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Quantitative x-ray dark-field computed tomography

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Physics in Medicine & Biology
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The basic principles of x-ray image formation in radiology have remained essentially unchanged since Röntgen first discovered x-rays over a hundred years ago. The conventional approach relies on x-ray attenuation as the sole source of contrast and draws exclusively on ray or geometrical optics to describe and interpret image formation. Phase-contrast or coherent scatter imaging techniques, which can be understood using wave optics rather than ray optics, offer ways to augment or complement the conventional approach by incorporating the wave-optical interaction of x-rays with the specimen. With a recently developed approach based on x-ray optical gratings, advanced phase-contrast and dark-field scatter imaging modalities are now in reach for routine medical imaging and non-destructive testing applications. To quantitatively assess the new potential of particularly the grating-based dark-field imaging modality, we here introduce a mathematical formalism together with a material-dependent parameter, the so-called linear diffusion coefficient and show that this description can yield quantitative dark-field computed tomography (QDFCT) images of experimental test phantoms.
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IOP PUBLISHING PHYSICS IN MEDICINE AND BIOLOGY
Phys. Med. Biol. 54 (2009) 2747–2753 doi:10.1088/0031-9155/54/9/010
Soft-tissue phase-contrast tomography with an x-ray
tube source
Martin Bech1, Torben H Jensen1, Robert Feidenhans1, Oliver Bunk2,
Christian David2and Franz Pfeiffer2,3,4
1Niels Bohr Institute, University of Copenhagen, DK-2100 Copenhagen, Denmark
2Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland
3´
Ecole Polytechnique F´
ed´
erale de Lausanne, CH-1015 Lausanne, Switzerland
E-mail: bech@fys.ku.dk and franz.pfeiffer@ph.tum.de
Received 14 January 2009, in final form 9 March 2009
Published 15 April 2009
Online at stacks.iop.org/PMB/54/2747
Abstract
We report the first experimental soft-tissue phase-contrast tomography results
using a conventional x-ray tube source, with a millimeter-sized focal spot.
The setup is based on a Talbot–Lau grating interferometer operated at a
mean energy of 28 keV. We present three-dimensional ex vivo images of a
chicken heart sample, fixated in formalin. The results clearly demonstrate
the advantageous contrast attainable through phase-contrast imaging over
conventional attenuation-based approaches.
1. Introduction
X-ray radiography has been used for medical imaging since the discovery of x-rays more than
a hundred years ago. By the development of computed tomography (CT), x-ray imaging could
be further improved and non-destructive three-dimensional (3D) views of internal structures
became possible (Cormack 1963, Hounsfield 1973). In particular, for medical diagnostics
applications, x-ray CT became an invaluable tool during the last 30 years.
Today the contrast in x-ray CT images is essentially limited by the maximum tolerable
dose, and the resulting statistical constraints when measuring the x-ray attenuation precisely
along the ray trajectories. Since the absorption coefficients of soft tissue are very close to that
of water, it is very difficult to distinguish internal features in the soft material.
One way to improve the contrast is through the use of x-ray phase-contrast imaging
techniques (Snigirev et al 1995, Wilkins et al 1996). Over the last few years, essentially three
different techniques have been developed: propagation-based phase-contrast imaging (Mayo
et al 2003, Cloetens et al 2006), crystal or grating analyzer-based phase-contrast imaging
(Zhong et al 2000,Keyril
¨
ainen et al 2002,Bravin2003, Clauser 1998,Davidet al 2002,
4Present address: Department of Physics, Technical University of Munich, 85747 Garching, Germany.
0031-9155/09/092747+07$30.00 © 2009 IOP Publishing Ltd Printed in the UK 2747
2748 M Bech et al
Figure 1. Schematic view of the experimental setup. Not to scale. The G0 grating acts as
a slit array, producing parallel line sources. The sample is placed immediately in front of the
interferometer, and the detector is placed immediately after. The distance Lbetween gratings G0
and G1, and the distance dbetween gratings G1 and G2 are indicated in the figure.
Momose et al 2003), and crystal interferometer-based phase-contrast imaging (Bonse and
Hart 1965, Momose et al 1995, Beckmann et al 1999). In particular, the recent studies of
x-ray phase-contrast imaging using a grating interferometer at a synchrotron demonstrate that
it is possible to distinguish subtle details in soft materials that are indistinguishable in standard
absorption-based x-ray tomography (Weitkamp et al 2005, Momose et al 2006,Pfeifferet al
2007a,Davidet al 2007b).
