Download - Evaluation of the near threshold 7 Li( p , n ) 7 Be accelerator-based irradiation system for BNCT
Evaluation of the near threshold 7Li(p,n)7Be accelerator-based irradiation system for BNCT
A treatable protocol depth (TPD)-based characterization of neutron fields
Gerard Bengua
Presentation Outline• Introduction• New protocol-based evaluation
indices• Characterization of BDE Materials• TPD-based evaluation of near-
threshold proton energies• Effects of variations in 7Li-target
thickness• Gaussian proton beams for the
near threshold 7Li(p,n)7Be reaction
Introduction
Boron Neutron Capture Therapy
highly selective killing of tumor cells with simultaneous sparing of normal cells
Introduction
Success ofSuccess of
BNCTBNCT
Boron Compoundthat preferably delivers higher 10B
concentration in tumor than in healthy cells
Method for determining 10B concentration
for accurate timing of neutron irradiation
Neutron irradiation field
that can provide a high flux of thermal neutrons at sites where 10B accumulates
Introduction
Neutron sources for BNCT
Radioisotopic source
252Cf
Nuclear Reactorscapable of producing high neutron flux with stable therapeutic properties for
BNCT
(Bay
anov
et a
l, 19
98)
Accelerator-based Neutron Sources
(ABNS)can produce epithermal beam source
with small fast neutron, thermal neutron and -ray contamination and feasible for a hospital-based BNCT
Introduction
Introduction• Accelerator-based
neutron source for BNCTAdvantages:
Hospital-based implementation of BNCT Familiarity of oncologist, medical physicist and technicians with
accelerators in hospitals Public acceptance
Introduction
Reaction Bombarding energy (MeV)
Neutron production rate (n/min-mA)
Average neutron energy at 0 (MeV)
Maximum neutron energy (MeV)
7Li(p,n) 2.5 5.34x1013 0.55 0.7869Be(p,n) 4.0 6.0x1013 1.06 2.129Be(d,n) 1.5 1.3x1013 2.01 5.8113C(d,n) 1.5 1.09x1013 1.08 6.77
• Accelerator-based neutron source for BNCT
• Candidate reactions Candidate reactions for ABNSfor ABNS
Introduction• Accelerator-based
neutron source for BNCT• Candidate reactions for
ABNS• The 7Li(p,n)7Be
reaction Moderated neutron usage – Ep ~ 2.5MeV
Near-threshold neutron Near-threshold neutron productionproduction
lower ave. neutron energy = no need for dedicated moderators
neutrons are kinematically collimated
more compact irradiation systemThreshold
energy: 1.881MeV
Introduction• Accelerator-based
neutron source for BNCT• Candidate reactions for
ABNS• The 7Li(p,n)7Be
reaction Moderated neutron usage – Ep ~ 2.5MeV
Near-threshold neutron Near-threshold neutron productionproduction
feasibility for BNCT irradiation demonstrated by Tanaka et al (2002)
Introduction• Accelerator-based
neutron source for BNCT• Candidate reactions for
ABNS• The 7Li(p,n)7Be reaction• Recent research
output of our group1. Proposed new and more comprehensivenew and more comprehensive dose evaluation indices dose evaluation indices
for BNCT based on actual dose protocol; 2. Established a method for the characterization of neutron fieldsmethod for the characterization of neutron fields for
BNCT;3. Evaluated the various components of the near-threshold
7Li(p,n)7Be-ABNS for BNCT using the and ;
New Protocol-based Evaluation Indices
Treatable Region:Treatable Region:(1) the tumor dose from HCP is
greater than or equal to the treatment protocol dose for tumors;
(2) the dose to healthy tissue do not exceed the tissue tolerance dose from either HCP or gamma rays set by protocol;
The Treatable Protocol Depth Treatable Protocol Depth (TPD)(TPD) is the maximum depth of the treatable region relative to the surface facing the incident neutron beam. For
symmetric geometries, this is located at the central axis.
Dose components of the Dose components of the intra-operative BNCT for intra-operative BNCT for brain tumorbrain tumor (Nakagawa et al., 2003)
HCP HCP +
Treatable Dose (Gy) 15 * *Tolerance Dose (Gy) 15 10 *
*No particular dose is currently specified in the protocol
Background and Definitions
BNCT dose components
BNCT dose components
Normalized dose components based on dose protocol
The Treatable Treatable
Protocol Depth Protocol Depth (TPD)(TPD)
is equal to whichever is
shallower between PD(hcp)
and PD().
