AAAS

Research
Volume 2021, Article ID 9892152, 18 pages
https://doi.org/10.34133/2021/9892152

Review Article
Recent Development in X-Ray Imaging Technology: Future
and Challenges

Xiangyu Ou ,1 Xue Chen,2 Xianning Xu ,2 Lili Xie,1 Xiaofeng Chen,1 Zhongzhu Hong,1
Hua Bai ,2 Xiaowang Liu ,2 Qiushui Chen ,1,3 Lin Li,2 and Huanghao Yang 1,3
1
MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University,
Fuzhou 350108, China
2
Frontiers Science Center for Flexible Electronics, Xi’an Institute of Flexible Electronics (IFE) and Xi’an Institute of Biomedical
Materials & Engineering, Northwestern Polytechnical University, 127 West Youyi Road, Xi’an 710072, China
3
Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China, Fuzhou 350108, China

Correspondence should be addressed to Hua Bai; [email protected], Xiaowang Liu; [email protected],

and Huanghao Yang; [email protected]

Received 4 September 2021; Accepted 23 November 2021; Published 26 December 2021

Copyright © 2021 Xiangyu Ou et al. Exclusive Licensee Science and Technology Review Publishing House. Distributed under a
Creative Commons Attribution License (CC BY 4.0).

X-ray imaging is a low-cost, powerful technology that has been extensively used in medical diagnosis and industrial
nondestructive inspection. The ability of X-rays to penetrate through the body presents great advances for noninvasive imaging
of its internal structure. In particular, the technological importance of X-ray imaging has led to the rapid development of high-
performance X-ray detectors and the associated imaging applications. Here, we present an overview of the recent development
of X-ray imaging-related technologies since the discovery of X-rays in the 1890s and discuss the fundamental mechanism of
diverse X-ray imaging instruments, as well as their advantages and disadvantages on X-ray imaging performance. We also
highlight various applications of advanced X-ray imaging in a diversity of fields. We further discuss future research directions
and challenges in developing advanced next-generation materials that are crucial to the fabrication of flexible, low-dose, high-
resolution X-ray imaging detectors.

1. Introduction scattering [7]. Their ratios are determined by both the nature
of the matter and the energy of incident X-rays. Typically, in
X-rays are a type of ionizing radiation with a wavelength a low-energy X-ray region, X-ray photons are mainly
ranging from 0.01 to 10 nm [1, 2]. When X-rays travel absorbed by the object through the photoelectric effect, while
through a matter, they are transmitted, absorbed, or scat- the Compton scattering is dominant in low-Z materials and
tered. The processes of scattering and absorption depend high-energy photons [8, 9].
on the attenuation ability of the matter and are governed The excellent penetration ability of X-rays has made X-
by Lambert-Beer’s Law (eq. (1)): ray imaging a powerful medical imaging modality [10].
The advances in X-ray imaging have stimulated the progress
I = I o e−ud , ð1Þ in diagnostic radiography technologies, physically describing
the skeleton, including fractures, luxation, bone disease, and
where I is the intensity of transmitted X-ray photons, I o is the location of foreign matters [11, 12]. Such imaging infor-
the initial intensity of X-ray photons, μ is the linear attenu- mation is particularly useful for guiding the surgery [13].
ation coefficient, and d is the thickness of the matter [3–6]. Apart from the medical applications, X-ray imaging is fur-
The attenuation ability is dominated by a combination of ther extensively used for nondestructive industrial and safety
the photoelectric effect, Compton scattering, and Rayleigh inspection [14]. Undoubtedly, the development of X-ray
2 Research

(a) Anode
(Tungsten
filament) X-rays

Energetic
electrons Signals processing

Cathode
Imaging area
X-ray generator Detector X-ray image

(b)

Period of film-screen radiography Period of digital radiography

Chemical Digital
processing detector ADC DAC
X-ray pattern Image X-ray pattern Analog signal Digital signal Image

The discovery Glass plates Cellulose Automatic The fisrt Fujifilm patented Amorphous silicone-cesi-
of X-rays and for radiogra- acetate-based film generation of the process of um iodide (or gadolinium)
the landmark phy requiring film with processor computed photostimulated flat-panel detector and
of high X-ray imporving was tomography phosphor for obtain- selenium-based flat-panel
radiography exposure fire safety produced came out ing radiography detector were introduced

1890s 1900s 1910s 1920s 1930s 1940s 1950s 1960s 1970s 1980s 1990s 2000s Present

Calcium tungstate Flexible flim Fujifilm first High-efficient nanocrys-

X-ray flim with Wireless
for fluoroscopy and based on cellulose commercialized tals-based FPD coupled
blue tinted base to flat-Panel
double emulsion nitrate base and computed with imaging informat-
improve the digital
coated films were films were placed radiography in ics including AI, ML,
viewing comfort detectors
produced in the cassete 1983 BD.

Figure 1: (a) Schematic illustration of an X-ray imaging system. The system constitutes an X-ray generator and an X-ray detector with a
signal processing system. X-ray beam produced by the X-ray generator passes through the object (e.g., patient’s chest) to arrive at the X-
ray detector, followed by the signal processing to produce a visible image. (b) The development of X-ray radiography with the evolution
of X-ray detectors. The development can be mainly divided into film-screen radiography and digital radiography. The film-screen
radiography converts a latent X-ray pattern into a visible image through tedious chemical processing, whereas digital radiography goes
through a series of signal conversions to obtain the X-ray image. ADC: analog-to-digital conversion; DAC: digital-to-analog conversion;
AI: artificial intelligence; ML: machine learning; DB: big data.

imaging for over a century has promoted the advancement X-ray spectrum is affected by accelerating voltage, filament
of a wide range of disciplines from fundamental researches heating voltage and current, and cathode materials.
to practical applications. The X-ray imaging system converts the X-ray photons
An X-ray imaging system typically comprises an X-ray transmitted from the object into a visible image that can be
generator and an X-ray imaging detector (Figure 1(a), left used for evaluating the internal structures. The X-ray detec-
panel) [15]. The X-ray generator is made of two electrodes tor is placed behind objects to record the transmitted X-rays
sealed into an evacuated chamber. Once powered on, the for producing an X-ray pattern (Figure 1(a), right panel).
cathode made of tungsten filament can produce energic elec- This pattern is subsequently converted into a visible two-
trons through a thermionic effect when it is heated to 2200°C dimensional (2D) radiographic image or three-dimensional
by the electric current. When an accelerating voltage is radiographic image through tomography. Finally, the
applied, X-rays are produced during energy changes of contrast-based X-ray images are generated based on the
fast-moving electrons when they collide and interact with attenuation difference of the objects within the matter
the anode material under a vacuum. The lost energies are towards X-rays [18–20].
converted into bremsstrahlung and characteristic X-rays. In this review, we give a detailed overview of the recent
Typically, 80% of the X-ray photons emitted by the diagnos- development of X-ray imaging technologies, including
tic X-ray generator are bremsstrahlung [16, 17]. The output film-screen radiography and digital radiography, according
Research 3

X-rays X-rays
X-rays Scintillators
Protective layer

Absorption coefficiency
screen CaWO4
Phosphor layer 1 mR

Relative photon flux

Reflecting or
absorbing layer 50 mR Light 100 kV
Intensifying screen Substrate Film Gd2O2S

Protective layer Equivalent

Back panel Emulsion images
Adhesive
X-ray film cassette
Substrate 60 kV
X-ray film Intensified radiography 0 20 40 60 80 100
Photon energy (keV)
(a) (b) (c)

