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Dissertations / Theses on the topic 'Positron emission tomography'
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1
Andrews, Thomasin Catharine. "Positron emission tomographic [tomography] studies in Huntingdon's disease." Thesis, University of London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271604.
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Strother, S. C. (Steven Charles) 1955. "Quantitation in positron emission tomography." Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=72815.
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Wills, A. J. "Positron emission tomography studies of tremor." Thesis, Queen Mary, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297290.
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Bailey, Dale L. "Quantification in 3D positron emission tomography." Thesis, University of Surrey, 1996. http://epubs.surrey.ac.uk/770395/.
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Acquisition and reconstruction of data in three-dimensional positron emission tomography (3D PET) was introduced in 1990 almost 20 years after the first PET scanners were developed. 3D PET offers a significant sensitivity improvement over conventional, sliceoriented 2D PET, but at the cost of a three-fold increase in acceptance of scattered events. In addition, processing time is increased and new methods for applying corrections such as for photon attenuation, calibration, and detector/geometry normalisation are required. 3D PET raised concerns that the high quantitative accuracy that was possible with 2D PET (with its moderate sensitivity) would not be matched in 3D, primarily because of the greatly increased scattered photon component in the measured data. The aim of this thesis was to develop methods that enable quantitatively accurate measurements with 3D PET. A technique to correct for scattered photons prior to reconstruction has been developed, implemented and assessed. A device for normalising the data for detector efficiency and the geometry of the cylindrical detector system has been developed, and the factors affecting reconstruction investigated. A new approach to calibration of the reconstructed data to produce images of activity concentration which is independent of scatter has been implemented. Finally, the techniques have been applied to data from brain scans of human subjects. Evaluation of images reconstructed from 3D PET demonstrates that the methodology developed in this work produces data accurate to within 10% of the true activity concentration in an object with reasonably homogeneous density. 3D PET is shown to be as accurate as 2D PET, but with a sensitivity advantage that improves signal-to-noise by approximately a factor of three in the human brain and slightly less in other regions of the body.
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Shu, Chengyi Jenny. "Positron emission tomography of immune responses." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1679380111&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Palmer, Matthew Rex. "Noise propagation in quantitative positron emission tomography." Thesis, University of British Columbia, 1985. http://hdl.handle.net/2429/25131.
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Image noise in Positron Emission Tomography (PET) is the result of statistical fluctuation in projection data. The variance properties of images obtained with the UBC/TRIUMF PETT VI tomograph are studied by analytical methods, computer simulations, and phantom experiments. The PETT VI image reconstruction algorithm is described and analyzed for noise propagation properties. Procedures for estimating both point-wise (pixel) and region of interest (ROI) variances are developed: these include the effects of corrections for non-uniform sampling, detector efficiency variation, object self-attenuation and random coincidences.
The analytical expression for image-plane variance is used in computer simulations to isolate the effects of the various data corrections: It is shown that the image precision is degraded due to non-uniform sampling of the projections. The RMS noise is found to be increased by 9% due to the wobble motion employed in PETT VI.
Analytical predictions for both pixel and ROI variances are verified with phantom experiments. The average error between measured and predicted ROI variances due to noise in emission data for a set of seven regions placed on a 20 cm cylindrical phantom is 9.5%. Images showing variance distributions due to noise in emission data and due to noise in transmission data are produced from human subject brain scan data collected by the UBC/TRIUMF PET group. The maximum ratio of image variance due to noise in transmission data to that due to noise in emission data is calculated as 2.6 for a typical FDG study, and 0.082 for a typical fluorodopa study. Total RMS noise varies between 0.4% and 11.6% for a typical set of ROI's placed on mid-brain slices reconstructed from these data sets.
Procedures are suggested for improving the statistical accuracy of quantitative PET measurements.Applied Science, Faculty of
Electrical and Computer Engineering, Department of
Graduate
7
Sayeed, Abdul. "Positron emission tomography analysis of Alzheimer's disease." Thesis, University of Surrey, 2001. http://epubs.surrey.ac.uk/842834/.
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Alzheimer's Disease (AD) is a major concern for the elderly population, currently affecting over 670,000 people in the UK. With the continual increase in the age of the population the problem is expected to rise. There is no known cure to the condition and a definite diagnosis cannot be made in life. Clinical diagnosis is considered to be approximately 80% - 90% accurate, sometimes taking up to a year to assess. Early detection could aid in the care and possible development of better treatments or even a cure. AD has been shown to alter the structure and global texture of the brain. Studies using Magnetic Resonance imaging (MRI) and Computerised Tomography (CT) have been used to detect these changes with some success by some researchers. Positron Emission Tomography (PET) imaging is a functional imaging modality and in theory before structural changes are evident functional changes should be apparent. Therefore we utilise PET images for this study. This thesis will exploit the fact that AD alters the global texture of the brain. Texture features extracted from fluoro-deoxy-glucose (FDG) PET images and sinograms of the brain will be used. Most texture feature extraction methods fail, due to poor signal to noise ratio so we will use a novel texture feature extraction method known as the Trace transform - triple features, which can extract features directly from raw data acquired by PET scanners. Classifiers will be used to aid in the separation of the two groups, namely AD patients and normal controls. The Trace transform - triple feature method has proven its potential as a good feature extraction technique. It enabled us to achieve classification accuracy of up to 93% on raw sinogram data using a combination of five features. This result is very good compared with the clinical accuracy of 80% reported by most researcher. It is comparable to results obtained by Kippenhan et al [52, 53, 51, 50], who used regional metabolic activity using PET and a neural network classifier. Monomial features extracted from images achieved accuracies as high as 87%. These features are good discriminators, however, they suffer from lack of scaling invariance. This is problematic as brain sizes do vary considerably. The use of registration and extraction of regional information failed to produce fruitful results. This is principally due to poor registration. The registration failed primarily because a very small cross section of the brain was available. Also the effect of AD alters the structure of the brain. Since the registration relies on matching structure, it becomes questionable whether one can actually register automatically a very degraded AD brain. Gender and age are crucial to the progress of Alzheimer's disease. Age and gender matching is not sufficient to get the best results. This thesis has shown that performance gains of up to 11% can be attained by simply incorporating age and/or gender into the classification model. However, the maximum classification accuracy was not improved any further.
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Andrée, Bengt. "Positron emission tomography in serotonergic drug development /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4779-1/.
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Spinelli, Antonello Enrico. "Quantitative dynamic imaging using positron emission tomography." Thesis, Institute of Cancer Research (University Of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406697.
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Prevett, Martin Charles. "Positron emission tomography in idiopathic generalised epilepsy." Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296348.
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Dikaios, Nikolaos. "Respiratory motion correction for positron emission tomography." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609967.
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Al-Azmi, Darwish. "Simultaneous positron and single photon emission tomography." Thesis, University of Surrey, 1995. http://epubs.surrey.ac.uk/770250/.
