Radiation metabolomics. 2. Dose- and time-dependent urinary excretion of deaminated purines and pyrimidines after sublethal gamma-radiation exposure in mice

Gamma-radiation exposure of humans is a major public health concern as the threat of terrorism and potential hostile use of radiological devices increases worldwide. We report here the effects of sublethal gamma-radiation exposure on the mouse urinary metabolome determined using ultra-performance liquid chromatography-coupled time-of-flight mass spectrometry-based metabolomics. Five urinary biomarkers of sublethal radiation exposure that were statistically significantly elevated during the first 24 h after exposure to doses ranging from 1 to 3 Gy were unequivocally identified by tandem mass spectrometry. These are deaminated purine and pyrimidine derivatives, namely, thymidine, 2'-deoxyuridine, 2'-deoxyxanthosine, xanthine and xanthosine. Furthermore, the aminopyrimidine 2'-deoxycytidine appeared to display reduced urinary excretion at 2 and 3 Gy. The elevated biomarkers displayed a time-dependent excretion, peaking in urine at 8-12 h but returning to baseline by 36 h after exposure. It is proposed that 2'-deoxyuridine and 2'-deoxyxanthosine arise as a result of gamma irradiation by nitrosative deamination of 2'-deoxycytidine and 2'-deoxyguanosine, respectively, and that this further leads to increased synthesis of thymidine, xanthine and xanthosine. The urinary excretion of deaminated purines and pyrimidines, at the expense of aminopurines and aminopyrimidines, appears to form the core of the urinary radiation metabolomic signature of mice exposed to sublethal doses of ionizing radiation.

The production and composition of rat sebum is unaffected by 3 Gy gamma radiation

The aim of this work was to use metabolomics to evaluate sebum as a source of biomarkers for gamma-radiation exposure in the rat, and potentially in man. Proof of concept of radiation metabolomics was previously demonstrated in both mouse and rat urine, from the radiation dose- and time-dependent excretion of a set of urinary biomarkers.

Radiation metabolomics. 1. Identification of minimally invasive urine biomarkers for gamma-radiation exposure in mice

Gamma-radiation exposure has both short- and long-term adverse health effects. The threat of modern terrorism places human populations at risk for radiological exposures, yet current medical countermeasures to radiation exposure are limited. Here we describe metabolomics for gamma-radiation biodosimetry in a mouse model. Mice were gamma-irradiated at doses of 0, 3 and 8 Gy (2.57 Gy/min), and urine samples collected over the first 24 h after exposure were analyzed by ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOFMS). Multivariate data were analyzed by orthogonal partial least squares (OPLS). Both 3- and 8-Gy exposures yielded distinct urine metabolomic phenotypes. The top 22 ions for 3 and 8 Gy were analyzed further, including tandem mass spectrometric comparison with authentic standards, revealing that N-hexanoylglycine and beta-thymidine are urinary biomarkers of exposure to 3 and 8 Gy, 3-hydroxy-2-methylbenzoic acid 3-O-sulfate is elevated in urine of mice exposed to 3 but not 8 Gy, and taurine is elevated after 8 but not 3 Gy. Gene Expression Dynamics Inspector (GEDI) self-organizing maps showed clear dose-response relationships for subsets of the urine metabolome. This approach is useful for identifying mice exposed to gamma radiation and for developing metabolomic strategies for noninvasive radiation biodosimetry in humans.

Radiation dose optimized lateral expansion of the field of view in synchrotron radiation X-ray tomographic microscopy

Volumetric data at micrometer level resolution can be acquired within a few minutes using synchrotron-radiation-based tomographic microscopy. The field of view along the rotation axis of the sample can easily be increased by stacking several tomograms, allowing the investigation of long and thin objects at high resolution. On the contrary, an extension of the field of view in the perpendicular direction is non-trivial. This paper presents an acquisition protocol which increases the field of view of the tomographic dataset perpendicular to its rotation axis. The acquisition protocol can be tuned as a function of the reconstruction quality and scanning time. Since the scanning time is proportional to the radiation dose imparted to the sample, this method can be used to increase the field of view of tomographic microscopy instruments while optimizing the radiation dose for radiation-sensitive samples and keeping the quality of the tomographic dataset on the required level. This approach, dubbed wide-field synchrotron radiation tomographic microscopy, can increase the lateral field of view up to five times. The method has been successfully applied for the three-dimensional imaging of entire rat lung acini with a diameter of 4.1 mm at a voxel size of 1.48 microm.

Radiation dose reduction in computer assisted navigation for functional endoscopic sinus surgery--cadaver head experiments and clinical implementation

Computed tomography based navigation for endoscopic sinus surgery is inflationary used despite of major public concern about iatrogenic radiation induced cancer risk. Studies on dose reduction for CAS-CT are almost nonexistent. We validate the use of radiation dose reduced CAS-CT for clinically applied surface registration.

