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Experimental imaging and profiling of absorbed dose in
phantoms exposed to epithermal neutron beams for
neutron capture therapy
G. Gambarini and C. Colombi
Dipartimento di Fisica, Università di Milano, and INFN, Sezione di Milano, Milan, Italy
Abstract. Absorbed-dose images and depth-dose profiles have been measured in a tissue-equivalent phantom exposed
to an epithermal neutron beam designed for neutron capture therapy. The spatial distribution of absorbed dose has been
measured by means of gel dosimeters, imaged with optical analysis. From differential measurements with gels having
different isotopic composition, the contributions of all the components of the neutron field have been separated. This
separation is important, owing to the different biological effectiveness of the various kinds of emitted radiation. The
doses coming from the reactions 1H(n,γ)2H and 14N(n,p)14C and the fast-neutron dose have been imaged. Moreover, a
volume simulating a tumour with accumulation of 10B and/or 157Gd has been incorporated in the phantom and the doses
due to the reactions with such isotopes have been imaged and profiled too. The results have been compared with those
obtained with other experimental techniques and the agreement is very satisfactory.
of the completeness of the information that can be
obtained utilizing gel dosimeters in NCT and also of
showing absorbed dose distribution in situations not
yet reported in literature.
INTRODUCTION
The promising features continuously achieved by
neutron capture therapy (NCT) encourage the
development of all the correlated multidisciplinary
research. In the field of radiation dosimetry, this
therapy requires complex measurements and
computations, both for what concerns beam controls
and for in-phantom dose determinations aimed at
validating treatment planning [1]. The complexity of
performing exhaustive determinations of absorbed
dose comes from the multiplicity of the energy release
and absorption mechanisms in neutron fields. The
various secondary radiations are characterized by
different transport and interaction modalities in
materials. Therefore, it is mandatory to perform
precise evaluation of the absorbed dose in tissue,
separating the dose contributions whose biological
effect is different.
ABSORBED DOSES IN NEUTRON
CAPTURE THERAPY
The therapy is based on the energy released by the
secondary radiation emitted in nuclear reactions of
thermal neutrons with suitable isotopes, selectively
accumulated in tumor tissues. The more convenient
isotope has appeared to be 10B, because of the high
cross section of the reaction with thermal neutrons
10
B(n,α)7Li
(σ = 3837 b)
and of the high LET (linear energy transfer) and RBE
(relative biological effectiveness) of the emitted
charged particles. In fact, boron neutron capture
therapy (BNCT) is now the common application of
this therapy in clinical trials. The higher cross section
is presented by 157Gd, but the low LET and RBE of the
secondary radiation generated by the reaction
157
Gd(n,γ)158Gd
(σ = 255000 b)
have limited the interest in developing the therapy
involving such an isotope. Recently, some increases in
the interest towards this isotope has occurred as a
Gel dosimeters have shown to give the possibility
of in-phantom imaging and profiling the absorbed dose
[2-4], separating the contributions of the various
secondary radiation components. Some results
obtained by means of Fricke-infused gel dosimeters
are here shown, with the purpose of giving new proof
CP680, Application of Accelerators in Research and Industry: 17th Int'l. Conference, edited by J. L. Duggan and I. L. Morgan
© 2003 American Institute of Physics 0-7354-0149-7/03/$20.00
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The absorbed dose results to be proportional to the
difference of optical absorption (OD) before and after
irradiation. The difference of OD is obtained from the
logarithm of the ratio of GL values before and after.
Therefore, from light transmittance images, detected
before and after exposure, dose images are obtained by
means of proper algorithms and of pixel-to-pixel
image elaboration [6].
result of the radiobiological studies which have
revealed good effects for cell killing, which are
attributed to the electrons emitted in the above cited
reaction owing to internal conversion or Auger
electrons. Moreover, the fact that gadolinium is
commonly used as image intensifier in nuclear
magnetic resonance imaging (NMRI) suggests to
enquire the feasibility of determining the spatial
distribution of boron in patients by means of NMRI,
bounding a proper amount of gadolinium, besides
boron, to the same carrier.
