Diacylglycerol kinase delta overexpression improves glucose clearance and protects against the development of obesity.

BACKGROUND AND AIM: Diacylglycerol kinase (DGK) isoforms catalyze an enzymatic reaction that removes diacylglycerol (DAG) and thereby terminates protein kinase C signaling by converting DAG to phosphatidic acid. DGKδ (type II isozyme) downregulation causes insulin resistance, metabolic inflexibility, and obesity. Here we determined whether DGKδ overexpression prevents these metabolic impairments. METHODS: We generated a transgenic mouse model overexpressing human DGKδ2 under the myosin light chain promoter (DGKδ TG). We performed deep metabolic phenotyping of DGKδ TG mice and wild-type littermates fed chow or high-fat diet (HFD). Mice were also provided free access to running wheels to examine the effects of DGKδ overexpression on exercise-induced metabolic outcomes. RESULTS: DGKδ TG mice were leaner than wild-type littermates, with improved glucose tolerance and increased skeletal muscle glycogen content. DGKδ TG mice were protected against HFD-induced glucose intolerance and obesity. DGKδ TG mice had reduced epididymal fat and enhanced lipolysis. Strikingly, DGKδ overexpression recapitulated the beneficial effects of exercise on metabolic outcomes. DGKδ overexpression and exercise had a synergistic effect on body weight reduction. Microarray analysis of skeletal muscle revealed common gene ontology signatures of exercise and DGKδ overexpression that were related to lipid storage, extracellular matrix, and glycerophospholipids biosynthesis pathways. CONCLUSION: Overexpression of DGKδ induces adaptive changes in both skeletal muscle and adipose tissue, resulting in protection against HFD-induced obesity. DGKδ overexpression recapitulates exercise-induced adaptations on energy homeostasis and skeletal muscle gene expression profiles.

Glutamine Regulates Skeletal Muscle Immunometabolism in Type 2 Diabetes.

Dysregulation of skeletal muscle metabolism influences whole-body insulin sensitivity and glucose homeostasis. We hypothesized that type 2 diabetes-associated alterations in the plasma metabolome directly contribute to skeletal muscle immunometabolism and the subsequent development of insulin resistance. To this end, we analyzed the plasma and skeletal muscle metabolite profile and identified glutamine as a key amino acid that correlates inversely with BMI and insulin resistance index (HOMA-IR) in men with normal glucose tolerance or type 2 diabetes. Using an in vitro model of human myotubes and an in vivo model of diet-induced obesity and insulin resistance in male mice, we provide evidence that glutamine levels directly influence the inflammatory response of skeletal muscle and regulate the expression of the adaptor protein GRB10, an inhibitor of insulin signaling. Moreover, we demonstrate that a systemic increase in glutamine levels in a mouse model of obesity improves insulin sensitivity and restores glucose homeostasis. We conclude that glutamine supplementation may represent a potential therapeutic strategy to prevent or delay the onset of insulin resistance in obesity by reducing inflammatory markers and promoting skeletal muscle insulin sensitivity.

Discovery of thymosin ß4 as a human exerkine and growth factor.

Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in interorgan cross talk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin ß4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X was also acutely increased in the plasma of exercising humans irrespective of the insulin resistance condition or exercise mode. Treatment of mice with TMSB4X did not ameliorate the metabolic disruptions associated with diet induced-obesity, nor did it enhance muscle regeneration in vivo. However, TMSB4X increased osteoblast proliferation and neurite outgrowth, consistent with its WADA classification as a prohibited growth factor. Therefore, we report TMSB4X as a human exerkine with a potential role in cellular cross talk.

Group IIA secreted phospholipase A2 (PLA2G2A) augments adipose tissue thermogenesis.

