Photon-counting Computed Tomography Imaging Research Articles

Diagnostic Accuracy of Contrast-Enhanced Thoracic Photon-Counting Computed Tomography for Opportunistic Locoregional Staging of Breast Cancer Compared With Digital Mammography: A Prospective Trial.

Accurate locoregional staging is crucial for effective breast cancer treatment. Photon-counting computed tomography (PC-CT) is an emerging technology with high spatial resolution and the ability to depict uptake of contrast agents in tissues, making it a promising tool for breast cancer imaging. The aim of this study was to establish the feasibility of locoregional staging of breast cancer through contrast-enhanced thoracic PC-CT, assess its diagnostic performance, and compare it with that of digital mammography (DM). Patients with newly diagnosed breast cancer, DM, and indication of thoracic CT staging were prospectively enrolled in this clinical cohort study over a period of 6 months. Participants underwent contrast-enhanced thoracic PC-CT and breast magnetic resonance imaging in prone position. After blinding to patient data, 2 radiologists independently rated PC-CT and DM regarding the following 6 characteristics: (1) diameter of the largest mass lesion, (2) infiltration of cutis/pectoral muscle/thoracic wall, (3) number of mass lesions, (4) presence/absence of adjacent ductal carcinoma in situ (DCIS), (5) tumor conspicuity, and (6) diagnostic confidence. Reference standard was generated from consensus reading of magnetic resonance imaging combined with all histopathological/clinical data by an independent adjudication committee applying TNM eighth edition. Among 32 enrolled female subjects (mean ± SD age, 59 ± 13.0 years), diagnostic accuracy for T-classification was higher for PC-CT compared with DM (0.94 vs 0.50, P < 0.01). Moreover, the correlation of the number of detected tumor masses with the reference standard was stronger for PC-CT than for DM (0.72 vs 0.50, P < 0.01). We observed that PC-CT significantly (P < 0.04) outperformed DM regarding not only sensitivity (0.83 and 0.25, respectively) but also specificity (0.99 and 0.80, respectively) for adjacent DCIS. The κ values for interreader reliability were higher for PC-CT compared with DM (mean 0.88 vs 0.54, respectively; P = 0.01). Photon-counting computed tomography outperformed DM in T-classification and provided higher diagnostic accuracy for the detection of adjacent DCIS. Therefore, opportunistic locoregional staging of breast cancer in contrast-enhanced thoracic PC-CT is feasible and could overcome limitations of DM with the potential to improve patient management.

Advanced photon counting CT imaging pipeline for cardiac phenotyping of apolipoprotein E mouse models.

Cardiovascular disease (CVD) is associated with the apolipoprotein E (APOE) gene and lipid metabolism. This study aimed to develop an imaging-based pipeline to comprehensively assess cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT). 123 mice grouped based on APOE genotype (APOE2, APOE3, APOE4, APOE knockout (KO)), gender, human NOS2 factor, and diet (control or high fat) were used in this study. The pipeline included PCCT imaging on a custom-built system with contrast-enhanced in vivo imaging and intrinsic cardiac gating, spectral and temporal iterative reconstruction, spectral decomposition, and deep learning cardiac segmentation. Statistical analysis evaluated genotype, diet, sex, and body weight effects on cardiac measurements. Our results showed that PCCT offered high quality imaging with reduced noise. Material decomposition enabled separation of calcified plaques from iodine enhanced blood in APOE KO mice. Deep learning-based segmentation showed good performance with Dice scores of 0.91 for CT-based segmentation and 0.89 for iodine map-based segmentation. Genotype-specific differences were observed in left ventricular volumes, heart rate, stroke volume, ejection fraction, and cardiac index. Statistically significant differences were found between control and high fat diets for APOE2 and APOE4 genotypes in heart rate and stroke volume. Sex and weight were also significant predictors of cardiac measurements. The inclusion of the human NOS2 gene modulated these effects. This study demonstrates the potential of PCCT in assessing cardiac structure and function in mouse models of CVD which can help in understanding the interplay between genetic factors, diet, and cardiovascular health.

Leveraging 3D Bioprinting and Photon-Counting Computed Tomography to Enable Noninvasive Quantitative Tracking of Multifunctional Tissue Engineered Constructs.

