1. Analysis by Monte-Carlo simulations of the characteristics of nano and micro dosimeters for real time measurements in radiotherapy and medical physics
Abdulhamid ChaikhPhD, Jacques BalossoMD,PhD
Grenoble University Hospital, Department of Radiation Oncology
University Grenoble-Alpes, Grenoble, France
Micaela CunhaPhD, Etienne TestaPhD, Michaël BeuvePhD
Université de Lyon, Université Lyon 1, CNRS, France
IN2P3, UMR 5822, IPNL, F Villeurbanne, France
A.Chaikh et al®, August Frankfurt

2. Context Introduction and purpose Materials and methods
Results and discussion
Conclusion and perspectives 2

3. Radiotherapy & medical physics
Introduction
The goal of radiotherapy is to deliver a radiation dose to treat the cancer using X-Ray generators :
Maximizing the Tumor Control Probability
Minimizing Probabilities of Normal Tissue Complications (organs at risk)
By using multiple “cross fired” beams varying from a technique to another
A treatment plan must be calculated and validated, two methods are available:
Physical model: Using physical quantities and statistics (DVH)
Measurements : “In vivo dosimetry” in real time using a dosimeter
Currently : at beam entrance using a macro semiconductor placed on the patient skin
More recently : an implantable micro dosimeter placed in the target volumes
Tolerance constrain between planned dose and measured dose: ± 5% 3

4. In-vivo dosimetry with implanted micro dosimeter
Introduction
Example of dose measurement using a µ-dosimeter : DorGaN project -France
Irradiation Off
Irradiation ON
Optical fiber
Fiber connector
µ -dosimeter (900 µm)
Gallium Nitride
RL signal
Patient
Linked Optical fiber
Bi-channel
Photo detection
Dose (Gy) 4

5. Available mico/macro dosimeters for radiotherapy
Purpose
Objective Of
This study 5

6. Why do we need an implantable µ/nano dosimeter?
Purpose
In practice radiotherapy:
93% of “In-vivo dosimetry” is based on diodes in France (ASN, 2013)
Entrance dose
The available dosimeters are imperfect and need a correction factors
Ideal in-vivo dosimeter desired
Implanted micro / nano dosimeter
High accuracy and high precision < 5%
Reproducibility < 2%
No correction factors
Intended clinical use:
Real-time absolute dose monitoring
at target volume in the patient
Toward in-situ dosimetry and dose
guided radiotherapy 6

7. Monte-Carlo simulations
Materials & methods
Monte-Carlo simulation method, widely used for radiotherapy:
Modeling linear accelerator in medical physics
Tracks individual particle histories (photon /electrons)
Dose calculation 7

8. Monte-Carlo simulations
Materials & methods
Monte-Carlo simulations were carried out to:
Evaluate the influence of the dosimeter size on the measured dose
Characterize the size of micro / nano dosimeter for radiotherapy
As small as possible
With high accuracy ( < 5%) and high reproducibility
Principle :
Estimate the level of dose fluctuations
Determine the probability p (%) of error in dose measurements 8

9. Simulations of micro/nano dosimeter
Materials & methods
Simulation of the irradiation of a water volume with photons
X = Y = Z: 50 to 200 µm
Cylindrical targets simulate the dosimeters :
Placed in the irradiated water volume (“water space”)
Density equivalent to water
The target length was set as equal to the diameter :
Smallest radius (nm): < 1 µm
Intermediate radius (µm) : 1 µm to 9 µm
Largest radius (µm): ≥ 10 µm 9

10. Simulations of micro/nano dosimeter
Materials & methods
Source
modelling
X (µm)
Y (µm)
Z (µm)
60Cobalt
Beam
Water
volume
Dosimeter
Scheme of the transversal view of the irradiated water phantom
The nano dosimeter (circle) is placed
The dots represent the energy transfer points after the interaction of the electrons with the medium
dosimeter 10

11. Modelization of doses in the targets
Materials & methods
60Cobalt source was simulated to generate the photon beam:
Irradiate the water phantom with 1.3 MeV photons
Doses simulated using only electrons generated by Compton effect
The simulated doses were :
Lower dose : 0.1Gy – 1Gy: delivered dose by one beam
Intermediate dose : 1Gy – 2Gy: daily fraction on clinical routine
Higher dose : > 2 Gy : hypofractionated treatment plans
electron
Deposited dose
Scattering
photon
60Cobalt 11

12. Measurements of deposited doses in the targets
Materials & methods
Using the concept of micro-dosimetry :
The specific energy “zt” in the target is defined as the cumulated energy transferred by the radiation over the mass “mt” of the target :
zt = ε / mt
<zt> is the mean specific energy in the targets over many irradiation configurations with the same dose D
The probability (p%) that a measurement yields a value outside of confidence intervals :
[<z>- γ *<z> ; <z> + γ *<z>]
γ varied from to 3% to 10% 12