Despite these good results at synchrotron radiation sources, the data recorded at ordinary
x-ray tubes have not yet demonstrated clear advantages in soft-tissue phase-contrast CT.
Here, we now present the first tomographic phase-contrast images obtained with a grating
interferometer, which demonstrate that high soft-tissue contrast can also be obtained with
standard x-ray tube sources and centimeter-sized samples.
2. Experimental setup
In the experiments presented here, a grating interferometer and a PILATUS 100K detector
module were used. The setup was installed at a Seifert ID 3000 x-ray generator operated at
40 kV/30 mA, with an effective source size of 0.8 mm (hor) ×0.4 mm (ver). The detector
had 487 ×195 pixels, with a pixel size of 172 ×172 μm2, yielding a total field of view of
83 ×33 mm2.
2.1. Interferometer
For phase-contrast x-ray imaging, we used a grating-based interferometer with three gratings in
Talbot–Lau geometry (Pfeiffer et al 2006); see figure 1. The setup comprises an x-ray source,
one grating after the source, the sample (on a tomographic rotation stage), two gratings after
the sample and the image detector. The gratings are source grating G0, phase grating G1 and
analyzer grating G2. Grating G1 is a pure Si grating, whereas gratings G0 and G2 are Si/Au
absorption gratings made by etching into a Si wafer and subsequent electro-plating of Au as
described elsewhere (David et al 2007a).
The grating G0 is mounted close to the source, and ensures a suitable horizontal transverse
coherence length of the x-ray beam for each line source created by G0. The interferometer
consisting of gratings G1 and G2 is located at a distance of L=1.4 m from the source. G1 has
Soft-tissue phase-contrast tomography 2749
a period of 3.5 μm, and a depth of 36 μm corresponding to a phase shift of πat 28 keV. Due
to the Talbot self-imaging effect (Talbot 1836), interference fringes are formed at fractional
Talbot distances corresponding to
a=jg2
1
8λ
(in plane-wave geometry), where jis an odd integer, g1is the period of the phase grating G1
and λis the wavelength. To account for magnification due to the divergent beam geometry of
our experiment, the actual fractional Talbot distances dare rescaled by
d=jg2
1
8λ
L+d
L
=La
La.
In the current experiment, the setup was operated at the fifth fractional Talbot distance (j =5)
corresponding to d=20 cm. The period g2of grating G2 was 2 μm, which is equal to
the interference fringe period caused by grating G1. The source grating G0 has a period of
g0=g2×L/d =14 μm, ensuring that the interference patterns from neighboring source
lines will overlap at G2 (David et al 2007a). The sample should be located immediately in
front of G1, and the detector should be immediately behind G2. In the current experiment,
these distances were approximately 50 mm and 30 mm, respectively.
2.2. Data acquisition and processing
Differential phase-contrast images are extracted from the raw image data recorded during a
phase stepping scan in the following way: a number of exposures are made while stepping the
analyzer grating G2 transversely over one period of the grating. The recorded intensity is thus
a function of pixel position (px,p
y)and grating position xg. As the analyzer grating G2 has
the same period as the interference pattern caused by G1, the exact position of the interference
pattern can be extracted from the measured intensity I(p
x,p
y,x
g), transmitted through G2.
The shift of the interference pattern from a refracted beam relative to that of the undisturbed
beam is a direct measure of the refraction angle. Knowing the angle of refraction, it is trivial
to calculate the gradient of the total phase shift =2πα/λ, and the total phase shift by
integration. By using computed tomography techniques, it is then possible to quantitatively
reconstruct a three-dimensional map of the refractive index: n=1δ+iβ. The real part δ
is related to the total electron density ρand the wavelength λby
δ=ρr0λ2
2π,
where r0=2.82 ×1015 m is the Thomson scattering length (Als-Nielsen and McMorrow
2001). The imaginary part βof the refractive index nis related to the absorption coefficient
μ=4πβ/λ. The tomographic reconstruction of the attenuation data was carried out using
standard filtered back-projection using a Ram-Lak filter, as described, e.g., in Kak and Slaney
(2001). The differential phase-contrast signal was reconstructed using an imaginary filter
(Hilbert transform) and back-projection, as previously described in Pfeiffer et al (2007b,
2007c).
3. Results
To test the applicability of x-ray tubes for phase-contrast CT on soft tissue, we have measured
phase-contrast images of a chicken heart in a tomography setup. The heart was fixated in 4%
2750 M Bech et al
(a) (b)
Figure 2. X-ray images of a chicken heart. (a) Conventional x-ray image, attenuation contrast.
