Theranostic SPECT reconstruction for improved resolution: application to radionuclide therapy dosimetry

BACKGROUND: SPECT-derived dose estimates in tissues of diameter less than 3× system resolution are subject to significant losses due to the limited spatial resolution of the gamma camera. Incorporating resolution modelling (RM) into the SPECT reconstruction has been proposed as a possible solution; however, the images produced are prone to noise amplification and Gibbs artefacts. We propose a novel approach to SPECT reconstruction in a theranostic setting, which we term SPECTRE (single photon emission computed theranostic reconstruction); using a diagnostic PET image, with its superior resolution, to guide the SPECT reconstruction of the therapeutic equivalent. This report demonstrates a proof in principle of this approach. METHODS: We have employed the hybrid kernelised expectation maximisation (HKEM) algorithm implemented in STIR, with the aim of producing SPECT images with PET-equivalent resolution. We demonstrate its application in both a dual 68Ga/177Lu IEC phantom study and a clinical example using 64Cu/67Cu. RESULTS: SPECTRE is shown to produce images comparable in accuracy and recovery to PET with minimal introduction of artefacts and amplification of noise. CONCLUSION: The SPECTRE approach to image reconstruction shows improved quantitative accuracy with a reduction in noise amplification. SPECTRE shows great promise as a method of improving SPECT radioactivity concentrations, directly leading to more accurate dosimetry estimates in small structures and target lesions. Further investigation and optimisation of the algorithm parameters is needed before this reconstruction method can be utilised in a clinical setting

Story in health and social care

This paper offers a brief consideration of how narrative, in the form of people‟s own stories, potentially figures in health and social care provision as part of the impulse towards patient-centred care. The rise of the epistemological legitimacy of patients‟ stories is sketched here. The paper draws upon relevant literature and original writing to consider the ways in which stories can mislead as well as illuminate the process of making individual treatment care plans

A classification of smooth embeddings of 3-manifolds in 6-space

We work in the smooth category. If there are knotted embeddings S^n\to R^m, which often happens for 2m<3n+4, then no concrete complete description of embeddings of n-manifolds into R^m up to isotopy was known, except for disjoint unions of spheres. Let N be a closed connected orientable 3-manifold. Our main result is the following description of the set Emb^6(N) of embeddings N\to R^6 up to isotopy. The Whitney invariant W : Emb^6(N) \to H_1(N;Z) is surjective. For each u \in H_1(N;Z) the Kreck invariant \eta_u : W^{-1}u \to Z_{d(u)} is bijective, where d(u) is the divisibility of the projection of u to the free part of H_1(N;Z). The group Emb^6(S^3) is isomorphic to Z (Haefliger). This group acts on Emb^6(N) by embedded connected sum. It was proved that the orbit space of this action maps under W bijectively to H_1(N;Z) (by Vrabec and Haefliger's smoothing theory). The new part of our classification result is determination of the orbits of the action. E. g. for N=RP^3 the action is free, while for N=S^1\times S^2 we construct explicitly an embedding f : N \to R^6 such that for each knot l:S^3\to R^6 the embedding f#l is isotopic to f. Our proof uses new approaches involving the Kreck modified surgery theory or the Boechat-Haefliger formula for smoothing obstruction.Comment: 32 pages, a link to http://www.springerlink.com added, to appear in Math. Zei

The effect of an antenatal lifestyle intervention in overweight and obese women on circulating cardiometabolic and inflammatory biomarkers: secondary analyses from the LIMIT randomised trial

Background: Maternal overweight and obesity during pregnancy is associated with insulin resistance, hyperglycaemia, hyperlipidaemia and a low-grade state of chronic inflammation. The aim of this pre-specified analysis of secondary outcome measures was to evaluate the effect of providing antenatal dietary and lifestyle advice on cardiometabolic and inflammatory biomarkers. Methods: We conducted a multicentre trial in which pregnant women who were overweight or obese were randomised to receive either Lifestyle Advice or Standard Care. We report a range of pre-specified secondary maternal and newborn cardiometabolic and inflammatory biomarker outcomes. Maternal whole venous blood was collected at trial entry (mean 14 weeks gestation; non-fasting), at 28 weeks gestation (fasting), and at 36 weeks gestation (non-fasting). Cord blood was collected after birth and prior to the delivery of the placenta. A range of cardiometabolic and inflammatory markers were analysed (total cholesterol, triglycerides, non-esterified fatty acids, high-density lipoprotein cholesterol, insulin, glucose, leptin, adiponectin, C-reactive protein, granulocyte macrophage-colony stimulating factor, interferon gamma, TNF-α, and interleukins 1β, 2, 4, 5, 6, 8, and 10). Participants were analysed in the groups to which they were randomised, and were included in the analyses if they had a measure at any time point. results: One or more biological specimens were available from 1951 women (989 Lifestyle Advice and 962 Standard Care), with cord blood from 1174 infants (596 Lifestyle Advice and 578 Standard Care). There were no statistically significant differences in mean cardiometabolic and inflammatory marker concentrations across pregnancy and in infant cord blood between treatment groups. Estimated treatment group differences were close to zero, with 95% confidence intervals spanning a range of differences that were short of clinical relevance. There was no evidence to suggest that the intervention effect was modified by maternal BMI category. Conclusions: Despite our findings, it will be worth considering potential relationships between cardiometabolic and inflammatory markers and clinical outcomes, including longer-term infant health and adiposity. Trial Registration: Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426 ; Date Registered 09/03/2007).Lisa J. Moran, Louise M. Fraser, Tulika Sundernathan, Andrea R. Deussen, Jennie Louise, Lisa N. Yelland, Rosalie M. Grivell, Anne Macpherson, Matthew W. Gillman, Jeffrey S. Robinson, Julie A. Owens and Jodie M. Dod

Intricate environment-modulated genetic networks control isoflavone accumulation in soybean seeds

<p>Abstract</p> <p>Background</p> <p>Soybean (<it>Glycine max </it>[L] Merr.) seed isoflavones have long been considered a desirable trait to target in selection programs for their contribution to human health and plant defense systems. However, attempts to modify seed isoflavone contents have not always produced the expected results because their genetic basis is polygenic and complex. Undoubtedly, the extreme variability that seed isoflavones display over environments has obscured our understanding of the genetics involved.</p> <p>Results</p> <p>In this study, a mapping population of RILs with three replicates was analyzed in four different environments (two locations over two years). We found a total of thirty-five main-effect genomic regions and many epistatic interactions controlling genistein, daidzein, glycitein and total isoflavone accumulation in seeds. The use of distinct environments permitted detection of a great number of environment-modulated and minor-effect QTL. Our findings suggest that isoflavone seed concentration is controlled by a complex network of multiple minor-effect loci interconnected by a dense epistatic map of interactions. The magnitude and significance of the effects of many of the nodes and connections in the network varied depending on the environmental conditions. In an attempt to unravel the genetic architecture underlying the traits studied, we searched on a genome-wide scale for genomic regions homologous to the most important identified isoflavone biosynthetic genes. We identified putative candidate genes for several of the main-effect and epistatic QTL and for QTL reported by other groups.</p> <p>Conclusions</p> <p>To better understand the underlying genetics of isoflavone accumulation, we performed a large scale analysis to identify genomic regions associated with isoflavone concentrations. We not only identified a number of such regions, but also found that they can interact with one another and with the environment to form a complex adaptable network controlling seed isoflavone levels. We also found putative candidate genes in several regions and overall we advanced the knowledge of the genetics underlying isoflavone synthesis.</p