Unsupervised Segmentation of 5D Hyperpolarized Carbon-13 MRI Data Using a Fuzzy Markov Random Field Model

Hyperpolarized MRI with 13C-labelled compounds is an emerging clinical technique allowing in vivo metabolic processes to be characterized non-invasively. Accurate quantification of 13C data, both for clinical and research purposes, typically relies on the use of region-of-interest analysis to detect and compare regions of altered metabolism. However, it is not clear how this should be determined from the five-dimensional data produced and most standard methodologies are unable to exploit the multidimensional nature of the data. Here we propose a solution to the novel problem of 13C image segmentation using a hybrid Markov random field model with continuous fuzzy logic. The algorithm fully utilizes the multi-dimensional data format in order to classify each voxel into one of six distinct classes based on its metabolic characteristics. Bayesian priors fully incorporate spatial, temporal and ratiometric contextual information whilst image contrast from multiple spectral dimensions are considered concurrently by using an analogy from color image segmentation. Performance of the algorithm is demonstrated on in silico data where the superiority of the approach over a reference thresholding method is consistently observed. Application to in vivo animal data from a pre-clinical subcutaneous tumor model illustrates the ability of the MRF algorithm to successfully detect tumor location whilst avoiding image artefacts. This work has the potential to assist the analysis of human hyperpolarized 13C data in the future.CJD is jointly funded by the National Institute for Health Research (NIHR), Cambridge Biomedical Research Centre and GlaxoSmithKline (GSK). The authors acknowledge further research support from Cancer Research UK (C19212/A911376, C19212/A16628), the Cancer Research UK/Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester, the CRUK Cambridge Centre and Cambridge Experimental Cancer Medicine Centre

From Molecular Cores to Planet-forming Disks with SIRTF

The SIRTF mission and the Legacy programs will provide coherent data bases for extra-galactic and Galactic science that will rapidly become available to researchers through a public archive. The capabilities of SIRTF and the six legacy programs are described briefly. Then the cores to disks (c2d) program is described in more detail. The c2d program will use all three SIRTF instruments (IRAC, MIPS, and IRS) to observe sources from molecular cores to protoplanetary disks, with a wide range of cloud masses, stellar masses, and star-forming environments. The SIRTF data will stimulate many follow-up studies, both with SIRTF and with other instruments.Comment: 6 pages, from Fourth Cologne-Bonn-Zermatt-Symposium, The Dense Interstellar Matter in Galaxie

Determinants of adults' intention to vaccinate against pandemic swine flu

This article has been made available through the Brunel Open Access Publishing Fund.This article has been made available through the Brunel Open Access Publishing Fund.Background: Vaccination is one of the cornerstones of controlling an influenza pandemic. To optimise vaccination rates in the general population, ways of identifying determinants that influence decisions to have or not to have a vaccination need to be understood. Therefore, this study aimed to predict intention to have a swine influenza vaccination in an adult population in the UK. An extension of the Theory of Planned Behaviour provided the theoretical framework for the study. Methods: Three hundred and sixty two adults from the UK, who were not in vaccination priority groups, completed either an online (n = 306) or pen and paper (n = 56) questionnaire. Data were collected from 30th October 2009, just after swine flu vaccination became available in the UK, and concluded on 31st December 2009. The main outcome of interest was future swine flu vaccination intentions. Results: The extended Theory of Planned Behaviour predicted 60% of adults’ intention to have a swine flu vaccination with attitude, subjective norm, perceived control, anticipating feelings of regret (the impact of missing a vaccination opportunity), intention to have a seasonal vaccine this year, one perceived barrier: “I cannot be bothered to get a swine flu vaccination” and two perceived benefits: “vaccination decreases my chance of getting swine flu or its complications” and “if I get vaccinated for swine flu, I will decrease the frequency of having to consult my doctor,” being significant predictors of intention. Black British were less likely to intend to have a vaccination compared to Asian or White respondents. Conclusions: Theoretical frameworks which identify determinants that influence decisions to have a pandemic influenza vaccination are useful. The implications of this research are discussed with a view to maximising any future pandemic influenza vaccination uptake using theoretically-driven applications.This article is available through the Brunel Open Access Publishing Fund

Does a 'direct' transfer protocol reduce time to coronary angiography for patients with non-ST-elevation acute coronary syndromes? A prospective observational study.

