Ex-vivo atherosclerotic plaque characterization using spectral photon-counting CT: Comparing material quantification to histology.

BACKGROUND AND AIMS: Atherosclerotic plaques are characterized as being vulnerable to rupture based on a series of histologically defined features, including a lipid-rich necrotic core, spotty calcification and ulceration. Existing imaging modalities have limitations in their ability to distinguish between different materials and structural features. We examined whether X-ray spectral photon-counting computer tomography (SPCCT) images were able to distinguish key plaque features in a surgically excised specimen from the carotid artery with comparison to histological images. METHODS: An excised carotid plaque was imaged in the diagnostic X-ray energy range of 30-120 keV using a small-bore SPCCT scanner equipped with a Medipix3RX photon-counting spectral X-ray detector with a cadmium telluride (CdTe) sensor. Material identification and quantification (MIQ) images of the carotid plaque were generated using proprietary MIQ software at 0.09 mm volumetric pixels (voxels). The plaque was sectioned, stained and photographed at high resolution for comparison. RESULTS: A lipid-rich core with spotty calcification was identified in the MIQ images and confirmed by histology. MIQ showed a core region containing lipid, with a mean concentration of 260 mg lipid/ml corresponding to a mean value of -22HU. MIQ showed calcified regions with mean concentration of 41 mg Ca/ml corresponded to a mean value of 123HU. An ulceration of the carotid wall at the bifurcation was identified to be lipid-lined, with a small calcification identified near the breach of the artery wall. CONCLUSIONS: SPCCT derived material identification and quantification images showed hallmarks of vulnerable plaque including a lipid-rich necrotic core, spotty calcifications and ulcerations.

Gadolinium K-edge angiography with a spectral photon counting CT in atherosclerotic rabbits.

PURPOSE: The purpose of this study was to investigate the feasibility of gadolinium-K-edge-angiography (angio-Gd-K-edge) with gadolinium-based contrast agents (GBCAs) as obtained with spectral photon counting CT (SPCCT) in atherosclerotic rabbits. MATERIALS AND METHODS: Seven atherosclerotic rabbits underwent angio-SPCCT acquisitions with two GBCAs, with similar intravenous injection protocol. Conventional and angio-Gd-K-edge images were reconstructed with the same parameters. Regions of interest were traced in different locations of the aorta and its branches. Hounsfield unit values, Gd concentrations, signal-to-noise (SNR) and contrast-to-noise (CNR) were calculated and compared. The maximum diameter and the diameter of the aorta in regard to atherosclerotic plaques were measured by two observers. Images were subjectively evaluated regarding vessels' enhancement, artefacts, border sharpness and overall image quality. RESULTS: In the analyzable six rabbits, Gd-K-edge allowed visualization of target vessels and no other structures. HU values and Gd concentrations were greatest in the largest artery (descending aorta, 5.6 ± 0.8 [SD] mm), and lowest in the smallest (renal arteries, 2.1 ± 0.3 mm). While greater for conventional images, CNR and SNR were satisfactory for both images (all P < 0.001). For one observer there were no statistically significant differences in either maximum or plaque-diameters (P = 0.45 and all P > 0.05 in post-hoc analysis, respectively). For the second observer, there were no significant differences for images reconstructed with the same parameters (all P < 0.05). All subjective criteria scored higher for conventional images compared to K-edge (all P < 0.01), with the highest scores for enhancement (4.3-4.4 vs. 3.1-3.4). CONCLUSION: With SPCCT, angio-Gd-K-edge after injection of GBCAs in atherosclerotic rabbits is feasible and allows for angiography-like visualization of small arteries and for the reliable measurement of their diameters.

Clinical commissioning of the first point-of-care spectral photon-counting CT for the upper extremities.

