Essay: Boron Neutron Capture Therapy (BNCT)

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ABSTRACT

Boron Neutron Capture Therapy (BNCT) technique needs a special design methodology. In this work, a new design method for a multilayer spectrum shifter is proposed in order to improve the design process of epithermal BNCT beams for research reactors. This design method is based on two concepts: stepwise spectrum shifting, and separation of the design process into two design stages, namely the material(s) selection and the thickness(es) determination. Java-based Nuclear Information Software (JANIS) and Monte Carlo N’Particle code ‘MCNP5’ have been used for cross sections computations and beam design, respectively. In order to validate the developed methodology, it has been applied on two cases studies using two different neutron spectra as neutron sources: a Watt fission neutron spectrum and a leakage neutron spectrum of a typical MTR-TYPE reactor. The different beam components have been designed but more concern has been given for the spectrum shifter. Various parametric studies have been done for the selected spectrum shifter materials using the MTR-TYPE reactor spectrum. For both cases studies, comparisons have been done between the proposed spectrum shifter and the well-known patent material ‘FLUENTALTM’. The results of comparisons confirm that the proposed design outperforms the patent material ‘FLUENTALTM’. These results indicate that the developed design method in this work could generate efficient and effective spectrum shifters for epithermal BNCT beams in research reactors. The proposed method has some advantages as: time saving, simplicity, effectiveness, and efficiency. Therefore, this method may be extended to be applied for other BNCT facilities such as accelerator-based BNCT as well as other epithermal beams used for different applications.

TABLE OF CONTENTS

ABSTRACT 1
TABLE OF CONTENTS 3
LIST OF FIGURES 5
LIST OF TABLES 7
CHAPTER 1
INTRODUCTION 9
Boron Neutron Capture Therapy (BNCT) 9
General requirements of BNCT Facility at a Nuclear Research Reactor 9
Desired Neutron Beam Parameters 14
General beam properties 14
Epithermal beam intensity 16
Incident beam quality 17
Beam size 19
CHAPTER 2
REVIEW OF LITERATURE 20
Reactor And Beam Design Considerations 20
Approaches to Using Reactors for Epithermal Neutron
BNCT 29
Performance of Some Current Epithermal Neutron Irradiation Facilities 31
CHAPTER 3
METHODOLOGY 34
BNCT beam configuration 34
Proposed spectrum shifter design methodology 36
First stage: Material selection 38
3.2.2 Second stage: Thickness determination 39
CHAPTER 4
RESULTS AND DISCUSSION 41
Introduction 41
BNCT beam design using Watt fission neutron spectrum 41
Reflector, Collimator, and Shield 41
Spectrum shifter 42
First stage: Material selection 45
Second stage: Thickness determination 46
Thermal neutron filter 47
Gamma filter 47
Optimum position of the thermal neutron filter 48
Validation of proposed spectrum shifter design methodology
using a Watt fission neutron spectrum source 49
BNCT beam design for a typical MTR-TYPE reactor 51
4.3.1 Reflector, Collimator, and Shield
First thermal neutron filter 53
Spectrum shifter 53
Second thermal neutron filter 54
Gamma filter 55
Collimator thickness 56
Validation of proposed spectrum shifter design methodology
in a typical MTR-TYPE reactor 57
Parametric analysis for the selected spectrum shifter materials 57
4.4.1 Verification of material sequence 65
CHAPTER 5
CONCLUSIONS AND RECOMMENDATIONS 68
REFERENCES 69

