Multiple Source Phototherapy in Breast Cancer: A Viability Study

A. Lopes

1,2

, A. Gabriel

1,2

, J. Machado

1,2

, P. Ribeiro

1,3

, R. Gomes

4,5

, Jo

ao M. P. Coelho

4,5

C. O. Silva

, C. P. Reis

5,6

, J. P. Santos

1,2

and P. Vieira

1,2

Department of Physics, Faculdade de Ci

encias e Tecnologia da Universidade Nova de Lisboa,

R. Quinta da Torre, Monte da Caparica, Portugal

LIBPhys, Faculdade de Ci

encias e Tecnologia da Universidade Nova de Lisboa, Monte da Caparica, Portugal

CEFITEC, Faculdade de Ci

encias e Tecnologia da Universidade Nova de Lisboa, Monte da Caparica, Portugal

Laborat

orio de

Optica, Lasers e Sistemas, Faculdade de Ci

encias da Universidade de Lisboa, Lisboa, Portugal

Instituto de Biof

ısica e Engenharia Biom

edica, Faculdade de Ci

encias da Universidade de Lisboa, Lisboa, Portugal

CBiOS - Centre for Research in Biosciences & Health Technologies, Lus

ofona University, Lisboa, Portugal

Keywords:

Near Infrared, Spectroscopy, GAMOS, Monte Carlo, Phototerapy, Breast Cancer.

Abstract:

Radiation therapy is one of many common treatments applied to breast cancer. Most usual radiation sources ap-

plied are ionizing radiation, such as γ-rays and X-rays, and non-ionizing radiation such as ultraviolet radiation.

The possibility of using near infrared light to photoactivate a drug inside an 8 cm diameter biological object is

discussed in this work via Monte Carlo simulations. Two simulation setups performed in the Geant4/GAMOS

framework are presented in order to study the viability of photoactivating a drug by using several near infrared

light sources. The overall objective of this technique is to minimize energy concentrated at objects surface

and maximize it in a predeﬁned region of interest. Results show an increase energy absorption in the desired

region of interest inside a 8 cm object, when a higher absorption particle is present. With the use of multiple

sources it is possible to photoactivate the drug while causing minimal damage to the surface of the radiated

object.

1 INTRODUCTION

Radiation therapy, or radiotherapy, is one of the stan-

dard treatments for patients with breast cancer. Con-

ventional ionizing radiotherapy is performed using X-

rays and γ-rays combined with chemotherapy. This

method is usually employed after surgery to improve

cancer treatment (Sarkar et al., 2013). On the other

hand non-ionizing ultraviolet (UV) radiation, which

utilizes phototherapy techniques, is employed to treat

skin cancer diseases which can develop from ionizing

radiation therapies(Costa et al., 2014). There are sev-

eral advantages and disadvantages to either of these

types of ionizing and non-ionizing radiations. In the

ﬁrst case radiation will penetrate the biological tis-

sue but it is known to cause serious side effects that

one must take into account. In the latter case effective

low light penetration into subcutaneous tissue is the

biggest disadvantage (Sarkar et al., 2013).

To study the possibility of using near infrared

(NIR) radiation is one of the aims of this work. NIR

light is a non-ionizing radiation that produce even

less undesired side effects and has greater effective

penetration than UV radiation. NIR light sources

would be applied in treatment of breast tissue and

other melanoma beyond the subcutaneous surface by

photoactivating gold nanoparticles with drug carry-

ing capabilities and biocompatible coatings. The use

of multiple radiation sources to minimize skin le-

sions and optimize energy in a speciﬁc region is the

main idea behind this work and was also discussed

in (Gabriel et al., 2015). By adding multiple sources

our intention is to optimize the energy ratio between

biological tissue surface and a predeﬁned region of

interest. Monte Carlo simulations were carried on

to study this possibility as they are the reference in

the realm of simulations of light interactions with bi-

ological tissues (Zhu and Liu, 2013). To perform this

simulation it is used the Geant4/GAMOS framework

which has already been validated by other authors as

shown in (Glaser et al., 2013; Morhard et al., 2014).

