Quantification and correction of distortion in diffusion-weighted MRI at 1.5 and 3 T in a muscle-invasive bladder cancer phantom for radiotherapy planning

OBJECTIVE: Limited visibility of post-resection muscle-invasive bladder cancer (MIBC) on CT hinders radiotherapy dose escalation of the residual tumour. Diffusion-weighted MRI (DW-MRI) visualises areas of high tumour burden and is increasingly used within diagnosis and as a biomarker for cancer. DW-MRI could, therefore, facilitate dose escalation, potentially via dose-painting and/or accommodating response. However, the distortion inherent in DW-MRI could limit geometric accuracy. Therefore, this study aims to quantify DW-MRI distortion via imaging of a bladder phantom. METHODS: A phantom was designed to mimic MIBC and imaged using CT, DW-MRI and T2W-MRI. Fiducial marker locations were compared across modalities and publicly available software was assessed for correction of magnetic susceptibility-related distortion. RESULTS: Fiducial marker locations on CT and T2W-MRI agreed within 1.2 mm at 3 T and 1.8 mm at 1.5 T. The greatest discrepancy between CT and apparent diffusion coefficient (ADC) maps was 6.3 mm at 3 T, reducing to 1.8 mm when corrected for distortion. At 1.5 T, these values were 3.9 mm and 1.7 mm, respectively. CONCLUSIONS: Geometric distortion in DW-MRI of a model bladder was initially >6 mm at 3 T and >3 mm at 1.5 T; however, established correction methods reduced this to <2 mm in both cases. ADVANCES IN KNOWLEDGE: A phantom designed to mimic MIBC has been produced and used to show distortion in DW-MRI can be sufficiently mitigated for incorporation into the radiotherapy pathway. Further investigation is therefore warranted to enable individually adaptive image-guided radiotherapy of MIBC based upon DW-MRI

Multimodal analysis of the effects of dexamethasone on high-altitude cerebral oedema : protocol for a pilot study

Background Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. Methods/design D4H is a double-blind placebo-controlled randomised trial assessing the effect of dexamethasone on hypoxia-induced cerebral oedema. In total, 20 volunteers were randomised in pairs to receive either 8.25 mg dexamethasone or normal saline placebo intravenously after 8 h of hypoxia with an FiO2 of 12%. Serial MRI images of the brain and spinal cord were obtained at hours 0, 7, 11, 22 and 26 of the study along with serum and urinary markers to correlate with the severity of cerebral oedema and the effect of the intervention. Discussion MRI has been used to identify changes in cerebral vasculature in the development of AMS and HACE. Dexamethasone is effective at reducing the symptoms of AMS; however, the mechanism of this effect is unknown. If this study demonstrates a clear objective benefit of dexamethasone in this setting, future studies may be able to demonstrate that dexamethasone is an effective therapy for oedema associated with brain and spinal cord ischaemia beyond AMS

Magnetic resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema

Rapid ascent to high altitude commonly results in acute mountain sickness, and on occasion potentially fatal high-altitude cerebral edema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. We report a study in which 12 subjects were exposed to a FiO2 = 0.12 for 22 h and underwent serial magnetic resonance imaging sequences to enable measurement of middle cerebral artery velocity, flow and diameter, and brain parenchymal, cerebrospinal fluid and cerebral venous volumes. Ten subjects completed 22 h and most developed symptoms of acute mountain sickness (mean Lake Louise Score 5.4; p < 0.001 vs. baseline). Cerebral oxygen delivery was maintained by an increase in middle cerebral artery velocity and diameter (first 6 h). There appeared to be venocompression at the level of the small, deep cerebral veins (116 cm3 at 2 h to 97 cm3 at 22 h; p < 0.05). Brain white matter volume increased over the 22-h period (574 ml to 587 ml; p < 0.001) and correlated with cumulative Lake Louise scores at 22 h (p < 0.05). We conclude that cerebral oxygen delivery was maintained by increased arterial inflow and this preceded the development of cerebral edema. Venous outflow restriction appeared to play a contributory role in the formation of cerebral edema, a novel feature that has not been observed previously

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Improved thyroid hypoechogenicity following bariatric-induced weight loss in euthyroid adults with severe Obesity-a pilot study

Background: Obesity may affect both biochemical thyroid function tests; and thyroid morphology, as assessed using ultrasound scans (US). The aim of the present pilot study was to explore whether weight loss achieved by bariatric surgery alters thyroid US morphology including gray-scale measurements; and/or function in euthyroid adults with severe obesity. Methods: Euthyroid adults (> 18 years) with body mass index (BMI) ≥40 kg/m2 and negative thyroid peroxidase antibodies were assessed at baseline (pre-surgery) and after achieving at least 5% weight loss of their baseline body weight following bariatric surgery. Anthropometric assessments, biochemical/hormonal measurements (TSH, free-T4, free-T3, reverse-T3, and leptin) and thyroid US with gray-scale histogram analysis were performed at the baseline and post-surgery follow-up. Results: Ten Caucasian, euthyroid patients (women/men: 8/2; age: 48.6 ± 3.1 years; BMI: 51.4 ± 1.8 kg/m2) successfully completed this study with significantly decreased body weight (> 5% weight loss), waist circumference and serum leptin levels post-surgery (mean post-surgery follow-up duration: 16.5 ± 2.5 months). In parallel to the observed bariatric-induced weight loss, thyroid US echogenicity increased by 25% (p = 0.03), without significant changes in thyroid volume. No significant changes in thyroid function tests were detected. No significant correlations were observed between the increase in thyroid echogenicity and the decreases in anthropometric parameters and circulating leptin. Conclusion: Our results indicate that in euthyroid adults with severe obesity, marked weight loss achieved by bariatric surgery is associated with a parallel significant increase in the thyroid US echogenicity, suggesting that morphological changes of the thyroid in obesity are reversible with weight loss

