Volumetric Monochromatic X-ray Tomography of the Lungs
Cynthia B. Paschala,b, Frank E. Carrollb,c,d, John A. Worrellb, Marcus H. Mendenhallc, Robert Traegerb,
James W. Watersd, Caryl N. Brzymialkiewicza, Gwen A. Banksa
a
b
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235
Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37235
c
W.M. Keck Free Electron Laser Center, Vanderbilt University, Nashville, TN 37235
d
Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235
ABSTRACT
Monochromatic x-rays were produced by inverse Compton scattering resulting from counter-propagation of a tunable free
electron laser electron beam and its own infrared photon beam. In a manner analogous to electron beam CT, a mechanism
was developed here for obtaining multiple projection views with monochromatic x-rays by deflecting x-rays off of mosaic
crystals mounted on rotating stages. These crystals are both energy and angle selective. X-rays are detected digitally when
they strike a phosphorescent screen mounted in front of a CCD camera. Using this system, multiple projection images of a
three-dimensional (3D) phantom and of rat lungs ex vivo were obtained. In an alternate micro-CT arrangement, rat lungs in
situ were imaged by rotating the rat in front of both a polychromatic beam from a molybdenum target x-ray tube and the
same beam monochromatized with a mosaic crystal. In the first arrangement, depth information was revealed by relative
position changes of features seen in each projection and the ~0.16 mm thick walls of a catheter were visible in the images.
Using conventional tomography, the projections were reconstructed into slice images. Overall, these monochromatic x-ray
imaging methods offer reduced x-ray dose, the potential for improved contrast resolution, and now 3D information.
Keywords: monochromatic, x-ray, imaging, tomography, three-dimensional, pulmonary, lungs
1. INTRODUCTION
Since their discovery over a century ago, x-rays have formed the foundation of diagnostic imaging, allowing views inside the
body, albeit with three dimensions projected into a two-dimensional (2D) image. With the advent of computed tomography
(CT) scanners in the early 1970’s, x-rays could be used for tomographic imaging, that is, 2D imaging of an essentially 2D
slice, allowing for a finite slice thickness. Today, high-resolution computed tomography (HRCT) is the clinical standard for
in vivo cross-sectional imaging of the lungs. Under good conditions, 1000 micron resolution in plane and 1 to 1.5 mm axial
resolution can be achieved with HRCT. On rare occasions, in plane resolution of approximately 100 to 300 microns is
possible. Unfortunately, many diseases that affect the lungs including asthma, emphysema, and the spectrum of diseases
included in interstitial fibrosis feature some anatomic abnormalities that are below the level of resolution of current HRCT
techniques. While in theory, higher resolution is achievable, it would require a significant increase in the already fairly high
x-ray dose associated with HRCT. Prototypes for higher resolution micro-CT scanners for small samples such as mice exist,
but such technology will not scale up well for routine clinical imaging of the human torso. In addition, the scatter associated
with the higher energy x-rays that make up part of the spectrum of the typical x-ray source limits resolution. Further, the
complex three-dimensional (3D) microanatomy of the lung is not always optimally visualized in the standard cross-section
displayed by HRCT. A technology is needed for high spatial and contrast resolution imaging of lung tissues in three
dimensions with reduced x-ray dose.
Methods have recently been developed to produce monochromatic x-rays, that is, x-rays of a single energy, that are tunable
within an energy range and geometry that can be applied to imaging of lungs. A monochromatic x-ray beam offers the
advantages of eliminating low energy x-rays that contribute a disproportionate share of the radiation dose, while at the same
time eliminating higher energy x-rays that are more likely to scatter and thus add noise to the images. Since the attenuation
of x-rays is a function of both tissue type and x-ray energy, a monochromatic source allows images to be a function of tissue
type only, thus improving contrast resolution and offering the possibility of improved tissue characterization. The challenge
in applying this novel development is that current monochromatic x-ray sources cannot be rotated, as is typical with HRCT.
This paper demonstrates two approaches to addressing this limitation -- beam deflection by rotating mosaic crystals in a
manner analogous to electron beam CT and rotation of the target.
2. BACKGROUND
X-ray attenuation coefficients are a
function of both tissue type (e.g., normal
vs. cancerous) and photon energy.
Differential attenuation as a function of
tissue type is the basis for image contrast
in x-ray imaging. Johns and Yaffe
demonstrated that, for energies below 31
keV, neoplastic breast tissues have
higher linear attenuation coefficients, ,
than normal tissues and, perhaps more
importantly, that the differences increase
with decreasing x-ray energy down to 20
keV (the lowest energy tested in that
study) [1]. Monochromatic x-rays in the
14.15 to 18.0 keV energy range from a
synchrotron were used to measure the
linear attenuation coefficients of normal,
cancerous, and fatty breast tissues in
addition to human cell line tumors
grown in rats [2].
Attenuation
coefficients differed by tissue type and
the
measured
's
were
quite
reproducible for individual tissue
samples. Using synchrotron radiation,
Burattini also found that monochromatic
x-ray images of breast tissues had higher
contrast and better resolution [3].