LIST OF FIGURES

Fig. 1.1 schematic for BNCT irradiation facility 10
Fig. 1.2 Comparison of flux-depth distributions for thermal and epithermal neutrons 16
Fig. 1.3 Typical spectrum shifting arrangement 21
Fig. 1.4 Example of an effort to minimize core-to-patient distance 22
Fig. 3.1 Schematic diagram BNCT beam configuration 35
Fig. 4.1. Group ratios for the studied materials 43
Fig. 4.2. Group ratios for the studied materials 44
Fig. 4.3. Schematic diagram of the final beam MCNP model for case 49
Fig. 4.4. Beam inlet normalized neutron energy spectrum for case 2 52
Fig. 4.5. Beam inlet gamma energy spectrum for case 2 52
Fig. 4.6. Schematic diagram of the final beam MCNP model for case 57
Fig. 4.7. Change in fast and epithermal currents for 7LiF with
Thickness 61
Fig. 4.8. Change of fast neutron groups to epithermal current ratios for 7LiF with thickness 61
Fig. 4.9 Change in fast and epithermal currents for AlF3 with
Thickness 62
Fig. 4.10. Change of fast neutron groups to epithermal current ratios for AlF3 with thickness 62
Fig. 4.11. Change in fast and epithermal currents for 60Ni with
Thickness 63
Fig. 4.12. Change of fast neutron groups to epithermal current ratios for 60Ni with thickness 63
Fig. 4.13. Performance of selected materials: 7LiF, AlF3, and 60Ni at thicknesses 4-60 cm 63
Fig. 4.14. Performance of selected materials: 7LiF, AlF3, and 60Ni
at thicknesses 4-60 cm for the 3rd fast neutron group 65
Fig. 4.15A. Performance of selected materials: 7LiF, AlF3, and 60Ni
at thicknesses 4-60 cm for the 2nd fast neutron group 66
Fig. 4.15B. Performance of selected materials: 7LiF, AlF3, and 60Ni
at thicknesses 4-24 cm for the 2nd fast neutron group 66
Fig. 4.16. Performance of selected materials: 7LiF, AlF3, and 60Ni
at thicknesses 4-60 cm for the 1st fast neutron group 66

LIST OF TABLES

Table 1.1 Facility characteristics and beam performance figures of merit for various clinical NCT centers determined by in-air and in-phantom measurements using BPA and where available (in brackets) a hypothetical advanced boron compound 31
Table 3.1 The layers and fast groups numbers, energy groups, and corresponding fast neutron groups 37
Table 4.3 In air beam port quality parameters for the empty beam for
case 1 42
Table 4.4 Neutron in air beam port quality parameters after adding reflector, collimator, and shield for case 1 42
Table 4.5 The efficient & selected materials of each layer and corresponding neutron & energy groups for case 1 45
Table 4.6 In air beam port quality parameters after adding the first spectrum shifter layer for case 1 46
Table 4.7 In air beam port quality parameters after adding the second spectrum shifter layer for case 1 46
Table 4.8 In air beam port quality parameters after adding the third (last) spectrum shifter layer for case 1 47
Table 4.9 In air beam port quality parameters after adding the thermal filter for case 1 47
Table 4.10 In air beam port quality parameters after adding the gamma filter for case 1 48
Table 4.11Comparison between in air beam port quality parameters when placement of the thermal filter in two different positions for case 1 49
Table 4.23 Comparison between in air beam port parameters of the proposed spectrum shifter and FLUENTALTM for case 1 50
Table 4.12 In air beam port quality parameters for the empty beam for case 2 51
Table 4.13 Neutron in air beam port quality parameters after adding reflector, collimator, and shield for case 2 53
Table 4.14 In air beam port quality parameters after adding the first thermal filter for case 2 53
Table 4.15 The selected materials and optimum thickness for each spectrum shifter layer for case study two 54
Table 4.16 In air beam port quality parameters after adding the first spectrum shifter layer for case 2 54
Table 4.17 In air beam port quality parameters after adding the second spectrum shifter layer for case 2 54
Table 4.18 In air beam port quality parameters after adding the third (last) spectrum shifter layer for case 2 55
Table 4.19
In air beam port quality parameters after adding the second thermal filter for case 2 55
Table 4.20
In air beam port quality parameters after adding the gamma filter for case 2 56
Table 4.21
Final in air beam port quality parameters after adding two Bismuth gamma filters for case 2 56
Table 4.22
Comparison between in air parameters when using Pb collimator with thickness 10 and 20 cm for case 2 57
Table 4.24
Comparison between in air beam port parameters of the proposed spectrum shifter and FLUENTALTM for case 2 59

CHAPTER 1
INTRODUCTION

Boron Neutron Capture Therapy (BNCT)

Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumour cells in which boron-10 compound has been accumulated [1].
General requirements of BNCT Facility at a Nuclear Research Reactor

The design and construction of a BNCT facility in a nuclear research reactor is a very demanding task. From the engineering and physical viewpoint, the general requirements to house a complete facility in the confines of a reactor building are [2]:
i) there should be a sufficient and adequate fluence rate of neutrons that emanate through a large diameter beam tube, that itself preferably faces a large source area of the neutron source.
ii) there must be suitable space at the exit side of the beam, to accommodate a large working area for building the irradiation room.
iii) the facility should be freely accessible such that the patient, who may be unable to walk, can be readily and easily brought into the irradiation room from outside.
Furthermore, outside the reactor building confinement:
iv) there should be space allocated outside the reactor building to house facilities for the reception and preparation of the patient prior to entering the facility for treatment. However, this latter condition, providing that there is sufficient space within the reactor building, may apply to within the building.

