Dissertations / Theses on the topic 'Pre-clinical imaging'
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1
Bianchi, Andrea. "Magnetic resonance imaging techniques for pre-clinical lung imaging." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0060/document.
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Dans ce travail, les s´séquences Imagerie par Résonance Magnétique (IRM) radiales à temps d’écho ultra-court (UTE) sont analysées pour évaluer leur potentiel dans l’étude non-invasive de différents modèles expérimentaux de maladies pulmonaires chez la souris. Chez le petit animal, les séquences radiales UTE peuvent efficacement limiter l’impact négatif sur la qualité de l’image dû au déphasage rapide des spins causé par les nombreuses interfaces air/tissu. En plus, les séquences radiales UTE sont moins sensibles aux artefacts de mouvement par rapport aux séquences Cartésiennes classiques. En conséquence, chez le petit animal, les séquences radiales UTE peuvent permettre d’obtenir des images du poumon avec une résolution bien inférieure au millimètre avec des rapports signal/bruit importants dans le parenchyme pulmonaire, tout en travaillant en conditions physiologiques (animaux en respiration spontanée). Dans cette thèse, il sera démontré que les séquences d’IRM protonique UTE sont outils efficaces dans l’étude quantitative et non-invasive de différents marqueurs distinctifs de certaines pathologies pulmonaires d’intérêt général. Les protocoles développés serontsimples, rapides et non-invasifs, faciles à implémenter, avec une interférence minimale sur la pathologie pulmonaire étudiée et, en définitive, potentiellement applicables chez l’homme. Il sera ainsi démontré que l’emploi des agents de contraste, administrés via les voies aériennes, permet d’augmenter la sensibilité des protocoles développés. Parallèlement, dans cette thèse des protocoles suffisamment flexibles seront implémentés afin de permettre l’étude d’un agent de contraste paramagnétique générique pour des applications aux poumonsIn this work, ultra-short echo time (UTE) Magnetic Resonance Imaging (MRI) sequences are investigated as flexible tools for the noninvasive study of experimental models of lung diseases in mice. In small animals radial UTE sequences can indeed efficiently limit the negative impact on lung image quality due to the fast spin dephasing caused by the multiple air/tissue interfaces. In addition, radial UTE sequences are less sensitive to motion artifacts compared to standard Cartesian acquisitions. As a result, radial UTE acquisitions can provide lung images in small animals at sub-millimetric resolution with significant signal to noise ratio in the lung parenchyma, while working with physiological conditions (freely-breathing animals). In this thesis, UTE proton MRI sequences were shown to be efficient instruments to quantitatively investigate a number of hallmarks in longitudinal models of relevant lung diseases with minimal interference with the lung pathophysiology, employing easilyimplementable fast protocols. The synergic use of positive contrast agents, along with anadvantageous administration modality, was shown to be a valuable help in the increase of sensitivity of UTE MRI. At the same time, UTE MRI was shown to be an extremely useful and efficacious sequence for studying positive contrast agents in lungs
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Almeida, Gilberto Serrano de. "Pre-clinical imaging evaluation of the PARP inhibitor rucaparib." Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/2033.
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Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA-binding enzyme involved in DNA repair by the base-excision pathway. The inhibition of PARP1 is being investigated as a cancer treatment. Rucaparib (CO338) is a potent PARP 31 inhibitor currently in Phase II clinical development. In this thesis P in vivo MR Spectroscopy (MRS) and Dynamic Contrast Enhanced (DCE) MRI were used to study acute effects of rucaparib on energy metabolism and tumour vasculature. 1 31 18 18 Ex vivo H and P-MRS, and in vivo [ F]FLT and [ F]FDG-PET, were used to study effects of treatment with rucaparib on tumour metabolism and proliferation. A2780 and SW620 tumours implanted in mice were scanned in a horizontal Varian 7T MR system. Two i.v. injections of the MRI contrast agent gadoteridol were given 90 minutes apart with dynamic phosphorus MRS acquired following the injection of rucaparib, temozolomide or both drugs in combination. The 18 18 same tumours were evaluated by [ F]FLT- and [ F]FDG-PET after 5 daily treatments with rucaparib, temozolomide or the combination, and the livers of PARP1 knock out (KO) and wild type (WT) mice treated in a similar manner 1 31 were analysed by ex vivo H and P-MRS. Tumour uptake of gadoteridol changed significantly after treatment with hydralazine and higher doses of rucaparib in SW620 tumours, and following 31 hydralazine and 1mg/Kg of rucaparib in A2780 tumours. P-MRS studies revealed an increase in the inorganic phosphate (Pi) to β-NTP ratio, consistent with impairment of tumour energy metabolism following hydralazine treatment. 18 [ F]FLT-PET demonstrated a significant reduction in the SUV values in the 18 rucaparib/temozolomide combination group in SW620 tumours, and [ F]FDG- PET revealed a non-significant reduction in tumour metabolism in A2780 1 tumours. H ex vivo MRS demonstrated an increase in the liver NAD concentrations after treatment with rucaparib, but a decrease following the treatment with temozolomide, regardless of the PARP1 status. Together, these pre-clinical imaging studies have shown that MR can be used 18 to investigate the acute anti-vascular effects of rucaparib, that [ F]FLT-PET predicted subsequent changes in tumour volume following combined rucaparib 1 and temozolomide treatment, and that ex vivo H-MRS can be used in mechanistic studies of PARP inhibition. Both MRI/MRS and PET are potential pharmacodynamic and surrogate response imaging biomarkers for PARP inhibitors.
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Namati, Eman, and eman@namati com. "Pre-Clinical Multi-Modal Imaging for Assessment of Pulmonary Structure, Function and Pathology." Flinders University. Computer Science, Engineering and Mathematics, 2008. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20081013.044657.
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In this thesis, we describe several imaging techniques specifically designed and developed for the assessment of pulmonary structure, function and pathology. We then describe the application of this technology within appropriate biological systems, including the identification, tracking and assessment of lung tumors in a mouse model of lung cancer.
