Journal of

Imaging

Review
Spectral Photon-Counting Computed Tomography: A Review
on Technical Principles and Clinical Applications
Mario Tortora 1 , Laura Gemini 1 , Imma D’Iglio 1 , Lorenzo Ugga 1 , Gaia Spadarella 1 and
Renato Cuocolo 2,3, *

1 Department of Advanced Biomedical Sciences, University of Naples “Federico II”, Via Sergio Pansini 5,
80131 Naples, Italy; [email protected] (M.T.); [email protected] (L.G.);
[email protected] (I.D.); [email protected] (L.U.); [email protected] (G.S.)
2 Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Via Sergio Pansini 5,
80131 Naples, Italy
3 Department of Medicine, Surgery and Dentistry, University of Salerno, Via Salvador Allende 43,
84081 Baronissi, Italy
* Correspondence: [email protected]

Abstract: Photon-counting computed tomography (CT) is a technology that has attracted increasing
interest in recent years since, thanks to new-generation detectors, it holds the promise to radically
change the clinical use of CT imaging. Photon-counting detectors overcome the major limitations of
conventional CT detectors by providing very high spatial resolution without electronic noise, provid-
ing a higher contrast-to-noise ratio, and optimizing spectral images. Additionally, photon-counting
CT can lead to reduced radiation exposure, reconstruction of higher spatial resolution images, re-



duction of image artifacts, optimization of the use of contrast agents, and create new opportunities


for quantitative imaging. The aim of this review is to briefly explain the technical principles of
Citation: Tortora, M.; Gemini, L.;
photon-counting CT and, more extensively, the potential clinical applications of this technology.
D’Iglio, I.; Ugga, L.; Spadarella, G.;
Cuocolo, R. Spectral
Photon-Counting Computed Keywords: photon-counting computed tomography; diagnostic imaging; CT imaging
Tomography: A Review on Technical
Principles and Clinical Applications.
J. Imaging 2022, 8, 112. https://
doi.org/10.3390/jimaging8040112 1. Introduction
Academic Editors: Giuseppe Placidi, The aim of this article is to present one of the most promising new technologies that
Mrinal Mandal and has been recently introduced in the field of medical imaging, spectral photon-counting
Mustapha Bouhrara computed tomography (SPCCT). This method has been demonstrated to be superior
to current generation computed tomography (CT) scanners, based on double-source or
Received: 25 February 2022
dual-energy CT (DECT) technology, and introduced in clinical practice in 2005 [1], whose
Accepted: 14 April 2022
applications are well known in the literature [2–6]. In order to appreciate the advantages
Published: 15 April 2022
and possible novel clinical applications of SPCCT, it is necessary to be familiar with its basic
Publisher’s Note: MDPI stays neutral physical principles and main differences from conventional CT and DECT. An overview of
with regard to jurisdictional claims in the state of the art of SPCCT technology is now proposed and followed by a discussion of
published maps and institutional affil- potential clinical applications.
iations.
2. Technical Principles
CT devices currently in use in clinical practice employ energy-integrating detectors
(EIDs) equipped with scintillator elements and septa. The incident X-rays are absorbed in a
Copyright: © 2022 by the authors.
scintillator, which converts the X-rays into visible light. This process generates a shower
Licensee MDPI, Basel, Switzerland.
of visible light secondary photons. These are absorbed by a photodiode that generates an
This article is an open access article
electrical signal proportional to the total deposited energy, including electronic noise [7].
distributed under the terms and
conditions of the Creative Commons
Septa are separate detector elements and are crucial to avoid light photon leakage between
Attribution (CC BY) license (https://
them; however, they limit the geometric dose efficiency (Figure 1, left panel) [8,9]. Photon-
creativecommons.org/licenses/by/ counting detectors (PCDs) convert individual X-ray photons directly into an electrical
4.0/). signal without first transforming them into visible light. The PCDs are made by coupling

J. Imaging 2022, 8, 112. https://doi.org/10.3390/jimaging8040112 https://www.mdpi.com/journal/jimaging

J. Imaging 2022, 8, 112 2 of 12

a semiconductor sensor with a readout circuit. Each photon interacting with the sensor
produces electron-hole pairs, which drift towards the electrodes under the effect of a bias
voltage applied to the sensor (Figure 1, right panel). The charge carriers collected by the
pixels generate an electrical signal with a height proportional to the energy deposited by
the interacting photon. By implementing one or more energy thresholds, PCDs can sort
the incoming photons according to their energy, excluding the electronic noise. Ideally,
an optimal system would be one where the charge carriers produced by each photon are
collected by a single pixel. When the charge cloud is produced by a single interaction
spread over multiple pixels, there is a reduction in spatial resolution (blurred image) and
the contrast-to-noise ratio [10]. This issue, called charge sharing, also affects the energy
resolution of a PCD, and it is enhanced as the ratio of sensor thickness to pixel size increases.
To limit this effect, CdTe or CZT sensors are preferred to silicon sensors. In fact, if compared
to silicon, the high atomic number and density of CdTe and CZT allow for a high detection
efficiency with a reduced thickness [11]. Moreover, essential for system optimization is a
fast detector able to count single photons [12–14]. In fact, pulse pileup may determine a
loss of photon count, increasing the image noise. This phenomenon appears as multiple
photons rapidly reach the sensor, causing overlapping photon pulses [15]. As stated above,
this effect can be minimized by designing smaller pixels and faster counters [16–18].

Figure 1. Schematic representation of two different CT systems as follows: on the left, an integrated
energy detector (EIDs) with scintillator and septa. The X-rays absorbed by the scintillator are
converted into visible light, and a swarm of photons is absorbed by a photodiode that generates an
electrical signal. On the right, a photon-counting detector (PCDs) that directly converts X-rays into
an electrical signal.

The spatial resolution obtainable with any conventional CT detector is mainly deter-
mined by the detector element size, with smaller ones improving the spatial resolution.
Since PCDs do not have scintillators and septa, they can be fabricated with smaller elements
compared to EIDs [19,20].
Spectral data can be employed through the following two mechanisms: the weighting
of energy and the decomposition of the material.
With the first, greater weights are assigned to specific energy bins in order to improve
image quality. As an example, by increasing the weight of low-energy bins, it would be
possible to increase the contrast-to-noise ratio (CNR) between soft tissues [21,22]. Several
image- and projection-based weighting techniques have been proposed to also increase
J. Imaging 2022, 8, 112 3 of 12

the visibility of contrast agents and correct for beam-hardening artifacts [23–25]. Basis
material decomposition algorithms assume that absorption can be modeled as a linear
combination of bases [26]. The number of bases that can be selected is limited by the
number of spectral data (e.g., with N spectral data, a maximum of N bases can be selected).
By imposing mass or volume conservation constraints, the number of bases can be extended
to N + 1). This generates a set of base image maps, each of which contains the equivalent
material concentration on a voxel-by-voxel basis. These images can be used to directly
assess the distribution of a certain element within the image, such as a contrast medium for
iodine/water basis (Figure 2). In addition, this technology also allows for virtual images to
be generated either in monochrome, without contrast, or with color overlays.

Figure 2. Graphical representation of the ability of the photon-counting system to determine different
energy spectra. In particular, the system is capable, by subtracting the raw CT data with defined
low-energy thresholds to obtain differentiated data based on the “energy bin” to which it belongs
and produce different maps based on the concentration of the materials under examination after
spectrum processing by specific material decomposition algorithm (e.g., iodine, water, and calcium).