A Very Sensitive 21cm Survey for Galactic High-Velocity HI

Very sensitive HI 21cm observations have been made in 860 directions at dec >= -43deg in search of weak, Galactic, high-velocity HI emission lines at moderate and high Galactic latitudes. One-third of the observations were made toward extragalactic objects. The median 4-sigma detection level is NHI = 8x10^{17} cm^-2 over the 21' telescope beam. High-velocity HI emission is detected in 37% of the directions; about half of the lines could not have been seen in previous surveys. The median FWHM of detected lines is 30.3 km/s. High- velocity HI lines are seen down to the sensitivity limit of the survey implying that there are likely lines at still lower values of NHI. The weakest lines have a kinematics and distribution on the sky similar to that of the strong lines, and thus do not appear to be a new population. Most of the emission originates from objects which are extended over several degrees; few appear to be compact sources. At least 75%, and possibly as many as 90%, of the lines are associated with one of the major high-velocity complexes. The Magellanic Stream extends at least 10 deg to higher Galactic latitude than previously thought and is more extended in longitude as well. Although there are many lines with low column density, their numbers do not increase as rapidly as NHI^-1, so most of the HI mass in the high-velocity cloud phenomenon likely resides in the more prominent clouds. The bright HI features may be mere clumps within larger structures, and not independent objects.Comment: 88 pages includes 22 figures Accepted for Publication in ApJ Suppl. June 200

Experience in implementing harvest strategies in Australia's south-eastern fisheries

The Southern and Eastern Scalefish and Shark Fishery (SESSF) is a complex multi-species fishery, with 34 stock units under quota management, for which a harvest strategy framework was developed in 2005. The framework involves the application of a set of tier-based harvest control rules (HCR) designed to provide a precautionary approach to management. The harvest strategy framework has been applied from 2005 to 2007, resulting in substantial reductions in quotas across the fishery. The experience in implementing the framework, both positive and negative, is described, and general lessons are drawn. Key lessons include the importance of formally testing such strategies using management strategy evaluation, the impact of external management drivers on implementation of the approach, the need to define strategies for setting "bycatch quotas" in multi-species fisheries, and the need for flexibility and pragmatism in the early stages of implementing such an approach

H2, HD, and CO at the edge of 30 Dor in the LMC: the line of sight to Sk-69 246

FUSE and IUE observations of Sk -69 246, a WN 6 star to the north of 30 Dor, reveal the existence of LMC interstellar gas in at least 3 velocity components.In one of these components FUSE spectra show strong absorption by molecular hydrogen with a column density of log N(H_2)=19.6. We investigate the physical conditions in this cloud, which is probably located near the H II region surrounding Sk -69 246. HD and CO with column densities of about 13.9 and 13.0 dex, respectively, are detected. The N(CO)-to-N(H_2) ratio is consistent with values found in the Galaxy. From the population of the rotational levels of H_2 we derive a gas temperature of 72 K and a radiation field U=3*10^-15 erg/(s*cm^3) at 1000 nm. The fractional abundance f=2N(H_2)/[N(H I)+2N(H_2)] is approximately 0.07, rather high for an E(B-V)<0.1.Comment: 8 pages, 8 figures, accepted for publication in A&

Tiny-Scale Molecular Structures in the Magellanic Clouds (Part 1)

We report on the {\small FUSE} detections of the HD and CO molecules {\bf on the lines of sight towards three Large Magellanic stars}: Sk $-$67D05, Sk $-$68D135, and Sk $-$69D246. HD is also detected for the first time {\bf on the lines of sight towards two Small Magellanic Cloud stars}: AV 95 and Sk 159. While the HD and CO abundances are expected to be lower in the Large Magellanic Cloud where molecular fractions are a third of the Galactic value and where the photodissociation flux is up to thousands times larger, we report an average HD/H$_2$ ratio of 1.4$\pm$0.5 ppm and CO/H$_2$ ratio ranging from 0.8 to 2.7 ppm similar to the Galactic ones. We tentatively identify a deuterium reservoir (hereafter D--reservoir) towards the Small Magellanic Cloud, along the light path to AV 95. We derive a D/H ratio ranging from 1. 10$^{-6}$ to 1.1 10$^{-5}$.Comment: 34 pages, 10 tables, 12 figures, accepted for publication in A&