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Emission computed tomography involves external measurements of gamma photons emitted from within the object under investigation in order to map the radioactive distribution into a two-dimensional array within a slice of interest. Both positron emission tomography (PET) and single photon emission computed tomography (SPECT) constitute the two types of emission computed tomography. PET and SPECT differ radically in almost every aspect of system design; radionuc1ide employed, radiation detectors and arrangement, collimation (electronic, mechanical), processing electronics as well as data acquisition, handling and correction. A prototype scanning-rig incorporating two collimated BOO scintillation detectors has been used to carry out PET experiments utilising 6SOe line sources (positron-emitter) and a perspex phantom of 50-mm in diameter to simulate a small animal i.e. a rat's head. Modifications for the experimental scanning-rig allowed the collection of the singles events in the PET studies in such a way that they could be reconstructed to provide SPECT images for the radioactive distribution under investigation. This property allowed a simultaneous collection of PET and SPECT data for the same object under exactly the same conditions. Two data sets are generated from each tomographic experiment; one is for PET and the other is for SPECT. Each data set is corrected separately for the required corrections i.e. scattering and attenuation before reconstruction, and then two images are produced for each study. The outcome from this work is the comparison between the two images of PET and positron SPECT obtained. The line spread function curves taken for various depths and the image profiles for studies in air and perspex show that PET provides better spatial resolution than positron SPECT. This property of PET is further confirmed by the MTF curves and the fidelity test. Using a collimation aperture of 3- mm wide, the spatial resolution values in air were found to be 3.2 +/- 0.45 mm and 7.4 +/- 0.45 mm FWHM for PET and SPECT respectively. The images of the two line sources with a 10-mm centre-to-centre separation are partially resolved in the SPECT images whereas a sufficient separation between the two sources is achieved in PET. Image combination has been applied in order to obtain a hybrid image which contains the advantages from both PET and SPECT. A straightforward averaging and multiplication of the two images of PET and SPECT were found useful to provide images with enhanced quality. The multiplication process provided images with significantly improved quality for the PE T images. When evaluating the image quality of the line source in air, the fidelity test values are 0.71 and -1.11 for PET and SPECT respectively. The image combination resulted in an image with fidelity values of 0.92 when the two images are multiplied and 0.12 when their averaging was obtained.
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Bai, Wenjia. "Respiratory motion correction in positron emission tomography." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:f73b144d-5287-4600-8b82-74229dc0eb31.
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In this thesis, we develop a motion correction method to overcome the degradation of image quality introduced by respiratory motion in positron emission tomography (PET), so that diagnostic performance for lung cancer can be improved. Lung cancer is currently the most common cause of cancer death both in the UK and in the world. PET/CT, which is a combination of PET and CT, providing clinicians with both functional and anatomical information, is routinely used as a non-invasive imaging technique to diagnose and stage lung cancer. However, since a PET scan normally takes 15-30 minutes, respiration is inevitable in data acquisition. As a result, thoracic PET images are substantially degraded by respiratory motion, not only by being blurred, but also by being inaccurately attenuation corrected due to the mismatch between PET and CT. If these challenges are not addressed, the diagnosis of lung cancer may be misled. The main contribution of this thesis is to propose a novel process for respiratory motion correction, in which non-attenuation corrected PET images (PET-NAC) are registered to a reference position for motion correction and then multiplied by a voxel-wise attenuation correction factor (ACF) image for attenuation correction. The ACF image is derived from a CT image which matches the reference position, so that no attenuation correction artefacts would occur. In experiments, the motion corrected PET images show significant improvements over the uncorrected images, which represent the acquisitions typical of current clinical practice. The enhanced image quality means that our method has the potential to improve diagnostic performance for lung cancer. We also develop an automatic lesion detection method based on motion corrected images. A small lung lesion is only 2 or 3 voxels in diameter and of marginal contrast. It could easily be missed by human observers. Our method aims to provide radiologists with a map of potential lesions for decision so that diagnostic efficiency can be improved. It utilises both PET and CT images. The CT image provides a lung mask, to which lesion detection is confined, whereas the PET image provides distribution of glucose metabolism, according to which lung lesions are detected. Experimental results show that respiratory motion correction significantly increases the success of lesion detection, especially for small lesions, and most of the lung lesions can be detected by our method. The method can serve as a useful computer-aided image analysing tool to help radiologists read images and find malignant lung lesions. Finally, we explore the possibility of incorporating temporal information into respiratory motion correction. Conventionally, respiratory gated PET images are individually registered to the reference position. Temporal continuity across the respiratory period is not considered. We propose a spatio-temporal registration algorithm, which models temporally smooth deformation in order to improve the registration performance. However, we discover that the improvement introduced by temporal information is relatively small at the cost of a much longer computation time. Spatial registration with regularisation yields similar results but is superior in speed. Therefore, it is preferable for respiratory motion correction.
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Herbert, Deborah Jane. "Novel detector development for positron emission tomography." Thesis, University of Southampton, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395915.
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Deng, Chuang. "System identification in dynamic positron emission tomography /." View abstract or full-text, 2008. http://library.ust.hk/cgi/db/thesis.pl?ECED%202008%20DENG.
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Sassi, Andrea. "PET (Positron Emission Tomography) e tomografia computerizzata." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amslaurea.unibo.it/4961/.
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Michelgård, Palmquist Åsa. "Positron Emission Tomography (PET) Studies in Anxiety Disorders." Doctoral thesis, Uppsala universitet, Institutionen för neurovetenskap, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-129713.
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Anxiety disorders are very common and the primary feature is abnormal or inappropriate anxiety. Fear and anxiety is often mediated by the amygdala, a brain structure rich in substance P (SP) and neurokinin 1 (NK1) receptors. To learn more about how the human amygdala is modulated by fear and anxiety in event-triggered anxiety disorders and to investigate if the SP/NK1 receptor system is affected, regional cerebral blood flow (rCBF) ([15O]-water; Study I and II) and the SP/NK1 receptor system ([11C]GR205171; Study III and IV) were studied with positron emission tomography (PET). In Study I we investigated the neural correlates of affective startle modulation in persons with specific phobia by measuring rCBF during exposure to fearful and non-fearful pictures, paired and unpaired with acoustic startle stimuli. Fear-potentiated startle was associated with activation of the affective part of the anterior cingulate cortex and the left amygdaloid–hippocampal area. In Study II short-term drug treatment effects on rCBF in patients diagnosed with social phobia was evaluated, comparing the NK1 receptor antagonist GR205171 to the selective serotonin reuptake inhibitor citalopram and placebo. Social anxiety and neural activity in the medial temporal lobe including the amygdala was significantly reduced by both drugs but not placebo. In Study III we investigated if activity in the SP/NK1 receptor system in the amygdala would be affected by fear provocation in individuals with specific snake or spider phobia. Fear provocation was associated with a decreased uptake of the NK1 antagonist [11C]GR205171 in the amygdala, possibly explained by an increase in endogenous SP release occupying the NK1 receptors. Study IV was conducted to explore the resting state NK1 receptor availability in PTSD patients as compared to healthy controls. Increased resting state binding of the tracer [11C]GR205171 in the amygdala of patients with PTSD suggested an increased amount of available receptors. In summary, fear and fear-potentiated startle modulates the human amygdala, possibly through the SP/NK1 receptor system.