Group IIA secreted phospholipase A2 (PLA2G2A) hydrolyzes glycerophospholipids at the sn-2 position resulting in the release of fatty acids and lysophospholipids. C57BL/6 mice do not express Pla2g2a due to a frameshift mutation (wild-type [WT] mice). We previously reported that transgenic expression of human PLA2G2A in C57BL/6 mice (IIA+ mice) protects against weight gain and insulin resistance, in part by increasing total energy expenditure. Additionally, we found that brown and white adipocytes from IIA+ mice have increased expression of mitochondrial uncoupling markers, such as uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor-gamma coactivator, and PR domain containing 16, suggesting that the energy expenditure phenotype might be due to an increased thermogenic capacity in adipose tissue. Here, we further characterize the impact of PLA2G2A on thermogenic mechanisms in adipose tissue. Metabolic analysis of WT and IIA+ mice revealed that even when housed within their thermoneutral zone, IIA+ mice have elevated energy expenditure compared to WT littermates. Increased energy expenditure in IIA+ mice is associated with increased citrate synthase activity in brown adipose tissue (BAT) and increased mitochondrial respiration in both brown and white adipocytes. We also observed that direct addition of recombinant PLA2G2A enzyme to in vitro cultured adipocytes results in the marked induction of UCP1 protein expression. Finally, we report that PLA2G2A induces the expression of numerous transcripts related to energy substrate transport and metabolism in BAT, suggestive of an increase in substrate flux to fuel BAT activity. These data demonstrate that PLA2G2A enhances adipose tissue thermogenesis, in part, through elevated substrate delivery and increased mitochondrial content in BAT.

Secretory Phospholipase A2s in Insulin Resistance and Metabolism.

The phospholipases A2 (PLA2) superfamily encompasses enzymes commonly found in mammalian tissues and snake venom. Many of these enzymes have unique tissue distribution, function, and substrate specificity suggesting distinct biological roles. In the past, much of the research on secretory PLA2s has analyzed their roles in inflammation, anti-bacterial actions, and atherosclerosis. In recent studies utilizing a variety of mouse models, pancreatic islets, and clinical trials, a role for many of these enzymes in the control of metabolism and insulin action has been revealed. In this review, this research, and the unique contributions of the PLA2 enzymes in insulin resistance and metabolism.

Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages.

Prevalence of obesity among infants and children below 5 years of age is rising dramatically, and early childhood obesity is a forerunner of obesity and obesity-associated diseases in adulthood. Childhood obesity is hence one of the most serious public health challenges today. Here, we have identified a mother-to-child lipid signaling that protects from obesity. We have found that breast milk-specific lipid species, so-called alkylglycerol-type (AKG-type) ether lipids, which are absent from infant formula and adult-type diets, maintain beige adipose tissue (BeAT) in the infant and impede the transformation of BeAT into lipid-storing white adipose tissue (WAT). Breast milk AKGs are metabolized by adipose tissue macrophages (ATMs) to platelet-activating factor (PAF), which ultimately activates IL-6/STAT3 signaling in adipocytes and triggers BeAT development in the infant. Accordingly, lack of AKG intake in infancy leads to a premature loss of BeAT and increases fat accumulation. AKG signaling is specific for infants and is inactivated in adulthood. However, in obese adipose tissue, ATMs regain their ability to metabolize AKGs, which reduces obesity. In summary, AKGs are specific lipid signals of breast milk that are essential for healthy adipose tissue development.

Secretory phospholipase A2 group IIA enhances the metabolic rate and increases glucose utilization in response to thyroid hormone.

