1,721,030 research outputs found
Functional lung assessment using hyperpolarised xenon gas magnetic resonance imaging
Get PDFPurpose
Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. The standard method for assessing lung function in COPD is spirometry, which provides global lung function information but is a poor predictor of disability and quality of life. The overall aim of this thesis is to develop utility of hyperpolarised xenon gas magnetic resonance imaging (HP 129Xe-MRI) as a technique to evaluate regional lung function.
Methods
Studies were approved by the National Research Ethics Service (NRES). Eleven volunteers and 25 patients with COPD underwent HP 129Xe-MRI, pulmonary function tests (PFTs) and quantitative computerised tomography (QCT).
Gravitational-dependent gradients of HP 129Xe-MRI were compared between prone and supine postures in healthy volunteers. Lobar quantification of HP 129Xe-MRI was completed in COPD patients, who also underwent time-resolved HP 129Xe-MRI and HP 129Xe-MRI pre- and post-salbutamol to determine feasibility of detecting regional delayed ventilation and post-intervention change. The relationship between study measures was assessed using Pearsonâs correlation coefficient.
Results
HP 129Xe-MR ventilation gradients were more marked in the supine than prone posture in healthy volunteers, whereas diffusion-weighted gradients were more uniform. HP 129Xe-MRI was successfully quantified according to pulmonary lobes and correlated with lobar lung anatomy (QCT) and global functional transfer capability (TLCO) (r=-0.61, p<0.005). Delayed ventilation was observed with time-resolved breath-hold HP 129Xe-MRI. Differential regional ventilation change was detected with HP 129Xe-MRI post-salbutamol.
Conclusion
These data demonstrate technical optimisation of HP 129Xe-MRI in healthy volunteers and COPD patients. Successful generation of lobar HP 129Xe-MRI parameters offers an automated analysis method that can be adopted into the clinical workflow. Finally proof-of-principle data have identified roles for HP 129Xe-MRI in evaluating regional treatments and assessing therapeutic response. Future work will evaluate the role of HP 129Xe-MRI in patient selection for lung volume reduction therapy and as a surrogate end-point in drug development studies. </p
Radionuclide imaging of angiogenesis
Get PDFAngiogenesis is a fundament al process in the survival, growth and spread of cancers. In recent years several therapies have been developed to interfere with this process. Despite initial optimism these agents have rarely provided durable clinical responses. Methods capable 0f assessing angiogenesis are required to help develop effective anti-angiogenic approaches Radionuclide imaging is one potential method of assessing angiogenesis. VEGF and integrin expression are two key factors in regulation of angiogenesis in tumours and provide potential targets for radionuclide imaging of angiogenesis. This thesis investigates whether targeting of VEGF and integrins can be performed to image angiogenesis and if treatment with antiangiogenic therapy can be detected via such imaging. VEGF imaging was successfully performed by radiolabelling bevacizumab, a monoclonal antibody directed against all isoforms of VEGF, with 111 indium for SPECT imaging. This agent was validate in vitro and in vivo mouse xenograft models, and appears to bind to matrix and cell membrane associated VEGF within tumours. lntegrin imaging was attempted using 99Tc-maraciclatide, another SPECT imaging agent. This is a commercial agent based on the RGD tripeptide sequence and binds primarily to α,β3 and α,β5 integrins. It was assessed in a clinical trial and compared with histological markers of angiogenes' in patients with colorectal, renal and breast tumours. There was an inverse relationship between 99mTc•maraciclatide uptake and β13 vascular density but no correlation with other angiogenic markers. Both tracers were investigated in a preclinical xenograft model with antiangiogenic therapies Rapamycin, an mTOR inhibitor, increased uptake of 111ln-bnDTPA-bevacizumab and decrease uptake of 99"'Tc-maraciclatide. These responses corresponded with an increase in VEGF an decrease in β3 integrin levels in the tumours. Rapamycin therapy was also associated with reduction in blood vessel number and changes in perfusion as demonstrated by DCE•MRI. The effect of bevacizumab therapy on 99Tc•maraciclatide uptake was also investigated. Bevacizumab had no significant effect on either 99mTc-maraciclatide uptake or β3 integrin levels. These preliminary results demonstrate that both radiotracers have potential for imagin, angiogenesis and detecting response to angiogenic therapies. They also highlight the complex nature of the angiogenic process and that further work is necessary to determine the clinical usefulness of these agents.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Quantitative assessment of tumour response to therapy by diagnostic ultrasound
Get PDFChemotherapy forms the mainstay of treatment for patients with liver tumours, which has a number of significant side effects. Treatment response is often assessed some time after commencement of treatment. A quantitative method to detect early liver tumour response to chemotherapy would be beneficial to facilitate termination of ineffective treatment and to minimise unnecessary side effects. This thesis investigated firstly whether fractal analysis of contrast enhanced computed tomography (ceCT) images of colorectal liver metastases could be used to detect early response to chemotherapy. Secondly, a technique based on Nakagami imaging of ultrasound radio-frequency (RF) signals was developed, initially using data from a xenograft mouse tumour model, as a potential early predictor of tumour response. This was subsequently tested using clinical ultrasound data collected from patients undergoing chemotherapy treatment for liver tumours. Mean fractal dimension (FD) obtained from fractal analysis of volumetric ceCT images of colorectal liver metastases was confirmed as a reliable quantitative parameter to detect tumour tissue changes. There was however no significant difference in the interval change of mean FD from baseline between responding and non-responding metastases. Based on the current study, fractal analysis is unable to detect early liver tumour response to chemotherapy. Development of an ultrasound-based tissue assessment technique was then performed, owing to the advantages of ultrasound imaging. A Nakagami imaging-based volumetric tissue assessment technique was developed using backscattered RF ultrasound data from xenograft mice tumour treated in an investigation of high intensity focused ultrasound mediated chemotherapy delivery. The percentage of pre- Rayleigh regions (%PRR) obtained from the new analysis technique demonstrated an indirect correlation with the tumour volume. Interval reduction in %PRR from baseline was also found to be significantly greater in tumours that responded to treatment. These observations confirmed the potential of Nakagami imaging-based techniques to detect early tumour response to treatment. The technique was subsequently used to analyse volumetric ultrasound datasets collected from patients undergoing chemotherapy treatment for liver tumours. The %PRR was found to indirectly correlate with the axial diameter of the liver tumour. Additionally, interval increase in the %PRR between follow-up and baseline study was found to be significantly higher in responding compared to non-responding tumours. These preliminary results demonstrated the potential of the Nakagami imaging-based volumetric tissue assessment technique to detect early response of liver tumour to chemotherapy. Further work is recommended prior to translation into clinical practice
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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