Glycyrrhizin ameliorating sterile inflammation induced by low-dose radiation exposure.

Glycyrrhizin (GL) is a direct inhibitor of HMGB1 which acts as an alarmin when excreted into the extracellular space. High-dose radiation in radiotherapy induces collateral damage to the normal tissue, which can be mitigated by GL inhibiting HMGB1. The purpose of this study was to assess changes in HMGB1 and pro-inflammatory cytokines and to evaluate the protective effect of GL after low-dose radiation exposure. BALB/c mice were irradiated with 0.1 Gy (n = 10) and 1 Gy (n = 10) with GL being administered to half of the mice (n = 5, respectively) before irradiation. Blood and spleen samples were harvested and assessed for oxidative stress, HMGB1, pro-inflammatory cytokines, and cell viability. HMGB1 and pro-inflammatory cytokines increased and cell viability decreased after irradiation in a dose-dependent manner. Oxidative stress also increased after irradiation, but did not differ between 0.1 Gy and 1 Gy. With the pretreatment of GL, oxidative stress, HMGB1, and all of the pro-inflammatory cytokines decreased while cell viability was preserved. Our findings indicate that even low-dose radiation can induce sterile inflammation by increasing serum HMGB1 and pro-inflammatory cytokines and that GL can ameliorate the sterile inflammatory process by inhibiting HMGB1 to preserve cell viability.

Gadolinium retention in rat abdominal organs after administration of gadoxetic acid disodium compared to gadodiamide and gadobutrol.

PURPOSE: To compare gadolinium retention in the abdominal organs after administration of gadoxetic acid disodium, a liver-specific contrast agent, compared to gadodiamide and gadobutrol. METHODS: Three types of gadolinium-based contrast agents (GBCAs) were administered to rats. A single (gadodiamide and gadobutrol, 0.1 mmol/kg; gadoxetic acid disodium, 0.025 mmol/kg) or double label-recommended dose was intravenously administered once (Group 1), a single dose was administered 4 times (Group 2) and a single dose with or without a chelating agent (intraperitoneal injection immediately after each GBCA administration) was administered (Group 3). Rats were sacrificed after 1, 4, and 12 weeks and gadolinium concentrations in the liver, spleen, kidney, muscle, and bone were measured by inductively coupled plasma mass spectrometry. P values less than 0.05 were considered statistically significant. RESULTS: More gadolinium was retained with a double dose compared to a single dose, but there was no observed significant difference in gadolinium retention after a double dose compared to a single dose (P > .05). Gadodiamide was retained the most in all tissues followed by gadobutrol and gadoxetic acid disodium. Residual gadolinium was significantly less at 4 weeks compared to 1 week (P < .05), but no further decrease was observed after 4 weeks (P > .05). The presence of the chelating agent did not significantly decrease the concentration of residual gadolinium (P > .05). CONCLUSION: Gadolinium was retained the least in abdominal organs after gadoxetic acid disodium was administered and most of the residual gadolinium was excreted 4 weeks after GBCA administration when a label-recommended dose was administered. A commercially available chelation therapy agent could not reduce gadolinium retention.

Computed tomographic beam-hardening artefacts: mathematical characterization and analysis.

This paper presents a mathematical characterization and analysis of beam-hardening artefacts in X-ray computed tomography (CT). In the field of dental and medical radiography, metal artefact reduction in CT is becoming increasingly important as artificial prostheses and metallic implants become more widespread in ageing populations. Metal artefacts are mainly caused by the beam-hardening of polychromatic X-ray photon beams, which causes mismatch between the actual sinogram data and the data model being the Radon transform of the unknown attenuation distribution in the CT reconstruction algorithm. We investigate the beam-hardening factor through a mathematical analysis of the discrepancy between the data and the Radon transform of the attenuation distribution at a fixed energy level. Separation of cupping artefacts from beam-hardening artefacts allows causes and effects of streaking artefacts to be analysed. Various computer simulations and experiments are performed to support our mathematical analysis.

Nanoscale iodized oil emulsion: a useful tracer for pretreatment sentinel node detection using CT lymphography in a normal canine gastric model.