Secretory phospholipase A2 group IIA (PLA2G2A) is a phospholipase which has a role in inflammation, atherogenesis, and host defense. Previously, we found that PLA2G2A protects mice on high-fat diets from weight gain and insulin resistance. Here, we examined the regulation of PLA2G2A and the metabolic changes that occur in response to variations in thyroid status. In particular, the impact of PLA2G2A on the brown adipose tissue (BAT) thermogenic gene expression was explored. We induced hypothyroidism in C57BL/6 and PLA2G2A-overexpressing (IIA+) mice over a 10 wk period or treated them with thyroid hormone (T3) for 5 wk. There were no significant changes in PLA2G2A abundance in response to thyroid status. The energy expenditure of hypothyroid IIA+ mice did not increase; however, the energy expenditure, substrate utilization, insulin sensitivity, and glucose tolerance were all elevated in the IIA+ mice given T3. Moreover, white adipocytes from IIA+ mice were much more prone to "beiging," including increased expression of brown adipose thermogenic markers such as uncoupling protein 1 (UCP1), PR domain containing 16, and early B cell factor 2. Finally, the BAT of IIA+ mice had increased UCP1 and other proteins indicative of mitochondrial uncoupling and nonshivering adaptive thermogenesis. These data reveal a novel role for PLA2G2A on adipose tissue thermogenesis depending on thyroid status.-Kuefner, M. S., Deng, X., Stephenson, E. J., Pham, K., Park, E. A. Secretory phospholipase A2 group IIA enhances the metabolic rate and increases glucose utilization in response to thyroid hormone.

Sex-specific differences in hepatic steatosis in obese spontaneously hypertensive (SHROB) rats.

BACKGROUND: Patients with metabolic syndrome, who are characterized by co-existence of insulin resistance, hypertension, hyperlipidemia, and obesity, are also prone to develop non-alcoholic fatty liver disease (NAFLD). Although the prevalence and severity of NAFLD is significantly greater in men than women, the mechanisms by which gender modulates the pathogenesis of hepatic steatosis are poorly defined. The obese spontaneously hypertensive (SHROB) rats represent an attractive model of metabolic syndrome without overt type 2 diabetes. Although pathological manifestation caused by the absence of a functional leptin receptor has been extensively studied in SHROB rats, it is unknown whether these animals elicited sex-specific differences in the development of hepatic steatosis. METHODS: We compared hepatic pathology in male and female SHROB rats. Additionally, we examined key biochemical and molecular parameters of signaling pathways linked with hyperinsulinemia and hyperlipidemia. Finally, using methods of quantitative polymerase chain reaction (qPCR) and western blot analysis, we quantified expression of 45 genes related to lipid biosynthesis and metabolism in the livers of male and female SHROB rats. RESULTS: We show that all SHROB rats developed hepatic steatosis that was accompanied by enhanced expression of SREBP1, SREBP2, ACC1, and FASN proteins. The livers of male rats also elicited higher induction of Pparg, Ppara, Slc2a4, Atox1, Skp1, Angptl3, and Pnpla3 mRNAs. In contrast, the livers of female SHROB rats elicited constitutively higher levels of phosphorylated JNK and AMPK and enhanced expression of Cd36. CONCLUSION: Based on these data, we conclude that the severity of hepatic steatosis in male and female SHROB rats was mainly driven by increased de novo lipogenesis. Moreover, male and female SHROB rats also elicited differential severity of hepatic steatosis that was coupled with sex-specific differences in fatty acid transport and esterification.

Secretory phospholipase A2 group IIA modulates insulin sensitivity and metabolism.

Secretory phospholipase A2 group IIA (PLA2G2A) is a member of a family of secretory phospholipases that have been implicated in inflammation, atherogenesis, and antibacterial actions. Here, we evaluated the role of PLA2G2A in the metabolic response to a high fat diet. C57BL/6 (BL/6) mice do not express PLA2g2a due to a frameshift mutation. We fed BL/6 mice expressing the human PLA2G2A gene (IIA+ mice) a fat diet and assessed the physiologic response. After 10 weeks on the high fat diet, the BL/6 mice were obese, but the IIA+ mice did not gain weight or accumulate lipid. The lean mass in chow- and high fat-fed IIA+ mice was constant and similar to the BL/6 mice on a chow diet. Surprisingly, the IIA+ mice had an elevated metabolic rate, which was not due to differences in physical activity. The IIA+ mice were more insulin sensitive and glucose tolerant than the BL/6 mice, even when the IIA+ mice were provided the high fat diet. The IIA+ mice had increased expression of uncoupling protein 1 (UCP1), sirtuin 1 (SIRT1), and PPARγ coactivator 1α (PGC-1α) in brown adipose tissue (BAT), suggesting that PLA2G2A activates mitochondrial uncoupling in BAT. Our data indicate that PLA2G2A has a previously undiscovered impact on insulin sensitivity and metabolism.