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Steinman, Aaron H. "A simulator for small positron emission tomography cameras." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ28853.pdf.
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Gravel, Paul. "Positron emission tomography of extra-striatal dopamine release." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112625.
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Altered dopamine (DA) neurotransmission is implicated in neurological and psychiatric disorders. Positron Emission Tomography (PET) imaging of DA release has mainly been restricted to striatal areas, rich in D2/D 3 receptors, owing to the moderate affinity of the radioligands used. To measure extra-striatal DA release, where D2/D3 receptor concentrations are much smaller, an approach using a high affinity radioligand, such as [18F]Fallypride, is required. The aim of the present study was to investigate in healthy volunteers the suitability of [ 18F]Fallypride to measure variations in D2/D3 receptor occupancy, as a function of amphetamine-induced DA release, in extra-striatal regions. Six healthy male volunteers underwent two 18F-Fallypride PET sessions, following the double-blind oral administration of 0.3 mg/kg of d-amphetamine (Dexedrine) or placebo (lactose), counter-balanced for order. Following amphetamine administration, D2/D3 receptor occupancy of 18F-Fallypride was significantly reduced in striatum, but also in extra-striatal regions, including substantia nigra, amygdala, thalamus, hippocampus, and cortical areas.
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Hirani, Ella. "Central serotonergic function measured using positron emission tomography." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427986.
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Chen, Jun L. "Automatic reference region localisation in positron emission tomography." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416490.
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Alzahrani, Seraj Omar. "Positron emission tomography imaging probes targeting chemokine receptors." Thesis, University of Hull, 2016. http://hydra.hull.ac.uk/resources/hull:16079.
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Positron emission tomography (PET) is a highly sensitive nuclear medicine imaging technique. PET is used to accurately diagnose cancer and can detect early stage tumours. Molecular probes containing a positron emitting metal radioisotope (such as ⁶⁴Cu or ⁶⁸Ga) need to give a stable complex in vivo as well as targeting biomarkers or metabolic processes within the tumour. The roles of chemokine receptors in multiple disease stages have been demonstrated. The CXCR4 and CCR5 chemokine receptors have been implicated in cancer, as well as other disease states including HIV infection and chronic inflammatory diseases, including asthma and rheumatoid arthritis. Incorporation of a positron emitting radioisotope into a CXCR4 or CCR5 specific antagonist compound could allow visualisation of physiological locations with high expression levels of these receptors to characterise the disease. The small molecule CXCR4 antagonist AMD3100 (Plerixafor) has been approved for clinical use as a haematopoietic stem cell mobilising agent and also exhibits anti-HIV, anti-inflammatory and anti-tumour activity. Configurationally restricted analogues of AMD3100 complexed to metal ions have improved binding characteristics compared to AMD3100 and its metal complexes. A synthetic pathway to obtain series of configurationally restricted macrocyclic compounds (analogues of AMD3100) fixed in the trans IV configuration, has been developed and the copper(II), zinc(II) and nickel(II) complexes characterised. Their biological properties (anti-HIV, cytotoxicity and Ca²⁺ signalling inhibition) were evaluated to allow selection of compounds to be radiolabelled with ⁶⁴Cu²⁺ for evaluation as a PET imaging agent targeting CXCR4. The most active trans IV complexes, bis(zinc(II))- 1,4-xylyl bis(methyl side-bridged cyclam and bis(zinc(II))-1,4-xylyl bis(benzyl sidebridged cyclam) have EC₅₀ values of 516 and 247 nM respectively in the anti-HIV assay with cyotoxicity (CC₅₀) values of 42800 and 39600 nM respectively. However, the novel mixed metal trans II complex (copper(II)zinc(II))-1,4-xylyl bis(sidebridged cyclam) has a higher binding affinity with an EC₅₀ value of 3 nM (four times more potent than AMD3100) and cytotoxicity CC₅₀ value greater than 10 µM. Bis(zinc(II))-1,4-xylyl bis(side-bridged cyclam) was successfully radiolabelled with ⁶⁴Cu²⁺ via transmetallation to form (⁶⁴Cu (zinc(II))-1,4-xylyl bis(side-bridged cyclam) with a crude radiochemical yield of 92%. A derivative of known CCR5 antagonist TAK-779 containing a carboxylic acid functional group 2-(p-tolyl)-6,7-dihydro-5H-benzo[7]annulene-8-carboxylic acid 18 was prepared. A DO3A compound with a spacer terminating in a primary amine (tritert-butyl 2,2',2''-(10-(2-((2-aminoethyl)amino)-2-oxoethyl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetate) was successfully conjugated to compound 18 forming a potential CCR5 targeting compound that could be radiolabelled with gallium-68 for PET imaging applications. Preliminary in vitro affinity assays indicated that the modification of the structure had disrupted the CCR5 binding and some structural modification redesign may be required. Radiolabelling of the conjugate compound 2-(p-tolyl)-6,7-dihydro-5Hbenzo[7]annulene-8-amidoethyl-DOTA with gallium-68 was carried out. A crude radiochemical yield of ca. 100% was achieved to give ⁶⁸Ga-(2-(p-tolyl)-6,7-dihydro-5H-benzo[7]annulene-8-amidoethyl-DOTA) which is stable in buffer and against transferring challenge for over four hours.
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Cockbill, Andrew John Paul. "Spatio-temporal image reconstructiuon for positron emission tomography." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609735.
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Hughes, Stephen. "Polyazamacrocycles as potential Positron Emission Tomography (PET) agents." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/47610/.
