Spectral Photon-counting CT Research Articles

An In vivo Pilot Study to Estimate the Swelling of the Aneurysm Wall Rabbit Model Generated with Pulsed Fluid Against the Aneurysm Wall.

This study addresses the critical issue of evaluating the risk of rupture of unruptured intracranial aneurysms (UIAs) through the assessment of the mechanical properties of the aneurysm wall. To achieve this, an original approach based on the development of an in vivo deformation device prototype (DDP) of the vascular wall is proposed. The DDP operates by pulsing a physiological fluid onto the vascular wall and measuring the resulting deformation using spectral photon counting computed tomography (SPCCT) imaging. In this preliminary study conducted on a rabbit animal model, an aneurysm was induced on the carotid artery, followed by deformation of the aneurysm sac wall using the DDP. The change in luminal volume of the aneurysm sac induced by the deformation of the vascular wall was then quantified. The initial experimental results demonstrated an increase in the luminal volume of the aneurysm sac in relation to the increased flow rate of the fluid pulsed by the DDP onto the arterial wall. Measurement of the pressure generated by the DDP in relation to the different flow rate values imposed by the pulsation system revealed experimental values of the same order of magnitude as dynamic blood pressure. Furthermore, theoretical pressure values on the deformed area, calculated using Euler's theorem, appeared to be correlated with experimental pressure measurements. This equivalence between theory and experiment is a key element in the use of the DDP for estimating the mechanical properties of the vascular wall, particularly for the use of finite element models to characterise the stress state of the deformed vascular wall. This preliminary work thus presents a novel, innovative, and promising approach for the evaluation and management of the risk of rupture of unruptured intracranial aneurysms.

Targeted K-Edge Nanoprobes From Praseodymium and Hafnium for Ratiometric Tracking of Dual Biomarkers using Spectral Photon Counting CT.

Utilizing metal nanoprobes with unique K-edge identities to visualize complementary biological activities simultaneously can provide valuable information about complex biological processes. This study describes the design and preparation of an innovative pair of K-edge metal nanoprobes and demonstrates the feasibility of their simultaneous quantitative detection using spectral photon-counting computed tomography (SPCCT). Glycosaminoglycan (GAG) capped nanoparticles (ca. 15-20nm) targeting two distinct components of the cartilage tissue, namely, aggrecan (acan) and aggrecanase (acanase) are designed and synthesized. These targeted nanoparticles comprised of praseodymium (Pr) and hafnium (Hf), with well-separated K-edge energies, enable simultaneous and ratiometric imaging of dual biomarkers in cartilage tissue. Following extensive physico-chemical characterization of the ligand-targeted particles, the feasibility of homing dual biomarkers in vitro is demonstrated. The material discrimination and simultaneous quantification of these targeted particles are also achieved and corroborated with inductively coupled plasmon spectroscopy. For the first time, the use of praseodymium is reported as a contrast agent for SPCCT imaging and demonstrates the ability to pair it with hafnium nanoprobes for multicontrast imaging of diseases. Importantly, the potential for ratiometric molecular imaging and tracking of osteoarthritis (OA) progression is shown with SPCCT K-edge based imaging approach.

The polychromatic retrigger: a new tool to mitigate pileup in spectral photon-counting computed-tomography

The polychromatic retrigger: a new tool to mitigate pileup in spectral photon-counting computed-tomography

Spectral Photon-Counting Computed Tomography: Technical Principles and Applications in the Assessment of Cardiovascular Diseases.

Spectral Photon-Counting Computed Tomography (SPCCT) represents a groundbreaking advancement in X-ray imaging technology. The core innovation of SPCCT lies in its photon-counting detectors, which can count the exact number of incoming x-ray photons and individually measure their energy. The first part of this review summarizes the key elements of SPCCT technology, such as energy binning, energy weighting, and material decomposition. Its energy-discriminating ability represents the key to the increase in the contrast between different tissues, the elimination of the electronic noise, and the correction of beam-hardening artifacts. Material decomposition provides valuable insights into specific elements' composition, concentration, and distribution. The capability of SPCCT to operate in three or more energy regimes allows for the differentiation of several contrast agents, facilitating quantitative assessments of elements with specific energy thresholds within the diagnostic energy range. The second part of this review provides a brief overview of the applications of SPCCT in the assessment of various cardiovascular disease processes. SPCCT can support the study of myocardial blood perfusion and enable enhanced tissue characterization and the identification of contrast agents, in a manner that was previously unattainable.

