International Journal of Engineering Trends and Technology (IJETT) – Volume 29 Number 2 - November 2015
A review of X-ray in line phase contrast imaging in diagnosis
of cardiac embolization and malignant tissue
Akshay V. Dhamankar#1, Dheeraj Dandanaik#2, Smit Shah#3, Purva C. Badhe#4
#1, #2, #3 - U.G. Student, #4 - Assistant Professor, Biomedical Engineering Department,
D.J. Sanghvi College of Engineering, Mumbai, India.
Abstract—Histological changes in the tissues cause
change in the density of tissue. Such a change of
tissue density was noted in Lymph node metastasis, in
the growth of malignant tumors and in embolization
of cardiac micro-vessels. This change in tissue
density could be visualized using X-ray phase
contrast imaging. Using x-ray phase contrasting as
the underlying principle for imaging these density
changes, certain applications excelled in concluding
notable diagnostic data. We have reviewed these
applications which use the XILPCI technique. They
include; imaging of metastasis of Lymph nodes,
imaging of malignant gastric tumors and imaging of
embolized cardiac vessels. To conclude the review,
we have compared and summarized conventional xray imaging technique and x-ray phase contrast
imaging technique using suitable data from research
and other references.
Keywords— x-ray phase contrast imaging,
embolization, medical imaging, cancer, tomography,
cardiac, radiology, metastasis.
I.
INTRODUCTION
II.
PHASE CONTRAST X-RAY
IMAGING(XPCI)
When x ray passes through an object, the object
causes change of amplitude as well as phase in the
resultant (traversed) x ray beam. Traditional X ray
imaging is based on image obtained from attenuation
differences caused by absorption of x rays as they
pass through a subject body. But most subjects are
better phase shifters than absorbers. The phase
changes observed are 1000 times more than the
changes taking place in the traversed x ray beam due
to absorption. In XPCI, it allows imaging of objects
which are conventionally considered invisible to x
rays. For materials that produce poor attenuation, if x
ray wavelength is short, the short changes of density
can produce greater phase shifts thereby gaining high
phase contrast. The spatial resolution reaches micron
scale by this method. This can produce very fine
microstructure [3].
III.
X ray imaging was invented by William C.
Roentgen. In today’s diagnostic radiology, x-ray finds
its use in clinical X ray imaging, Computer
Tomography, angiography etc. X ray beam generators
produce x rays which are passed through the patient
body to obtain a clinical image. This image is
obtained due to attenuation of the x ray beam as it
traverses through the patient body. The image is
obtained on a photographic plate or on a screen, with
the help of detectors in case of a digital x ray.
Conventional methodology needs more processing of
radiographic film. Also, the ionizing radiation
produced due to x ray imaging may be carcinogenic
and may prove harmful to some patients if exposed to
longer duration of time [1].
Radio contrast agents are a type of medical contrast
agents used to improve the visibility of soft tissue
in X-ray imaging procedures such as computed
tomography (CT), radiography,
and fluoroscopy.
Radio
contrast
agents
are
typically iodine or barium composites or colloidal
dispersions. When a contrast agent improves the
visibility of an area of tissue, it is called "contrast
enhancing". Modern iodinated contrast agents are
well tolerated. The major side effects of radio-
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contrast are anaphylactic reactions and contrastinduced nephropathy [2].
APPLICATIONS
A. Phase Contrast Imaging In 3-D Cardiac
Embolization Imaging [4].
The article introduces itself with the primary
problems associated due to cardiac vessel
embolization. Where, embolization means occlusion
of a vessel by one or more bodies which can be
arising due to clotting of blood or accumulation of fat
globules. The main problem arising due to
embolization is Myocardial Infarction or commonly
known as a heart attack. In case of a cardiac
infarction, blood flow to the heart stops and injury to
cardiac muscles is caused.
The research states that clinical observations state
that Reperfusion helps in recovery from MI. however
reperfusion can cause oxidative damage to tissues or
even inflammation due to sudden histamine response.
The author’s also states that even after reperfusion,
some coronary micro-vessels remain blocked. This
blockage can be a cause of chest pain or other severe
symptoms of Myocardial Infarction. Lack of restored
blood supply to these vessels can cause further
oxidative damage, also called as ischemia. The
research shows how these micro vessels can be
studied to eliminate problems with microembolization.
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International Journal of Engineering Trends and Technology (IJETT) – Volume 29 Number 2 - November 2015
Two adult rats of approximately 250gm of body
weight were anaesthetized by 4.5ml/kg of chloral
hydrate. The heart tissue was formalin fixed and
Barium sulphate was used as the contrast agent to
obtain contrast. 5um thick sections were sliced and
stained with H and E stain.