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The synthesis of ligand systems and complexes thereof suitable for use as positron emission tomography (PET) agents is studied herein. The ligands 6,6’-(1,4-diazepane- 1,4-diyl)bis(3-aminobenzoate) (HPR), 6,6’-(piperazine-1,4-diyl)bis(3-aminobenzoate) (PipR.2HCl), 6,6’,6”-(1,4,7-triazonane-1,4,7-triyl)tris(3-aminobenzoate) (TACNR), 1,4-bis(2-amino-4-tolyl)- 1,4-diazepane (HPTol), 1,4-bis(2-amino-4-trifluoromethylphenyl)-1,4-diazepane (HPCF3 ), di-tert-butyl 4,4’-(1,4-diazepane-1,4-diyl)bis(3-aminobenzoate) (HPtButyl), 1,3-bis(2-amino- 4-tolyl)-1,3-diazacyclohexane (PipTol), 1,4,7-tris(2-amino-4-trifluoromethylphenyl)-1,4,7- triazacyclononane (TACNCF3), have been studied. Ni(II), Cu(II), and Zn(II) complexes of these ligands have been synthesised, DFT calculations have elucidated structural configuration, whilst x-ray crystal structures of NiHPtButyl, and CuTACNCF3 have been determined. EPR measurements of CuHPR have been taken. A series of triazine core compounds have been prepared for use as model compounds for targeting molecules. The compound Tz(EtGly)(BocGuan)Cl has been synthesised with the required arms to selectively bind to the integrin αvβ3. DO3A moieties have been added to these ligands, and mass spectra analysis of the coordination products with a series of metals has been determined. NO2A derived compounds 2,2’-(7-tosyl-1,4,7-triazonane-1,4-diyl)diaceticacid (TsTACNA2) and 2,2’-(7-(4-nitrophenyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NPhTACNA2) have been studied,with the x-ray crystallography of the copper complexes completed. Positron emmision tomography (PET) studies of the complexes have also been undertaken and show high levels of complexation at ng scales, with moderate stability in human serum. Glutaric acid functionalised compounds (2S,2’S)-2,2’-(1,4-diazepane-1,4-diyl)dipentanedioic acid (HPGlut), 2,2’,2”-(1,4,7-triazonane-1,4,7-triyl)tripentanedioic acid (TACNGlut), and 2,2’-(4,11-dimethyl-1,4,8,11-tetraazacyclotetradecane-1,8-diyl)dipentanedioic acid (DMiii iv CGlut) have been synthesised, with the copper complex of DMCGlut affording structural determination. The Mn(II) and Gd(III) complexes of the DMCGlut ligand system have been studied by xylenol orange UV titration for their metal-ligand binding ratio, with the Mn(II) system showing a 1:1 binding ratio, whilst the Gd(III) complex showed no binding at all. Synthesis of the trispyrazylborate analogue, tris(4-methyl-2-(2-pyridine)pyrazyl)borate (MeTpPy), was unsuccessful, however, the bis- (MeDpPy) and tetra- (MeQpPy) substituted analogues were successfully synthesised.
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Sitt, Steve. "POSITRON EMISSION TOMOGRAPHY UTILIZATION DEVELOPMENT IN HONG KONG." OpenSIUC, 2012. https://opensiuc.lib.siu.edu/theses/932.
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The introduction of clinical Positron Emission Tomography (PET) in oncology in the 1990s has substantially changed the management of patients with cancer and become one of the diagnostic modalities with the fastest growth worldwide (Buck et al., 2010). The major hurdle delaying the proliferation of PET was partly due to its high initial investment and insufficient third-party reimbursement (Keppler & Conti, 2001). Hong Kong, a region with about half the economic strength of Germany, was able to sustain a higher ratio of PET-CT scanners than that of Germany. Through the study of the PET utilization in Hong Kong, this research is to (i) explore the factors contributing to this phenomenon; and (ii) find out if those factors are applicable to other developing countries. The key factors found contributed to a higher ratio of PET-CT scanners in Hong Kong were: 1) medical expertise in a regionally profound disease; 2) the direct payment culture which enables an economically efficient and a cost-effective operation; 3) the influx of patients from neighboring countries; and 4) the reputation of its medical services. Applying these factors, citizens in developing countries were able to have access to the latest and expensive medical technology.
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Maas, Marnix Christiaan. "Monolithic scintillator detectors for high-resolution positron emission tomography /." Amsterdam : IOS Press, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?u20=9781586039356.
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Örlefors, Håkan. "Positron Emission Tomography in the Management of Neuroendocrine Tumors." Doctoral thesis, Uppsala University, Department of Medical Sciences, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3356.
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Neuroendocrine tumors (NET´s) are often characterized by overproduction of peptide hormones. In spite of pronounced clinical symptoms, the tumor lesions can be small and difficult to detect. The general aim of this thesis was to investigate, in vitro and in vivo, some of the potential monoamine pathways present in NET´s, using radiolabeled tracers for positron emission tomography (PET), with the intention to explore the value of PET-imaging in the management of NET´s.
We used the 11C-labeled serotonin precursor 5-hydroxy tryptophan (HTP) as the tracer for imaging of NET´s. More than 95% of the subjects displayed a high tracer uptake on PET and tumor detection rate with PET was higher in >50% of the patients compared both to computed tomography (CT) and somatostatin receptor scintigraphy (SRS). The primary tumor was imaged by PET in 84% (16/19), compared to 47% and 42% for SRS and CT, respectively. Tumor visibility was better with PET due to a higher tumor-to-background ratio and a better spatial resolution. There was a strong correlation (r = .907) between changes in urinary-5-hydroxy indole acetic acid and changes in transport rate of 11C-5-HTP during treatment, indicating the use of PET in treatment monitoring of NET´s.
Pretreatment with carbidopa decreased the urinary radioactivity concentration four-fold and significantly (p<0.001) increased the tumor tracer uptake. This greatly improved image interpretation and tumor lesion detection.
A screening for expression of monoamine pathways in NET´s revealed a high in vitro binding of the monoamineoxidase-A ligand harmine to tumor sections. PET examinations with 11C-harmine could visualize tumors in all patients, including non-functioning endocrine pancreatic tumors (EPT´s).
Finally, the in vitro turnover and in vivo distribution of the amino acids glutamate, glutamine and aspartate was investigated. Limited uptake in vivo indicates the lack of utility for these substances as PET-tracers for imaging and characterization of NET´s.
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Pointoin, Barry William. "Model-based randoms correction for 3D positron emission tomography." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31046.
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Random coincidences (randoms) are frequently a major source of image degradation and
quantitative inaccuracies in positron emission tomography. Randoms occurring in the true
coincidence window are commonly corrected for by subtracting the randoms measured in a
delayed coincidence window. This requires additional processing demands on the tomograph and
increases the noise in the corrected data. A less noisy randoms estimate may be obtained by
measuring individual detector singles rates, but few tomographs have this capability. This work
describes a new randoms correction method that uses the singles rates from an analytic calculation,
rather than measurements. This is a logical and novel extension of the model-based methods
presently used for scatter correction.
The singles calculation uses a set of sample points randomly generated within the preliminary
reconstructed radioactivity image. The contribution of the activity at each point to the singles rate
in every detector is calculated using a single photon detection model, producing an estimate o f the
singles distribution. This is scaled to the measured global singles rate and used to calculate the
randoms distribution which is subtracted from the measured image data.
This method was tested for a MicroPET R4 tomograph. Measured and calculated randoms
distributions were compared using count profiles and quantitative figures of merit for a set of
phantom and animal studies. Reconstructed images, corrected with measured and calculated
randoms, were also analysed.
The calculation reproduced the measured randoms rates to within ≤ 1.4% for all realistic studies.
The calculated randoms distributions showed excellent agreement with the measured, except that
the calculated sinograms were smooth. Images corrected with both methods showed no significant
differences due to biases. However, in the situations tested, no significant difference in the noise
level o f the reconstructed images was detected due to the low randoms fractions of the acquired
data. The model-based method of randoms correction uses only the measured image data and the global
singles rate to produce smooth and accurate random distributions and therefore has much lower
demands on the tomograph than other techniques. It is also expected to contribute to noise
reduction in situations involving high randoms fraction.Science, Faculty of
Physics and Astronomy, Department of
Graduate
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Frykholm, Peter. "Cerebral ischemia studied with positron emission tomography and microdialysis." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5319-8/.