3D bioprinting is revolutionizing the fields of personalized and precision medicine by enabling the manufacturing of bioartificial implants that recapitulate the structural and functional characteristics of native tissues. However, the lack of quantitative and noninvasive techniques to longitudinally track the function of implants has hampered clinical applications of bioprinted scaffolds. In this study, multimaterial 3D bioprinting, engineered nanoparticles (NPs), and spectral photon-counting computed tomography (PCCT) technologies are integrated for the aim of developing a new precision medicine approach to custom-engineer scaffolds with traceability. Multiple CT-visible hydrogel-based bioinks, containing distinct molecular (iodine and gadolinium) and NP (iodine-loaded liposome, gold, methacrylated gold (AuMA), and Gd2 O3 ) contrast agents, are used to bioprint scaffolds with varying geometries at adequate fidelity levels. In vitro release studies, together with printing fidelity, mechanical, and biocompatibility tests identified AuMA and Gd2 O3 NPs as optimal reagents to track bioprinted constructs. Spectral PCCT imaging of scaffolds in vitro and subcutaneous implants in mice enabled noninvasive material discrimination and contrast agent quantification. Together, these results establish a novel theranostic platform with high precision, tunability, throughput, and reproducibility and open new prospects for a broad range of applications in the field of precision and personalized regenerative medicine.

Detection performance of pixelated lutetium-yttrium oxyorthosilicate (LYSO) scintillators for high-resolution photon-counting CT imaging.

High-resolution photon-counting detector (PCD) computed tomography (CT) imaging is increasingly used for several applications. Recent technological advances in CT instrumentation have introduced various types of radiation detectors. Therefore, this work aims at evaluating the lutetium-yttrium oxyorthosilicate (LYSO) scintillator for use in PCD CT from a detector point of view. To do so, a mini-CT prototype was designed and constructed based on the pixelated LYSO blocks. The detector comprises four 10 × 10 linearly arranged LYSO blocks coupled with four position-sensitive photomultiplier tubes. The prototype utilizes a point gamma-ray source along with a cone-beam collimator. An in-home MATLAB-based data processing software package was also developed for storing the list-mode data, event positioning, and energy windowing. A set of experiments were conducted to assess the performance of the constructed energy-resolved LYSO:Ce detector for mini-CT imaging. The results show good crystal identification for all blocks with a maximum peak-to-valley ratio of 3.48. In addition, the findings confirm that the developed detector is position-sensitive. The 20% energy window provides an optimal performance by simultaneously providing good crystal identification and a scatter removal factor of 0.71. A 96% uniformity was also observed when the detector was irradiated with a uniform flood. The spatial resolution of the mini-CT prototype in the x- and y-directions was calculated to be 0.9 and 0.93mm, respectively, corrected for a magnification factor of 2.5. It is concluded that the pixelated LYSO crystal is a promising alternative to the current detectors and would be the scintillator of choice for high-resolution PCD CT imaging tasks.

Abstract MP207: A Precision Medicine Approach For Non-invasive, Longitudinal, And Quantitative Monitoring Of Cardiac Tissue-engineered Scaffolds

3D bioprinting has revolutionized personalized and precision medicine by enabling the manufacturing of tissue constructs that precisely recapitulate the cellular and functional features of native tissues. In cardiac regenerative medicine, printed scaffolds have shown tremendous potential in repairing damaged heart, however, their clinical applications have been limited by the lack of precise noninvasive tools to monitor the patch function following implantation. By integrating state-of-the-art 3D bioprinting and photon-counting computed tomography (PCCT), this study introduces a new approach for bioengineering defect-specific scaffolds and monitoring their function. We prepared distinct CT-visible bioinks containing a variety of molecular or nanoparticle (NP) contrast agents, including iodine and gadolinium molecules, Au NPs, Gd 2 O 3 NPs, and iodine-loaded liposomes ( Fig 1A-B ). In vitro release experiments showed relatively rapid diffusion-controlled depletion of molecular contrast agents from scaffolds. In contrast, NP agents showed more stable encapsulation and only a partial, degradation-mediated release for up to 3 weeks of incubation ( Fig 1C-D ). Next, PCCT imaging was performed on various scaffold geometries printed using bioinks laden with Gd 2 O 3 or Au NPs. Results demonstrated CT visibility with differential contrast between different patch regions that corresponded to the designed geometries ( Fig 1E ). Finally, we evaluated the in vivo CT imaging of bioprinted patches after their subcutaneous implantation in a mouse model. CT images demonstrated adequate signal from implanted grafts ( Fig 1F ). Together, these results establish a novel precision medicine platform for non-invasive monitoring of medical devices which can open new prospects for a broad range of tissue engineering applications. Figure 1. 3D Bioprinting of CT-visible cardiac patches. A-B: Design of bioinks functionalized with molecular (left) and nanoparticle (right) CT contrast agents ( A ) and their bioprinting ( B ). C-D: In vitro release of contrast agents from printed patches. E: CAD design (left), CT image (middle), and PCCT material decomposition (right) for multi-contrast bioprinted scaffolds. F: In vivo CT imaging of printed patch, laden with Au NPs, implanted subcutaneously into a mouse torso.

