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Single Photon Emission Tomography Approach for Online Patient

Dose Assessment in Boron Neutron Capture Therapy

Daniel M Minskya,b,c*

, Alejandro Valdaa,b, Andrés J Kreiner

a,b,c and

Alejandro A Burlona,b

aComisión Nacional de Energía Atómica, Departamento de Física, Av. Gral. Paz 1499,

1650, San Martín, Argentina

bUniversidad Nacional de San Martín, Escuela de Ciencia y Tecnología, M. de Irigoyen

3100, 1650, San Martín, Argentina

cCONICET, Av. Rivadavia 1917, 1033, Buenos Aires, Argentina

Abstract. A tomographic imaging system for the measurement of the spatial distribution of the absorbed dose

during a Boron Neutron Capture Therapy (BNCT) session is presented. The 10B(n,α)7Li boron neutron capture

reaction produces a 478 keV gamma ray in 94% of the cases. Therefore its detection can serve as a basis for a

non-invasive online absorbed dose determination since the dose absorbed by the tumor and healthy tissue

strongly depends on the boron uptake and the neutron flux. For this purpose, a dedicated tomographic imaging

system based on Single Photon Emission Computed Tomography is proposed. Monte Carlo numerical

simulations are used for the system design aimed to have a spatial resolution of 1 cm. Prototypes based on

CdZnTe semiconductor detectors and LaBr3(Ce) scintillators with optimized shielding were designed with

Monte Carlo simulations. They were built and tested in reactor and accelerator based BNCT facilities. A

projection of a phantom with two tumors with 400 ppm of 10B was successfully measured at the accelerator

facility of the University of Birmingham.

KEYWORDS: BNCT; SPECT; dosimetry; prompt-gamma detection.

1. Introduction

Boron neutron capture therapy (BNCT) [1] is a radiation therapy modality under development for the

treatment of some types of cancers like melanoma and glioblastoma multiforme. It is performed in two

steps: first, a stable isotope of boron (10B) is administered to the patient via a carrier drug and then the

patient is irradiated with an epithermal neutron beam. The neutrons are moderated as they penetrate

into the patient’s tissue and reach the tumor with thermal energy. 10B has a high thermal neutron

capture cross section (3840 b) leading to the 10B(n,α)

7Li reaction. The emitted charged particles have a

high linear energy transfer (LET) and they deliver all their energy (1.47 MeV for the α particle and

0.84 MeV for the 7Li) in a short range (9 µm for the α particle and 5 µm for the

7Li). Hence only the

cells in close proximity to the reaction point may suffer a lethal effect.

In BNCT the dose delivered to a patient depends both on the neutron beam quality and on the

selectivity and concentration of the drug used as the boron vector. As a consequence of the several

neutron interactions with the different nuclei present in tissue, the dose delivered has several

components with high and low LET. However in tumors having a typical boron concentration of 40

ppm, the neutron capture reactions in boron contribute to about 80 % of the total dose. The boron

concentrations in tumour and in healthy tissue needed for the dose assessment are currently inferred

from (a) the pharmacokinetics of the boron compound obtained from biodistribution studies not

necessarily performed on the specific patient to be treated and (b) the measurement of 10B

concentration in patient’s blood samples before and after irradiation. This method has large

uncertainties due to patient-to-patient variability and provides only global concentration values in

tumour and in healthy tissue. Finally the patient dose is evaluated from these 10B concentrations

together with a simulated neutron flux.

* Presenting author, E-mail: minsky@tandar.cnea.gov.ar

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A better technique is hence necessary to improve the dosimetry in BNCT. In this regard it is important

to point out that in 94 % of the neutron captures in 10B, the

7Li ion is emitted in an excited state which

promptly decays through a characteristic 478 keV gamma-ray. As the linear attenuation coefficient in

tissue at this energy is about 0.1 cm-1, the gamma-rays escape out of the patient’s body to a large

extent. Therefore the extracorporeal measurement of the 478 keV prompt-gamma radiation can be

performed and directly related to the boron dose component. Moreover, the use of a radiation

detection system with imaging (in particular, tomographic) capabilities could provide a non-invasive

way to determine the boron dose distribution (dose mapping) delivered to the patient as well as an

online dose monitoring. Several groups have studied different approaches for this online dosimetry [2, 6].

In this work we present the design of a SPECT (Single-Photon Emission Computed Tomography)

imaging system especially dedicated to operate under the particular conditions (gamma-ray and

neutron radiation background) present in a BNCT treatment room. The system is designed in order to

provide the boron dose distribution with a spatial resolution of about 1 cm. Results of Monte Carlo

numerical simulations for the final system are presented as well as numerical and experimental results

obtained with a prototype systems using CdZnTe semiconductor detectors and LaBr3(Ce) scintillation

detectors.