Geant4 is a powerful simulation tool that was devel-

oped for nuclear and particle physics experiments.

GAMOS framework offers the necessary extension of

Lopes, A., Gabriel, A., Machado, J., Ribeiro, P., Gomes, R., Coelho, J., Silva, C., Reis, C., Santos, J. and Vieira, P.

Multiple Source Phototherapy in Breast Cancer: A Viability Study.

DOI: 10.5220/0005794902470250

In Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2016) - Volume 1: BIODEVICES, pages 247-250

ISBN: 978-989-758-170-0

247

Geant4 to perform Monte Carlo simulations for Med-

ical Physics applications. Its tissue optics plug-in was

also used because it offers the possibility of simulat-

ing photons interacting with biological tissue and in

the NIR range of the spectrum.

2 MATERIALS AND METHODS

2.1 Geometry and Optical Properties

The input parameters as well as the scattering theory

used in GAMOS were ﬁrstly deﬁned in order to begin

the simulation. The use of literature values to perform

this study was our ﬁrst approach. However several pa-

rameters for the same variables in different references

were found (van Veen et al., 2004; Jacques, 2013)

which produced distinct simulations results. The out-

put results from these parameters were not consis-

tent with other groups’ experimental results (Gibson

et al., 2005) because photons were not penetrating

deep enough into the tissue. To overcome these dif-

ﬁculties, we conducted an experiment in which the

optical properties of a piece of pig lard were mea-

sured, and determined the best simulation parame-

ters ﬁtted to experimental results. These results will

be published elsewhere and were based on (Gaigalas

et al., 2009). In the present work it is assumed the

simulated photons’ interaction with the pig lard pro-

duce similar results as photons’ interaction in breast

tissue. The Mie Henyey-Greenstein scattering the-

ory model was chosen because it has been proven by

other groups to be the best to perform these kind of

simulations (Jacques, 2013). To determine the Mie

and anisotropy scattering coefﬁcients we use a MAT-

LAB script based on the work described in (Bohren

and Huffman, 2007) and developed by Scott Prahl and

Christian Maetzler in (Jacques and Maetzler, 2002).

This software calculates both coefﬁcients given aver-

age sphere dimensions, fractional volume and refrac-

tive indexes of tissue. The selected simulations in-

put values were the ones which matched our pig lard

experimental results and were chosen from a wide

range of values taken from several referenced articles

(Jacques, 2013; Wang et al., 2005; Jacques, 1996).

The refractive index of the simulated object was taken

from (Bashkatov et al., 2005). Two different setups

were simulated and are described in the next para-

graphs.

2.1.1 Setup #1

To minimize geometry dependences, we performed a

simulation in a homogeneous cylinder with 8 cm di-

Figure 1: System geometry for setup #2.

ameter and 4 cm height as a ﬁrst approach for mod-

elling a section of the tumour site. Future work will

comprise the study of the geometry contribution to the

simulation results, namely the dependence on the an-

gle between the beam axis and the solid surface and

when one considers different solid geometries.

2.1.2 Setup #2

A sphere was included in the centre of the volume of

setup #1 with 1 cm diameter and higher absorption. It

intents to mimic the optical properties of the photoac-

tivated drug that its supposed to be aggregated around

the tumour. Gold nanoparticles to be activated in the

NIR range were developed by other members of this

project. They also measured their optical properties

so the spheres absorption coefﬁcient was estimated

based on their studies. These studies will be pub-

lished elsewhere. A picture of this setup is displayed

in Fig.1.

Both simulation setups consider 16 sources with

a wavelength of 810 nm each aimed to the centre of

the cylinder, equally spaced out around the object and

equidistant from its lateral surface.

Input values of the GAMOS simulations are

shown below:

• Wavelength: 810 nm

• Refractive Index: 1.44

• Mie scattering coefﬁcient: 221.69 cm

−1

• Scattering anisotropy: 0.97

• Cylinders absorption coefﬁcient: 0.01 cm

−1

• Spheres absorption coefﬁcient: 1.00 cm

−1

For each setup 2 million events were generated.