Since full energy-dependent attenuation is considered, the resulting images can, in

theory, be completely free of beam-hardening artifacts [27–30]. Regarding artifacts, SPCCT
also has the potential to reduce blooming by means of improved spatial resolution and
material decomposition [7]. As we will see later, this is relevant for several applications,
such as cardiovascular imaging.
In recent years, numerous prototypes of CT scanners with photon-counting technology
have been tested [11,31]. These experiments have confirmed, compared to conventional
devices, an improvement in terms of energy weighting and a clear reduction of electronic
noise even at low radiation exposure doses. This translates to better imaging resolution
paired with a dramatic radiation dose reduction. With reference to the use of contrast
media, the SPCCT guarantees the unique opportunity to use multiple contrast media other
than iodine [7]. Among the molecules of greatest scientific interest, we have nanoparticles
labeled with gold and platinum [32–35]. In this regard, it is interesting to outline the
differences between SPCCT and DECT. Both methods can discriminate between different
contrast agents, but with fundamental basic differences. DECT is limited to discerning only
two predefined energy spectra, usually high (140 kV) and low (80 kV) [36,37]. Therefore,
using this technology, one can break down attenuations into up to two components [38],
as only two measurements per voxel are performed, but by including volume (or mass)
conservation constraints, it is possible to extend the decomposition up to three components
with only two measurements [39,40].
J. Imaging 2022, 8, 112 4 of 12

Using SPCCT, on the other hand, it is possible to discern more than two different
contrast agents in each voxel at the time of acquisition, with different pharmacokinetics
in the same biological system. This allows for the generation of separate quantitative
maps for each component, with up to five photon-counting measurements (six bins) per
voxel [41]. The components commonly identified in pre-clinical studies were the following:
two non-K-edge materials (e.g., water and iodine) and one or two K-edge materials (e.g.,
gadolinium and gold) [42,43]. As reported by Si-Mohamed et al. [44], SPCCT is able to
accurately decompose the material for both unmixed (iodine, gadolinium, and gold) and
mixed (iodine-gadolinium and gadolinium-gold mixtures) solutions. However, there is
an underestimation of the contrast power for mixed solutions, and, among the K-edge
materials, gadolinium has a greater contrast than gold in relation to the better equilibrium
of photons in a range of 120 kV, which determines a more accurate decomposition of this
material. Therefore, SPCCT enables multicolor quantitative imaging. As a result, it should
be possible to perform imaging of multiple uptake phases of a given tissue/organ within a
single slice scan by injecting contrast agents sequentially at different time points.

3. Clinical Applications
3.1. Head and Neck Imaging
SPCCT has the potential to improve the quality of carotid and intracranial angiography
imaging compared to conventional single-energy TC and DECT [27]. In particular, it has
been reported that this technique minimizes electronic noise and beam-hardening artifacts
in internal carotid artery segments close to surrounding bone [45]. Spectral material
decomposition is feasible for vascular imaging in this human district [36], with the technical
advantages mentioned above and a reduction in overall radiation dose [20]. Another field
of application of SPCCT in the head and neck district is the staging of laryngeal and
hypo-pharyngeal cancer, for which it is essential to identify the degree of invasion of
the laryngeal cartilages. Since the density of non-ossified laryngeal cartilage is similar to
that of tumors in conventional CT imaging, greater spatial resolution, as well as material
decomposition and differentiation techniques allowed by SPCCT, may lead to improved
lesion local staging [46].

3.2. Temporal Bone Imaging

A high spatial resolution, guaranteed by SPCCT, is essential for temporal bone imaging,
where a high-resolution study of small structures such as auditory ossicles is required.
Initial studies were performed in pigs’ cadavers [47], followed by phantom and cadaver
studies [48,49]. The results showed that SPCCT guarantees the clear visualization of crucial
anatomical structures, such as the stapes superstructure, with a lower radiation dose than
conventional CT scanners.

3.3. Chest Imaging

Preclinical studies have found that SPCCT has the potential to improve the detection of
pulmonary nodules and the assessment of other lung structures [50]. In particular, the high
spatial resolution allowed by SPCCT, compared to conventional CT scanners in current
clinical use, leads to a more precise assessment of nodules and the smallest pulmonary
structures such as the terminal divisions of the bronchial tree and the interstitium. Al-
together, SPCCT guarantees a strong improvement in detectability of both lesions with
low-contrast compared to surrounding parenchyma (e.g., ground glass nodule) and lesions
with high-contrast (e.g., solid nodule). For example, SPCCT has proven superior to DECT
for the detection of solitary pulmonary nodules, and it is worth noting that a less than 2
mm-diameter ground glass nodule surrounded by an extension ring was clearly seen only
with SPCCT, confirming the potential information gain with this technology [51]. Com-
pared to DECT [52], the lower electronic noise level and higher spatial resolution of SPCCT
are confirmed in this domain. Several studies [51,53] support the technical improvements
of PCDs, making SPCCT a promising tool for radiation dose optimization, which is a crucial
J. Imaging 2022, 8, 112 5 of 12

aspect in improving the risk-benefit ratio of CT lung cancer screening. For the study of
pulmonary parenchyma, SPCCT can revolutionize the role of imaging in the detection of
interstitial lung disease and pathological key signs including intra-lobular reticulations,
bronchiectasis, and honeycombing [54–56]. Distal airways and bronchial imaging still
represent challenges for even the most experienced radiologists. Recent studies [50,57]
have shown an improvement in the detection of high-order bronchi compared with con-
ventional CT systems. In addition, bronchi, bronchioles, vessels, and walls of bronchioles
could be visualized more distinctly with SPCCT compared to high-resolution CT. Last but
not least, in reference to pulmonary vascular diseases in the setting of the coronavirus
disease 19 pandemic, there is hope for better monitoring of the distal pulmonary vascular
involvement [58].

3.4. Breast Imaging

Currently, SPCCT is not used for breast imaging, although numerous experimental
studies have investigated how PCDs in a dedicated breast CT system could guarantee
advantages for the detection of small lesions and the differentiation of soft tissues [59,60].
The use of PCDs in the detection of breast cancer bone metastases is included in the
following section on musculoskeletal imaging.

