Clinical Implications of Photon-Counting Computed Tomography Technology: History
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Filippo Cademartiri
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Antonella Meloni
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Laura Pistoia
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Giulia Degiorgi
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Alberto Clemente
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Carmelo De Gori
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Vincenzo Positano
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Simona Celi
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Sergio Berti
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Michele Emdin
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Daniele Panetta
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Luca Menichetti
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Bruna Punzo
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Carlo Cavaliere
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Eduardo Bossone
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Luca Saba
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Riccardo Cau
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Ludovico La Grutta
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Erica Maffei

The photon-counting detector (PCD) is a new computed tomography detector technology (photon-counting computed tomography, PCCT) that provides substantial benefits for cardiac and coronary artery imaging. Compared with conventional CT, PCCT has multi-energy capability, increased spatial resolution and soft tissue contrast with near-null electronic noise, reduced radiation exposure, and optimization of the use of contrast agents. This new technology promises to overcome several limitations of traditional cardiac and coronary CT angiography (CCT/CCTA) including reduction in blooming artifacts in heavy calcified coronary plaques or beam-hardening artifacts in patients with coronary stents, and a more precise assessment of the degree of stenosis and plaque characteristic thanks to its better spatial resolution. 

  • photon-counting computed tomography
  • computed tomography angiography
  • coronary computed tomography

1. Clinical Implications of Photon-Counting CT Technology

The main clinical translation of new PCCT technology in the cardiac field application is related to the higher spatial resolution and to the multiparametric/multi-energetic nature of the information collected.
The presence of semiconductor materials and the detector element size results in higher spatial resolution [1][2][3]. This provides a much more detailed capability of visualization of smaller anatomical structures with more contrast resolution, including coronary lumen and stent patency. Improved spatial resolution can be also helpful for a better evaluation of high-risk plaque features, namely low-attenuation plaques, spotty calcifications, positive remodeling, and napkin-ring sign [3][4]. PCCT technology enables the counting of both the cumulative number of photons and their energy distribution, leading to improved contrast-to-noise ratio and energy discrimination capabilities. This translates into increased iodine contrast, reduced administered radiation dose, or reduced contrast media volume required to obtain comparable enhancement [5][6][7]. Finally, multi-energy capabilities of PCCT detectors could be useful to reduce metal artifact, differentiate components of coronary atherosclerosis plaque, and discern between different exogenous contrast agents [3][5][8][9][10].

2. Coronary Lumen

The PCCT system provides clinical benefits in the luminal assessment of coronary arteries, enabling improved spatial resolution and contrast-to-noise ratio [6].
In a recent prospective study of 14 patients who underwent both PCCT and conventional CT angiography, PCCT demonstrated a score improvement for overall quality and diagnostic confidence of 57% (95% CI: 41, 72) and 55% (95% CI: 39, 70), respectively, and 48% (95% CI: 33, 63), 51% (95% CI: 35, 67), and 69 (95% CI: 53, 82) for coronary proximal lumen, coronary distal lumen, and coronary wall, respectively [11]. These findings were also supported by a phantom study reporting that PCCT images had a 2.3-fold increased detectably index for coronary lumen in comparison with conventional CT images [11]. In an in vitro study, PCCT was compared with EID under various conditions of simulated patient size (small, medium, and large), demonstrating lower noise magnitude and higher noise frequency peak with better spatial resolution compared to EID [12]. Moreover, PCCT can be advantageous in quantifying luminal stenosis in heavily calcified plaques in comparison with conventional CT scanners, as demonstrated in a recent phantom study, especially for concentric heavy calcified plaque configuration [13]. Similar results were also reported by Li et al., who demonstrated a reduction in partial volume and blooming artifacts resulting in a finer stenosis assessment [14]. In parallel, PCCT enables CCT K-edge imaging using a gadolinium-based contrast agent. An ex vivo coronary artery study showed an improved luminal depiction with clear differentiation among the intravascular gadolinium-based contrast agent, calcified plaque, and stent material [15]. Similar results have also been recently described using iodinated contrast agents [16].
A different approach to assess the vessel lumen is the use of emerging image reconstruction algorithms based on spectral CT [17]. Allmendinger et al. investigated the performance of a novel calcium-removal image reconstruction algorithm (called PureLumen) to eliminate only the calcified contribution of an anthropomorphic thorax phantom attached to an artificial motion device, simulating realistic cardiac motion [17]. The authors demonstrated decreased blooming artifacts and an improvement in image interpretability [17]. PCCT enables an “always available” multi-energy discrimination, overcoming a current dilemma in cardiac CT, represented by the infeasibility of high temporal resolution and multi-energy imaging acquisition [18].
In addition, improved spatial resolution of PCCT allows a proportion of improvement in diagnostic quality for pericoronary fat tissue of 36% (95% CI: 22, 52) in comparison with conventional CT scanners [11].

