Deep Few-view High-resolution Photon-counting Extremity CT at Halved Dose for a Clinical Trial.

The latest X-ray photon-counting computed tomography (PCCT) for extremity allows multi-energy high-resolution (HR) imaging for tissue characterization and material decomposition. However, both radiation dose and imaging speed need improvement for contrast-enhanced and other studies. Despite the success of deep learning methods for 2D few-view reconstruction, applying them to HR volumetric reconstruction of extremity scans for clinical diagnosis has been limited due to GPU memory constraints, training data scarcity, and domain gap issues. In this paper, we propose a deep learning-based approach for PCCT image reconstruction at halved dose and doubled speed in a New Zealand clinical trial. Particularly, we present a patch-based volumetric refinement network to alleviate the GPU memory limitation, train network with synthetic data, and use model-based iterative refinement to bridge the gap between synthetic and real-world data. The simulation and phantom experiments demonstrate consistently improved results under different acquisition conditions on both in- and off-domain structures using a fixed network. The image quality of 8 patients from the clinical trial are evaluated by three radiologists in comparison with the standard image reconstruction with a full-view dataset. It is shown that our proposed approach is essentially identical to or better than the clinical benchmark in terms of diagnostic image quality scores. Our approach has a great potential to improve the safety and efficiency of PCCT without compromising image quality.

Selective Organ-Targeting Hafnium Oxide Nanoparticles with Multienzyme-Mimetic Activities Attenuate Radiation-Induced Tissue Damage.

Radioprotective agents hold clinical promises to counteract off-target adverse effects of radiation and benefit radiotherapeutic outcomes, yet the inability to control drug transport in human organs poses a leading limitation. Based upon a validated rank-based multigene signature model, radiosensitivity indices are evaluated of diverse normal organs as a genomic predictor of radiation susceptibility. Selective ORgan-Targeting (SORT) hafnium oxide nanoparticles (HfO2 NPs) are rationally designed via modulated synthesis by α-lactalbumin, homing to top vulnerable organs. HfO2 NPs like Hensify are commonly radioenhancers, but SORT HfO2 NPs exhibit surprising radioprotective effects dictated by unfolded ligands and Hf(0)/Hf(IV) redox couples. Still, the X-ray attenuation patterns allow radiological confirmation in target organs by dual-beam spectral computed tomography. SORT HfO2 NPs present potent antioxidant activities, catalytically scavenge reactive oxygen species, and mimic multienzyme catalytic activities. Consequently, SORT NPs rescue radiation-induced DNA damage in mouse and rabbit models and provide survival benefits upon lethal exposures. In addition to inhibiting radiation-induced mitochondrial apoptosis, SORT NPs impede DNA damage and inflammation by attenuating activated FoxO, Hippo, TNF, and MAPK interactive cascades. A universal methodology is proposed to reverse radioenhancers into radioprotectors. SORT radioprotective agents with image guidance are envisioned as compelling in personalized shielding from radiation deposition.

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.

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

Correction for 'LHRH conjugated gold nanoparticles assisted efficient ovarian cancer targeting evaluated via spectral photon-counting CT imaging: a proof-of-concept research' by Dhiraj Kumar et al., J. Mater. Chem. B, 2023, 11, 1916-1928, https://doi.org/10.1039/D2TB02416K.

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.

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.

Components of carotid atherosclerotic plaque in spectral photon-counting CT with histopathologic comparison.

OBJECTIVES: This study aimed to demonstrate the effectiveness of spectral photon-counting CT (SPCCT) in quantifying fibrous cap (FC) thickness, FC area, and lipid-rich necrotic core (LRNC) area, in excised carotid atherosclerotic plaques by comparing it with histopathological measurements. METHODS: This is a single-center ex vivo cross-sectional observational study. Excised plaques of 20 patients (71 +/- 6 years; 13 men), obtained from carotid endarterectomy were scanned with SPCCT using standardized acquisition settings (120k Vp/19 µA; 7-18 keV, 18-30 keV, 30-45 keV, 45-75 keV, and 75-118 keV). FC thickness, FC area, and LRNC area were quantified and compared between high-resolution 3D multi-energy CT images and histopathology using the Wilcoxon signed-ranks test and Bland-Altman analysis. Images were interpreted twice by two radiologists separately, blinded to the histopathology; inter- and intra-rater reliability were assessed with the intra-class correlation coefficients (ICC). RESULTS: FC thickness and FC area did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements (p value range 0.15-0.51 for FC thickness and 0.053-0.30 for FC area). For the LRNC area, the p value was statistically non-significant for reader 1 (range 0.36-0.81). The Bland-Altman analysis showed mean difference and 95% confidence interval for FC thickness, FC area, and LRNC area, 0.04 (-0.36 to 0.12) square root mm, -0.18 (-0.34 to -0.02) log10 mm2 and 0.10 (-0.088. to 0.009) log10 mm2 respectively. CONCLUSION: The result demonstrated a viable technique for quantifying FC thickness, FC area, and LRNC area due to the combined effect of high spatial and energy resolution of SPCCT. KEY POINTS: • SPCCT can identify and quantify different components of carotid atherosclerotic plaque in ex vivo study. • Components of atherosclerotic plaque did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements.

