstruction.


4


3x3x10 cm^3

YAG:Ce

crystals

43

Tracking with multiple scattering

Actual proton trajectory

L → curved trajectory with narrow confidential limits→ Most Likely Path of the proton inside the object.

Measurements: entry andexit positions and angles

LMost Likely Path (MLP)calculation

+


44

INFN-Prima pCT apparatus

Beam test at Trento proton Therapy Centre experimental beam lineProton energy: nominal 211 MeV (198 MeV at phantom) 5x20 cm2 field-of-view


45

Tracker architecture

X-side view1° level FPGA

2° level FPGA


46

Sviluppo di un sistema di imaging

tomografico con protoni per adroterapia


10

Electron Density Phantom

used for calibration Anthropomorphous phantom Radiography showing

implanted metallic

prosthesys

Phantoms

Phantoms are used during tests on proton beam to simulate the presence

of the patient and to determine the ultimate performance of the apparatus.

CIRS Proton Therapy dosimetry head. Mod. 731 HN


Anthropomorphous phantomX-Ray radiographies

Tomography region


48

Anthropomorphous phantom tomography

Matteo Intravaia - INFN Firenze 14th Trento Workshop - Trento

February 27th 2019 49

Anthropomorphous phantom tomography

64 axial slicesvoxels: 600x600x812mm3 0.3mm3

400 angles (0.9 deg. uniform spacing)About 3.7 x 107 events (selected)

First and last slices have low statistics (outside field of view)Movie starts from lower jaw ends at upper teeth (5.2 cm range)

Total estimated dose 1.5mGy

Much lower contrast with respect to the X-Ray images mainly because of the physics of the interactions: important Z dependence for X-Ray, density dependence for protons→BUT it is what is needed for hadron therapy.


50

1.2x108 events in 400 angles

Metallic prosthesis artifacts• In presence of implanted metal prosthesis, the treatment plan is difficult

to define because of xCT severe artifacts, which degrade the image quality and negatively influence the RSP map determination.

• pCT is less sensitive to high Z materials than xCT→more accurate RSP maps nearby metallic implants.

Tests are planned to quantify the influence of these structures on the treatment quality

pCT xCT


51

Electron density phantom→8 lateral plugs:1) Liver 1.07 gcm-3

2) Lung exhale 0.50 gcm-3

3) Breast 0.99 gcm-3

4) Bone 1.53 gcm-3

5) Muscle 1.06 gcm-3

6) Bone 1.16 gcm-3

7) Adipose 0.96 gcm-3

8) Lung inhale 0.20 gcm-3

→Central plug:Liquid water vial

→‘Water equivalent’ plastic material (Plastic Water LR) bulk.

1

2

3

4

5

6

7

8


52

Electron density phantom tomography

• 1.6 mm thick central horizontal slice

• All inserts are visible

• Quantitative analysis of measured vs expected RSP correlation (next slide)

Next slide section


53

108 events in 400 angles

RSP correlation

Excellent correlation (deviation < 1%)!


54

Conclusions• Advanced imaging and dosimetry systems needed to

get increased accuracy in radiotherapy treatment plans;

• Diamond potentially best suited for X-ray radiotherapy due to energy independence of its response (tissue equivalence );

• Diamond dosimeter array not yet available commercially; a prototype manufactured and tested in Florence under IMRT and VMAT treatment plans shows promising results;


• Increased accuracy in proton therapy by direct evaluation of Relative Stopping Powers

• proton Computed Tomography (pCT) system manufactured and testedunder a 200MeV p beam for pre-clinical study at Trento proton Therapy Centre;• Measured RSP values agree with the expected ones at level of 1%; • Technique proves to be potentially beneficial in the presence on prosthesys

55

hadron imaging and x-ray dosimetry systems in clinical radiotherapy · 2019-05-15 · hadron...

Documents