Gold nanoparticles spectral CT imaging and limit of detectability in a new materials contrast-detail phantom

This study involves the synthesis, characterization, and spectral photon counting CT (SPCCT) imaging of gold nanoparticles tailored for enhancing the contrast of small cancer lesions. We used the modified Turkevich method to produce thiol-capped gold nanoparticles (AuNPs) at different concentrations (20, 15, 10, 5, 2.5, 1.25, 0.6 mg/ml). We thoroughly characterized the AuNPs using Transmission Electron Microscopy (TEM), X-ray diffraction spectroscopy (XRD), Dynamic Light Scattering (DLS), and UV–visible absorption spectroscopy. To assess the AuNPs contrast enhancing performance, we designed and built a new material contrast detail phantom for CT imaging and determined the minimum detectable concentrations of AuNPs in simulated lesions of small diameters (1, 2, 3, and 5 mm). The synthesized AuNPs are spherical with an average size of approximately 20 ± 4 nm, with maximum UV absorption occurring at 527 nm wavelength, and exhibit a face-centered cubic structure of gold according to XRD analysis. The synthesized gold nanoparticles demonstrated high contrast in SPCCT, suggesting their potential as contrast agents for imaging cancer tissues. The AuNPs image contrast was directly proportional to the AuNPs concentration. We are the first to determine that the lowest visually distinguishable contrast was achieved at a gold concentration of 5 mg/ml for a 2 mm simulated lesion. For 1 mm size lesion the smallest visible concentration was 10 mg/ml. This newly developed phantom can be used for determining the minimal concentration required for various high-Z nanoparticles to produce detectable contrast in X-ray imaging for small-size simulated lesions.

Assessment of material identification and quantification in the presence of metals using spectral photon counting CT.

Spectral Photon Counting Computed Tomography (SPCCT), a ground-breaking development in CT technology, has immense potential to address the persistent problem of metal artefacts in CT images. This study aims to evaluate the potential of Mars photon-counting CT technology in reducing metal artefacts. It focuses on identifying and quantifying clinically significant materials in the presence of metal objects. A multi-material phantom was used, containing inserts of varying concentrations of hydroxyapatite (a mineral present in teeth, bones, and calcified plaque), iodine (used as a contrast agent), CT water (to mimic soft tissue), and adipose (as a fat substitute). Three sets of scans were acquired: with aluminium, with stainless steel, and without a metal insert as a reference dataset. Data acquisition was performed using a Mars SPCCT scanner (Microlab 5×120); operated at 118 kVp and 80 μA. The images were subsequently reconstructed into five energy bins: 7-40, 40-50, 50-60, 60-79, and 79-118 keV. Evaluation metrics including signal-to-noise ratio (SNR), linearity of attenuation profiles, root mean square error (RMSE), and area under the curve (AUC) were employed to assess the energy and material-density images with and without metal inserts. Results show decreased metal artefacts and a better signal-to-noise ratio (up to 25%) with increased energy bins as compared to reference data. The attenuation profile also demonstrated high linearity (R2 >0.95) and lower RMSE across all material concentrations, even in the presence of aluminium and steel. Material identification accuracy for iodine and hydroxyapatite (with and without metal inserts) remained consistent, minimally impacting AUC values. For demonstration purposes, the biological sample was also scanned with the stainless steel volar implant and cortical bone screw, and the images were objectively assessed to indicate the potential effectiveness of SPCCT in replicating real-world clinical scenarios.

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.

Spectral photon-counting CT: Image quality evaluation using a metal-containing bovine bone specimen