Sensitivity center

Br– e- Film in
Ag+ Ag+ Ag+ X-rays
Ag+ 3.5 Shoulder region
Br- Br– Exposure e e–
–
(Overexposure)
–
Br e- 3.0
Ag+ Ag+ Ag+ Ag+
Ag+ Br– Ag+ e– 2.5

Film optical density

AgBr crystal Straight line region
2.0 (Normal exposure)
e– Ag+ e–
1.5
e– Ag+ e– Ag+
e– e– 1.0
e– Ag+ e– Ag+ Toe region
Ag+ 0.5 (Underexposure)
+
Ag+ Ag Base plus fog density

Latent image Developer Fixer Wash Dry Log relative radiation exposure

X-ray film chemical processing

(d) (e) (f)

Figure 2: Film-screen radiography system. (a) Scheme of an X-ray film cassette and profiles of intensifying screen and X-ray film. The
lightweight film cassette made of metal materials features a carbon fiber protective shield, intensifying screens, X-ray film, and a back
panel. (b) The comparison of X-ray film direct exposure to X-rays (left) with that of X-ray film in combination with a scintillators
screen. (c) X-ray absorption spectra of gadolinium oxysulphide (GOS, red), calcium tungsten (CaWO4, orange), and X-ray emission
spectra of 60 kV (sky blue) and 100 kV (dark blue) X-rays. The atomic number of rare-earth elements ranges from 57 to 70 with the K
-edge between 39 and 61 keV. (d) Upon X-ray irradiation, the free silver ions aggregate in negatively charged sensitivity centers to
acquire an electron, forming the latent image region. (e) The latent image in the film was converted into the visible image through
photochemical processing including development, fixation, washing, and drying. (f) The characteristic curve of the film-screen system in
response to X-ray exposure, which can be divided into three parts including the toe region (blue), the straight-line region (yellow), and
the shoulder region (red). Notably, base plus fog is the background intensity of the unexposed film produced by accident light
irradiation. The optical intensity is a function of X-ray exposure plotted on a logarithmic scale. (a) is reprinted with permission from ref.
[21], copyright 2013 Author. (c) is reprinted with permission from ref. [22], copyright 2008 Elsevier Ltd. (f) is reprinted with permission
from ref. [23], copyright 2019 Elsevier Springer Nature Singapore Pte Ltd.

to the evolution of X-ray detectors in the imaging system. In light-sensitive emulsion show great promise in radiography,
each section, we start with a description of the structure of they are fragile, heavy, expensive, and difficult for operation
the device and the corresponding working principle. The and storage.
advantages and disadvantages of each X-ray imaging system The challenges in radiographic plates promoted the
are further discussed. This review is ended with a perspective development of substitutive substrate materials with flexibil-
on the further development direction of X-ray radiography. ity, portability, transparency, and relative thinness. The pho-
tographic film consisting of cellulose nitrate and emulsion
2. Film-Screen Radiography was first developed to replace the glass plate. Since the cellu-
lose nitrate was flammable, nonflammable cellulose triace-
2.1. Substrate Materials. The first X-ray image was taken by a tate materials such as polyester materials were used for X-
radiographic plate several months after the X-rays discov- ray film instead [25].
ered by Röntgen, where the finger bones and the ring of
his wife were clearly imaged [24]. The radiography mani- 2.2. X-Ray Film and Cassette. As illustrated in Figure 2(a),
fested its original application in medical diagnosis and was the X-ray cassette has a flat, lightproof metal box consisting
further used for the identification of jewelry and art collec- of an intensifying screen and a radiographic film. The top
tion and nondestructive detection of metallic objects in the protective layer made of opaque carbon fiber shows nearly
industry soon. Although photographic plate-based X-ray no radiation absorption. The back layer of the cassette utiliz-
detectors made of a glass plate coated with a thick layer of ing a thin layer of lead with an atomic number of 82 is
4 Research

designed to avoid potential backscattered radiation from the mulate to form photosensitive spots, thereby forming a
transmitted X-rays [21]. The X-ray film consists of the pro- latent image (Figure 2(d)).
tective layer, emulsion, adhesive, and polymer substrate. The After the X-ray film exposure, it was chemically proc-
substrate is coated with a thick layer of photosensitive emul- essed to obtain a visible image that can be displayed by
sion on both sides to increase the X-ray absorption for mit- transillumination on an appropriate view box for further
igating blurring. Typically, the emulsion layer is made of evaluation. As shown in Figure 2(e), this processing involves
innumerable silver-halide compounds mixed with gelatin development, fixation, washing, and drying. [31]. During a
material [26, 27]. However, the sensitivity of X-ray imaging typical development process, electrons from the developer
is very limited when the emulsion is directly exposed to X- migrate to sensitized grains and convert the silver ions into
rays, and this is largely attributed to its low X-ray absorption black silver particles to form a visible image on the film.
efficiency. After leaving the developer solution, the unexposed silver
bromide on the film is dissolved and removed in the fixer
solution containing acetic acid and sodium thiosulfate. At
2.3. Intensifying Screen and Its Composition. Although silver
the same time, sodium sulfite and aluminum chloride in
halide crystals can be directly exposed by the X-rays, a high
the fixer solution are used as a preservative and a hardener,
dosage of X-rays with a risk of irradiation damage is
respectively. Finally, the processed film is washed to remove
required for qualified X-ray imaging. To reduce the radia-
the fixer solution through a water bath and dried in a cham-
tion dose, a fluorescent intensifying screen made of scintilla-
ber in which the hot air is circulating [32].
tors was introduced for converting X-rays into ultraviolet to
visible (UV-Vis) light to sensitize the radiographic film [28].
Figure 2(b) indicates that a radiographic film coupling with 2.5. Characteristic Curve of a Radiographic Film. The perfor-
an intensifying screen substantially decreases the X-ray mance of an X-ray film is strongly related to the radiation
exposure as compared to exposing the radiographic film exposure on a logarithm scale. Contrast is the difference in
directly. Of which, 95% of the silver halide crystals are effi- luminance or color, making an object distinguishable. For
ciently reduced via the visible light produced by intensifying a specific radiographic film, the contrast depends on the
screen, and the remaining are reduced by the direct interac- design of the film, the amount of exposure, and the chemical
tion with X-rays. processing conditions. As described in Figure 2(f), there are
The scintillators act as the energy mediator for intensify- three different regions in the characterization curve includ-
ing screens, and thus their performance plays a significant ing the toe region (blue), straight-line region (yellow), and
role in determining image quality. Over the decades, high- shoulder region (red) from the bottom to the top. The toe
quality scintillators are developed to reduce X-ray exposure. and shoulder regions with shallow slopes correspond to
Calcium tungstate (CaWO4), a class of scintillator emitting underexposure and overexposure, respectively. The overex-
blue light under X-ray exposure, is utilized for X-ray energy posed image in the shoulder region implies that the silver
conversion by Thomas Edison thanks to its strong X-ray ions have been reduced to silver atoms, whereas the image
stopping power and high X-ray scintillation efficiency. How- will be underexposed and generally useless in the toe region.
ever, the absorption coefficiency of CaWO4 is not optically The normal exposure region is the nearly straight-line por-
matched to the spectra at 60-100 keV X-rays, as demon- tion where a well-exposed image is produced (with a density
strated in Figure 2(c) [22]. The development of scintillators between 0.5 and 2.75) [23].
with improved absorption in low X-ray energy is desired.
Rare-earth-activated materials with high atomic numbers
in the range from 57 to 70 (K-edges between 39 and 3. Computed Radiography
61 keV) exhibit high X-ray attenuation and scintillation effi-
3.1. Substitution of Film-Screen Radiography by Computed
ciency, such as lanthanum bromide oxide, lanthanum oxy-
Radiography. Although conventional film-screen radiogra-
sulfide, and GOS. A rare-earth-based scintillating screen
phy has contributed extraordinarily to medical diagnosis
has a low radiation dosage of about 2-3 times less than the
and industrial inspection since 1895, it suffered from several
CaWO4 screen with superior X-ray image quality.
limitations, including complicated chemical processing, low
automatic processing efficiency, high costs of film materials,
2.4. Chemical Processing for the Radiographic Film. The time and labor consumption, inconvenient images storage
chemical process to capture an X-ray image using a radio- and communications, and environmental pollution
graphic film involves the formation of a latent image and [33–35]. To this end, digital radiography was developed to
then developing an X-ray image [29, 30]. Silver-halide crys- replace film-screen radiography. This new technology
tals have a cubic phase structure with lattice points occupied involves using a digital detector to convert X-ray patterns
by negatively charged bromide (or iodide) ions and posi- into digital signals which are subsequently processed and
tively charged silver ions. The silver halides absorb the pho- displayed on the screen for observation. It mainly comprises
ton energy of visible light or X-rays and release electrons to imaging acquisition, laser stimulation, electric signal pro-
form electron-hole pairs, and the released electrons combine cessing, image display, postprocessing, storage, and commu-
with silver ions in the photosensitive center composed of nication components [36]. In addition, when compared with
defects (point defects, dislocations, etc.) in the crystals to film-screen radiography (FSR, blue dotted line), computed
produce neutral silver atoms. As a result, silver atoms accu- radiography shows an improved linear exposure range
Research 5