Attenuation coefficients decreased with
increasing photon energy. The tissue
and energy dependency of x-ray
attenuation coefficients unfortunately
can result in subtle tissue dependent
attenuation differences between a region
of normal cells and a region in which
cancerous cells have infiltrated normal
tissue being masked by differential
attenuation of a polychromatic x-ray
beam. With a monochromatic x-ray
beam, such subtle tissue dependent
differences are more likely to be
detected.
crystal 2
C
12o
A
B
6o
crystal 1
(a)
rotating
assembly
crystal 2
imaging
region
axis B
crystal 1
power cable
(b)
Figure 1. (a) Schematic of crystal rotator. X-ray source at A (or beam entering
at A) radiates a narrow beam to mosaic crystal 1. The 17.5 keV x-rays incident
at 6o are deflected by 6o to crystal 2, which is tuned to deflect these x-rays as
shown. The crystals rotate about the axis B, causing the beam to sweep over a
conical trajectory with vertex at the intersection of axis B with plane C. The
shaded region at the trajectory vertex is the imaging region. (b) Photograph of
crystal rotator used to make images in Figure 2 and Figure 3. A patent
application is pending for this device.
3. MATERIALS AND METHODS
In a manner analogous to electron beam CT, a mechanism was developed here for obtaining multiple projection views with
monochromatic x-rays by deflecting x-rays off of mosaic crystals mounted on rotating stages. These crystals are both energy
and angle selective, with selective tuning accomplished by changing the angle of the crystals with respect to axis B of Figure
1(a). The mosaic crystal rotator tomographic system maintains x-ray beam source, imaging target and detector stationary.
The crystals rotate to acquire different projection angles and are translated along the source-target axis to sweep the beam
over a larger region. X-rays are detected digitally when they strike a phosphorescent screen mounted in front of a CCD
camera. The CCD camera detects visible light produced when x-rays interact with the screen and the resulting images, with a
full field of 1100 x 1050 pixels, are recorded. With a standard 50 mm, f2.8 lens focused on the screen at approximately 30
cm away, the nominal resolution was 130 microns. Eight projection images of a three-dimensional phantom, containing
multiple targets, and rat lungs in situ were obtained with this mechanism. In addition, an image without any attenuating
target was obtained (the “white” image) to assess beam uniformity and an image with the x-ray source turned off was
obtained (the “dark” image) to use for CCD camera dark current correction.
Correction for dark current in the CCD camera and flat-fielding to remove the effects of beam non-uniformity, caused
primarily by heterogeneity of the mosaic crystals was accomplished for each projection image, P i, by the following
computation:
Pi, corrected 
Pi - Dark
(1)
White - Dark
To reconstruct slices from the projection images, a focal plane (“conventional”) tomography approach [4] was used in which
appropriate combination of the different projection images brings a single plane into focus and blurs out the other planes.
In an alternate micro-CT arrangement, rat and mouse lungs in situ were imaged by rotating the animal in front of both a
polychromatic fan-beam from a molybdenum target x-ray tube and the same beam monochromatized to 17.5 keV with a
mosaic crystal, also in a fan-beam geometry. As before but with a with an f1.2 lens focused on a screen only 12 cm away,
the nominal resolution was 50 microns with actual resolution, as measured with a line pair phantom, being better than 5
lp/mm. A device, consisting of an x-ray transparent plastic tube supported on the top and bottom by rotating stages, was used
to hold an athymic nude mouse and projections from 0 to 180, in 5increments were obtained in addition to projections at
210, 240, 270, 300, and 330. The redundant projection pairs (e.g., 0 and 180, 30 and 210, etc.) were used to
determine the center of rotation with respect to the center of the acquired images. A back-projection algorithm [5] was used
to reconstruct the 42 projections into a stack of tomographic images, each representing a 50 micron thick plane.
3. RESULTS
Using the crystal rotator mechanism, projection images of ex vivo edematous rat lungs were produced with an example
(corrected for dark current and flat fielded) shown in Figure 2. Note that the walls of
a 16 gauge catheter (diameter 1.8 mm, walls ~0.16 mm thick) from which the lungs
were suspended are visible in the image. For the phantom, projection images
acquired via movement of the crystal rotator, after removal of the dark current and
flat-fielding correction, are shown in Figure 3.
Using a focal plane (“conventional”) tomography approach, 3D reconstructions of the
projection images in Figure 3 were created and are shown in Figure 4. The shallow
angle of the tomographic arc limits the through plane resolution possible with this
approach [6] and provides impetus for revising the data acquisition scheme. Ongoing work as proposed as part of this project involves reassessing the data
acquisition scheme to better facilitate the use of cone beam back projection
algorithms for more data efficient and more spatially accurate volumetric
reconstruction than is possible with the focal plane tomography approach.
Figure 2. Projection image of ex
vivo rat heart-lung bloc made with
the crystal rotation and digital
detection system. The trachea is
secured on a 16 gauge catheter
(O.D. 1.8 mm), the 0.16 mm thick
walls of which are seen in the
image (arrow).
