Prompt GammaRay Imaging for Small Animals

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Prompt Gamma-Ray Imagingfor Small Animals

• Libai Xu
• Center of Engineering Applications of
  Radioisotopes
• Department of Nuclear Engineering
• North Carolina State University
• Sep. 6th. 2006

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OUTLINE

• Introduction
• System Design
• Neutron Tomography
• Prompt Gamma-ray Imaging
• Some critical questions
• Absorbed Dose to Small Animals
• High Energy Prompt Gamma-Ray Detection
• Conclusions
• Future work

3
Introduction

• Overview
• Literature Reviews
• Review of small animal imaging
• Review of in vivo neutron applications
• Review of prompt gamma imaging

4
Overview
Introduction

• Prompt Gamma Activation Analysis
• Identify elements and their abundance
• Prompt Gamma-ray Imaging
• Identify elements, abundances, and positions

5
Potential Applications
Introduction

• NCT (Neutron Capture Therapy) for Cancer
  treatment
• Selectively deliver 10B or Gd to the tumor
• Irradiate the tumor region with low energy
  neutrons
• The short range of the 10B(n,a)7Li reaction
  products restricts most of the dose to the tumor
  cells

?
Coderre, J. A. and Morris, G. M. 1999. The
radiation biology of boron neutron capture
therapy Radiat. Res. 151 1-18
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System Diagram
Introduction
7
Review of small animal imaging
Introduction

• Why small animal imaging is important?
• an non-invasive tool to build animal models of
  human diseases.
• Save animals, reduce cost
• Get more complete data, especially for
  longitudinal studies
• Currently available imaging systems for small
  animals
• Anatomical Imaging
• Micro-CT, MRI, Ultrasound
• Detailed info about tissue structure and
  composition
• Functional Imaging
• Micro-PET, Micro-SPECT
• Spatial distribution or evolution of radio
  nuclides in the body

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Review of in vivo neutron applications
Introduction

• PGNAA (Prompt Gamma Neutron Activation Analysis)
• Human body elemental analysis
• NCT (Neutron Capture Therapy) for Cancer
  treatment
• Boron
• Gd

Coderre, J. A. and Morris, G. M. 1999. The
radiation biology of boron neutron capture
therapy Radiat. Res. 151 1-18
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Review of prompt gamma-ray imaging
Introduction

• ?-ray telescope in BNCT
• Measure Boron distribution

Verbakel, W. F. A. R. et al (1997). A r-ray
telescope for on-line measurements of low boron
concentrations in a head phantom for BNCT.
Nuclear Instruments and Methods in Physics
Research A 394, 163-172
Barker, H. B. and Maier, M. R. (2005). The
STING imaging system based on using neutrons and
gammas. Nuclear Instruments and Methods in
Physics Research A 542, 288-289
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• Introduction
• System Design
• Neutron Tomography
• Comparison between X-rays and Neutrons
• Tomography Simulation
• Prompt Gamma-ray Imaging
• System Modeling
• Imaging
• Some critical questions
• Conclusions
• Future work

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Comparison between X-rays and Neutrons
Neutron Tomography

• Neutrons interact with the nuclei of the atoms
• X-rays interact with the electrons in the shells

Fig. 2-2 Comparison Between X-ray and Neutron
Attenuation
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Comparison between X-rays and Neutrons
Neutron Tomography
Table 2-1 Attenuation Coefficients of Some
Materials for X-rays and Neutrons
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Fundamentals of Tomography
Neutron Tomography
System Setup
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MCNP Simulation
Neutron Tomography
MCNP is used to generate projections
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Neutron Tomography
A
B
A
B
B
A
A
B
A
B
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Phantom
Neutron Tomography
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Neutron Tomography
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Neutron Tomography
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Neutron Tomography
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Neutron Tomography
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Summary for Neutron Tomography
Neutron Tomography

• The attenuation coefficient of X-rays is mainly
  determined by object density, but for thermal
  neutrons, it is more related to the hydrogen
  concentration of objects. Totally different
  information is achieved by X-ray imaging and
  neutron imaging.
• Scattering background is severe in neutron
  tomography. The possible solution is using a
  collimation grid made by a nanotube (Kumakhov,
  2000) to filter the scattered component.