*BDE – Boron dose enhancer( Unit : mm )
H2O Phantom(180diam×200)
Central axisProton
38
TPD = 0.45 cm
0 2 4 6 8 10 120
1
2
3
4
5
No BDEGaussian spectrum, = 0.030MeVProton energy, Ep, ave= 1.900MeV
HCP dose to healthy tissue HCP dose to tumor Gamma dose to tumor
and healthy tissue
Dos
e R
ate
(Gy/
h/m
A)
Central Axis Depth (cm)
TPD = 2.11 cm
0 2 4 6 8 10 120
1
2
3
4
5
D
ose
Rat
e (G
y/h/
mA
)
Central Axis Depth (cm)
HCP dose to healthy tissue HCP dose to tumor Gamma dose to tumor
and healthy tissue
Gaussian spectrum, = 0.030MeVProton energy, Ep, ave= 1.900MeV 1cm Polyethylene BDE
BDE*
( Unit : mm )
H2O Phantom(180diam×200)
Central axisProton
38
( Unit : mm )
H2O Phantom(180diam×200)
Central axisProton
38BDE*
TPD = 2.91 cm
0 2 4 6 8 10 120
1
2
3
4
5
2cm Polyethylene BDEGaussian spectrum, = 0.030MeVProton energy, Ep, ave= 1.900MeV
HCP dose to healthy tissue HCP dose to tumor Gamma dose to tumor
and healthy tissue
Dos
e R
ate
(Gy/
h/m
A)
Central Axis Depth (cm)
The relationship between BDE thickness and PD(hcp), PD() and TPD.
TPDmax peak of the TPD versus BDE thickness curve
BDE(TPDmax)the BDE thickness
corresponding to TPDmax
The relationship between BDE thickness and PD(hcp), PD() and TPD.
Characterization of BDE materials
Objective
To determine possible optimization criteria for selecting appropriate BDE materials for BNCT.
In particular,
1. Evaluate the effects of various candidate BDE materials on the BNCT dose components;
2. Examine the characteristics of candidate BDE materials in relation to the Treatable Protocol Depth (TPD) and other pertinent figures of merit;
Calculation ParametersCandidate BDE
MaterialsChemical formula
Polyethylene (C2H4)n
Perdeuterated ethylene (C2D4)n
Teflon (C2F4)n
Fluoroethene (C2H3F1)n
1,2-difluoroethene (C2H2F2)n
Trifluoroethene (C2H1F3)n
Beryllium Be
Graphite C
Heavy Water D2O
Lithium fluoride 7LiF
Incident proton energy: 1.900MeV (mono-energetic)7Li-target thickness: 2.33mBDE diameter: 18cmBDE thickness: Variable (chosen in order to attain
the TPDmax for each BDE material)BDE material: Variable
Calculation Method
Neutron production -ray production
Particle transport
Dose calculation
Evaluation of dose distribution
Flowchart of Calculation Flowchart of Calculation ProceduresProcedures
Calculation Method
Neutron production -ray production
Particle transport
Dose calculation
Evaluation of dose distribution
Flowchart of Calculation Flowchart of Calculation ProceduresProcedures
Neutron production at the Neutron production at the 77Li-targetLi-target
• Lee et al.’s code: calculation of neutron yields from thin 7Li-target for the near threshold 7Li(p,n)7Be reaction
• Bethe’s stopping power formula: derivation of 7Li-target thickness
Calculation Method
Neutron production -ray production
Particle transport
Dose calculation
Evaluation of dose distribution
Flowchart of Calculation Flowchart of Calculation ProceduresProcedures
Production of gamma-rays from proton-Production of gamma-rays from proton-induced reactionsinduced reactions
*Neutron induced production of gamma-rays are included in the MCNP simulation
ReactionThreshold
energy(MeV)
Photon energy(MeV)
7Li(p,p’)7Li 0.550 0.478
27Al(p,p’)27Al0.875 0.844
1.052 1.01427Al(p,)24Mg 1.420 1.369
27Al(p,)28Si0 1.779
0 2.839
Calculation Method
Neutron production -ray production