PurposeTo find the optimal imaging parameters for a photon-counting detector CT (PCD-CT) and to compare it to an energy-integrating detector CT (EID-CT) in terms of image quality and metal artefact severity using a metal-containing bovine knee specimen. MethodsA bovine knee with a stainless-steel plate and screws was imaged in a whole-body research PCD-CT at 120 kV and 140 kV and in an EID dual-source CT (DSCT) at Sn150 kV and 80/Sn150 kV. PCD-CT virtual monoenergetic 72 and 150 keV images and EID-CT images processed with and without metal artefact reduction algorithms (iMAR) were compared. Four radiologists rated the visualisation of bony structures and metal artefact severity. The Friedman test and Wilcoxon signed-rank test with Bonferroni’s correction were used. P-values of ≤ 0.0001 were considered statistically significant. Distributions of HU values of regions of interest (ROIs) in artefact-affected areas were analysed. ResultsPCD-CT 140 kV 150 keV images received the highest scores and were significantly better than EID-CT Sn150 kV images. PCD-CT 72 keV images were rated significantly lower than all the others. HU-value variation was larger in the 120 kV and the 72 keV images. The ROI analysis revealed no large difference between scanners regarding artefact severity. ConclusionPCD-CT 140 kV 150 keV images of a metal-containing bovine knee specimen provided the best image quality. They were superior to, or as good as, the best EID-CT images; even without the presumed advantage of tin filter and metal artefact reduction algorithms. PCD-CT is a promising method for reducing metal artefacts.

Photon-counting spectral CT reconstruction with sparse and double low-rank components fusion

ObjectivePhoton-counting CT (computed tomography) has aroused more attention. The relatively high dose of X-ray increases concerns about radiation, dose reduction can mitigate radiation risk, however, projection data within energy channel suffers from strong noise, leading to degraded results. Besides, there is high correlation among channels since the multi-channel data is captured from the same object, which should be utilized to improve reconstruction quality. To suppress noise while preserving details in reconstruction and improve material decomposition accuracy, we proposed a novel optimization-based spectral CT reconstruction method with a fusion framework. MethodsTwo results were obtained by implementing two iterative reconstructions with different constraints and can be treated as complementary components. The first constraint is sparsity, the second constraint is double low-rank, moreover, a heuristic strategy is designed to solve double low-rank constrained optimization. We developed a guided filter based fusion framework to fuse sparse component and double low-rank component. ResultsExperimental results showed that our method achieved satisfying visualization, higher values of PSNR (peak signal-to-noise ratio) and SSIM (structure similarity), moreover, lower material decomposition error in this work.Conclusion.Our method can well perform spectral CT reconstruction under low-signal-to-ratio situation and it has decent performance in noise suppression, edge preserving and material discrimination.

Quantification of cartilage and subchondral bone cysts on knee specimens based on a spectral photon-counting computed tomography

Spectral photon-counting computed tomography (SPCCT) is a new technique with the capability to provide mono-energetic (monoE) images with high signal to noise ratio. We demonstrate the feasibility of SPCCT to characterize at the same time cartilage and subchondral bone cysts (SBCs) without contrast agent in osteoarthritis (OA). To achieve this goal, 10 human knee specimens (6 normal and 4 with OA) were imaged with a clinical prototype SPCCT. The monoE images at 60 keV with isotropic voxels of 250 × 250 × 250 µm3 were compared with monoE synchrotron radiation CT (SR micro-CT) images at 55 keV with isotropic voxels of 45 × 45 × 45 µm3 used as benchmark for cartilage segmentation. In the two OA knees with SBCs, the volume and density of SBCs were evaluated in SPCCT images. In 25 compartments (lateral tibial (LT), medial tibial, (MT), lateral femoral (LF), medial femoral and patella), the mean bias between SPCCT and SR micro-CT analyses were 101 ± 272 mm3 for cartilage volume and 0.33 mm ± 0.18 for mean cartilage thickness. Between normal and OA knees, mean cartilage thicknesses were found statistically different (0.005 < p < 0.04) for LT, MT and LF compartments. The 2 OA knees displayed different SBCs profiles in terms of volume, density, and distribution according to size and location. SPCCT with fast acquisitions is able to characterize cartilage morphology and SBCs. SPCCT can be used potentially as a new tool in clinical studies in OA.

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

Background and aimsAtherosclerotic 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. MethodsAn 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. ResultsA 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. ConclusionsSPCCT 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

PurposeThe 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 methodsSeven 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. ResultsIn 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). ConclusionWith 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.

