Radiation Measurements 137 (2020) 106409
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High-resolution X-ray imaging applications of hybrid-pixel photon counting
detectors Timepix
Jan Dudak a, b, *
a
b
Institute of Experimental and Applied Physics, Czech Technical University in Prague, Husova 240/5, 110 00 Prague, Czech Republic
Faculty of Biomedical Engineering, Czech Technical University in Prague, Namesti Sitna 3105, 272 01, Kladno, Czech Republic
A R T I C L E I N F O
A B S T R A C T
Keywords:
Photon counting detectors
X-ray imaging
X-ray radiography
Computed tomography
Medipix and Timepix type hybrid-pixel photon counting detectors were originally developed and intended as
particle trackers at the Large Hadron Collider at CERN. Nevertheless, the applicability of Medipix technology is
much broader and exceeds the field of high energy physics. The unique features of Medipix devices – namely the
dark-current-free quantum-counting, energy-determination and steep point-spread function – make them a
powerful tool for imaging using ionizing radiation. This work provides insight into the applied results of Medipix
technology from fields of transmission X-ray imaging and X-ray fluorescence (XRF) imaging. The history of
Medipix technology is briefly described. The detectors are then characterized by means of key parameters
connected with imaging techniques. Medipix detectors are compared with conventional X-ray imaging cameras
and their advantages and disadvantages are discussed. Finally, the methodology principles of high X-ray
transmission radiography and XRF imaging are explained and a number of applications from different fields of
science are demonstrated.
1. Introduction
The history of X-ray imaging started in 1895, when X-radiation was
discovered and described. Very soon after that X-ray radiography
became an essential tool of medical diagnostic care (Bushberg, 2002).
The photographic plate was used as a standard detection technology for
decades. The rapid development of imaging X-ray detectors came much
later with the introduction of the first digital detection technologies. The
Medipix detectors are a relatively new family of radiation-sensitive de
vices utilizing the particle/photon counting approach. Despite Medipix
being originally developed for high energy physics, its advantages for
other fields of science were very quickly recognized. Nowadays, Medipix
type detectors are used for radiation imaging, digital dosimetry,
educational purposes and many other applications. This paper is focused
on summarizing the use of Medipix detectors in the field of X-ray
imaging.
The first generation of the Medipix chip was introduced in the 1990s
at CERN to serve for tracking of high-energy particles at the Large
Hadron Collider. It provided a pixelated array of 64 � 64 pixels with a
170 μm pixel pitch (Bisogni, 1998). Several new generations of the
Medipix chip have been successfully developed by the established
Medipix Collaboration since that time.
With further development and new generations of the chip coming,
the Medipix technology has found a number of applications outside the
field of high energy physics. The aim of the Medipix collaboration was
clear from the very beginning – to create a highly versatile radiation
imaging detector of superior quality. This original goal can still be seen
from the former logo of the collaboration, since the very first radio
graphic image (a metal wire formed into the shape of the letter “M”)
acquired with a Medipix chip was used.
The successors of Medipix1 have provided additional functionality, a
smaller pixel pitch and a larger sensor area compared to the first gen
eration. Medipix2 provided a significantly smaller pixel pitch (55 μm)
and increased sensor area (14 � 14 mm2 with an array of 256 � 256
pixels) (Llopart, 2002). The Timepix chip enabled the analysis of the
time-of-arrival of each detected particle or position-sensitive spectro
scopic measurement as the energy of detected particles can be directly
estimated (Llopart et al., 2007). The ability to perform fully spectro
scopic measurements was a break-through in the field of X-ray radio
graphic imaging and computed tomography (CT). The evaluation of the
incident beam spectrum provides additional information on the
elemental composition of the imaged sample compared to conventional
* Institute of Experimental and Applied Physics, Czech Technical University in Prague, Husova 240/5, 110 00 Prague, Czech Republic.
E-mail address:
/>Received 19 February 2019; Received in revised form 20 September 2019; Accepted 3 June 2020
Available online 8 June 2020
1350-4487/© 2021 The Author.
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J. Dudak
Radiation Measurements 137 (2020) 106409
radiography. Medipix3 was designed with two user-adjustable energy
thresholds per pixel and with on-board processing addressing the issue
of charge sharing between neighboring pixels (Gimenez et al., 2011).
For purposes of spectroscopic imaging, the Medipix3 chip can be used in
the so-called superpixel mode. Superpixels are clusters of four read-out
pixels behaving like a single detection unit. Such an approach obviously
sacrifices the spatial resolution of the detector, but on the other hand
each superpixel provides eight adjustable energy thresholds. Timepix3
ensures the option to simultaneously measure the time of arrival and the
energy of the detected particles in a data-driven read-out mode (Frojdh
et al., 2015). Timepix4, currently under development, promises to
introduce pixels smaller than 55 μm thanks to the utilization of TSMC 65
nm technology for the chip design and with more pixels situated on each
chip. Furthermore, it will be four-side buttable, therefore, a straight
forward assembly of large-area detector arrays with continuous sensi
tivity will become possible (Campbell et al., 2016).
The photon counting detectors (PCD) utilize two construction ap
proaches – monolithic or hybrid. The detectors of Medipix type use the
hybrid-pixel construction characterized with separated sensor and readout chips interconnected using bump-bonding technology. The hybridpixel construction is more versatile as the sensor and read-out chips
are individual units, thus it is possible to use various sensor materials.
The sensor chips have mostly been manufactured from silicon, never
theless, a number of alternative sensor materials have appeared.
Considering the application of Medipix technology for X-ray imaging
purposes, the major limitation of silicon is in its quantum efficiency.
Semi-insulating materials containing high-Z elements (CdTe, CdZnTe,
GaAs) seem to be a promising solution for this limitation in future.
The weakness of Medipix technology, that limited its wider appli
cability in X-ray imaging, used to be the size of the sensor. Two square
centimeters of sensor area were not convenient for real-life X-ray im
aging. There is a possibility to scan larger samples into a set of tiles using
a high-precision remote-control positioning system. Nevertheless, such
an approach is only suitable for 2D radiography. Performing a CT scan
with the necessity of moving the detector to several positions during
each projection would result in an unbearable scan time prolongation.