2. Design considerations for a complete system

The system was designed for imaging the boron captures in a patient head. In a complete BNCT

treatment there are about 2×109 emissions of 478 keV photons per cubic centimeter in tumor. This

emission number is determined by the dose needed to obtain a significant tumor control without

exceeding the maximum healthy tissue dose. Considering an intrinsic detector efficiency of the order

of 10 % and a collimator geometrical efficiency of the order of 10−3%, there is a small number of

events expected to be detected during the treatment that finally will limit the image quality. As a

compromise between detector efficiency and spatial resolution we designed our collimators to obtain 1

cm resolution at a distance of 20 cm with a geometrical efficiency 3.4×10−3%. In order to largely cover

a transaxial field of view of 20 cm, a collimator of 23.7 cm in lateral length was chosen; having 37

parallel holes with 4.4 mm in diameter. This collimator configuration can house an array of 37

independent detectors [6].

For the tomographic acquisition a total of 20 angular positions (evenly spaced at 9 degrees, from 0 to

171 degrees) are considered giving a total of 740 projection data. The image consists of 21×21 pixels

of 1 cm × 1 cm size each. The algorithm chosen for the tomographic reconstruction was Expectation

Maximization - Maximum Likelihood (EM-ML) [7]. The system matrix A needed for the

reconstruction was calculated by Monte Carlo numerical simulations using the MCNP v5.140

code [8]; attenuation, scatter in collimator and photoelectric absorption in the scintillator were

considered.

Figure 1: (a) Phantom used in the numerical simulations. (b) Reconstructed image with acquired

Poisson statistical noise negligible. (c) Reconstructed image having a 10 % signal to noise ratio in the

most significant projection.

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The MCNP code was also used for simulating the acquisition of the phantom shown in Fig. 1. This

phantom consists of a water-filled cylinder of 8 cm radius containing four cylindrical tumors of

different radii: 0.25, 0.5, 0.75 and 1 cm. The activity concentration was 4 (arbitrary units) for tumors

and 1 for the rest of the phantom in agreement with the concentration ratio between tumor and healthy

tissue found for p-boronphenylalanine (BPA), the usual boron carrier drug in BNCT [1]. The energy

of the simulated gamma emission was 478 keV. The simulations take into account the attenuation and

scattering processes in the phantom and the collimator but no other sources of background such as

gamma rays produced by neutron capture in hydrogen. Fig. 1 also shows the reconstructed images for

two cases: where the statistical fluctuations (Poisson noise) in the acquired projections are negligible

and where the signal to statistical fluctuation ratio in the projections is 10 %.

3. Prototype design

3.1 Collimator and detectors

The collimator was designed in order to maximize the detection efficiency with a spatial resolution of

1 cm at the center of the field of view (FOV). The detector to FOV center was chosen to be 60 cm due

to practical considerations. Therefore the other dimensions resulted in 0.5cm for the hole diameter and

30 cm for the collimator length with a geometric efficiency of 4.34×10-6.

Two kind of detectors were tested in the prototype: CdZnTe room-temperature semiconductors and

LaBr3(Ce) scintillation detectors. The CdZnTe have a size of 5×5×5 mm3 and LaBr3(Ce) are 2.54 cm ×

2.54 cm (diameter × height) cylindrical scintillators. The CdZnTe prototype was tested in the BNCT

facility located in the RA6 reactor of the Centro Atómico Bariloche (Argentina) and the scintillator-

based prototype in the accelerator based BNCT facility (AB-BNCT) of the University of Birmingham

(United Kingdom).

3.2 Shielding

The shielding was designed for blocking not only gammas but also neutrons, since they can generate

gamma contamination inside the detectors. The proposed shielding, in the case of the prototype for the

AB-BNCT facility, consists of several layers as shown in Fig. 2: an external layer of a moderator

material with high concentration of hydrogen (paraffin) mixed with lithium (14% in mass of NatLi2CO3) to thermalize and capture neutrons, a second layer of lead to shield from gammas and a

layer of 95% 6Li enriched lithium carbonate to capture residual thermal neutrons before reaching the

detector.

Figure 2: Detector shielding. A material with high hydrogen content thermalizes the neutrons, a lead

layer blocks gammas and a 6Li layer captures thermal neutrons before reaching the detectors.

The proposed shielding has been simulated with MCNP 5 for different paraffin and lead thicknesses in

order to estimate the expected background under the 478keV peak. Two different contributions to the

background have been taken into account: the gamma background coming from outside the detectors

and the gamma background generated inside them by neutron captures. The background decreases

Detector

6Li2CO3

Pb

Collimator

Paraffin with NatLi2CO3

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with the lead thickness due to attenuation of the external gamma rays, and it also reduces with the

moderator thickness since it prevents captures in the crystal and the subsequent gamma production.