Virtual monochromatic images for coronary artery imaging with a spectral photon-counting CT in comparison to dual-layer CT systems: a phantom and a preliminary human study

ObjectivesTo evaluate the quality of virtual monochromatic images (VMIs) from spectral photon-counting CT (SPCCT) and two energy-integrating detector dual-energy CT (EID-DECT) scanners from the same manufacturer, for the coronary lumen.MethodsA 21-cm section of the Mercury v4.0 phantom was scanned using a cardiac CT protocol. VMIs from 40 to 90 keV were reconstructed using high-resolution (HR) parameters for EID-DECT and SPCCT (CB and HRB kernels at 0.67 mm slice thickness, respectively). Ultra-high-resolution (UHR) parameters were used in addition to SPCCT (detailed-2 kernel, 0.43 mm slice thickness). Noise-power-spectrum (NPS), task-based transfer function (TTF), and detectability index (d′) were computed for 2-mm-diameter lumen detection. In consensus, two radiologists analyzed the quality of the images from 8 patients who underwent coronary CTA on both CT systems.ResultsFor all keV images, fpeak, f50, and d′ were higher with SPCCT. The fpeak and f50 were higher with UHR-SPCCT with greater noise and lower d′ compared to those of the HR-SPCCT images. Noise magnitude was constant for all energy levels (keV) with both systems, and lower with HR images, and d′ decreased as keV decreased. Subjective analysis showed greater lumen sharpness and overall quality for HR and UHR-SPCCT images using all keV, with a greater difference at low keV compared to HR-EID-DECT images.ConclusionHR and UHR-SPCCT images gave greater detectability of the coronary lumen for 40 to 90 keV VMIs compared to two EID-DECT systems, with benefits of higher lumen sharpness and overall quality.Key Points• Compared with 2 dual-energy CT systems, spectral photon-counting CT (SPCCT) improved spatial resolution, noise texture, noise magnitude, and detectability of the coronary lumen.• Use of ultra-high-resolution parameters with SPCCT improved spatial resolution and noise texture and provided high detectability of the coronary lumen, despite an increase in noise magnitude.• In eight patients, radiologists found greater overall image quality with SPCCT for all virtual monochromatic images with a greater difference at low keV, compared with dual-energy CT systems.

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

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 tolerancelevels. 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 QAprogram. The specific dimensions of the scanner with a 125mm diameter gantry and a small voxel size of 0.1×0.1×0.1mm3 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 thescanner. 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 1.8lp· mm-1 and 5.0lp· mm-1 at 10%, respectively. The calculated effective slice thickness ranged between 0.15and 0.16mm for the five energy bins and for a reconstructed voxel size of 0.1×0.1×0.1mm3 . 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 ) for a custom-made 100mm diameter phantom was 9.32mGy. 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 thepatient. 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 internationalrecommendations.

Spectral Photon-Counting CT Imaging of Gold Nanoparticle Labelled Monocytes for Detection of Atherosclerosis: A Preclinical Study.

A key process in the development of atherosclerotic plaques is the recruitment of monocytes into the artery wall. Using spectral photon-counting computed tomography we examine whether monocyte deposition within the artery wall of ApoE-/- mouse can be detected. Primary mouse monocytes were labelled by incubating them with 15 nm gold nanoparticles coated with 11-mercaptoundecanoic acid The monocyte uptake of the particle was confirmed by electron microscopy of the cells before injection into 6-week-old apolipoprotein E deficient (ApoE-/-) mouse that had been fed with the Western diet for 10 weeks. Four days following injection, the mouse was sacrificed and imaged using a MARS spectral photon counting computed tomography scanner with a spectral range of 7 to 120 KeV with five energy bins. Imaging analysis showed the presence of X-ray dense material within the mouse aortic arch which was consistent with the spectral characteristic of gold rather than calcium. The imaging is interpreted as showing the deposition of gold nanoparticles containing monocytes within the mouse aorta. The results of our study determined that spectral photon-counting computed tomography could provide quantitative information about gold nanoparticles labelled monocytes in voxels of 90 × 90 × 90 µm3. The imaging was consistent with previous micro-CT and electron microscopy of mice using the same nanoparticles. This study demonstrates that spectral photon-counting computed tomography, using a MARS small bore scanner, can detect a fundamental atherogenic process within mouse models of atherogenesis. The present study demonstrates the feasibility of spectral photon-counting computed tomography as an emerging molecular imaging modality to detect atherosclerotic disease.