(b) Phase-contrast image. The images show a single projection, which is part of a 375 image
projection dataset. The images are displayed using a linear gray scale. The transmission values
(a) are given relative to water. The phase-contrast values (b) are given as the transverse shift of the
interference pattern in the plane of G2. The white scale bar corresponds to 5 mm.
formalin solution and kept in a cylindrical plastic container. The container was submerged in
a water bath as illustrated in figure 1.
The tomography data were recorded with 16 phase steps per projection and a total of
375 projections, covering a 360sample rotation. In this proof-of-principle experiment the
exposure time was 10 s per frame, yielding a total exposure time of 13 h. Please note that the
current measurement has not been optimized for low radiation dose or short exposure time.
In an improved setup, one could reduce the number of phase steps from 16 to 4, and with a
high power x-ray source, gratings for higher energy, and a detector with a higher quantum
efficiency, the exposure time and radiation dose would be lowered considerably. Figure 2
shows the conventional x-ray transmission image and the phase-contrast image from a single
projection. The fact that muscle tissue and water have almost the same attenuation coefficient
makes it difficult to see the heart in the standard x-ray image. But the less-dense adipose tissue
in the top part of the image is visible. In the differential phase-contrast image, the contour of
the heart can be faintly distinguished from the surrounding water.
Though the image contrast in a single projection (figure 2) is relatively poor, images with
much higher contrast can be obtained from virtually slicing the tomographically reconstructed
3D volume, owing to the increased statistics obtained through the many projections. As
illustrated in figures 3(a) and (e), the adipose tissue visible in figure 2is clear and distinct in
the reconstructed absorption contrast image. But the signal from the heart muscle itself is still
comparable to the background noise level. In the phase tomography dataset, figures 3(b)–(d)
and (f)–(h), both the adipose tissue and the heart muscle itself are clearly visible.
In the processing of the data, a flat-field correction of the beam transmitted through the
water tank (40 mm thickness) without the sample in place is used to correct for inhomogeneities
in the illumination and the sensitivity response of the detector. As a result the attenuation
is normalized to that of water during reconstruction, and hence the data are subsequently
calibrated to the table values for the index of refraction for water. The table values are
μ=0.36 cm1and δ=2.94 ×107(Henke et al 1993), respectively.
To provide a quantitative comparison of absorption contrast to phase contrast, figure 4,
left panel, displays the pixel values along the red bold-dashed line in figures 3(a), (b), (e) and
(f). We observe that the differences in the attenuation values (μ) between the heart tissue
and water are buried in the noise level, whereas they are well resolved in the corresponding
phase-contrast signals (δ). The improved contrast is further exposed in figure 4, right panel,
which shows a histogram representation of all pixels in the axial slices in figures 3(a) and
(b). In the phase-contrast histogram two distinct peaks are seen at δ=2.94 ×107and
Soft-tissue phase-contrast tomography 2751
(a) (b) (c) (d)
(e) (f) (g) (h)
Figure 3. Slices through the reconstructed 3D tomography volume. (a) Axial slice, absorption
contrast. (b)–(d) Axial slices, phase contrast. (e) Frontal slice, absorption contrast. (f)–(h) Frontal
slices, phase contrast. The images are displayed on a linear gray scale. The absorption-contrast
gray scale ranges from μ=0.31 cm1to μ=0.41 cm1(symmetrically around the water peak),
and the phase-contrast gray scale ranges from δ=2.8×107to δ=3.2×107(covers water
and muscle tissue). Frontal and axial slices are vertically ordered pairwise such that they intersect
in the red dashed line. Voxel values along the red dashed lines of panels (a), (b), (e) and (f) are
plotted in figure 4(left panel). The black scale bar corresponds to 5 mm.
0.2
0.25
0.3
0.35
0.4
0.45
Attenuation coefficient (μ) [cm ]
Attenuation coefficient
Index of refraction
00.5 11.5 22.5 33.52.6
2.7
2.8
2.9
3
3.1
3.2
x 10
Index of refraction (δ)
Position in sample [cm]
0.2
0.25
0.3
0.35
0.4
0.45
Attenuation coefficient (μ) [cm ]
Attenuation coefficient
Index of refraction
0500 1000 1500 2000
2.6
2.7
2.8
2.9
3
3.1
3.2
x 10
Index of refraction (δ)
Voxel count
Figure 4. Left panel: plot of absorption coefficient μand the real part of refractive index δalong
the red dashed line in figures 3(a), (b), (e) and (f). Right panel: histogram of the voxels in the
entire axial slice in figures 3(a) and (b).