The design and development of a Large Image Microscope Array (LIMA), an integrated whole organ serial sectioning and imaging system, is described with emphasis on whole lung tissue. This system provides a means for acquiring 3D pathology of fixed whole lung specimens with no infiltrative embedment medium using a purpose-built vibratome and imaging system. This system enables spatial correspondence between histology and non-invasive imaging modalities such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), providing precise correlation of the underlying 'ground truth' pathology back to the in vivo imaging data. The LIMA system is evaluated using fixed lung specimens from sheep and mice, resulting in large, high-quality pathology datasets that are accurately registered to their respective CT and H&E histology.
The implementation of an in vivo micro-CT imaging system in the context of pulmonary imaging is described. Several techniques are initially developed to reduce artifacts commonly associated with commercial micro-CT systems, including geometric gantry calibration, ring artifact reduction and beam hardening correction. A computer controlled Intermittent Iso-pressure Breath Hold (IIBH) ventilation system is then developed for reduction of respiratory motion artifacts in live, breathing mice. A study validating the repeatability of extracting valuable pulmonary metrics using this technique against standard respiratory gating techniques is then presented.
The development of an ex vivo laser scanning confocal microscopy (LSCM) and an in vivo catheter based confocal microscopy (CBCM) pulmonary imaging technique is described. Direct high-resolution imaging of sub-pleural alveoli is presented and an alveolar mechanic study is undertaken. Through direct quantitative assessment of alveoli during inflation and deflation, recruitment and de-recruitment of alveoli is quantitatively measured. Based on the empirical data obtained in this study, a new theory on alveolar mechanics is proposed.
Finally, a longitudinal mouse lung cancer study utilizing the imaging techniques described and developed throughout this thesis is presented. Lung tumors are identified, tracked and analyzed over a 6-month period using a combination of micro-CT, micro-PET, micro-MRI, LSCM, CBCM, LIMA and H&E histology imaging. The growth rate of individual tumors is measured using the micro-CT data and traced back to the histology using the LIMA system. A significant difference in tumor growth rates within mice is observed, including slow growing, regressive, disappearing and aggressive tumors, while no difference between the phenotype of tumors was found from the H&E histology. Micro-PET and micro-MRI imaging was conducted at the 6-month time point and revealed the limitation of these systems for detection of small lesions ( < 2mm) in this mouse model of lung cancer. The CBCM imaging provided the first high-resolution live pathology of this mouse model of lung cancer and revealed distinct differences between normal, suspicious and tumor regions. In addition, a difference was found between control A/J mice parenchyma and Urethane A/J mice normal parenchyma, suggesting a 'field effect' as a result of the Urethane administration and/or tumor burden. In conclusion, a comprehensive murine lung cancer imaging study was undertaken, and new information regarding the progression of tumors over time has been revealed.
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Assadian, Sarah. "Rodent FDG-PET imaging for the pre-clinical assessment of novel glioma therapies." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101836.
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The rapid discovery of novel therapeutic agents, targeting the specific mechanism of cancer progression, invasion and angiogenesis, necessitates the development and validation of efficient techniques to assess the therapeutic efficacy of these drugs in vivo. Recently the development of dedicated PET scanners for the imaging of small animals, such as the microPET system (CTI Concorde R4), has allowed for the high-resolution functional and molecular imaging of murine and rodent models of disease. This study, investigates the ability of microPET imaging, using the 18F labelled 2-fluoro-2-deoxyglucose (FDG) PET tracer, to detect the therapeutic efficacy of novel targeted therapies in a rat model of glioma. This technique potentially allows for the rapid and high-throughput assessment of tumour response and evaluation of efficacy of such therapeutic agents in vivo at the pre-clinical stage and will, consequently, facilitate the translation of these novel drugs from the discovery to the clinical phases.La découverte accélérée de nouvelles molécules thérapeutiques qui ciblent lesmécanismes de progression du cancer tels que l'invasion et l'angiogenèse, nécessite lamise au point et la validation de techniques efficaces qui permettent d'évaluer l'efficacitéthérapeutique de ces agents in vivo. Le développement récent des scanners detomographie à émission de positron (TEP) dédiés à l'imagerie de petits animaux(microPET, CT! Concorde R4), permet aujourd'hui d'obtenir une image fonctionnelle etmoléculaire de haute résolution des modèles rongeurs. Cette étude s'intéresse au potentieldu 18F-2-fluoro-2-deoxyglucose (FDG) en utilisant l'imagerie microPET dansl'évaluation de l'efficacité de nouveaux agents thérapeutiques dans un modèle de gliomechez le. rat. Cette technique pourrait éventuellement mener à une évaluation rapide et àgrande échelle de la réponse tumorale, ainsi que la mesure de l'efficacité d'agentsthérapeutiques in vivo au stade d'étude préclinique. Globalement, cette étude a pour butde faciliter la transition entre la découverte de nouvelles molécules thérapeutiques et leursapplications cliniques.
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Ambrosini, Valentina <1975>. "Pre-clinical imaging: small animal pet and CT applications in pneumology, oncology and cardiology." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2008. http://amsdottorato.unibo.it/1087/.
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Chen, Liu Qi. "Development and Application of AcidoCEST MRI for Evaluating Tumor Acidosis in Pre-Clinical Cancer Models." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/323450.