Morphology of the distal thoracic duct and the right lymphatic duct in different head and neck pathologies: an imaging based study.

BACKGROUND: The purpose of this study was to assess the influence of head and neck pathologies on the detection rate, configuration and diameter of the thoracic duct (TD) and right lymphatic duct (RLD) in computed tomography (CT) of the head and neck. METHODS: One hundred ninety-seven patients were divided into the subgroups "healthy", "benign disease" and "malignant disease". The interpretation of the images was performed at a slice thickness of 3 mm in the axial and coronal plane. In each case we looked for the distal part of the TD and RLD respectively and subsequently evaluated their configuration (tubular, sacciform, dendritic) as well as their maximum diameter and correlated the results with age, gender and diagnosis group. RESULTS: The detection rate in the study population was 81.2 % for the TD and 64.2 % for the RLD and did not differ significantly in any of the subgroups. The predominant configuration was tubular. The configuration distribution did not differ significantly between the diagnosis groups. The mean diameter of the TD was 4.79 ± 2.41 mm and that of the RLD was 3.98 ± 1.96 mm. No significant influence of a diagnosis on the diameter could be determined. CONCLUSIONS: There is no significant influence of head/neck pathologies on the CT detection rate, morphology or size of the TD and RLD. However our study emphasizes that both the RLD and the TD are detectable in the majority of routine head and neck CTs and therefore reading physicians and radiologists should be familiar with their various imaging appearances.

Influence of Cardiac MR Imaging on DNA Double-Strand Breaks in Human Blood Lymphocytes.

PURPOSE: To evaluate the ability of magnetic resonance (MR) imaging to induce deoxyribonucleic acid (DNA) damage in patients who underwent cardiac MR imaging in daily routine by using γ-H2AX immunofluorescence microscopy. MATERIALS AND METHODS: This study complies with the Declaration of Helsinki and was performed according to local ethics committee approval. Informed patient consent was obtained. Blood samples from 45 patients (13 women, 32 men; mean age, 50.3 years [age range, 20-89 years]) were obtained before and after contrast agent-enhanced cardiac MR imaging. MR imaging-induced double-strand breaks (DSBs) were quantified in isolated blood lymphocytes by using immunofluorescence microscopy after staining the phosphorylated histone variant γ-H2AX. Twenty-nine patients were examined with a myocarditis protocol (group A), 10 patients with a stress-testing protocol (group B), and six patients with flow measurements and angiography (group C). Paired t test was performed to compare excess foci before and after MR imaging. RESULTS: The mean baseline DSB level before MR imaging and 5 minutes after MR imaging was, respectively, 0.116 DSB per cell ± 0.019 (standard deviation) and 0.117 DSB per cell ± 0.019 (P = .71). There was also no significant difference in DSBs in these subgroups (group A: DSB per cell before and after MR imaging, respectively, 0.114 and 0.114, P = .91; group B: DSB per cell before and after MR imaging, respectively, 0.123 and 0.124, P = .78; group C: DSB per cell before and after MR imaging, respectively, 0.114 and 0.115, P = .36). CONCLUSION: By using γ-H2AX immunofluorescence microscopy, no DNA DSBs were detected after cardiac MR imaging.

Influence of Different Antioxidants on X-Ray Induced DNA Double-Strand Breaks (DSBs) Using γ-H2AX Immunofluorescence Microscopy in a Preliminary Study.