δ=3.07 ×107, corresponding to water and heart tissue, respectively. It is also noteworthy
that the cylindrical sample container and adipose tissue are distinguishable in the phase-
contrast signal at δ=2.71 ×107and δ=2.75 ×107, respectively. The absorption
histogram has only two peaks, one at μ=0.36 cm1corresponding to water/heart, and the
other at μ=0.24 cm1, corresponding to adipose tissue/plastic. This clearly illustrates far
better contrast using the phase signal.
Note that the y-axis scales on left and right panels of figure 4are identical.
2752 M Bech et al
4. Conclusions
In summary, we have presented the first, grating-based experimental soft-tissue phase-contrast
computed tomography results using a conventional x-ray tube source with millimeter-sized
focal spot. The results clearly demonstrate the advantageous contrast attainable through
phase-contrast imaging over conventional attenuation-based approaches.
We have particularly shown that a quantitative analysis of the sample composition is
feasible on the basis of the phase-contrast data, even though the absorption data hardly
provide any contrast at all. More precisely, we have demonstrated that quantitative electron
densities can be obtained from the measured δvalues. For a chicken heart test sample fixated
in formalin, we deduced electron densities of ρ=3.49 ×1023 cm3for the muscle tissue,
ρ=3.13×1023 cm3for the adipose tissue and ρ=3.08 ×1023 cm3for the plastic cylinder,
when calibrating against an electron density for water of ρ=3.34 ×1023 cm3.
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... The amplitude of the curves is related to the dark-field signal, but it is not currently implemented in our model. The processing steps have been described previously and are well-known in the field(Pfeiffer et al 2007, Bech et al 2010. ...
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Objective. To enable practical interferometry-based phase contrast CT using standard incoherent x-ray sources, we propose an imaging system where the analyzer grating is replaced by a high-resolution detector. Since there is no need to perform multiple exposures (with the analyzer grating at different positions) at each scan angle, this scheme is compatible with continuous-rotation CT apparatus, and has the potential to reduce patient radiation dose and patient motion artifacts. Approach. Grating-based x-ray interferometry is a well-studied technique for imaging soft tissues and highly scattering objects embedded in such tissues. In addition to the traditional x-ray absorption-based image, this technique allows reconstruction of the object phase and small-angle scattering information. When using conventional incoherent, polychromatic, hard x-ray tubes as sources, three gratings are usually employed. To sufficiently resolve the pattern generated in these interferometers with contemporary x-ray detectors, an analyzer grating is used, and consequently multiple images need to be acquired for each view angle. This adds complexity to the imaging system, slows image acquisition and thus increases sensitivity to patient motion, and is not dose efficient. By simulating image formation based on wave propagation, and proposing a novel phase retrieval algorithm based on a virtual grating, we assess the potential of a analyzer-grating-free system to overcome these limitations. Main results. We demonstrate that the removal of the analyzer-grating can produce equal image contrast-to-noise ratio at reduced dose (by a factor of 5), without prolonging scan duration. Significance. By demonstrating that an analyzer-free CT system, in conjuction with an efficient phase retrieval algorithm, can overcome the prohibitive dose and workflow penalties associated grating-stepping, an alternative path towards realizing clinical inteferometric CT appears possible.
... Integrating this coefficient over the ray path length then yields the total amount of SAXS. This has been successfully applied to achieve quantitative computed tomography reconstructions [8]. The model has, however, not yet been applied directly to ray tracing simulations, where it can be used to simplify and speed up the simulation process. ...
... The Talbot-Lau implementation was also proven to be suitable for CT implementations and, like with other differential methods, retrieval of the USAXS was rapidly demonstrated (Pfeiffer et al., 2008). Also in this case, the retrieved USAXS signal can be cast as a line integral and fed to a CT reconstruction algorithm (Wang et al., 2009;Bech et al., 2010). More recently, an intriguing possibility was demonstrated by rotating the sample around the optical axis as well as around the 'standard' CT axis of rotation (orthogonal to the optical axis and parallel to the grating trenches), which was proven to yield directional information on the microstructure of the sample (Bayer et al., 2014), albeit at the cost of a more complex and lengthy acquisition procedure. ...
