Chronic ephedrine administration decreases brown adipose tissue activity in a randomised controlled human trial: implications for obesity.

AIMS/HYPOTHESIS: Brown adipose tissue (BAT) activation increases energy expenditure and may have therapeutic potential to combat obesity. The primary activating and adaptive signal for BAT is via ß-adrenergic signalling. We previously demonstrated that human BAT is acutely responsive to oral administration of the sympathomimetic, ephedrine. Here we aimed to determine whether adaptive thermogenesis can be induced via chronic treatment with ephedrine. METHODS: Twenty-three healthy young men, recruited from the general public in Melbourne, Australia, who were non-smokers, physically inactive and non-medicated with no prior history of cardiovascular disease or diabetes were recruited for this study. They were assigned to receive either 1.5 mg kg(-1) day(-1) ephedrine ('active' group; n = 12, age 23 ± 1 years, BMI 24 ± 1 kg/m(2)) or placebo (n = 11; 22 ± 2 years, 23 ± 2 kg/m(2)) for 28 days in a randomised (computer-generated random order sequence), placebo-controlled, parallel-group trial. Participants and all investigators were blinded to treatments. Body composition was measured before and after the intervention by dual energy X-ray absorptiometry. BAT activity, measured via (18)F-fluorodeoxyglucose positron emission tomography-computed tomography, in response to a single dose of 2.5 mg/kg ephedrine, was the primary outcome measure to be determined before and after the 28 day treatment period. RESULTS: Twenty-eight individuals were randomised and consented to the study. Twenty-three completed the trial and only these participants were included in the final analyses. After 28 days of treatment, the active group lost a significant amount of total body fat (placebo 1.1 ± 0.3 kg, ephedrine -0.9 ± 0.5 kg; p < 0.01) and visceral fat (placebo 6.4 ± 19.1 g, ephedrine -134 ± 43 g; p < 0.01), with no change in lean mass or bone mineral content compared with the placebo group. In response to acute ephedrine, BAT activity (change in mean standardised uptake value: placebo -3 ± 7%, ephedrine -22 ± 6%) and the increase in systolic blood pressure were significantly reduced (p < 0.05) in the active group compared with placebo. CONCLUSIONS/INTERPRETATION: Chronic ephedrine treatment reduced body fat content, but this was not associated with an increase in BAT activity. Rather, chronic ephedrine suppressed BAT glucose disposal, suggesting that chronic ephedrine treatment decreased, rather than increased, BAT activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02236962 FUNDING: This study was funded by the National Health and Medical Research Council of Australia Program Grant (1036352) and the OIS scheme from the Victorian State Government.

Comparison of contemporaneous left ventricular ejection fraction (LVEF) obtained from planar gated cardiac blood pool scans (GCBPS) and Tl-201 gated myocardial perfusion scans (MPS) using a novel solid state dedicated cardiac camera.

BACKGROUND: There is limited data on the concordance of left ventricular ejection fraction (LVEF) obtained via solid state dedicated cardiac cameras (SSD) and gated cardiac blood pool scans (GCBPS). This study aimed to examine the agreement of LVEF measured during GCBPS and Tl-201 myocardial perfusion scans (MPS) using SSD. METHODS: Seventy six patients were enrolled. Following stress MPS with 0.8 Mbq/kg (0.022 mCi/kg) Tl-201 and 8-frame gated rest studies after additional 15 Mbq (0.41 mCi) Tl-201, LVEFs were obtained using ECToolbox (ECT) and quantitative gated SPECT (QGS) software. Same day 16-frame planar GCBPS were performed. Interobserver variability was compared and LVEF results were compared using paired t tests, Pearson's correlation and the differences of the LVEF were plotted against GCBPS values. RESULTS: For GCBPS, ECT and QGS, the mean (±SD) LVEF was 52% ± 14%, 61% ± 18% and 48% ± 19%, respectively. When compared to GCBPS, ECT and QGS, LVEFs had similar R values of 0.85 and 0.83, respectively, and mean differences [95% limits of agreement (LA)] of -8.6% (-27.4% to +10.2%, P < .001) and 4.2% (-17.2% to +25.6%, P = .001), respectively. CONCLUSION: While the LVEF obtained by ECT or QGS demonstrates a statistically significant correlation with GCBPS, they are significantly different and the wide 95% LA suggest that Tl-201 MPS LVEFs derived from either software package are not interchangeable with GCBPS results.

Quantifying the effects of iodine contrast media on standardised uptake values of FDG PET/CT images: an anthropomorphic phantom study.