Particle transport
Dose calculation
Evaluation of dose distribution
Flowchart of Calculation Flowchart of Calculation ProceduresProcedures
Neutron and gamma-ray transport in Neutron and gamma-ray transport in the irradiation systemthe irradiation system
• Monte-carlo n-particle (MCNP) transport code (MCNP4C2, MCNPX)
• Particle tally: neutron and gamma-ray flux
• Estimated relative error of calculated data < 5%
• S(,) thermal neutron scattering tables
Calculation Method
Neutron production -ray production
Particle transport
Dose calculation
Evaluation of dose Evaluation of dose distributiondistribution
Flowchart of Calculation Flowchart of Calculation ProceduresProcedures
Calculation of absorbed dose in tumor Calculation of absorbed dose in tumor and healthy tissueand healthy tissue
• Absorbed dose = flux * KERMA factor• Tissue composition: H(11.1), C(12.7),
N(2.0), O(74.2)
Calculation Method
Neutron production -ray production
Particle transport
Dose calculation
Evaluation of dose distribution
Flowchart of Calculation Flowchart of Calculation ProceduresProcedures
Evaluation of dose distributionEvaluation of dose distribution
Evaluation indices: Treatable protocol depth (TPD), Heavy-charged particle protocol depth (PD(hcp)), Gamma-ray protocol depth (PD())
Applied dose protocol: Intra-operative BNCT dose protocol for brain tumors
Dependence of PD(), PD(hcp) and TPD on BDE thickness
Materials with Materials with (C2X4)n structure
Dependence of PD(), PD(hcp) and TPD on BDE thicknessM
ater
ials
with
Mat
eria
ls w
ith (C(C
22HHxxFF
yy)) nn stru
ctur
est
ruct
ure
Dependence of PD(), PD(hcp) and TPD on BDE thicknessM
ater
ials
Mat
eria
ls w
ithou
t hyd
roge
nwi
thou
t hyd
roge
n
BDE Material**TPDmax
(cm)BDE(TPDmax)
(cm)
Tumor dose rate from HCP at TPDmax
(Gy/hr/mA)No BDE 3.10* - 2.109
(C2H4)n 4.06 1.19 1.428
(C2H3F)n 4.09 1.86 1.152
(C2H2F2)n 4.16 2.77 0.927
(C2HF3)n 4.44 4.52 0.583
Beryllium metal 4.66 4.64 0.449
(C2D4)n 4.70 5.67 0.443
Graphite 4.81 7.27 0.275
(C2F4)n 4.82 13.54 0.097
D2O 4.89 8.06 0.3157LiF 4.99 14.76 0.069
TPDmax, BDE(TPDmax) and Tumor dose rate at TPDmax for the candidate BDE materials evaluated in this study
The following parameters together with other practical considerations may be used for choosing suitable BDE materials for BNCT:
TPDTPDmaxmax deeper is better for deep-seated tumors
BDE(TPDBDE(TPDmaxmax)) thinner is better from the view point of dose rate reduction and material handling
TPD versus BDE thickness curveTPD versus BDE thickness curve smaller dependence of TPD on BDE thickness is better to avoid large variations in TPD for small changes in BDE thickness
Summary
TPD-based evaluation of near threshold proton energies for the 7Li(p,n)7Be production of neutrons for BNCT
To evaluate the characteristics of neutron fields from the 7Li(p,n)7Be reaction at near-threshold incident proton
energies with the treatable protocol depth (TPD) as the primary index of evaluation
Objective
Incident Proton Energy: Incident Proton Energy: 1.900 MeV1.900 MeV
BackgroundIncident Proton Energy: Incident Proton Energy: 1.885 MeV1.885 MeV
Incident Proton Energy: Incident Proton Energy: 1.900 MeV1.900 MeV
BackgroundIncident Proton Energy: Incident Proton Energy: 1.885 MeV1.885 MeV
Incident Proton Energy: Incident Proton Energy: 1.900 MeV1.900 MeV