Iterative Reconstruction Algorithm for Abdominal Multidetector CT at Different Tube Voltages: Assessment of Diagnostic Accuracy, Image Quality, and Radiation Dose in a Phantom Study

To assess the diagnostic accuracy, image quality, and radiation dose of an iterative reconstruction algorithm compared with a filtered back projection (FBP) algorithm for abdominal computed tomography (CT) at different tube voltages.

An education and training programme for radiological institutes: impact on the reduction of the CT radiation dose

To establish an education and training programme for the reduction of CT radiation doses and to assess this programme's efficacy.

[Strategies for reducing the CT radiation dose]

The rapid technical advances in computed tomography have led to an increased number of clinical indications. Unfortunately, at the same time the radiation exposure to the population has also increased due to the increased total number of CT examinations. In the last few years various publications have demonstrated the feasibility of radiation dose reduction for CT examinations with no compromise in image quality and loss in interpretation accuracy. The majority of the proposed methods for dose optimization are easy to apply and are independent of the detector array configuration. This article reviews indication-dependent principles (e.g. application of reduced tube voltage for CT angiography, selection of the collimation and the pitch, reducing the total number of imaging series, lowering the tube voltage and tube current for non-contrast CT scans), manufacturer-dependent principles (e.g. accurate application of automatic modulation of tube current, use of adaptive image noise filter and use of iterative image reconstruction) and general principles (e.g. appropriate patient-centering in the gantry, avoiding over-ranging of the CT scan, lowering the tube voltage and tube current for survey CT scans) which lead to radiation dose reduction.

Detection of pancreatic tumors, image quality, and radiation dose during the pancreatic parenchymal phase: effect of a low-tube-voltage, high-tube-current CT technique--preliminary results

To intraindividually compare a low-tube-voltage (80 kVp), high-tube-current (675 mA) computed tomographic (CT) technique with a high-tube-voltage (140 kVp) CT protocol for the detection of pancreatic tumors, image quality, and radiation dose during the pancreatic parenchymal phase.

Low-tube-voltage, high-tube-current multidetector abdominal CT: improved image quality and decreased radiation dose with adaptive statistical iterative reconstruction algorithm--initial clinical experience

To investigate whether an adaptive statistical iterative reconstruction (ASIR) algorithm improves the image quality at low-tube-voltage (80-kVp), high-tube-current (675-mA) multidetector abdominal computed tomography (CT) during the late hepatic arterial phase.

Radiation dose optimization in pediatric temporal bone computed tomography: influence of tube tension on image contrast and image quality

The purpose of this experimental study was to investigate the effect of tube tension reduction on image contrast and image quality in pediatric temporal bone computed tomography (CT).

Dose modulated retrospective ECG-gated versus non-gated 64-row CT angiography of the aorta at the same radiation dose: Comparison of motion artifacts, diagnostic confidence and signal-to-noise-ratios

To compare ECG-gated and non-gated CT angiography of the aorta at the same radiation dose, with regard to motion artifacts (MA), diagnostic confidence (DC) and signal-to-noise-ratios (SNRs).

Meta-analysis: diagnostic performance of low-radiation-dose coronary computed tomography angiography

A new radiation dose-saving technique for noninvasive coronary artery imaging with computed tomography (CT) is available.

Effect of patient size on radiation dose for abdominal MDCT with automatic tube current modulation: phantom study

OBJECTIVE: The purpose of this study was to evaluate in a phantom study the effect of patient size on radiation dose for abdominal MDCT with automatic tube current modulation. MATERIALS AND METHODS: One or two 4-cm-thick circumferential layers of fat-equivalent material were added to the abdomen of an anthropomorphic phantom to simulate patients of three sizes: small (cross-sectional dimensions, 18 x 22 cm), average size (26 x 30 cm), and oversize (34 x 38 cm). Imaging was performed with a 64-MDCT scanner with combined z-axis and xy-axis tube current modulation according to two protocols: protocol A had a noise index of 12.5 H, and protocol B, 15.0 H. Radiation doses to three abdominal organs and the skin were assessed. Image noise also was measured. RESULTS: Despite increasing patient size, the image noise measured was similar for protocol A (range, 11.7-12.2 H) and protocol B (range, 13.9-14.8 H) (p > 0.05). With the two protocols, in comparison with the dose of the small patient, the abdominal organ doses of the average-sized patient and the oversized patient increased 161.5-190.6%and 426.9-528.1%, respectively (p < 0.001). The skin dose increased as much as 268.6% for the average-sized patient and 816.3% for the oversized patient compared with the small patient (p < 0.001). CONCLUSION: Oversized patients undergoing abdominal MDCT with tube current modulation receive significantly higher doses than do small patients. The noise index needs to be adjusted to the body habitus to ensure dose efficiency.