For this reason, development has continued not only in chip archi
tecture but an effort has also been placed into increasing the sensitive
area of the detectors. The first success in this field was introduced by
Medipix2 collaboration as the Quad detector – four Timepix chips bumpbonded to a common semiconductor sensor. The Quad uses the layout of
2 by 2 chips providing a sensitive area of 28 � 28 mm2 (see Fig. 1).
Similar attempts of multiple read-out chips connected to a common
sensor layer were introduced as Hexa (2 by 3 chips, 512 � 768 pixels)
and LAMBDA – Large Area Medipix Based Detector Array (2 by 6 chips)
(Zuber et al., 2014; Pennicard et al, 2011). Building larger detectors this
way turned out to be impractical due to manufacturing complications
and the low yield from the wafer. Furthermore, since Medipix chips have
been three-sides tileable up until the present, while the fourth side has
been kept for chip peripheries, it has not been possible to bond more
than two chip rows to a common sensor. Therefore, to achieve a larger
detector area, the assembling of several detector modules to an array has
been necessary. The RELAXd project developed by Nikhef and PAN
alytical provided a read-out board for Quad detectors perpendicular to
the sensor plane (Vykydal et al., 2008). The perpendicular position of
the sensor and the read-out board enabled putting several Quad as
semblies into a 2D array. Similarly, it is possible to assemble several
LAMBDA modules into an array too. In the case of Hexa modules, only
the creation of a row of several devices is possible. All mentioned de
tector arrays have been used mostly for X-ray diffraction measurements.
Since it is not possible to assemble them without insensitive gaps be
tween adjacent modules, their applicability for X-ray radiography is
questionable. Canas et al. aimed to build a Medipix-based detector with
the field of view reaching an area of 24 by 30 cm2 for use in
mammography (Canas et al., 2011). The developed device was built of
an array of 11 by 9 Medipix2 chips. The individual assemblies were
positioned with gaps proportional to the chip size. Each scan, therefore,
consisted of four sub-acquisitions in different positions of the detector
array to cover the whole area that were automatically stitched together.
A significant step forward came with introducing of edgeless sensors.
Omitting the guard ring around the sensor perimeter has enabled
assembling individual detectors to rows with virtually no insensitive
gaps. The edgeless sensors have then been utilized by WidePIX tech
nology developed at the Institute of Experimental and Applied Physics,
Czech Technical University in Prague (IEAP CTU). WidePIX detectors
solve the problem of chip peripheries preventing the assembly of 2D chip
arrays. The WidePIX concept is based on building of chip rows and their
later arrangement into a 2D array. The adjacent rows are slightly
overlapping, so the peripheries of the first row are covered by sensors of
the second row and so on. The largest detector built this way is
WidePIX10�10, shown in Fig. 2, created out of 100 individual Timepix
chips to produce a continuously sensitive area of approximately 14 by
14 cm2 (2560 � 2560 pixels) (Jakubek et al., 2014). Until now, just one
such detector has been built and it is operated at the Centre of Excellence
Telc (CET), Czech Republic.
The current necessity of roof-like rows tiling should be omitted once
the Timepix4, currently under development, is released. Timepix4 will
be 4-side buttable as it utilizes the TSV (through-silicon-via) technology
Fig. 1. Timepix Quad detector with a FITPix readout interface. The detector consists of four Timepix chips bump-bonded to a common silicon sensor layer. The
detector provides an array of 512 by 512 pixels and a total sensitive area of 28 by 28 mm2. (For interpretation of the references to color in this figure legend, the
reader is referred to the Web version of this article.)
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Radiation Measurements 137 (2020) 106409
Fig. 2. WidePIX10�10 – a view inside. The detector consists of an array of 10 by 10 Timepix chips precisely aligned to provide a continuously sensitive area of
approximately 14 by 14 cm2 (2560 � 2560 pixels). Courtesy of Jan Jakubek, IEAP CTU, ADVACAM s.r.o.
allowing the signal to be read out using copper-filled holes passing
through the chip.
already commercially available on the market including one system
utilizing Medipix technology.
1.1. High resolution X-ray imaging with a laboratory set-up
1.2. High resolution X-ray imaging in cone-beam geometry
Intensive research and development in the field of laboratory X-ray
sources and digital detector technology constantly pushes the limits of
achievable spatial resolution of transmission X-ray imaging approaches.
Spatial resolution at the level of several microns used to be the domain of
synchrotron facilities for a long time. Nowadays, such a resolution is
routinely achievable using laboratory X-ray imaging systems. Using the
state-of-the-art laboratory X-ray sources with suitable detector tech
nology, it is possible to reach a resolution even deeply below 1 μm.
Besides the utilization of nano-focus X-ray tubes, that are probably
the most popular sources for high resolution X-ray transmission radi
ography and CT, there are also other attempts focused on sub-micron
precision X-ray imaging. An electron gun from a scanning electron mi
croscope can be modified and used for X-ray projection imaging. Spatial
resolution better than 60 nm achieved this way was demonstrated
(Mayo et al., 2005). Another well-known option is the employment of
suitable optics like Fresnel zone plates (FZP). X-ray microscopes
equipped with FZP have been successfully used for the imaging of in
dividual cells with spatial resolution of 30 nm (Jacobsen, 1999).
Although both of the mentioned approaches offer superior spatial res
olution, the application field is relatively narrow and the set-up is rather
complicated. Especially in the case of FZP – their use is restricted for
energies lower than 10 keV and a monochromatic beam is demanded. It
is clear that such a beam can be used for transmission imaging of
extremely small objects only. The SEM-based source can work with
energies up to approximately 30 keV, but the beam intensity is very low
and thus long acquisition times are inevitable.
As it has already been stated, nano-focus X-ray tubes are the most
popular sources for high resolution X-ray transmission imaging. The
detail detectability of an X-ray imaging system with the latest state-ofthe-art nano-focus tube can reach 150 nm (Excillum, 2018). That is an
order of magnitude worse than SEM-based sources or FZP, but on the
other hand, a polychromatic beam with 60 kVp can be used. Further
more, an X-ray tube is much more versatile and easy-to-use as it pro
duces a divergent beam that enables the scanning of samples in a wide
range of sizes. Several X-ray nano-CT systems with nano-focus tubes are
Laboratory X-ray imaging systems dedicated for high resolution
imaging usually utilize a nano-focus X-ray tube as the radiation source.