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Tumor acidosis is an important biomarker in cancer. We have developed a noninvasive imaging method, termed acidosis Chemical Exchange Saturation Transfer (acidoCEST) MRI to measure extracellular pH (pHe) in the tumor microenvironment. Chapter 1 introduces the importance of measuring tumor acidosis and presents various imaging modalities and their shortcoming to measure pHe. Chapter 2 describes the optimization of acidoCEST MRI for in vivo pHe measurement. The acidoCEST MRI protocol consists of a CEST-FISP acquisition and Lorentzian line shape fittings. We determined the optimal saturation time, saturation power and bandwidth, 5 sec, 2.8 µT and 90 Hz respectively. We also tried various routes of administration to increase contrast agent uptake in the tumor. We decided upon 200 µL bolus followed by 150 µL/hr infusion. The optimized acidoCEST MRI protocol was tested on a mammary carcinoma mouse model of MDA- MB-231. Our method can detect an increase in pHe in the bladder and tumor of the mice treated with bicarbonate. We used this optimized acidoCEST MRI method to measure pHe in lymphoma tumor model of Raji, Ramos and Granta 519 as described in Chapter 3. Pixel-wise pHe maps showed tumor heterogeneity. The pHe of Raji, Ramos and Granta 519 were determined to be mildly acidic with no significant difference. Chapter 4 describes the evolution of pixel-wise analysis in more detail. Besides the pHe map and spatial heterogeneity, we were able to determine the % contrast agent uptake. We monitored these biomarkers in two different mammary carcinoma mouse models, MDA- MB-231 and MCF-7 longitudinally and made comparisons between the different tumor models: MCF-7 were more acidic, more heterogeneous and faster growing than MDA- MB-231.
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Jones, Bernard Lee. "Development of dosimetry and imaging techniques for pre-clinical studies of gold nanoparticle-aided radiation therapy." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/43727.
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Cancer is one of the leading causes of death worldwide, and affects roughly 1.5 million new people in the United States every year. One of the leading tools in the detection and treatment of cancer is radiation. Tumors can be detected and identified using CT or PET scans, and can then be treated with external beam radiotherapy or brachytherapy. By taking advantage of the physical properties of gold and the biological properties of nanoparticles, gold nanoparticles (GNPs) can be used to improve both cancer radiotherapy and imaging. By infusing a tumor with GNPs, either using passive extravasation of nanoparticles by the tumor vasculature or active targeting of an antibody-conjugated nanoparticle to a specific tumor marker, the higher photon cross-section of gold will cause more radiation dose to be deposited in the tumor during photon-based radiotherapy. In principle, this would allow escalation of dose to the tumor while not increasing the dose to normal healthy tissue. Additionally, if a tumor infused with GNPs was irradiated by an external kilo-voltage source, the fluorescence emitted by the gold atoms would allow one to localize and quantify the GNP concentration. This work has two main aims: to quantify the GNP-mediated dose enhancement during GNRT on a nanometer scale, and to develop a refined imaging modality capable of quantifying GNP location and concentration within a small-animal-sized object. In order to quantify the GNP-mediated dose enhancement on a nanometer scale, a computational model was developed. This model combines both large-scale and small-scale calculations in order to accurately determine the heterogeneous dose distribution of GNPs. The secondary electron spectra were calculated using condensed history Monte Carlo, which is able to accurately take into account changes in beam quality throughout the tumor and calculate the average energy spectrum of the secondary charged particles created. Then, the dose distributions of these electron spectra were calculated on a nanometer scale using event-by-event Monte Carlo. The second aim is to develop an imaging system capable of reconstructing a tomographic image of GNP location and concentration in a small animal-sized object by capturing gold fluorescence photons emitted during irradiation of the object by an external beam. This would not only allow for localization of GNPs during gold nanoparticle-aided radiation therapy (GNRT), but also facilitate the use of GNPs as imaging agents for drug-delivery or other similar studies. The purpose of this study is to develop a cone-beam implementation of XFCT that meets realistic constrains on image resolution, detection limit, scan time, and dose. A Monte Carlo model of this imaging geometry was developed and used to test the methods of data acquisition and image reconstruction. The results of this study were then used to drive the production of a functioning benchtop, polychromatic cone-beam XFCT system.
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Landuyt, Willy. "Intra-tumoural blood vessels and hypoxia: targets for treatment and imaging to improve anti-cancer therapies pre-clinical investigations /." [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 2002. http://arno.unimaas.nl/show.cgi?fid=7247.
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Onthank, David C. "Prediction of "First Dose in Human" for radiopharmaceuticals/imaging agents based on allometric scaling of pharmacokinetics in pre-clinical animal models." Link to electronic dissertation, 2005. http://www.wpi.edu/Pubs/ETD/Available/etd-011006-132234/.
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Adcock, Jane Elizabeth St Vincent's Clinical School UNSW. "The reliability and clinical validity of functional magnetic resonance imaging in the assessment of language in pre-surgical patients with temporal lobe epilepsy." Awarded by:University of New South Wales. St Vincent's Clinical School, 2005. http://handle.unsw.edu.au/1959.4/22484.
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Defining language lateralisation is important to minimise morbidity in patients treated surgically for temporal lobe epilepsy (TLE). Functional magnetic resonance imaging (fMRI) offers a promising, non-invasive, alternative strategy to the Wada test. Here, fMRI has been used to study healthy controls and patients with TLE in order (i) to define language-related activation patterns and their reproducibility; (ii) to compare lateralisation determined by fMRI with that from the Wada test; and (iii) to explore the usefulness of multiple fMRI language paradigms. 18 healthy controls (12 right-handed and 6 left-handed) and 24 pre-operative TLE patients (19 right-handed: 12 left-TLE, 7 right-TLE; 5 left-handed: 2 right-TLE, 3 left-TLE) were studied using fMRI. Four fMRI language paradigms used: phonetic and semantic fluency, and the naming of living and non-living things. The data for all 4 tasks were acquired during a single scanning session on two occasions. All patients also underwent Wada testing. In patients and controls, phonetic and semantic fluency tasks were robustly activating and strongly lateralising. Quantified language-related lateralisation from fMRI verbal fluency data was highly reproducible and concordant with the lateralisation of the Wada test. Both fluency tasks identified patients with atypical language lateralisation, including 4/12 right-handed patients with left-TLE and 4/5 left-handed TLE patients, regardless of the side of epileptic focus. In comparison, the two confrontational naming tasks were not strongly lateralising and did not reliably agree with Wada lateralisation in either 12 right-handed controls or 19 right-handed patients with TLE. However, there was a difference in the pattern of fMRI activation in right-handed pat ients with left-TLE. Left-TLE patients had a more right lateralised network of activation when naming living things relative to non-living things, suggesting that some patients may be at risk of a category specific naming decline for non-living things after left anterior temporal lobectomy. These results demonstrate that non-invasive fMRI measures of languagerelated lateralisation may provide a practical and reliable alternative to invasive testing for pre-surgical language lateralisation in patients with TLE. The high proportion of TLE patients showing atypical language lateralisation suggests considerable plasticity of language representation in the brains of patients with intractable TLE.