Each source has 1 ps pulse with Gaussian distribution

BIODEVICES 2016 - 9th International Conference on Biomedical Electronics and Devices

248

in wavelength and position of σ

= 3 nm and σ

= 0.5

mm, respectively.

3 RESULTS

The simulation results for setup # 1 are presented

in Fig.2 which shows a top-view of the absorption

interactions of photons with the tissue inside the

cylinder. The X-Y plane is measured in mm while

the Z-axis represents the number of counts in each

X-Y bin and is integrated in height. As expected from

an homogeneous tissue the results show equivalent

number of interactions when considering the same

radius. The exception lies at the edge of the object

where photon beams enter the tissue, where one can

see a higher number of counts. This behaviour is

expected because of the higher density of photons

present in where the photon beams are aimed.

The simulation results for setup # 2 are also

displayed in Fig.2. A top view of the absorption

interactions inside the cylinder setup is presented.

Besides demonstrating the same radius dependency

on absorbed photons and the same higher density on

the number of counts where the photon beams are

aimed, this result also show a higher density on the

number of counts inside the object where the higher

absorption sphere lies.

Energy densities present in the region of interest

were computed with and without the sphere, consid-

ering the number of photons that are absorbed in the

predeﬁned region of interest. When one does not

consider the absorber sphere in the centre of the ob-

ject the energy density is 1.2 × 10

−27

J/cm

. When

the absorber sphere is present the energy density is

40 × 10

−27

J/cm

4 DISCUSSION

Scattering and absorption simulation studies of pho-

tons interaction with biological tissues were studied

in (Gabriel et al., 2015). Absorption interactions with

the tissue are studied in this work. There are two rea-

sons for presenting only absorption studies. Firstly,

when considering a same volume, there is more than 1

absorption interaction per each 10000 scattering inter-

actions in average. This can be showed with the ratio

between the scattering and absorption coefﬁcients. If

we proceeded with scattering and absorption interac-

tion plots the results would be masked as ﬂuctuations.

# counts

100

200

300

400

500

600

700

800

900

1000

X (mm)

-50 -40 -30 -20 -10 0 10 20 30 40 50

Y (mm)

-50

-40

-30

-20

-10

# counts

100

200

300

400

500

600

700

800

900

1000

X (mm)

-50 -40 -30 -20 -10 0 10 20 30 40 50

Y (mm)

-50

-40

-30

-20

-10

Figure 2: Absorption interactions inside the object of setup

#1 on top and setup # 2 below.

Also only when photons are absorbed the drug is pho-

toactivated by the deposited energy. The most impor-

tant remark on the results of setup #2 when compared

to setup #1: there is a greater number of absorption

interactions in the centre of the object due to higher

absorption of the drug supposedly aggregated to the

tumour.

The results present in this paper also give a no-

tion of what kind of energy ratio is expected between

the location of the beam entrance and the region of

interest where the drug is located. Enhancement of

this ratio allow prevention of skin lesions when try-

ing to photoactivate the drug. Another possible way

of increasing this ratio is using multiple sources offset

in time in order to create constructive interferences in

the interest region within the tissue.

Since we are considering the same generated

events between the two setups, one can compare the

energy density among the two setups, and it is approx-

imately 30 times higher. This is also an indicator of

Multiple Source Phototherapy in Breast Cancer: A Viability Study

249

the viability of this radiation technique.

5 CONCLUSIONS

We have presented a study about the use of NIR light

to photoactivate a drug which aggregates around the

tumour site inside an object with 8 cm. We have

shown by using multiple sources for irradiating an ho-

mogeneous tissue absorption interactions behave sim-

ilarly on equal radius distances, while minimizing the

energy absorption at its surface. When higher absorp-

tion drug particles are simulated inside the object re-

sults show they can be photoactivated thus enabling

treatment in the tumour area, while minimizing the

damage to the surrounding healthy tissues.

In future work it will be important to make the

model more realistic by including skin and vasculari-

sation. It will be also important to optimise the source

distribution and modulation in order to maximize the

power delivery in the region of interest.