BackgroundIncident Proton Energy: Incident Proton Energy: 1.885 MeV1.885 MeV
Higher proton energy
Higher dose rate for all BNCT dose
components
More effective for treatment
Calculation MethodIncident proton energy 7Li-target thickness Polyethylene BDE thickness
1.885-1.920 MeV(mono-energetic)
Variable; depends on proton energy From 0 to 3cm
Simulation parameters
ProtonEnergy(MeV)
NeutronYield(x1010
n/mC)
Ave.NeutronEnergy(MeV)
Max.NeutronEnergy(MeV)
Ave.Emission
Angle(deg)
Max.Emission
Angle(deg)
1.885 0.26 32 54 12 201.890 0.63 34 67 17 301.895 1.05 36 78 20 381.900 1.49 38 87 23 451.905 1.95 40 96 26 521.910 2.41 42 105 28 601.915 2.88 44 113 30 701.920 3.35 47 121 32 180
PD(hcp) and PD() curves generated by near-threshold proton energies
TPD curves generated by near-threshold proton energies
Proton Energy (MeV)
TPDmax (cm)
BDE(TPDmax) (cm)
1.885 4.75 0
1.890 4.43 0
1.895 4.06 0.96
1.900 3.88 1.12
1.905 3.75 1.23
1.910 3.65 1.33
1.915 3.54 1.43
1.920 3.45 1.50
TPD curves generated by near-threshold proton energies
Proton Energy (MeV)
TPDmax (cm)
BDE(TPDmax) (cm)
1.885 4.75 0
1.890 4.43 0
1.895 4.06 0.96
1.900 3.88 1.12
1.905 3.75 1.23
1.910 3.65 1.33
1.915 3.54 1.43
1.920 3.45 1.50
Higher proton energy
Higher ave.neutron energy
Lower relative difference between dose to tumor and
to healthy tissue
The Colored The Colored arrows indicate arrows indicate the TPDthe TPDmaxmax
ProtonEnergy(MeV)
TPDmax(cm)
BDE(TPDmax)(cm)
HCP DoseRatetoTumor
atTPDmax(Gy/h/mA)
RequiredProtonCurrent for15Gy/hDoseatTPDmax(mA)
1.885 4.75 0 0.30 49.421.890 4.43 0 0.77 19.361.895 4.06 0.96 1.07 14.001.900 3.88 1.12 1.46 10.291.905 3.75 1.23 1.83 8.211.910 3.65 1.33 2.17 6.901.915 3.54 1.43 2.50 6.011.920 3.45 1.50 2.83 5.30
TPDmax, BDE(TPDmax), HCP dose rate at TPDmax and the required proton current to deliver 15 Gy per hour at TPDmax
Central axis distribution of HCP dose rate to tumor
Gray-shaded region indicates the depths beyond the treatable
region
Colored region indicates the depths within the treatable
region
Central axis distribution of HCP dose rate to tumor
Proton Energy (MeV)
HCP dose rate to tumor
at 3cm(Gy/h/mA)
Required proton current
for 15Gy/h(mA)
1.885 0.39 38.01
1.890 0.95 15.73
1.895 1.34 11.22
1.900 1.77 8.50
1.905 2.16 6.94
1.910 2.51 5.97
1.915 2.83 5.31
1.920 3.15 4.77
The choice of the suitable proton energy will depend on the desired HCP dose rate
to tumor.
As an example, consider a tumor located at 3cm.
Proton energies closer to
7Li(p,n)7Be threshold
Deeper TPDmax Good for treating deep-seated tumors
Very low dose rate at
TPDmax
Will be clinically viable when accelerators with high proton currents
become available
Higher near threshold
proton energies
(≳1.9MeV)
Greater dose rate to tumor at
relatively shallow TPDmax
Faster treatment time and/or lower required proton
current
Summary
Variation in 7Li-target thickness for near threshold 7Li(p,n)7Be neutron production
for BNCT
Objective
To investigate the range of allowable 7Li-target thickness in the production of neutrons for BNCT via the near-threshold
7Li(p,n)7Be reaction
Background
7Li-target thickness for near-threshold neutron production at 1.900MeV tmin = 2.33 m; minimizes gamma production in 7Li-target
Thicker 7Li-targets may be needed to extend target life-time if solid targets are used.