The setup consists of a mono-chromator which
converts multi-energy X-ray beams into single energy
x-ray beam ready to be bombarded onto the target
tissue. The tunable energy range was from 8 to 72.5
KeV, with the energy resolution of about 0.5%. In the
experiment, it was adjusted to 16.5 KeV. A high
resolution (2048 x 2048) Charged couple device helps
convert the traversed beam into a 2-D image. Filtered
images using the technique of back projection are
obtained from the rotating stage of the sample. Back
Projection images obtained were used to render2-D
cross sections of the organ under consideration. Using
3-D Surface rendering algorithm structures In
MATLAB 2009, it was possible to develop a 3-D
reconstructed image of the organ under consideration.
The overall setup is shown in Figure 1(a). Figure 1(b)
shows the CCD detected XPCI image of the heart
under consideration.
The distance between sample and detector was
0.28 m. The exploration time was 3.5 seconds. For
CT experiment, the spatial resolution of the detector
was 4008 ×2672 pixels. After the sample stage
rotated by 180 degree, 1254 projection images were
achieved, with an exposure time of 90 ms each. The
distance between sample and detector was 0.52 m.
The surface dose was about2.66 mGy for each
projection.
Fig 1(b) –X-ray phase contrasted image of the Heart under
consideration[5].
From this 3D model, we could directly find how
many micro-vessels were blocked, where they were
obstructed and roughly identify where the heart
muscle lacked reperfusion (red part in Figure
2(a)).Figures 2b, 2c, 2d depict respective histological
slices from the actual sample. The Sliced images
obtained are anatomically accurate and show absolute
similarity in dimensions.
Fig 2 – (a) Cardiac vessel tree 3-D rendered model,
(b), (c), (d) Histological slices [ Up to down ],
Red Area in Figure 2.(a) depicts MI affected area [5].
Fig 1(a) - XPCI graphic flow chart [5].
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The comparison between imaged slices and
histological slices can be seen in Figure 3. The figure
sliced from the rendered image shows accuracy in
anatomical dimensions and is a better resolution
image than regular X-ray images.
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International Journal of Engineering Trends and Technology (IJETT) – Volume 29 Number 2 - November 2015
transmitted x-rays. The refractive index n is a slightly
smaller than the number of 1, can be written as: n =
1−δ−iβ
Fig 3 - XPCI image slice vs. Histological slice of organ under
consideration[5].
Advantages: - The XPCI images obrtained showed
high spatial resolution with enhanced contrast and
details as compared to conventional radiographic
images. Also the anatomical accuracy in
dimensions of image slices was high when
compared with the histological slices.
1) Disadvantages: - The organ under consideration
and the subject were still life considerations. A
beating heart would introduce much more motion
artifacts than the experiments could suggest. So a
method needs to be developed for imaging live
specimens.
B. Investigation Of Gastrointestinal Cancers In
Mice Using X-Ray In-Line Phase Contrast
Imaging [3].
Malignancy is one of the world’s leading causes of
death. Gastric cancer is one of the most frequent
causes of cancer-related death in Asia. Early detection
and treatment of gastric cancers is still the focus of
cancer prevention and treatment. Traditional x-ray
images of the human skeleton are high-resolution
images but that of the human abdominal organs and
soft tissues is very poor. Early cancer detection
mainly depends on radiographic imaging. The current
gastrointestinal examination methods mainly consist
of Computer tomography, Magnetic Resonance
Imaging (MRI), endoscopy and gas-barium double
contrast X-ray gastro-intestinalgraphy. The spatial
image resolution of these devices is on the millimetrescale. A new imaging method called as X-ray in-line
phase contrast imaging (abbreviated as XILPCI) has
emerged which is mainly based on the change in
phase of a transmitted x-ray beam. X-ray in line phase
contrast of soft tissues provides micrometer scale
spatial resolution.
Human gastric cancer cells were implanted into
the stomachs of nude mice and after 3-11 days after
cell implantation, the nude mice were dissected and
their stomachs were removed.The particles emerging
from the synchrotron facility were used to produce 2dimensional images of biological tissue using a
contrast. The beam-line partial facility is depicted as
Figure 1. XILPCI is also termed Fresnel diffraction or
coaxial phase contrast imaging. The beam line partial
facility uses multi-color light sources, thus they
eliminate the need for using monochromatic systems.