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Örlefors, Håkan. "Positron emission tomography in the management of neuroendocrine tumors /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3356.
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Hakyemez, Hélène. "Dopamine and monetary reward : two positron emission tomography studies." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101132.
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Striatal dopamine is well known to be involved in reward. Indeed, drug of abuse allowed DA release in the striatum as previous PET experiment demonstrated. Here, is investigated the change of DA in different conditions of monetary reward in healthy subjects to identify which subcomponent of reward provokes Dopamine release using 11C Raclopride of PET. In a first time we scan 10 healthy male subjects 3 times in different conditions: unpredictable monetary reward, novel visual and audio stimuli, and sensorimotor control. In a second time, we compared different amounts of work load to get monetary reward. Unpredictable passive reward as well as novelty failed to release significantly DA in comparison to the sensorimotor control task. Conditions of increasing effort to obtain the reward failed to release DA in comparison to the condition of passive receipt of reward. Limitations of the PET technique, as well as the paradigm's ones are presented.
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Jenkins, Ieuan Harri. "Positron emission tomography studies of the human and disease." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298770.
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Schottlander, David. "Quantitative reconstruction and post-processing in positron emission tomography." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510219.
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Richardson, Mark Philip. "Positron emission tomography investigation of cortical malformations causing epilepsy." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313814.
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Layfield, Dominick 1971. "Functional lung imaging in humans using Positron Emission Tomography." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/29634.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2003.Includes bibliographical references (p. 186-187).
This thesis deals with a method of functional lung imaging using Positron Emission Tomography (PET). In this technique, a radioactive tracer, nitrogen-13, is dissolved in saline solution, and injected into a peripheral vein. By analysis of the tracer kinetics through the lung, measured using PET, a three-dimensional image of perfusion and ventilation can be generated. In the first part of this thesis, a new tracer-preparation system, suitable for use in human subjects, is described. The system is remotely operated, highly automated, and incorporates numerous redundant safeguards to protect the patient. The second part of the thesis details a formal approach to the analysis of the experimental data. A model of the tracer in the right heart and lungs is developed, and used to estimate physiological parameters for large to medium-sized regions of diseased lung. As regions of interest are made smaller, the amount of imaging noise in PET data increases. Consequently parameter estimates become less reliable as finer resolution is used. In order to retain as much spatial information as possible, a new approach is explored, in which voxels with similar kinetics are grouped together, and parameters are estimated for the whole group; in this way, spatial resolution is conserved at the expense of parametric discretization. The viability of the approach is demonstrated by high-resolution analysis of ventilation dysfunction in asthmatic subjects.
by Dominick Layfield.
Ph.D.
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Pakzad, F. "Molecular imaging using positron emission tomography in gastrointestinal malignancy." Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19224/.
Full textAbstract:
Positron Emission Tomography (PET) with 18F-FDG has emerged as a powerful tool in oncology. Furthermore, recent advent of PET/CT and novel tracers are continually expanding its role. This thesis investigates its application in two solid cancer models. In the diagnosing of primary pancreatic cancer, 18F-FDG PET/CT was shown to be more accurate than conventional CT. It did not add information to locoregional staging of disease but impacted management of patients with potentially operable tumours, by accurately confirming the presence / absence of metastases. In the pre-operative staging of patients with colorectal liver metastases (CLM), 18F- FDG PET/CT was also superior to CT in assessing extrahepatic disease, where it again impacted management. The accuracy of detecting hepatic disease was similar for both. Compared to PET alone, PET/CT improved the accuracy of lesions localization and interpretation. Next, the feasibility of imaging with the novel thymidine analogue tracer 18F-FLT was investigated. Overall, 18F-FLT PET was less accurate than 18F-FDG in detecting lesions in both cancer types, thus suggesting it to be an unsuitable tracer for routine diagnosis and staging. In the cohort of pancreatic cancer patients, 18F-FLT uptake (SUVs) were found to strongly correlate with the immunohistochemical proliferation marker, Ki-67 antigen. This supported 18F-FLT‟s potential role as a surrogate marker of proliferation. The prognostic implications of these require further investigation. Finally, an in vitro model was use to examine early changes in 18F-FLT uptake in response to treatment with cytotoxics. At 2 hours following pulse treatment with 5-fluorouracil, (and before changes in cell numbers and cell cycle phase were seen), a dose dependent increase in 18F-FLT uptake was seen. No change was observed with 18F-FDG nor following Cisplatin treatment. This adaptive response may have a role as an early predictor of response to 5-FU (and potentially other antimetabolites), which requires further investigation.
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Griffin, Rowena. "New bifunctional chelates for use in positron emission tomography." Thesis, University of Leicester, 2007. http://hdl.handle.net/2381/29994.
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This project has focussed on synthesising a range of bifunctional chelators (BFCs) for use in nuclear medicine, in particular positron emission tomography (PET). When such BFCs are complexed to a M(III) ion the overall charge on the complex varies between -1 and -3; this is expected to affect the renal clearance and biodistribution of these complexes.;A range of novel BFCs were produced; the synthesis of each requiring the use of new di-ester pendant arms. The BFCs were coupled to a range of moieties, including a patented biologically active peptide designed to locate at the site of angiogenesis, in order to allow the imaging of tumours to take place. The ultimate aim of the project was to couple the biologically active peptide to a tert-butyl deprotected BFC. This was achieved using various methodologies and reagents. The solution behaviour of the corresponding Eu(III) complex was studied. The hydration state of the peptide-coupled BFC was found to be q = 1, with 1 H NMR spectroscopy indicating a 4:1 mixture of square antiprismatic (SAP) : twisted square antiprismatic (TSAP) geometric isomers in solution.;Complexes of Ga(III), Eu(III), Y(III) and In(III) were synthesised with various benzylamine and N-Benzoyl-Gly-Lys coupled and tert-butyl protected BFCs. These were studied by 1H NMR and fluorescence spectroscopy where possible to provide an insight into their solution behaviour. Luminescent lifetime measurements indicated that the hydration state of all Eu(III) complexes was q = 1, indicating an 8-coordinate complex (with respect to ligand) with the ninth site occupied by a water. 1H NMR spectroscopy revealed the predominant geometric isomer in solution to be SAP, usually with a 4 : 1 ratio of SAP:TSAP. Selected benzylamine and N-Benzoly-Gly-Lys coupled BFCs were radiolabelled with 68Ga, using microwave heating for 1 min in order to illustrate their potential use in PET. This proved to be a superior method of radiolabelling on a small scale when compared to conventional heating.
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Zhu, Wenxia. "Development of Molecular Imaging Probes for Positron Emission Tomography." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1333944487.
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Detorie, Nicole Christine. "Lesion quantification in respiratory motion compensated positron emission tomography." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1925793241&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Chan, David. "Positron Emission Tomography as a biomarker in neuroendocrine neoplasms." Thesis, The University of Sydney, 2020. https://hdl.handle.net/2123/22452.