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Onthank, David C. "Prediction of "First Dose in Human" for Radiopharmaceuticals/Imaging Agents Based on Allometric Scaling of Pharmacokinetics in Pre-Clinical Animal Models." Digital WPI, 2006. https://digitalcommons.wpi.edu/etd-dissertations/443.
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It is an FDA requirement that the“first in human" dose be based on pre-clinical animal model efficacy and safety testing to ensure a safe entry into Phase I clinical trials. Pre-clinical safety and efficacy models range from mouse to non-human primates. Interspecies scaling of pharmacokinetic parameters is therefore important for predicting drug doses in human clinical trials, although it continues to be less than optimal. Understanding the disposition of the compound in different species through in vitro and in vivo experiments is necessary to ensure appropriate species are selected for human estimates. Data for three imaging agents and a pharmacological stress agent (Oncology tumor agent (DPC-A80351), Thrombus agent (DMP-444), Infection agent (RP-517) Pharmacological stress agent (DPC-A78445-00)) that entered clinical trials and an imaging agent being developed (RP845), were assessed for scaling accuracy. Initially, pharmacokinetic data from animal models were used to extrapolate to human though body weight allometric scaling. Subsequently, the impact of adjusting for plasma protein binding and the impact of metabolic stability in the different models were examined. Allometric scaling of animal pharmacokinetic parameters (clearance (CL), half-life (t½) and volume of distribution (Vdss)) achieved a prediction of the human pharmacokinetic parameter within 13 to 109% of the observed values. This prediction was further improved by adjusting for plasma protein binding of the drug, and achieved an estimate within 5 to 57% of the clinically observed values. Since the parent compound was the dominant species (>95%) in the circulation, metabolic stability was not used as a correction factor. Weight based allometric scaling was further examined for an atherosclerotic plaque targeted radiopharmaceutical imaging agent, RP845-Tc-99m, currently in development. Pharmacokinetic parameters were determined in mouse, rat and rabbit followed by allometric scaling to predict the non-human primate values. Differences between predicted versus observed non-human primate Cl, t½ and Vdss were 40%, 52% and 8%, respectively. Correcting for plasma protein binding improved the prediction for Cl and t½ to within 12 and 3 %, respectively. The Vdss prediction, however became less accurate (38% difference). Since blood clearance is the major parameter in predicting human dose, the improvement from 40% to 12% was important. The plasma protein binding adjusted animal data was then used with allometric scaling to predict human CL, t½ and Vdss. The predicted values were 7.6 mL/min/kg, 70.6 minutes and 0.87 L/kg respectively. Based on the predicted human blood clearance and the dose required to image atherosclerosis in a rabbit model, the estimated human dose would be unacceptably high. This demonstrates how allometric scaling can be used in research projects to assess clinical feasibility. The impact of metabolism differences influencing the reliability of various species to predict for man was highlighted by DPC-A78445-00. DPC-A78445-00 is being developed as an alternative to exercise in myocardial perfusion imaging for the evaluation of coronary artery disease. DPC-A78445-00 was rapidly metabolized to the carboxylic acid by mouse and rat blood in vitro and in vivo, however longer stability was observed in the dog. In vitro human blood data was consistent with the dog, suggesting that mouse and rat would not be representative species. DPC-A78445-00 plasma protein binding was at a similar, moderate level in rat, dog and human plasma and metabolism by hepatocytes was similar in dog and human. Phase I human clinical trial testing determined the area under the blood concentration-time curve (AUC) and clearance predicted by the dog were within 32% of the human values. Overall, body weight based allometric scaling of pharmacokinetic parameters from animal models, when corrected for plasma protein binding, yielded reliable predictions of the human pharmacokinetics (within 50%) for radiopharmaceutical imaging agent. However, although predictive scaling from animal data can give insight into feasibility of compounds working in human, it is important to identify species differences with respect to metabolic stability. This allometric scaling method provides an additional tool to better predict doses in human for novel Medical Imaging agents.
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Thornton, R. C. "Imaging brain networks in focal epilepsy : a prospective study of the clinical application of simultaneous EEG-fMRI in pre-surgical evaluation." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1425726/.
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Epilepsy is a common disorder with significant associated morbidity and mortality. Despite advances in treatment, there remain a minority of people with pharmacoresistant focal epilepsy for whom surgery may be beneficial. It has been suggested that not enough people are offered surgical treatment, partly owing to the fact that current non-invasive techniques do not always adequately identify the seizure onset zone so that invasive EEG is required. EEG-fMRI is an imaging technique, developed in the 1990s (Ives, Warach et al. 1993) which identifies regions of interictal epileptiform discharge associated haemodynamic changes, that are concordant with the seizure onset zone in some patients (Salek-Haddadi, Diehl et al. 2006). To date there has been no large scale prospective comparison with icEEG and postoperative outcome. This thesis presents a series of experiments, carried out in a cohort of patients scanned using EEG-fMRI as part of a multi-centre programme, designed to investigate the relationship between EEG-fMRI and intracranial EEG and to assess its potential role in pre-surgical evaluation of patients with focal epilepsy. The results suggested that positive, localised IED-related BOLD signal changes were sensitive for the seizure onset zone, as determined on icEEG, both in patients neocortical epilepsies, but were not predictive of outcome. Widespread regions of positive IEDrelated BOLD signal change were associated with widespread or multifocal abnormalities on icEEG and poor outcome. Patterns of haemodynamic change, identified using both data driven and EEG derived modeling approaches, correspond to regions of seizure onset on icEEG, but improvements for modeling seizures are required. A study of a single seizure in a patient who underwent simultaneous icEEGfMRI, showed similar findings. An exploratory investigation of fMRI-DCM in EEG-fMRI, suggested it can provide information about seizure propagation and this opens new avenues for the non-invasive study of the epileptic network and interactions with function.