An X-ray tube emits X-ray photons in a divergent beam with point-like
origin. The divergent geometry, frequently called cone-beam, allows
the projection of the imaged object to be magnified as the beam spreads.
The magnified projection then covers more pixels of the detector and,
therefore, the sampling density of the obtained image is increased (see
Fig. 3 A and B). Thanks to the cone-beam geometry, it is possible to
achieve much higher resolution compared to the native resolution of the
used detector unit. The magnification factor (M) is given as a ratio be
tween the source-to-detector distance (SDD) and the source-to-object
distance (SOD). The actual sampling density is usually denoted as an
effective pixel size (EPS) and is given by the physical dimensions of the
detector pixel divided by the used magnification factor. The increase of
M inevitably sacrifices the field of view (FOV). Therefore, large-area and
finely pixelated detectors are needed.
The major limitation of the maximum achievable spatial resolution
of an imaging system is the size of the focal spot of the source. Once the
EPS becomes smaller than the focal spot size, the spatial resolution
cannot be further improved as the image will become blurred due to the
penumbra effect (see Fig. 3 C). The focal spot size of the X-ray source is,
therefore, of key importance in the case of high-resolution X-ray imag
ing. X-ray tubes with a highly focused electron beam also have, unfor
tunately, a drawback. The electron beam power density at the target
must be controlled otherwise a thin anode of the X-ray tube would be
quickly destroyed by dissipating heat. The X-ray beam intensity is much
lower compared to widely used micro- and mini-focus sources.
Since the photon flux is limited, the acquisition time of each pro
jection has to be inevitably prolonged to obtain projections with suffi
cient statistics. Therefore, the exposure time can vary from several
seconds to tens of seconds. Photon counting detectors have proven
themselves to be an excellent choice in this case. As PCDs acquire data
without dark current, the shutter can be open for an arbitrary time
period and the noise of the data is still given by Poisson distribution
alone.
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Radiation Measurements 137 (2020) 106409
Fig. 3. X-ray imaging in cone-beam geometry. The diverging beam enables changing the magnification factor by changing the distance from the source to the sample
(SOD). The magnification factor M, given as the ratio of the source-to-detector distance (SDD) and SOD, affects the sampling density (effective pixel size – EPS) of the
final image and, therefore, also the achieved spatial resolution as can be seen from the comparison of A) and B). The maximal useful magnification of an X-ray
imaging system is limited by the size of the focal spot. Once the EPS becomes smaller than the focal spot size the resolution does not further improve, but the obtained
image suffers from penumbral blur (C).
An example of a CT scan carried out with sub-micrometer resolution
can be seen in Fig. 4. The figure shows volume rendering of a fossil
foraminifera sample (foraminifera are single-celled marine organisms
which have inhabited the Earth for more than 500 million years) scan
ned with an effective pixel size of 830 nm using the WidePIX4�5 detector
and the FeinFocus FXE-160.51 multifocus X-ray tube at IEAP CTU. The
left part of the figure shows the volume rendering of the whole sample
while the right part reveals the inner parts of the sample filled with
pyrite crystals. The tube was operated in the nano-focus mode with 50
kVp and 20 μA. The dataset consisted of 720 projections (10 s acquisition
time each), with a 0.5� angular step.
experimental imaging systems and has not been widely used in
commercially available devices yet. Nowadays, considering X-ray im
aging with a resolution at the level of 1 μm or less, the most frequently
used detector technology is a CCD (charge-coupled device) chip with a
thin scintillation sensor. Such cameras provide extremely high pixel
granularity – very often pixels smaller than 10 μm – and the total
number of pixels as well (10 megapixels or more). Therefore, it is easy to
perform CT scans with an extremely small EPS simultaneously with a
wide field of view using these detectors. The key disadvantage of scin
tillation sensors is that the emitted light spreads evenly in all directions
within the sensor and, therefore, the spatial resolution of such a camera
depends more on sensor thickness than on the pixel size. Since the
thickness of a scintillation sensor is typically larger than pixel di
mensions, the point spread function (PSF) of these devices is usually
much wider than pixel size. On the contrary, Medipix technology fea
tures 55 μm pixels but the PSF has a box-like shape and its width is
proportional to the pixel size due to the high bias voltage applied to the
sensor. It was previously demonstrated that a Medipix2 detector offers a
1.3. Advantages of Medipix technology in the field of high-resolution Xray imaging
Medipix and Timepix detectors offer a set of unique features that can
be extremely useful when high resolution X-ray radiography and CT are
discussed. However, the Medipix technology has mostly been utilized in
Fig. 4. Example of a high-resolution CT scan
of a sample of foraminifera performed with a
WidePIX4�5 detector and the FeinFocus FXE160.51 multifocus X-ray tube at the Institute
of Experimental and Applied Physics CTU in
Prague. The left part of the figure shows
volume rendering of the whole sample while
the right part enables seeing the inner parts
of the sample filled with pyrite crystals. The
sample was scanned with 830 nm EPS, the
tube was operated in the nano-focus mode
with 50 kVp and 20 μA. The dataset con
sisted of 720 projections with a 0.5� angular
step. The sample was kindly provided by
Katarina Holcova (Department of Micro
Palaentology, Faculty of Science, Charles
University).
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J. Dudak
Radiation Measurements 137 (2020) 106409
comparable resolution as the X-ray CCD camera CRYCAM (Tous et al.,
2011). The experimental comparison of the contrast and modulation
transfer function (PSF) showed that the Medipix2 device with its 55 μm
pixels provided a spatial resolution of 10.69 lp/mm (line pairs per
millimeter) while the CRYCAM camera with 9 μm pixels offered spatial
resolution of 13.44 lp/mm. A similar experiment was later repeated
comparing Timepix with an 11 Mpix CCD X-ray camera with 9 μm pixel
pitch and a 22 μm thick Gadox scintillation sensor installed in a Bruker
1172 scanner (Dudak et al., 2017). The CCD detector was designed to be
operated in three different binning modes – full resolution (9 μm pixels),
2 � 2 pixels (18 μm pixels) and 4 � 4 pixels (36 μm pixels). Analysis of a
slanted edge captured by both detectors showed that the PSF of the
Timepix chip has approximately the same width of PSF at FWHM as the
tested CCD camera operated in the 2 � 2 pixels binning mode (18 μm
pixels). It was also demonstrated that the steep PSF of Timepix detectors
enables improving detail detectability within the reconstructed CT data
by voxel space oversampling (Dudak et al., 2017). Conventionally, the
CT data are reconstructed with a voxel size proportional to EPS.
