elemental distribution in biological samples using x

Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
X-ray Fluorescence and X-ray Transmission
Microtomography Imaging System
G. R. Pereira(1)*, H.S. Rocha(1), M. J. Anjos (2), P. Faria(3),
C. A. Pérez (4) and R. T. Lopes (1).
(1) Nuclear Instrumentation Laboratory – COPPE / UFRJ, Brazil
P.O. Box 68509, 21945-970, Fax: +55 (021) 25628444, [email protected]
(2) Physics Institute - UERJ, Brazil
(3) Brazilian National Cancer Institute – LNLS, Brazil
(4) Brazilian Synchrotron Light Source, Brazil
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
OBJECTIVE
The main of this work is to determine the
elemental and absorption distribution map in
tissue samples.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
INTRODUCTION
•New techniques have been developed using excellent
properties of synchrotron radiation such as high photon
flux, the broad energy spectrum and the natural
collimation.
•In many studies, it is necessary to analyze biological
tissues with small details that have close attenuation
coefficients where transmission tomography is not
adjusted.
•Some properties also depend on the
distribution of elements inside of the sample.
individual
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
INTRODUCTION
• In order to get the distribution of an element in particular,
fluorescence properties and the tomographic techniques
can simultaneously be used.
• A technique for fluorescence tomography was attempted
for the first time in 1989 by Cesareo and Mascarenhas.
• Since then, several papers have been presented in this area.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
INTRODUCTION
• One complication of fluorescence tomography is the
reconstruction calculations that are more complex than
transmission tomography’s algorithm. Hogan et al (1990)
proposed adapting one of the algorithms used in X-ray
transmission tomography.
• The simplest algorithm is based on the classical back
projection algorithm used in transmission tomography. A
algorithm more accurate applies corrections for absorption
before and after the fluorescence point.
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Federal University of Rio de Janeiro -BRAZIL
INTRODUCTION
• The choice for breast tissue samples was accomplished with the
world tendency to find diagnostic techniques for cancer and other
diseases.
• The fluorescence mapping of iron, copper and zinc is very
important in diagnostics.
• The biochemistry of these elements suggests that these metals may
play an important role in carcinogenesis. However, the evidence
linking iron, copper and zinc to cancer is far from conclusive. Using
X-ray fluorescence tomography it can be obtained the elemental
map of this metals without sample preparation.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
THEORY
For a particular element i and an atomic level ,
the fluorescence radiation hitting the energy
dispersive detector can be obtained through
integration over y’
Transmission
Detector
D
y’
y

I i ( , x' )  I 0  dy ' f ( , x' , y ' ) p( x' , y ' ) g ( , x' , y ' )
x’

Rotation

y'
Det
( l )' dl
 B (x ',y')Fdy

e
fg (p((,x,xx'',,',yy')y' )')dy' 
e dN
elem dy '. ; ;
x
1
4
( x ', y ')
D
x’ = x cos  + y sin 
y ’ = - x sin  + y cos 
Translation
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
THEORY
If the solid angle defined by the detector surface is almost constant
and the attenuation is small (μB ≈ μF ≈ 0) then
f ( , x' , y' )  1, g ( , x' , y' )  g  cte