Gel dosimetry has revealed peculiar characteristics
that are very advantageous for NCT. The modalities
with which the energy is released and absorbed are
very near to those in tissue. For neutron fields, in
particular, it is possible to obtain a tissue-equivalent
matrix in which neutron interactions are similar to
those in tissue. The transport characteristics and the
mechanisms of energy release and absorption of the
secondary radiation generated by neutron reactions are
similar to those in tissue. Moreover, it is possible to
make convenient variations to the isotopic composition
of the gel in order to separate the various contributions
to the absorbed dose. The basic gel composition is:
Agarose [C12H14O5(OH)4] 1% of the final weight
Ferrous Sulphate solution
[1 mM Fe(NH4)2(SO4)2⋅6H2O]
Sulphuric Acid [25 mM H2SO4]
Xylenol-Orange [0.165 mM C31H27N2Na5O13S].
Other dose components have to be determined,
normally released in tissue also in absence of boron or
gadolinium accumulation: the dose due to the reactions
of thermal neutrons with hydrogen and nitrogen:
1
H(n,γ)2H
(σ = 0.33 b)
14
N(n,p)14C
(σ = 1.81 b)
and the fast-neutron dose, which is mainly released by
recoil protons owing to the elastic scattering of
neutrons with H nuclei.
IN-PHANTOM IMAGING OF
ABSORBED DOSE
The imaging method is based on radiochromic geldosimeters obtained by incorporating Ferrous-sulphate
and Xylenol-orange in Agarose-gel matrix. The effect
of ionizing radiation results in changes of the optical
absorption of visible light [5]. Transmittance images of
conveniently shaped layers of this dosimetric gel are
detected utilizing a CCD camera. An example of gel
layer irradiated in phantom is shown in Fig. 1. The gel
layer is placed on the illuminator for transmittance
image detection. The strip of gray level (GL) standards
is utilized for amending illumination instability.
In a gel layer having the standard composition and
placed in a phantom exposed to epithermal neutron
beams, the absorbed dose is due to the whole γ-dose
component (background and reactions of thermal
neutrons with hydrogen and eventually with
gadolinium) and to the fast-neutron. If to the previous
gel composition an isotope is added, responsible for
reactions with thermal neutrons with production of
charged particles, such as 10B or 14N, the measured
dose also contains this dose contribution. From the
comparative analysis of dose images detected with this
gel and with the standard one, the dose from charged
particles can be separated.
For separating γ-dose and fast-neutron dose, a
method as been proposed based on comparative
analysis of dose images detected with a standard gel
layer and a layer of gel made with heavy water [3].
It is possible to compose phantoms of the desired
shape and structure or to insert layers of dosimeter-gel
in anthropomorphic phantoms. After exposure, the
imaging of the gel-dosimeters allows obtaining the
imaging of the absorbed dose. Suitable gel
compositions and operation modalities have been
studied, aimed at imaging and profiling the various
dose contributions in tissue-equivalent phantoms both
FIGURE 1. GL image of a gel layer after exposure in the
epithermal column of the TAPIRO reactor, detected with
the CCD camera.
1103
conventional techniques. The γ-dose component has
been mapped by means of thermoluminescence
dosimeters (TLDs) and the neutron fluence has been
measured with activation technique and TLDs also.
with and without boron and also in phantoms
containing a volume with accumulation of 157Gd.
The phantom utilized in this experiment, shown in
Fig. 2(a), is a cylinder (14 cm of height and 16 cm of
diameter) made in polyethylene because its content of
hydrogen is near that in tissue. Dose images in the
central plane have been detected. Dosimeters and
simulated tumors have been suitably placed, in order
to avoid empty spaces in the phantom that could cause
alterations of neutron transport.
RESULTS
Exposures have been performed in the epithermal
column of the fast research reactor TAPIRO of ENEA
(Casaccia, Italy). Phantoms faced the collimator
(having squared shape, 10 cm × 10 cm)with the
phantom axis on the neutron beam axis.
Gamma and fast-neutron doses have been imaged
in the central plane of a polyethylene phantom and in a
phantom in which a cylindrical polyethylene volume
(3 cm of height and 7 cm of diameter) has been
replaced with agarose-gel containing gadolinium, in
order to simulate a big tumor. Natural gadolinium has
been incorporated, in the proper amount so to have
100 ppm of 157Gd. The scheme of this phantom is
shown in Fig. 2(b). The obtained results, reported in
Fig. 3, show that the presence of gadolinium in the
above amount gives noticeable increase of γ-dose in all
the phantom. It is important to underline that 100 ppm
of 157Gd is a low amount, principally with respect to
that proposed for therapy purposes.
