7/14/2015
Ke Li, PhD
1.
Department of Medical Physics, University of Wisconsin, Madison, WI
Department of Radiology, University of Wisconsin, Madison, WI
2.

Basic Science Team









Dr. Joe Zambelli
Dr. Nick Bevins
Dr. Zhihua Qi
Dr. Pascal TheriaultLauzier
Clinical Team
 UW Radiology
Dr. Guang-Hong Chen
Dr. Ran Zhang
John Garrett
Yongshuai Ge
▪ Dr. Wendy DeMartini
▪ Dr. Amy Fowler
 UW Pathology
▪ Dr. Andreas Friedl
 UW Surgery
▪ Dr. Lee Wilke

Industrial Partner
 Dr. Zhenxu Jing (Hologic Inc.)
 Dr. Baorui Ren (Hologic Inc.)
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“If X-rays be indeed ultra-violet light, then that light must posses
the following properties…It is not refracted in passing from air
into water, carbon bisulphide, aluminum, rock-salt, glass or zinc.”
-W.C. Roentgen, translated from “On a New Kind of Rays,” 1896
However, based on quantum mechanics developed after
Roentgen discovered x-rays, we now understand that just like
any other form of electromagnetic radiation, x-rays can also be
described as a wave and should be able to refract.
Our question is to ask how to use the wave nature of x-rays to
generate images for future medical applications?
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1
7/14/2015
n


2

(1  n) L 
2

  (l )dl   r   (l )dl
e
e
n  1    i
 r 2
 ee
2
10
10
 and 
10
10
10
10
10
10
Real Part
(refraction)
Imaginary Part
(absorption)


( p   c )
4
4
Index of refraction components vs. Energy
-6
-7
-8
-9
-10
-11
-12


-13
15
20
25
30
40
50
60
70
80
100
150
Energy (keV)
The real and imaginary parts, δ (Sanchez-del-Rio and Dejus 2003) and β (Chantler, et al 2003), of the
complex refractive index of breast tissue.
600 nm Visible Light
nglass  nair  0.5
Refraction angle: as large as
50 degrees
5
30 keV X-Ray
n  1 
 glass   air  0.0000007
Refraction angle: about one
millionth of a degree

200 miles
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G2
G1
G0
Spatially coherent
x-ray beam
Standard x-ray
source
coh


p0
d k
d 01
p12
8
A. Momose, “Phase-sensitive imaging and phase tomography using X-ray interferometers”, Optical Express, 11 (2303) (2003)
T. Weitkamp, et al, “X-ray phase imaging with a grating interferometer,” Opt. Exp. 12(16), pp. 6296–304, 2005.
F. Pfeiffer, et al, “Phase retrieval and differential phase-contrast imaging with low-brilliance x-ray sources,” Nature Physics 2, pp.
258–261, Apr 2006.
7
G2
I
Si
Au
xg
Detector Signal (arb. units)
Pixel
∫
xg
xg


I  I 0  I1 cos  2
 d 
p2


Phase Step Modulation
800
750
700
650
0
5
10
15
20
Grating Position (m)
25
30
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3
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d
I
G2
Si
∫
Au
xg
Pixel
d  dobject  dbackground
d 
2 d
  0.3  106  
p2
Talbot-Lau interferometer amplifies the
refraction angles by one million times
to make them measurable!
xg
10

pm
p2
p1
11
1
arg(
1

)
(b) Phase
(c) Small-angle Scatter
1
(a) 2D Fourier Transform
(d) Attenuation
Bevins, Zambelli, Li, Qi, Chen, Medical Physics (2012)
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k=1
k=2
k=4
2
Intensity
k=3
4
1
3
k
Y. Ge, K. Li, J. Garrett, G.-H. Chen, Optics Express (2014)
Row 1
Row 2
one detector pixel
Row 3
Row 4
4.8 µm, one period of
the diffraction pattern
Row 5
Scanning electron microscope (SEM) image

One term of the equation describing the measured
intensity has not been used.
xg


I  I 0  I1 cos  2  d 
p2



This term reflects the amplitude of the intensity
change as phase measurement is performed.