Reflecting mirrior PMT

FSR
Log grey scale value Laser source Light guide

Optical density
Electrical signal

Focusing lens
ADC

CR
Imaging plate Digitization
10:1 (approx)
Roller
1 10 100 1000 10000
Log relative radiation exposure
(a) (b)

(I) X-rays
Protective layer
Phosphor layer Gd2O2S:Tb
Electroconductive
BaFBr:Eu

Absorption coefficiency
layer
Support layer CsI:Tl
Light shield layer

(II) (III)

10 30 50 70 90 110 130
Photon energy (keV)
(c) (d)

e– e– e– Light stimulation Conduction band

Excited state
X-rays
e– e– Transfer
Electron trap Latent image Electron trap
Recombination
Luminescence
Hole trap Hole trap Ground state
luminescent center
Valence band
Radiation storage process Photo-stimulated luminescence process

(e)

Figure 3: Computed radiography and its imaging mechanism. (a) The characteristic exposure curve of film-screen radiography (FSR, blue
dotted line) and computed radiography (CR, red line). The film-screen radiography shows a linear exposure range of 10 : 1, and the digital
radiography shows a linear exposure of 104 : 1. (b) Schematic diagram showing a typical computed radiography reader system and the
corresponding image readout process. (c) Schematic diagram of the cross-section of the imaging plate (I). Scanning electron microscope
(SEM) image of the structured (III) and unstructured (II) phosphors. (d) X-ray absorption spectra of thallium-doped cesium iodide (CsI:
Tl, green), terbium-doped gadolinium oxysulphide (GOS: Tb, orange), and europium-doped barium fluobromide (BaFBr: Eu2+, blue) as
a function of X-ray photon energy. (e) The physical process of photostimulation using BaFBr: Eu2+ phosphors. It can be divided into
two steps, including radiation storage (light yellow) and photostimulated luminescence (light blue). The X-rays penetrating the object are
absorbed by phosphors, creating a lot of electron-hole pairs, which subsequently migrate to emitting centers or are captured by
metastable energy traps. Electrons and holes in the metastable energy traps absorb low-energy laser irradiation to overcome the energy
barrier, escaping from the traps, followed by recombination at emitting centers to generate photostimulated luminescence. (a, b) are
reprinted with permission from ref. [38], copyright 2007 Elsevier Ltd. (d) is reprinted with permission from ref. [41], copyright 2007
American College of Radiology.
6 Research

(104 : 1), suggesting a wide range of radiation exposure can also be used as phosphors in imaging plates benefitting
(Figure 3(a)) [37, 38]. from their easy preparation in the form of a needle-like
structure array, the quick latent image loses (tens of seconds)
3.2. Image Readout Process of Computed Radiography. Com- limit their further use for computed radiography systems
puted radiography, firstly introduced by Fujifilm in 1983, is a (Figure 3(c), (I)).
technology on the basis of recording the latent image in a The commercial materials for the phosphor layer are
photostimulable phosphor-contained imaging plate through BaFBr: Eu2+ and CsBr: Eu2+ (Figure 3(c), (II)). Trace
laser-light stimulation [39, 40]. A computed radiography amounts of Eu2+ activators are doped to replace Ba2+ ions
system mainly comprises two components, including an in the crystal to form the luminescent centers. Such a doping
imaging plate and a computed radiography reader. They treatment can alter the structure and consequently the phys-
are designed to store the latent image of the X-ray attenua- ical properties of the photostimulated phosphors [44, 45]. As
tion pattern in the imaging plate and to read out the stored compared with the rare-earth-based materials used in the
latent image through the reader, respectively. On a separate screen system, BaFBr: Eu2+ shows efficient X-ray absorption
note, the computed radiography reader (point-scan, laser in the range from 35 to 50 keV because of low K-edge
flying spot) consists of a set of subcomponents, such as the absorption of barium, as presented in Figure 3(d). Beyond
stimulating laser source, reflecting mirror, light collection this range, either GOS:Tb phosphors or CsI: Tl phosphors
guide, and photomultiplier tubes (PMT) [38]. display better performance, allowing their widespread appli-
During a computed radiographic imaging process, an X- cation in indirect flat-panel X-ray detectors or optically
ray attenuation pattern transmitted from the object is stored coupled digital radiography systems [41, 46].
in photostimulable phosphors embedded into the imaging
plate, leaving a latent image [42]. Then, a laser raster scan- 3.4. The Mechanism of Photostimulated Luminescence. The
ning can be used to read out the stored imaging information possible energy transfer mechanism inside the photostimu-
through releasing the photostimulated luminescence using lated phosphors is illustrated in Figure 3(e). The in situ gen-
photomultiplier tubes. Thereafter, in situ generated lumines- erated electron-hole pair concentration within phosphors is
cence signals were converted to electric signals for generat- proportional to the absorbed radiation energy of the host lat-
ing high-quality images by an analog-to-digital converter tice. In addition, X-ray patterns transmitted from the object
(Figure 3(b)). The imaging plate can be repeatedly used by could interact with halide ions to displace them into intersti-
removing the residual energy within the phosphors through tial host sites, thus creating halide ion vacancies and intersti-
intense laser light [43]. However, the residual energy in the tials. Electrons and holes are captured by traps, leading to
imaging plate cannot be completely erased since it is hard the formation of latent images. Subsequently, the electrons
to release all the trapped energy in phosphors by a laser and holes can spontaneously escape from the traps at ambi-
scanning. It is essential to extend the erasure time and ent conditions, resulting in the gradual deterioration of the
increase the erasure cycle to eliminate all the residual energy storing energies. When the scanning laser light is applied,
for further use. the carriers trapped in the defects absorb enough energy
from stimulation light to overcome the energy barrier, mov-
3.3. The Composition of the Imaging Plate and the Property ing freely in the crystal until the occurrence of recombina-
of Phosphors. In computed radiography, an imaging plate tion to release their energy to luminescence centers (e.g.,
is used to replace the intensifying screen and photographic Eu2+) accompanied by emitting the light-stimulated lumi-
film. As shown in Figure 3(c), the protective layer on both nescence. At last, the carriers still trapped should be effec-
sides prevents the imaging plate from being scratched, tively excited to empty residual energy to prevent the
ensuring the durability of the imaging plate and allowing generation of a ghost image in the next use [47, 48].
laser transmission. The phosphors layer, which can store
the latent image, is made of phosphors mixed with a poly- 4. Flat-Panel Detector-Based Radiography
mer binder. The electroconductive layer prevents the image
quality from degrading by static electricity. The support 4.1. The Origin of Flat-Panel-Based Digital Radiography.
layer in the middle endowed the imaging plate with a certain With the advancement of photolithography and microelec-
mechanical strength. The backscatter radiation is blocked by tronic fabrication technology, large-area, flat-panel-based
the light shield layer with a lead backing. digital radiography was developed in the early 1990s [49].
Regarding the phosphors within the imaging plate, there Digital radiography technology converts the incident X-ray
are three prerequisites: first, the emission of the phosphors is photons into electrical charges and reads the images using
required to overlap with the maximum quantum efficiency photoelectric conversion arrays, displaying a faster readout
wavelength of the photomultiplier; second, the irradiated time than computed radiography [50]. Low-dose, real-time
phosphors should exhibit a fast response to the laser scan- X-ray imaging using flat-panel detectors has been widely
ning for fast imaging; third, no significant signal deteriora- used for clinical diagnosis, including chest X-rays, dental
tion for at least 8 h is required for practical use. However, X-rays, mammography, and lumbar spine X-rays. Digital
there are almost no phosphors that can simultaneously sat- radiography is also used in industrial inline nondestructive
isfy the above three aspects at the same time. Among them, inspection, such as high-resolution analysis of circuit boards
BaFX: Eu2+ (X = Cl, Br, or I) phosphor family has been for solder joint porosity measurements and defects detec-
extensively studied. Although RbBr: Tl+ and CsBr: Eu2+ tion. Moreover, digital radiography has been widely used
Research 7