Nevertheless in the case of sharp projection data, it was shown to be
profitable to make voxels smaller. Experimental testing showed that the
oversampling of the voxel space by the factor 2–3 suppresses partial
volume effects and improves the detail detectability in the data.
The experimental comparison also demonstrated that the Timepix
detector, due to noiseless counting, provides a higher contrast-to-noise
ratio (CNR) and thus better detectability of fine details with the same
image statistics in the projection (Dudak et al., 2016). Such a compari
son is demonstrated in Fig. 5. A sample of ex-vivo mouse liver was
scanned with a large area Timepix detector and an X-ray CCD camera
with 9 μm pixels and a 22 μm thick Gadox (Gd2O2S:Tb) scintillator. Both
images were measured with 4.3 μm EPS. The Timepix detector (Fig. 5
left) revealed details down to 15 μm while the detail detectability of the
CCD camera was approximately 60 μm due to significantly lower CNR
(Fig. 5 right).
resolution scanner capable of performing a CT scan with EPS within the
range from 50 nm to 5.5 μm (Nachtrab et al., 2015). Furthermore, the
utilization of a Medipix detector enables performing a K-edge absorp
tionmetry simultaneously. A high-end nano-focus tube with a spot size
of 100 nm is used as the radiation source in this case. A large area de
tector was needed to ensure reasonable FOV considering the high
magnification factors needed to achieve the demanded resolution. A
dedicated detector unit based on four Hexa assemblies arranged into a
row producing the total sensor area of approximately 170 � 28 mm2
(3072 � 512 pixels) was designed for this purpose. The FOV can be from
0.15 to 16 mm depending on the actually set magnification factor using
such a detector. A typical scan time with NanoXCT is approximately 10 h
since the detection rate is approximately 2360 events per pixel in 5 min.
Nevertheless, the projection image quality does not suffer from
increased image noise, since Medipix detectors work in the
dark-current-free mode. After a successful demonstration of the system
viability, it was used as a prototype for the development and production
of a commercially available product – RayScan Nano (2019).
1.5. Analysis of cultural heritage artifacts using X-rays
Cultural heritage is a field where a lot of inspection methods of other
fields of science find their applications. Historical artifacts are analyzed
to verify their authenticity, estimate the age, evaluate the current con
dition of the artifacts or to find hidden damage etc. X-rays are not the
only radiation being utilized in this field by far. One can use almost all
wavelengths of the electromagnetic spectrum to analyze historic arti
facts. Frequently, fine art researchers utilize illumination using the IR or
UV spectrum to obtain information that remains hidden in visible light.
However, considering the energy and penetrability of IR or UV photons,
it is clear that these assessments can only provide information on the
surface layers. On the contrary, X-rays penetrates the matter easily and
can deliver information from structures situated deeply below the
surface.
Beside X-ray radiography or CT, other options for the utilization of Xrays in cultural heritage artifacts have been introduced. An alternative
option is the analysis of artworks using X-ray fluorescence (XRF) pho
tons. Since XRF photons have a discrete energy spectrum, the radiation
carries information on the elemental composition of the material emit
ting XRF photons.
In this section, the analysis of cultural heritage artifacts like historic
painted artworks or sculptures will be discussed.
1.4. X-ray microscope and the NanoXCT system
An extreme approach considering the spatial resolution has been
introduced by Fraunhofer IIS. Medipix technology was used in the
development of an X-ray microscope and a laboratory scale nano-CT
system providing spatial resolution deeply below 1 μm. The X-ray mi
croscope was introduced in 2011 and it was based on the use of an
electron gun originally designed for an electron microscope focused on a
very thin transmission tungsten target (Nachtrab et al., 2011). The
achieved focal spot size of the source was 50 nm as the thickness of the
target was only 0.1 μm. The detector unit consisted of a Medipix2 MXR
device in quad configuration. The smallest achievable EPS was 55 nm as
the construction of the device allowed data acquisition with a magnifi
cation factor up to 1000. The second approach called NanoXCT is a high
1.6. Large area scanning
The routine use of Medipix technology for the imaging of painted
artworks has become practically possible with the introducing of largearea detectors as most historical pieces of art have a rather large size.
Fig. 5. X-ray projection of an ex-vivo liver lobe of a laboratory mouse scanned with a large area Timepix detector (left) and a 11megapixel CCD X-ray camera with a
22 μm thick Gadox scintillation sensor (right). The EPS was set to 4.3 μm in both cases and the exposure times were adjusted to get the same image statistics. While
the Timepix detector revealed fine veins down to 15 μm in diameter, the smallest features captured by the CCD camera were approximately 60 μm in size (Dudak
et al., 2016).
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Radiation Measurements 137 (2020) 106409
However, even with the employment of the largest available detectors, it
is usually not possible to scan most of the artworks in a single acquisi
tion. The sample has to be, in this case, scanned in a set of slightly
overlapping sub-acquisitions that are later merged together. An example
of such a scan can be seen in Fig. 6. A painting from 19th century
�
“Cernohorka”
(dimensions of 22 by 28 cm) was scanned in 12 tiles using
Widepix10�5 and the final radiography provides an image resolution of
4450 � 5600 pixels (Zemlicka, 2016).
