Accurate attenuation correction is essential for quantitative positron emission tomography. Typically, this correction is based on a coincidence transmission measurement using an external source of positron emitter, which is positioned close to the detectors. This technique suffers from poor statistical quality and high dead time losses, especially with a high transmission source strength. We have proposed and tested the use of single photon transmission measurement with a rotating rod source, to measure the attenuation correction factors (ACFs). The singles projections are resampled into the coincidence geometry using the detector positions and the r,)d source location. A nonparalyzable dead time correction algorithm was developed for the block detectors used in the McMaster PET scanner. Transaxial resolution is approximately 6 mm, which is comparable to emission scanning performance. Axial resolution is about 25 mm, with only crude source collimation. ACFs are underestimated by approximately 10% due to increased crossplane scatter, compared to coincidence transmission scanning. Effective source collimation is necessary to obtain suitable axial resolution and improved accuracy. The response of the correction factors to object density is linear to within 15%, when comparing singles transmission measurement to current coincidence transmission measurement. The major advantage of using singles transmission measurement IS a dramatically increased count rate. A factor of seven increase in count rate over coincidence scanning is possible with a 2 mCi transmission rod source. There are no randoms counted in singles transmission scans, which makes the measured count rate nearly linearly proportional with source activity. Singles detector dead time is approximately 6% in the detectors opposite a 2 mCi rod source. Present hardware and software precludes the application of this technique in a clinical environment. We anticipate that real time acquisition of detector singles can reduce the transmission scanning time to under 2 minutes, and produce attenuation coefficient images with under 2% noise. This is a significant improvement compared to the current coincidence transmission technique. / Thesis / Master of Science (MS)

This study attempts to develop a method for absolute quantitation in Positron Emission Tomography. This includes the definition of the dimension and the position of a tumour in the brain as well as the evaluation of the amount of drug delivered to the tumour and to surrounding tissues in a pixel-by-pixel way, from the image. The defined objectives can be achieved using the calibrated FWHM values of the distribution of events in the tumour image, versus distance, to determine the dimension and the position of the tumour. The concentration activity in the tumour and the tumour-to-nontumour activity ratios can be obtained from the image, using a modified filter and the calibration of the tomograph. The colour scale of the image can be expressed in absolute units (μCi/ml) and the concentration activity can be evaluated in each pixel of the image or in each volume element of the body. / Thesis / Master of Science (MS)