3. Coronary Stent

Current state-of-the-art CT scanners do not always allow optimal assessment of the vessel lumen in patients with coronary stents due to several technical issues (e.g., metallic, blooming, and beam-hardening artifacts, as well as limited spatial resolution) [19][20].
In a recent in vitro study, PCCT was compared with conventional CT scanners in the evaluation of 18 different coronary stents. The authors reported superior in-stent visibility, and fewer blooming and partial volume artifacts, with a smaller increase in the attenuation of the lumen inside the stent for PCCT [4]. These results were also confirmed in different in vitro studies [21][22].
Recently, several in-human studies investigated the advantages of PCCT in coronary stent evaluation [11][23]. Boccalini et al. compared the image quality of in vivo coronary stents between PCCT and conventional CT, reporting a superior stent and lumen visibility with fewer artifacts and lower dose radiation (25.7 mGy for PCCT vs. 35.7 mGy for conventional CT, p = 0.02) [23]. Similar results were also reported by Si-Mohamed et al., who compared the quality of CCT scans obtained with PCCT technology and conventional CT scanners [11]. The authors described a proportion of improvement with PCCT images for coronary stent of 92% (95% CI: 71, 98) in diagnostic quality with a lower mean dose-length product (411 mGy vs. 592 ± 171, p < 0.01) [11].

4. Coronary Artery Calcium Score

Coronary artery calcium (CAC) is generally quantified on CT using the Agatston score [24][25][26]. The factor used for the calculation of the Agatston score is selected according to fixed HU thresholds and is highly dependent on the maximum attenuation of a calcified plaque [25][26]. PCCT allows for reducing the level of electronic noise, resulting in less image noise, fewer streak artifacts, and more stable Hounsfield unit (HU) numbers [27][28]. In an in vitro study, coronary calcium scoring was compared between PCCT and conventional CT scanners, reporting a comparable CAC score for the routine clinical protocol [29]. Further, PCCT increased detectability and accuracy in CAC with a reduced slice thickness [29]. Symons et al. investigated the performance of PCCT at standard and reduced radiation doses in a dedicated cardiac CT phantom, ten ex vivo hearts, and ten asymptomatic volunteers [30]. Phantom and in vivo human studies demonstrated the potential of PCCT to improve CAC score image quality and/or to reduce radiation dose while maintaining diagnostic image quality [30].
An excellent correlation and agreement were demonstrated between the CAC score derived from PCCT and conventional CT in 26 calcified coronary lesions from 5 cadaveric hearts [31], supporting the potential use of the Agatston score derived from PCCT in clinical practice.
Eberhard et al. investigated the accuracy of the CAC score on PCCT in comparison with conventional CT scanners and explored the optimal virtual mono-energetic images and iterative image reconstruction algorithm at different radiation doses in a phantom and patients [32]. The study showed decreasing CAC score at increasing iterative image reconstruction algorithm levels (p < 0.001) and increasing keV levels (p < 0.001) [32].
PCCT may also have substantial benefits for aortic valve calcification score imaging. In an initial report of five patients who underwent transcatheter aortic valve replacement planning CT using a novel PCCT, an excellent correlation of aortic valve calcium score and volumes between virtual non-contrast and true-contrast images (r = 0.945, p = 0.01; r = 0.938, p = 0.01; respectively) was demonstrated [33].

5. Atherosclerotic Plaque Composition

Besides stenosis assessment, a growing body of evidence has emphasized the need for a more detailed evaluation of atherosclerotic plaque morphology and characteristics [34][35][36][37][38][39]. Direct visualization of coronary plaque components (e.g., thin cap fibroatheroma, microcalcifications) is problematic in conventional CT scanners [40][41][42]. PCCT, thanks to its improved spatial resolution, provides an improvement in diagnostic quality for coronary calcification and noncalcified plaque of 100% and 45% (95% CI: 28, 63), respectively [11]. In an in vitro study, PCCT provided superior detectability for simulated 0.5 mm thick non-calcified plaques (AUC ≈ 95% vs. AUC ≈ 75%) and lipid-rich atherosclerotic plaques (AUC = 85% vs. AUC = 77.5%) in comparison with EID [12].
Further, spectral analysis also allows multi-material mapping via a material decomposition algorithm. A preliminary ex vivo study investigated the capabilities of PCCT to differentiate components of coronary atherosclerosis plaque in 23 histologically demonstrated atheromatous plaques from post-mortem human coronary arteries [43]. PCCT was demonstrated to identify plaque components by measuring differences in contrast agent concentration and spectral attenuation [43]. Another ex vivo study confirmed the significant potential of PCCT to distinguish components of vulnerable atherosclerotic plaque (calcium, iron, lipid surrogate, and cellular surrogate) based on their different photo-electric and Compton effects with good correlation with histological slices [44]. Furthermore, Jorgensen et al. demonstrated the ability of PCCT to quantify vasa vasorum density as a marker of early atherosclerosis changes in perfusion of the arterial wall [45].
A recent ex vivo study explored the effectiveness of PCCT to quantify vulnerable plaque features (e.g., fibrous cap thickness, fibrous cap area, and lipid-rich necrotic core area) and compared PCCT features with histological measurements. PCCT and histological measurement of fibrous cap thickness, fibrous cap area, and lipid-rich necrotic core area did not show significant differences (p > 0.05) [46].