The final radiography can easily consist of hundreds of megapixels as
the dataset is formed typically of several tens or even hundreds of subacquisitions. Depending on the size of the scanned painting and the
construction of the scanner, there are two options on how the scan can
be performed. The painting can be either scanned using the simulta
neous movement of both the source and detector or with the fixed po
sition of the X-ray source, while the detector is moving. The first
approach requires the precise synchronization of the detector and source
movement. Since the irradiation of one tile at a time is sufficient, the
source and detector can be very close to each other, thus high beam
intensity leading to shorter exposure time is achieved. On the other
hand, this approach can induce geometry artifacts in the final assembled
radiographies since overlapping regions were captured with different
parallax. This fact limits the applicability of the mentioned approach
especially in the case of thicker samples like paintings on wooden boards
or sculptures. The other scanning approach avoids the parallax problem,
on the other hand it is not suitable for large paintings, since the field of
view is limited by the X-ray beam cone angle and scanning speed is also
slowed due to a lower photon flux.
Fig. 7 shows how surprising results can, in particular cases, be pro
vided by an X-ray inspection of painted artworks. The oil-on-canvas
painting “Holy Family” was borrowed for the X-ray radiographic in
spection from a private collection. The dimensions of the painting were
84 � 65.7 cm and after the X-ray scan, a radiographic image consisting
of approximately 23000 � 18600 pixels – an equivalent of ca. 433
megapixels – was obtained. The presented image was created as an
overlay of the partially transparent X-ray image (grayscale) and optical
photography (color). The X-ray inspection revealed that the landscapeoriented surface motive originating from the beginning of the 20th
century hides another painted motive with portrait-orientation dated to
the baroque period.
The Institute of Experimental and Applied Physics of Czech Technical
University in Prague in cooperation with the Academic Material
Research Laboratory of Painted Artworks of the Academy of Fine Arts in
Prague designed and constructed an X-ray imaging system utilizing
Medipix technology for the scanning of painted artworks (see Fig. 8).
The system consists of a shielded cabinet enclosing two identical frames
with long-range linear motorized stages holding a micro-focus X-ray
tube and a large-area Timepix detector. Both frames move simulta
neously in a mirror-like manner and provide a field of view up to one
square meter. A scanned painting is mounted on a dedicated sample
stage between the scanning frames. The samples can be scanned with a
resolution within the range from 50 to 15 μm due to the fact that both
the SDD and SOD of the system are adjustable.
1.7. Energy-sensitive transmission radiography
Since photon counting detectors in general are operated with one or
more user-adjustable energy thresholds, or in the case of Timepix, can
provide a fully spectroscopic response, these devices can be used for
Fig. 6. An example of a painting scanned as a set of 12 tiles before (left) and after the final assembly (right). Partially overlapping tiles are merged together using
�
image registration techniques. Painting from the 19th century “Cernohorka”,
private collection Prague. Measured at the IEAP CTU micro-CT laboratory equipped
with a Hamamatsu L8601-01 X-ray tube operated at 80 kVp and a large area detector Widepix10�5 (Zemlicka, 2016).
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Radiation Measurements 137 (2020) 106409
Fig. 7. Holy Family, oil on canvas: An overlay of X-ray radiography (grayscale) and optical photography (color) images. The X-ray scan revealed a baroque motive
that was over-painted at the beginning of 20th century. The dimensions of the painting were 84 � 65.7 cm. The final radiography consists of an array of approx
imately 23000 � 18600 pixels – equivalent of almost 433 megapixels. The presented image was kindly provided by Jan Zemlicka (Institute of Experimental and
Applied Physics, Czech Technical University in Prague) and Janka Hradilova (Academic Material Research Laboratory of Painted Artworks). The painting was
borrowed from a private collection.
energy-sensitive or so-called spectral X-ray imaging. In the case of
normal radiography the detector senses changes in the incident beam
intensity. Energy-sensitive radiography, on top of that, resolves changes
in the beam spectrum. The detection and proper interpretation of these
changes can be used for the analysis of the material composition of a
sample as linear attenuation coefficients are energy-dependent and
characteristic for each element.
Spectroscopic imaging is feasible with all detector types belonging to
the Medipix family. Timepix devices can provide a fully spectroscopic
response using the Time-over-threshold mode and proper cluster anal
ysis. However, the ToT mode also brings disadvantages concerning
application in X-ray imaging. A successful cluster analysis requires
sparsely occupied frames without pile-ups. Thousands of such frames are
needed to create an X-ray projection with reasonable statistics.
Considering that the read-out speed of a large area detector is not faster
than 10 frames per second, the exposure time for an X-ray projection of
considerable quality becomes extremely long. Therefore, sequential
scanning of several acquisitions in the Medipix mode with different
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Radiation Measurements 137 (2020) 106409
Fig. 8. X-ray scanning system for the imaging of painted artworks developed by the Institute of Experimental and Applied Physics CTU in Prague and the Academic
Material Research Laboratory of Painted Artworks of the Academy of Fine Arts in Prague. The system consists of two identical motorized frames designed to cover a
field of view of 1 m2 and an adjustable sample holder. The whole set-up is situated in a walk-in shielded cabinet (Zemlicka, 2016).
thresholds can shorten the exposure time significantly. The detected
spectrum can then be divided into several narrow energy bins using the
subtraction of frames with different thresholds.
Fine pixel segmentation of a Timepix chip, which degrades its energy
resolution, can on the other hand be easily used for topology mapping
using fluorescence photons. Once suitable optics is selected and moun
ted in front of the chip, a 2D image based on XRF photons can be ob
tained. The simplest solution can be offered by a pinhole collimator. A
pinhole camera enables projecting a 2D area of the investigated object
with high spatial resolution. The obvious disadvantage of a pinhole
collimator is its low geometric efficiency as just a small fraction of the
emitted photons is accepted. Furthermore, the probability of production
of an XRF photon must be considered. Therefore, the use of intensive
sources and long exposure times are inevitable.
1.8. X-ray fluorescence imaging
The applicability of Timepix detectors in the analysis of cultural
heritage artifacts is not only limited to transmission radiography. The
non-destructive spectroscopic evaluation of the elemental composition
of artwork using an X-ray fluorescence (XRF) is a highly demanded task.
Hand-held devices with a pencil beam and a silicon drift detector for
spectroscopic XRF analysis are available on the market. These devices
provide great spectral sensitivity, hence the ability to clearly identify
various elements (i.e. energy resolution 122 eV FWHM at 5.9 keV in the
case of a spectroscopic camera by AMPTEK (Amptek, 2018)), on the
other hand they are not suitable for making XRF-based topology map
s/images since these devices have been designed just for local analyses.