3.5. Cardiovascular Imaging

Conventional CT systems can rule out coronary artery disease in relatively large nor-
mal vessels, but their specificity remains low, as precisely measuring the degree of stenosis
requires very high spatial resolution. Additionally, calcified plaques are often affected
by blooming artifacts. The increased spatial resolution of SPCCT allows for increased
detectability and more accurate coronary artery calcium (CAC) volume estimation with the
classic Agatston score and the minimization of blooming artifacts. These conclusions are
the result of observations in phantom studies as well as in-vivo human experiences [61,62].
Another interesting application of this technology is to determine the extent of damage
in a myocardial infarction using a double-contrast agent. Cardiac imaging with a multi-
contrast agent is possible by injecting the gadolinium-based contrast 10 min before the
SPCCT and the iodinated contrast immediately before the scan. Gadolinium and iodine
maps are then obtained using the previously mentioned material decomposition technique.
For myocardial infarct versus remote myocardium, the contrast-to-noise ratio was maxi-
mized on the gadolinium-enhanced maps, while for myocardial infarct versus the blood
pool, it was optimal on iodine maps. Combined first-pass iodine and late gadolinium maps
enabled the quantitative separation of the blood pool, scar, and remote myocardium with
accurate scar delineation [63]. Remaining in the domain of coronary heart disease, the use
of these techniques is also very promising for the study of endovascular stents. There are
specific technical issues when imaging coronary stents with current CT scanners in clinical
practice. These include metallic, blooming, and beam-hardening artifacts, in addition
to partial volume effects due to relatively low spatial resolution. With conventional CT
scanners, the lumen of the coronary stent can be visualized accurately in a still unsatisfac-
tory percentage of cases [64–67]. In the study by Mannil et al. [68], SPCCT was directly
compared with the best available detection technology currently available in the clinical
setting. Thus, the following best results were observed for PCDs-based CT technology
with significantly improved image quality: 16% better lumen display within the stent;
fewer blooming and partial volume artifacts that are reflected in a 37% lower increase in
the attenuation of the lumen inside the stent. In the assessment of stent features, SPCCT
has offered superior image quality, which can result in new diagnostic capabilities and
potentially enable novel applications. A clear assessment of the stenosis internal to the stent
and the adjacent residual lumen was possible, which allowed highly reliable non-invasive
assessments of the actual grade and extent of the stenosis [69]. Although drug-eluting
stents significantly reduce the number of in-stent stenoses [70], these are still highly relevant
complications [71], negatively impacting clinical outcomes [72]. Future screening with
J. Imaging 2022, 8, 112 6 of 12

SPCCT could be an option to identify these complications and select patients in need of
repeat angioplasty.
Another application in the vascular field concerns the determination of aortic stent
or graft endoleaks. In this setting, SPCCT in combination with a dual-contrast agent
injection protocol can reduce the conventional TC acquisition phases without sacrificing
diagnostic accuracy for endoleak detection and classification. It is thus possible to capture
the fluid dynamics of the endoleaks and allow a confident differential diagnosis with intra-
aneurysmal calcifications in a single CT scan. This new approach will realize a relevant
reduction in the radiation burden for patients undergoing CT surveillance after aortic
endovascular aneurysm repair [73].

3.6. Abdominal Imaging

Diagnostic imaging of liver disease is very common in clinical practice, often requiring
a dedicated multiphase CT acquisition protocol for both benign and malignant lesions, such
as hemangiomas, hepatocellular carcinoma (HCC), and metastases [74–76]. A retrospective
in-silico study assessed SPCCT’s ability to depict characteristic arterial and portal venous
enhancement with a single scan, allowing for streamlined lesion detection and characteri-
zation, again with additional benefits in terms of reduced radiation exposure dose [77]. As
previously stated, this is due to multi-color imaging allowed by SPCCT, producing multiple
image maps containing different information [78]. Regarding the liver, preclinical studies
on rabbits focused on the administration of iodine- and gadolinium-based contrast medi-
ums at different time points prior to CT scanning, leading the first to provide information
usually obtained in the portal phase while the second to arterial phase images.
Peritoneal metastases are indicative of terminal disease in most abdominal malig-
nancies. Still, over the past decades, the development of cytoreductive surgery with
or without intraperitoneal chemotherapy has led to improved patient survival for this
population [79–81]. For example, this approach has been tested in colorectal cancer, ob-
taining improved oncological outcomes [82]. In this context, preoperative assessment of
the peritoneal tumor burden is essential for the selection of patients eligible for potentially
curative treatment [83,84]. Magnetic resonance imaging (MRI) and hybrid imaging pairing
positron emission tomography and CT have shown good diagnostic performance, but these
modalities are mainly used as a complement to CT evaluation [83,85–87]. However, even
though CT imaging offers a high spatial and temporal resolution, its main drawback is the
lack of contrast resolution [88,89]. Therefore, current peritoneal imaging could also take
advantage of the promising opportunities provided by SPCCT. An initial experimental
study in rats [90], using a double-contrast agent injection protocol (i.e., intravenous iodine
and intraperitoneal gadolinium or the reverse protocol) into the peritoneal and vascular
compartments at different administration times, demonstrated a much greater sensitivity
(65%) of SPCCT for small lesions (defined as <5 mm) compared to a sensitivity of 11% re-
ported by Koh et al. using conventional CT [88]. If these results can be translated to clinical
practice, the higher sensitivity provided by SPCCT could avoid unnecessary “open-close”
surgical procedures.

3.7. Musculoskeletal Imaging

Articular cartilage is a highly specialized tissue, composed of water, collagen fibers,
and proteoglycans [91,92]. Due to its avascular nature and limited capability for regenera-
tion, an acute joint injury may induce post-traumatic osteoarthritis with a loss of proteo-
glycans, breakdown of fibers, and an increase in water content [93,94]. By estimating the
concentration of two contrast agents (non-ionic gadolinium-based gadoteridol and cationic
iodinated CA4+) [36], SPCCT could provide information directly indicative of the water and
proteoglycan content in the articular cartilage [95]. Therefore, contrast-enhanced SPCCT
imaging has potential use for the assessment of articular cartilage health and monitoring
the evolution of osteoarthritis [96].
J. Imaging 2022, 8, 112 7 of 12

Osteoarthritis represents the most common cause of disability, and it can be managed
by arthroplasty, especially for the knee [97]. Despite its frequent use, almost 20% of
patients report residual symptoms and functional limitations after surgical treatment [98].
Establishing the cause of symptoms and pain is fundamental to proper management, as
revision surgery with an uncertain diagnosis has a poor outcome [99]. The currently
available imaging techniques are important, but each modality presents its own limitations.
For example, radiography and fluoroscopy cannot delineate soft tissues; ultrasound may
depict effusions and soft tissue structures but cannot satisfactorily evaluate the prosthesis
or surrounding bony structure; conventional CT is limited by beam-hardening artifacts;
MRI is subject to metallic susceptibility artifacts caused by the prosthesis [100]. In a study
reported by Lau et al. [101], SPCCT could clearly identify polyethylene inserts and metallic
tray wear as the causes of prosthesis failure. These could not be identified on standard
pre-operative imaging.
SPCCT technology has other potential applications in the domain of musculoskeletal
imaging. For example, its material decomposition capabilities can be used to reconstruct
calcium-free images (i.e., non-calcium virtual images), allowing the evaluation of bone
edema without the need for MRI [102]. Furthermore, SPCCT can detect and characterize
the deposition of calcium crystals within the articular cartilage with high sensitivity and
relatively good specificity, as reported in the recent literature [103]. SPCCT is also the
only imaging technology capable of distinguishing between calcium pyrophosphate and
hydroxyapatite deposits, both when present in isolation and coexisting in the same joint
cartilage. This could provide new insights into the pathogenesis of crystal deposition
rheumatic diseases and aid in identifying new potential therapeutic targets.
Regarding the field of oncology, bone metastases are very frequent. Taking breast
cancer as an example, bone involvement is the common distant form of metastasis [104,105].
These lesions cause high morbidity with mortality hazard ratios of 5–6 compared to patients
without metastatic bone lesions [106]. In this regard, it is essential to correctly diagnose
their presence to guide the most correct therapeutic process. SPCCT may allow us to
identify smaller bone lesions with submillimeter spatial resolution, potentially leading to
a more precocious diagnosis. Its properties could also be used to differentiate between
true tumor growth and changes associated with therapy, mainly in a sclerotic sense (i.e.,
pseudo-progression). In particular, SPCCT reaches resolutions comparable with bone
trabecular diameters [107] and the resulting high-resolution images may allow for the
detection of metastatic changes in shorter intervals compared to conventional CT and MRI
imaging [108].