(a)
Simulated tumour
0.15
Dose Rate (Gy/min)
γ dose in phantom
n
with simulated tumour
FriXy-Gel
TLD
γ dose in phantom
without simulated tumour
FriXy-Gel
TLD
0.1
0.05
Fast neutron dose
0
0
(b)
Gel-dosimeter layers
Tumour
4
8
Depth in phantom (cm)
12
FIGURE 3. Gamma dose components in the phantom with
and without a simulated tumor containing 100 ppm of 157Gd
and dose component due to fast neutrons.
FIGURE 2.
View of the cylindrical phantom during
preparation for exposure. The phantom contain a simulated
tumor (3 cm of height and 7 cm of diameter) with 100 ppm
of 157Gd.
In case of 157Gd accumulation, the dose component
coming from internal conversion and Auger electrons
has also been measured. The energy released by
electrons is a very small fraction of the total but its
determination is important because at present many
radiobiology studies concerning the efficacy of such a
dose are in development. Therefore, also the electron
In order to check the consistency of the obtained
results, dose and fluence measurements have been
performed in the central plane of the phantom utilizing
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The results shown here give further confirmation of
the validity of gel dosimetry in NCT. In fact, the
profiles of dose components in phantoms exposed to
epithermal neutrons are usually calculated by means
computer simulations, because no other experimental
techniques allows obtaining images and profiles of the
absorbed doses.
dose component has been measured with gel
dosimeters. In order to also inspect the consistency of
such results, the obtained electron dose profiles have
been compared with values evaluated on the basis of
kerma factors.
In conclusion, the measured doses are: 1) γ-dose,
coming in small fraction from reactor background and
mainly from thermal neutron reactions with H and
with157Gd, when gadolinium is present in the phantom;
2) proton-dose, due to thermal neutron reactions with
nitrogen; 3) fast-neutron dose; 4) if gadolinium is
present in the phantom, internal conversion and Auger
electron dose, caused by the reactions of thermal
neutron with 157Gd.
Moreover, the results reported above give
preliminary information that can contribute to the
valuation of the convenience of employing gadolinium
in NCT.
ACKNOWLEDGEMENTS
In Fig. 4(a) an example of the dose rate profiles
along the axis of the phantom is shown and in Fig. 4(b)
the same components are shown, multiplied by their
RBE values.
The work was partially supported by INFN (Italy)
and partially by MURST (Prot. 970916835_002 and
Prot. 2001062789_002). Authors are grateful to all the
staff of ENEA’s TAPIRO reactor, G. Rosi, O. Fiorani,
A. Perrone, G. Possenti and P. Di Venanzio, for their
efficient collaboration during phantom exposures.
Authors are grateful to Dr. G.Ranghetti and
Dr. P.Giammello of ROYALITE PLASTICS s.r.l.,
Div. Caleppio, for having supplied polystyrene plates
for transparent windows of gel-dosimeter samples.
0.2
Electrons
Dose Rate (Gy/min)
0.16
Gamma
(a)
Recoil proton
0.12
Thermal neutron(Nitrogen)
Total
0.08
0.04
REFERENCES
0
0
Gd
4
8
1. Watkins P., Moss R. L., Stecher-Rasmussen F. and
Voorbraak W., “Dosimetry for BNCT in theory and
pratice” in Advances in Neutron Capture Therapy, edited
by B. Larsson et al., Amsterdam: Elsevier, 1997, Vol. I,
pp. 141-146.
12
Depth in phantom (cm)
0.3
Dose Rate RBE (Gy/min)
Thermal neutron(Nitrogen)
0.24
Recoil proton
(b)
2. Gambarini G., Agosteo S., Marchesi P., Nava E., Palazzi
P., Pecci A., Rosi G. and Tinti R., Appl. Radiat. Isot. 53,
765-772 (2000).
Electrons
0.18
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0.12
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Lietti B., Mauri M. and Rosi G. IEEE Transactions on
Nuclear Science 48, 780-784 (2001).
Total
0.06
4. Gambarini G., Birattari C., Colombi C., Pirola L.and
Rosi G., Radiat. Prot. Dosim. 101, 419-422 (2002).
0
0
Gd
4
8
12
Depth in phantom (cm)
5. Appleby A. and Leghrouz A., Med. Phys. 18, 309-312
(1991).
FIGURE 4. Dose rate profiles (a) and dose rate RBE
profiles (b) in the central axis of a cylindrical phantom
containing a simulated tumor with 100 ppm of 157Gd,
exposed in epithermal column of a TAPIRO reactor.
6. Gambarini G., Gomarasca G., Pecci A., Pirola L.,
Marchesini R. and Tomatis S., Nucl. Instr. and Meth.
A422, 643-648 (1999).
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