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Aginsky, Kerith Dana. "Clinical and imaging features of the lumbar spine in elite male schoolboy cricketers : the effect of a pre-season lumbar stabilisation intervention." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3222.
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Includes abstract.Includes bibliographical references (p. 221-240).
Current evidence indicates that schoolboy cricketers are at a high risk of injury to the lumbar spine. This is particularly relevant in the case of fast bowlers who bowl with a high degree of shoulder counter-rotation. There, however, is a lack of evidence in the literature with respect to injury research of all cricketing disciplines, as fast bowlers receive the most attention. After reviewing the literature it was evident that the effect of a cricket-specific lumbar stabilisation exercise intervention in an attempt to reduce lower back pain and alter other physiological variables, had never been studied. Previous interventions in cricketers have focused only on fast bowlers in an attempt to decrease the degree of shoulder counter-rotation. However, these studies either took two years to observe a decrease or were unsuccessful.
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Schädlich, Andreas Verfasser], Karsten [Akademischer Betreuer] [Mäder, Achim [Akademischer Betreuer] Göpferich, and Jörg [Akademischer Betreuer] Kreßler. "Pre‐clinical in vivo studies of parenteral drug delivery systems using non‐invasive multispectral fluorescence imaging : [kumulative Dissertation] / Andreas Schädlich. Betreuer: Karsten Mäder ; Achim Göpferich ; Jörg Kreßler." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2013. http://d-nb.info/1045194824/34.
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Maczka, Melissa May. "Investigations into the effects of neuromodulations on the BOLD-fMRI signal." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:96d46d4d-480b-48d7-9f2d-060e76c5f8aa.
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The blood oxygen level dependent functional MRI (BOLD-fMRI) signal is an indirect measure of the neuronal activity that most BOLD studies are interested in. This thesis uses generative embedding algorithms to investigate some of the challenges and opportunities that this presents for BOLD imaging. It is standard practice to analyse BOLD signals using general linear models (GLMs) that assume fixed neurovascular coupling. However, this assumption may cause false positive or negative neural activations to be detected if the biological manifestations of brain diseases, disorders and pharmaceutical drugs (termed "neuromodulations") alter this coupling. Generative embedding can help overcome this problem by identifying when a neuromodulation confounds the standard GLM. When applied to anaesthetic neuromodulations found in preclinical imaging data, Fentanyl has the smallest confounding effect and Pentobarbital has the largest, causing extremely significant neural activations to go undetected. Half of the anaesthetics tested caused overestimation of the neuronal activity but the other half caused underestimation. The variability in biological action between anaesthetic modulations in identical brain regions of genetically similar animals highlights the complexity required to comprehensively account for factors confounding neurovascular coupling in GLMs generally. Generative embedding has the potential to augment established algorithms used to compensate for these variations in GLMs without complicating the standard (ANOVA) way of reporting BOLD results. Neuromodulation of neurovascular coupling can also present opportunities, such as improved diagnosis, monitoring and understanding of brain diseases accompanied by neurovascular uncoupling. Information theory is used to show that the discriminabilities of neurodegenerative-diseased and healthy generative posterior parameter spaces make generative embedding a viable tool for these commercial applications, boasting sensitivity to neurovascular coupling nonlinearities and biological interpretability. The value of hybrid neuroimaging systems over separate neuroimaging technologies is found to be greatest for early-stage neurodegenerative disease.
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Castets, Charles. "Développements méthodologiques en IRM pré-clinique chez le petit animal : apports de l’acquisition spirale pour l’imagerie paramétrique et fonctionnelle." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0307/document.