Full textAbstract:
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms with varying modes of treatment. Positron Emission Tomography (PET) is increasingly used in imaging of NENs to predict biology and to guide management. 68Ga-DOTATATE PET avidity predicts low-grade, indolent tumours, whereas 18F-FDG PET avidity predicts high-grade, aggressive tumours. In this thesis, I explore PET-based biomarkers for use in patients with advanced NEN. Chapter 1 is a literature review of biomarkers in NEN with a specific focus on PET imaging. Chapter 2 proposes a semi-quantitative 5-point scale (the “NETPET score”) for the interpretation of dual DOTATATE/FDG PET in NEN and validates its prognostic ability in a retrospective study. Chapter 3 involves imaging analysis of FDG PET to derive the metabolic tumour volume and total lesion glycolysis indices, demonstrating their value as prognostic biomarkers over and above that of FDG SUVmax. Chapter 4 is a lesion-based analysis of CT and dual PET in NEN patients undergoing PRRT. Measurement of lesion diameters and PET indices (such as SUVmax) failed to yield any candidate imaging-based predictive biomarkers to predict PRRT response in NEN. Chapter 5 summarises the progress made thus far and future directions in research. We conclude that dual PET is a promising tool to investigate NEN tumoural heterogeneity, that metabolic tumour volume is a new prognostic biomarker in NEN, and that further research will further define the population of NEN patients who will benefit most from dual PET
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Liu, Chen-Yi. "Characterization of silicon photomultiplier readout designs for use in positron emission tomography systems." Institute of Electrical and Electronics Engineers, 2011. http://hdl.handle.net/1993/18339.
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Geiger-mode avalanche photodiodes, or silicon photomultipliers, are promising light sensors for the next generation Positron Emission Tomography (PET) scanners. The sensor is being used in the scanner’s gamma ray detector to measure scintillation light. This thesis describes the test results of three gamma ray detectors that utilize silicon photomultipliers. The first one is a commercial detector, and the other two are custom made. The detectors are tested for their 511 keV photon energy and timing resolution, as well as their ability to measure light from small scintillator crystals. The two custom made detectors had smaller active area, but outperformed the commercial detector in energy resolution. The introduction of buffer amplifiers improved the timing resolution of one detector. All three detectors had their crystal decoding ability limited by signal multiplexing and the sensor’s dark noise. Finally, a detector design was proposed for the PET system being developed in our group.
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Dagher, Alain. "A technique for improving data acquisition and resolution in positron emission tomography /." Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=65390.
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Marrero, Cofino Gisela. "Positron Emission Tomography (PET) for the early detection of sunitinib-induced cardiotoxicity." Mémoire, Université de Sherbrooke, 2014. http://hdl.handle.net/11143/5939.
Full textAbstract:
Abstract: Sunitinib (Sutent®) is a multitargeted, small molecule receptor tyrosine kinase inhibitor used as an anti-cancer drug. It has increased the overall survival rate of metastatic renal cell carcinoma patients as well as the survival time of patients with pancreatic neuroendocrine tumors. Although the clinical use of sunitinib is a significant leap forward in the therapy of those cancers, its induction of cardiac toxicity in a substantial fraction of patients remains a critical problem. Sunitinib may cause hypertension, arrhythmias, drop of the left ventricular ejection fraction and congestive heart failure, fatal in some cases. These side effects are a frequent reason for interruption of its use. The mechanism(s) underlying sunitinib cardiotoxicity are not fully understood. Similar to other receptor tyrosine kinase inhibitors, it binds to a large number of cellular kinases, thus it can affect multiple cellular processes. In vivo, the pattern of toxicity is complex and unpredictable, with symptomatic heart failure sometimes observed early during treatment. The pattern of events preceding the onset of symptomatic cardiac dysfunction during treatment is not established. This represents a significant problem for the clinical diagnosis of cardiovascular complications before they become symptomatic. The identification and early detection of those events would be highly-beneficial for the clinical management of anti-cancer therapy with sunitinib. Positron Emission Tomography (PET) is recognized for its ability to probe metabolic and functional aspects of myocardial function. Under the working concept that heart failure can occur early during sunitinib treatment, and may be sustained by early myocardial metabolic and structural alterations, we performed a study with the objective of assessing the use of PET for the early detection of sunitinib-induced ardiotoxicity. For this, we established a model of cardiotoxicity in C57BL/6 male mice given 80mg/Kg/day of sunitinib or water, orally for 4 weeks. General and cardiac toxicity were monitored by biochemical, microscopical (H&E, immunofluorescence and electron microscopy) as well as gene expression analyses and blood pressure measurements. PET scans were performed weekly using [superscript 11]C-acetate and [superscript 18]F-FDG to evaluated the myocardial blood flow (MBF), myocardial oxidative metabolism through the quantification of oxygen consumption (MVO[subscript 2]), glucose uptake (K[subscript i]), myocardial metabolic rate of glucose (MMRG) and the left ventricular ejection fractions (LVEF). We found that sunitibib was cardiotoxic as revealed by histopathology, immunostaining and electron microscopy. Signs of inflammation and tissue remodeling were found by gene expression analyses and collagen staining. No hypertension or renal damage were detected on the study. FDG-PET revealed an early decrease of the LVEF, indicative of cardiac dysfunction, which developed into grade-2 heart failure by the end of the study. However, no signs of alterations in cardiac metabolism were uncovered by FDG- or [superscript 11]C-acetate-PET. Our results hint that the onset of sunitinib-induced contractile dysfunction may occur in the absence of hypertension or overt metabolic damage and call for further studies with longer treatments to clearly mark the onset of metabolic cardiotoxicity. // Résumé: Le sunitinib est un inhibiteur de tyrosine kinase qui est utilisée comme agent anticancéreux. Bien que l'utilisation clinique du sunitinib représente une percée significative pour le traitement de certains cancers, ce médicament s’avère cardiotoxique chez plusieurs patients, une situation qui est problématique. Le sunitinib peut provoquer une hypertension, des arythmies, une chute de la fraction d'éjection ventriculaire gauche et une insuffisance cardiaque congestive qui peut être fatale. Le mécanisme responsable de la cardiotoxicité de sunitinib n’est pas encore bien compris. Comme plusieurs autres inhibiteurs des récepteurs de la tyrosine kinase, il se lie à un grand nombre de kinases et peut affecter de nombreux processus cellulaires. In vivo, les mécanismes responsables de la toxicité sont complexes et imprévisibles et une insuffisance cardiaque est parfois observée tôt pendant le traitement. La séquence des évènements menant à l'apparition d’une dysfonction cardiaque pendant le traitement n’est pas connue. Cela pose un problème important pour le diagnostic de complications cardiovasculaires avant qu'elles ne deviennent symptomatiques. Une identification précoce de ces événements néfastes serait très bénéfique pour le suivi du traitement au sunitinib. La tomographie d'émission par positrons (TEP) est une méthode reconnue pour l’évaluation du métabolisme et de la fonctionnalité du myocarde. Selon notre hypothèse de travail, une insuffisance cardiaque peut survenir rapidement pendant le traitement au sunitinib, elle est l’expression d’altérations structurelles et métaboliques au niveau du myocarde; ces modifications se produisent tôt pendant le traitement. Nous avons effectué une étude pour évaluer la faisabilité d’utiliser l’imagerie TEP pour