Hitchhiking probiotic vectors to deliver ultra-small hafnia nanoparticles for 'Color' gastrointestinal tract photon counting X-ray imaging.

Gastrointestinal (GI) tract is one of the hard-to-reach target tissues for the delivery of contrast agents and drugs mediated by nanoparticles due to its harsh environment. Herein, we overcame this barrier by designing orally ingestible probiotic vectors for 'hitchhiking' ultrasmall hafnia (HfO2) (∼1-2 nm) nanoparticles. The minute-made synthesis of these nanoparticles is accomplished through a simple reduction reaction. These nanoparticles were incubated with probiotic bacteria with potential health benefits and were non-specifically taken up due to their small size. Subsequently, the bacteria were lyophilized and packed into a capsule to be administered orally as the radiopaque contrast agents for delineating the GI features. These nano-bio-hybrid entities could successfully be utilized as contrast agents in vivo in the conventional and multispectral computed tomography (CT). We demonstrated in 'color' the accumulated nanoparticles using advanced detectors of the photon counting CT. The enhanced nano-bio-interfacing capability achieved here can circumvent traditional nanoparticle solubility and delivery problems while offering a patient friendly approach for GI imaging to replace the currently practiced barium meal.

Carotid Artery Plaque Calcifications: Lessons From Histopathology to Diagnostic Imaging.

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.

Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance.

Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role in the nitric oxide (NO) story as a NO-donating compound, establishing the precise mechanism of how GTN exerts its medicinal benefit has proven to be far more difficult. This review brings together the explosive and vasodilatory nature of this three-carbon molecule while providing an update on the likely in vivo pathways through which GTN, and the rest of the organic nitrate family, release NO, nitrite, or a combination of both, while also trying to explain nitrate tolerance. Over the last 20 years the alcohol detoxification enzyme, aldehyde dehydrogenase (ALDH), has undoubtedly emerged as the front runner to explaining GTN's bioactivation. This is best illustrated by reduced GTN efficacy in subjects carrying the single point mutation (Glu504Lys) in ALDH, which is also responsible for alcohol intolerance, as characterized by flushing. While these findings are significant for anyone following the GTN story, they appear particularly relevant for healthcare professionals, and especially so, if administering GTN to patients as an emergency treatment. In short, although the GTN puzzle has not been fully solved, clinical study data continue to cement the importance of ALDH, as uncovered in 2002, as a key GTN activator.

Deep learning based spectral CT imaging.

Spectral computed tomography (CT) has attracted much attention in radiation dose reduction, metal artifacts removal, tissue quantification and material discrimination. The x-ray energy spectrum is divided into several bins, each energy-bin-specific projection has a low signal-noise-ratio (SNR) than the current-integrating counterpart, which makes image reconstruction a unique challenge. Traditional wisdom is to use prior knowledge based iterative methods. However, this kind of methods demands a great computational cost. Inspired by deep learning, here we first develop a deep learning based reconstruction method; i.e., U-net with Lpp-norm, Total variation, Residual learning, and Anisotropic adaption (ULTRA). Specifically, we emphasize the various multi-scale feature fusion and multichannel filtering enhancement with a denser connection encoding architecture for residual learning and feature fusion. To address the image deblurring problem associated with the L22- loss, we propose a general Lpp-loss, p>0. Furthermore, the images from different energy bins share similar structures of the same object, the regularization characterizing correlations of different energy bins is incorporated into the Lpp- loss function, which helps unify the deep learning based methods with traditional compressed sensing based methods. Finally, the anisotropically weighted total variation is employed to characterize the sparsity in the spatial-spectral domain to regularize the proposed network In particular, we validate our ULTRA networks on three large-scale spectral CT datasets, and obtain excellent results relative to the competing algorithms. In conclusion, our quantitative and qualitative results in numerical simulation and preclinical experiments demonstrate that our proposed approach is accurate, efficient and robust for high-quality spectral CT image reconstruction.

Spectral CT imaging of human osteoarthritic cartilage via quantitative assessment of glycosaminoglycan content using multiple contrast agents.