L'imagerie médicale remonte à la fin du XIXe siècle avec la découverte des rayons X par Röntgen. Depuis, de nombreuses modalités d'imagerie ont été développées, et sont aujourd'hui utilisées dans une large gamme d'indications cliniques. L'imagerie TEP (Tomographie par Émission de Positron) est une modalité fonctionnelle, quantitative et ayant une haute sensibilité, ce qui en fait une modalité de choix, notamment en cancérologie. Hélas, sa diffusion est freinée en comparaison avec le scanner ou l'imagerie par résonance magnétique, en raison de son coût notamment. C'est dans ce contexte que s'insère cette thèse, qui a pour objectif de montrer la faisabilité d'un imageur TEP ambulatoire dédié au suivi thérapeutique en cancérologie. À partir de développements instrumentaux originaux (localisation des gammas par division de lumière dans des barreaux scintillateurs, lecture à l'aide de Silicon PhotoMultiplier, géométrie compacte), ces travaux s'efforcent de baisser les coûts tout en restant compétitif en terme de performances. Dans un premier temps, une étude extensive de la division de lumière à travers toute une série de paramètres (longueur des barreaux scintillateurs, revêtement optique, matériau scintillateur, traitement des données) a été menée. Une résolution spatiale inférieure à 5 mm pour un barreau de 75 mm de LYSO emballé dans du teflon a notamment été obtenue. À partir de cette configuration, une première image a été reconstruite, à partir de deux modules en coïncidence, offrant une résolution spatiale de 5 mm pour un tel imageur. Enfin, toute une série de simulations a été menée, à partir des données expérimentales et avec une géométrie originale. En particulier, les performances ont été mesurées à partir du protocole NEMA, un standard permettant de comparer les performances à travers la littérature. Une résolution spatiale intrinsèque de l'ordre de 4 mm a été obtenue, soit meilleure que le marché actuel. La sensibilité de l'ordre de 2.5 cps/kBq est revanche relativement basse par rapport à l'existant, mais s'explique par un champ de vue axial restreint. Enfin, le potentiel en terme de quantification a été adressé, et est comparable au marché actuel. / Medical imaging first began at the end of the XIXth century with the discover of X-rays by Röntgen. Then, numerous imaging modalities have been developed and are used now for a wide range of cases. Positron Emission Tomography (PET) has a high sensitivity, is functional and quantitative, thus being of high interest in cancer monitoring. Nevertheless, PET is not as much spread in hospitals as magnetic resonance imaging and scanner. In this context, this work aims to prove the faisability of PET dedicated for cancer monitoring. Thanks to instrumental developments such as light sharing in scintillating crystals, use of Silicon Photomultipliers, and an original geometry, cost is expected to be reduced while having same performances as commercial devices. An extensive study of light sharing within scintillating barrels has been made, through many parameters (crystal length, coating, data analysis...). An intrinsic spatial resolution of 4 mm has been measured over a 75 mm long crystal of LYSO, coated with teflon. From such a configuration, a first image has been reconstructed using two modules in coincidence. A spatial resolution of 5 mm has been measured in the image. Finally, Monte Carlo simulations has been made with experimental data as input, in order to measure the performances of the final PET device. Thanks to NEMA standard protocol, performances has been measured and compared to other systems. A spatial resolution of 4 mm has been reached, for a sensitivity of 2.5 cps/kBq. Quantification problem has been assessed, providing results similar to existing devices.

<p>Patients suffering from different forms of neurodegenerative diseases, such as: Creutzfeldt Jacob Disease (CJD), Alzheimer disease (AD), mild cognitive impairment (MCI), frontotemporal dementia and Parkinson’s disease (PD) were examined with Positron Emission Tomography (PET) and the combination of different radiotracers: ¹⁵O-water, N-[¹¹C-methyl]-L-deuterodeprenyl (DED), [¹⁸F] 2-fluorodeoxyglucose: (FDG), N-methyl-[¹¹C]2-(4-methylaminophenyl)-6-hydroxybenzothiazole (PIB) and L-[¹¹C]-3,4-dihydroxiphenyl-alanine (DOPA). The radiotracers and the combinations of different radiotracers were selected with the intention to detect, in the brain, patterns of neuronal dysfunction, astrocytosis, axon degeneration or protein aggregation (amyloid), in the brain which are pathognomonic for specific diseases and may contribute to improve clinical differential diagnoses. Examinations in healthy volunteers were performed to allow comparisons with patients. In addition, animal studies were conducted to complement the information. In some cases, the PET findings could be compared with the results of autopsies.</p><p>In contrast to the micropathology, in which only a limited part of a tissue (obtained post-mortem or by biopsy) is inspected, one PET acquisition provides an image of the whole system (e.g.: the brain and the cerebellum). This form of imaging pathology is “<i>in vivo</i>”, where the examination is innocuous for the patient. </p><p>This thesis is an attempt to stimulate the development of new tracers, new tracer combinations and methods that directly or indirectly describe the anatomo-physiopathological changes produced in the brain in neurodegenerative diseases. A better description of different diseases can be obtained, confirming or questioning the clinical diagnoses and widening our understanding of the mechanisms underlying neurodegeneration. Different pathologies can produce similar symptoms and thus causing confusion regarding clinical diagnosis. The used PET combinations improved the accuracy of the diagnoses. The incipient knowledge emerging from a new neuroimaging pathology in combination with other disciplines may open the way to new classifications of dementias and neurodegenerative diseases based on an “<i>in vivo</i>” pathology. </p>