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System Modeling
Prompt Gamma-ray Imaging

• Current Available Codes
• MCNP5
• CEARCPG
• GEANT4
• Requirements for PGI
• Be capable to simulate coincident gamma rays
• Be capable to simulate repeated structures
• 3-D Visualization

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Neutron Capture Reaction
Prompt Gamma Imaging
12C
13C
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Prompt Gamma Imaging
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Hg prompt gamma-ray spectrum
SPECT-like Trial
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Neutron Capture Reaction by Geant4
Prompt Gamma Imaging

• Prompt gamma rays are produced in coincidence.
• 2) Prompt gamma-ray intensity information is
  agreed with ENSDF

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Prompt Gamma-Ray Yields
Prompt Gamma Imaging
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Prompt Gamma-Ray Yields
Prompt Gamma Imaging
Capture reactions for each component in soft
tissue (per 1.E6 thermal neutrons)
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Benchmark Experiments
Prompt Gamma Imaging

• Pure Hg

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• Pure Gd

187kev
785kev
956kev
1190kev
6750kev
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Prompt Gamma-Ray Imaging
Imaging Methods

• Mechanical collimations

sample
Detector plane
Pinhole
Coincident detector
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SPECT-like Trial
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SPECT-like Trial
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Projection Images
SPECT-like Trial
370kev prompt gamma rays
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Prompt Gamma-Ray Imaging
Imaging Methods

• Electronic collimations

Positron Emission Tomography
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Angular Correlations
PET-like Trial
Reference Robley D. Evans The Atomic Nucleus
isotropy (a20, a40) co (a21/8,
a41/24) -34 (a2-3, a44).
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Expectation Maximization
PET-like Trial
The formula for EM algorithm can be derived
(1) Start with o initial estimate ,
satisfying
(2) Iterative function
(3) If the required accuracy for the numerical
convergence has been achieved, then stop.
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Phantom
PET-like Trial
Radius15cm Width of detector1cm Size of grids
3232 Detector number 32 x (i) i 1, 1024 y (j)
j1,496 a (i, j) Activity ratio of
ABC12.54.5
Where x (i) represents the activity density in
every grid. y (j) represents the observed data in
every detector pair. a (i, j) represents the
probability that one coincident event emitted
from grid x (i) is detected by detector pair
y(j). So known conditions y (j) and a (i, j).
Unknown x (i). Initial starting guess uniform
distribution.
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Reconstructed Images
PET-like Trial
Phantom
PET
-34
co and isotropy
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Summary for PGI

• Geant4 is capable of simulating coincidence gamma
  rays
• Angular correlations among prompt gamma rays are
  capable of imaging, but only for very strong
  angular correlations such as -34.
• If not considering the coincidence among prompt
  gamma rays and using the same imaging techniques
  as SPECT, we still could get images

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• Introduction
• System Design
• Neutron Tomography
• Prompt Gamma-ray Imaging
• Some critical questions
• Absorbed Dose to Small Animals
• High Energy Prompt Gamma-Ray Detection
• Conclusions
• Future Work

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Absorbed Dose for Mice

• Method 1

H
C
N
O
MCNP5 and F6 tally

• A Bozkurt, T C Chao and X G Xu, 2000,
  Fluence-to-dose conversion coefficients from
  monoenergetic neutrons below 20Mev based on the
  VIP-Man anatomical model, Phys. Med. Biol. 45
  3059-3079.

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Method 2
Absorbed dose for mice
All (n, ?) reactions and 14N(n,p)14C
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Method 2
Absorbed dose for mice
Step 1 Calculate how many capture reactions
occur for each element. neutron flux,
thermal neutron capture cross section, atom
density are all known
Step 2 Calculate how much energy is
deposited per capture for each element
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Absorbed dose for mice
Method 2
By (n, ?) capture of H, C, O, and N
By 14N(n,p)14C
The absorbed dose caused by (n, ?) Capture of Hg
is
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Summary of Results
Absorbed dose for mice
Flux 106 / cm2 s. 30-min scan time
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Comparison with MicroCT
Absorbed dose for mice

• According to Chow et al. (2001) the average CT
  dose for a mouse is 10 cGy in a 3-D
  high-resolution X-ray CT system, MicroCAT
  (40kVp/0.500mmAl/250ms/400uA). This dose is
  approximately 1 of LD50/30 for a mouse (9 Gy),
  which is a measure of lethal dose to 50 of the
  population after 30 days.