When an X-ray goes through a specimen the
refractive index can be used to describe the
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Fig 4 – In the picture of BL13W1 beam-line partial facility;
1. A multidimensional specimen table.
2. An X-ray CCD. It obtained specimens’ projective images with
high-resolution.
3. The precise guide rail [3].
The real component δ represents phase; and
imaginary part β represents absorption term. β is
associated with the linear absorption coefficient of the
material.
X-ray phase contrasting (XILPCI) provides
greater absorption of x-rays by soft tissue thereby
resulting in high resolution images. The gastric
specimens were imaged by a charge coupled device
(CCD) of 9 μm image resolution. Gray level cooccurrence matrices (GLCM) from images of the
regions of interest were used to distinguish between
benign and malignant gastric regions. In GLCM
method, we used the 9 Gray level co-occurrence
matrices. Namely; (GLCM) texture characteristics of
angular second moment (ASM), inertia, inverse
difference moment (IDM), entropy, correlation, sum
average (SA), difference average (DA), sum entropy
(SE), and difference entropy (DE). The co-occurrence
matrix is defined as (C)ij. Since each variable (T) of
matrix is not exactly same we standardise the data
before solving correlation coefficient of data.
Eigen vectors denoted as [li1 li2 li3...li9] of Which is
denoted by Fi=[li1 li2 li3...li9] x[T1 T2 T3 ….T9]
(i=1,2,3,4…9).[3] Support vector machines were
used to derive a pattern between stages of gastric
cancerous growth in the mice. The phase contrast
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International Journal of Engineering Trends and Technology (IJETT) – Volume 29 Number 2 - November 2015
images as shown in Figure.2 of a 5-day old mice
containing gastric cancerous growth are better than
the traditional absorption CT images obtained without
the use of contrast agents. There is no change in gray
level information and the image of gastric wall is not
clear.
Fig 2 - The traditional absorption CT image of the 5-day-old mouse
gastric cancer specimen [3].
Fig 3. The XILPCI CT image of the 5-day-old mouse gastric cancer
specimen (a) The coronal image of nude mouse gastric cancer
specimen.
(b) The transverse image in dotted line position
The results of the component analysis of the texture
parameters based on GLCM of normal regions
exceeds a threshold of 8.5 but those of cancer regions
is lesser than or equal to 8.5. The accuracy of
classification of different stages of gastric specimens
was found out to be around 83% with the help of
SVMs.
patients, and a non-invasive method for identification
of harmful lymph nodes would be of particular
interest for non-Sentinel node candidates.
1) Disadvantage of the current method:- This
method only has therapeutic value in patients with
infected nodes. Failure to detect cancerous
metastases in the sentinel node(s) can lead to an
unfavourable result — there may still be
carcinogenic cells in the lymph node. In addition to
that, there is no significant evidence that patients
who have a full lymph node dissection as an effect
of a positive sentinel lymph node result have
enhanced survival compared to those who do not
have a complete dissection until later in their disease,
when the lymph nodes can be sensed by a doctor.
Such patients may be exposed to the risk of
lymphedema by unnecessary dissection.
2) Proposed principle proceedings:- Lymph node
identification by safe pre-operative and non-invasive
methods holds great impetus. Pre-operative imaging
techniques could help avoid axillary surgery if
results are in favour of the patient. If not, the nodes
can be removed during operative phase and proper
treatment can be initiated faster. Minute variations in
density of human tissue are difficult or impossible to
gauge with conventional X-ray’s, but they can be
imaged by grating-based phase-contrast X-ray
tomography. Due to wave-optical interaction of xrays with biological tissue, the contrast available
with phase-contrast imaging is very high than
conventional X-ray absorption imaging. Hence, the
changes in density caused by invasive cancer can be
visualized. Here we report high phase-contrast
imaging using synchrotron radiation applied to
human lymph nodes.
C. Screening Of Metastatic Lymph Nodes by X-Ray
Phase-Contrast Tomography [6].
Regional axillary nodes are imaged by sentinel
node technique. Sentinel node is the one which is first
affected by a nearby malignant tumour. Sentinel
nodes can be one to three in number. Before biopsy is
performed on a sentinel node, a colloidal dispersion
of radio isotope is injected into the surrounding tissue
of the malignant tumour. The contrast provided by the
radio labelled isotope is visualized by a gamma
camera, to reveal the sentinel node(s) and lymph
nodes that are causing the wear of the tissue in the
vicinity of tumour. A specialist technician identifies
the sentinel node with a small Geiger counter probe
and performs a biopsy for pathological examination
and analysis. If the nodes show malignant metastatic
deposits, an auxiliary dissection is performed.