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IMAGING with hard X-rays is an important diagnostic tool in medicine, biology and materials science. Contact radiography and tomography using hard X-rays provide information on internal structures that cannot be obtained using other non-destructive methods. The image contrast results from variations in the X-ray absorption arising from density differences and variations in composition and thickness of the object. But although X-rays penetrate deeply into carbon-based compounds, such as soft biological tissue, polymers and carbon-fibre composites, there is little absorption and therefore poor image contrast. Here we describe a method for enhancing the contrast in hard X-ray images of weakly absorbing materials by resolving phase variations across the X-ray beam1-4. The phase gradients are detected using diffraction from perfect silicon crystals. The diffraction properties of the crystal determine the ultimate spatial resolution in the image; we can readily obtain a resolution of a fraction of a millimetre. Our method shows dramatic contrast enhancement for weakly absorbing biological and inorganic materials, compared with conventional radiography using the same X-ray energy. We present both bright-field and dark-field phase-contrast images, and show evidence of contrast reversal. The method should have the clinical advantage of good contrast for low absorbed X-ray dose.
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IN conventional radiography, X-rays which pass through an object along different paths are differentially absorbed, and the intensity pattern of the emerging beam records the distribution of absorbing materials within the sample. An alternative approach is phase-contrast radiography, which instead records variations of the phase of the emerging radiation. Such an approach offers improved contrast sensitivity, especially when imaging weakly absorbing samples. Unfortunately, current phase-contrast imaging techniques1-11 generally require highly monochromatic plane-wave radiation and sophisticated X-ray optics, so their use is greatly restricted. Here we describe and demonstrate a simplified scheme for phase-contrast imaging based on an X-ray source having high spatial (but essentially no chromatic) coherence. The method is compatible with conventional polychromatic micro-focus X-ray tube sources, is well suited to large areas of irradiation, can operate with a lower absorbed dose than traditional X-ray imaging techniques, and should find broad application in clinical, biological and industrial settings.
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As different methods to improve diffraction enhanced imaging are proposed, the authors introduce a simple algorithm that follows the original idea of Chapman et al. [Phys. Med. Biol. 42, 2015 (1997)] , but extend it to a general object featuring absorption, refraction, and ultrasmall-angle scattering. The information relative to the three effects is decoupled, requiring only three images in input. Simulation and experiment give accurate results, provided the refraction and scattering angles are small compared to the rocking curve width. The proposed algorithm can be readily and fruitfully implemented in several applications, particularly when time and dose constraints are relevant.
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We have shown so far that 3D structures in biological sot tissues such as cancer can be revealed by phase-contrast x- ray computed tomography using an x-ray interferometer. As a next step, we aim at applications of this technique to in vivo observation, including radiographic applications. For this purpose, the size of view field is desired to be more than a few centimeters. Therefore, a larger x-ray interferometer should be used with x-rays of higher energy. We have evaluated the optimal x-ray energy from an aspect of does as a function of sample size. Moreover, desired spatial resolution to an image sensor is discussed as functions of x-ray energy and sample size, basing on a requirement in the analysis of interference fringes.
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First Talbot interferometry in the hard X-ray region was demonstrated using a pair of transmission gratings made by forming gold stripes on glass plates. By aligning the gratings on the optical axis of X-rays with a separation that caused the Talbot effect by the first grating, moire fringes were produced inclining one grating slightly against the other around,the optical axis. A phase object placed in front of the first grating was detected by moire-fringe bending. Using the technique of phase-shifting interferometry, the differential phase corresponding to the phase object could also be measured. This result suggests that X-ray Talbot interferometry is a novel and simple method for phase-sensitive X-ray radiography.
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Differential phase-contrast X-ray imaging has been performed in a Talbot-Lau configuration, where a multiline X-ray source was used instead of a combination of a hard-X-ray multiple slit and a normal focus X-ray generator. When the multiple slit is used, a high aspect ratio structure is needed and slit width should be below 10 mum for its function. The fabrication and use of such a multislit can be omitted using the presented configuration. The multiline X-ray source was developed by making grooves on a tungsten rotating anode, which was irradiated by an electron beam to generate X-rays. An array of 10 mum line sources with a pitch of 30 mum was formed and combined with a 4.5 mum pitch phase grating and a 5.3 mum pitch amplitude grating to generate differential phase contrast. With a total exposure time of 40 s, a differential phase image depicting cartilages was obtained.
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An x-ray interferometer has been developed that uses two transmission phase gratings to analyze wave front distortions in the hard x-ray range. The interferometer is insensitive to mechanical drift and vibrations, and it is tunable over a wide range of photon energies. This setup was used for differential phase contrast imaging of low-absorbing test objects. We obtained micrographs with moiré fringes of good visibility, which revealed the local phase shift gradient caused by the objects. A comparison with numerically simulated images indicates that quantitative analysis of unknown phase objects is possible. © 2002 American Institute of Physics.