13. Influence of dosimeter size on the measured doses
Results & discussion
Largest radius : 10 µm-dosimeter
The effect of fluctuations is less significant than in the other cases
The distributions of specific energy are Gaussian curves
The zt values at the peak match the average specific energy in the targets
The relative width of the distributions decreases as the irradiation dose increases
The increase in the dose resulted in a higher number of energy-transfer points and thus in a reduction of the relative statistical fluctuations
Note: <zt > corresponds to % of the irradiation dose since a part of the energy is converted to heat and is not considered 13

14. Influence of dosimeter size on the measured doses
Results & discussion
Intermediate radius: 1 µm < r < 10 µm dosimeter
The dose distribution is no longer symmetrical, showing a tail at higher values of specific energy
As the irradiation dose increases, the distribution peak shifts to higher values of specific energy, closer to the value of <zt>
As the dose and radius increase the distribution of energy tends to a Gaussian curve
Probability distribution of specific energies :
1 µm, 1 Gy
1 µm, 0.1 Gy 14

15. Influence of dosimeter size on the measured doses
Results & discussion
For the smallest radius : r ≤ 0.1 µm nano-dosimeter
The effect of fluctuations is very significant: very large range of specific energies a nano-dosimeter may receive
The dosimeter is very likely to receive no energy at all
The shape of the distribution is:
Characterized by one photon interaction
Independent of the irradiation dose
0.1 µm, 0.1 Gy
Probability distribution of specific energies 15

16. Influence of dosimeter size on the measured doses
Results & discussion
Dose effect with a small radius of 0.3 μm
Lower doses ≤ 0.3 Gy :
Structure close to the one of 0.1 μm dosimeters
Dose values ≥ 1 Gy :
The shape is similar to that of 1 μm dosimeters
Probability distribution of specific energies
0.3 µm, 0.1 Gy
0.3 µm, 3 Gy 16

17. Influence of dosimeter size on the measured doses
Results & discussion
Higher delivered dose using micro dosimeter
Conditions:
Irradiated dose 10 Gy
Radius : 10 µm
Gaussian curve
Measured dose in the target 8.1 Gy
Error of measurements  20 %
10 µm, 10 Gy 17

18. Probability of dose measurements p (%)
Results & discussion
Probability p (%) to obtain dose measurements outside the range
[<z> -γ * <z> ; <z> + γ * <z>] with γ varing from 3 to 10%
For the same radius:
A smaller dose results in a higher p %, which in turn decreases for a larger γ
For the same dose:
p % decreases as the radius increases
p % is lower for a larger interval around <z>
In particular :
p % is equal to zero when “r =10 μm”, “D= 10 Gy” and γ is “5% or 10%”
This means that in these cases all the specific energies are contained in the interval considered.
0.1 Gy
0.3 Gy
1 Gy
3 Gy
10 Gy 18

19. Characterization of µ/nano dosimeter
Conclusion & perspectives
Characterization of the size of an implantable dosimeter at µ and nano scales for clinical use with radiation oncology
The specific energy probability distributions is strongly dependent on :
Target size radius
Delivered dose level
A dose value < 0.3 Gy, none of the dosimeter radii would allow for a reproducible measurement of the irradiation dose
The best results obtained
With a µ-dosimeter “r = 10 µm”
Distributions of energy is close to Gaussian curve
But still ~ 20 % of the measurements would be outside the interval confidence 19

20. Characterization of µ/nano dosimeter
Conclusion & perspectives
The ability of the dosimeter to yield measurements is dependent on
Size
Deposited dose
Strong correlation between the accuracy of measured doses and the dosimeter size
An excessively small radius renders the measurements chaotic and not statistically-reproducible, even for a dose as high as 10 Gy
A target radius of 10 μm may allow for a better reproducibility of the measurements in a wider range of doses
Recommended radius of dosimeter for radiotherapy “r > 10 µm” to
satisfy the dose tolerance of ± 5% 20

21. Reference
[1] Abdulhamid Chaikh, Michaël BEUVE, Jacques BALOSSO. Nanotechnology in Radiation Oncology. Int J Cancer Ther Oncol 2015 ; 3(2): 3217; DOI: /ijcto.32.17
[2] Abdulhamid Chaikh, Arnaud GAUDU, Jacques Balosso. Monitoring methods for skin dose in interventional radiology. Int J Cancer Ther Oncol; 3(1): DOI: /ijcto
[3] Chaikh A, Balosso J, Giraud JY, Wang R, Pittet P, Luc GN. Characterization of GaN dosimetry for 6MV photon beam in clinical conditions. Radiation measurements; 2014:
[4]
[5] Gervais B, Beuve M, Olivera G H, Galassi M E. Numerical simulation of multiple ionization and high LET effects in liquid water radiolysis. Radiat. Phys. Chem 2006; 75(4):

22. Acknowledgements
The authors acknowledge the financial support of the French National Research Agency (ANR-11-TECS-018)
Remerciements :
France HADRON
The PRIMES “LabEx”
Dr. Patrick Pittet
Dr. Jean Yves Giraud
A.Chaikh et al®, August Frankfurt

23. Thank you for your attention