On the contrary, a Timepix detector, despite the fact that it provides a
fully spectroscopic response, cannot compete with these hand-held
spectrometers by means of energy resolution. The energy resolution of
a Timepix detector with a 300 μm silicon sensor is approximately 3 keV
and, therefore, it is not possible to use it for the direct identification of
the characteristic lines, considering that the energy difference between Z
and Zỵ1 elements is ca. 500 eV. The energy resolution and thus the
capability to resolve the elemental composition of the analyzed object
can, however, be improved under certain circumstances. The per-pixel
response of the whole detector can be calibrated using pure character
istic lines of targeted elements if the a-priori information of the global
elemental composition of the object to be analyzed is available. The
calibration data are then used as base vectors for spectral decomposition
of the later XRF scan. It was demonstrated that elements heavier than
potassium can be identified this way (Tichy et al., 2008; Zemlicka et al.,
2009).
1.8.1. XRF pinhole camera with Timepix
A prototype of a pinhole-based XRF camera was constructed to
evaluate the applicability of Timepix technology for XRF imaging at
IEAP CTU (Zemlicka, 2016). The prototype utilized a RasPIX camera
equipped with a custom-made pinhole collimator with a 100 μm aper
ture. The collimator position was adjustable, so it was possible to align it
with the sensor and also to adjust the distance between the sensor and
thus change the field of view of the obtained image. The XRF camera was
mounted on a shared base plate with a Mini-X X-ray tube and revolver
with a set of aluminum filters dedicated for the modulation of the mean
energy of the X-ray tube spectrum (see Fig. 9).
See an example of the applied use of the camera for the XRF mapping
of technological copies of historic paintings in Fig. 10. The figure shows
a photograph of a ROI of a technological copy of the Gothic period
painting “Epitaph of Margaret” and an XRF map created from photons in
the energy range 10–12 keV where a characteristic L-line of lead is ex
pected. Since lead used to be used as a component of white pigments in
history, the brightest areas of the XRF image are expected to match with
the white areas of the ROI.
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Radiation Measurements 137 (2020) 106409
typically metal based (Fe, Co, Pb, Hg, Zn …). For that reason, XRF
analysis of the surface can provide information of its elemental
composition or reveal previous restorations of the investigated artwork
as organic pigments are usually used nowadays.
2. Imaging applications of Medipix detectors in industry and
material engineering
X-ray CT is usually connected with an imaging and analysis of pro
duction parts in the industrial field. Since those are frequently manu
factured from various types of metal, silicon as a sensor material is
unfortunately inconvenient as its quantum efficiency is very low, above
approximately 30 keV. Novel sensor materials (CdTe, CdZnTe, GaAs)
become extremely useful here as they provide reasonable detection ef
ficiency up to 100 keV. For example a 1 mm thick CdTe sensor provides
detection efficiency higher than 50% for 120 keV photons (Greiffenberg
et al., 2011).
The other extensively developing material engineering field utilizing
X-ray CT is the development of composite parts. Composites are
extremely lightweight and simultaneously durable. Such materials are
highly sought-after i.e. in the aeronautics industry. Micro-CT techniques
can easily reveal an inner imperfection like a delamination of composite
layers etc. Medipix detectors can be very useful in this field due to
energy-resolving capabilities. Energy sensitive X-ray radiography and
CT can visualize the variations in the density of the investigated object
but also provide valuable information on its elemental composition.
That is possible due to the characteristic behavior of the linear attenu
ation coefficient with respect to the energy for all elements or materials.
To distinguish and quantify different materials, dual-energy CT is widely
used in both the industrial and medical field. There are several ap
proaches based on using a pair of sources with a different kVp value and
a pair of detectors, fast kVp switching of a single source or a single
source with a detector consisting of two layers (McCollough et al.,
2015). Photon counting detectors enable further extend these ap
proaches – either by selecting a detection threshold i.e. precisely
matching a searched absorption edge or by a fully spectroscopic
response opening access to so-called spectral imaging. It was already
demonstrated that CT using Timepix technology is suitable for the ma
terial decomposition of metallic-organic composite materials (Pichotka
et al., 2015).
Although the industrial field usually relies on highly attenuating
materials, the ability of Medipix technology to acquire data with
extremely high CNR is profitable in this area as well. The Micro-CT
laboratory at CET, Czech Republic is equipped with an in-house built
high resolution CT system that operates the WidePIX10�10 detector. CET
has published impressive works on the border between medicine and
Fig. 9. Prototype of a pinhole-based XRF camera based on the utilizing of a
RasPIX device, Mini-X tube and a revolver holding beam-modulating filters
mounted on a common plate.
1.8.2. XRF mapping in combination with micro-CT
Recently, an interesting approach putting together X-ray micro-CT
techniques with XRF-based mapping was presented and successfully
demonstrated on a Baroque wooden sculpture (Vavrik et al, 2016,
Vavrik, 2019). The approach is based on measurements of a CT scan
together with X-ray fluorescence photons emitted from the object sur
face. The measurement was carried out at CET using a patented modular
CT scanner called TORATOM equipped with two orthogonally mounted
X-ray tubes (Fila et al., 2015). While the first one was used for the CT
scan, the other one was used for the excitation of XRF photons (see
Fig. 11). The XRF signal was detected using a Timepix-based gamma
camera containing a 300 μm Si sensor and a 1000 μm CdTe sensor ar
ranged into a telescope. The XRF images obtained during the scan were
then mapped onto the surface of the 3D model obtained after the CT data
reconstruction. While the CT-based voxel model provides information
on the inner structures and overall shape of the objects (Fig. 12 left), the
XRF mapping helps to identify the elemental composition of surface
layers (Fig. 12 right). The XRF image targets the elements expected in
the pigments – Fe (Kα 6.4 keV), Zn (Kα 8.64 keV) and Ag (Kα 22.16 keV)
– coded in red, green and blue, respectively.