4. Conclusions
SPCCT has the potential to dramatically alter the clinical use of CT in the coming years.
By using energy-resolving detectors instead of EID, these new CT systems can substantially
reduce image noise, increase the spatial resolution, and use K-edge imaging to measure
the concentration of specific elements with reduced radiation doses compared to current
standards. These properties can be useful in the evaluation of multiple anatomical districts,
where it is necessary to identify small physiological and pathological structures, as well as
for the use of different contrast agents, even concurrently, as shown in our review.

Author Contributions: Conceptualization: R.C. and G.S.; Methodology: L.U., L.G. and I.D.; Writing—
original draft preparation: M.T.; Writing—review and editing: R.C. All authors have read and agreed
to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data sharing not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
J. Imaging 2022, 8, 112 8 of 12

References
1. Flohr, T.; Ulzheimer, S.; Petersilka, M.; Schmidt, B. Basic principles and clinical potential of photon-counting detector CT. Chin. J.
Acad. Radiol. 2020, 3, 19–34. [CrossRef]
2. Vliegenthart, R.; Pelgrim, G.J.; Ebersberger, U.; Rowe, G.W.; Oudkerk, M.; Schoepf, U.J. Dual-Energy CT of the Heart. Am. J.
Roentgenol. 2012, 199, S54–S63. [CrossRef] [PubMed]
3. Lu, G.M.; Zhao, Y.; Zhang, L.J.; Schoepf, U.J. Dual-Energy CT of the Lung. Am. J. Roentgenol. 2012, 199, S40–S53. [CrossRef]
[PubMed]
4. Marin, D.; Boll, D.T.; Mileto, A.; Nelson, R.C. State of the Art: Dual-Energy CT of the Abdomen. Radiology 2014, 271, 327–342.
[CrossRef]
5. Mallinson, P.I.; Coupal, T.M.; McLaughlin, P.D.; Nicolaou, S.; Munk, P.L.; Ouellette, H.A. Dual-Energy CT for the Musculoskeletal
System. Radiology 2016, 281, 690–707. [CrossRef]
6. Siegel, M.J.; Ramirez-Giraldo, J.C. Dual-Energy CT in Children: Imaging Algorithms and Clinical Applications. Radiology 2019,
291, 286–297. [CrossRef]
7. Willemink, M.J.; Persson, M.; Pourmorteza, A.; Pelc, N.J.; Fleischmann, D. Photon-counting CT: Technical Principles and Clinical
Prospects. Radiology 2018, 289, 293–312. [CrossRef]
8. Leng, S.; Bruesewitz, M.; Tao, S.; Rajendran, K.; Halaweish, A.F.; Campeau, N.G.; Fletcher, J.G.; McCollough, C.H. Photon-
counting Detector CT: System Design and Clinical Applications of an Emerging Technology. RadioGraphics 2019, 39, 729–743.
[CrossRef]
9. Flohr, T.G.; Stierstorfer, K.; Süß, C.; Schmidt, B.; Primak, A.N.; McCollough, C.H. Novel ultrahigh resolution data acquisition and
image reconstruction for multi-detector row CT. Med. Phys. 2007, 34, 1712–1723. [CrossRef]
10. Engel, K.J.; Spies, L.; Vogtmeier, G.; Luhta, R. Impact of CT detector pixel-to-pixel crosstalk on image quality. In Medical Imaging
2006: Physics of Medical Imaging; Flynn, M.J., Hsieh, J., Eds.; SPIE: Bellingham, WA, USA, 2006; p. 61422F.
11. Danielsson, M.; Persson, M.; Sjölin, M. Photon-counting x-ray detectors for CT. Phys. Med. Biol. 2021, 66, 03TR01. [CrossRef]
12. Taguchi, K.; Iwanczyk, J.S. Vision 20/20: Single photon counting x-ray detectors in medical imaging. Med. Phys. 2013, 40, 100901.
[CrossRef] [PubMed]
13. Xu, C.; Danielsson, M.; Bornefalk, H. Evaluation of Energy Loss and Charge Sharing in Cadmium Telluride Detectors for
Photon-Counting Computed Tomography. IEEE Trans. Nucl. Sci. 2011, 58, 614–625. [CrossRef]
14. Shikhaliev, P.M.; Fritz, S.G.; Chapman, J.W. Photon counting multienergy x-ray imaging: Effect of the characteristic x rays on
detector performance. Med. Phys. 2009, 36, 5107–5119. [CrossRef] [PubMed]
15. Jenkins, P.J.B.; Schmidt, T.G. Experimental study of photon-counting CT neural network material decomposition under conditions
of pulse pileup. J. Med. Imaging 2021, 8, 013502. [CrossRef]
16. Alvarez, R.E. Signal to noise ratio of energy selective x-ray photon counting systems with pileup. Med. Phys. 2014, 41, 111909.
[CrossRef] [PubMed]
17. Taguchi, K.; Zhang, M.; Frey, E.C.; Wang, X.; Iwanczyk, J.S.; Nygard, E.; Hartsough, N.E.; Tsui, B.M.W.; Barber, W.C. Modeling the
performance of a photon counting x-ray detector for CT: Energy response and pulse pileup effects. Med. Phys. 2011, 38, 1089–1102.
[CrossRef]
18. Wang, A.S.; Harrison, D.; Lobastov, V.; Tkaczyk, J.E. Pulse pileup statistics for energy discriminating photon counting x-ray
detectors. Med. Phys. 2011, 38, 4265–4275. [CrossRef]
19. Baek, J.; Pineda, A.R.; Pelc, N.J. To bin or not to bin? The effect of CT system limiting resolution on noise and detectability. Phys.
Med. Biol. 2013, 58, 1433–1446. [CrossRef]
20. Pourmorteza, A.; Symons, R.; Reich, D.S.; Bagheri, M.; Cork, T.E.; Kappler, S.; Ulzheimer, S.; Bluemke, D.A. Photon-Counting CT
of the Brain: In Vivo Human Results and Image-Quality Assessment. Am. J. Neuroradiol. 2017, 38, 2257–2263. [CrossRef]
21. Shikhaliev, P.M. Beam hardening artefacts in computed tomography with photon counting, charge integrating and energy
weighting detectors: A simulation study. Phys. Med. Biol. 2005, 50, 5813–5827. [CrossRef]
22. Kalluri, K.S.; Mahd, M.; Glick, S.J. Investigation of energy weighting using an energy discriminating photon counting detector for
breast CT. Med. Phys. 2013, 40, 081923. [CrossRef] [PubMed]
23. Schmidt, T.G. Optimal “image-based” weighting for energy-resolved CT. Med. Phys. 2009, 36, 3018–3027. [CrossRef] [PubMed]
24. Schmidt, T.G. CT energy weighting in the presence of scatter and limited energy resolution. Med. Phys. 2010, 37, 1056–1067.
[CrossRef] [PubMed]
25. Giersch, J.; Niederlöhner, D.; Anton, G. The influence of energy weighting on X-ray imaging quality. Nucl. Instrum. Methods Phys.
Res. Sect. A Accel. Spectrometers Detect. Assoc. Equip. 2004, 531, 68–74. [CrossRef]
26. Alvarez, R.E.; Macovski, A. Energy-selective reconstructions in X-ray computerised tomography. Phys. Med. Biol. 1976, 21, 002.
[CrossRef]
27. Leng, S.; Zhou, W.; Yu, Z.; Halaweish, A.; Krauss, B.; Schmidt, B.; Yu, L.; Kappler, S.; McCollough, C. Spectral performance
of a whole-body research photon counting detector CT: Quantitative accuracy in derived image sets. Phys. Med. Biol. 2017,
62, 7216–7232. [CrossRef]
28. Yu, L.; Christner, J.A.; Leng, S.; Wang, J.; Fletcher, J.G.; McCollough, C.H. Virtual monochromatic imaging in dual-source
dual-energy CT: Radiation dose and image quality. Med. Phys. 2011, 38, 6371–6379. [CrossRef]
J. Imaging 2022, 8, 112 9 of 12