BACKGROUND: Radiation exposure occurs in X-ray guided interventional procedures or computed tomography (CT) and γ-H2AX-foci are recognized to represent DNA double-strand breaks (DSBs) as a biomarker for radiation induced damage. Antioxidants may reduce the induction of γ-H2AX-foci by binding free radicals. The aim of this study was to establish a dose-effect relationship and a time-effect relationship for the individual antioxidants on DSBs in human blood lymphocytes. MATERIALS AND METHODS: Blood samples from volunteers were irradiated with 10 mGy before and after pre-incubation with different antioxidants (zinc, trolox, lipoic acid, ß-carotene, selenium, vitamin E, vitamin C, N-acetyl-L-cysteine (NAC) and Q 10). Thereby, different pre-incubation times, concentrations and combinations of drugs were evaluated. For assessment of DSBs, lymphocytes were stained against the phosphorylated histone variant γ-H2AX. RESULTS: For zinc, trolox and lipoic acid regardless of concentration or pre-incubation time, no significant decrease of γ-H2AX-foci was found. However, ß-carotene (15%), selenium (14%), vitamin E (12%), vitamin C (25%), NAC (43%) and Q 10 (18%) led to a significant reduction of γ-H2AX-foci at a pre-incubation time of 1 hour. The combination of different antioxidants did not have an additive effect. CONCLUSION: Antioxidants administered prior to irradiation demonstrated the potential to reduce γ-H2AX-foci in blood lymphocytes.

Successful treatment of a patient with middle aortic syndrome and renovisceral involvement using aorto-aortic bypass: case report and review of recent literature.

Middle aortic syndrome (MAS), defined as localized abdominal or thoracic aortic hypoplasia, represents an extraordinary rare condition, often diagnosed in younger patients with severe renal hypertension. Etiology is divided into congenital and acquired causes (e.g., Takayasu disease). Because of its extremely unfavorable course, treatment of symptomatic patients is mandatory, whereas open surgery with aorto-aortic bypass or patch aortoplasty is considered the standard therapy. This report describes a case of a 19-year-old Macedonian woman presenting with MAS and renal hypertension who was successfully treated with aorto-aortic bypass, including reconstruction of both renal and the hepatic and superior mesenteric arteries, and reviews the current literature.

X-ray induced formation of γ-H2AX foci after full-field digital mammography and digital breast-tomosynthesis.

PURPOSE: To determine in-vivo formation of x-ray induced γ-H2AX foci in systemic blood lymphocytes of patients undergoing full-field digital mammography (FFDM) and to estimate foci after FFDM and digital breast-tomosynthesis (DBT) using a biological phantom model. MATERIALS AND METHODS: The study complies with the Declaration of Helsinki and was performed following approval by the ethic committee of the University of Erlangen-Nuremberg. Written informed consent was obtained from every patient. For in-vivo tests, systemic blood lymphocytes were obtained from 20 patients before and after FFDM. In order to compare in-vivo post-exposure with pre-exposure foci levels, the Wilcoxon matched pairs test was used. For in-vitro experiments, isolated blood lymphocytes from healthy volunteers were irradiated at skin and glandular level of a porcine breast using FFDM and DBT. Cells were stained against the phosphorylated histone variant γ-H2AX, and foci representing distinct DNA damages were quantified. RESULTS: Median in-vivo foci level/cell was 0.086 (range 0.067-0.116) before and 0.094 (0.076-0.126) after FFDM (p = 0.0004). In the in-vitro model, the median x-ray induced foci level/cell after FFDM was 0.120 (range 0.086-0.140) at skin level and 0.035 (range 0.030-0.050) at glandular level. After DBT, the median x-ray induced foci level/cell was 0.061 (range 0.040-0.081) at skin level and 0.015 (range 0.006-0.020) at glandular level. CONCLUSION: In patients, mammography induces a slight but significant increase of γ-H2AX foci in systemic blood lymphocytes. The introduced biological phantom model is suitable for the estimation of x-ray induced DNA damages in breast tissue in different breast imaging techniques.