6. Multi-Contrast-Material Applications

This game-changing technology enables different exogenous contrast agents to be discerned and takes full advantage of the capability of K-edge imaging with the introduction of novel contrast agents (e.g., nanoparticles). K-edge imaging enables the recognition of the binding energy between the inner electron shell and the atom as a specific signature, permitting a specific and quantitative evaluation of different contrast agents [3]. These novel contrast agents promise to overcome some limitations of iodine-based agents, including rapid circulation, short retention time, and the similar HU value of iodine to that of calcium at high kilovolt tube voltages [47]. The feasibility of using PCCT to perform multi-contrast imaging of three contrast materials was recently demonstrated in different phantom studies, allowing the creation of a separate material density map for each contrast agent [1][3][10][48][49].
A recent in vivo study explored the capability of PCCT to simultaneously discriminate between three contrast agents, namely, intravenous gadolinium and iodine, and oral bismuth, in an animal model, and reported the feasibility of PCCT to differentiate the three K-edge contrast agents in vivo [50].
Recent works have been performed on the use of nanoparticles for PCCT [15][48][51][52][53][54][55]. Si-Mohamed compared PCCT-enabled K-edge imaging in combination with gold nanoparticles with conventional CT images, histologic examination, and transmission electron microscopy data to detect the macrophage burden within rabbit atherosclerotic aortas [48]. A good correlation between the gold concentration and the macrophage area was found (r = 0.82; 95% CI: 0.67, 0.91; p = 0.001), highlighting the potential role of PCCT in atherosclerosis in terms of plaque composition and vulnerability [48]. Another in vivo and phantom study demonstrated the potential of PCCT in association with a gold high-density lipoprotein nanoparticle contrast agent to identify macrophage burden, calcifications, and stenosis of atherosclerosis plaques [56].
Similarly, tungsten-based and ytterbium-based contrast media have shown to improve atherosclerotic imaging with respect to lumen and plaque visualization [57][58]. Further potential applications of nanoparticles include visualization of tumor vasculature, detection of bleeding, and vascular abnormalities after treatment. Riederer et al. investigated the potential of PCCT to discriminate between liquid embolic agents and iodinated contrast medium using a tantalum-based contrast [59]. The authors demonstrated in a phantom study that PCCT can provide a tantalum density map, differentiating between tantalum and iodine, and enabling the reduction in artifacts due to the liquid embolic agents in patients after vascular occlusion therapy [59]. Gold nanoparticles and liposomal iodine were used in an in vivo study to quantify tumor blood volume and vascular permeability as indicators of cancer angiogenesis [60]. The conjunction of PCCT with gold nanoparticles in the study by Moghiseh et al. allowed the identification and quantification of specific monoclonal antibody-labeled gold nanoparticles with accurate detection of tumor heterogeneity [61].