29. Johnson, T.R.C.; Krauß, B.; Sedlmair, M.; Grasruck, M.; Bruder, H.; Morhard, D.; Fink, C.; Weckbach, S.; Lenhard, M.; Schmidt, B.;
et al. Material differentiation by dual energy CT: Initial experience. Eur. Radiol. 2007, 17, 1510–1517. [CrossRef]
30. Pourmorteza, A.; Symons, R.; Henning, A.; Ulzheimer, S.; Bluemke, D.A. Dose Efficiency of Quarter-Millimeter Photon-Counting
Computed Tomography. Investig. Radiol. 2018, 53, 365–372. [CrossRef]
31. Ballabriga, R.; Alozy, J.; Bandi, F.N.; Campbell, M.; Egidos, N.; Fernandez-Tenllado, J.M.; Heijne, E.H.M.; Kremastiotis, I.; Llopart,
X.; Madsen, B.J.; et al. Photon Counting Detectors for X-Ray Imaging with Emphasis on CT. IEEE Trans. Radiat. Plasma Med. Sci.
2021, 5, 422–440. [CrossRef]
32. Fornaro, J.; Leschka, S.; Hibbeln, D.; Butler, A.; Anderson, N.; Pache, G.; Scheffel, H.; Wildermuth, S.; Alkadhi, H.; Stolzmann, P.
Dual- and multi-energy CT: Approach to functional imaging. Insights Imaging 2011, 2, 149–159. [CrossRef] [PubMed]
33. Müllner, M.; Schlattl, H.; Hoeschen, C.; Dietrich, O. Feasibility of spectral CT imaging for the detection of liver lesions with
gold-based contrast agents—A simulation study. Phys. Med. 2015, 31, 875–881. [CrossRef] [PubMed]
34. Cormode, D.P.; Skajaa, T.; Fayad, Z.A.; Mulder, W.J.M. Nanotechnology in Medical Imaging. Arterioscler. Thromb. Vasc. Biol. 2009,
29, 992–1000. [CrossRef] [PubMed]
35. Si-Mohamed, S.; Cormode, D.P.; Bar-Ness, D.; Sigovan, M.; Naha, P.C.; Langlois, J.-B.; Chalabreysse, L.; Coulon, P.; Blevis, I.;
Roessl, E.; et al. Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold
nanoparticle biodistribution in vivo. Nanoscale 2017, 9, 18246–18257. [CrossRef] [PubMed]
36. McCollough, C.H.; Leng, S.; Yu, L.; Fletcher, J.G. Dual- and Multi-Energy CT: Principles, Technical Approaches, and Clinical
Applications. Radiology 2015, 276, 637–653. [CrossRef]
37. Goodsitt, M.M.; Christodoulou, E.G.; Larson, S.C. Accuracies of the synthesized monochromatic CT numbers and effective atomic
numbers obtained with a rapid kVp switching dual energy CT scanner. Med. Phys. 2011, 38, 2222–2232. [CrossRef]
38. Pelgrim, G.J.; van Hamersvelt, R.W.; Willemink, M.J.; Schmidt, B.T.; Flohr, T.; Schilham, A.; Milles, J.; Oudkerk, M.; Leiner, T.;
Vliegenthart, R. Accuracy of iodine quantification using dual energy CT in latest generation dual source and dual layer CT. Eur.
Radiol. 2017, 27, 3904–3912. [CrossRef]
39. Liu, X.; Yu, L.; Primak, A.N.; McCollough, C.H. Quantitative imaging of element composition and mass fraction using dual-energy
CT: Three-material decomposition. Med. Phys. 2009, 36, 1602–1609. [CrossRef]
40. Long, Y.; Fessler, J.A. Multi-Material Decomposition Using Statistical Image Reconstruction for Spectral CT. IEEE Trans. Med.
Imaging 2014, 33, 1614–1626. [CrossRef]
41. Schlomka, J.P.; Roessl, E.; Dorscheid, R.; Dill, S.; Martens, G.; Istel, T.; Bäumer, C.; Herrmann, C.; Steadman, R.; Zeitler, G.; et al.
Experimental feasibility of multi-energy photon-counting K-edge imaging in pre-clinical computed tomography. Phys. Med. Biol.
2008, 53, 4031–4047. [CrossRef]
42. Roessl, E.; Brendel, B.; Engel, K.-J.; Schlomka, J.-P.; Thran, A.; Proksa, R. Sensitivity of Photon-Counting Based Edge Imaging in
X-ray Computed Tomography. IEEE Trans. Med. Imaging 2011, 30, 1678–1690. [CrossRef] [PubMed]
43. Roessl, E.; Proksa, R. K-edge imaging in x-ray computed tomography using multi-bin photon counting detectors. Phys. Med. Biol.
2007, 52, 4679–4696. [CrossRef] [PubMed]
44. Si-Mohamed, S.; Bar-Ness, D.; Sigovan, M.; Tatard-Leitman, V.; Cormode, D.P.; Naha, P.C.; Coulon, P.; Rascle, L.; Roessl, E.; Rokni,
M.; et al. Multicolour imaging with spectral photon-counting CT: A phantom study. Eur. Radiol. Exp. 2018, 2, 34. [CrossRef]
[PubMed]
45. Symons, R.; Reich, D.S.; Bagheri, M.; Cork, T.E.; Krauss, B.; Ulzheimer, S.; Kappler, S.; Bluemke, D.A.; Pourmorteza, A. Photon-
Counting Computed Tomography for Vascular Imaging of the Head and Neck. Investig. Radiol. 2018, 53, 135–142. [CrossRef]
[PubMed]
46. Kuno, H.; Onaya, H.; Iwata, R.; Kobayashi, T.; Fujii, S.; Hayashi, R.; Otani, K.; Ojiri, H.; Yamanaka, T.; Satake, M. Evaluation
of Cartilage Invasion by Laryngeal and Hypopharyngeal Squamous Cell Carcinoma with Dual-Energy CT. Radiology 2012,
265, 488–496. [CrossRef] [PubMed]
47. Leng, S.; Yu, Z.; Halaweish, A.; Kappler, S.; Hahn, K.; Henning, A.; Li, Z.; Lane, J.; Levin, D.L.; Jorgensen, S.; et al. A high-
resolution imaging technique using a whole-body, research photon counting detector CT system. In Medical Imaging 2016: Physics
of Medical Imaging; Kontos, D., Flohr, T.G., Lo, J.Y., Eds.; SPIE: Bellingham, WA, USA, 2016; p. 97831I.
48. Rajendran, K.; Voss, B.A.; Zhou, W.; Tao, S.; DeLone, D.R.; Lane, J.I.; Weaver, J.M.; Carlson, M.L.; Fletcher, J.G.; McCollough, C.H.;
et al. Dose Reduction for Sinus and Temporal Bone Imaging Using Photon-Counting Detector CT With an Additional Tin Filter.
Investig. Radiol. 2020, 55, 91–100. [CrossRef]
49. Zhou, W.; Lane, J.I.; Carlson, M.L.; Bruesewitz, M.R.; Witte, R.J.; Koeller, K.K.; Eckel, L.J.; Carter, R.E.; McCollough, C.H.; Leng, S.
Comparison of a Photon-Counting-Detector CT with an Energy-Integrating-Detector CT for Temporal Bone Imaging: A Cadaveric
Study. Am. J. Neuroradiol. 2018, 39, 1733–1738. [CrossRef]
50. Kopp, F.K.; Daerr, H.; Si-Mohamed, S.; Sauter, A.P.; Ehn, S.; Fingerle, A.A.; Brendel, B.; Pfeiffer, F.; Roessl, E.; Rummeny, E.J.; et al.
Evaluation of a preclinical photon-counting CT prototype for pulmonary imaging. Sci. Rep. 2018, 8, 17386. [CrossRef]
51. Si-Mohamed, S.A.; Miailhes, J.; Rodesch, P.-A.; Boccalini, S.; Lacombe, H.; Leitman, V.; Cottin, V.; Boussel, L.; Douek, P. Spectral
Photon-Counting CT Technology in Chest Imaging. J. Clin. Med. 2021, 10, 5757. [CrossRef]
52. Si-Mohamed, S.A.; Greffier, J.; Miailhes, J.; Boccalini, S.; Rodesch, P.-A.; Vuillod, A.; van der Werf, N.; Dabli, D.; Racine, D.;
Rotzinger, D.; et al. Comparison of image quality between spectral photon-counting CT and dual-layer CT for the evaluation of
lung nodules: A phantom study. Eur. Radiol. 2022, 32, 524–532. [CrossRef]
J. Imaging 2022, 8, 112 10 of 12