The effect of calyculin A on the dephosphorylation of the histone γ-H2AX after formation of X-ray-induced DNA double-strand breaks in human blood lymphocytes.

PURPOSE: The purpose of this study was to investigate the effect of calyculin A on the number of γ-H2AX foci (phosphorylated histone variant 2AX) in lymphocytes after in vitro and in vivo irradiation with rather low doses as they are used in diagnostic and interventional radiology. MATERIALS AND METHODS: For in vitro experiments blood samples of 14 healthy volunteers were irradiated with different doses (10, 50, 100 mGy) and incubated with (0.01, 0.1, 1, 10 nM) or without calyculin A for up to 2 hours. Non-irradiated samples with and without calyculin A served as controls. For in vivo evaluation blood samples were collected from seven patients undergoing computed tomography (CT) both with 1 nM calyculin A containing vials and vials without calyculin A. Foci were quantified in isolated lymphocytes using γ-H2AX immunofluorescence microscopy. RESULTS: 1 nM calyculin A led to a complete inhibition of γ-H2AX foci loss in irradiated samples whereas no inhibition of p53 binding protein 1 (53 BP1) foci was found. Lower concentrations of the phosphatase inhibitor did not have a sufficient effect on foci decrease. Calyculin A did not affect foci levels in non-irradiated samples. If no calyculin A was added into the vial before the blood draws detectable CT-induced foci levels were lower in all patients with a reduction of the medians of 35%. CONCLUSIONS: Using γ-H2AX immunofluorescence microscopy calyculin A can be a useful tool to mark the induced γ-H2AX foci after low dose irradiation and to avoid an underestimation of the real deoxyribonucleic acid (DNA) damage in in vitro and in vivo experiments.

MRI-guided core biopsy of the prostate in the supine position--introduction of a simplified technique using large-bore magnet systems.

OBJECTIVES: To introduce a simplified technique for MRI-guided core biopsies (MRGB) of the prostate in the supine position using large-bore magnet systems. METHODS: Fifty men with a history of negative transrectal ultrasound-guided biopsies underwent MRGB in either a 1.5-T (13/50) or 3.0-T (37/50) wide-bore MRI unit. MRGBs were conducted with the patients in a supine position using a dedicated MR-compatible biopsy device. RESULTS: We developed a dedicated positioning device for the supine position. Using this device, the biopsies were performed successfully in all patients. Apart from minor rectal bleeding, only one patient developed a major side effect (urosepsis). Histology revealed prostate cancer in 25/50 (50 %) patients. CONCLUSIONS: The new technique appears feasible. Its major advantage is the more comfortable and patient-friendly supine position during the biopsy without the need to modify the MRI system's patient table. KEY POINTS: • A novel positioning device for MRI-guided prostate biopsies has been developed. • Biopsies can be performed in the patient-friendly supine position. • The positioning device can be utilised without modifying the MRI's patient table.

Induction and repair of DNA double-strand breaks in blood lymphocytes of patients undergoing ¹8F-FDG PET/CT examinations.