OBJECTIVE: National guidelines recommend 'early' coronary angiography within 96 h of presentation for patients with non-ST elevation acute coronary syndromes (NSTE-ACS). Most patients with NSTE-ACS present to their district general hospital (DGH), and await transfer to the regional cardiac centre for angiography. This care model has inherent time delays, and delivery of timely angiography is problematic. The objective of this study was to assess a novel clinical care pathway for the management of NSTE-ACS, known locally as the Heart Attack Centre-Extension or HAC-X, designed to rapidly identify patients with NSTE-ACS while in DGH emergency departments (ED) and facilitate transfer to the regional interventional centre for 'early' coronary angiography. METHODS: This was an observational study of 702 patients divided into two groups; 391 patients treated before the instigation of the HAC-X pathway (Pre-HAC-X), and 311 patients treated via the novel pathway (Post-HAC-X). Our primary study end point was time from ED admission to coronary angiography. We also assessed the length of hospital stay. RESULTS: Median time from ED admission to coronary angiography was 7.2 (IQR 5.1-10.2) days pre-HAC-X compared to 1.0 (IQR 0.7-2.0) day post-HAC-X (p<0.001). Median length of hospital stay was 3.0 (IQR 2.0-6.0) days post-HAC-X v 9.0 (IQR 6.0-14.0) days pre-HAC-X (p<0.0005). This equates to a reduction of six hospital bed days per NSTE-ACS admission. CONCLUSIONS: The introduction of this novel care pathway was associated with significant reductions in time to angiography and in total hospital bed occupancy for patients with NSTE-ACS

Why I tense up when you watch me: inferior parietal cortex mediates an audience’s influence on motor performance

The presence of an evaluative audience can alter skilled motor performance through changes in force output. To investigate how this is mediated within the brain, we emulated real-time social monitoring of participants’ performance of a fine grip task during functional magnetic resonance neuroimaging. We observed an increase in force output during social evaluation that was accompanied by focal reductions in activity within bilateral inferior parietal cortex. Moreover, deactivation of the left inferior parietal cortex predicted both inter- and intra-individual differences in socially-induced change in grip force. Social evaluation also enhanced activation within the posterior superior temporal sulcus, which conveys visual information about others’ actions to the inferior parietal cortex. Interestingly, functional connectivity between these two regions was attenuated by social evaluation. Our data suggest that social evaluation can vary force output through the altered engagement of inferior parietal cortex; a region implicated in sensorimotor integration necessary for object manipulation, and a component of the action-observation network which integrates and facilitates performance of observed actions. Social-evaluative situations may induce high-level representational incoherence between one’s own intentioned action and the perceived intention of others which, by uncoupling the dynamics of sensorimotor facilitation, could ultimately perturbe motor output

Effective Feedback to Improve Primary Care Prescribing Safety (EFIPPS) a pragmatic three-arm cluster randomised trial:designing the intervention (ClinicalTrials.gov registration NCT01602705)