BACKGROUND: Acceptance testing and quality assurance (QA) of computed tomography (CT) scans are of great importance to ensure the appropriate performance of the systems. However, current standards and guidelines do not include a dedicated QA program for spectral photon-counting CT (SPCCT), nor adapted tolerance levels. PURPOSE: To evaluate the technical performance, in terms of image quality and radiation dose, of the first point-of-care SPCCT for the upper extremities (MARS Extremity 5X120, MARS Bioimaging Ltd., Christchurch, New Zealand) and to establish a comprehensive QA program. METHODS: The specific dimensions of the scanner with a 125 mm diameter gantry and a small voxel size of 0.1 × 0.1 × 0.1 mm3 require the use of suitable phantoms and evaluation techniques. Indicators such as CT number accuracy, image noise, uniformity, and slice thickness were assessed to characterize the image quality. The in-plane and longitudinal spatial resolutions were evaluated by means of the modulation transfer function (MTF). Noise power spectra (NPS) were calculated to further evaluate the image noise. Material identification capabilities were assessed using clinically relevant high-Z materials (iodine, gold, gadolinium, and calcium). A 100-mm diameter CTDI-like phantom was used to measure the dose indices. A complete radiation survey was carried out to measure the radiation exposure at different points around the scanner. RESULTS: The proposed QA program is based on international and local recommendations as well as practical experience. It includes standardised CT tests and SPCCT-specific methods. Additional methodologies to further assess the system performance are also presented. Tolerance levels are discussed and revised when appropriate. Both in-plane and longitudinal high spatial resolutions were evidenced by the MTF measurements with 1.8 lp· mm-1 and 5.0 lp· mm-1 at 10%, respectively. The calculated effective slice thickness ranged between 0.15 and 0.16 mm for the five energy bins and for a reconstructed voxel size of 0.1 × 0.1 × 0.1 mm3 . Reference values of the linear attenuation coefficient of water have been calculated and used to assess the CT number uniformity of water. Evaluation of the CT number accuracy and stability of various clinically relevant materials showed excellent spectral correlation and linearity between HU values and concentrations (r2 > 0.99). The NPS showed less noise correlation between slices than within transverse slice, as well as a systematic increase at low spatial frequencies. The volume CT dose index (CTDI v o l $_{vol}$ ) for a custom-made 100 mm diameter phantom was 9.32 mGy. Radiation measurements around the scanner showed that it is completely shielded except for the access port, and that no additional protective measures are necessary for the patient. CONCLUSIONS: A routine QA framework for SPCCT systems has been proposed. Image quality and radiation dose were assessed using newly designed phantoms, relevant metrics, and automated algorithms. Baseline values were established and tolerance levels discussed for the MARS SPCCT scanner based on collected data and international recommendations.

High-resolution synchrotron K-edge subtraction CT allows tracking and quantifying therapeutic cells and their scaffold in a rat model of focal cerebral injury and can serve as a reference for spectral photon counting CT.

Background: The objective of this study was to demonstrate that synchrotron K-edge subtraction tomography (SKES-CT) can simultaneously track therapeutic cells and their encapsulating carrier, in vivo, in a rat model of focal brain injury using a dual-contrast agent approach. The second objective was to determine if SKES-CT could be used as a reference method for spectral photon counting tomography (SPCCT). Methods: Phantoms containing different concentrations of gold and iodine nanoparticles (AuNPS/INPs) were imaged with SKES-CT and SPCCT to assess their performances. A pre-clinical study was performed in rats with focal cerebral injury which intracerebrally received AuNPs-labelled therapeutic cells encapsulated in a INPs-labelled scaffold. Animals were imaged in vivo with SKES-CT and back-to-back with SPCCT. Results: SKES-CT revealed to be reliable for quantification of gold and iodine, whether alone or mixed. In the preclinical model, SKES-CT showed that AuNPs remained at the site of cell injection, while INPs expanded within and/or along the lesion border, suggesting dissociation of both components in the first days post-administration. Compared to SKES-CT, SPCCT was able to correctly locate gold, but not completely located iodine. When SKES-CT was used as reference, SPCCT gold quantification appeared very accurate both in vitro and in vivo. Iodine quantification by SPCCT was also quite accurate, albeit less so than for gold. Conclusion: We here provide the proof-of-concept that SKES-CT is a novel method of choice for performing dual-contrast agent imaging in the context of brain regenerative therapy. SKES-CT may also serve as ground truth for emerging technologies such as multicolour clinical SPCCT.

