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.

Detection of Trace Elements Se, Cu, and Zn Levels in Biological Samples of Drug Abusers: Halani Sindh, Pakistan.

Illicit drug use has become a global issue, posing significant health, socioeconomic, and cultural risks. The study examined essential trace metals: selenium, zinc, and copper in blood concentrations, as well as in serum and scalp hair samples, from 240 male drug-abuse subjects/patients aged 18-45, categorized into three age groups. The study compared 45 healthy subjects of the same age group using an acid digestion method supported by a microwave oven during sample preparation. The technique of atomic absorption spectrometry was employed to identify essential and toxic elements, utilizing certified reference materials for accuracy. According to a recent study, plasma zinc and selenium concentrations in drug abusers are lower than those in referent subjects, potentially increasing vulnerability to infection due to poor nutritional status or other contaminants.

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.

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.

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.

Clinical Utility of Multi-Energy Spectral Photon-Counting Computed Tomography in Crystal Arthritis.

OBJECTIVE: To determine whether novel multi-energy spectral photon-counting computed tomography (SPCCT) imaging can detect and differentiate between monosodium urate (MSU), calcium pyrophosphate (CPP), and hydroxyapatite (HA) crystal deposits ex vivo. METHODS: A finger with a subcutaneous gouty tophus and a calcified knee meniscus excised at the time of surgery were obtained. The finger was imaged using plain x-ray, dual-energy CT (DECT), and multi-energy SPCCT. Plain x-ray and multi-energy SPCCT images of the meniscus were acquired. For validation purposes, samples of the crystals were obtained from the tophus and meniscus, and examined by polarized light microscopy and/or x-ray diffraction. As further validation, synthetic crystal suspensions of MSU, CPP, and HA were scanned using multi-energy SPCCT. RESULTS: Plain x-ray of the gouty finger revealed bone erosions with overhanging edges. DECT and multi-energy SPCCT both showed MSU crystal deposits; SPCCT was able to show finer detail. Plain x-ray of the calcified meniscus showed chondrocalcinosis consistent with CPP, while SPCCT showed and differentiated CPP and HA. CONCLUSION: Multi-energy SPCCT can not only detect, differentiate, and quantify MSU crystal deposits in a gouty finger ex vivo, but also specifically detect, identify, and quantify CPP within an osteoarthritic meniscus, and distinguish them from HA crystal deposits. There is potential for multi-energy SPCCT to become useful in the diagnosis of crystal arthropathies.

Spectral Photon-Counting Molecular Imaging for Quantification of Monoclonal Antibody-Conjugated Gold Nanoparticles Targeted to Lymphoma and Breast Cancer: An In Vitro Study.

The purpose of the present study was to demonstrate an in vitro proof of principle that spectral photon-counting CT can measure gold-labelled specific antibodies targeted to specific cancer cells. A crossover study was performed with Raji lymphoma cancer cells and HER2-positive SKBR3 breast cancer cells using a MARS spectral CT scanner. Raji cells were incubated with monoclonal antibody-labelled gold, rituximab (specific antibody to Raji cells), and trastuzumab (as a control); HER2-positive SKBR3 breast cancer cells were incubated with monoclonal antibody-labelled gold, trastuzumab (specific antibody to HER2-positive cancer cells), and rituximab (as a control). The calibration vials with multiple concentrations of nonfunctionalised gold nanoparticles were used to calibrate spectral CT. Spectral imaging results showed that the Raji cells-rituximab-gold and HER2-positive cells-trastuzumab-gold had a quantifiable amount of gold, 5.97 mg and 0.78 mg, respectively. In contrast, both cell lines incubated with control antibody-labelled gold nanoparticles had less gold attached (1.22 mg and 0.15 mg, respectively). These results demonstrate the proof of principle that spectral molecular CT imaging can identify and quantify specific monoclonal antibody-labelled gold nanoparticles taken up by Raji cells and HER2-positive SKBR3 breast cancer cells. The present study reports the future potential of spectral molecular imaging in detecting tumour heterogeneity so that treatment can be tuned accordingly, leading to more effective personalised medicine.

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.

Quantitative imaging of excised osteoarthritic cartilage using spectral CT.

OBJECTIVES: To quantify iodine uptake in articular cartilage as a marker of glycosaminoglycan (GAG) content using multi-energy spectral CT. METHODS: We incubated a 25-mm strip of excised osteoarthritic human tibial plateau in 50 % ionic iodine contrast and imaged it using a small-animal spectral scanner with a cadmium telluride photon-processing detector to quantify the iodine through the thickness of the articular cartilage. We imaged both spectroscopic phantoms and osteoarthritic tibial plateau samples. The iodine distribution as an inverse marker of GAG content was presented in the form of 2D and 3D images after applying a basis material decomposition technique to separate iodine in cartilage from bone. We compared this result with a histological section stained for GAG. RESULTS: The iodine in cartilage could be distinguished from subchondral bone and quantified using multi-energy CT. The articular cartilage showed variation in iodine concentration throughout its thickness which appeared to be inversely related to GAG distribution observed in histological sections. CONCLUSIONS: Multi-energy CT can quantify ionic iodine contrast (as a marker of GAG content) within articular cartilage and distinguish it from bone by exploiting the energy-specific attenuation profiles of the associated materials. KEY POINTS: • Contrast-enhanced articular cartilage and subchondral bone can be distinguished using multi-energy CT. • Iodine as a marker of glycosaminoglycan content is quantifiable with multi-energy CT. • Multi-energy CT could track alterations in GAG content occurring in osteoarthritis.