Peer reviewedPublisher PD

Heparan sulphate synthetic and editing enzymes in ovarian cancer

Several angiogenic growth factors including fibroblast growth factors 1 and 2 (FGF1 and FGF2) depend on heparan sulphate (HS) for biological activity. We previously showed that all cellular elements in ovarian tumour tissue synthesised HS but biologically active HS (i.e. HS capable of binding FGF2 and its receptor) was confined to ovarian tumour endothelium. In this study, we have sought to explain this observation. Heparan sulphate sulphotransferases 1 and 2 (HS6ST1 and HS6ST2) attach sulphate groups to C-6 of glucosamine residues in HS that are critical for FGF2 activation. These enzymes were strongly expressed by tumour cells, but only HS6ST1 was found in endothelial cells. Immunostaining with the 3G10 antibody of tissue sections pretreated with heparinases indicated that HS proteoglycans were produced by tumour and endothelial cells. These results indicated that, in contrast to the endothelium, HS produced by tumour cells may be modified by cell-surface heparanase (HPA1) or endosulphatase (SULF). Protein and RNA analysis revealed that HPA1 was strongly expressed by ovarian tumour cells in eight of ten specimens examined. HSULF-1, which removes specific 6-O-sulphate groups from HS, was abundant in tumour cells but weakly expressed in the endothelium. If this enzyme was responsible for the lack of biologically active HS on the tumour cell surface, we would expect exogenous FGF2 binding to be preserved; we showed previously that this was indeed the case although FGF2 binding was reduced compared to the endothelium and stroma. Thus, the combined effects of heparanase and HSULF could account for the lack of biologically active HS in tumour cells rather than deficiencies in the biosynthetic enzymes

Feasibility of metabolic imaging of hyperpolarized 13C-pyruvate in human breast cancer

Introduction Imaging of the breast with hyperpolarized 13C yields new challenges compared to imaging the prostate [1]. E.g. large anteroposterior B0 gradients [2] require correction and the anatomy and patient positioning need a new, highly optimized RF coil array for achieving sufficient SNR/spatial resolution. As a first step, we have investigated single-breast imaging in the coronal plane. Methods A BRCA gene carrier with a 38-mm diameter grade 3 triple-negative invasive ductal carcinoma was studied on a 3T MRI (GE Healthcare) using a prototype 8-channel 13C breast coil (Rapid Biomedical), containing 2 transmit/receive coils and 6 receive-only covering both breasts in a prone position. 1H imaging was performed with the body coil. Following injection of 40ml of 250mM 13C-pyruvate, polarized to c. 25%, a 1-minute time series of spirals with IDEAL encoding (3) was collected (flip angle 10°, TR=260ms, 8-step cycle, time resolution 2.08s, 3 x 3-cm thick slices, 3mm gap, 40-pt spiral, 24cm coronal FOV, real pixel size 12 x 12 x 30mm). IDEAL reconstruction of images was optimized separately for each slice to enable independent frequency offsets to be applied. Kinetic modelling was performed in MATLAB, with automated tumour segmentation. Results Tumour pixels were identified by the segmentation algorithm only in the tumour-containing slice 2, and the average estimated flux from pyruvate to lactate kPL within this ROI was 0.022 s-1 (Fig. 1). The frequency shift of pyruvate relative to slice 2 was +6 Hz in slice 3 and -34 Hz in slice 1, confirming a sharp gradient in B0 approaching the nipple, which was corrected by optimizing slices separately (Fig 2). Images of lactate and pyruvate summed over the time course (Fig 3) showed strong signal of both metabolites over the tumour in slice 2, lower pyruvate in the slice toward the chest wall, and no consistent signal in slice 1. Conclusion This first-in-Europe study in breast cancer established the feasibility of obtaining metabolite images with high temporal and moderate spatial resolution in humans in vivo following administration of hyperpolarized 13C-pyruvate. Coronal image orientation allowed application of significant corrections for a known limitation, the anteroposterior B0 gradient, as well as a small FOV to improve spatial resolution. Kinetic rate constants within the tumour were found to be consistent with previous reports in human prostate cancer (1). References 1) Nelson SJ et al. Sci Transl Med 5, 198ra108 (2013). 2) Maril N, et al. Magn. Reson. Med. 2005; 54:1139-1145. 3) Wiesinger F, et al. Magn Reson Med 2012; 68:8-16