Assessing metabolism and injury in acute human traumatic brain injury with magnetic resonance spectroscopy: current and future applications

Traumatic brain injury triggers a series of complex pathophysiological processes. These include abnormalities in brain energy metabolism; consequent to reduced tissue pO₂ arising from ischaemia or abnormal tissue oxygen diffusion, or due to a failure of mitochondrial function. In-vivo magnetic resonance spectroscopy (MRS) allows non-invasive interrogation of brain tissue metabolism in patients with acute brain injury. Nuclei with ‘spin’ e.g. ¹H, ³¹P and ¹³C, are detectable using MRS and are found in metabolites at various stages of energy metabolism, possessing unique signatures due to their chemical shift or spin-spin interactions (J-coupling). The most commonly used clinical MRS technique, ¹H MRS, uses the great abundance of hydrogen atoms within molecules in brain tissue. Spectra acquired with longer echo-times include N-acetylaspartate, creatine and choline. N-acetylaspartate, a marker of neuronal mitochondrial activity related to ATP, is reported to be lower in patients with TBI than healthy controls, and the ratio of N-acetylaspartate/creatine at early time points may correlate with clinical outcome. ¹H MRS acquired with shorter echo-times produces a more complex spectrum, allowing detection of a wider range of metabolites. ³¹P MRS detects high energy phosphate species, which are the end-products of cellular respiration: adenosine triphosphate (ATP) and phosphocreatine. ATP is the principal form of chemical energy in living organisms, and phosphocreatine (PCr) is regarded as a readily mobilised reserve for its replenishment during periods of high utilisation. The ratios of high energy phosphates are thought to represent a balance between energy generation, reserve and use in the brain Additionally, the chemical shift difference between Pi and PCr enables calculation of intracellular pH. ¹³C MRS detects the ¹³C-isotope of carbon in brain metabolites. As the natural abundance of ¹³C is low (1.1%), ¹³C MRS is typically performed following administration of ¹³C-enriched substrates which permits tracking of the metabolic fate of the infused ¹³C in the brain over time, and calculation of metabolic rates in a range of biochemical pathways, including glycolysis, the tricarboxylic acid (TCA) cycle, and glutamate-glutamine cycling. The advent of new hyperpolarization techniques to transiently boost signal in ¹³C-enriched MRS in-vivo studies shows promise in this field and further developments are expected.The funding bodies acknowledged on the paper are: PJAH is supported by a National Institute for Health Research (NIHR) Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship and the National Institute for Health Research Biomedical Research Centre, Cambridge. PJAH and KLHC are supported by the NIHR Biomedical Research Centre, Cambridge. MGS is supported by PH’s NIHR Research Professorship. AS is funded by the NIHR via an award to the Cambridge NIHR/Wellcome Trust Clinical Research Facility

Brain hypoxia mapping in acute stroke: Back-to-back T2′ MR versus 18F-fluoromisonidazole PET in rodents

Background Mapping the hypoxic brain in acute ischemic stroke has considerable potential for both diagnosis and treatment monitoring. PET using (18)F-fluoro-misonidazole (FMISO) is the reference method; however, it lacks clinical accessibility and involves radiation exposure. MR-based T2' mapping may identify tissue hypoxia and holds clinical potential. However, its validation against FMISO imaging is lacking. Here we implemented back-to-back FMISO-PET and T2' MR in rodents subjected to acute middle cerebral artery occlusion. For direct clinical relevance, regions of interest delineating reduced T2' signal areas were manually drawn. Methods Wistar rats were subjected to filament middle cerebral artery occlusion, immediately followed by intravenous FMISO injection. Multi-echo T2 and T2* sequences were acquired twice during FMISO brain uptake, interleaved with diffusion-weighted imaging. Perfusion-weighted MR was also acquired whenever feasible. Immediately following MR, PET data reflecting the history of FMISO brain uptake during MR acquisition were acquired. T2' maps were generated voxel-wise from T2 and T2*. Two raters independently drew T2' lesion regions of interest. FMISO uptake and perfusion data were obtained within T2' consensus regions of interest, and their overlap with the automatically generated FMISO lesion and apparent diffusion coefficient lesion regions of interest was computed. Results As predicted, consensus T2' lesion regions of interest exhibited high FMISO uptake as well as substantial overlap with the FMISO lesion and significant hypoperfusion, but only small overlap with the apparent diffusion coefficient lesion. Overlap of the T2' lesion regions of interest between the two raters was ∼50%. Conclusions This study provides formal validation of T2' to map non-core hypoxic tissue in acute stroke. T2' lesion delineation reproducibility was suboptimal, reflecting unclear lesion borders.This study was funded by an EU Grant (EUSTROKE Health-F2-2008-2022131). DJW was funded by an MRC collaborative grant (G0600986), RM by the NIHR Cambridge Biomedical Research Centre, and UJK by a fellowship from the Deutsche Forschungsgemeinschaft (Je 598/1-1)