Top electrode
X-rays
++++
Scintillator
Scintillator
Pixeled α-Si α-Se
Blocking layer
Light TFT
TFT
Optical lens
Light Charge amplifier
Data line Glass substrate
Indirect conversion TFT arrays Direct conversion
Charge-coupled device array
(a) (b)

X-ray 1

Contrast
Modulation transfer function

0.8

0.6 MTF SNR

Unstructured scintillator DQE

0.4
X-ray

0.2 Resolution Noise

Direct
Indirect
0 WS
Structured scintillator 0 1 2 3
Spatial frequency (lp/mm)

(c) (d) (e)

Figure 4: Flat-panel-based digitized radiography and the technical factors influencing imaging quality. (a) Schematic illustration of an
optical len-coupled indirect conversion digitized radiography system based on a charge-coupled device. The incident X-rays are
converted into UV-Vis light by the scintillators and further into electric signals after being focused by an optical lens and directed to the
charge-coupled device array. (b) The schematic illustration of the internal construction of a flat-panel detector (middle panel), which
could be classified into indirect conversion flat-panel detector (left panel) and direct conversion flat-panel detector (right panel) based on
the X-ray energy conversion modality. For indirect conversion, X-rays transmitting through the scintillator (purple) are converted into
UV-Vis light, which is further converted into an electrical charge by the pixelated amorphous silicon photodiodes (α-Si; violet), whereas
X-ray photons are directly converted into electrical charge in a direct conversion detector. TFT: thin-film transistor. (c) The schematic
diagrams (left panel) and line spread function (right panel) of the unstructured and structured scintillators. The X-ray-induced visible
luminescence in the unstructured scintillators exhibits a severe scattering in all directions to reduce the imaging spatial resolution,
resulting in a wide line spread function. The structured scintillators consist of phosphors in a needle-like structure in favor of reducing
the lateral scattering of light, contributing to a narrow line spread function. (d) Comparison of the modulation transfer function (MTF)
for direct conversion flat-panel detector (red) and indirect conversion flat-panel detector (blue). (e) Relationships between image quality
parameters, including detective quantum efficiency (DQE), modulation transfer function (MTF), signal-to-noise ratio (SNR), and Wiener
spectra, and physical image measurements, including contrast, resolution, and noise. Panel (a) is reprinted with permission from ref.
[51], copyright 2007 RSNA. Panel (c) is reprinted with permission from ref. [56], copyright 2011 American Institute of Physics. Panel (e)
is reprinted with permission from ref. [57], copyright 2008 Elsevier Ltd.

in X-ray security scanners in train stations and airports for reduce the number of photons reaching the charge-coupled
the screening of dangerous goods and prohibited items. device arrays, which may result in low quantum efficiency
The charge-coupled device-based detector appeared in and high image noise, and thus lead to poor image quality.
1990 was the first large-area flat-panel-based radiography. Meanwhile, the optical coupling may also cause geometric
A charge-coupled device is made of metal-oxide- distortions and light scattering and consequently a reduced
semiconductor capacitors as a light-sensitive sensor for imaging spatial resolution. Besides, high-working tempera-
recording images. In general, a large number of charge- tures give rise to signal noise within the charge-coupled
coupled devices are coupled to create a detector array for device itself, deteriorating the image quality. Although the
large-area detection. The incident X-ray photons can be con- electric cooling charge-coupled device could alleviate this
verted into visible luminescence by scintillators (e.g., CsI: Tl, effect, it has an unacceptably high cost. In addition, the size
and GOS: Tb). Next, the luminescence is directed to the limitation of the charge-coupled device and the optical cou-
charge-coupled device array using an optical lens system pling method make it rigid to fabricate a large-area X-ray
(Figure 4(a)) [51, 52]. However, the optical lens system can detector [53].
8 Research