53. Symons, R.; Cork, T.E.; Sahbaee, P.; Fuld, M.K.; Kappler, S.; Folio, L.R.; Bluemke, D.A.; Pourmorteza, A. Low-dose lung cancer
screening with photon-counting CT: A feasibility study. Phys. Med. Biol. 2017, 62, 202–213. [CrossRef] [PubMed]
54. Watadani, T.; Sakai, F.; Johkoh, T.; Noma, S.; Akira, M.; Fujimoto, K.; Bankier, A.A.; Lee, K.S.; Müller, N.L.; Song, J.-W.; et al.
Interobserver Variability in the CT Assessment of Honeycombing in the Lungs. Radiology 2013, 266, 936–944. [CrossRef] [PubMed]
55. Raghu, G.; Collard, H.R.; Egan, J.J.; Martinez, F.J.; Behr, J.; Brown, K.K.; Colby, T.V.; Cordier, J.-F.; Flaherty, K.R.; Lasky, J.A.;
et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and
Management. Am. J. Respir. Crit. Care Med. 2011, 183, 788–824. [CrossRef]
56. Ferda, J.; Vendiš, T.; Flohr, T.; Schmidt, B.; Henning, A.; Ulzheimer, S.; Pecen, L.; Ferdová, E.; Baxa, J.; Mírka, H. Computed
tomography with a full FOV photon-counting detector in a clinical setting, the first experience. Eur. J. Radiol. 2021, 137, 109614.
[CrossRef] [PubMed]
57. Bartlett, D.J.; Koo, C.W.; Bartholmai, B.J.; Rajendran, K.; Weaver, J.M.; Halaweish, A.F.; Leng, S.; McCollough, C.H.; Fletcher, J.G.
High-Resolution Chest Computed Tomography Imaging of the Lungs. Investig. Radiol. 2019, 54, 129–137. [CrossRef] [PubMed]
58. Onishi, H.; Taniguchi, Y.; Matsuoka, Y.; Yanaka, K.; Izawa, Y.; Tsuboi, Y.; Mori, S.; Kono, A.; Nakayama, K.; Emoto, N.; et al.
Evaluation of microvasculopathy using dual-energy computed tomography in patients with chronic thromboembolic pulmonary
hypertension. Pulm. Circ. 2021, 11, 2045894020983162. [CrossRef] [PubMed]
59. Rößler, A.-C.; Kalender, W.; Kolditz, D.; Steiding, C.; Ruth, V.; Preuss, C.; Peter, S.C.; Brehm, B.; Hammon, M.; Schulz-
Wendtland, R.; et al. Performance of Photon-Counting Breast Computed Tomography, Digital Mammography, and Digital Breast
Tomosynthesis in Evaluating Breast Specimens. Acad. Radiol. 2017, 24, 184–190. [CrossRef]
60. Shikhaliev, P.M. Soft tissue imaging with photon counting spectroscopic CT. Phys. Med. Biol. 2015, 60, 2453–2474. [CrossRef]
61. Van der Werf, N.R.; Si-Mohamed, S.; Rodesch, P.A.; van Hamersvelt, R.W.; Greuter, M.J.W.; Boccalini, S.; Greffier, J.; Leiner, T.;
Boussel, L.; Willemink, M.J.; et al. Coronary calcium scoring potential of large field-of-view spectral photon-counting CT: A
phantom study. Eur. Radiol. 2022, 32, 152–162. [CrossRef]
62. Symons, R.; Sandfort, V.; Mallek, M.; Ulzheimer, S.; Pourmorteza, A. Coronary artery calcium scoring with photon-counting CT:
First in vivo human experience. Int. J. Cardiovasc. Imaging 2019, 35, 733–739. [CrossRef]
63. Symons, R.; Cork, T.E.; Lakshmanan, M.N.; Evers, R.; Davies-Venn, C.; Rice, K.A.; Thomas, M.L.; Liu, C.-Y.; Kappler, S.; Ulzheimer,
S.; et al. Dual-contrast agent photon-counting computed tomography of the heart: Initial experience. Int. J. Cardiovasc. Imaging
2017, 33, 1253–1261. [CrossRef] [PubMed]
64. Maintz, D.; Juergens, K.-U.; Wichter, T.; Grude, M.; Heindel, W.; Fischbach, R. Imaging of coronary artery stents using multislice
computed tomography: In vitro evaluation. Eur. Radiol. 2003, 13, 830–835. [CrossRef] [PubMed]
65. Mahnken, A.H.; Buecker, A.; Wildberger, J.E.; Ruebben, A.; Stanzel, S.; Vogt, F.; Günther, R.W.; Blindt, R. Coronary Artery Stents
in Multislice Computed Tomography. Investig. Radiol. 2004, 39, 27–33. [CrossRef] [PubMed]
66. Maintz, D.; Seifarth, H.; Raupach, R.; Flohr, T.; Rink, M.; Sommer, T.; Özgün, M.; Heindel, W.; Fischbach, R. 64-slice multidetector
coronary CT angiography: In vitro evaluation of 68 different stents. Eur. Radiol. 2006, 16, 818–826. [CrossRef] [PubMed]
67. Maintz, D.; Burg, M.C.; Seifarth, H.; Bunck, A.C.; Özgün, M.; Fischbach, R.; Jürgens, K.U.; Heindel, W. Update on multidetector
coronary CT angiography of coronary stents: In vitro evaluation of 29 different stent types with dual-source CT. Eur. Radiol. 2009,
19, 42–49. [CrossRef]
68. Mannil, M.; Hickethier, T.; von Spiczak, J.; Baer, M.; Henning, A.; Hertel, M.; Schmidt, B.; Flohr, T.; Maintz, D.; Alkadhi, H.
Photon-Counting CT. Investig. Radiol. 2018, 53, 143–149. [CrossRef]
69. Bratke, G.; Hickethier, T.; Bar-Ness, D.; Bunck, A.C.; Maintz, D.; Pahn, G.; Coulon, P.; Si-Mohamed, S.; Douek, P.; Sigovan, M.
Spectral Photon-Counting Computed Tomography for Coronary Stent Imaging. Investig. Radiol. 2020, 55, 61–67. [CrossRef]
70. Stettler, C.; Wandel, S.; Allemann, S.; Kastrati, A.; Morice, M.C.; Schömig, A.; Pfisterer, M.E.; Stone, G.W.; Leon, M.B.; de Lezo,
J.S.; et al. Outcomes associated with drug-eluting and bare-metal stents: A collaborative network meta-analysis. Lancet 2007,
370, 937–948. [CrossRef]
71. Smits, P.C.; Vlachojannis, G.J.; McFadden, E.P.; Royaards, K.-J.; Wassing, J.; Joesoef, K.S.; van Mieghem, C.; van de Ent, M. Final
5-Year Follow-Up of a Randomized Controlled Trial of Everolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization
in Daily Practice. JACC Cardiovasc. Interv. 2015, 8, 1157–1165. [CrossRef]
72. Chen, M.S.; John, J.M.; Chew, D.P.; Lee, D.S.; Ellis, S.G.; Bhatt, D.L. Bare metal stent restenosis is not a benign clinical entity. Am.
Heart J. 2006, 151, 1260–1264. [CrossRef]
73. Dangelmaier, J.; Bar-Ness, D.; Daerr, H.; Muenzel, D.; Si-Mohamed, S.; Ehn, S.; Fingerle, A.A.; Kimm, M.A.; Kopp, F.K.; Boussel,
L.; et al. Experimental feasibility of spectral photon-counting computed tomography with two contrast agents for the detection of
endoleaks following endovascular aortic repair. Eur. Radiol. 2018, 28, 3318–3325. [CrossRef] [PubMed]
74. Belghiti, J.; Cauchy, F.; Paradis, V.; Vilgrain, V. Diagnosis and management of solid benign liver lesions. Nat. Rev. Gastroenterol.
Hepatol. 2014, 11, 737–749. [CrossRef] [PubMed]
75. Kim, T.; Murakami, T.; Takahashi, S.; Tsuda, K.; Tomoda, K.; Narumi, Y.; Oi, H.; Sakon, M.; Nakamura, H. Optimal phases of
dynamic CT for detecting hepatocellular carcinoma: Evaluation of unenhanced and triple-phase images. Abdom. Imaging 1999,
24, 473–480. [CrossRef] [PubMed]
76. Soyer, P.; Poccard, M.; Boudiaf, M.; Abitbol, M.; Hamzi, L.; Panis, Y.; Valleur, P.; Rymer, R. Detection of Hypovascular Hepatic
Metastases at Triple-Phase Helical CT: Sensitivity of Phases and Comparison with Surgical and Histopathologic Findings.
Radiology 2004, 231, 413–420. [CrossRef]
J. Imaging 2022, 8, 112 11 of 12