Detection of early osteoarthritis to stabilize or reverse the damage to articular cartilage would improve patient function, reduce disability, and limit the need for joint replacement. In this study, we investigated nondestructive photon-processing spectral computed tomography (CT) for the quantitative measurement of the glycosaminoglycan (GAG) content compared to destructive histological and biochemical assay techniques in normal and osteoarthritic tissues. Cartilage-bone cores from healthy bovine stifles were incubated in 50% ioxaglate (Hexabrix®) or 100% gadobenate dimeglumine (MultiHance®). A photon-processing spectral CT (MARS) scanner with a CdTe-Medipix3RX detector imaged samples. Calibration phantoms of ioxaglate and gadobenate dimeglumine were used to determine iodine and gadolinium concentrations from photon-processing spectral CT images to correlate with the GAG content measured using a dimethylmethylene blue assay. The zonal distribution of GAG was compared between photon-processing spectral CT images and histological sections. Furthermore, discrimination and quantification of GAG in osteoarthritic human tibial plateau tissue using the same contrast agents were demonstrated. Contrast agent concentrations were inversely related to the GAG content. The GAG concentration increased from 25 µg/ml (85 mg/ml iodine or 43 mg/ml gadolinium) in the superficial layer to 75 µg/ml (65 mg/ml iodine or 37 mg/ml gadolinium) in the deep layer of healthy bovine cartilage. Deep zone articular cartilage could be distinguished from subchondral bone by utilizing the material decomposition technique. Photon-processing spectral CT images correlated with histological sections in healthy and osteoarthritic tissues. Post-imaging material decomposition was able to quantify the GAG content and distribution throughout healthy and osteoarthritic cartilage using Hexabrix® and MultiHance® while differentiating the underlying subchondral bone.

Multi-energy spectral photon-counting computed tomography (MARS) for detection of arthroplasty implant failure.

To determine whether state-of-the-art multi-energy spectral photon-counting computed tomography (MARS) can detect knee arthroplasty implant failure not detected by standard pre-operative imaging techniques. A total knee arthroplasty (TKA) removed from a patient was reviewed. The extracted prosthesis [NexGen Legacy Posterior Stabilized (LPS) TKA] was analyzed as were pre-operative imaging examination and compared with a MARS-CT examination obtained of the extracted TKA prosthesis. Radiographs, fluoroscopy, ultrasound and MRI preoperatively did not reveal the cause of the implant failure. MARS CT images of the extracted prosthesis clearly showed the presence of posteromedial polyethylene and tibial tray wear which is compatible with the clinical appearance of the extracted TKA. MARS can identify polyethylene insert and metallic tibial tray wear as a cause of TKA failure, that could not be identified with on standard pre-operative imaging. Although clinical MARS CT system is still under development, this case does illustrate its potential clinical usefulness. This is the first study to document how MARS CT imaging can detect orthopedic implant failure not detected by standard current imaging techniques. This system has a potential clinical application in orthopedic patients.

Acceptability of a feasibility randomized clinical trial of a microenterprise intervention to reduce sexual risk behaviors and increase employment and HIV preventive practices (EMERGE) in young adults: a mixed methods assessment.

BACKGROUND: Acceptability is a critical requisite in establishing feasibility when planning a larger effectiveness trial. This study assessed the acceptability of conducting a feasibility randomized clinical trial of a 20-week microenterprise intervention for economically-vulnerable African-American young adults, aged 18 to 24, in Baltimore, Maryland. Engaging MicroenterprisE for Resource Generation and Health Empowerment (EMERGE) aimed to reduce sexual risk behaviors and increase employment and uptake of HIV preventive behaviors. METHODS: Thirty-eight participants were randomized to experimental (n = 19) or comparison group (n = 19). The experimental group received text messages on job openings plus educational sessions, mentoring, a start-up grant, and business and HIV prevention text messages. The comparison group received text messages on job openings only. Qualitative and quantitative post-intervention, in-person interviews were used in addition to process documentation of study methods. RESULTS: Our results found that the study design and interventions showed promise for being acceptable to economically-vulnerable African-American young adults. The largely positive endorsement suggested that factors contributing to acceptability included perceived economic potential, sexual health education, convenience, incentives, and encouraging, personalized feedback to participants. Barriers to acceptability for some participants included low cell phone connectivity, perceived payment delays, small cohort size, and disappointment with one's randomization assignment to comparison group. Use of peer referral, network, or wait-list designs, in addition to online options may enhance acceptability in a future definitive trial. Expanding administrative and mentoring support may improve overall experience. CONCLUSION: Microenterprise interventions are acceptable ways of providing young adults with important financial and sexual health content to address HIV risks associated with economic vulnerability. TRIAL REGISTRATION: ClinicalTrials.gov. NCT03766165 . Registered 04 December 2018.

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.

Understanding the role of chaplains in supporting patients and healthcare staff.

