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


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



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)



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

)



and healthy tissue

Gaussian spectrum, = 0.030MeVProton energy, Ep, ave= 1.900MeV 1cm Polyethylene BDE

BDE*

( Unit : mm )


Central axisProton

38

( Unit : mm )


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


and healthy tissue

Dos

e R

ate

(Gy/

h/m

A)


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


Particle transport

Dose calculation



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


Particle transport

Dose calculation



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


Particle transport

Dose calculation



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


Particle transport

Dose calculation

Evaluation of dose Evaluation of dose distributiondistribution


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


Particle transport

Dose calculation



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





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


Dependence of TPD on the 7Li-target thickness and BDE thickness

tmin=2.33m


tupper is the limit of the 7Li-thickness

that will result in the deepest attainable TPD for each BDE

thickness

tmin=2.33m


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


BDE thickness

(cm)


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


BDE thickness

(cm)


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


BDE thickness

(cm)


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


BDE thickness

(cm)


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


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


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


Fluctuations in the incident

proton energy will result in a significant

reduction in TPD for irradiations without BDE


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

Documents

Evaluation of the near threshold 7 Li( p , n ) 7 Be accelerator-based irradiation system for BNCT