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L’IRM est de plus en plus utilisée pour diagnostiquer et évaluer un très grand nombre de pathologies. Cette technique présente cependant deux inconvénients majeurs. En effet, les examens restent encore très longs (notamment en imagerie 3D) et la quantification est très difficile par rapport à d’autres modalités comme la tomographie par émission de positons. L’objectif de ce travail de thèse a été de diminuer significativement les temps d’acquisition nécessaires pour l’imagerie volumique et de développer des techniques quantitatives robustes, permettant d’effectuer des suivis longitudinaux.Pour cela, des méthodes innovantes ont été développées à très haut champ magnétique (7T) et validées sur des modèles murins sains et pathologiques. Trois développements majeurs sont ressortis de cette thèse. Tout d’abord, une mesure rapide des temps de relaxation longitudinale (T1) a été développée.Cette méthode basée sur une approche Look-Locker a été couplée avec un échantillonnage en empilement de spirales et a permis d’obtenir au niveau cardiaque des cartes T1 en 3D sur des souris saines et des modèles d’infarctus du myocarde en moins de 15 minutes. Ensuite, une approche dite« spiral-in » a été couplée avec une méthode de multi-échos de spin afin d’accélérer la mesure des temps de relaxation transversale (T2). Cette méthode a permis d’obtenir des cartes T2 en 3D sur des cerveaux de souris saines et métastatiques en moins de 20 minutes. Enfin, une approche hybride couplant les avantages de l’acquisition spiralée et ceux de l’échantillonnage radial a été développée.Cette méthode a été couplée avec une technique de Golden-Angle pour échantillonner aléatoirement l’espace de Fourier et a permis pour la première fois de visualiser une angiographie 3D d’un foie de souris en respiration libre en moins de 12 minutes. Toutes les méthodes développées dans ce travail ont été validées au niveau de leur robustesse et démontrent que l’IRM peut être une technique à la fois rapide et quantitative. Ces développements pourront être transférés vers la clinique dans de futurs travauxMRI is more and more used to diagnose and assess a wide range of pathologies. However, this technique is still limited by two disadvantages. Indeed, the acquisition times are too long(especially in 3D) and the quantification is still difficult compared to other techniques like positron emission tomography. The aim of this PhD project was to significantly reduce acquisition times required for 3D imaging and to develop robust quantitative techniques allowing longitudinal studies.To these ends, innovative methods have been developed at very high magnetic field (7T) and validated on healthy and diseased mouse models. Three major developments arose from this work. Firstly, a fast measurement of the longitudinal relaxation time (T1) has been developed. This method based on a Look-Locker approach was coupled with a sampling using stack-of-spirals and allowed to get T1 mapsin 3D in healthy and myocardial infarction models in less than 15 minutes. Then, a "spiral-in" approach was coupled with a multi spin echoes acquisition to accelerate the measurement of the transverse relaxation time (T2). This method allowed to get T2 maps in 3D of healthy and metastatic mouse brains in less than 20 minutes. Finally, a hybrid approach combining the advantages of the spiral acquisition with those of the radial sampling has been developed. This method has been coupled with a Golden-Angle technique for randomly sampling the k-space and allowed for the first time to display a 3Dangiography of a mouse liver in free breathing in less than 12 minutes. All the protocols developed inthis PhD project were validated in terms of robustness and showed that MRI can be a technique both rapid and quantitative. These developments will be transferred to the clinic in future works
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Audigier, Chloé. "Modélisation de l’ablation radiofréquence pour la planification de la résection de tumeurs abdominales." Thesis, Nice, 2015. http://www.theses.fr/2015NICE4071/document.
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L'ablation par radiofréquence (ARF) de tumeurs abdominales est rendue difficile par l’influence des vaisseaux sanguins et les variations de la conductivité thermique, compliquant la planification spécifique à un patient donné. En fournissant des outils prédictifs, les modèles biophysiques pourraient aider les cliniciens à planifier et guider efficacement la procédure. Nous introduisons un modèle mathématique détaillé des mécanismes impliqués dans l’ARF des tumeurs du foie comme la diffusion de la chaleur et la nécrose cellulaire. Il simule l’étendue de l’ablation à partir d’images médicales, d’après lesquelles des modèles personnalisés du foie, des vaisseaux visibles et des tumeurs sont segmentés. Dans cette thèse, une nouvelle approche pour résoudre ces équations basée sur la méthode de Lattice Boltzmann est introduite. Le modèle est d’abord évalué sur des données de patients qui ont subi une ARF de tumeurs du foie. Ensuite, un protocole expérimental combinant des images multi-modales, anatomiques et fonctionnelles pré- et post-opératoires, ainsi que le suivi de la température et de la puissance délivrée pendant l'intervention est présenté. Il permet une validation totale du modèle qui considère des données les plus complètes possibles. Enfin, nous estimons automatiquement des paramètres personnalisés pour mieux prédire l'étendu de l’ablation. Cette stratégie a été validée sur 7 ablations dans 3 cas cliniques. A partir de l'étude préclinique, la personnalisation est améliorée en comparant les simulations avec les mesures faites durant la procédure. Ces contributions ont abouti à des résultats prometteurs, et ouvrent de nouvelles perspectives pour planifier et guider l’ARFThe outcome of radiofrequency ablation (RFA) of abdominal tumors is challenged by the presence of blood vessels and time-varying thermal conductivity, which make patient-specific planning extremely difficult. By providing predictive tools, biophysical models may help clinicians to plan and guide the procedure for an effective treatment. We introduce a detailed computational model of the biophysical mechanisms involved in RFA of hepatic tumors such as heat diffusion and cellular necrosis. It simulates the extent of ablated tissue based on medical images, from which patient-specific models of the liver, visible vessels and tumors are segmented. In this thesis, a new approach for solving these partial differential equations based on the Lattice Boltzmann Method is introduced. The model is first evaluated against clinical data of patients who underwent RFA of liver tumors. Then, a comprehensive pre-clinical experiment that combines multi-modal, pre- and post-operative anatomical and functional images, as well as the interventional monitoring of the temperature and delivered power is presented. This enables an end-to-end validation framework that considers the most comprehensive data set for model validation. Then, we automatically estimate patient-specific parameters to better predict the ablated tissue. This personalization strategy has been validated on 7 ablations from 3 clinical cases. From the pre-clinical study, we can go further in the personalization by comparing the simulated temperature and delivered power with the actual measurements during the procedure. These contributions have led to promising results, and open new perspectives in RFA guidance and planning
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Teixeira, Joana Maria Rodrigues. "Automation of co-registration of pre-clinical RPC-PET images with animal MRI." Master's thesis, 2019. http://hdl.handle.net/10316/87898.