Due to weight and space limitations, the shielding lead and paraffin layers have been chosen to be

10 cm thick each. Under this condition the expected background count rate is 120 cps for the

measurements at the AB-BNCT facility.

4. Experimental results

Fig. 3 shows the built scintillator-based prototype placed in the BNCT accelerator facility of the

University of Birmingham.

Figure 3: Experimental setup with the shielding partially removed.

The collimator resolution has been tested with the CdZnTe detectors; Fig. 4 shows the measured and

simulated responses. A simple phantom containing a 241Am point source has been used to test the

reconstruction algorithm. The source was placed in a 9.22 cm radius cylindrical phantom at 4 cm from

its axis. The acquisition and reconstruction scheme was as in the designed final setup: 20 projections

of 41 bins each reconstructed on a 21×21 image matrix using the EM-ML algorithm. The

reconstructed image is shown in Fig. 4.

Figure 4: Comparison of experimental

spatial resolution of the collimators with

simulations.

Figure 5: Reconstructed image of a phantom with a

point 241Am source.

-1.0 -0.5 0.0 0.5 1.0

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Experimental Simulation

Nor

mal

ized

inte

nsity

Off-axis position [cm]

R=0.97cm

-10 -8 -6 -4 -2 0 2 4 6 8 10 -10-8-6-4-20246810

5000

10000

15000

20000

25000

Y [c

m]

X [cm]

Reconstructed Intensity[Bq]

Beam shapping

assembly

Beam Port

SPECT

prototype

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A cylindrical water-filled phantom (radius 9.22 cm) containing a cylindrical tumor model (radius 3

cm) having 1000 ppm in 10B concentration was used to perform measurements with the CdZnTe

prototype in the RA6 reactor BNCT facility. Fig. 6 shows a detailed view, around the 478 keV region,

of spectra obtained when the tumor is placed respectively inside and outside the detector FOV. In both

of them appears the 511 keV annihilation peak. The boron capture peak is visible when the tumor is in

front of the detector although it is difficult to quantify due to the low statistics caused by the low

detector efficiency.

Figure 6: Measured spectra (detailed view) obtained with the CdZnTe system when the tumor is (is

not) in the detector FOV.

350 400 450 500 550 600 6500.10

0.15

0.20

0.25

Tumor zone Blank zone

C

ount

ing

Rat

e [s

-1]

Energy [keV]

The γ background was measured with the LaBr3(Ce) system mounted at the BNCT accelerator facility

of the Birmingham University and a spurious 478 keV peak was found. Those photons came from

captures in the photomultiplier tube which is made of borosilicate. A 2 mm Cd layer between the

paraffin and the lead reduced this unwanted peak and also the background (Fig. 7).

Figure 7: A Cd layer between paraffin and lead reduced the spurious signal coming from neutron

captures in the photomultiplier tube.

A projection of the water-filled phantom with two tumors (400ppm 10B and 3cm in diameter each) has

been measured (Fig. 8). Fig. 9 shows the difference between the tumor and a pure water region. The

small 478 keV peak in the water measurement is due to the remaining captures in the photomultiplier

tubes. The projection spectra were adjusted with a simple model: an exponential background, a

Gaussian 478 keV peak and a Gaussian 511 keV annihilation peak. After correction for remnant 478

keV, the measured profile across the phantom and tumors is shown in Fig. 10. Comparison with

MCNP simulations shows a very good agreement.

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Figure 8: Cross section of the water-filled cylindrical phantom with 2 tumors with 400ppm of 10B

used in the experiments.

Figure 9: Spectra measured at Birmingham’s BNCT facility from a tumor and at a water region.

Figure 10: Measured and simulated profiles of a phantom with two tumors. The shaded areas indicate

tumor positions.

4. Conclusions

A tomographic device for online dosimetry in BNCT has been proposed. Monte Carlo numerical

simulations were used to evaluate its imaging performance. First results indicate that it would be

possible to recover boron concentrations with an uncertainty of 10 % in tumors with 2 cm in diameter.

Prototypes have been designed, built and tested in a reactor-based BNCT facility and in an accelerator-

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based one. The LaBr3(Ce) system performed better than CdZnTe system mainly for its better detection

efficiency. A profile of a phantom has been measured showing very good agreement with the

simulations. Although the background must be further reduced, this work shows the feasibility of such

a system.

Acknowledgements

The authors wish to thank Drs. S. Green, C. Wojnecki and. Z. Ghani for their help in performing the

experiments in the BNCT accelerator facility of the University of Birmingham and Drs. O. Calzetta,

H.R. Blaumann and J. Longhino for their help in performing the experiments in the RA6 reactor

BNCT facility at the Centro Atómico Bariloche. The authors also acknowledge the financial support

provided by ANPCyT, CNEA, CONICET and UNSAM.

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