Patients suffering from different forms of neurodegenerative diseases, such as: Creutzfeldt Jacob Disease (CJD), Alzheimer disease (AD), mild cognitive impairment (MCI), frontotemporal dementia and Parkinson’s disease (PD) were examined with Positron Emission Tomography (PET) and the combination of different radiotracers: 15O-water, N-[11C-methyl]-L-deuterodeprenyl (DED), [18F] 2-fluorodeoxyglucose: (FDG), N-methyl-[11C]2-(4-methylaminophenyl)-6-hydroxybenzothiazole (PIB) and L-[11C]-3,4-dihydroxiphenyl-alanine (DOPA). The radiotracers and the combinations of different radiotracers were selected with the intention to detect, in the brain, patterns of neuronal dysfunction, astrocytosis, axon degeneration or protein aggregation (amyloid), in the brain which are pathognomonic for specific diseases and may contribute to improve clinical differential diagnoses. Examinations in healthy volunteers were performed to allow comparisons with patients. In addition, animal studies were conducted to complement the information. In some cases, the PET findings could be compared with the results of autopsies. In contrast to the micropathology, in which only a limited part of a tissue (obtained post-mortem or by biopsy) is inspected, one PET acquisition provides an image of the whole system (e.g.: the brain and the cerebellum). This form of imaging pathology is “in vivo”, where the examination is innocuous for the patient. This thesis is an attempt to stimulate the development of new tracers, new tracer combinations and methods that directly or indirectly describe the anatomo-physiopathological changes produced in the brain in neurodegenerative diseases. A better description of different diseases can be obtained, confirming or questioning the clinical diagnoses and widening our understanding of the mechanisms underlying neurodegeneration. Different pathologies can produce similar symptoms and thus causing confusion regarding clinical diagnosis. The used PET combinations improved the accuracy of the diagnoses. The incipient knowledge emerging from a new neuroimaging pathology in combination with other disciplines may open the way to new classifications of dementias and neurodegenerative diseases based on an “in vivo” pathology.

Die Positronen-Emissions-Tomographie (PET) bei der Schwerionentherapie ist eine wichtige Methode zur Qualitätskontrolle in der Tumortherapie mit Kohlenstoffionen. Die vorliegende Arbeit beschreibt die Verbesserungen des PET-Verfahrens, wodurch sich in der Folge präzisere Aussagen zur Dosisapplikation treffen lassen. Aufbauend auf den Grundlagen (Kap. 2) werden die Neuentwicklungen in den drei darauf folgenden Abschnitten (Modellierung des Abbildungsprozesses bei der PET, Streukorrektur für PET bei der Schwerionentherapie, Verarbeitung der rekonstruierten PET-Daten) beschrieben. Die PET-Methode bei der Schwerionentherapie basiert auf dem Vergleich zwischen den gemessenen und vorausberechneten Aktivitätsverteilungen. Die verwendeten Modelle in der Simulation (Erzeugung der Positronenemitter, deren Ausbreitung, der Transport und der Nachweis der Annihilationsquanten) sollten so präzise wie möglich sein, damit ein aussagekräftiger Vergleich möglich wird. Die Genauigkeit der Beschreibung der physikalischen Prozesse wurde verbessert und zeiteffiziente Algorithmen angewendet, die zu einer erheblichen Verkürzung der Rechenzeit führen. Die erwarteten bzw. die gemessenen räumlichen Radioaktivitätsverteilungen werden mit einem iterativen Verfahren rekonstruiert [Lau99]. Die gemessenen Daten müssen hinsichtlich der im Messobjekt auftretenden Comptonstreuung der Annihilationsphotonen korrigiert werden. Es wird ein geeignetes Verfahren zur Streukorrektur für die Therapieüberwachung vorgeschlagen und dessen Realisierung beschrieben. Zur Einschätzung der Güte der Behandlung wird die gemessene und die simulierte Aktivitätsverteilung verglichen. Dazu wurde im Rahmen der vorliegenden Arbeit eine Software entwickelt, das die rekonstruierten PET-Daten visualisiert und die anatomischen Informationen des Röntgentomogramms mit einbezieht. Nur durch dieses Auswerteverfahren war es möglich, Fehler im physikalischen Strahlmodell aufzudecken und somit die Bestrahlungsplanung zu verbessern.