High-resolution X-ray imaging applications of hybrid-pixel photon counting detectors Timepix

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.

Available online 8 June 2020

1350-4487/© 2021 The Author Published by Elsevier Ltd This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

High-resolution X-ray imaging applications of hybrid-pixel photon counting

detectors Timepix

Jan Dudaka,b,*

aInstitute of Experimental and Applied Physics, Czech Technical University in Prague, Husova 240/5, 110 00 Prague, Czech Republic

bFaculty 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

Keywords:

Photon counting detectors

X-ray imaging

X-ray radiography

Computed tomography

A B S T R A C T 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

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

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

time-of-arrival of each detected particle or position-sensitive spectro-scopic measurement as the energy of detected particles can be directly

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: jan.dudak@cvut.cz

Radiation Measurements

https://doi.org/10.1016/j.radmeas.2020.106409

Received 19 February 2019; Received in revised form 20 September 2019; Accepted 3 June 2020

radiography Medipix3 was designed with two user-adjustable energy

thresholds per pixel and with on-board processing addressing the issue

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

et al., 2015) Timepix4, currently under development, promises to

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

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 read-

out chips interconnected using bump-bonding technology The hybrid-

pixel 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 bump-

bonded to a common semiconductor sensor The Quad uses the layout of

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 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

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

chips to produce a continuously sensitive area of approximately 14 by

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.)

allowing the signal to be read out using copper-filled holes passing

through the chip

1.1 High resolution X-ray imaging with a laboratory set-up

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

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

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-of-

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

already commercially available on the market including one system utilizing Medipix technology

1.2 High resolution X-ray imaging in cone-beam geometry

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

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 propro-jections 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

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

An example of a CT scan carried out with sub-micrometer resolution

foraminifera sample (foraminifera are single-celled marine organisms

which have inhabited the Earth for more than 500 million years)

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

1.3 Advantages of Medipix technology in the field of high-resolution X-

ray 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

experimental imaging systems and has not been widely used in commercially available devices yet Nowadays, considering X-ray

used detector technology is a CCD (charge-coupled device) chip with a thin scintillation sensor Such cameras provide extremely high pixel

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

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

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)

Fig 4 Example of a high-resolution CT scan

of a sample of foraminifera performed with a WidePIX4�5 detector and the FeinFocus FXE- 160.51 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)

comparable resolution as the X-ray CCD camera CRYCAM (Tous et al.,

pixels provided a spatial resolution of 10.69 lp/mm (line pairs per

resolution of 13.44 lp/mm A similar experiment was later repeated

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

pixels) It was also demonstrated that the steep PSF of Timepix detectors

enables improving detail detectability within the reconstructed CT data

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

scanned with a large area Timepix detector and an X-ray CCD camera

(Fig 5 right)

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

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

achieved focal spot size of the source was 50 nm as the thickness of the

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

resolution scanner capable of performing a CT scan with EPS within 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

(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

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 X- rays 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

1.6 Large area scanning

The routine use of Medipix technology for the imaging of painted artworks has become practically possible with the introducing of large- area 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)

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

“�Cernohorka” (dimensions of 22 by 28 cm) was scanned in 12 tiles using

The final radiography can easily consist of hundreds of megapixels as

the dataset is formed typically of several tens or even hundreds of sub-

acquisitions 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 landscape- oriented 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

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

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)

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

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

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

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

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

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 Zþ1 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

2009)

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

1.8.1 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

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

See an example of the applied use of the camera for the XRF mapping

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

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)

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

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

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

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

XRF mapping helps to identify the elemental composition of surface

– 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

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

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

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

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

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

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)

material engineering focused on the micro-CT analysis of biocompatible

bone scaffolds fabricated from nanoparticulate bioactive glass

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

reached in the case of the fibrin sample See the microstructure of cell

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 read- out 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

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

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

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)

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.)