PURPOSE: The purpose of this study was to evaluate DNA double-strand breaks (DSBs) in blood lymphocytes of patients undergoing positron emission tomography (PET)/CT using γ-H2AX immunofluorescence microscopy and to differentiate between (18)F-fluorodeoxyglucose (FDG) and CT-induced DNA lesions. METHODS: This study was approved by the local Ethics Committee and complies with Health Insurance Portability and Accountability Act (HIPAA) requirements. After written informed consent was obtained, 33 patients underwent whole-body (18)F-FDG PET/CT (3 MBq/kg body weight, 170/100 reference mAs at 120 kV). The FDG PET and CT portions were performed as an initial CT immediately followed by the PET. Blood samples were obtained before, at various time points following (18)F-FDG application and up to 24 h after the CT scan. Distinct foci representing DSBs were quantified in isolated lymphocytes using fluorescence microscopy after staining against the phosphorylated histone variant γ-H2AX. RESULTS: The DSB values at the various time points were significantly different (p < 0.001). The median baseline level was 0.08/cell (range 0.06-0.12/cell). Peaks of radiation-induced DSBs were found 30 min after (18)F-FDG administration (median excess foci 0.11/cell, range 0.06-0.27/cell) and 5 min after CT (median excess foci 0.17/cell, range 0.05-0.54/cell). A significant correlation between CT-induced DSBs and dose length product was obtained (ρ = 0.898, p < 0.001). After 24 h DSB values were still slightly but significantly elevated (median foci 0.11/cell, range 0.10-0.14/cell, p = 0.003) compared to pre-exposure levels. CONCLUSION: PET/CT-induced DSBs can be monitored using γ-H2AX immunofluorescence microscopy. Peak values may be obtained 30 min after (18)F-FDG injection and 5 min after CT. The radionuclide contributes considerably to the total DSB induction in this setting.

Attenuation-based automatic kilovolt selection in abdominal computed tomography: effects on radiation exposure and image quality.

OBJECTIVES: Dose reduction has become a major issue in computed tomography (CT). The benefit of kilovolt (kV) reduction has been demonstrated in CT angiography. We sought to evaluate an attenuation-based fully automated kV-selection and milliampere second-adaption algorithm for CT and to assess radiation dose and image quality in comparison with a standard 120 kV protocol in contrast-enhanced (CE) portal-venous thoracoabdominal imaging. MATERIALS AND METHODS: One hundred patients (mean age, 58.4 ± 5.7 years; mean body mass index [BMI], 26.1 ± 5.1 kg/m(2)) underwent CE CT using automated selection of the tube potential (80-140 kV) with milliampere second adaption based on the attenuation profile of the scout scan. The estimated CT dose index was recorded for the proposed scan setting and standard 120-kV protocol. Regions of interest measurements were performed at different locations for objective assessment of image quality. Signal-to-noise ratio and contrast-to-noise ratio (CNR) were calculated. The subjective image quality was assessed by 2 observers with a 4-point scale using previous CT examinations with the 120-kV standard protocol as the reference for comparison. RESULTS: The kV-selection algorithm could be applied in all examinations without problems. Image quality was high, and there were no significant differences compared with previous examinations of the patients performed at 120 kV. Eighty kilovolts was used in 9% of examinations (mean BMI, 22.8 ± 2.8 kg/m(2)); 100 kV, in 75% (mean BMI, 23.7 ± 4.7 kg/m(2)); 120 kV, in 16% (mean BMI, 30 ± 3.3 kg/m(2)); and 140 kV, in a single case (BMI, 49.4 kg/m(2)). The average estimated CT dose index reduction was 25.3% in the 80-kV group, 14.5% in the 100-kV group, and 11.4% overall. The CNR did not differ significantly, whereas the signal-to-noise ratio was significantly higher in the 80- and 100-kV examinations. CONCLUSION: The attenuation-based kV-selection algorithm was demonstrated to be applicable in clinical routine of CE thoracoabdominal CT, to keep CNR constant, and to result in a significant dose reduction while preserving image quality.

Normalized metal artifact reduction in head and neck computed tomography.