ACKNOWLEDGMENTS

This work was partially supported by national

funding by the Portuguese FCT - Fundac¸

ao para

a Ci

encia e Tecnologia through the projects

PTDC/BBB-BMD/0611/2012, UID/BIO/00645/2013

and PD/BD/105920/2014.

REFERENCES

Bashkatov, A. N., Genina, E. A., Kochubey, V. I., and

Tuchin, V. V. (2005). Optical properties of human

skin, subcutaneous and mucous tissues in the wave-

length range from 400 to 2000nm. Journal of Physics

D: Applied Physics, 38(15):2543.

Bohren, C. F. and Huffman, D. R. (2007). Appendix A:

Homogeneous Sphere, pages 477–482. Wiley-VCH

Verlag GmbH.

Costa, M. M., Silva, S., and et al. (2014). Phototherapy 660

nm for the prevention of radiodermatitis in breast can-

cer patients receiving radiation therapy: study proto-

col for a randomized controlled trial. BioMed Central,

15.

Gabriel, A., Machado, J., Gomes, R., Coelho, J., Silva, C.,

Reis, C., Santos, J., and Vieira, P. (2015). Concen-

trated photoactivation: focusing light through scat-

tering. In World Congress on Medical Physics and

Biomedical Engineering, June 7-12, 2015, Toronto,

Canada, volume 51, pages 1727–1730, Toronto,

Canada.

Gaigalas, A. K., He, H.-J., and Wang, L. (2009). Measure-

ment of absorption and scattering with an integrating

sphere detector: Application to microalgae. Journal

of Research of the National Institute of Standards and

Technology, 114(2):69.

Gibson, A. P., Hebden, J. C., and Arridge, S. R. (2005).

Recent advances in diffuse optical imaging. Physics

in Medicine and Biology, 50(4).

Glaser, A. K., Kanick, S. C., Zhang, R., Arce, P., and

Pogue, B. W. (2013). A gamos plug-in for geant4

based monte carlo simulation of radiation-induced

light transport in biological media. Optical Society

of America, 4(5):741–759.

Jacques, S. and Maetzler, C. (2002).

http://omlc.org/software/mie/.

Jacques, S. L. (1996). Origins of tissue optical properties in

the uva visible and nir regions.

Jacques, S. L. (2013). Optical properties of biological tis-

sues: a review. Physics in Medicine and Biology,

58(11):R37.

Morhard, R., Jeffery, H., and McEwan, A. (2014).

Simulation-based optimization of a near-infrared

spectroscopic subcutaneous fat thickness measuring

device. Engineering in Medicine and Biology Soci-

ety (EMBC), 36th Annual International Conference of

the IEEE, pages 510–513.

Sarkar, J. S., Rajput, S., Tripathi, A. K., and Mandal, M.

(2013). Targeted therapy against egfr and vegfr us-

ing zd6474 enhances the therapeutic potential of uv-b

phototherapy in breast cancer cells. Molecular Can-

cer, 12.

van Veen, R. L. P., Sterenborg, H., Pifferi, A., Torricelli,

A., and Cubeddu, R. (2004). Determination of VIS-

NIR absorption coefﬁcients of mammalian fat, with

time-and spatially resolved diffuse reﬂectance and

transmission spectroscopy. Proc. Biomedical Topical

Meetings, on CD-ROM, Paper SF5, Optical Society of

America, Washington, DC.

Wang, X., Pogue, B. W., Jiang, S., Song, X., Paulsen,

K. D., Kogel, C., Poplack, S. P., and Wells, W. A.

(2005). Approximation of mie scattering parameters

in near-infrared tomography of normal breast tissue in

vivo. Journal of Biomedical Optics, 10(5):051704–

051704–8.

Zhu, C. and Liu, Q. (2013). Review of monte carlo model-

ing of light transport in tissues. Journal of Biomedical

Optics, 18:73–100.

BIODEVICES 2016 - 9th International Conference on Biomedical Electronics and Devices

250