However, the technique is not viable for all cancer
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Fig 1 - Setup of the procedure.
3)
Sample: - Seventeen still life samples of
lymph nodes were formed by formalin fixation and by
embedding paraffin. Lymph nodes used in evaluation
were from specimens from women with invasive
ductal breast carcinoma. All the samples were
weighed measured on the longest axis and were
bisected prior to formalin-fixation. About 50% of the
formalin Fixed-paraffin-embedded lymph node was
used for evaluation and the other for routine
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International Journal of Engineering Trends and Technology (IJETT) – Volume 29 Number 2 - November 2015
histological examination. A monochromatic x-ray
beam at 23 KeV was used for imaging.
The Si phase grating (G1, p-phase shifting) was
produced using Photo-lithography technique and wet
chemical etching. The Au Absorption grating (G2)
was produced Using soft X-ray lithography. The field
of view was limited horizontally by the detector
resolution and vertically by the X-ray beam size thus
to avoid a narrow field of view, multiple images of
sample were taken the data was reconstructed to form
an image with a wider field of view.
4) Analysis:- Without upper and with lower panels
metastatic deposits from patients detected with
invasive ductal breast carcinoma. The lymphoid
cavities can easily be distinguished in the images of
the benign lymph nodes. The edges clearly mark the
border between the metastatic majority (brighter) of
the lymph node and the minor part of the node with
undamaged normal cells (darker).
IV.
COMPARISON
with standard absorption x-ray imaging. In conclusion,
we describe a new method using x-ray in line phasecontrast tomography that has a high sensitivity and
specificity [7] for detection of lymph node metastases
and micro vessel density changes. The method has a
higher scope in prospective clinical applications and
it may lead to non-invasive Treatment of cancerous
tissue and cardiac malfunctions using such imaging
techniques in the near future. However, all these tests
were carried out on still life specimens. Live
specimen imaging is still an issue to be resolved due
to the high amount of motion artefacts induced in the
output images.
VI.
[1].
[2].
[3].
Conventional X-rays are based on attenuation
caused after beam has passed through the object.
However XPCI is based on changes in phase of the
beam after it has passed through the object.
Conventional methods are less sensitive to density
changes of tissue. XPCI is very sensitive to changes
in tissue density. Conventional method does not need
spatially coherent beam of x-rays. XPCI needs
spatially coherent beams of x-rays. These are the
differences between the Conventional methods of xrays and XPCI.
TABLE I
[4].
[5].
[6].
[7].
REFERENCES
www.medicalradiation.com/types-of-medicalimaging/imaging-using-x-rays/radiography-plain-xrays.
Haberfeld, H, ed. (2009). Austria-Codex (in German)
(2009/2010
ed.).
Vienna:
ÖsterreichischerApothekerverlag. ISBN 3-85200-196-X.
Q. Tao and S. Luo,” multilevel Investigation of gastric
cancers in nude mice using X-ray in-line phase contrast
imaging,” Zhang et al.:Bio-Medical Engineering OnLine
2014 13:101.
L. Zhang, K. Wang, F. Zheng, X. Li and Shuqian Luo,” 3D
Cardiac microvessels embolization imaging based on Xray phase contrast imaging”, Zhang et al. BioMedical
Engineering OnLine 2014, 13:62
http://www.biomedical-engineeringonline.com/content/13/1/62
T. H. Jensen1, M. Bech, T. Binderup, A.Bottiger, C.David,
T.Weitkamp, I.Zanette, E.Reznikova9, J. Mohr, F. Rank,
R
.Feidenhans’l,
A.Kjær,
L.Højgaard,
F.Pfeiffer,”Imaging
of
Metastatic
Lymph Nodes by X-ray Phase-Contrast
Micro-Tomography”, PLoS ONE 8(1): e54047.
doi:10.1371/journal.pone.0054047
https://en.wikipedia.org/wiki/Sensitivity_and_specificity
SR
NO.
Conventional X-rays
I
Based ON attenuation
caused after beam has
passed through the
object.
Less sensitive to
density changes of
tissue.
Spatially coherent
beam of x rays is not
required.
II
III
V.
X-ray Phase contrast
imaging
Based on the change in
phase of the beam after it
has passed through the
object
Highly sensitive to density
changes in tissue.
Spatial coherence is a
necessity to perform XPCI.
SUMMARY
We summarize that x-ray phase-contrast imaging
can precisely detect density variations to obtain visual
information regarding sentinel lymph node
involvement in case of malignancy, embolized
cardiac micro vessels as well as malignant thoracic
tumours all of which were previously inaccessible
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