Bicolor K-edge spectral photon-counting CT imaging for the diagnosis of thoracic endoleaks: A dynamic phantom study

PurposeThe purpose of this study was to investigate the feasibility of identifying and characterizing the three most common types of endoleaks within a thoracic aorta aneurysm model using bicolor K-edge imaging with a spectral photon-counting computing tomography (SPCCT) system in combination with a biphasic contrast agent injection. Materials and methodsThree types of thoracic endoleaks (type 1, 2 and 3) were created in a dynamic anthropomorphic thoracic aorta phantom. Protocol consisted in an injection of an iodinated contrast material followed 80 seconds after an injection of a gadolinium-based contrast agent (GBCA). The phantom was scanned using a clinical prototype SPCCT during bicolor phase imaging consisting in an early distribution of GBCA and a late distribution of iodine. Conventional and spectral images were reconstructed for differentiating between the contrast agents and measuring their respective attenuation values and concentrations inside and outside the stent graft. ResultsConventional images failed to provide specific dynamic imaging contrast agents in the aneurysmal sac and outside the stent graft while spectral images differentiated their specific distribution. In type 1 and 3 thoracic endoleaks, GBCA concentration was measured outside the stent graft at 6.1 ± 3.7 (standard deviation [SD]) mg/mL and 6.0 ± 4.0 (SD) mg/mL, respectively, in favor of an early blood flow. In type 2 thoracic endoleak, iodine was measured outside the stent graft at 24.3 ± 5.5 (SD) mg/mL in favor of a late blood flow in the aneurysmal sac. ConclusionBicolor K-edge imaging enabled SPCCT allows a bicolor characterization of thoracic aorta endoleaks in a single acquisition in combination with a biphasic contrast agent injection.

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.

LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: a proof-of-concept research.

Emerging multifunctional nanoparticulate formulations take advantage of nano-meter scale size and surface chemistry to work as a therapeutic delivery agent and a diagnostic tool for non-invasive real-time monitoring using imaging technologies. Here, we evaluate the selective uptake of 18 nm and 80 nm sized gold nanoparticles (AuNPs) by SKOV3 (4 times higher) ovarian cancer (OC) cells (compared to OVCAR5) in vitro, quantified by inductively coupled plasma (ICP) and MARS spectral photon-counting CT imaging (MARS SPCCT). Based on in vitro analysis, pristine AuNPs (18 nm) and surface modified AuNPs (18 nm) were chosen as a contrast agent for MARS SPCCT. The chemical analysis by FTIR spectroscopy confirmed the luteinizing hormone-releasing hormone (LHRH) conjugation to the AuNPs surface. For the first time, LHRH conjugated AuNPs were used for in vitro and selective in vivo OC targeting. The ICP-MS analysis confirmed preferential uptake of LHRH modified AuNPs by organs residing in the abdominal cavity with OC nodules (pancreas: 0.46 ng mg-1, mesentery: 0.89 ng mg-1, ovary: 1.43 ng mg-1, and abdominal wall: 2.12 ng mg-1) whereas the MARS SPCCT analysis suggested scattered accumulation of metal around the abdominal cavity. Therefore, the study showed the exciting potential of LHRH conjugated AuNPs to target ovarian cancer and also as a potential contrast agent for novel SPCCT imaging technology.

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.

One-step iterative reconstruction approach based on eigentissue decomposition for spectral photon-counting computed tomography.

Purpose: We propose a one-step tissue characterization method for spectral photon-counting computed tomography (SPCCT) using eigentissue decomposition (ETD), tailored for highly accurate human tissue characterization in radiotherapy. Methods: The approach combines a Poisson likelihood, a spatial prior, and a quantitative prior constraining eigentissue fractions based on expected values for tabulated tissues. There are two regularization parameters: for the quantitative prior, and for the spatial prior. The approach is validated in a realistic simulation environment for SPCCT. The impact of and is evaluated on a virtual phantom. The framework is tested on a virtual patient and compared with two sinogram-based two-step methods [using respectively filtered backprojection (FBP) and an iterative method for the second step] and a post-reconstruction approach with the same quantitative prior. All methods use ETD. Results: Optimal performance with respect to bias or RMSE is achieved with different combinations of and on the cylindrical phantom. Evaluated in tissues of the virtual patient, the one-step framework outperforms two-step and post-reconstruction approaches to quantify proton-stopping power (SPR). The mean absolute bias on the SPR is 0.6% (two-step FBP), 0.6% (two-step iterative), 0.6% (post-reconstruction), and 0.2% (one-step optimized for low bias). Following the same order, the RMSE on the SPR is 13.3%, 2.5%, 3.2%, and 1.5%. Conclusions: Accurate and precise characterization with ETD can be achieved with noisy SPCCT data without the need to rely on post-reconstruction methods. The one-step framework is more accurate and precise than two-step methods for human tissue characterization.