OBJECTIVE: Artifacts from dental hardware affect image quality and the visualization of lesions in the oral cavity and oropharynx in computed tomography (CT). Therefore, magnetic resonance imaging is considered the imaging modality of choice in this region. Standard methods for metal artifact reduction (MAR) in CT replace the metal-affected raw data by interpolation, which is prone to new artifacts. We developed a generalized normalization technique for MAR (NMAR) that aims to suppress algorithm-induced artifacts and validated the performance of this algorithm in a clinical trial. MATERIAL AND METHODS: A 3-dimensional forward projection identifies the metal-affected raw data in the original projections after metal is segmented in the image domain by thresholding. A prior image is used to normalize the projections before interpolation. The original raw data are divided pixel-wise by the projection data of the prior image and, after interpolation, are denormalized again. Data from 19 consecutive patients with metal artifacts from dental hardware were reconstructed with standard filtered backprojection (FBP), linear interpolation MAR (LIMAR), and NMAR. The image quality of slices containing metal was analyzed for the severity of artifacts and diagnostic value; magnetic resonance imaging performed the same day on a 3-T system served as a reference standard in all cases. RESULTS: A total of 260 slices containing metal dental hardware were analyzed. A total of 164 slices were nondiagnostic with FBP, 157 slices with LIMAR, and 87 slices with NMAR. The mean (SD) number of slices per patient with severe artifacts was 10.1 (3.7), 9.6 (4.6), and 5.4 (3.6) and the mean (SD) number of slices with artifacts affecting diagnostic confidence was 3.3 (1.7), 4.9 (2.9), and 3.7 (1.9) for FBP, LIMAR, and NMAR, respectively (P < 0.001). Pairwise comparison did not show significant differences between FBP and LIMAR (P = 0.40), but there were significant differences between FBP and NMAR as well as LIMAR and NMAR (both P < 0.001). Interobserver agreement was excellent (κ = 0.974). Two malignant lesions were unmasked with NMAR image reconstructions. No algorithm-related artifacts were detected in regions that did not contain metal in NMAR images. CONCLUSION: Normalized MAR has the potential to improve image quality in patients with artifacts from dental hardware and to improve the diagnostic accuracy of CT of the oral cavity and oropharynx.

Effect of antioxidants on X-ray-induced γ-H2AX foci in human blood lymphocytes: preliminary observations.

PURPOSE: To investigate the effect of a radioprotective oral agent containing a formulation of antioxidants and glutathione-elevating compounds on the extent of x-ray-induced γ-H2AX foci formation. MATERIALS AND METHODS: The study was approved by local ethics committee and informed consent was obtained from each subject. In vitro experiments with blood lymphocytes of 25 healthy volunteers were performed without antioxidants and with antioxidants added either before or immediately after irradiation (10 mGy). For in vivo/in vitro tests, blood samples were obtained before, 15, 30, and 60 minutes (n=17) after, and 2, 3, and 5 hours (n=11) after oral ingestion of antioxidant pills and were irradiated (10 mGy). DNA double-strand breaks (DSBs) were quantified in isolated lymphocytes 5 minutes (in vitro and in vivo/in vitro) and 15 minutes (in vitro) after irradiation by enumerating γ-H2AX foci. To validate the data, additional in vitro experiments with use of 53BP1 as another independent marker for DSBs were performed. Nonirradiated samples served as controls. Statistical analyses were performed by using Wilcoxon rank-sum tests (in vitro), repeated-measures test, and Dunnett test (in vivo/in vitro). RESULTS: In the in vitro experiments, 15-minute preincubation with antioxidants significantly reduced mean γ-H2AX foci levels by 23% (P<.0001), whereas addition of antioxidants immediately after irradiation did not lead to a reduction of x-ray-induced foci (P=.6905). Mean 53BP1 foci were also reduced by preincubation with the radioprotectant. In the in vivo/in vitro tests, oral pretreatment with antioxidants also led to a significant reduction of γ-H2AX foci formation; administration 60 minutes before irradiation resulted in a mean foci reduction of 58% (P<.0001). CONCLUSION: The tested formulation of antioxidants significantly reduced formation of γ-H2AX and 53BP1 foci after irradiation at a radiologic radiation dose typical for computed tomographic imaging; administration 60 minutes prior to irradiation seems to be appropriate and leads to a significant reduction in foci.