4.2. Evolution of Thin-Film Transistor Array-Based Digital which improves the spatial resolution, making unstructured
Radiography. By contrast, flat-panel detectors with large- scintillators superior to that achieved by the structured scin-
area photoelectric arrays allow the integration with an X- tillators, as illustrated in Figure 4(c) [56, 66, 67].
ray energy conversion layer and thin-film transistor (TFT)
array-based electronic readout layer [54]. Unlike charge- 4.3. Primary Physical Parameters of X-Ray Imaging. A high-
coupled devices with coupling optical lenses systems, TFT- quality digital radiographic image is important for accurate
based flat-panel X-ray detector is capable of achieving low- testing and diagnosis. The X-ray imaging quality can be eval-
dose, real-time X-ray imaging through coupling an energy uated by three primary parameters, including spatial resolu-
transfer layer and large-area pixelated TFT arrays tion, contrast, and noise (Figure 4(e)). The physical
(Figure 4(b), middle panel)), becoming popular for applica- parameters are generally evaluated by measurements of Wie-
tions in angiography, radiography, and mammography. ner spectra (WS), modulation transfer function (MTF), and
According to the difference in the pathway of converting signal-to-noise ratio (SNR) [57].
X-ray radiation to charge carriers, flat-panel X-ray detectors
are categorized into indirect conversion systems and direct 4.3.1. Spatial Resolution. The ability to distinguish adjacent
conversion systems [55]. details in an object and its related sharpness can be defined
by spatial resolution. For digital systems, the spatial resolu-
4.2.1. Direct Conversion X-Ray Detector. Direct conversion tion relates to the pixel size in the matrix, which is crucial
X-ray flat-panel detector is fabricated by depositing a layer to achieving a high spatial resolution for digital X-ray imag-
of X-ray-sensitized materials onto pixelated TFT arrays ing [68]. This parameter could be measured using a narrow
capable of directly converting X-ray photons into electrical slit, a sharp-edged object, and a bar test pattern. In most
charges that allow being transferred to thin-film transistors cases, a line spread function is used for narrow slit imaging.
(Figure 4(b), right panel) [58]. The most commonly used For instance, α-Se-based direct conversion flat-panel X-ray
photoconductor material is amorphous selenium (α-Se) fab- detectors exhibit better imaging spatial resolution than that
ricated by evaporation at high temperatures [59]. Upon X- of indirect conversion flat-panel detectors since the former
ray irradiation, the α-Se photoconductor can absorb the X- has nearly no light scattering.
ray energy and convert it into charge carriers which are pro-
portional to the incident X-ray photons. The hole-electron 4.3.2. Contrast. The contrast is another key parameter used
pairs generated in the photoconductor travel along the field for evaluating X-ray imaging quality. It refers to the relative
lines parallelly with limited lateral diffusion because of the brightness of two positions in an X-ray image by measuring
electric field applied in the α-Se. Holes can be collected by the characteristic exposure curve of an X-ray imaging sys-
the positive bias electrode, whereas electrons can be collected tem. For producing a useful image, the contrast is described
by collection electrodes. The charges are stored on the stor- by a dynamic range of an X-ray detector in response to var-
age capacitor and then are subsequently read out by thin- ious X-ray dose exposure. When compared with screen-film
film transistors. Each pixel is effectively separated by the radiography, digital radiography exhibits a much wider and
field-shaping in the α-Se layer, contributing to a high- linear dynamic range, reducing the risk of overexposure or
quality X-ray image [60]. underexposure. Moreover, the differences between specific
tissues (e.g., bones and soft tissue) could be reflected in
4.2.2. Indirect Conversion X-Ray Detector. Indirect conver- one image through post-processing without further expo-
sion flat-panel X-ray detector is made of a layer of scintilla- sure [69].
tor thin-film on the top for X-ray energy conversion,
pixelated amorphous silicon (α-Si) photodiode arrays adja- 4.3.3. Noise. The noise signals originating from various
cent to scintillators, and a TFT array (Figure 4(b), left panel) sources (e.g. collection element, coupling element, capture
[61]. When X-ray irradiates the flat-panel X-ray detectors, element, etc.) are characterized by the variations of signals
X-ray photons are converted into visible luminescence by in an X-ray image of a uniform object [70]. The noise of
scintillators and subsequently converted into electric charges an X-ray detector is important for determining image qual-
by the α-Si photodiode arrays. Eventually, the electric ity. The factor of Wiener spectra (WS) is used to measure
charges are recorded by a TFT array [62]. the noise variation of an X-ray image, indicative of the func-
The most widely used scintillators are CsI: Tl with a tional relationship between spatial frequency and the corre-
thickness of 150-600 μm and terbium-doped GOS: Tb [63, sponding noise.
64]. The scintillators deposited in indirect flat-panel X-ray
detectors can be either unstructured or structured thin-film 4.3.4. Modulation Transfer Function (MTF). The spatial res-
layers. For the unstructured scintillators, such as GOS: Tb olution of an X-ray imaging detector can be measured by the
powder crystals (turbid phosphors), the emitted light travel- MTF. More specifically, the MTF is used to convert the
ing in the materials may spread to the neighboring pixels, values of object contrast into contrast intensity levels of an
resulting in a reduced spatial resolution. This matter could X-ray image [71]. As mentioned above, due to the limited
be overcome by utilizing structure scintillators, like CsI: Tl lateral scattering, the MTF for direct conversion flat-panel
consisting of discrete and parallel “needles” with 5-10 μm X-ray detectors is obviously higher than that measured by
wide [65]. In this case, the X-ray-excited luminescence only the typical indirect conversion flat-panel X-ray detectors,
travels along with the fiber-like crystal to the photodiodes, as presented in Figure 4(d).
Research 9

4.3.5. Detective Quantum Efficiency (DQE). DQE is currently the development of six-generation CT (vi); the seventh-
used as the standard measurement to evaluate image quality generation CT scanner consists of a multiple detector array
in radiography and assess the efficiency of an X-ray imaging and a cone-shaped X-ray beam (vii).
detector in detecting X-ray photons [72]. Remarkably, the More importantly, dual- and multienergy CT was
DQE takes into consideration the signal-to-noise ratio allowed to be constructed by equipped dual- and multi-X-
(SNR) and the system noise. The DQE indicates the perfor- ray tubes, permitting to operate at different tube voltages
mance of the X-ray imaging detector in terms of X-ray imag- to make dual and multienergy scanning possible
ing quality and the X-ray radiation dose. The DQE for (Figure 5(b)). The merits of dual- and multienergy CT lie
digital radiography is higher than that for conventional in the fact that data sets at two different photon spectra
screen-film radiography, indicating that digital radiography can be obtained simultaneously upon a single scanning. Fur-
can convert a higher proportion of incident radiation into thermore, the dual-energy algorithm can increase the con-
image signals compared to conventional screen-film radiog- trast of bone, which is powerful to directly visualize the
raphy. In particular, the DQE for CsI: Tl-based indirect flat- iodinated vessels without interference. As a result, dual-
panel detector could reach 40-45% at 0.5 lp/mm, while that energy CT is widely used in angiography to create a virtual
for computed radiography is generally less than 30% at 0.5 noncontrast image.
lp/mm.
5.2. Application of 3D Radiography. As is presented in
5. Computed Tomography (CT) Figure 5(d), medical CT scanner is extensively used to screen
the size, types, location, and numbers of pulmonary nodules,
5.1. The Development of Three-Dimensional (3D) which could offer an accurate assessment of the risk for fur-
Radiography. Regarding projection radiography, a large pro- ther treatment. Recent studies showed that CT is valuable for
portion of the depth information is lost since all structural the COVID-19 diagnosis [76]. CT helps to obtain the path-
details from a 3D object are projected on a 2D plane X-ray ophysiology characters of COVID-19 infected person, such
detector, producing an overlapped radiographic image, as consolidations of the lungs and bilateral/peripheral
which will lead to misinterpretation of the internal struc- ground-glass opacities. These data provide the most intuitive
tures. Fortunately, a new technique named CT was devel- and precise diagnosis information, thereby greatly enhanc-
oped to overcome this limitation in the 1970s [73]. As ing diagnostic efficiency.
shown in Figure 5(a), series of projection images are Apart from the medical application, CT technology is
acquired from various angles to generate tomographic also introduced to industrial nondestructive inspection in
images. A 3D image is then obtained by reconstructing these early 1980. Industrial CT is a promising nondestructive tool
tomographic images using computer algorithms [74, 75]. for characterizing the flaws, inclusions, cracks, and insuffi-
Compared with projection radiography, CT can provide cient fusion within the body of materials [78–80]. For
comprehensive 3D anatomical reconstructions and has a instance, the 3D pore structure of coal samples can be
greater diagnostic capability. obtained through CT to reproduce the precise distribution
The first applicable CT scanner, consisting of an X-ray of coal pore and pore structure (Figure 5(e)). The heteroge-
generator and two collimated sodium iodide crystals- neity inside different coal samples can be directly observed,
photomultiplier detectors, was invented by Godfrey N. providing insights into the structure-dependent attributes
Hounsfield in 1968. Hounsfield was awarded the Nobel Prize of coal, including gas transport, thermomechanical, and fail-
for his contribution to CT. From then on, seven generations ure behaviors.
of the CT have developed, including updating the shape of As an added benefit, the tomography technology is able
X-ray source from pencil to cone, increasing the number of to perform 3D imaging of nano- to microsized biological
imaging slices and detectors, and changing the scanning organisms when coupling with X-ray microscopy [81–83].
mode from rotation and translation to helical scanning This combined technology enables the diffraction limit of
(Figure 5(c)). the conventional microscope to be overcome because of
The first CT scanner uses a rotate/translate system using shorter wavelength X-ray photons. This feature sug-
equipped with an X-ray generator with a pinhole collimator gests its power in elucidating the detailed structural informa-
to produce the collimated X-rays (i); the second-generation tion of in vivo or ex vivo biological samples with a cellular
CT scanner incorporates an X-ray generator, which could resolution. Note that an emerging transmission soft X-ray
produce a narrow, fan-shaped X-ray beam, and increases microscope could generate 3D cell imaging at a nanoscale
the X-ray sensor number (ii); the third-generation scanner resolution based on the difference in X-ray absorption
involves a fan-shaped X-ray beam with an angle ranging between organic matter and water, filling the gap between
between 40 and 60 degrees, which enable scanning the object cryoelectron tomography and fluorescence superresolution
in a rotated modality (iii); the fourth-generation CT system microscopy (Figure 5(f)) [77].
employs a rotating X-ray tube and a stationary, closed X-
ray detector ring to alleviate the ring artifacts produced by 6. X-Ray Microscopy
the third generation (iv); the fifth-generation CT scanner is
composed of no moving parts, and the electron beam is 6.1. The Development of X-Ray Microscopy. Optical micros-
directed around the target ring, allowing for all stationary copy is great of significance to study microstructures [84].
instrumentation (v); the addition of a slip ring stimulated Fluorescence microscopy provides an approach to image
10 Research