Spectral CT imaging: Technical principles of dual-energy CT and multi-energy photon-counting CT.

Spectral computed tomography (CT) imaging encompasses a unique generation of CT systems based on a simple principle that makes use of the energy-dependent information present in CT images. Over the past two decades this principle has been expanded with the introduction of dual-energy CT systems. The first generation of spectral CT systems, represented either by dual-source or dual-layer technology, opened up a new imaging approach in the radiology community with their ability to overcome the limitations of tissue characterization encountered with conventional CT. Its expansion worldwide can also be considered as an important leverage for the recent groundbreaking technology based on a new chain of detection available on photon counting CT systems, which holds great promise for extending CT towards multi-energy CT imaging. The purpose of this article was to detail the basic principles and techniques of spectral CT with a particular emphasis on the newest technical developments of dual-energy and multi-energy CT systems.

Ytterbium Nanoparticle Contrast Agents for Conventional and Spectral Photon-Counting CT and Their Applications for Hydrogel Imaging.

Significant work has been done to develop nanoparticle contrast agents for computed tomography (CT), with a focus on identifying safer and more effective formulations. Contrast agents for spectral photon-counting computed tomography (SPCCT), a fast-growing imaging modality derived from conventional CT, have also recently gained considerable attention. In this study, we explored the synthesis of ultrasmall ytterbium nanoparticles (YbNP) and demonstrated that, potentially, they can be used as conventional CT and SPCCT contrast agents. These nanoparticles were tested in vitro for their cytotoxicity and contrast-generating properties with a variety of imaging systems. When scanned with conventional CT and SPCCT at clinically relevant energies, YbNP are significantly more attenuating than gold nanoparticles (AuNP), the contrast agents that have been most well studied. Furthermore, YbNP were studied for their potential application for labeling and monitoring hydrogels. The presence of the YbNP payload in hydrogels allowed for hydrogel localization and tracking in vivo. Additionally, the in vivo imaging results revealed that YbNP generate higher contrast when compared to AuNP used as a label. In summary, this is the first research study to examine ultrasmall YbNP as conventional CT and SPCCT contrast agents, as well as using them in a hydrogel system to make it radiopaque. These findings underscore YbNP's utility as CT and SPCCT contrast agents, as well as their potential for tracking hydrogels in vivo.

Multicolor spectral photon counting CT monitors and quantifies therapeutic cells and their encapsulating scaffold in a model of brain damage.

Rationale & aim: Various types of cell therapies are currently under investigation for the treatment of ischemic stroke patients. To bridge the gap between cell administration and therapeutic outcome, there is a need for non-invasive monitoring of these innovative therapeutic approaches. Spectral photon counting computed tomography (SPCCT) is a new imaging modality that may be suitable for cell tracking. SPCCT is the next generation of clinical CT that allows the selective visualization and quantification of multiple contrast agents. The aims of this study are: (i) to demonstrate the feasibility of using SPCCT to longitudinally monitor and quantify therapeutic cells, i.e. bone marrow-derived M2-polarized macrophages transplanted in rats with brain damage; and (ii) to evaluate the potential of this approach to discriminate M2-polarized macrophages from their encapsulating scaffold. Methods: Twenty one rats received an intralesional transplantation of bone marrow-derived M2-polarized macrophages. In the first set of experiments, cells were labeled with gold nanoparticles and tracked for up to two weeks post-injection in a monocolor study via gold K-edge imaging. In the second set of experiments, the same protocol was repeated for a bicolor study, in which the labeled cells are embedded in iodine nanoparticle-labeled scaffold. The amount of gold in the brain was longitudinally quantified using gold K-edge images reconstructed from SPCCT acquisition. Animals were sacrificed at different time points post-injection, and ICP-OES was used to validate the accuracy of gold quantification from SPCCT imaging. Results: The feasibility of therapeutic cell tracking was successfully demonstrated in brain-damaged rats with SPCCT imaging. The imaging modality enabled cell monitoring for up to 2 weeks post-injection, in a specific and quantitative manner. Differentiation of labeled cells and their embedding scaffold was also feasible with SPCCT imaging, with a detection limit as low as 5,000 cells in a voxel of 250 × 250 × 250 µm in dimension in vivo. Conclusion: Multicolor SPCCT is an innovative translational imaging tool that allows monitoring and quantification of therapeutic cells and their encapsulating scaffold transplanted in the damaged rat brain.