This approach might be extremely useful i.e. for the analysis of his
toric wooden statues as the one used in the presented proof-of-concept
measurement. Wooden statues used to be typically decorated by a thin
polychrome layer or were sometimes covered by precious metals like
silver or gold. Even the historical pigments used in polychrome are
Fig. 10. XRF mapping of the region of interest (approximately 4 � 4 cm2) of a technological copy of the Gothic period painting “Epitaph of Margaret”. Photo of the
scanned area (left) and an XRF map created from photons with the energy of 10–12 keV where an L-line of lead is expected (right) (Zemlicka, 2016).
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Radiation Measurements 137 (2020) 106409
walls within the GG-BAG sample visualized using the WidePIX10�10
detector in Fig. 13.
2.1. 4D CT
The fourth dimension of a CT scan usually means the employment of
time. It allows the analysis of changes within the investigated object
during a certain time period. The same object is scanned repeatedly in a
series of CT scans and then the differences between individual datasets
are observed. Since each of the datasets consists typically from hundreds
of projections, 4D CT analysis usually places strict requirements on the
scanning time. The basic assumption of a CT scan is that the object is
stable during scanning otherwise motion artifacts are induced. The
temporal sampling should be, therefore, faster than the fastest expected
changes in the object. The Shannon sampling theorem should be obeyed
in the ideal case. Depending on the dynamics of the observed process
each of the CT scans has to be captured within a few seconds or even
faster. A CT scanner suitable for such an approach must fulfill several
requirements. A powerful radiation source is a necessity as a huge
amount of photons has to be delivered in a short time. The detector readout has to be very fast to be able to acquire tens or hundreds of frames
per second. The quantum efficiency of the detector should be as high as
possible. And finally, the speed of the sample rotation stage has to be
considered as well.
Kumpova et al. carried out a 4D CT analysis of the crack development
in samples of concrete at the CT laboratory of CET (Kumpova et al.,
2016b). The modular CT system TORATOM and large-area Time
pix-based detector arranged in a row of 5 chips with a 1 mm thick CdTe
sensor capable of reading out 42 frames per second was used for the
study. The work analyzed the formation and propagation of cracks in
imaged samples during a three point bending test with a continuously
increasing load. Eleven subsequent CT scans with a resolution of ca. 36
μm were acquired. Each scan consisted of 400 angular projections with
the total time of 50 s per scan. The tube was operated at 60 kVp with
96W of output power. After all the datasets were processed and recon
structed, a visualization of differences between subsequent datasets
clearly showed the development of cracks and enabled quantitatively
analyzing properties of the studied material.
Kytyr et al. used the same set-up for on-fly tomography for the
analysis of deformations of GG-BAG bone scaffolds (Kytyr et al., 2017).
In this particular work, a modular Timepix-based detector system with a
Fig. 11. The TORATOM CT system at the Centre of Excellence Telc, Czech
Republic, prepared for the scanning of a polychrome wooden baroque sculpture
using micro-CT and an XRF mapping (courtesy of Daniel Vavrik, Centre of
Excellence Telc).
material engineering focused on the micro-CT analysis of biocompatible
bone scaffolds fabricated from nanoparticulate bioactive glass rein
forced gelan-gum (GG-BAG) and fibrin fibers (Kumpova et al., 2016a;
Vavrik et al., 2018). Since both GG-BAG and fibrin exert very low X-ray
absorption contrast, it is complicated to visualize them using conven
tional X-ray cameras. The work concludes that the used Timepix de
tector provided three times better detail detectability than a flat-panel
detector used for comparison and a spatial resolution of 1 μm was
reached in the case of the fibrin sample. See the microstructure of cell
Fig. 12. Example of an obtained micro-CT slice of the scanned sculpture (left) and volume rendering of the reconstructed dataset with an XRF image mapped on its
surface (right). While the CT data provides information on the overall shape and inner structures of the object, the XRF mapping helps to analyze the elemental
composition of the thin polychrome layer at the surface of the sculpture. The XRF image visualizes the presence of the elements expected in the pigments – Fe, Zn and
Ag – coded in red, green and blue, respectively (courtesy of Daniel Vavrik, Centre of Excellence Telc). (For interpretation of the references to color in this figure
legend, the reader is referred to the Web version of this article.)
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Radiation Measurements 137 (2020) 106409
Fig. 13. High resolution CT scan of a GG-BAG bone scaffold sample scanned with use of WidePIX10�10 detector. The left part shows volume rendering of the whole
sample while the right part presents a transversal slice revealing the fine microstructure of scaffold cell walls in great detail and contrast (courtesy of Ivana Kumpova,
CET Telc, Czech Republic).
fast parallel read-out was used to reach the demanded scanning speed
(Vavrik et al., 2014). Four modular devices were assembled together to
provide a sensor area of 512 by 512 pixels and simultaneously operated.
The samples were mounted in a dedicated loading stage and total of 34
datasets was scanned under a gradually increasing load. The constructed
volumes were then used for digital volume correlation analysis revealing
the dislocations of the inner microstructure. See Fig. 14 illustrating the
amount of the deformation of the sample at four different loading states.
The fastest CT scan performed with a Timepix-based detector was
carried out and published by Vavrik et al. (2017). The paper presents
results of a 4D CT scan of a vitamin C pill being dissolved in water. The
experimental scan was performed again at the CET X-ray laboratory
using a modular Timepix-based detector with parallel read-out capa
bility. The tube was operated at 60 kVp with 50W output power. The
source-to-detector distance was set to 150 mm only to achieve maximal
possible beam intensity. The whole scan consisted of 30000 projections
(3.4 ms exposure time) captured within 2 min while the sample stage
performed 120 revolutions. The data income rate was so high that it was
not possible to write the data directly to HDD. It had to be kept in RAM
and was written to HDD offline after the measurement finished. The data
were then divided into 240 individual CT datasets covering a 180� range
each. Despite the fact that motion blur caused by the continuous
movement of the stage was observed, the dissolving process was suc
cessfully captured. The authors conclude that even much faster CT scans
would be feasible. The scanning rate was limited by the rotation table
speed and beam intensity while the detector itself could have been
capable of capturing data significantly faster.