This study aimed to quantify the amount of change in Standardised Uptake Values (SUVs) of PET/CT images by simulating the set-up as closely as possible to the actual patient scanning. The experiments were conducted using an anthropomorphic phantom, which contained an amount of radioactivity in the form of Fluorodeoxyglucose (FDG) in a primary plastic test tube and one litre saline bags, including the insertion of bony structures and another two test tubes containing different concentrations of iodine contrast media. Standard scanning protocols were employed for the PET/CT image acquisition. The highest absolute differences in the SUVmax and SUVmean values of the saline bags were found to be about 0.2 and 0.4, respectively. The primary test tube showed the largest change of 1.5 in both SUVs; SUV max and SUVmean. However, none of these changes were found to be statistically significant. The clinical literature also contains no evidence to suggest that the changes of this magnitude would change the final diagnosis. Based on these preliminary data, we propose that iodine contrast media can be used during the CT scan of PET/CT imaging, without significantly affecting the diagnostic quality of this integrated imaging modality.

Contributions of subdiaphragmatic activity, attenuation, and diaphragmatic motion to inferior wall artifact in attenuation-corrected Tc-99m myocardial perfusion SPECT.

BACKGROUND: Subdiaphragmatic activity and diaphragmatic motion both contribute to inferior wall artifacts in technetium 99m myocardial perfusion single photon emission computed tomography (SPECT). METHODS AND RESULTS: We used an anthropomorphic phantom with ventricular wall activity, liver/spleen inserts containing variable Tc-99m activity, and variable vertical (diaphragmatic) motion amplitude. SPECT and transmission scans were obtained on a GE Optima NX camera. Data were processed by use of filtered backprojection or attenuation correction (AC). Resulting myocardial activity maps were analyzed with standardized inferior-anterior and anterior-lateral wall ratios. At a subdiaphragmatic-myocardial activity ratio of 0.5:1, inferior wall attenuation predominates, producing a cold artifact. AC corrects inferior wall activity to the level of the anterior wall irrespective of diaphragmatic motion. At a subdiaphragmatic-myocardial activity ratio of 1:1, inferior wall counts vary widely depending on the proximity of subdiaphragmatic activity to the ventricle. With increasing diaphragmatic amplitude, the overlap of subdiaphragmatic activity and inferior wall worsens, leading to a complex mixture of cold and hot artifacts, not corrected by AC. CONCLUSIONS: Concentration and proximity of subdiaphragmatic Tc-99m activity relative to myocardium comprise a major factor in the nature and severity of inferior wall artifacts. If the subdiaphragmatic Tc-99m concentration is equivalent to that in the myocardium, complex, potentially uninterpretable hot and cold inferior wall artifacts are produced.

Staff exposure to ionizing radiation in a major trauma centre.

BACKGROUND: The purpose of the present paper was to determine the safety of staff members with regard to ionizing radiation in a major trauma centre in a 19-month period. METHODS AND RESULTS: A group of five doctors, five nurses and a trauma orderly wore personal radiation monitors under lead aprons while at work. The highest individual cumulative result after 586 days was 0.18 mSv for a nurse. If the exposure rate to ionizing radiation was constant, this would be equivalent to 0.114 mSv per year. Therefore the results are well below the recommended occupational dose limit of 20 mSv per year. CONCLUSION: Wearing of lead aprons during trauma resuscitation appears to be safe and provides adequate protection.

Effect of mechanically simulated diaphragmatic respiratory motion on myocardial SPECT processed with and without attenuation correction.

UNLABELLED: The goal of this study was to assess the effect of diaphragmatic respiratory motion on inferior wall cold artifact in myocardial SPECT and to assess the ability of attenuation correction (AC) to correct for this artifact in the presence of diaphragmatic motion. METHODS: We used an anthropomorphic phantom with ventricular wall activity, variable ventricular caudal tilt, attenuating liver and spleen cold inserts, and variable vertical (diaphragmatic) motion amplitude and pattern. Cardiac SPECT images were acquired on a gamma camera with dual scanning transmission line sources and commercially available AC software (with scatter correction and iterative reconstruction). The acquired data were processed either using filtered backprojection or with the AC software. The resulting myocardial activity maps were processed with polar plots and with standardized inferior-to-anterior and anterior-to-lateral wall ratios. RESULTS: Subdiaphragmatic attenuation reduces inferior wall counts and this component of inferior wall artifact is fully corrected by AC relative to anterior wall counts both with and without diaphragmatic respiratory motion. In the phantom, diaphragmatic motion artifact manifests as reduction in relative count density in both the anterior wall and the inferior wall relative to the lateral wall, which is not corrected by AC. This artifact becomes more marked with increasing respiratory amplitude and its symmetry depends on the pattern of diaphragmatic motion. CONCLUSION: Images with AC acquired at small respiratory amplitudes (approximately 2 cm) in the phantom resemble images with AC found in published normal patient databases. These results support a clinical need for respiratory gating of myocardial SPECT images.