AIM: To investigate attitudes towards chaplaincy in NHS Scotland, including the role of the chaplain in supporting healthcare staff. METHOD: This was a qualitative study that involved semi-structured interviews with four chaplains working throughout NHS Scotland. The research transcripts were analysed, and themes were identified and examined. FINDINGS: Two main themes were identified from the interviews: understanding the role of the chaplain; and understanding the future role of the chaplain. The sub-themes identified were: healthcare staff members' perceptions; chaplains' perceptions; generic chaplaincy services; and becoming an allied healthcare profession. CONCLUSION: The findings of this study suggest that chaplains are increasingly providing support to healthcare staff, alongside their role in providing support to patients. The researchers also identified that chaplains in Scotland are adopting an increasingly educational role and that, in the future, they may adopt reflective practice programmes to assist them in managing increased requests for chaplaincy support from healthcare staff. It was also acknowledged that chaplaincy services may also be required to become an allied healthcare profession in the future, which may require chaplains to provide an increasingly generic and less religious service.

Increased separability of K-edge nanoparticles by photon-counting detectors for spectral micro-CT.

BACKGROUND: X-ray CT/micro-CT methods with photon-counting detectors (PCDs) and high Z materials are a hot research topic. One method using PCDs allows for spectral imaging in 5 energy windows while conventional X-ray detectors only collect energy-integrating data. OBJECTIVE: To demonstrate the enhanced separation of contrast materials by using PCDs, multivariate analysis, and linear discriminant methods. METHODS: Phantoms containing iodine and aqueous nanomaterials were scanned on a MARS spectral micro-CT. Image volumes were segmented into separate material-specific populations. Contrast comparisons were made by calculating T2 test statistics in the univariate, pseudo-conventional and multivariate, spectral CT data sets. Separability after Fisher discriminant analysis (FDA) was also assessed. RESULTS: The T2 values calculated for material comparisons increased as a result of the spectral expansion. The majority of the tested contrast agents showed increased T2 values by a factor of ∼2 -3. The total significant T2 statistics in the pure and mixed lanthanide image sets increased in the spectral data set. CONCLUSION: This work consolidates the groundwork for photon-counting-based material decomposition with micro-CT, facilitating future development of novel nanomaterials and their preclinical applications.

Induced macrophage activation in live excised atherosclerotic plaque.

Atherosclerotic plaques are complex tissues containing many different cell types. Macrophages contribute to inflammation, formation of the necrotic core, and plaque rupture. We examined whether macrophages in plaque can be activated and compared this to monolayer cells. The volume of calcium in the plaque was compared to the level of macrophage activation measured by total neopterin output. Carotid plaque samples were cut into 3 mm sections and cultured for up to 96 h. Live sections were stimulated with interferon-γ, phytohaemagglutinin or phorbol 12-myristate 13-acetate. Macrophage activation and oxidative stress were monitored by total neopterin (oxidized and non-oxidized 7,8-dihydroneopterin) and neopterin levels every 24 h for up to 4 d. The calcium content of two plaques was investigated by spectral imaging. Direct stimulation of macrophages in plaque sections with interferon-γ caused a sustained increase in neopterin (p = .037) and total neopterin (p = .003). The addition of phorbol 12-myristate 13-acetate to plaque had no significant effect on total neopterin production (p = .073) but increased neopterin (p = .037) whereas phytohaemagglutinin caused a significant increase in both neopterin and total neopterin (p = .0279 and .0168). There was an inverse association (R2 = 0.91) between the volume of calcium and macrophage activation as measured by total neopterin production in stimulated plaque tissue. Resident macrophages within excised carotid plaque activated either directly or indirectly generate the biomarkers 7,8-dihydroneopterin and neopterin. Macrophage activation rather than the oxidative environment is associated with plaque calcification.

Beam profile assessment in spectral CT scanners.

In this paper, we present a method that uses a combination of experimental and modeled data to assess properties of x-ray beam measured using a small-animal spectral scanner. The spatial properties of the beam profile are characterized by beam profile shape, the angular offset along the rotational axis, and the photon count difference between experimental and modeled data at the central beam axis. Temporal stability of the beam profile is assessed by measuring intra- and interscan count variations. The beam profile assessment method was evaluated on several spectral CT scanners equipped with Medipix3RX-based detectors. On a well-calibrated spectral CT scanner, we measured an integral count error of 0.5%, intrascan count variation of 0.1%, and an interscan count variation of less than 1%. The angular offset of the beam center ranged from 0.8° to 1.6° for the studied spectral CT scanners. We also demonstrate the capability of this method to identify poor performance of the system through analyzing the deviation of the experimental beam profile from the model. This technique can, therefore, aid in monitoring the system performance to obtain a robust spectral CT; providing the reliable quantitative images. Furthermore, the accurate offset parameters of a spectral scanner provided by this method allow us to incorporate a more realistic form of the photon distribution in the polychromatic-based image reconstruction models. Both improvements of the reliability of the system and accuracy of the volume reconstruction result in a better discrimination and quantification of the imaged materials.