X-ray tube
Rotation
Series of 2D projection images
Collimator

z Collimator
y

x (i)

Detector and
electronics Reconstruction with
3D image filtered back projection
represented Slice 1
Slice 2 Slice 3
Slice 3 Slice 2
Reconstruction slices Slice 1
(ii)
(a) (b)

CT
i ii iii iv v vi vii
generations
X-ray source

Detector
(c)

Radiologists- CNN+ Radiologists+ CNN+

1.0
Nuclear
member
0.8 Channel
Nucleoli
Sample 1 Sample 2 Sample 3
0.6
Radiologists+ CNN- Radiologists- CNN-
0.4
L 13 %
0.2 M 17 %
ER 3 %
V 2%
0 Sample 1 Sample 2 Sample 3 E 65 %
COVID-19(+)
probability
(d) (e) (f)

Figure 5: Demonstration of CT. (a) Schematics illustrating the working principle of CT scanning and imaging. The collimated X-ray
photons penetrating through the object are recorded using an X-ray detector, which is positioned opposite to the X-ray generator. In a
typical CT scanning, the solid-state detectors rotate around the object in synchrony with an X-ray generator to produce a series of 2D
projection images. Subsequently, the 2D slice images are obtained after reconstruction with filtered back projection. Eventually, a 3D
tomographic image is reconstructed through computer algorithms. (b) The structure of dual-energy CT (i) and multienergy CT (ii). The
dual-energy CT or multienergy CT is equipped with two- or multi-X-ray generators, which allow simultaneous acquisition of images
under two- or multienergy level X-rays in a single scan. (c) The development history of CT. The evolution of CT has gone through
seven generations. (d) Combined diagnosis of CT and an artificial intelligence algorithm deep convolutional neural network (CNN) on
four sectioned chest images. CT images are used as input data for the CNN model; subsequently, the output images (right panel) are
presented as the heat maps, where red indicates a high risk of COVID-19 infection. (e) The reconstructed 3D porous structure of six
coal samples. The pore size distribution, pore volume, porosity, and permeability data could be obtained. (f) The 3D X-ray images
showing the volume fraction of organelles (bottom panel) and the nuclear membrane (top panel). L: lysosomes; M: mitochondria; ER:
endoplasmic reticulum; V: vesicles; E: external. (d) is reprinted with permission from ref. [76], copyright 2020 The Author(s), under
exclusive license to Springer Nature America, Inc. (f) is reprinted with permission from ref. [77], copyright 2010 Nature America, Inc.

the structures at a microscale resolution by taking advan- by Abbe or Rayleigh laws [85, 86]. The imaging resolution
tage of site-specific fluorescence labeling. However, the can be significantly enhanced to a few angstroms using an
imaging resolution of fluorescence microscopy is largely electron beam as the incident light in transmission elec-
limited by the wavelength of UV-Vis light, as confined tron microscopy [87]. This technology shows considerable
Research 11