Data traffic compression in spectral photon-counting CT imaging based on human visual characteristics

Spectral computed tomography (CT) with photon-counting detectors (PCDs) can provide a variety of cross-sectional images, showing improved diagnostic capability at low radiation doses. PCDs acquire and divide signals of each energy intensity into separate energy bins and improve the count rate by pixel size miniaturization, which can simultaneously increase spatial resolution. Nevertheless, PCDs do show some limitations in data processing. Acquisition of large-spectrum data requires large spaces of an analog-to-digital converter (ADC) and a memory in each pixel, and this process generates massive amounts of data traffic. The conventional compression techniques used in CT imaging are not suitable for such traffic because they are applied to the CT image data, not the projection data stored by PCDs. This study aimed to secure ADC and memory space and compress the data traffic while maintaining high image resolution by using a number of energy bin's information for computing. This approach was based on a composite method using CT images from high spatial resolution non-spectral CT and low spatial resolution spectral CT. The resolution in non-spectral CT was recognized by assigning grayscale values, while the resolution for spectral CT was maintained with a pseudocolor scale based on visual characteristics. In this paper, we evaluated the image quality against the compression rate to verify our concept.

MDM-PCCT: Multiple Dynamic Modulations for High-Performance Spectral PCCT Imaging

Photon counting computed tomography (PCCT) has the ability to identify individual photons, resulting in quantitative material identification. Meanwhile, several technical challenges still exist in current PCCT imaging systems, including increased noise and suboptimal bin selection. These nonideal effects can substantially degrade the reconstruction performance and material estimation accuracy. To address these issues, in this work, we present a novel system for high-performance spectral PCCT imaging, which is a combination of multiple dynamic modulations, interpolation-based measurements processing strategy and advanced reconstruction method. For simplicity, this new PCCT imaging system is referred to as "MDM-PCCT". Specifically, the multiple dynamic modulations consist of dynamic kVp modulation, dynamic spectrum modulation and dynamic energy threshold modulation. In the dynamic kVp modulation, three kVp values, i.e., 80, 110 and 140, are included, and the tube voltage waveform follows a sinusoidal curve which is more practical than the rectangular curve in the fast kV switching mode. In the dynamic spectrum modulation, the X-ray spectra are processed by selective spatial-spectral filters to balance the X-ray fluxes and increase the spectral separation. In the dynamic energy threshold modulation, the energy threshold is adaptively changed to determine the optimal bin selection. Furthermore, we propose an energy threshold determination method and interpolation-based measurements processing strategy to address the issue of non-uniform and sparse-view PCCT measurements, respectively. In addition, by considering the intrinsic characteristics of the MDM-PCCT images, we utilize an enhanced total variation regularized model for images reconstruction. Finally, numerical and preclinical studies demonstrate that the presented MDM-PCCT imaging system is capable of yielding uniform and high-fidelity PCCT measurements with noise consistency, and the presented reconstruction method further improves the image quality and material decomposition accuracy.

Feasibility of improving vascular imaging in the presence of metallic stents using spectral photon counting CT and K-edge imaging

Correct visualization of the vascular lumen is impaired in standard computed tomography (CT) because of blooming artifacts, increase of apparent size, induced by metallic stents and vascular calcifications. Recently, due to the introduction of photon-counting detectors in the X-ray imaging field, a new prototype spectral photon-counting CT (SPCCT) based on a modified clinical CT system has been tested in a feasibility study for improving vascular lumen delineation and visualization of coronary stent architecture. Coronary stents of different metal composition were deployed inside plastic tubes containing hydroxyapatite spheres to simulate vascular calcifications and in the abdominal aorta of one New Zealand White (NZW) rabbit. Imaging was performed with an SPCCT prototype, a dual-energy CT system, and a conventional 64-channel CT system (B64). We found the apparent widths of the stents significantly smaller on SPCCT than on the other two systems in vitro (p < 0.01), thus closer to the true size. Consequently, the intra-stent lumen was significantly larger on SPCCT (p < 0.01). In conclusion, owing to the increased spatial resolution of SPCCT, improved lumen visualization and delineation of stent metallic mesh is possible compared to dual-energy and conventional CT.