la détection précoce de la cardiotoxicité induite par le sunitinib. La première étape a été de développer un modèle de cardiotoxicité chez des souris. L’induction de la cardiotoxicité s’est faite par administration orale pour une période de quatre semaines, soit de sunitinib 80mg/Kg/jour ou d'eau pour les souris contrôles. Le suivi inclut la mesure de la pression sanguine, l’évaluation des altérations biochimiques, l’expression de certains gènes et un examen histologique du myocarde. Un suivi par imagerie TEP a été effectué chaque semaine avec du [indice supérieur 11]C-acétate et du [indice supérieur 18]F-FDG afin d'évaluer le flux sanguin myocardique (MBF), le métabolisme oxydatif du myocarde incluant la consommation d'oxygène (MVO2), l'absorption du glucose (K[indice inférieur i]), le taux métabolique oxydatif du glucose (MMRG) ainsi que la fraction d'éjection ventriculaire gauche (FEVG). Les résultats que nous avons obtenus par histopathologie, immunocoloration et microscopie électronique montrent que notre modèle est capable d’induire une cardiotoxicité. Nous avons également observé des évidences d'inflammation et de remodelage tissulaire à partir de l’étude de l'expression de certains gènes et de l’analyse de l’accumulation de collagène. Nous n’avons pas observé d’hypertension ni de lésions rénales. La TEP avec [indice supérieur 18]FDG a montré une diminution rapide de la FEVG, une indication d’une dysfonction cardiaque qui a été classée comme insuffisance cardiaque de grade 2 à la fin de l'étude. Cependant, aucun signe de modifications du métabolisme cardiaque n’a été mis en évidence par TEP/[indice supérieur 18]FDG- ou TEP/[indice supérieur 11]C-acétate. Nos résultats laissent penser que l'apparition de la dysfonction contractile induite par sunitinib peut se produire en l'absence d'hypertension ou de dommages métaboliques manifestes. De nouvelles études avec des traitements plus longs permettraient peut être de mieux définir le début de la cardiotoxicité métabolique.
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Bauer, Florian. "Detector Considerations for Time-of-Flight in Positron Emission Tomography." Doctoral thesis, Stockholms universitet, Fysikum, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-31587.
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Positron-Emission-Tomography (PET) is a modern imaging technique in nuclear medicine providing quantitative 3D distribution of a radioactive tracer substance in the human body. The gamma-detector is the first link in the chain of components that constitutes a PET. It converts incoming radiation into optical light pulses, which are detected by photo multiplier tubes. Here the light is converted into electric pulses, to be further processed by the acquisition electronics. Improving detector sensitivity and resolution is of great value in research and in clinical practice. The focus of this work is to improve the detector to give it time-of-flight (TOF) capabilities, in order to further improve sensitivity, which in turn leads to increased image quality, faster scan time and/or reduced dose exposure for the patient. Image quality has improved over the years, but losses in image quality have been reported for heavy patients, due to increased attenuation, and more dispersed counts over a larger volume. Instrumentation limits are still significant in heavy patient images, but the incorporation of TOF information promises to alleviate some of the limitations. In order to improve the timing resolution of the detector fast photo-multipliers and a novel scheme to extract the event timing trigger from a detector by using the summed dynode signal were investigated. When designing new PET detectors, it is important to have detailed understanding and control of the light sharing mechanisms in the crystal arrays. Therefore it was necessary to perform optical simulations and single crystal light output measurements to derive a model for an LSO block detector. Another way to improve the image quality is to use the depth-of-interaction (DOI) of the gamma ray within the detector. It is shown that a multi-layer phoswich detector comprised of LSO with different decay times and TOF capability, combines the benefits of TOF and DOI in one detector, maximizing the effective sensitivity gain.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 7: Submitted.
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Rudd, James H. F. "Imaging atherosclerotic plaque inflammation with [18F]- fluorodeoxyglucose positron emission tomography." Thesis, University of Cambridge, 2003. https://www.repository.cam.ac.uk/handle/1810/243719.
Full textAbstract:
Inflammation is important in both the pathogenesis and outcome of atherosclerosis. Plaques containing numerous inflammatory cells, particularly macrophages, have a high risk of rupture, whereas those with fewer inflammatory cells are at lower risk. The current ‘gold standard’ technique for imaging atherosclerosis is x-ray contrast angiography, which provides high-resolution definition of the site and severity of luminal stenoses, but no information about plaque inflammation. Quantification of plaque inflammation is desirable both to predict risk of plaque rupture and to monitor the effects of atheroma-modifying therapies. This is important since recent studies strongly suggest that HMG Co-A reductase inhibitors promote plaque stability by decreasing plaque macrophage content and activity without substantially reducing plaque size and therefore angiographic appearance. FDG is a glucose analogue that is taken up by cells in proportion to their metabolic activity. In this work, the central hypothesis was that plaque inflammation could be visualised and quantified non-invasively using FDG-PET. Initially, THP-1 monocytes and buffy-coat macrophages were stimulated with cellular activators, and the effect on deoxyglucose uptake was observed. It was demonstrated that both types of cell accumulated deoxyglucose in proportion to their metabolic activity. Next, FDG uptake was assessed in endarterectomy specimens from patients with symptomatic carotid disease. Autoradiography of excised plaques confirmed accumulation of deoxyglucose in macrophage-rich areas. Subsequently, co-registered FDG-PET imaging was performed in patients with transient ischaemic attack. FDG accumulated within carotid plaques, with significantly more FDG being taken up into symptomatic plaques than contralateral asymptomatic lesions. Finally, a rabbit model of atherosclerosis was established to investigate two related questions: firstly, whether an animal PET scanner (MicroPet) might detect atheroma, and secondly whether FDG-PET could image and perhaps quantify both atheroma progression and regression. Aortic atheroma was identified by FDG-PET, but full quantification was not possible, because the microPet system is currently unable to perform studies with attenuation correction. In summary, it has been shown, both in vitro and in vivo, that inflammation within atherosclerotic plaques can be successfully imaged by FDG-PET. In addition, pilot data from an experimental study of atherosclerosis in rabbits suggested that serial imaging with this technique might be useful for monitoring the effects of anti-atheroma drugs.
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Ling, Tao. "High resolution gamma detector for small-animal positron emission tomography /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/9751.
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Ting, Richard. "Novel catalysis, photocaging, and positron emission tomography through bioconjugate chemistry." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/7530.
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This thesis is comprised of three projects that serve to address current topics in the field of bioorganic chemistry.
Chapter 1 describes the emulation of enzyme catalysis through the kinetic analysis of the
DNAzyme 9₂₅-11t, a combinatorially selected RNase A mimic utilizing imiclazole and amine
groups hybridized to DNA. The rate constants measured for this system are the largest to date
for M²⁺ -independent self cleavage (0.020 min⁻¹), trans cleavage (0.28 ± 0.02 min⁻¹), and
multiple turnover (0.030 ± 0.002 min⁻¹) by a biomimetic system at physiological ionic strength
and pH. These constants rival most combinatorially selected metal dependent DNAzymes and
naturally occurring ribozymes even at physiological concentrations of M²⁺.