The basic design can be broken down into specific components, which formed the basis of one of the 2 Working Groups held at the Prague Workshop, entitled: ‘How to build up an irradiation facility for BNCT’. The Working group defined the following 9 components, based on the schematic simplification, shown in figure 1.1, where each numbered component represents:

Fig. 1.1 schematic for BNCT irradiation facility

1. Reactor
2. Beam tube
3. Patient
4. Irradiation room
5. Control room
6. Reception area
7. Beam dosimetry/characterisation
8. Beam monitors
9. Beam shutter

Following are some details for each component requirements:
1. The Reactor
In BNCT, there is no singly-available reactor-type that may be regarded as the ideal reactor to develop a BNCT facility. Over the decades a wide variety of reactor-types have been utilised, as the neutron source for a BNCT facility. The closest single design could be a TRIGA, however even this may vary in power and configuration, e.g. utilisation of the thermal column or beam tube.
2. The beam tube The neutrons, and gammas, emanating from the reactor, need to be moderated, filtered and/or attenuated, such that the required beam intensity and average neutron energy are within the requirements, which themselves can vary depending on the type of tumours to be treated. The recommended beam parameters will be discussed in details later.
3. The patient
The type of tumour to be treated will also influence the beam design, whether an epithermal beam or thermal beam is required. Also whether the patient can only be treated in a horizontal position or seated, will influence the design.
4. The irradiation room
If a patient is to be treated in a horizontal position, and especially if brain tumours are to be treated, there should be sufficient space, such that the treatment table can be rotated ”90 degrees about the beam axis. Preferably, the central beam axis should be at least 1m vertically above the floor. The room itself should contain most if not all facilities expected in a conventional radiotherapy room, e.g. cameras, laser positioning devices, ease-of-access, etc.
5. The control or observation room
The patient and the facility need to be monitored. Monitoring equipment such as, puls-oxymeters, TV monitors, microphones, radiation level instrumentation, radiation monitors measuring the beam characteristics, all need to be housed in an area or room, where the medical and physics staff can comfortably sit and observe the patient and radiation beam parameters. Such a room should be next to the irradiation room and be at least 10m2.
6. Reception area or building
Next to, or outside but close to the entrance to the reactor, an area or dedicated building should be available, where the patient can be received prior to treatment. It will be necessary to prepare the patient, e.g. infusion of the drug, change of clothing, medical examination. The area or building should also have the provisions of an office, for the medical staff, a waiting room, for accompanying relatives, as well as,, of course, a WC.
7. Beam dosimetry/characteristion
The radiation beam is a mixture of neutrons, of all energies, and gamma rays. The beam must be thoroughly characterized, as part of any quality assurance system, as well as, being absolutely necessary, in order that accurate and reliable calculations, especially for treatment planning can be performed. There are a variety of techniques available to characterize such a beam. The irradiation room should be designed such that any eventual measurements can be readily carried out.
8. The beam monitors
A beam monitoring system must be available that can measure the radiation beam during treatment and have the capacity to automatically close the beam when the required radiation dose is achieved or when an emergency situation occurs. As in conventional radiotherapy, all safety systems should be backed-up by an independent, second device acting in case of failure of the first. In BNCT, a beam monitoring system normally consists of four beam monitors: two 235U fission chambers (neutron counters) and two GM-tubes (gamma ray counters), which are located close to the beam line, usually in the wall of the beam tube or in the (fixed) collimator, downstream from any beam shutter. The automatic opening and closing of the beam should be controlled by the fission chambers, according to a pre-set number of monitor counts which correspond to the required boron dose delivered at the dose group identification point in a patient. Both fission chambers are pre-set to close the shutters, which are automatically triggered when the target counts are reached. The fission chambers, as well as the GM-tubes, should be monitored and the counts and count rates displayed on two independent computer systems. As an additional back-up for beam shutter closure, i.e. if the monitoring system fails, a timer should be available, with a pre-set time at 2% above the given irradiation time. If called into use, closure of the beam shutters is automatically triggered.
9. Beam shutter
Depending on the reactor-type utilized, a beam shutter or shutters are necessary, such that the radiation can be stopped or reduced sufficiently in intensity, such that staff can enter the irradiation room. Some reactors, such as the HFR at Petten, operate 24 hours a day, as such the beam shutters must open and close without any mutual effect on the operation of the reactor and to reduce radiation levels to levels where the staff can enter the room. At some facilities, such as low power, TRIGA reactors, the reactor itself is shut-down as part of the treatment procedure. Beam shutters are generally made of layers of lead and borated or lithiated polyethylene. Opening and closing of the beams must be performed remotely, with emergency back-up facilities to shut the shutters, if the power supply fails. The shutters must be equipped with interlock devices to enable automatic shut-down when the required dose is achieved or in emergencies. If necessary, it should be possible to close the beam shutter(s) manually, if any electrical failure occurs. As a last resort, the beam operator has the mandate to instruct the reactor operators to scram the reactor.