Quantitative imaging performance of MARS spectral photon-counting CT for radiotherapy.

PURPOSE: To evaluate the quantitative imaging performance of a spectral photon-counting computed tomography (SPCCT) scanner for radiotherapy applications. An experimental comparison of the quantitative performance of a Siemens dual-energy CT (DECT) and a MARS SPCCT scanner is performed to estimate physical properties relevant to radiotherapy of human substitute materials and contrast agent solutions. In human substitute materials, the accuracy of quantities relevant to photon therapy, proton therapy, and Monte-Carlo simulations, such as the electron density, proton stopping power, and elemental composition is evaluated. For contrast agent solutions, the accuracy of the contrast agent concentrations and the virtual non-contrast (VNC) electron density is evaluated. METHODS: Human tissue substitute phantoms (Gammex 467 and 472) as well as diluted solutions of contrast agents (iodine and gadolinium based) are scanned with two commercial systems: a Siemens dual-source CT (SOMATOM Definition Flash, Siemens Healthineers, Forchheim, Germany) and a MARS spectral photon-counting micro-CT (MARS V5.2, MARS Bioimaging Ltd., Christchurch, New Zealand). Material decomposition is performed in a maximum a posteriori framework with an optimized material basis tailored to characterize either human substitute materials or contrast agents in the context of experimental multi-energy CT data. RESULTS: The root-mean-square error (RMSE) of the electron density calculated over all Gammex inserts is reduced from 1.09 to 0.89% when going from DECT to SPCCT. For the proton stopping power, the RMSE is reduced from 1.92 to 0.89%. Elemental mass fractions of hydrogen, carbon, nitrogen, oxygen, and calcium are more accurately estimated with the MARS scanner. The RMSE on the iodine-based contrast agents concentration is reduced from 0.27 to 0.12 mg/mL with SPCCT, and the VNC electron density from 0.40 to 0.22%. CONCLUSION: In the present phantom study, a MARS photon-counting scanner provides superior accuracy compared to a Siemens SOMATOM Definition Flash DECT scanner to quantify physical parameters relevant to radiotherapy. This work experimentally demonstrates the benefits of using more energies to characterize human tissue equivalent materials. This highlights the potential of SPCCT for particle therapy, where more accurate tissue characterization is needed, as well as for Monte-Carlo based planning, which requires accurate elemental mass fractions.

Discrimination Between Calcium Hydroxyapatite and Calcium Oxalate Using Multienergy Spectral Photon-Counting CT.

OBJECTIVE: We aimed to determine whether multienergy spectral photon-counting CT could distinguish between clinically relevant calcium crystals at clinical x-ray energy ranges. Energy thresholds of 15, 22, 29, and 36 keV and tube voltages of 50, 80, and 110 kVp were selected. Images were analyzed to assess differences in linear attenuation coefficients between various concentrations of calcium hydroxyapatite (54.3, 211.7, 808.5, and 1169.3 mg/cm3) and calcium oxalate (2000 mg/cm3). CONCLUSION: The two lower concentrations of hydroxyapatite were distinguishable from oxalate at all energy thresholds and tube voltages, whereas discrimination at higher concentrations depended primarily on the energy thresholds used. Multienergy spectral photon-counting CT shows promise for distinguishing these calcium crystals.