Adolescents’ responses to the promotion and flavouring of e-cigarettes

Objectives The purpose of the study is to examine adolescents’ awareness of e-cigarette marketing and investigate the impact of e-cigarette flavour descriptors on perceptions of product harm and user image. Methods Data come from the 2014 Youth Tobacco Policy Survey, a cross-sectional in-home survey conducted with 11–16 year olds across the UK (n = 1205). Adolescents’ awareness of e-cigarette promotion, brands, and flavours was assessed. Perceptions of product harm, and likely user of four examples of e-cigarette flavours was also examined. Results Some participants had tried e-cigarettes (12 %) but regular use was low (2 %) and confined to adolescents who had also smoked tobacco. Most were aware of at least one promotional channel (82 %) and that e-cigarettes came in different flavours (69 %). Brand awareness was low. E-cigarettes were perceived as harmful (M = 3.54, SD = 1.19) but this was moderated by product flavours. Fruit and sweet flavours were perceived as more likely to be tried by young never smokers than adult smokers trying to quit (p < 0.001). Conclusions There is a need to monitor the impact of future market and regulatory change on youth uptake and perceptions of e-cigarettes

Anatomical and biomechanical evaluation of the tension band technique in patellar fractures

Tension band wiring for patellar fractures is common, but some recent reports refer to disadvantages of this approach. Our anatomical and biomechanical study focused on use of tension band techniques in patellar fractures. The anatomy of the patella and tendon insertion was examined with knee magnetic resonance imaging (MRI) and correlated with the technical requirements of the tension band. Tension band wiring over tendinous tissue was simulated and calculated with a cyclic biomechanical test on cow patellae. According to tension band templating on the MRI section, Kirschner wire insertion was needed for the tension band to turn over the tendinous tissue. The tension band became more stable while turning over less tendinous tissue and more adjacent bone surface. Nevertheless, cyclic loading tests indicate that all tension band applications in this study lose their initial stability. Excessive initial compression by the tension band resulted in bending of the Kirschner wire and thus reduction failure. For optimum stabilisation, tension force transfer should be done directly on bone or at least material that protects the tendon would be useful

Assessment of Surface Water Contamination from Coalbed Methane Fracturing-Derived Volatile Contaminants in Sullivan County, Indiana, USA

There is a growing concern over the contamination of surface water and the associated environmental and public health consequences from the recent proliferation in hydraulic fracturing in the USA. Petroleum hydrocarbon-derived contaminants of concern [benzene, toluene, ethylbenzene, and xylene (BTEX)] and various dissolved cations and anions were spatially determined in surface waters around 14 coalbed methane fracking wells in Sullivan County, IN, USA. At least one BTEX was detected in 69% of sampling sites (n=13) and 23% of sampling sites were found to be contaminated with all of the BTEX. Toluene was the most common BTEX compound detected across all sites, both upstream and downstream from coalbed methane fracking sites. The calcium (~60 ppm) and sulfates (~175 ppm) were the dominant cations and anions, respectively, in surface water around the fracking sites. This study represents the first report of BTEX contamination in surface water from coalbed methane hydraulic fracturing wells

The politics of regulatory enforcement and compliance: Theorizing and operationalizing political influences

There is broad consensus in the literature on regulatory enforcement and compliance that politics matters. However, there is little scholarly convergence on what politics is or rigorous theorization and empirical testing of how politics matters. Many enforcement and compliance studies omit political variables altogether. Among those that address political influences on regulatory outcomes, politics has been defined in myriad ways and, too often, left undefined. Even when political constructs are explicitly operationalized, the mechanisms by which they influence regulatory outcomes are thinly hypothesized or simply ignored. If politics is truly as important to enforcement and compliance outcomes as everyone in the field seems to agree, regulatory scholarship must make a more sustained and systematic effort to understand their relationship, because overlooking this connection risks missing what is actually driving regulatory outcomes. This article examines how the construct of “politics” has been conceptualized in regulatory theory and analyzes how it has been operationalized in empirical studies of regulatory enforcement and compliance outcomes. It brings together scholarship across disciplines that rarely speak but have much to say to one another on this subject in order to constitute a field around the politics of regulation. The goal is to sharpen theoretical and empirical understandings of when and how regulation works by better accounting for the role politics plays in its enforcement