Reference Chow, P.L., A.L. Goertzen, F. Berger,
J.J. DeMarco, A.F. Chatziioannou, 2001, Monte
Carlo model for estimation of dose delivered to
small animals during 3D high resolution X-ray
computed tomography, Nuclear Science Symposium
Conference Record, 2001 IEEE, Nov. 2001, Vol. 3,
1678-1681.
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Comparison with MicroPET
Absorbed dose for mice
100 uCi 18F is injected into the mouse body
How much disintegration happens
Absorbed dose caused by one disintegration
Positron 249.8kev/decay Gamma 1022kev/decay
Total Absorbed Dose
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Comparison with PET/CT
Absorbed dose for mice

• Absorbed dose in PET/CT
• CT 40kVp/0.500mmAl/250ms/400uA
• PET 100 uCi 18F
• 100 mGy52 mGy152 mGy
• Absorbed dose in PGI
• Flux 106 / cm2 s. 30-min scan time
• 0.8 mGy by body composition
• 0.55 mGy by 1 Hg

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Summary for Absorbed Dose
Absorbed dose for mice

• The absorbed dose to a 30-gram mouse by PGI
  (Neutron flux 108 /cm2 s, 30-min scan time) is
  equivalent to that when the mouse is scanned by a
  combined PET/CT system (CT40kVp/0.500mmAl/250ms/4
  00uA, PET 100 uCi 18F).

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High Energy Prompt Gamma-Ray Detection

• The common prompt gamma-ray energy range is from
  several kev to 11Mev.
• Pair production will be dominant for high energy
  gamma ray.
• Typical size of MicroPET scanners is 2mm2mm10mm
• 1Mev electron has 1mm range in LSO crystal
• Angular distribution of pair production is
  isotropic or forward?

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MCNP5
High energy ? detection
Robley D. Evans, The Atomic Nucleus, McGRAW-Hill
Book Company, London, 1955.
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Results
High energy ? detection
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Comparison between Isotropic and Actual Forward
Angular Distributions
High energy ? detection
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Detection efficiency for 2mm2mm10mm
High energy ? detection
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Detection Efficiencies for Various LSO Detector
Sizes
High energy ? detection
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Summary for High Energy r Detection

• Detection with small LSO crystals for imaging
  applications is adequate for low- and high-energy
  gamma rays where either the photoelectric or pair
  production interactions dominate, but not as well
  for the intermediate range of gamma rays where
  the Compton scatter interaction dominates.

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• Introduction
• System Design
• Neutron Tomography
• Prompt Gamma-ray Imaging
• Some critical questions
• Absorbed Dose to Small Animals
• High Energy Prompt Gamma-Ray Detection
• Conclusions
• Future Work

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Conclusions

• 1. From the aspect of imaging, the angular
  correlations among prompt gamma rays are capable
  of imaging, but only for very strong angular
  correlations such as -34. If not considering
  the coincidence among prompt gamma rays and using
  the same imaging techniques as SPECT, we could
  get images. However, the new problem is that
  gamma-ray energy here is much higher than that in
  SPECT. New features of collimators are required
  to solve this problem.

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Conclusions

• 2. From the aspect of radiation dose to small
  animals, the equivalent dose for a mouse when
  imaged with a thermal neutron beam with a flux of
  10 8/ cm 2 s in 30 minutes will be equivalent to
  that when imaged with a combined PET/CT system
  (For CT, 40kVp/0.500mmAl/250ms/400uA and For PET,
  100uCi 18F).

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Conclusions

• 3. From the aspect of gamma-ray yields, the
  gamma-ray yields are low for most elements in the
  normal concentrations. It indicates that PGI is
  not a general application for all elements. Only
  some elements with very high cross section are
  suitable, such as Hg, Cd, Gd, et al. Or in
  certain cases, the concentrations of elements are
  very high and their cross sections are not very
  small, such as H in organic body, and B in BNCT.

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Future Work

• Variance reduction techniques for Geant4
• Nuclear data libraries, especially for nuclear
  structure data
• Nanotube may be utilized as collimation grids and
  to reduce scattered neutron background
• More accurate voxel-based mouse phantom

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Thank You