Development of LSI for a new kind of photon-counting computed tomography using multipixel photon counters

X-ray imaging with computed tomography (CT) is widely used for nondestructive imaging of the interior of the human body. In the next decade, photon-counting X-ray CT is expected to reduce the dose needed and enable multicolor imaging. Recently, we proposed a novel photon-counting method that uses a multipixel photon counter (MPPC), with a significantly high signal gain (∼106) and fast temporal response (a few nanoseconds), combined with a high-speed scintillator. To realize photon-counting CT imaging in a wide area irradiated by an extremely high X-ray flux (106-107 Hz/mm2), a multichannel MPPC system is required. Thus, we developed a large-scale integrated circuit (LSI) with ultrafast signal-processing capability for use with a 16-channel MPPC. The developed LSI can extract a pulse current from an MPPC array with a large detector capacitance (∼200 pF) by utilizing an electrical circuit with low input impedance. The LSI offers a high photon count rate above 25 MHz/pixel with noise equal to 1.7 μA for a dynamic range of ∼ 1.3 mA and an energy resolution of 32 % (FWHM) at 60 keV, thereby enabling ultrafast multicolor CT imaging.

Spectral prior image constrained compressed sensing (spectral PICCS) for photon-counting computed tomography

Photon-counting computed tomography (PCCT) is an emerging imaging technique that enables multi-energy imaging with only a single scan acquisition. To enable multi-energy imaging, the detected photons corresponding to the full x-ray spectrum are divided into several subgroups of bin data that correspond to narrower energy windows. Consequently, noise in each energy bin increases compared to the full-spectrum data. This work proposes an iterative reconstruction algorithm for noise suppression in the narrower energy bins used in PCCT imaging. The algorithm is based on the framework of prior image constrained compressed sensing (PICCS) and is called spectral PICCS; it uses the full-spectrum image reconstructed using conventional filtered back-projection as the prior image. The spectral PICCS algorithm is implemented using a constrained optimization scheme with adaptive iterative step sizes such that only two tuning parameters are required in most cases. The algorithm was first evaluated using computer simulations, and then validated by both physical phantoms and in vivo swine studies using a research PCCT system. Results from both computer-simulation and experimental studies showed substantial image noise reduction in narrow energy bins (43–73%) without sacrificing CT number accuracy or spatial resolution.

Photon counting x-ray imaging with K-edge filtered x-rays: A simulation study.

In photon counting (PC) x-ray imaging and computed tomography (CT), the broad x-ray spectrum can be split into two parts using an x-ray filter with appropriate K-edge energy, which can improve material decomposition. Recent experimental study has demonstrated substantial improvement in material decomposition with PC CT when K-edge filtered x-rays were used. The purpose of the current work was to conduct further investigations of the K-edge filtration method using comprehensive simulation studies. The study was performed in the following aspects: (1) optimization of the K-edge filter for a particular imaging configuration, (2) effects of the K-edge filter parameters on material decomposition, (3) trade-off between the energy bin separation, tube load, and beam quality with K-edge filter, (4) image quality of general (unsubtracted) images when a K-edge filter is used to improve dual energy (DE) subtracted images, and (5) improvements with K-edge filtered x-rays when PC detector has limited energy resolution. The PC x-ray images of soft tissue phantoms with 15 and 30 cm thicknesses including iodine, CaCO3, and soft tissue contrast materials, were simulated. The signal to noise ratio (SNR) of the contrast elements was determined in general and material-decomposed images using K-edge filters with different atomic numbers and thicknesses. The effect of the filter atomic number and filter thickness on energy separation factor and SNR was determined. The boundary conditions for the tube load and halfvalue layer were determined when the K-edge filters are used. The material-decomposed images were also simulated using PC detector with limited energy resolution, and improvements with K-edge filtered x-rays were quantified. The K-edge filters with atomic numbers from 56 to 71 and K-edge energies 37.4-63.4 keV, respectively, can be used for tube voltages from 60 to 150 kVp, respectively. For a particular tube voltage of 120 kVp, the Gd and Ho were the optimal filter materials to achieve highest SNR. For a particular K-edge filter of Gd and tube voltage of 120 kVp, the filter thickness 0.6 mm provided maximum SNR for considered imaging applications. While K-edge filtration improved SNR of CaCO3 and iodine by 41% and 36%, respectively, in DE subtracted images, it did not deteriorate SNR in general images. For x-ray imaging with nonideal PC detector, the positive effect of the K-edge filter was increased when FWHM energy resolution was degraded, and maximum improvement was at 60% FWHM. This study has shown that K-edge filtered x-rays can provide substantial improvements of material selective PC x-ray and CT imaging for nearly all imaging applications using 60-150 kVp tube voltages. Potential limitations such as tube load, beam hardening, and availability of filter material were shown to not be critical.