Chapters 2 and 3 discuss a novel photochemical motif, its application to biologically relevant
molecules, characterization of the photochemical mechanism, and its utility in the generation of
alkenes. Light is considered superior to other chemical reagents as its spatial and temporal
properties can be precisely controlled and its penetrative ability makes it a perfect reagent for
the non- invasive perturbation of cellular processes. Chapter 2 details the discovery of a novel
photochemical reaction and its use in photochemically regulating gene function and nucleic
acid chemistry. The chemistry described in Chapter 2 holds potential for the photocaging of all
adenine substrates, cofactors, and products in biological systems. Chapter 3 identifies the
photolytic mechanism and highlights its application to photolytic alkene synthesis. It is
predicted that the photolytic thioether mechanism identified in this chapter can be extrapolated
to the photolysis of a wide range of other aromatic thioethers.
Chapter 4 discusses the application of the ¹⁸F acceptor, boron, to most sensitive of in vivo
molecular imaging techniques: positron emission tomography. This aqueous approach
simplifies the state of the art by multiple chemical steps and multiplies the final specific
radioactivity of the final radiotracer by a factor of 3. This tool is expected to widen the
currently limited scope of biomarkers available for in vivo imaging and will enhance our ability
to image biochemical targets and pathways such that insight may be gained in the progression,
diagnosis, and treatment of disease.
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Kelly, Catherine. "Quantitative Modelling of Positron Emission Tomography Tracer Pharmacokinetics in Hypoxia." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491285.
Full textAbstract:
Tumour hypoxia is a hallmark of solid tumours and is associated with a poor prognosis and response to therapy. The molecular imaging modality Positron Emission Tomography (PET), in conjunction with radiolabelled molecules called tracers, is a promising technique for the non-invasive quantitation of tumour hypoxia. In this thesis we use mathematical modelling techniques to characterise the relationship between tumour hypoxia and PET tracer distribution. In the first section, we investigate the impact of tumour vasculature on spatial profiles of tissue oxygen. The geometry of vasculature is a key determinant of the degree of hypoxia. Both the modal intervessel distance and the degree of variation in geometry exert significant effects on oxygen profiles. \Ve extend previous models by representing the vasculature as a piecewise-smooth function. This enables the coarse-scale simulation of tissue oxygenation, with little loss of accuracy compared to higher resolution simulations. In the second section, we characterise the relationship between tumour vasculature, hypoxia and the spatiotemporal distribution of the hypoxic tracer, 3-[18F]fluoro-l-(2-nitrol- imidazolyl)-2-propanol (Fmiso). The spatiotemporal distribution of Fmiso is highly dependent on the proximity of tissue to the vasculature, in agreement with previous studies. This model enables us to analyse the assumptions of a simple model that is frequently used to extract hypoxic information from Fmiso-PET studies. We find that the simplified model relates well to our more complicated 'ground truth' in characterising the degree of hypoxia, but is less suited to describing tracer transport. In the final section, we investigate the potential of another tracer, [18F]-2-Deoxy-2fluoro- O-glucose (FOG), as a marker of hypoxia. The relationship between hypoxia and FOG distribution is more complicated than that of Fmiso, so it is necessary to model hypoxia-dependent and -independent factors. \Ve find that the colocalisation of Fmiso and FOG at the sub-millimetre level is unlikely, as a result of their mechanistic differences. The model predicts that the influence of hypoxia-independent regulation of FOG uptake precludes the use of FOG as a marker of hypoxia.
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Topping, Geoffrey John. "Manganese imaging with positron emission tomography, autoradiography, and magnetic resonance." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/46045.
Full textAbstract:
Manganese is a magnetic resonance imaging (MRI) contrast agent for small animals that can provide a blood-flow-independent measure of neuronal activation. Established Mn MRI methods have limited ability to measure concentrations of Mn or details of its distribution in vivo, which limits their experimental power. Positron emission tomography (PET) can measure quantitative distributions in vivo in small animals of positron-emitting radionuclides such as Mn-52, although has poorer spatial resolution than MRI. Autoradiography (AR) can also measure quantitative distributions of Mn-52, in ex vivo brain tissue, with spatial resolution similar to MRI.
This work has three primary goals: to develop and characterize Mn-52 as a radionuclide for PET in phantoms and in small animals, to develop a quantitative MRI method for measuring Mn concentration in the brain of small animals, and to validate the MRI results by comparisons with AR and PET.
Mn-52 was produced by proton irradiation of natural Cr foil, isolated by column chromatography, and used as a PET tracer for the first time in phantoms and in vivo in rats. Mn-52 phantom image quality metrics were similar to F-18, an established PET radionuclide. After systemic administration in rats, Mn-52 accumulation was seen in bones, but little was seen in the brain, due to the blood-brain barrier. Direct injection into the lateral ventricle effectively delivers Mn-52 throughout the rat brain. Mn-52 AR images were acquired and used for comparison with MRI.
MRI R1 relaxation rate maps of rat brain were acquired using a radiofrequency field strength independent inversion recovery Look-Locker sequence, and used to generate relaxation rate change and Mn concentration maps after Mn administration. These maps showed excellent quantitative agreement with PET and AR images of the same animal, confirming that MR R1 change accurately measures Mn concentration in rat brain in the range 0 to 0.1 mM, in the absence of other sources of R1 change. However, at some point above this concentration, measured R1 becomes inaccurate. Accordingly, Mn concentration mapping with MRI is a potentially useful tool to improve the experimental power of Mn-uptake imaging to assess neuronal activation.
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Gunn, Roger. "Mathematical modelling and identifiability applied to positron emission tomography data." Thesis, University of Warwick, 1996. http://wrap.warwick.ac.uk/36241/.
Full textAbstract:
Positron emission tomography (PET) is an in vivo tracer kinetic technique. This thesis is concerned with the analysis of data derived from PET studies in humans. There are two related themes in the thesis. Firstly, the derivation of mathematical models with particular reference to the modelling of radiolabelled metabolite formation in plasma and tissue. Secondly, the identifiability of model structures is examined, and a method for the reparameterisation of unidentifiable models is derived. Compartmental models describing the accumulation of radiolabelled metabolites in plasma following the intravenous administration of [11C]flumazenil and [11C]diprenorphine are presented. A theorem is presented which gives conditions for a unique solution to the spectral analysis approach (a kinetic modelling technique used in PET which is based on the a priori definition of a large set of basis functions). Mathematical techniques are presented for the analysis of expired 11CO2, a major labelled metabolite in many PET studies. This range of analytical and modelling techniques is then applied to the analysis of [11C]thymidine scans. [11C]Thymidine is a PET tracer being developed for the measure of tumour proliferation in cancer patients. The techniques developed in the thesis allow for the removal of the confounding labelled metabolite signals from both plasma and tissue data.