disadvantages in the observation of biological samples, espe- multilayer Laue lens are tiled to meet the Bragg condition
cially considering the tedious sample preparation process for the outer, smallest layer spacing, providing efficiency
including dehydration, formalin fixation, paraffin-embed- larger than conventional Fresnel zone plates. Multilayer Laue
ding, and section. Besides, the poor penetration depth of elec- lens of a 16 nm width was used to focus 20 keV photon
trons in biological samples has a limitation to imaging the energy of X-rays. Recently, a focal spot size smaller than
sample thickness larger than 100 nm. 10 nm was achieved by fabricating multilayer Laue lenses
By taking advantage of the powerful penetration and with sufficiently high numerical aperture. Besides, for 2D
nearly no scattering properties of X-rays, the emerging X- focusing, the two multilayer Laue lenses with different focal
ray microscopy techniques break the penetration depth lim- lengths are required to be positioned orthogonal to each
itation of transmission electron microscopy and allow the other.
intact sample to be imaged without specimen sectioning. Reflective optics are further developed to achieve the
The wavelength of X-ray locates at a range of 0.01-10 nm, imaging resolution of several nanometers by exploiting
which is suitable to be used as a light source for imaging bio- Kirkpatrick-Baez systems (Figure 6(e)). Grazing incidence
logical objects at a very high spatial resolution. It is worth reflective mirrors are capable of focusing hard X-rays and
noting that the penetration ability of soft X-rays is much enhancing X-ray reflection efficiency. Kirkpatrick-Baez mir-
greater than that of electrons. Meanwhile, the water is nearly rors are typically made from multilayers of dense metals or
transparent to X-rays compared to organic compounds at X- hard silicon carbide coated on silicon crystals with near
ray energy located at 284–540 eV (water window), where the atomic roughness. The efficiency of the Kirkpatrick-Baez
K absorption edges of carbon and oxygen are 284 eV and mirror is constrained by the shape and surface roughness.
540 eV, respectively (Figure 6(b)). Therefore, the develop- Since the refractive indices of all materials for X-rays are
ment of X-ray microscopy is very useful for imaging biolog- always slightly less than ones in vacuum and air, conven-
ical specimens with improved spatial resolution under wet tional optical refractive lenses are not available for X-ray
and normal pressure conditions (Figure 6(a)) [88]. Besides, focusing. In addition, an appropriate curvature radius and
the X-ray energies of 10-100 keV cover the spectroscopic fea- a double concave shape are essential for X-ray focusing
tures of all elements and offer the opportunity to detect ele- lenses, as illustrated in Figure 6(f). In 1996, compound
ments and probe chemical bonds of an object [89, 90]. refractive lenses were designed using parabolic concave
lenses [96]. To reduce X-ray absorption and increase com-
6.2. The Optics in X-Ray Microscopy. In the late 1940s, the pound refractive lenses’ efficiency, compound refractive
invention of grazing incidence mirror optics offers a great lenses are typically made of high-density, low-Z materials,
opportunity to develop X-ray microscopy. However, the such as lithium, boron, silicon, carbon, beryllium, or alumi-
technical issues of long exposure time and insufficient spatial num. Advantages in simple manufacture, low cost, small
resolution become a major challenge for the use of X-ray size, easy alignment, and tunable focal length make the com-
microscopy. In the 1970s, the development of high-quality pound refractive lenses great promise in hard X-ray
zone plates for high-energy X-ray focusing opens the mod- focusing.
ern era of X-ray microscopy. The high-quality X-ray focus-
ing optics are then extensively used to increase the spatial 6.3. General X-Ray Microscopy Modes. Current state-of-art
resolution of X-ray imaging. Nowadays, X-ray optics can X-ray microscopy includes full-view transmission X-ray
be well designed by combination with thin-film deposition, microscopy and scanning transmission X-ray microscopy
electron beam lithography, and nanofabrication with capa- [97, 98]. The full-view transmission X-ray microscopy is
bilities to improve diffractive, reflective, and refractive X- similar in principle to that of optical bright-field microscopy.
rays [91]. The Fresnel zone plates consist of several concen- X-rays travel through the focusing optics to irradiate the
tric rings of transparent zones and alternating opaque, as sample, and the transmitted X-rays are magnified by a zone
shown in Figure 6(c) [92]. The X-rays passing through the plate to provide a magnified projection onto the detector
transparent sections are diffracted and subsequently gener- [94]. As shown in Figure 6(g), the central stopper coupled
ate constructive interference, focusing on a small spot. with an order sorting aperture is applied to filtrate a certain
Hence, the zone plates can be used both as condenser and portion of X-rays which is not in the first-order diffraction.
objective for X-ray focusing. The zone plate-based micros- The sample is placed near the spot of the first-order diffrac-
copy is achievable for high-resolution imaging, which is tion. The X-rays penetrating out from the samples are mag-
largely determined by the zone plate’s outer width (Δr N ). nified using the microzone plates as an objective, projecting
The smaller outer zone width can lead to a higher spatial res- onto the X-ray detector. The imaging resolution of the full-
olution. The selection of the type of zone plate is determined view transmission X-ray microscopy depends on the outer
by several factors including photon energy, required spatial zone width (ΔrN ) of the zone plate, imaging geometry, and
resolution, and the number of zones. At present, a 12 nm illumination coherence. Since the quick acquisition of a 2D
spatial resolution has been successfully performed using projection image, a 3D image is reconstructed by many 2D
the 12 nm zone plate [93]. projection images from different angles of the sample.
The efficiency and resolution of hard-X-ray focusing are The scanning transmission X-ray microscopy is another
also achieved using a multilayer Laue lens with varied d- technology suitable for imaging the local scale structure.
spacing, a multilayer coating-based 1D zone plate fabricated Figure 6(h) shows the schematic setup of the scanning trans-
by magnetron sputtering [95]. As shown in Figure 6(d), the mission X-ray microscopy. A coherent part of X-rays from a
12 Research

X-ray energy (eV)

0 500 1000 1500
10.0
X-rays
Water

Oxygen edge
1/µ

Penetration distance (µm)

1.0 Electrons
Protein

Carbon edge
λelastic Protein
1/µ
ater
λ elasticW

ater
λ inelastic W
λinelastic Protein
10 µm 2 µm 2 µm
0.1
X-rays X-rays Visible light 0 100 200 300 400
Electron energy (keV)
(a) (b)

Fersnel zone plate Multilayer Laue lens KB mirror pair Compound refractive lenses
(c) (d) (e) (f)

Sample
Micro zone plate Aperture Sample
Condenser zone plate Condenser zone plate
Aperture
ure
objective

X-ray detector Raster scanning X-ray detector

Full-field transmission X-ray microscope Scanning transmission X-ray microscope
(g) (h)

Figure 6: X-ray microscopy setups and their optics. (a) X-ray and optical images of a fibroblast. The area outlined with yellow dashed in the
low-magnification image (left panel) is shown at a higher magnification image by the means of X-ray microscopy (middle panel) and optical
microscopy (right panel). (b) The penetration distances of X-rays and electrons in water and protein as a function of their energy. The lines
from left to right represent attenuation lengths (1/μ) of carbon (protein) and oxygen (H2O) for X-rays and the mean free paths (λ) of H2O
(elastic scattering), protein (elastic scattering), H2O (inelastic scattering), and protein (inelastic scattering), respectively. (c) A Fresnel zone
plate is made of several transparent and opaque concentric circulars with radially increasing line density. The central absorbing region is
responsible for suppressing the strong zero-order diffraction. (d) One-dimensional multilayer Laue lens for hard X-ray focusing.
Alternating layers are fabricated by the thin-film deposition technique to implement thin thickness and ultra-high aspect ratio. (e) A
Kirkpatrick-Baez mirror for hard X-ray focusing. Multilayer coatings were designed to increase the angles of operation and to perform
photon energy selection. (f) Compound refractive lenses for X-ray focusing at a range of 5-40 keV. A linear array of lenses is
manufactured by high-density low-atomic number materials. (g) Full-field transmission X-ray microscopy. A full-field image was
projected by a microzone plate onto the X-ray detector. (h) Scanning transmission X-ray microscopy. A zone plate is used to focus
coherent X-rays on the sample, whereas an X-ray-sensitive detector is used to capture X-ray images. The sample is mounted on a stage
having stepping or piezoelectric driven motors to perform the raster scan. (a, b) are reprinted with permission from ref. [88], copyright
1995 Cambridge University Press. (c)–(f) are reprinted with permission from ref. [94], copyright 2010 Macmillan Publishers Limited.

monochromator passes through the zone plate to produce a microscopy image is reconstructed since the sample is
diffraction-limited focal spot, and then the transmitted X- scanned in 2D perpendicular to the optical axis. The imaging
rays are detected. As a result, scanning transmission X-ray resolution is determined by several factors, including the
Research 13

CsPbBr3
nanocrystals 120º
0.08

X-ray photons 0.06

Protective Al foil

Current (nA)
Perovskite Au electrode
scintillator
0.04

0.02 0° 20°
Pixel α-silicon 40° 60°
Flexible PET
photodiode array 80° 120°
0
TFT sensor panel 0 0.02 0.04 0.06 0.08 0.1
Voltage (V)
(a) (b)

NH3Br-terminated SAMs
modified wafer [PbBr3] –octahedra

Si-integrated
MAPbBr3SC CH3NH3+

O
O Si(CH2)3NH3+
Seeding
O

Si
Growing

(c)

p-i-n diode

E (001)
Sensitivity (μC Gy –1cm –2)

(001) 20000 E (001)

RP
2D film
n
thi
10000

2D RP-(BA)2(MA)2PbI 10
0

0 2 4
Field (V mm–1)

(d) (e)