77. Muenzel, D.; Daerr, H.; Proksa, R.; Fingerle, A.A.; Kopp, F.K.; Douek, P.; Herzen, J.; Pfeiffer, F.; Rummeny, E.J.; Noël, P.B.
Simultaneous dual-contrast multi-phase liver imaging using spectral photon-counting computed tomography: A proof-of-
concept study. Eur. Radiol. Exp. 2017, 1, 25. [CrossRef] [PubMed]
78. Si-Mohamed, S.; Tatard-Leitman, V.; Laugerette, A.; Sigovan, M.; Pfeiffer, D.; Rummeny, E.J.; Coulon, P.; Yagil, Y.; Douek, P.;
Boussel, L.; et al. Spectral Photon-Counting Computed Tomography (SPCCT): In-vivo single-acquisition multi-phase liver
imaging with a dual contrast agent protocol. Sci. Rep. 2019, 9, 8458. [CrossRef]
79. Chua, T.C.; Moran, B.J.; Sugarbaker, P.H.; Levine, E.A.; Glehen, O.; Gilly, F.N.; Baratti, D.; Deraco, M.; Elias, D.; Sardi, A.; et al.
Early- and Long-Term Outcome Data of Patients With Pseudomyxoma Peritonei From Appendiceal Origin Treated by a Strategy
of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. J. Clin. Oncol. 2012, 30, 2449–2456. [CrossRef]
80. Van Driel, W.J.; Koole, S.N.; Sikorska, K.; Schagen van Leeuwen, J.H.; Schreuder, H.W.R.; Hermans, R.H.M.; de Hingh, I.H.J.T.;
van der Velden, J.; Arts, H.J.; Massuger, L.F.A.G.; et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N. Engl.
J. Med. 2018, 378, 230–240. [CrossRef]
81. Bonnot, P.-E.; Piessen, G.; Kepenekian, V.; Decullier, E.; Pocard, M.; Meunier, B.; Bereder, J.-M.; Abboud, K.; Marchal, F.; Quenet,
F.; et al. Cytoreductive Surgery with or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Peritoneal
Metastases (CYTO-CHIP study): A Propensity Score Analysis. J. Clin. Oncol. 2019, 37, 2028–2040. [CrossRef]
82. Quénet, F.; Elias, D.; Roca, L.; Goéré, D.; Ghouti, L.; Pocard, M.; Facy, O.; Arvieux, C.; Lorimier, G.; Pezet, D.; et al. Cytoreductive
surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases
(PRODIGE 7): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021, 22, 256–266. [CrossRef]
83. Dohan, A.; Hobeika, C.; Najah, H.; Pocard, M.; Rousset, P.; Eveno, C. Preoperative assessment of peritoneal carcinomatosis of
colorectal origin. J. Visc. Surg. 2018, 155, 293–303. [CrossRef] [PubMed]
84. Sugarbaker, P.H.; Sardi, A.; Brown, G.; Dromain, C.; Rousset, P.; Jelinek, J.S. Concerning CT features used to select patients for
treatment of peritoneal metastases, a pictoral essay. Int. J. Hyperth. 2017, 33, 497–504. [CrossRef] [PubMed]
85. Dohan, A.; Hoeffel, C.; Soyer, P.; Jannot, A.S.; Valette, P.-J.; Thivolet, A.; Passot, G.; Glehen, O.; Rousset, P. Evaluation of the
peritoneal carcinomatosis index with CT and MRI. Br. J. Surg. 2017, 104, 1244–1249. [CrossRef] [PubMed]
86. Laghi, A.; Bellini, D.; Rengo, M.; Accarpio, F.; Caruso, D.; Biacchi, D.; Di Giorgio, A.; Sammartino, P. Diagnostic performance of
computed tomography and magnetic resonance imaging for detecting peritoneal metastases: Systematic review and meta-analysis.
Radiol. Med. 2017, 122, 1–15. [CrossRef] [PubMed]
87. Torkzad, M.; Casta, N.; Bergman, A.; Ahlström, H.; Påhlman, L.; Mahteme, H. Comparison between MRI and CT in prediction of
peritoneal carcinomatosis index (PCI) in patients undergoing cytoreductive surgery in relation to the experience of the radiologist.
J. Surg. Oncol. 2015, 111, 746–751. [CrossRef] [PubMed]
88. Koh, J.-L.; Yan, T.D.; Glenn, D.; Morris, D.L. Evaluation of Preoperative Computed Tomography in Estimating Peritoneal Cancer
Index in Colorectal Peritoneal Carcinomatosis. Ann. Surg. Oncol. 2009, 16, 327–333. [CrossRef]
89. Marin, D.; Catalano, C.; Baski, M.; Di Martino, M.; Geiger, D.; Di Giorgio, A.; Sibio, S.; Passariello, R. 64-Section multi-detector
row CT in the preoperative diagnosis of peritoneal carcinomatosis: Correlation with histopathological findings. Abdom. Imaging
2010, 35, 694–700. [CrossRef]
90. Thivolet, A.; Si-Mohamed, S.; Bonnot, P.-E.; Blanchet, C.; Képénékian, V.; Boussel, L.; Douek, P.; Rousset, P. Spectral photon-
counting CT imaging of colorectal peritoneal metastases: Initial experience in rats. Sci. Rep. 2020, 10, 13394. [CrossRef]
91. Sophia Fox, A.J.; Bedi, A.; Rodeo, S.A. The Basic Science of Articular Cartilage: Structure, Composition, and Function. Sports
Health 2009, 1, 461–468. [CrossRef]
92. Hunziker, E.B.; Quinn, T.M.; Häuselmann, H.-J. Quantitative structural organization of normal adult human articular cartilage.
Osteoarthr. Cartil. 2002, 10, 564–572. [CrossRef]
93. Hosseininia, S.; Lindberg, L.R.; Dahlberg, L.E. Cartilage collagen damage in hip osteoarthritis similar to that seen in knee os-
teoarthritis: A case-control study of relationship between collagen, glycosaminoglycan and cartilage swelling. BMC Musculoskelet.
Disord. 2013, 14, 18. [CrossRef] [PubMed]
94. Andriacchi, T.P.; Mündermann, A.; Smith, R.L.; Alexander, E.J.; Dyrby, C.O.; Koo, S. A Framework for the in Vivo Pathomechanics
of Osteoarthritis at the Knee. Ann. Biomed. Eng. 2004, 32, 447–457. [CrossRef] [PubMed]
95. Bhattarai, A.; Honkanen, J.T.J.; Myller, K.A.H.; Prakash, M.; Korhonen, M.; Saukko, A.E.A.; Virén, T.; Joukainen, A.; Patwa, A.N.;
Kröger, H.; et al. Quantitative Dual Contrast CT Technique for Evaluation of Articular Cartilage Properties. Ann. Biomed. Eng.
2018, 46, 1038–1046. [CrossRef] [PubMed]
96. Paakkari, P.; Inkinen, S.I.; Honkanen, M.K.M.; Prakash, M.; Shaikh, R.; Nieminen, M.T.; Grinstaff, M.W.; Mäkelä, J.T.A.; Töyräs, J.;
Honkanen, J.T.J. Quantitative dual contrast photon-counting computed tomography for assessment of articular cartilage health.
Sci. Rep. 2021, 11, 5556. [CrossRef]
97. Turkiewicz, A.; Petersson, I.F.; Björk, J.; Hawker, G.; Dahlberg, L.E.; Lohmander, L.S.; Englund, M. Current and future impact
of osteoarthritis on health care: A population-based study with projections to year 2032. Osteoarthr. Cartil. 2014, 22, 1826–1832.
[CrossRef]
98. Bourne, R.B.; Chesworth, B.M.; Davis, A.M.; Mahomed, N.N.; Charron, K.D.J. Patient Satisfaction after Total Knee Arthroplasty:
Who is Satisfied and Who is Not? Clin. Orthop. Relat. Res. 2010, 468, 57–63. [CrossRef]
99. Mont, M.A.; Serna, F.K.; Krackow, K.A.; Hungerford, D.S. Exploration of Radiographically Normal Total Knee Replacements for
Unexplained Pain. Clin. Orthop. Relat. Res. 1996, 331, 216–220. [CrossRef]
J. Imaging 2022, 8, 112 12 of 12