Thicker targets = larger gamma ray component in neutron field
Gamma ray yield for the proton-induced reactions in the 7Li-target and aluminum backing material.
tmin=2.33m
Calculation Method
Incident proton energy7Li-target thickness
Polyethylene BDE thickness*
1.900 MeV(mono-energetic)
From tmin to 10tmin From 0 to 1.25cm
*Range of BDE thickness was chosen in order to attain the TPDmax for each condition
Simulation parameters
Dependence of TPD on the 7Li-target thickness and BDE thickness
tmin=2.33m
Dependence of TPD on the 7Li-target thickness and BDE thickness
tupper is the limit of the 7Li-thickness
that will result in the deepest attainable TPD for each BDE
thickness
tmin=2.33m
Dependence of TPD on the 7Li-target thickness and BDE thickness
Range of usable 7Li-target thicknessfor the BDE thickness used
tmin=2.33m
BDE thickness
(cm)
7Li-target thickness
range (m)
TPD (cm)
0 2.33-16.43 2.93
0.50 2.33-11.61 3.37
1.00 2.33-3.53 3.85
1.10 2.33 3.88
1.25 2.33 3.72
Dependence of TPD on the 7Li-target thickness and BDE thickness
BDE thickness
(cm)
7Li-target thickness
range (m)
TPD (cm)
0 2.33-16.43 2.93
0.50 2.33-11.61 3.37
1.00 2.33-3.53 3.85
1.10 2.33 3.88
1.25 2.33 3.72
Dependence of TPD on the 7Li-target thickness and BDE thickness
BDE thickness
(cm)
7Li-target thickness
range (m)
TPD (cm)
0 2.33-16.43 2.93
0.50 2.33-11.61 3.37
1.00 2.33-3.53 3.85
1.10 2.33 3.88
1.25 2.33 3.72
Dependence of TPD on the 7Li-target thickness and BDE thickness
BDE thickness
(cm)
7Li-target thickness
range (m)
TPD (cm)
0 2.33-16.43 2.93
0.50 2.33-11.61 3.37
1.00 2.33-3.53 3.85
1.10 2.33 3.88
1.25 2.33 3.72
Dependence of TPD on the 7Li-target thickness and BDE thickness
BDE thickness
(cm)
7Li-target thickness
range (m)
TPD (cm)
0 2.33-16.43 2.93
0.50 2.33-11.61 3.37
1.00 2.33-3.53 3.85
1.10 2.33 3.88
1.25 2.33 3.72
Dependence of TPD on the 7Li-target thickness and BDE thickness
Summary
• While thinner 7Li-targets are desirable because they produce less gamma rays, thicker targets may be used for as long as they do not reduce the attainable TPD.
Gaussian proton beams for neutron production with the near threshold
7Li(p,n)7Be reaction for BNCT
Objective
To evaluate the influence of incident proton energy fluctuations on the TPD in the near threshold 7Li(p,n)7Be
accelerator–based BNCT
Background
Cross-section for the 7Li(p,n)7Be reaction adapted from Liskien (1975)
• Ideal condition: mono-energetic incident proton energy
• Real condition: fluctuating incident proton energy
• Influence on stability of neutron production at near threshold energies
Calculation Method
Incident proton energy 7Li-target thickness Polyethylene BDE thickness*
Mono-energetic and Gaussian beams with
1.900MeV mean energy
tmin= 2.33m (fixed)From 0 to 4cm
*Range of BDE thickness was chosen in order to attain the TPDmax for each condition
Simulation parameters
Effect of Gaussian proton beams on the BNCT dose components
• Dose rates of all dose components increase with incident proton energy spread.
• Relative change in dose rate is greater for hcp than for gamma rays.
TPD curves for mono-energetic and Gaussian proton beams
TPD curves for mono-energetic and Gaussian proton beams
Fluctuations in the incident
proton energy will result in a significant
reduction in TPD for irradiations without BDE
TPD curves for mono-energetic and Gaussian proton beams
Fluctuations in the incident
proton energy will result in a significant
reduction in TPD for irradiations without BDE
Using suitable BDE material and thickness
will improve the attainable TPD even for highly fluctuating
incident proton beams
Summary
• An acceptable limit of the energy fluctuation for Gaussian incident proton beam would be about ±10keV.
• Introducing a suitable BDE material and thickness in the irradiation field can narrow down the difference in attainable TPDmax for an ideal mono-energetic beam and a Gaussian proton beam.
Summary
As we come closer to the realization of BNCT irradiation using ABNS, it is apparent that both near-threshold and moderated neutron usage of the 7Li(p,n)7Be reaction will be implemented depending on specific treatment requirements.
Regardless of the approach used in the neutron production and the design of the irradiation system, the new protocol-based evaluation indices and the method for evaluating neutron fields we defined in our study will be effective tools in providing a simple and more comprehensive way of evaluating the worthiness of neutron fields from ABNS for BNCT.
Thank you for your attention