BACKGROUND: Pretreatment identification of the sentinel lymph nodes (SLNs) in gastric cancer patients may have great advantages for minimally invasive treatment. No reliable method for the detection of SLNs during the pretreatment period in gastric cancer has been established. The aim of this study was to determine whether computed tomographic (CT) lymphography using nanoscale iodized oil emulsion via endoscopic submucosal injection can visualize LNs. METHODS: Five dogs underwent CT lymphography after endoscopic submucosal injection of 2 ml of a nanoscale iodized oil emulsion. CT images were taken before and 30, 90, and 210 min after contrast injection. Intraoperative SLN detection was performed using endoscopically injected indocyanine green lymphography for comparison. RESULTS: Computed tomographic lymphography with nanoscale iodized oil emulsion enabled the visualization of 19 enhanced LNs (mean = 3.8/dog, range = 3-6) with a 100% SLN detection rate. The locations of the SLNs were the lesser curvature (n = 7), greater curvature (n = 1), infrapyloric (n = 3), and left gastric (n = 8) areas. Contrast enhancement of SLNs continuously increased and peaked after 210 min at 142.4 ± 42.3 HU. No green LNs were visualized in the three locations that were detected by CT lymphography. However, no additional LNs were visualized using the dye method. The concordance rate based on the LNs between the SLNs on CT lymphography and the green LNs using the ICG method was 84% (16/19), whereas the concordance rate of the stations identified by CT lymphography and the dye method was 78.6% (11/14). CONCLUSIONS: Computed tomographic lymphography using nanoscale iodized oil emulsion is a promising tool for preoperative SLN detection for early gastric cancer if the biological safety of the nanoscale iodized oil emulsion can be established.

Feasibility of interstitial CT lymphography using optimized iodized oil emulsion in rats.

OBJECTIVES: To formulate an iodine-based contrast agent with an oil-in-water emulsion and to evaluate the feasibility of the agent for use as an interstitial computed tomographic (CT) lymphographic agent in a normal rat model. MATERIALS AND METHODS: The effect of iodized oil (lipiodol) content and the type of surfactant/cosurfactant on the resultant emulsion size and polydispersity was investigated to obtain an optimized lipiodol emulsion for CT lymphography. Optimized emulsions (144 mg/mL) were injected in the hind paws of 6 rats, using 0.5 mL per paw. As control groups, iopamidol solution and lipiodol diluted with squalene to adjust the injection volume with iodine concentration equivalent to the emulsions were used. Precontrast and postcontrast CT images up to 1 week after contrast agent injection were obtained. Time-enhancement curves of the popliteal lymph nodes were obtained. Analysis of variance and post hoc analysis with the Dunn procedure were used for comparing mean peak enhancement, time to peak enhancement, and sustained duration of contrast enhancement. RESULTS: Optimized emulsion formulations composed of 30% lipiodol and 282 mg/mL of 9:1 surfactant mixture (Tween 80:TPGS [alpha-tocopheryl polyethylene glycol succinate], Tween 80:Kollidon 12 PF, or Tween 80:Span 85) exhibited mean particle size less than 120 nm, and they were stable without significant particle size change up to 1 month. Targeted lymph nodes in all emulsion groups showed continuously increasing enhancement until 4 or 8 hours after injection, followed by continuous washout. Peak enhancement (time to peak enhancement) was 172.4 +/- 54.5 HU (Hounsfield unit) (384.0 +/- 131.5 minutes) for Tween 80:TPGS; 172.8 +/- 28.0 HU (432.0 +/- 107.3 minutes) for Tween 80:Kollidon 12 PF, and 177.2 +/- 68.9 HU (294.0 +/- 190.2 minutes) for Tween 80:Span 85. For iopamidol, peak enhancement of 153.0 +/- 46.1 HU (0.5 +/- 0.5 minutes) occurred early with rapid washout. For lipiodol as a reference agent, contrast enhancement continuously increased even 1 week after injection without washout (peak enhancement, 486.0 +/- 97.4 HU). Peak enhancement among the emulsion groups and the iopamidol group was not statistically different (P = 0.95). All emulsion groups showed more prolonged enhancement than the iopamidol group; enhancement duration for the emulsion groups was 534.0 +/- 481.1 minutes for Tween 80:TPGS; 957.0 +/- 524.8 minutes for Tween 80:Kollidon 12 PF; and 750.0 +/- 566.0 minutes for Tween 80:Span 85, and enhancement duration for iopamidol was 8.2 +/- 12.3 minutes (all P < 0.05 in multiple comparisons). However, there was no significant difference in enhancement duration among the 3 emulsion groups (P > 0.05). CONCLUSIONS: Iodized oil emulsion made with a surfactant mixture (Tween 80 as the main surfactant and TPGS, Kollidon 12 PF, or Span 85 as the cosurfactant) provided sufficient and sustained contrast enhancement on CT of targeted lymph nodes with washout on delayed phase.