Figure 7: Perovskites-based X-ray detectors. (a) Schematic illustration of the perovskite nanocrystals-based flat-panel detector by coating a
layer of CsPbBr3 nanoscintillators onto a commercial pixelated α-silicon thin-film-transistor (TFT) panel. (b) Schematic of a flexible
perovskite X-ray detector (left) and I-V curves of the flexible device under X-ray irradiation (right). (c) Scheme illustrating the
fabrication of Si-integrated MAPbBr3 single crystals. (d) Diagram of an X-ray detector based on 2D RP perovskite p-i-n thin-film. (e)
Photography of a bulk (NH4)3Bi2I9 single crystal (left) and X-ray sensitivity measurement of (NH4)3Bi2I9 single-crystal device in the
direction parallel and perpendicular to the (001) plane (right). (a) is reprinted with permission from ref. [104], copyright 2018 Springer
Nature Limited. (b) is reprinted with permission from ref. [20], 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. (c) is
reprinted with permission from ref. [60], copyright 2017 Macmillan Publishers Limited. (d) is reprinted with permission from ref. [107],
copyright 2020 American Association for the Advancement of Science. (e) is reprinted with permission from ref. [110], copyright 2019
Springer Nature Limited.

quality of focusing lenses, the precision of instrumental advantage of scanning transmission X-ray microscopy is its
setup, and the coherence of X-rays. The imaging resolution easy extension to multisignal, simultaneous detection in
can be improved by a higher-order focusing zone plate, combination with X-ray scattering, diffraction, fluorescence,
while the detection efficiency will be reduced. One key or electron emission yield [99].
14 Research

7. Material Opportunity for X-Ray Imaging and functional flexibility to synthesize lead-free perovskites
(Figure 7(e)) [110]. As such, 2D and zero-dimensional perov-
The rapid development in materials science offers a great skites are further developed for achieving X-ray detection
opportunity to revolutionize the future of X-ray imaging through tailoring ionic radius, chemical composition, and
technology. Over the past decades, scintillator materials, coordination environment based on the classical structure of
which can convert high-energy radiation into UV-Vis pho- ABX3 perovskites [111]. Recent studies have shown that many
tons, are critical to high-performance X-ray imaging. In heavy atom-contained double perovskites have merits of effi-
the early stage, CaWO4 and ZnS powders were widely used cient X-ray absorption, short decay time, and high stability,
for X-rays imaging. After the 1940s, scintillator crystals ideal for X-ray imaging [106, 112, 113].
(e.g. NaI: Tl, CsI: Tl, and Bi4Ge3O12) were gradually used Another focus of recent research is developing flexible X-
for fabricating high-performance X-ray detectors such as ray detectors that are applicable to 3D X-ray imaging of
commercial flat-panel detectors. However, conventional irregularly shaped objects. Very recently, lanthanide-doped
scintillators are synthesized through a solid-state method at fluoride materials prepared by wet chemical methods were
high temperatures, resulting in large crystals that are unsuit- developed for high-resolution, flexible X-ray luminescence
able for manufacturing large-area, flexible X-ray detectors. extension imaging. These materials prolonged radiolumines-
Recently, solution-processed materials have been devel- cence and X-ray memory after the stoppage of the X-ray
oped for advancing next-generation X-ray imaging technol- source, making it possible to fabricate flexible X-ray detec-
ogies with low cost, high sensitivity, and flexibility. In tors [114]. After rational surface coating, the persistent lumi-
particular, perovskites, featuring tunable bandgap, high pho- nescence intensity was enhanced by 6.5-fold, suggesting that
toluminescence quantum yields, narrow emission, and high the surface passivation can efficiently block the pathway of
charge-carrier mobility, have emerged as promising mate- energy quenching by defects on the surface. The X-ray
rials in photovoltaic devices, luminescence displays, and energy trapping capability and solution processibility allow
radiation detection [100–103]. The heavy atom-contained fabricating the flexible X-ray detectors through embedding
perovskites with efficient X-ray absorption show great the nanoscintillators into the soft substrate, which is promis-
potential in X-ray imaging applications. Lead-halide perov- ing for portable X-ray devices, point-of-care radiography,
skite nanocrystals can generate multicolor radioluminescence and nondestructive testing in special conditions [115].
upon X-ray irradiation [104]. The solution-processable and Apart from the inorganic scintillators, metal-free organic
easily scalable CsPbBr3 nanocrystals are synthesized to fabri- scintillators display great potential in large-area and flexible
cate large-area flat-panel X-ray detectors (Figure 7(a)). In X-ray detectors, by taking advantage of flexibility, solution-
addition, CsPbBr3 nanosheets synthesized at room tempera- processability, transparency, and ease to large-area fabrica-
ture can be assembled into a uniform and dense thin film as tion. To date, the scientific community mainly focuses on
an X-ray scintillating screen for high-resolution radiography developing lanthanide-doped materials, perovskites, and
[105]. Although indirect conversion-based X-ray detectors metal organic frames [116]. Considering that organic scintil-
are most popular in practical applications, they generally suf- lators composed of carbon, hydrogen, oxygen, and nitrogen
fer from a relatively low spatial resolution due to the optical elements show a relatively low X-ray attenuation coefficient,
crosstalk among neighboring pixels. the radioluminescence of organic scintillators can be bright-
X-ray imaging detectors based on direct conversion ened by introducing heavy atoms (such as chlorine, bro-
present the advantages of a high signal-to-noise ratio and mine, and iodine) to turn on the triplet excitons [117].
high resolution since the X-ray-generated charges can be Overall, the emerging advanced materials present opportu-
directly collected by pixelated arrays [106]. Liu et al. fabri- nities for promoting X-ray imaging technology with low-
cated a flexible X-ray detector using solution-processable dose, high-resolution, and portability, and the performance
perovskite nanocrystals by an inexpensive inkjet printing of X-ray imaging can be improved in the terms of device
method (Figure 7(b)) [20]. Tsai et al. put forward an ultra- physics, materials, and manufacturing methods.
sensitive X-ray detector by fabricating Ruddlesden-Popper
(RP) layered perovskites in a fully depleted p-i-n architecture 8. Conclusion and Perspectives
(Figure 7(d)) [107]. In 2015, Yakunin et al. reported that
perovskite crystals of methylammonium lead iodide X-ray imaging technology has been rapidly developed for
(MAPbI3) were developed to achieve indirect X-ray detec- various applications since 1895, offering new opportunities
tion with strong X-ray absorption and high sensitivity to scientific and industrial communities. Considering the
[108]. Compared to the commercial direct conversion fundamental and technical advances of X-ray detectors, we
X-ray detectors using amorphous selenide as a photo- have summarized various X-ray working mechanisms that
conductor, perovskites which feature low-cost, defect- are crucial for specialized applications. The contrast-based
tolerance, solution-processibility, and tunable bandgap X-ray imaging using a screen-film scintillation screen is a
hold great promise for X-ray imaging, which is pre- classical technique that greatly advances noninvasive medi-
sented in Figure 7(c) [60, 109]. Despite their great prog- cal imaging. The emergence of computed radiography has
ress, lead-halide perovskites suffer from the issues of led to the technological evolution for digital X-ray imaging
poor long-term stability, and the toxicity of lead composi- with more precise and instant information, while its sepa-
tion is harmful to the environment and human health. rated readout mechanism suffers from technical limitations
The diversity in substitution strategies offers the structural such as a high radiation dose and nondynamic imaging.
Research 15

Since the pioneering study in the 1990s, flat-panel X-ray China-Sweden Joint Mobility Project (51811530018), the
detectors have been most prominent for achieving real- Special Funded Project of China Postdoctoral Science Foun-
time digital radiography, which is popularly used in hospi- dation (2021T140117), Fundamental Research Funds for the
tals and industries in place of traditional computed radiogra- Central Universities, and Fujian Science & Technology
phy. In further development, CT integrating advanced Innovation Laboratory for Optoelectronic Information of
helical scanning techniques and image reconstruction tech- China (2021ZZ128).
niques is capable of providing comprehensive 3D structure
information, which is a well-established cardiac, pectoral, References
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