Figure 3. Projection images of a 3D phantom containing the letters “F” and “E” in different planes, the letters
"MXI" and a caduceus in one plane, and a Vanderbilt University shield in another plane. Neither the phantom nor
the x-ray source was moved to obtain these projections. Instead, the projections were obtained using the crystal
rotator shown in Figure 1 with each projection angle representing a different rotation. Depth information about the
phantom is revealed by the relative position changes of features seen in each projection image (e.g., note the varying
spatial relationship of caduceus and shield). A focal plane tomography reconstruction can resolve the third
dimension from these multiple projections as shown in Figure 4.
A projection image of a rat torso from the micro-CT experiment is shown in Figure 5 and a back projection reconstruction of
a 50 micron thick slice through a mouse torso is shown in Figure 6. Nominal in-plane resolution is 50 microns.
Figure 5. Projection image of a rat torso, obtained with a beam monochromatized by deflection off a mosaic crystal.
Nominal resolution is 50 microns.
4. DISCUSSION
Monochromatic x-rays have been produced by inverse Compton
scattering resulting from the counter-propagation of a tunable free
electron laser (FEL) electron beam and its own infrared photon beam
[7]at this institution. Since an FEL is tunable, the monochromatic xray beam is also tunable to energies in the range of 14 to 18 keV.
This method represents the first successful production of pulsed,
tunable monochromatic X-rays in a geometry that uniquely lends
itself to human imaging. This approach will soon be translated to a
new device that will be even better suited to the clinical
environment. This new device under construction uses a tabletop
terawatt laser and custom designed linac to deliver much higher flux
(1010 photons in 2 ps) for this type of imaging. The narrow
bandwidth “hard” X-rays are produced at energies from 15 to 50
Figure 6. Back-projection reconstruction of a
mouse torso, using only 42 projections. The ribs,
heart, and one vertebral body are seen. Nominal
resolution is 50 microns.
(a)
(b)
(c)
(d)
Figure 4. Image planes reconstructed from the projection images in Figure 3. Note that only items in the plane of the
reconstruction are in full focus - (a) "MXI" and caduceus, (b) "F", (c) "E", (d) shield.
keV that can be customized to the imaging task at hand. The properties of the new beam are such that it can be used for plain
films, time-of-flight imaging and phase contrast imaging. Because low energy photons are absent from the beam, the
radiation dose delivered by this beam is much lower than that received in normal radiographic techniques (nine to 46 times
lower for breast imaging [8, 9] and two times lower for the most challenging situation - angiography [10]). The absence of
high-energy photons decreases scatter, improving conspicuity of lesions. Softer monochromatic x-rays (7-12 keV) were
produced in a different FEL by intracavity Compton backscattering [11]; however, the configuration and energy range of that
experiment are not useful for medical imaging. Synchrotron radiation can also be used to generate monochromatic x-rays of
various energies [3, 12], however such an approach is not readily translated to the clinical setting.
In typical x-ray imaging, the x-ray source, target tissue, and detector (e.g., film-screen cassette) are all stationary. The
resulting projection image represents an integration of attenuation effects through the thickness of the tissue. Subtle, tissue-
dependent differences in attenuation coefficients are particularly difficult to detect in such an integrated view but become
more conspicuous in volumetric three dimensional (3D) tomographic views. Tomography requires movement of the source
with respect to the object being imaged in order to obtain the multiple projection views from which the tomogram is
reconstructed. In electron beam CT, source "movement" is accomplished by deflecting an electron beam in a circular path so
that it hits a ring anode around the subject, producing fan beams of x-rays needed to obtain multiple projection views.
Current sources of high flux monochromatic x-rays cannot be moved to acquire multiple projections. The device developed
here to rotate x-ray beams does provide 3D information needed for volumetric imaging but is limited in its utility by the
shallowness of the beam deflection angles in this embodiment. Steeper deflection angles would provide more through-plane
resolution in volumetric imaging but this improvement comes at a severe cost in terms of loss of beam flux [13]. Utilization
of imaging target rotation with the new monochromatic device under construction coupled with multi-layered mirrors (x-ray
deflecting crystals) is ideal for acquisition of data in a true cone-beam back projection geometry.
As noted, an alternative to moving the x-ray beam is to move the target tissue. Although not a clinically desirable approach,
such a method can be a reasonable starting point in the development of a technology. Indeed, by rotating the target tissue
instead of moving the source, three-dimensional x-ray CT images were obtained in this work and elsewhere [12, 14].
5. CONCLUSION
Monochromatic x-ray imaging offers the potential for high resolution imaging with reduced x-ray dose. Methods presented
in this paper demonstrate how such x-rays can be used for high resolution volumetric imaging of the lung. Monochromatic,
high resolution volumetric imaging offers the potential for increased contrast resolution and improved diagnostic capability
that may be very useful not only for patient diagnosis but for the evaluation of pulmonary drugs in small animal models.
ACKNOWLEDGMENTS
This work was supported by grants from the U.S. Office of Naval Research (ONR-N00014-94-1-1023 and ONR-N00014-991-0904). The Vanderbilt University W.M. Keck Foundation Free-Electron Laser Center is supported by Vanderbilt
University and by grants from the Keck Foundation.
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