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Cheltenham, United Kingdom

Dicken A.J.,Nottingham Trent University | Evans J.P.O.,Nottingham Trent University | Rogers K.D.,Cranfield University | Stone N.,University of Exeter | And 7 more authors.
Physics in Medicine and Biology | Year: 2015

There is a compelling need for accurate, low cost diagnostics to identify osteo-tissues that are associated with a high risk of fracture within an individual. To satisfy this requirement the quantification of bone characteristics such as 'bone quality' need to exceed that provided currently by densitometry. Bone mineral chemistry and microstructure can be determined from coherent x-ray scatter signatures of bone specimens. Therefore, if these signatures can be measured, in vivo, to an appropriate accuracy it should be possible by extending terms within a fracture risk model to improve fracture risk prediction. In this preliminary study we present an examination of a new x-ray diffraction technique that employs hollow annular and semi-annular beams to measure aspects of 'bone quality'. We present diffractograms obtained with our approach from ex vivo bone specimens at Mo K and W K energies. Primary data is parameterized to provide estimates of bone characteristics and to indicate the precision with which these can be determined. © 2015 Institute of Physics and Engineering in Medicine. Source

Dicken A.J.,Nottingham Trent University | Evans J.P.O.,Nottingham Trent University | Rogers K.D.,Cranfield University | Greenwood C.,Cranfield University | And 7 more authors.
Optics Express | Year: 2015

We demonstrate material phase identification by measuring polychromatic diffraction spots from samples at least 20 mm in diameter and up to 10 mm thick with an energy resolving point detector. Within our method an annular X-ray beam in the form of a conical shell is incident with its symmetry axis normal to an extended polycrystalline sample. The detector is configured to receive diffracted flux transmitted through the sample and is positioned on the symmetry axis of the annular beam. We present the experiment data from a range of different materials and demonstrate the acquisition of useful data with sub-second collection times of 0.5 s; equating to 0.15 mAs. Our technique should be highly relevant in fields that demand rapid analytical methods such as medicine, security screening and non-destructive testing. © 2015 Optical Society of America. Source

Greenwood C.,Cranfield University | Clement J.G.,University of Melbourne | Dicken A.J.,Nottingham Trent University | Evans J.P.O.,Nottingham Trent University | And 6 more authors.
Bone Reports | Year: 2015

Osteoporosis is clinically assessed from bone mineral density measurements using dual energy X-ray absorption (DXA). However, these measurements do not always provide an accurate fracture prediction, arguably because DXA does not grapple with 'bone quality', which is a combined result of microarchitecture, texture, bone tissue properties, past loading history, material chemistry and bone physiology in reaction to disease. Studies addressing bone quality are comparatively few if one considers the potential importance of this factor. They suffer due to low number of human osteoporotic specimens, use of animal proxies and/or the lack of differentiation between confounding parameters such as gender and state of diseased bone. The present study considers bone samples donated from patients (n. = 37) who suffered a femoral neck fracture and in this very well defined cohort we have produced in previous work fracture toughness measurements (FT) which quantify its ability to resist crack growth which reflects directly the structural integrity of the cancellous bone tissue. We investigated correlations between BV/TV and other microarchitectural parameters; we examined effects that may suggest differences in bone remodelling between males and females and compared the relationships with the FT properties. The data crucially has shown that TbTh, TbSp, SMI and TbN may provide a proxy or surrogate for BV/TV. Correlations between FT critical stress intensity values and microarchitecture parameters (BV/TV, BS/TV, TbN, BS/BV and SMI) for osteoporotic cancellous tissue were observed and are for the first time reported in this study. Overall, this study has not only highlighted that the fracture model based upon BMD could potentially be improved with inclusion of other microarchitecture parameters, but has also given us clear clues as to which of them are more influential in this role. © 2015. Source

Arnold D.T.,University of Bristol | Hooper C.E.,University of Bristol | Hooper C.E.,North Bristol Lung Center | Morley A.,North Bristol Lung Center | And 18 more authors.
British Journal of Cancer | Year: 2015

Background: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. Method: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. Results: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. Conclusions: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage. © 2015 Cancer Research UK. All rights reserved. Source

Hooper C.E.,University of Bristol | Hooper C.E.,North Bristol Lung Center | Lyburn I.D.,Cobalt Health | Searle J.,Cobalt Health | And 18 more authors.
British Journal of Cancer | Year: 2015

Background: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. Methods: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. Findings: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR≥4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001). Interpretation: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response. © 2015 Cancer Research UK. All rights reserved. Source

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