-
-
I(,x')  g  p(x',y')dy'   N elem(x',y')dy'
In this case, the concentration of the element is proportional to the
experimental projections and the usual algorithms of transmission
tomography can be used for fluorescence tomography.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
EXPERIMENT
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RECONSTRUCTION
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
EXPERIMENT
•
•
•
•
Operation Nominal Energy: 1.37GeV
Injection Energy: 500MeV
Electron Beam Current (maximum):
250 mA
Beam Life Time: 15 h
XRF
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
EXPERIMENT
White beam
(4-23) keV
Fluorescence
Ionization
Detector
Fluorescence
Chamber
Detector
Sample
Multilayer
Monochromator
Transmission
Detector
Two Sets of Slits
(200μm x 200μm) and
Transmission Detector
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Federal University of Rio de Janeiro -BRAZIL
RESULTS
Tomography images of paper filter (right: x-ray fluorescence and left:
Transmission)
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RESULTS
Tomographic images of polyethylene samples filled with a standard solutions of Cu
(200 ppm) (right: x-ray fluorescence and left: Transmission).
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Federal University of Rio de Janeiro -BRAZIL
RESULTS
(a)
(b)
(c)
Tomography images of lung sample (top: transmission and bottom: fluorescence) (a)Fe (b)
Cu, (c)Zn.
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Federal University of Rio de Janeiro -BRAZIL
RESULTS
X-Ray Fluorescence Tomography images of lung sample.
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Federal University of Rio de Janeiro -BRAZIL
RESULTS
(a)
(b)
(c)
Tomography images of coronary vein sample (top: transmission and bottom:
fluorescence) (a)Fe (b) Cu (c) Zn.
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Federal University of Rio de Janeiro -BRAZIL
RESULTS
(a)
(b)
(c)
Tomography images of heart sample (top: transmission and bottom: fluorescence) (a)Fe,
(b) Cu, (c) Zn.
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RESULTS
Cyst
Normal lobular
Adipose
breast
tissue
parenchyma
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Federal University of Rio de Janeiro -BRAZIL
RESULTS
Micro cyst
Sample of breast cancer
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RESULTS
Sample of breast
cancer after
chemotherapy
reduction.
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Federal University of Rio de Janeiro -BRAZIL
RESULTS
(a)
(b)
(c)
Tomography images of healthy breast tissue sample (top: transmission and bottom:
fluorescence) (a)Fe, (b) Cu, (c) Zn.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
RESULTS
(a)
(b)
(c)
Tomography images of malignant breast tumor sample (top: transmission and bottom:
fluorescence) (a)Fe (b) Cu, (c) Zn.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
RESULTS
(a)
(b)
(c)
Tomography images of benign breast tumor sample (top: transmission and bottom:
fluorescence) (a)Fe (b) Cu, (c) Zn.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
RESULTS
Iron
NORMALIZED Fe FLUORESCENCE
0.007
benign tumor
malignant tumor
normal tissue
0.006
0.005
0.004
0.003
0.002
0.001
0.000
1020
1035
1050
O
1065
O
1080
Sum Ray of the 30 and 31 projection
Normalized Fe fluorescence counting in 30º and 31º projection
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
RESULTS
Copper
benign tumor
tmalignant tumor
normal tissue
NORMALIZED Cu FLUORESCENCE
0.0005
0.0004
0.0003
0.0002
0.0001
0.0000
1020
1035
1050
1065
O
1080
o
Sum ray of the 30 and 31 projection
Normalized Cu fluorescence counting in 30º and 31º projection
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
RESULTS
Zinc
NORMALIZED Zn FLUORESCENCE
0.0014
benign tumor
malignant tumor
normal tissue
0.0012
0.0010
0.0008
0.0006
0.0004
0.0002
0.0000
-0.0002
1020
1035
1050
O
1065
1080
O
Sum ray of the 30 and 31 projection
Normalized Zn fluorescence counting in 30º and 31º projection
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
CONCLUSION
We have shown that was possible to visualize the
distribution of high atomic number elements on both,
artificial and tissues samples. It was possible to compare
the quantity of Zn, Cu and Fe for the breast tissue
sample and was verified that these elements have a
higher concentration on malignant tumor than normal
tissue.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
CONCLUSION
It will be necessary to measure more samples and
quantify the difference in concentration in one sample
and between normal and abnormal tissues to use the Xray fluorescence microtomography as an analytic tool to
analyze biological tissues.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
CONCLUSION
The better definition of the interfaces in X-ray
fluorescence images was striking and the spatial
resolution of the system can be optimized as a function of
the application. The experimental set up at XRF-LNLS
has shown to be very promising and this effort at
implementing X-ray fluorescence microtomography was
justified by the high quality of the images obtained.
Nuclear Instrumentation Laboratory
Federal University of Rio de Janeiro -BRAZIL
ACKNOWLEDGEMENTS
This work was partially supported by the National
Center for Science and Technology Development
(CNPq), Rio de Janeiro State Research Foundation
(FAPERJ) and Brazilian Synchrotron Light
Laboratory (LNLS).