Computed tomography with energy-resolved detection: a feasibility study

The feasibility of computed tomography (CT) with energy-resolved x-ray detection has been investigated. A breast CT design with multi slit multi slice (MSMS) data acquisition was used for this study. The MSMS CT includes linear arrays of photon counting detectors separated by gaps. This CT configuration allows for efficient scatter rejection and 3D data acquisition. The energy-resolved CT images were simulated using a digital breast phantom and the design parameters of the proposed MSMS CT. The phantom had 14 cm diameter and 50/50 adipose/glandular composition, and included carcinoma, adipose, blood, iodine and CaCO3 as contrast elements. The x-ray technique was 90 kVp tube voltage with 660 mR skin exposure. Photon counting, charge (energy) integrating and photon energy weighting CT images were generated. The contrast-to-noise (CNR) improvement with photon energy weighting was quantified. The dual energy subtracted images of CaCO3 and iodine were generated using a single CT scan at a fixed x-ray tube voltage. The x-ray spectrum was electronically split into low- and high-energy parts by a photon counting detector. The CNR of the energy weighting CT images of carcinoma, blood, adipose, iodine, and CaCO3 was higher by a factor of 1.16, 1.20, 1.21, 1.36 and 1.35, respectively, as compared to CT with a conventional charge (energy) integrating detector. Photon energy weighting was applied to CT projections prior to dual energy subtraction and reconstruction. Photon energy weighting improved the CNR in dual energy subtracted CT images of CaCO3 and iodine by a factor of 1.35 and 1.33, respectively. The combination of CNR improvements due to scatter rejection and energy weighting was in the range of 1.71–2 depending on the type of the contrast element. The tilted angle CZT detector was considered as the detector of choice. Experiments were performed to test the effect of the tilting angle on the energy spectrum. Using the CZT detector with 20° tilting angle decreased the tailing of the measured x-ray spectrum as compared to a conventional CZT detector. It was concluded that the energy-resolved MSMS CT with tilted angle CZT detector is potentially feasible and could provide a unique combination of photon counting, energy weighting, scatter rejection and single kVp dual energy subtraction CT imaging.

Investigation of the LabPET™ detector and electronics for photon-counting CT imaging

The development of new molecular probes targeting receptors with high specificity in selected cells and tissues highlights the importance of obtaining the anatomical context in Positron Emission Tomography (PET) imaging. This can be achieved using another imaging modality, such as X-ray Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), but the anatomic and molecular images obtained sequentially with different scanners must subsequently be co-registered and are subjected to motion artifacts. Conventional CT imaging also contributes a significant dose, which may compromise the benefits of longitudinal molecular imaging studies in the same subject. To overcome these difficulties, we have investigated the use of the LabPET™ detector and electronics as a multi-modal detection system. Based on fast light emitting inorganic scintillators individually coupled to avalanche photodiodes and parallel, low-noise, fast digital processing electronics, the proposed detector front-end is suitable for coincidence detection of annihilation radiation (511 keV) in PET and for ultra-fast low-energy X-ray photon counting in CT. This combined detection system enables concurrent PET/CT imaging while potentially achieving superior image contrast sensitivity for a given dose in CT photon-counting mode. Anatomical images with millimeter spatial resolution and sufficient tissue contrast for anatomical localization in small animals have been obtained with doses in the mGy range. The CT performance for dual-modality imaging of small animals was analyzed in terms of spatial resolution, noise and image contrast sensitivity as a function of dose.