DESIRED NEUTRON BEAM PARAMETERS [3]

General beam properties
Before addressing how to modify reactors and how to condition beams, it is first necessary to establish the beam characteristics desired for BNCT.
For BNCT, an adequate thermal neutron field has to be created in the boron-labelled tumour cells within a prescribed target volume. This means that for target volumes well below the surface, epithermal beams will generally be best, while for target volumes near the surface, thermal beams will suffice.
Figure 1.2 shows that an epithermal beam entering tissue creates a radiation field with a maximum thermal flux at a depth of 2’3 cm, which drops exponentially thereafter. The penetration of the beam can be increased by increasing the average energy of the epithermal neutrons and by increasing the forward direction of the beam, especially with small beam sizes. In contrast to the epithermal beam, which shows a skin-sparing effect, the thermal flux falls off exponentially from the surface. Thus, thermal neutron irradiations have been used for melanoma treatments in the skin, as well as with open craniotomy for glioma treatments. In general, however, the current trend for treatment of patients with brain tumours is to use epithermal neutron beams.
Radiobiology research for NCT, on the other hand, requires access to both thermal and epithermal beams. Clinical facilities can be used to study the effects of epithermal irradiation, but when studying the effect of boron carrier compounds using cell cultures or small animals, a pure thermal neutron field is preferred.

Most epithermal beams are accompanied by, and produce, other radiations that are not selectively absorbed by labelled cells, and therefore contribute to both normal and tumour tissue damage. It is clearly desirable to reduce these radiations as much as possible in the incident neutron beam. Since the bulk of the report will focus on patient related aspects, it can be stated that the beam design objective is to deliver an epithermal neutron fluence within a reasonable treatment time and to produce the desired thermal neutron fluence at tumour depth with minimal other radiations present.

Fig. 1.2 Comparison of flux-depth distributions for thermal and epithermal neutrons.

The two principal beam characteristics of interest are intensity and quality. Beam intensity will be the main determinant of treatment time. Beam quality relates to the types, energies, and relative intensities of all the radiations present.
Epithermal beam intensity
For the purposes of reporting beam intensity, the common definition for an epithermal energy range should be used, namely 0.5 eV to 10 keV. If other energy limits are used, they should be clearly reported. Current experience shows that a desirable minimum beam intensity would be 109 epithermal neutrons cm’2 s’1. Beams of 5 x 108 n cm’2 s’1 are useable, but result in rather long irradiation times.
When aiming at higher intensities (>1010) the advantages of shorter irradiation times must be weighed against those of improved beam quality. Where there is a choice to be made, most practitioners would rather have better quality rather than more intensity, within the constraint of having a reasonable treatment time (possibly extending up to one hour). Requiring immobilization of patients for significantly longer times reduces the clinical acceptability of BNCT as a therapy.
Tumour boron concentration will affect the requirements for beam intensity. If the boron concentration can be raised from the currently values, the beam intensity requirement (or treatment time) will be reduced proportionately. On the other hand, if the beam intensity is too low, it may be difficult to maintain the necessary boron concentration in the tumour for the total irradiation time required. To avoid unduly lengthy irradiation times, fractionation may be considered as an alternative. It could also provide opportunity for boron compound retargeting.

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