7. Myocardial Tissue Imaging

PCCT ensures dual-energy or multi-energy acquisition at a single X-ray tube potential thanks to its energy-discrimination capability. In contrast to DECT, PCCT can differentiate more than two contrast media in each voxel at the time of acquisition.
This technology can be applied to determine the extent of cardiac damage in myocardial infarction using a double-contrast agent. The first in vivo experiments were conducted in a canine model with myocardial infarction by injecting gadolinium-based and iodine contrast media [8]. The authors demonstrated that these multi-contrast agents can combine first-pass iodine and late gadolinium maps to discriminate between blood pool, scar, and remote myocardium [8].
Quantification of material concentration may be useful for myocardial perfusion analyses since this allows the exact quantification of the contrast agent in the myocardium [8][9][62]. Notably, iodine maps represent a well-known CT technique to assess myocardial perfusion and have also been validated for the quantification of myocardial late iodine enhancement on DECT [63][64]. The energy threshold capability of PCCT enables minimization of the spectral overlap of DECT, improving the contrast-to-noise ratio and the quantitative capabilities to estimate contrast media concentrations [3].
A recent case report demonstrated the usefulness of spectral CT in clinical practice [65]. Polacin et al. described a case report of a 61-year-old male with acute chest pain who underwent a PCCT scan for suspected acute coronary syndrome. Dual-energy-derived iodine maps from PCCT demonstrated a small ischemic transmural scar, confirmed with late gadolinium cardiac magnetic resonance [65].
Combined iodine/gadolinium injection imaging may be also useful for endovascular leak assessment, as recently demonstrated in a phantom study [66]. Material maps derived from PCCT allowed a reliable distinction of contrast media and aneurysmatic calcifications [66].
An in vivo study explored the radiomics features of the left ventricle myocardium in 30 patients using first-generation, whole-body, dual-source PCCT, reporting an association of coronary artery calcifications and texture analysis [67]. The authors highlighted the potential role of PCCT to overcome the well-known limitation of radiomics analysis in comparison with EID CT, thanks to its higher spatial resolution and contrast-to-noise ratio, and fewer artifacts [67]. Tharmaseelan et al. investigated the texture changes of periaortic adipose tissue in relationship with aortic calcifications using PCCT, demonstrating an association of periaortic adipose tissue with the presence of local aortic calcifications using radiomics analysis [68].
Recently, CT has been demonstrated to be an alternative method to extracellular volume fraction (ECV) quantification in comparison with cardiac magnetic resonance that represents the current non-invasive reference standard. The capability to characterize myocardial tissue using PCCT was emphasized in the in vivo study of Mergen et al. [69]. The authors investigated the feasibility and accuracy of extracellular volume quantification in 30 patients with severe aortic stenosis using PCCT with virtual mono-energetic and dual-energy iodine maps [69]. Virtual mono-energetic and dual energy-derived ECV quantification showed a high correlation (r = 0.87, p < 0.001) with narrow limits of agreements and a mean error of 0.9%.

8. Dose and Contrast Media Reduction

PCCT can boost the attenuation of iodinated contrast media. It is well known that the linear attenuation coefficient of iodine increases with decreasing X-ray energy. This physical aspect results in the possibility of using a lower amount of intravenous contrast media, achieving the same diagnostic results as a full-dose conventional CT examination. This was demonstrated for CCT in a phantom study where the use of virtual mono-energetic image reconstruction at 40 KeV on PCCT allowed reduction in the contrast media concentration by up 50% [70]. Several studies have shown an improved contrast-to-noise ratio using PCCT in comparison with conventional CT scanners, resulting in iodine contrast concentration reduction. Kappler et al. investigated these features in a water phantom, reporting an increased attenuation of iodine with similar image noise compared to conventional CT scanners [71].
An anthropomorphic phantom and ex vivo study investigated the iodine contrast-to-noise ratio in commercial-energy-integrated and PC detectors simulating four patient sizes at four tube potential settings [72]. The authors demonstrated a mean increase in contrast-to-noise ratio of 11%, 23%, 31%, and 38% in comparison with commercially available CT scanners at 80, 100, 120, and 140 kV, respectively [72]. Further, PCCT of a cadaveric human showed decreased artifacts (e.g., beam-hardening and blooming) in the high-energy bin images and improved contrast in low-energy bin images compared to energy-integrated-detector CT [72].
Sawall et al. explored the potential of PCCT to increase iodine contrast, reduce administered radiation dose, or reduce contrast media volume in a phantom of different sizes (small, medium, and large) using an energy-integrated-detector, single-bin PCCT, and two-bin PCCT [6]. The average contrast-to-noise ratio improved using all tube voltages and phantom sizes with an augmentation up to 30% (small: 10%, medium: 18%, large: 30%) with single-bin energy, and up to 37% (small: 13%, medium: 25%, large: 37%) with two-bin energy, highlighting a potential radiation dose reduction of up to 46% [6]. These findings suggested that PCCT can reduce the amount of contrast media required. In this regard, patients allergic to iodine or with renal insufficiency may benefit from spectral CT.
The improvement in electronic noise on image quality by PCCT was assessed for various cardiovascular applications at a low radiation dose. Superior quality of CAC scoring at low radiation doses was described in an in vitro, ex vivo, and in vivo study [30]. The absence of electronic noise in combination with improved soft-tissue contrast allowed the reduction in the radiation dose of CAC scoring [30]. A significant dose reduction (up to 67%) in CAC scoring was also described in an anthropomorphic thorax phantom study using virtual mono-energetic images from PCCT [73].

This entry is adapted from the peer-reviewed paper 10.3390/jcm12113627

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