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Dissertação de Mestrado Integrado em Engenharia Física apresentada à Faculdade de Ciências e TecnologiaA imagiologia médica é um dos recursos mais utilizados na medicina, sendo as suas principais aplicações no diagnóstico e terapêutica. Imagens obtidas através da fusão de duas modalidades de imagiologia médica apresentam vantagens consideráveis quando comparadas com images provenientes de uma só técnica de imagem, uma vez que combinam informação anatómica com informação funcional.Enquanto a Tomografia por Emissão de Positrões (PET) fornece informações específicas acerca do metabolismo, estudos de Imagiologia por Ressonância Magnética incluem formas anatómicas com elevado contraste, destacando-se o seu desempenho na distinção de tecidos moles. Desta forma, a combinação das duas técnicas fornece parâmetros funcionais combinados com informação espacial adicional. Neste projecto, pretendemos desenvolver uma interface gráfica para a automatização do co-registo de imagens obtidas em estudos de RPC-PET pré-clínico com images de MR animal de forma eficiente. A análise dos pacotes de software disponíveis para este propósito foi feita tendo em conta a amplitude de funcionalidades, a extensibilidade, a portabilidade entre plataformas, o tipo de licença e a possibilidade de aplicação em meio clínico. A plataforma de desenvolvimento do Interactive Data Language (IDL) destacou-se sobre os seus pares cumprindo todos pos requisitos necessários para o desenvolvimento deste projecto. O desenvolvimento do algoritmo de co-registro teve por base o método de medição de pontos de referência, usando a intensidade e a posição dos centroides dos cinco marcadores fiduciais colocados na cama usada em ambos os equipamentos de aquisição de imagem. A matriz da transformação de registo é determinada pela minimização da métrica de semelhança através de um processo de optimização, e aplicada ao volume de RCP-PET. Uma interface gráfica interactiva permite a visualização e manipulação dos volumes co-registados. O algoritmo de fusão foi aplicado a diferentes casos clínicos de imagiologia animal, adquiridos com e sem ratinhos marcados com diferentes radionuclídeos. O desemplenho do programa foi validado qualitativa e quantitativamente, tendo-se obtido um valor médio de TRE (Erro de registo relativamente ao volume alvo) de 1.906 mm. A avaliação das volumes resultantes do processo indica como principal fonte de erro o método de identificação do limiar de intensidade. Por último, foram feitas algumas considerações relativas a potencias melhorias do método desenvolvido.
Medical imaging is one of the most common resources in medicine, where the main applications are within disease diagnosis and monitoring of treatment. Images obtained resorting to two different procedures of medical imaging show considerable advantages when compared with single methods, as both anatomical and functional information are provided with more accuracy. While positron emission tomography (PET) provides a specific metabolic signal, magnetic resonance imaging (MRI) includes anatomical information with superior soft-tissue contrast: the combination of the two methods provides functional parameters and additional spatial information. In this work, we aim at developing a graphical interface for automating the co-registration of images obtained through a pre-clinical RPC-PET system and its image fusion with an animal magnetic resonance system efficiently. Software comparisons were performed considering the breadth of functionality, extensibility, cross-platform portability, and non-restrictive software license, as well as future applicability in clinical settings. It was considered that the Interactive Data Language (IDL) software development package is the one that best fits the current project. The co-registration algorithm is based on the landmarks measurements method grounded on the pixel intensity and the location of the centroids of the five artificial fiducial markers placed on the examination bed used on the two acquisition equipment. The registration transformation is determined by the minimization of the feature-based metrics. After this optimization process, the source image (RCP-PET) is transformed and interpolated. The merged volumes are displayed in a GUI that allows basic volume manipulation steps. The performance of the co-registration was evaluated by testing the algorithm in different datasets acquired with and without small animals (mice) labeled with several radionuclides. The registration results were qualitative and quantitative validated and for the 19 studies successfully merged the mean value for TRE (Target Registration Error) was 1.906 mm. The results obtained suggest that the major error source is related to the fiducial markers and the routine for threshold identification. Finally, considerations on potential improvements to the method are made.
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Baydack, Richard Stephen. "Pre-clinical changes during scrapie disease progression in hamsters, detected by Magnetic Resonance Imaging." 2009. http://hdl.handle.net/1993/3131.
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Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a group of invariably fatal neurodegenerative diseases of both humans and animals, thought to be caused by the abnormally folded prion protein PrPSc. Prion disease research continues to be faced by a number of difficult challenges. First, the unequivocal diagnosis of most prion diseases currently requires the post-mortem collection of central nervous system tissue, either for histological examination or Western blot analysis; second, a viable treatment for clinical stage disease has not yet been identified; third, the exact details of disease pathogenesis have not been elucidated; and fourth, the normal function of PrPC is not definitively known.
The primary objective of the studies presented here was to diagnose prion disease in live animals, using Magnetic Resonance Imaging (MRI). Increases in T2 relaxation time and apparent diffusion coefficient (ADC) were observed very early following the infection of Syrian golden hamsters with the 263K strain of scrapie. These changes were evident well before the appearance of either clinical symptoms or the typical histological changes characteristic of prion disease, suggesting that they are the result of the progressive accumulation of fluid, and that this may constitute a novel early marker of prion disease pathogenesis. Following the establishment of this model system, a secondary objective was composed: to test the viability of a potential treatment (pentosan polysulphate) using a number of different treatment regimens. It was determined that pentosan polysulphate (PPS) was ineffective as a treatment unless it was administered intra-cerebrally very early in infection, although it was shown to slow the appearance of the histological hallmarks of prion disease. In response to the results of these studies, a potential model was proposed, relating PrP, aquaporin-4 (AQP4) regulation, and oedema. Although speculative, this model may have implications for both normal PrPC function and disease pathogenesis.February 2009
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Yu, Jyun-gong, and 于峻功. "Complementary coded excitation for Improvement of Doppler Sensitivity in Pre-clinical Ultrasonic Imaging System." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/53872233935062296584.