100. Flierl, M.A.; Sobh, A.H.; Culp, B.M.; Baker, E.A.; Sporer, S.M. Evaluation of the Painful Total Knee Arthroplasty. J. Am. Acad.
Orthop. Surg. 2019, 27, 743–751. [CrossRef]
101. Lau, L.C.M.; Lee, W.Y.W.; Butler, A.P.H.; Chernoglazov, A.I.; Chung, K.Y.; Ho, K.K.W.; Griffith, J.; Butler, P.H.; Yung, P.S.H.
Multi-energy spectral photon-counting computed tomography (MARS) for detection of arthroplasty implant failure. Sci. Rep.
2021, 11, 1554. [CrossRef]
102. Kellock, T.T.; Nicolaou, S.; Kim, S.S.Y.; Al-Busaidi, S.; Louis, L.J.; O’Connell, T.W.; Ouellette, H.A.; McLaughlin, P.D. Detection of
Bone Marrow Edema in Nondisplaced Hip Fractures: Utility of a Virtual Noncalcium Dual-Energy CT Application. Radiology
2017, 284, 798–805. [CrossRef]
103. Bernabei, I.; Sayous, Y.; Raja, A.Y.; Amma, M.R.; Viry, A.; Steinmetz, S.; Falgayrac, G.; van Heeswijk, R.B.; Omoumi, P.; Pascart, T.;
et al. Multi-energy photon-counting computed tomography versus other clinical imaging techniques for the identification of
articular calcium crystal deposition. Rheumatology 2021, 60, 2483–2485. [CrossRef] [PubMed]
104. Coleman, R.E. Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity. Clin. Cancer Res. 2006, 12, 6243s–6249s.
[CrossRef] [PubMed]
105. Kennecke, H.; Yerushalmi, R.; Woods, R.; Cheang, M.C.U.; Voduc, D.; Speers, C.H.; Nielsen, T.O.; Gelmon, K. Metastatic Behavior
of Breast Cancer Subtypes. J. Clin. Oncol. 2010, 28, 3271–3277. [CrossRef] [PubMed]
106. Sathiakumar, N.; Delzell, E.; Morrisey, M.A.; Falkson, C.; Yong, M.; Chia, V.; Blackburn, J.; Arora, T.; Brill, I.; Kilgore, M.L.
Mortality following bone metastasis and skeletal-related events among women with breast cancer: A population-based analysis
of U.S. Medicare beneficiaries, 1999–2006. Breast Cancer Res. Treat. 2012, 131, 231–238. [CrossRef] [PubMed]
107. Eckstein, F.; Matsuura, M.; Kuhn, V.; Priemel, M.; Müller, R.; Link, T.M.; Lochmüller, E.-M. Sex Differences of Human Trabecular
Bone Microstructure in Aging Are Site-Dependent. J. Bone Miner. Res. 2007, 22, 817–824. [CrossRef]
108. Wehrse, E.; Sawall, S.; Klein, L.; Glemser, P.; Delorme, S.; Schlemmer, H.-P.; Kachelrieß, M.; Uhrig, M.; Ziener, C.H.; Rotkopf, L.T.
Potential of ultra-high-resolution photon-counting CT of bone metastases: Initial experiences in breast cancer patients. npj Breast
Cancer 2021, 7, 3. [CrossRef]