2.2. X-ray imaging in the time delay integration mode
The time delay integration (TDI) is a newly available operation mode
of Timepix devices potentially useful for scanning of large objects. The
TDI is a read-out principle widely used by CCD scanners dedicated for
the imaging of moving objects. Typically a 1D detector (single row of
pixels) is used. In the case of a Timepix device the TDI mode is suitable
for any configuration of 1 by N chips. Each point of the TDI-obtained
Fig. 14. Visualization of bone scaffold deformation at four different loading states. The displacement field is color-coded using the scale from blue to red pro
portional to the interval 0–1.5 mm dislocation (courtesy of Daniel Kytyr, Institute of Theoretical and Applied Mechanics of the Czech Academy of Sciences). (For
interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
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Radiation Measurements 137 (2020) 106409
image is created as an integration of 256 sub-acquisitions acquired while
the studied object was moving along the detector columns. The
continuous image is created at detector level by shifting the image
matrix by one row after each sub-acquisition is taken.
The TDI successfully suppresses image defects caused by dead or
noisy pixels as each point of the final image is obtained as a sum of 256
sub-acquisitions acquired by different pixels. On the other hand, the
detector has to be perfectly aligned with the object movement direction
and the speed of the object has to be synchronized with acquisition and
read-out time to avoid image blurring. Considering that the first 256
rows of the final image are produced by a various number of integrated
sub-acquisitions, the photon statistic in individual image rows is grad
ually changing. Therefore, the TDI is effective if the scan length is much
larger than the detector height only. Fig. 15 demonstrates the results of
the TDI scan of a laser-cut pattern in a thin steel plate (Zemlicka, 2016).
So far, the TDI mode has been successfully tested and is awaiting
further application use. An obvious field of use can be found in the online inspection of objects on a running belt (i.e. at airports, or in
factories).
mentioned fields obtained using Medipix2 and Timepix devices were
demonstrated in this paper. Timepix-based detectors provide, thanks to
the dark-current-free quantum counting, X-ray images with exception
ally high contrast-to-noise ratio. The steep point-spread function makes
these detectors an ideal choice for high-resolution applications. And
energy-resolving capabilities open the way to material recognition
based on advanced imaging techniques like dual-energy or spectral
radiography and CT or XRF-based imaging. Such a set of features
simultaneously provided by a single device is very unique and, there
fore, Timepix detectors are very versatile tools capable of covering a
wide range of imaging applications. Despite this, Timepix technology is
still mostly used in experimental science and is gradually finding its way
into the commercial field. There are several companies on the market
cooperating with the Medipix collaboration on further development of
the technology and selling devices in a variety of different versions.
Medipix and Timepix detectors have also already been utilized in
commercially available X-ray imaging systems in several cases. Beside
RayScan Nano, mentioned in section 2.3 of this paper, a spectral CT
scanner MARS (Medipix All Resolution System) for small animal imag
ing was introduced by the University of Canterbury, New Zealand
(MARS, 2019), and Fraunhofer IIS developed a compact and lightweight
micro-CT system called CT-Portable (2018).
Performance of the latest available generation – Timepix3 – was not
demonstrated in this paper, since wider experience and the applied re
sults of using Timepix3 for X-ray imaging has not been published yet.
The device is used mostly for particle tracking taking advantage of a new
mode providing simultaneous information on the position and time
stamp of an event. X-ray imaging can profit from faster data read-out,
lowering the minimal detection threshold and improved spectroscopic
capabilities provided by Timepix3.
The Timepix4, currently still under development, promises to bring a
smaller pixel pitch and 4-sides buttable chips. Especially the second
feature will be extremely important for X-ray imaging, since the
assembling of large-area gap-less detector arrays will become much
easier. The development of sensor materials proceeds simultaneously
with chip electronics. Silicon is still very popular, nevertheless, the
quality of sensors manufactured from semi-insulating materials con
taining high-Z elements like CdTe, CdZnTe, GaAs, etc. is better and
better. Such sensors should overcome the main limitation of silicon – its
low quantum efficiency for higher energies.
Photon counting detectors are on the rise. The application range is
becoming constantly wider thanks to its versatility and imaging per
formance. As a relatively new detection technology, it is still under
intensive development and the detectors have gradually changed from
3. Conclusions and outlook
The aim of the previous chapters was to briefly introduce the prin
ciples of high resolution X-ray imaging and present recent applications
of hybrid pixel photon-counting detectors of the Medipix family in this
field. The range of applications is constantly increasing along with the
progress of the technology itself, which is still under intensive devel
opment, and significantly exceeds the scope of this paper. X-ray imaging
is just one field of science where Medipix technology has been
employed. The Medipix device has grown from a chip carrying 4096
pixels (64 � 64 pixels) to large-area detectors with more than 6.5
megapixels (2560 � 2560 pixels). Apart from the increase of the detector
area, development has also been focused on building different advanced
detection geometries like multiple-layered particle tracking telescopes
or Compton cameras. New application areas have appeared as these
upgrades have been coming. Timepix devices are still used at the Large
Hadron Collider at CERN and for other high-energy physics experiments.
But due to its versatility, Timepix technology has also found its way into
satellites for the monitoring of radiation belts in outer space, to lowbackground underground laboratories searching for double beta decay
and other rare events or even to schools for educational use.
Concerning X-ray imaging, Medipix and Timepix technology have
been proven to be a highly useful tool in life sciences, material engi
neering and cultural heritage. Interesting applied results from the
Fig. 15. Laser-cut stainless steel pattern used for the testing of the TDI mode (left) and its X-ray radiography obtained this way (right). The intensity gradually
increases at the beginning of the scan as the number of rows used for integration raises. A slight blur can be observed at the end of the scan as the motorized stage
decelerated. Both effects can be avoided by continuous scanning (courtesy of Jan Zemlicka, Institute of Experimental and Applied Physics, Czech Technical University
in Prague).
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Radiation Measurements 137 (2020) 106409
experimental devices to easy-to-use and reliable cameras for highresolution X-ray imaging. And as energy-sensitive computed tomogra
phy becomes a highly demanded technique with potential use in in
dustry, life sciences and also in medicine it can be expected that photon
counting detectors will gain an important and stable position in the field
of X-ray imaging.
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Acknowledgements
This article was written in the framework of Medipix collaboration
and has been funded by European Regional Development Fund No.
CZ.02.1.01/0.0/0.0/16_019/0000766 “Engineering Applications of
Microworld Physics”.
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