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碩士國立臺灣科技大學
電機工程系
102
Coded excitation can improve the SNR by utilizing elongated waveform to increase the transmit energy. Besides, the axial resolution can be restored by pulse compressing the received echo. Thus, it can be used to enhance the sensitivity of Doppler flow estimation which it is often compromised by the weak blood flow scattering. Also, it could increase the penetration depth of high frequency ultrasound limitation which is resulted from frequency attenuation. The Golay Complementary Sequence (GCS) has the advantages of low range side lobe and low implementation cost, it is conventionally regarded as not applicable to blood flow detection because of potential motion artifact. In the GCS, the spectral difference of the main-lobe signal and the side-lobe signal is half of the pulse-repetition-frequency (PRF). Based on this property, it can be performed by decoding the received echoes with a low-pass filter whose cut-off frequency is PRF/4 in the slow-time domain to eliminate the motion artifact. Also, the performance of this technique has been verified in previous study. In this research, the PRF/4 filtering has been implemented in a high frequency ultrasound imaging system. The high frequency ultrasound imaging system is widely used in pre-clinical research to provide the flow information. We validate the efficacy of the Doppler flow image quality and SNR using in-vitro and in-vivo experiments. The in-vitro experiment shows that the SNR and the sensitivity could be improved while the different Doppler frequency shifts within ±PRF/4. Furthermore, aliasing occurs when the main-lobe signal is beyond the limit of ±PRF/4. The in-vivo experiment demonstrates that the sensitivity difference of the Right Common Carotid Artery of the mouse is not obvious because the acquisition frames from diastole and systole are not the same. In the kidney vessel, the depth of the flow detection could be increased in the vein of the kidney vessel, but the higher velocity in the artery of the kidney vessel causes aliasing. The abdominal aorta is the deepest vessel in the mouse. Conventionally, the flow estimation is not achievable when the transmit frequency is higher than 30MHz. However, when the transmit signal is GCS, the sensitivity can be as good as the conventional method even with the transmit frequency of 35MHz.
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Wang, Wei-Ting, and 王瑋婷. "Utilization of molecular imaging in monitoringand evaluating pre-clinical effects ofTaiwanofungus camphoratus on cancer treatmentand its potential in cancer reversion." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/63666905562981766822.
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碩士臺北醫學大學
生物醫學材料研究所
95
The fruiting body of Taiwanofungus camphoratus is well known in Taiwan as “niu-chang chih” or “jang-jy”. The objective of this research is to identify the bioactive compounds in Taiwanofungus camphoratus’s ethanol extract from solid-state growen with cancer reversion and anti-tumor activities. This non-invasive molecular imaging is useful in assessing tumor volume in vivo. By treating H441GL cells ( human non-small lungs cancer cells ) and HeLa cells ( human cervical cancer cells ) with ethanol extracts of Taiwanofungus camphoratus for 48 hrs. The ethanol extract was found to possess the highest anti-tumor activities with the IC50 values of 100?慊/ml and 300 ?慊/ml, respectively. Data from flow cytometry analysis indicated that Taiwanofungus camphoratus-mediated antiproliferation effect related to G0/G1 phase arrest on H441 cells. Moreover, this Taiwanofungus camphoratus –induced G0/G1 cell cycle arrest was associated with decrease the expression levels of cyclin A and increase in cyclin D2、cyclinE proteins . Dose-dependent treatment of H441GL cells with Taiwanofungus camphorate resulted in the inhibition of cell migration and commitment to cell necrosis. Taiwanofungus camphoratus induced tumorigenic HeLa cells to revert back to a normal-like phenotypic state (cancer reversion), such as the loss of alkaline phosphatase expression. This reversion was associated with the down- regulation of E7 oncoproteins and subsequent reactivation of p53/pRB gene. In vivo animal tumorigenicity studies were demonstrated that Taiwanofungus camphorates was effective inhibited tumor grow. These results suggest that Taiwanofungus camphorates may be used as a potent agent for cancer therapy.
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(8781065), Daniel R. McIlrath. "A STUDY OF RADIATION-INDUCED PULMONARY FIBROSIS (RIPF) IN MOUSE MODELS USING DIAGNOSTIC IMAGING." Thesis, 2020.
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Radiation-induced lung injury (RILI) is a common condition in the setting of lung and breast cancer. Often, patients who suffer from RILI experience pneumonitis and pulmonary fibrosis months after treatment. These pathologies have commonly been modeled using mice and observing their deterioration until mortality and quantifying pathology on histological sections.
With this study, we used a longitudinal microCT and a 7T MRI to characterize male C57Bl/6 mice irradiated with a single dose of 20 Gy to the whole thoracic area delivered by an X-Rad cabinent irradiator. CT was performed with a respiratory gating sequence at 2 week timepoints to construct an RIPF model. The fraction of RIPF to total lung volume was calculated at each time point from images, and the data was anaylzed using one-way ANOVA Welch and Dunnett’s T3 multiple comparisons tests. Tidal lung volumes were also calculated and anlyazed in a simlar manner. Mice were then imaged using MRI and CT at 0, 5, and 8 week timepoints to compare results. These results were analyzed for comparison (ANOVA and Dunnett’s T3) and correlation (Pearson’s r) with each other. Histology was later performed using H&E and Trichrome stains to provide ex-vivo verification of pathology. At the 10-12 week time point ( ) significant RIPF formed. Weeks proceeding showed increased significance until the 22+ week timepoint, which showed less statistical significance ( ) due to increased variance at this timepoint. Dunnett’s T3 test showed no significant differences between tidal lung volumes over time. Tests also showed no significant differences between CT and MRI results with a correlation coefficient of . Early in the study, problems arose when pre-marture mortality was occurring to a significant portion of our subjects. Analysis later showed issues during irradiation that resulted in significant dose being absorbed by the stomach. Adjusting our shiedling lead to increased early survival of our subjects enabling us to contine our study. Significant RIPF development was not significant until 10-12 weeks post-irradiation, then RIPF became more severe at proceeding timepoints. Tidal lung volume showed no significant deviation over the development of RIPF. This result is most likely affected by the variation of results at later timepoints, since several mice with severe RIPF were significantly hindered in their ability to breathe during the study. MRI results showed close correlation with CT results and prodcued similar values at early timepoints. However, noticeable differences were seen at later timepoints when significant RIPF developed ( ).
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McCormick, Patrick Neil. "Pre-clinical evaluation of [carbon-11]-(+)-PHNO as an agonist positron emission tomography (PET) radiotracer for imaging of the high-affinity state of the dopamine D2 receptor." 2006. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=442230&T=F.
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