Two factors: grating & beam quality (extrinsic),
and sample characteristic (intrinsic)

What kind of intrinsic characteristic of the image
object does this term offer?
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The dark field image can be extracted
using the normalized oscillation amplitude


I1
,
I0
VSAS 
 obj I 0bkgd I1obj
 obj bkgd
 bkgd
I 0 I1
Pfeiffer et al, Nature Materials (2008)
ln VSAS   
 
r2
dz SAS2 SAS
4 
R ( z)
Chen, Bevins, Zambelli, Qi, Opt. Express (2010)
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
Noise variance of phase contrast signal is
inversely proportional to the square of
visibility
2 

1
2
Maximizing fringe visibility is the key in
improving the imaging performance of phase
contrast imaging
Chen et al., Med Phys (2011)
Li et al., Med Phys (2013)
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Air
H2O
PMMA
POM
PTFE
Phase
Absorption
Effective Z
Qi, Zambelli, Bevins, and Chen, PMB, Vol. 55:2669-2677 (2010)
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Air
H2O
Wood
PMMA
POM
PTFE
The same phantom as previously described is used again, however this time with
the addition of a 2.3 mm diameter wooden dowel in the air-filled insert to provide a
small-angle scattering structure.
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Absorption
Phase Contrast
Bevins, Zambelli, Qi, and Chen, Proc SPIE (2010)
Dark Field
21
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x
y
Polyoxymethylene (POM)
Polycarbonate (PC)
PMMA
X-ray
Li, Ge, Garrett, Bevins, Zambelli, Chen, Medical Physics (2014)
Phase
Absorption
Differential
Phase
Li, Ge, Garrett, Bevins, Zambelli, Chen, Medical Physics (2014)
In a realistic clinical multi-contrast x-ray imaging
system, the absorption contrast mechanism
should not be relegated to a secondary position;
its performance should be maintained as much as
possible, allowing the complementary information
provided by phase contrast and dark field contrast
“free of charge”.
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Normalized Edge Spread Function
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1
Parallel; no gratings
Parallel; gratings
Perp.; no gratings
Perp.; gratings
0.8
0.6
0.4
0.2
0
1100
1150
1200 1250 1300
Pixel number
1350
Without G2
SPR
0.4
0.3
0.2
With G2
0.1

Improved grating fabrication methods
 Reznikova et al., Soft X-ray lithography of high aspect ratio
SU8 submicron structures. Microsystem Technologies (2008)
 Bevins, grating fabrication using liquid metal filling technique,
UW-Madison (2012)

Improved interferometer setup
 Stutman and Finkenthal, Glancing angle Talbot-Lau grating
interferometers for phase contrast imaging at high x-ray
energy, APL (2012)

Combination with single
photon counting detector
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Measured Fringe
Visibility (%)
15 cm x 15 cm total imaging area, 100 um
pixel size (XCounter AB, Sweden)
40
30
20
10
0
Previous Grating
New Grating
New Grating + PCD

Brain imaging

Lung imaging

Musculoskeletal imaging
 Brain tumor, Alzheimer’s disease
 Emphysema and fibrosis
 Osteoarthritis and rheumatoid arthritis

Abdominal imaging

Breast imaging
 Kidney stone
Absorption
Differential phase
Dark field
Imaged thickness: 5.5 cm
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Thickness: ~6.0 cm
Total volume: ~28 L
Total weight: ~25 kg
Thickness: ~20 cm
Absorption
Differential Phase
Dark Field
Absorption
DPC
Dark Field
Phase
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Thickness: ~3.5 cm
~ 15 cm
~ 15 cm
Human breast cadaver specimen,
dissected
Absorption
Absorption
Differential Phase
Differential Phase
Dark Field
Dark Field
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Absorption
DPC
Dark Field
Phase
Absorption
Differential Phase
Dark Field
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7/14/2015
Absorption
DPC
Dark Field
Phase
Absorption
Phase
Dark Field
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

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
X-ray differential phase contrast imaging is an innovative
method that is sensitive to x-ray refraction in matter
The method is particularly adapted to visualize weakly xray absorbing soft tissues and may provide
complementary information to conventional absorption
contrast imaging
The key factor of the performance of phase contrast
imaging is fringe visibility, which has been significantly
improved through recent technical advances
To fully understand the clinical benefit of this method, it
is essential to performance evaluations in a clinical
setting and without sacrificing the performance of
absorption imaging
Current DBT System
Future multi-contrast breast imaging system
Absorption
Phase
Mammography
DBT
Dark Field
Mammography
DBT
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Thank You
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