Assessment of Haemodynamic Response to Nonselective Beta-Blockers in Portal Hypertension by Phase-Contrast Magnetic Resonance Angiography

A significant unmet need exists for accurate, reproducible, noninvasive diagnostic tools to assess and monitor portal hypertension (PHT). We report the first use of quantitative MRI markers for the haemodynamic assessment of nonselective beta-blockers (NSBB) in PHT. In a randomized parallel feasibility study in 22 adult patients with PHT and a clinical indication for NSBB, we acquired haemodynamic data at baseline and after 4 weeks of NSBB (propranolol or carvedilol) using phase-contrast MR angiography (PC-MRA) in selected intra-abdominal vessels. T1 mapping of liver and spleen was undertaken to assess changes in tissue composition. Target NSBB dose was achieved in 82%. There was a substantial reduction from baseline in mean average flow in the superior abdominal aorta after 4 weeks of NSBB therapy (4.49±0.98 versus 3.82±0.86 L/min, P=0.03) but there were no statistically significant differences in flow in any other vessels, even in patients with >25% decrease in heart rate (47% of patients). Mean percentage change in liver and spleen T1 following NSBB was small and highly variable. In conclusion, PC-MRA was able to detect reduction in cardiac output by NSBB but did not detect significant changes in visceral blood flow or T1. This trial was registered with the ISRCTN registry (ISRCTN98001632)

Conceptualising knowledge for access in the sciences: academic development from a social realist perspective

Whilst arguing from a social realist perspective that knowledge matters in academic development (AD) curricula, this paper addresses the question of what knowledge types and practices are necessary for enabling epistemological access. It presents a single, in-depth, qualitative case study in which the curriculum of a science AD course is characterised using Legitimation Code Theory (LCT). Analysis of the course curriculum reveals legitimation of four main categories of knowledge types along a continuum of stronger to weaker epistemic relations: disciplinary knowledge, scientific literacies knowledge, general academic practices knowledge and everyday knowledge. These categories are ‘mapped’ onto an LCT(Semantics)(how meaning relates to both context and empirical referents) topological plane to reveal a curriculum that operates in three distinct but interrelated spaces by facing towards both the field of science and the practice of academia. It is argued that this empirically derived differentiated curriculum framework offers a conceptual means for considering the notion of access to ‘powerful’ knowledge in a range of AD and mainstream contexts

Understanding joint construction in the tertiary context

The importance of teacher-student collaboration in text production is well established in education literature (Cazden 1996; Green 1988; Mehan 1979). Teacher-student collaboration is a key feature of Sydney School Genre pedagogy, particularly in the Joint Construction stage of the Teaching Learning cycle. Joint Construction supports the literacy development of all students through dialogic exchanges that enable the co-creation of a target text (Rothery & Stenglin 1995). While this stage of the Teaching Learning cycle has been widely used across primary, secondary and tertiary contexts, teacher-student dialogue in text production has only been analysed in detail at a primary school level (see Hunt 1991 & 1994). This paper examines three Joint Construction lessons from the tertiary context. Using phasal analysis (Gregory 1985, 1988), it examines how different stages of Joint Construction achieve their goals. Using exchange structure analysis (Sinclair & Coulthard 1975; Berry 1981; Ventola 1987 & 1988; Martin 2007; Author 2007), which is located within the discourse semantic system of NEGOTIATION (Martin & Rose 2007), the paper provides a principled linguistic analysis of the conversational moves taking place

Diffusion-weighted imaging in uterine artery embolisation: do findings correlate with contrast enhancement and volume reduction?

Objectives The objective of this study was to determine the role of diffusion-weighted imaging (DWI) in uterine artery embolisation (UAE), and to assess the apparent diffusion coefficient (ADC) of the dominant fibroid and its relationship to contrast enhancement and fibroid volume reduction. Methods We carried out a retrospective study of 15 patients who underwent UAE. Calculations were performed at baseline and 6 months post-embolisation. Fibroid ADC (expressed in 10−3 mm2 s−1) was calculated using b=0 and b=1000 DWI values. Fibroid enhancement was compared with background myometrium by measuring signal-difference-to-noise ratio (SDNR). Fibroid volume was calculated using a prolate ellipse formula. Results There was a significant reduction (p<0.001) in fibroid ADC at 6 months (0.48; standard deviation, SD=0.26) as compared with baseline (1.01; SD=0.39). No significant change (p=0.07) was identified in 6-month myometrial ADC (1.09; SD=0.28) as compared with baseline (1.24; SD=0.20). Moderately strong and significant positive correlation was identified between baseline ADC and 6-month percentage volume reduction of the fibroid (correlation=0.66, p=0.007). No correlation was identified between SDNR and ADC at baseline or 6 months (r=0.01, p=0.97 and r=−0.13, p=0.64, respectively) or SDNR and percentage volume reduction at 6 months (correlation r=0.18, p=0.51). Conclusion Baseline ADC of dominant fibroids shows a moderately strong correlation with subsequent volume reduction at 6 months following UAE. No correlation was identified between ADC values and contrast enhancement on the baseline or 6-month scans. Further prospective evaluation is needed before DWI can be utilised in clinical practice. Advances in knowledge DWI imaging may provide additional information about UAE and possibly help to predict uterine volume reduction

Vascular biomechanics and molecular disease activity in the thoracic aorta: a novel imaging method

Aims The influence haemodynamics have on vessel wall pathobiology in aortic disease is incomplete. This aim of this study was to develop a repeatable method for assessing the relationship between aortic wall shear stress (WSS) and disease activity by fusing 4D flow cardiovascular magnetic resonance (CMR) with hybrid positron emission tomography (PET). Methods and results As part of an ongoing clinical trial, patients with bicuspid aortic valve (BAV) were prospectively imaged with both 18F-sodium fluoride (18F-NaF) PET, a marker of calcification activity, and 4D flow CMR. We developed novel software allowing accurate 3D co-registration and high-resolution comparison of aortic peak systolic WSS and 18F-NaF PET uptake (maximum tissue-to-background ratio). Intra-observer repeatability of both measurements was determined using Bland–Altman plots and intra-class correlation coefficients (ICCs). The relationship between localized WSS and 18F-NaF uptake was analysed using linear mixed-effect models. Twenty-three patients with BAV (median age 50 [44–55] years, 22% female) were included. Intra-observer repeatability for WSS (ICC = 0.92) and 18F-NaF (ICC = 0.91) measurements obtained within 1.4 ± 0.6 cm2 regions of interest was excellent. On multivariable analysis, 18F-NaF PET uptake was independently and negatively associated with WSS as well as diastolic blood pressure (both P < 0.05), adjusted for age. Conclusion Fused assessment of WSS and 18F-NaF PET uptake is feasible and repeatable, demonstrating a clear association between these two factors. This high spatial resolution approach has major potential to advance our understanding of the relationship between vascular haemodynamics and disease activity

Quantifying microcalcification activity in the thoracic aorta

Background: Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18F-sodium fluoride (18F-NaF) uptake in the thoracic aorta. Methods: Twenty patients underwent two hybrid 18F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each 18F-NaF quantification method was compared to validated cardiovascular risk scores. Results: Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease. Conclusions: AMA is a simple, rapid and reproducible method of quantifying global 18F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores