A dopamina (DA) é um neurotransmissor sintetizado nos neurônios dopaminérgicos da substância nigra, possuindo efeito importante sobre o Sistema Nervoso Central (SNC), dentre as quais a sensação de prazer e a motivação. Uma alteração nos transportadores de dopamina (DATs) se caracteriza por uma desordem progressiva do movimento devido à disfunção dos neurônios secretores de dopamina, gerando a Doença de Parkinson (DP). Por ser um distúrbio mais comum entre um espectro de doenças neurológicas, é necessário um estudo mais aprofundado para melhor diagnóstico. Esta dissertação apresenta um estudo do desempenho do filtro butterworth passa-baixa na reconstrução analítica Filtered Backprojection - FBP e reconstrução iterativa Ordered Subsets Expectation Maximization - OSEM, para garantir a qualidade da imagem de SPECT cerebral, adquirida pelo fantoma antropomórfico estriatal. Por avaliação interindividual de quatro especialistas em medicina nuclear, foram aplicadas notas para a análise visual das imagens, garantindo a qualidade da resolução espacial, contraste, ruído e diferenciação anatômica do corpo estriado. Para cada tipo de reconstrução, houve 49 imagens do corpo estriado, variando os valores das covariáveis apresentadas pelos algoritmos (iteração, subsets, ordem e frequência de corte). A fim de resultados consistentes, foram utilizados a regressão linear e o teste T-Student pareado. Os dados coletados demonstraram que é necessário utilizar um intervalo confiável de frequência de corte para FBP (0,9 a 1,6) e para OSEM (1,2 a 1,5) e variar a ordem de 0 a 10 que não influenciará a imagem. Para a reconstrução OSEM, ficou comprovado que o valor de iteração (i) e o número de subsets (s) que garantem melhor qualidade foram os mesmos que a empresa do algoritmo utilizado sugeriu (3i 8s). Esta, também, mostrou evidências de melhor qualidade da imagem, quando comparada à reconstrução FBP. Para uma imagem de qualidade, representando uma reconstrução confiável e uma análise visual segura, é necessário utilizar o intervalo de valores encontrados das covariáveis ordem e frequência de corte do filtro butterworth passa-baixa na reconstrução FBP e OSEM. Também é necessário utilizar o valor de iteração e subsets que a empresa sugeriu, e a reconstrução OSEM mostrou superioridade nas imagens comparadas à FBP, mas se o serviço não utilizar ainda este tipo de algoritmo, a imagem com FBP no intervalo proposto também garantirá a qualidade. / Dopamine is a synthesized neurotransmitter in dopaminergic neurons of the substantia nigra where it has an important effect on the central nervous system (CNS), such as the feeling of pleasure and motivation. A change in the dopamine transporters (DATs) is characterized by a progressive disorder of movement due to a dysfunction of the dopamine secreting neurons, causing Parkinson\'s Disease (PD). As it is a more common disorder among a spectrum of neurological diseases, further studies are necessary for a better diagnosis. This study presents an investigation on the performance of the low-pass butterworth filter in the Filtered Backprojection analytic reconstruction - FBP and Ordered Subsets Expectation Maximization iterative reconstruction - OSEM to ensure the quality of brain SPECT image, acquired by the anthropomorphic striatal phantom. By individual evaluation of four nuclear medicine specialists, grades were applied to the visual analysis of the images, ensuring the quality of the spatial resolution, contrast, noise and anatomical differentiation striatum. For each type of reconstruction, there were 49 pictures of the striatum, varying the values of covariates submitted by the algorithms (iteration, subsets, order and cutoff frequency). In order to obtain consistent results, we used linear regression and T-Student paired test. The collected data showed that it is necessary to use a reliable interval of cutoff frequency for both the FBP (0.9 to 1.6), and OSEM (1.2 to 1.5), and varying the order of 0 to 10, which does not influence the image. For OSEM reconstruction, it has been verified that the iteration value (i) and the number of subsets (s) ensuring best quality was the same as the company\'s algorithm suggested (3i 8s). This also showed evidence of better image quality when compared to FBP reconstruction. For an image quality, representing a reliable reconstruction and a safe visual analysis, you must use the range of values found of covariates order and cutoff frequency of the butterworth low-pass filter on the FBP and OSEM reconstruction. You must also use the iteration value and subsets that the company suggested and the OSEM reconstruction showed superiority on the images compared to FBP, but if the service does not use this type of algorithm, the image with FBP in the proposed range, also ensures quality.

Este foi um estudo retrospectivo de 18 pacientes com atrofia hipocampal (AH) e 21 pacientes com AH associada ao blurring do polo temporal (BPT), nos quais realizamos a investigação das alterações perfusionais ao SPECT (Single Photon Emission Computed Tomography) crítico, ao SPECT intercrítico e ao SISCOM (Subtraction Ictal SPECT Coregistered to MRI) e sua comparação com os dados de avaliação pré-cirúrgica. Os pacientes com BPT apresentaram início mais precoce da epilepsia, uma duração de epilepsia maior e um período maior de seguimento pós-operatório (PO). O padrão pefusional ipsilateral ao SPECT crítico, o qual denominamos de padrão -típico?, foi o padrão perfusional mais frequentemente encontrado em ambos os grupos de pacientes com e sem BPT. Ao SPECT intercrítico, a maioria dos pacientes com BPT apresentaram hipoperfusão ipsilateral no lobo temporal (LT) epileptogênico, enquanto que no grupo sem BPT esta hipoperfusão foi observada em metade dos pacientes. Ao SISCOM, o padrão perfusional -típico? foi novamente o mais encontrado em ambos os grupos com e sem BPT. Entretanto, os padrões considerados -atípicos? foram encontrados mais frequentemente nos pacientes com BPT, o que nos sugere um padrão de propagação das crises epilépticas discretamente diferente neste grupo com BPT, o qual envolve outras áreas dos LT bilateralmente. Contrariamente à nossa hipótese inicial, não encontramos associação entre a presença de BPT e a presença de hiperperfusão no polo temporal (PoT) seja ao SPECT crítico ou ao SISCOM. Por este achado, nossos dados não suportam a idéia de que o BPT seja resultado de alterações teciduais intercríticas secundárias a um maior envolvimento ou participação deste polo na geração ou propagação de crises epilépticas na epilepsia do lobo temporal (ELT) mesial. Por outro lado, nossos resultados sugerem que o PoT é uma região frequentemente envolvida pelas crises do LT. Particularmente, a hiperperfusão no PoT ipsilateral à AH ao SISCOM foi mais encontrada nos pacientes com casos clínicos típicos de ELT mesial, sugerindo que o PoT é mais frequentemente envolvido (um padrão típico) em crises epilépticas em casos clínicos com informações mais concordantes (clear cut) e sugestivas de ELT mesial unilateral / This was a retrospective study of 18 patients with hippocampal atrophy (HA) and 21 patients with HA associated to temporopolar blurring (TPB). We performed an investigation of perfusion changes of ictal single photon emission computed tomography (SPECT), interictal SPECT and subtraction ictal SPECT coregistered to magnetic resonance imaging (SISCOM) and its comparison with results of presurgical evaluation. Patients with TPB showed earlier epilepsy onset, longer duration of epilepsy and a longer period of post surgical follow-up. The ipsilateral perfusion pattern in the ictal SPECT, which we denominated -typical? pattern, was the most frequent in both groups of patients, with and wihout TPB. In the interictal SPECT, most of patients with TPB showed ipsilateral hypoperfusion to the epileptogenic temporal pole (TP), while in the group without TPB this hypoperfusion was observed in half of the patients. Through SISCOM, the typical perfusion pattern was the most frequent in both groups. However, the patterns considered -atypical? were found more frequently in patients with TPB, which suggests a pattern of propagation of epileptic seizures slightly different in the group with TPB, which involves other areas of TL bilaterally. Adversely to our hypothesis, we did not found association between the occurrence of TPB and the hyperperfusion in the TP neither in the ictal SPECT nor SISCOM. Based on this finding, our data does not support the idea that the BTP is a result of interictal secondary tissue changes due to a higher involvement or role of this pole in the generation or propagation of epileptic seizures in the mesial temporal lobe epilepsy (TLE). On the other hand, our results suggest that the TP is a region frequently involved by seizures of TL. Particularly, the hyperperfusion in the TP which is ipsilateral to the HA through SISCOM was the most found in patients with typical clinical cases of mesial TLE, suggesting that the TP is frequently involved (a typical pattern) in epileptic seizures of clinical cases with more concordant information (clearcut) and suggestive of unilateral mesial TLE

Para realizar a correção de atenuação em uma tomografia computadorizada por emissão de fóton único (SPECT, em inglês) é necessário medir e reconstruir o mapa dos coeficientes de atenuação utilizando uma leitura de um tomógrafo de transmissão, feita antes ou simultaneamente à leitura de emissão. Essa abordagem encarece a produção da imagem e, em alguns casos, aumenta consideravelmente a duração do exame, sendo a imobilidade do paciente um fator importante para o sucesso da reconstrução. Uma alternativa que dispensa a leitura de transmissão é reconstruir tanto a imagem de atividade quanto o mapa de atenuação somente através dos dados de uma leitura de emissão. Dentro dessa abordagem propusermos um método baseado no algoritmo criado por Censor, cujo objetivo é resolver um problema misto de viabilidade côncavo-convexo para reconstruir simultaneamente as imagens. O método proposto é formulado como um problema de minimização, onde a função objetivo é dada pela variação total das imagens sujeita à viabilidade mista de Censor. Os teste foram feitos em imagens simuladas e os resultados obtidos na ausência de ruídos, mesmo para uma pequena quantidade de dados, foram satisfatórios. Na presença de dados ruidosos com distribuição de Poisson o método foi instável e a escolha das tolerâncias, nesse caso, ainda é um problema aberto. / In order to perform attenuation correction in single photon emission computed tomography (SPECT), we need to measure and reconstruct the attenuation coefficients map using a transmission tomography scan, performed either sequentially or simultaneously with an emission scan. This approach increases the cost required to produce the image and, in some cases, increases considerably the scanning time, therefore the patient immobility is an important factor to the reconstruction success. An alternative that dispense the transmission scan is reconstruct both the activity image and the attenuation map only from emission scan data. In this approach we proposed a method based on the Censors algorithm, which objective is to solve a mixed convex-concave feasibility problem to reconstruct simultaneously all images. The method proposed is formulated as a minimization problem, where the objective function is given by the total variation of the images subject to Censors mixed feasibility. In the simulations, artificial images were used and the obtained results without noised data, even for small amount of data, were satisfactory. The method was unstable in the presence of Poisson distributed noise and the tolerance choice, in this case, is an open problem yet.

O objetivo deste trabalho foi avaliar a influência das correções de atenuação e espalhamento na reconstrução quantitativa em SPECT. O estudo foi baseado em diversas simulações de Monte Carlo, com ênfase especial no modelo torso-cardíaco matemático (MCAT). Para a reconstrução, foi utilizado o algoritmo iterativo ML-EM com projetor-retroprojetor modificado pelo mapa de atenuação. Para avaliar a correção de espalhamento, foram simulados os espectros energéticos, com múltiplas ordens de espalhamento Compton. O método da dupla janela de energia (Jaszczak) foi aplicado, devido a sua simplicidade, e as imagens corrigidas foram comparadas com as de fótons primários. Foram analisadas as escolhas das janelas do fotopico e espalhamento, além da dependência do fator de espalhamento k com a distribuição de atividades do objeto. Duas abordagens foram adotadas para a obtenção dos mapas de atenuação: a estimativa do mapa uniforme diretamente dos dados de emissão, sem o uso de imagens de transmissão; e o borramento de mapas não-uniformes, reconstruídos a partir das projeções por transmissão. A estimativa do mapa de atenuação diretamente dos sinogramas de emissão baseou-se nas condições de consistência da transformada de Radon atenuada. Neste caso, foram estudados os efeitos de diferentes contagens e vários coeficientes de atenuação iniciais sobre as imagens corrigidas. Os mapas de atenuação não-uniformes foram borrados com um \"kernei\" gaussiano, aplicados nas correções e os efeitos na quantificação foram analisados. Os espectros energéticos emitidos pelo modelo MCAT mostraram que os fótons espalhados não poderiam ser excluídos a contento, mesmo que fossem utilizadas janelas de aquisição estreitas sobre o fotopico. Em relação a correção de Jaszczak, verificou-se que a escolha das janelas de fotopico e espalhamento é crucial e confirmou-se que o valor de k é altamente dependente do objeto examinado. Dada uma estimativa inicial do mapa de atenuação, o uso das condições de consistência para estimar o mapa de atenuação uniforme, consistente com os dados de emissão do modelo MCAT simulado, resultou sempre em uma mesma forma, para quaisquer valores iniciais do conjunto de parâmetros. Apesar do erro diminuir com o aumento da contagem, o melhor coeficiente de atenuação não pôde ser obtido, mesmo em altas contagens. Isto se deve a presença dos fótons espalhados, que alteraram a solução das condições de consistência, reduzindo as dimensões do mapa. Os resultados indicaram que a correção de espalhamento é o fator mais importante na reconstrução quantitativa em SPECT. Com referência aos efeitos quantitativos da correção de atenuação, não foram observadas diferenças significativas com a utilização dos mapas borrados, enquanto que a correção com mapas uniformes mostrou-se menos eficaz. / The goal of this work is to evaluate the influence of scatter and attenuation correction methods in quantitative SPECT reconstruction. The study was based on several Monte Carlo simulations, with special emphasis on the mathematical cardiac-torso phantom (MCAT). Iterative ML-EM reconstruction with modified projector-backprojector was used. To evaluate the scatter correction, energy spectra were simulated for SPECT imaging including multiple order Compton scattered photons. The dual energy window method proposed by Jaszczak was applied and scatter corrected images were compared with primary photons images. The choice of the scattering and photopeak windows and the dependence of the scatter factor k with the activity distribution were also analysed. Two approaches were adopted for obtaining the maps for attenuation correction: the estimation of the attenuation maps directly from the emission data, without transmission imaging, and the blurring of non-uniform attenuation maps, reconstructed from transmission data. The estimation of attenuation maps directly from the emission sinograms was based on the consistency conditions of attenuated Radon transform. In this case, the effects of different counting rates and various initial attenuation coefficients on the corrected images were studied. The non-uniform attenuation maps were blurred with a gaussian kernel with different variances, applied in further corrections and their effects on quantitation were examined. Analysis of energy spectra emitted from the MCAT phantom showed that scattered photons cannot be totally excluded, even when narrow acquisition windows were used. As far as the Jaszczak correction is concerned, results showed that the choice of photopeak and secondary windows is crucial and that the value of k is highly dependent on the imaged object. Given an initial estimation of the attenuation map with a constant coefficient, the use of consistency conditions to estimate the uniform map, consistent with the emission data of simulated MCAT phantom, resulted in the same shape for any set of initial parameters. In spite of the fact that the error falls with increasing counting rate, higher counts are not able to determine the best attenuation coefficient. This is due to scattered photons, which alter the solution of consistency conditions, reducing the size of estimated maps. Results indicated that the scatter correction is the most important factor inquantitative SPECT reconstruction. Furthermore, no significant differences were observed in the quantitation, when using the blurred non- uniform attenuation maps in attenuation correction, while corrections with uniform maps proved to be less efficient

INTRODUÇÃO: A classificação recente das Crises Hipercinéticas (CH) proposta por Rheims et al. (2008) sugere dois padrões de CH, baseado na semiologia ictal (Tipos I e II): no Tipo I, a zona epileptogênica foi identificada na região ventral pré-frontal, enquanto que no Tipo II, na região mesial pré-motora. Estudos com SPECT ictal em pacientes com CH evidenciaram hiperperfusão nas regiões frontais e extrafrontais, incluindo ínsula e lobo temporal, além de áreas subcorticais, tais como cerebelo, tálamo, gânglios da base e tronco encefálico. OBJETIVO: Avaliar a rede neural ativada nas CH através do SPECT ictal, correlacionando-a aos dois subtipos de CH (Tipos I e II). MATERIAL E MÉTODOS: Uma amostra de 25 pacientes com idade entre 0 e 60 anos com CH que realizaram SPECT ictal foi submetida a análise do VEEG e das imagens do SPECT ictal a fim de determinar o tipo de CH e as áreas de hiperpefusão ativadas, bem como sua correlação. RESULTADOS: Nove pacientes (36%) tiveram CH do Tipo I, dez (40%), do Tipo II e seis (24%), do Tipo Misto. Não houve diferenças significativas entre os tipos de CH e a presença de semiologia ictal não hipercinética durante as crises, bem como o tempo de doença, frequência das crises, história familiar positiva e exame de neuroimagem anormal. A duração média do tempo de injeção do RF foi de 32,2 segundos. O SPECT demonstrou ativação difusa, com predomínio nas regiões subcorticais, temporal lateral, occipital mesial e frontal dorsolateral. Não houve correlação entre os diferentes tipos de CH e as áreas hiperperfundidas, exceto pela região occipital mesial, que foi significativamente maior no Tipo II. CONCLUSÃO: A classificação proposta por Rheims et al. (2008) é útil porém simplista, já que as CH abrangem uma fenomenologia complexa, não sendo possível classificar todos os pacientes em somente dois tipos (I e II). O SPECT ictal nesta amostra demonstrou a presença de hiperperfusão em diferentes áreas cerebrais, reforçando a hipótese de que uma rede neural ampla, que engloba as regiões frontais e possivelmente extrafrontais, incluindo áreas subcorticais, está envolvida na gênese destas crises. / BACKGROUND: The recent classification of hyperkinetic seizures (HS) proposed by Reims et al (2008) suggests two patterns of HS based on ictal symptomatology (Type I and II), whereas in Type I epileptogenic zone was identified in the ventromesial frontal córtex while in Type II, in the mesial premotor córtex. Ictal SPECT studies in patients with HS showed hyperperfusion in frontal and extrafrontal regions, including insula and temporal lobe, and subcortical areas, such as cerebellum, thalamus, basal ganglia and brain stem. OBJECTIVE: To evaluate the neural network activated in HS through the ictal SPECT and to correlate it to the two subtypes of HS (Type I and II). METHODS: We retrospective analyzed ictal signs and ictal SPECT data in 25 patients with HS aged between 0 and 60 years in order to determine the type of HS and the hyperperfused areas, as well as their correlation. RESULTS: Nine patients (36%) were classified as Type I, ten (40%) as Type II and 6 (24%) as a mixed type. There were no significant differences between the types of HS and the presence of non-hyperkinetic ictal semiology, as well as epilepsy duration, frequency of seizures, positive family history and abnormal neuroimage. The average injection duration time was 32.2 seconds. The ictal SPECT showed diffuse activation, predominantly in subcortical regions and the following areas: lateral temporal, mesial occipital and dorsolateral frontal cortex. There was no correlation between the different types of HS and the hyperperfused areas but the mesial occipital region that was significantly higher in Type II. CONCLUSION: The classification proposed by Rheims et al (2008) is useful but simplistic. Since the HS consists of a complex phenomenology, it is not possible to classify all patients in only two types (I and II). The ictal SPECT in this sample showed the presence of hyperperfusion in different brain areas, reinforcing the hypothesis that a broad neural network, which includes the frontal and possibly extrafrontal regions, including subcortical areas, are involved in the genesis of these seizures.

La nanomédecine est un secteur d’activité en plein essor depuis le développement des liposomes, nanovecteurs permettant d’encapsuler des molécules hydrosolubles ou amphiphiles pour la délivrance de médicament. Les nouveaux agents thérapeutiques synthétisés étant de plus en plus lipophiles, le développement de nouveaux vecteurs nanoparticulaires permettant leur transport constitue aujourd’hui un enjeu majeur. Les lipidots, nanoparticules lipidiques solides biocompatibles de 50 nm de diamètre, composées d’un mélange d’huile, de cire et de lécithine stabilisées par une couronne de surfactants pegylés, permettent de transporter des composés hautement hydrophobes en leur cœur. Des agents nucléaires pour la tomographie à émission monophotonique et des agents de fluorescence ont pu y être encapsulés pour l’évaluation de la biodistribution de ces nanoparticules chez la souris saine ainsi que dans différents modèles tumoraux. Un peptide de ciblage, le cRGD a également été greffé à la surface des lipidots afin d’adresser préférentiellement, dans les 3 premières heures après injection, les nanoparticules vers les tumeurs surexprimant les intégrines αvβ3. Une biodistribution particulière des lipidots dans les organes stéroïdiens (surrénales, ovaires) a été observée avec une localisation spécifique dans les zones synthétisant les hormones stéroïdiennes (le corps jaune pour les ovaires, la zone corticale pour les surrénales). Cette affinité unique a été mise à projet pour cibler des tumeurs hormono-dépendantes, ainsi que pour encapsuler des hormones ovariennes pour le traitement hormonal substitutif ou le contrôle de la procréation. / Nanomedicine is a fast growing field since the development of liposomes, nanovectors able to encapsulate in their core or phospholipid bilayer hydrophilic or amphiphilic molecules for drug delivery purposes. Nowadays, most of the new synthetized therapeutic compounds are hydrophobic, necessitating the development of new types of nanocargos. Lipidots, 50 nm diameter biocompatible solid lipid nanoparticles, composed of a mixture of oil, wax and lecithin stabilized by a shell of pegylated surfactants, are used to encapsulate highly hydrophobic compounds in their core for vectorization purpose. Nuclear agents for simple photon emission tomography, or near infrared fluorescent dyes, have been encapsulated in the lipidot core, to assess the biodistribution of these nanoparticles in healthy mice as well as in a large range of tumor models. A targeting peptide, the cRGD motif, was also grafted on the surface of lipidots to vectorize preferentially the nanoparticles to tumors overexpressing αvβ3 integrins. An unexpected lipidot biodistribution in steroid organs (adrenal, ovary) was observed, with a specific localization in areas of steroid hormones synthesis (corpus luteum in ovaries, cortex for adrenals). This unique lipidot affinity was used to target hormono-dependent cancer cells, as well as to encapsulate ovarian hormones, like estradiol or ethynil estradiol, for hormone substitution therapy or birth control.

Monte Carlo is an important and well established research tool used in emission tomography. While used extensively in research applications, these techniques are not typically implemented clinically due to their low detection efficiency and long acquisition times. In order to make this computational tool faster, the variance reduction technique known as convolution-based forced detection (CFD) has been implemented into the SIMIND MC code (CFD-SIMIND) by our group. Briefly, at each site of interaction within the object, photons are forced to travel in a direction perpendicular to the detector and are then convolved with a distance dependent blurring kernel specific to that collimator and photon energy. A similar CFD method has already been implemented as an option in the SIMIND Monte Carlo program. The study presented in Chapter 2 performs a comparison between a well established, non-VRT Monte Carlo program, GATE, with our accelerated CFD-SIMIND. The intent of this work is to establish if CFD-SIMIND can either replace or be used in conjunction with GATE in order to gain significant reduction in simulation times for low and medium energy isotopes. A number of simulation studies were performed using point sources in air and water, along with the 3D XCAT phantom and a rectangular sheet source for Tc-99m with low and medium energy collimator and In-111 with medium energy collimator. A comparison in the projection domain was then performed in terms of spatial resolution, sensitivity, image profiles and energy spectra. The study has shown percent differences of between 3−5% in sensitivity between CFD-SIMIND and GATE with mean universal image quality index value of 0.994 ± 0.009 and spatial resolution within 0.2 mm of each other. CFD-SIMIND offers a significant reduction in simulation time by a factor of 5−6 orders of magnitude compared to GATE. This acceleration time is useful for many applications. This study also provides an objective tool that can help to determine if CFD-SIMIND can be used in place of GATE in order to achieve images of sufficient quality within a reduced time and at much lower computational cost. Simultaneous multi-isotope SPECT imaging has a number of applications in cardiac, brain and cancer imaging. The major concern however, is the significant crosstalk contamination due to photon scatter between the different isotopes. The second study (Chapter 3) focuses on a method of downscatter compensation between two isotopes iii in simultaneous dual isotope SPECT acquisition applied to cancer imaging using Tc-99m and In-111. We have developed an iterative image reconstruction technique that simulates the photon down-scatter from one isotope into the acquisition window of a second isotope. Our approach uses CFD-SIMIND for the forward projection step in an iterative reconstruction algorithm. The MC estimated scatter contamination of a radionuclide contained in a given projection view is then used to compensate for the photon contamination in the acquisition window of other nuclide. We use a modified ordered subset-expectation maximization (OS-EM) algorithm named simultaneous ordered subset-expectation maximization (Sim-OSEM), to perform this step. In this study, we have undertaken a number of simulation tests and phantom studies to verify this approach. The proposed reconstruction technique was also evaluated by reconstruction of experimentally acquired phantom data. Reconstruction using Sim- OSEM showed very promising results in terms of contrast recovery and uniformity of object background compared to alternative reconstruction methods implementing alternative scatter correction schemes (i.e., triple energy window or separately acquired projection data). In this study the evaluation is based on the quality of reconstructed images and activity estimated using Sim-OSEM. In order to quantitate the possible improvement in spatial resolution and signal to noise ratio (SNR) observed in this study, further simulation and experimental studies are required. It is perceived that in simultaneous dual-isotope breast SPECT studies using 123I-labelled Z-MIVE and Tc-99m sestamibi, I-123 labelled Z-MIVE not only detects the presence of estrogen receptor (ER) but, also thought to complement Tc-99m sestamibi in differentiating between benign and malignant breast lesions for patients with breast cancer (Chapter 4). The major concern in simultaneous Tc-99m/I-123 SPECT is the significant crosstalk contamination between the different isotopes used. The current study focuses on a method of crosstalk (downscatter and spillover) compensation between two isotopes with data acquired using Thallium activated Sodium Iodide (NaI(Tl)) detector (Energy resolution 9.8% at 140 keV ) and Cadmium Zinc Telluride (CZT) detector (Energy resolution 5% 140 keV ) respectively. The study uses Sim- OSEM for crosstalk compensation between the isotopes. We have undertaken a number of simulation studies using our modeled breast phantom to verify this approach. Reconstruction using Sim-OSEM showed very promising results in terms of crosstalk and scatter compensation and uniformity of background. In our case images obtained using Sim-OSEM were comparable or even better than the images reconstructed from separately acquired projection data using analytical attenuation based reconstruction. This may be due to better small angle scatter compensation in case of Sim-OSEM as CFD-SIMIND based MC forward projector was used. Compensation of the image degradation effects (i.e. attenuation, scatter and collimator-detector response) is necessary for an accurate quantification in SPECT imaging. We have previously proposed an accelerated Monte Carlo (MC) based iterative SPECT reconstruction algorithm that accurately corrects for attenuation and scatter once provided with attenuation information (Chapters 3 and 4). This algorithm uses SIMIND MC program accelerated through the implementation of a variance reduction technique known as, convolution forced detection (CFD), (CFD-SIMIND). With ever increasing number of hybrid SPECT/CT systems, CT-based attenuation correction is becoming a standard clinical protocol. This co-registered CT image with SPECT data can also be used to incorporate anatomical information as a prior into a maximum a-posteriori (MAP) SPECT image reconstruction algorithm. The study presented in Chapter 5 proposes a MAP reconstruction algorithm that includes CFD-SIMIND as a forward projector and a CT-image as an anatomical prior (CFD-AMAP) for simultaneous compensation of scatter and attenuation and, enhancement of spatial resolution during reconstruction. We have performed a number of simulation and experimental studies to elaborate the advantages of CFD-AMAP. These studies show an accurate quantification (within ±5% and ±8% for simulation and experimental studies respectively) accompanied by a significant reduction in coefficient of variation (CoV ). This reduction of CoV results in an improved boundary delineation and the Gibbs artifact compensation. However, this compensation comes at the cost of loss of an overall contrast in the reconstructed images due to a more uniform distribution of estimated activity over the regions of interest (ROI’s). Further studies with more complex phantoms and real patient data, task-based ROC studies, improvement in CFD-SIMIND in terms of speed and use of better Bayesian image reconstruction algorithms are needed to elaborate on the strengths and weaknesses of this proposed MC based forward projector and to pave the way for CFD-SIMIND based image reconstruction algorithms from research to clinic. / Thesis / Doctor of Philosophy (PhD)

Thesis (MScMedSc (Medical Imaging and Clinical Oncology. Nuclear Medicine))--University of Stellenbosch, 2010. / Thesis presented in partial fulfillment of the requirements for the degree of Master of Science in Nuclear Medicine at Stellenbosch University. / ENGLISH ABSTRACT: Introduction: There is conflicting data on the value of single photon emission tomography (SPECT) for the diagnosis of neuropsychiatric SLE (NPSLE). Visual assessment of brain SPECT scans is the standard approach in clinical practice. However the definition and identification of significant changes may be limited by a high interobserver variability, especially in centres with limited experience. This may be reduced by a more objective semi-quantitative assessment. The objectives of this study were to determine the sensitivity and specificity of SPECT for the detection of NPSLE at our institution using visual assesment, to determine the additional value of using an objective semi-quantitative diagnostic criterion, and to investigate the correlation between abnormal perfusion pattern and clinical NPSLE classification in patients with active NPSLE. Material and methods: Nineteen patients with NPSLE and 19 normal controls were studied with brain SPECT. Scans were interpreted blindly by two nuclear medicine physicians using two methods; visual and semi-quantitative assessments. In the visual method, overall visual impression was recorded for each scan using a four point scale, where A=normal, B=probably normal, C=probably abnormal, and D=abnormal. In addition, each brain region was assigned a severity score from 0=normal perfusion to 3=severe hypoperfusion. In the semi-quantitative assessment, ten-band color scale was used, and perfusion deficit was quantified on the side with the lower color intensity comparing to the contralateral side. A score was given to the region with perfusion deficit according to the difference (in color bands) between the two hemispheres. Analysis was performed for the visual assessment method (overall impression and severity scores) and the semi-quantitative assessment method using a receiver operator characteristic (ROC) curve. Optimal cut-off points were determined and the accuracy of the different techniques was also compared statistically. Finally, the correlation was determined between the SPECT perfusion pattern and the clinical pattern of disease. Results: An ROC curve analysis for the overall visual impression resulted in an area under the curve of 0.76. At a cut-off point of C (probably abnormal), brain SPECT had 89% sensitivity and 57% specificity for the diagnosis of NPSLE. The severity score which include the total severity score and the modified total severity score resulted in areas under the curve of 0.75 and 0.79 respectively. The semi-quantitative assessment resulted in areas under the ROC curve of 0.80. Statistically, there was no difference between the overall visual impression, visual severity scores, and the semi-quantitative assessment. Agreement analysis between the SPECT pattern and clinical pattern of disease showed agreement in 91.6% in the diffuse pattern, whereas agreement in the focal pattern was seen in only 42.8%. Discussion and Conclusion: In this study, we found that brain SPECT is able to diagnose active NPSLE with a high sensitivity and moderate specificity. The overall visual impression, visual severity scores, and the semi-quantitative assessment showed no significant differences between the techniques. The use of the semi-quantitative assessment described may be useful in centers with limited experience in the interpretation of brain SPECT. The correlation between the SPECT pattern and clinical disease pattern may provide some insights into the pathophysiology of NPSLE. / AFRIKAANSE OPSOMMING: Inleiding: Daar is teenstrydige inligting oor die waarde van brein enkelfoton emissie tomografie (EFET) vir die diagnose van neuropsigiatriese SLE (NPSLE). Visuele beoordeling van brein EFET flikkergramme is die standaard benadering in kliniese praktyk. Die definisie en identifisering van betekenisvolle veranderinge mag egter beperk word deur 'n hoë inte-waarnemer wisseling, veral in sentra met beperkte ondervinding. Dit mag verminder word deur 'n meer objektiewe semi-kwantitatiewe beoordeling. Die doel van hierdie studie was om 1. Die sensitiwiteit en spesifisiteit van EFET vir die opspoor van NPSLE in ons instelling te bepaal, 2. Die bykomende waarde van 'n objektiewe semi-kwantitatiewe diagnostiese kriterium vas te stel, en 3. Die korrelasie tussen 'n abnormale perfusiepatroon en 'n kliniese NPSLE klassifikasie in pasiënte met aktiewe NPSLE te ondersoek. Materiaal en Metodes: Negentien pasiënte met NPSLE en 19 normale kontroles is met brein EFET bestudeer. Flikkergramme is blind deur twee kerngeneeskundiges geïnterpreteer, deur gebruik te maak van twee metodes, 'n visuele en semi-kwantitatiewe beoordeling. Vir elke flikkergram is 'n globale visuele indruk genoteer deur gebruik te maak van 'n 4-punt skaal, waar A=normaal, B=waarskynlik normaal, C= waarskynlik abnormaal, en D=abnormaal. Bykomend is 'n ernstigheidsgraad waarde van 0=normale perfusie tot 3=erge hipoperfusie vir elke breinstreek toegeken. Vir die semi-kwantitatiewe beoordeling is 'n telling vir streke met laer intensiteit vergeleke met die kontralaterale kant toegeken, volgens die verskille in kleurbande deur gebruik te maak van 'n tienbandskaal. Die visuele metodes vir die globale indruk, visuele ernstigheidsgraad waarde, en die semi-kwantitatiewe beoordeling is geanaliseer deur 'n relatiewe funksioneringskenmerk (receiver operator characteristic (ROC)) kurwe te gebruik en optimale afsnypunte te bepaal. Die akkuraatheid van die verskillende tegnieke is ook statisties vergelyk. Laastens is die korrelasie tussen die EFET perfusiepatroon en die kliniese siektepatroon bepaal. Resultate: 'n ROC kurwe analise vir die globale visuele indruk het gelei tot 'n area onder die kurwe van 0.77. By 'n afsnypunt van (C) het brein EFET 'n sensitiwiteit van 89% en 'n spesifisiteit van 57% vir die diagnose van NPSLE gehad. Die visuele ernstigheidsgraad telling, en die semi-kwantitatiewe beoordeling het onderskeidelik tot areas onder die ROC kurwe van 0.75 en 0.79 vir die visuele ernstigheidsgraad waarde, en 0.8 vir die semi-kwantitatiewe beoordeling gelei. Statisties was daar geen verskil tussen die globale visuele indruk, die visuele ernstigheidsgraad waarde, en die semi-kwantitatiewe beoordeling nie. Ooreenstemmingsanalise tussen die EFET patroon en kliniese siektepatrone het 'n ooreenstemming van 91.6% in die diffuse patroon getoon, terwyl die fokale patroon ooreenstemming van slegs 42.8% getoon het. Bespreking en Gevolgtrekkig: In hierdie studie is gevind dat brein EFET 'n diagnose van NPSLE kan maak met 'n hoë sensitiwiteit en gemiddelde spesifisiteit. Die globale visuele indruk, visuele ernstigheidsgraad waarde, en die semi-kwantitatiewe beoordeling wat beskryf is, het geen betekenisvolle verskille tussen die tegnieke getoon nie. Die gebruik van die semi-kwantitatiewe beoordeling wat beskryf is, mag van waarde wees in sentra met beperkte ondervinding in the interpretasie van brein EFET. Die korrelasie tussen die EFET patroon en kliniese siektepatrone mag insig gee in die patofisiologie van NPSLE.

We have developed a simulation of the AdaptiSPECT small-animal Single Photon Emission Computed Tomography (SPECT) imaging system. The simulation system is entitled SimAdaptiSPECT and is written in C, NVIDIA CUDA, and Matlab. Using this simulation, we have accomplished an analysis of the Scanning Linear Estimation (SLE) technique for estimating tumor parameters, and calculated sensitivity information for AdaptiSPECT configurations.SimAdaptiSPECT takes, as input, simulated mouse phantoms (generated by MOBY) contained in binary files and AdaptiSPECT configuration geometry contained in ASCII text files. SimAdaptiSPECT utilizes GPU parallel processing to simulate AdaptiSPECT images. SimAdaptiSPECT also utilizes GPU parallel processing to perform 3-D image reconstruction from 2-D AdaptiSPECT camera images (real or simulated), using a novel variant of the Ordered Subsets Expectation Maximization (OSEM) algorithm. Methods for generating the inputs, such as a population of randomly varying numerical mouse phantoms with randomly varying hepatic lesions, are also discussed.

The subject of this dissertation is the assessment and optimization of image quality for multiple-pinhole, multiple-camera SPECT systems. These systems collect gamma-ray photons emitted from an object using pinhole apertures. Conventional measures of image quality, such as the signal-to-noise ratio or the modulation transfer function, do not predict how well a system's images can be used to perform a relevant task. This dissertation takes the stance that the ultimate measure of image quality is to measure how well images produced from a system can be used to perform a task. Furthermore, we recognize that image quality is inherently a statistical concept that must be assessed for the average task performance across a large ensemble of images.The tasks considered in this dissertation are detection tasks. Namely we consider detecting a known three-dimensional signal embedded in a three-dimensional stochastic object using the Bayesian ideal observer. Out of all possible observers (human or otherwise) the ideal observer sets the absolute upper bound for detection task performance by using all possible information in the image data. By employing a stochastic object model we can account for the effects of object variability, which has a large effect on observer performance.An imaging system whose hardware has been optimized for ideal observer detection task performance is an imaging system that maximally transfers detection task relevant information to the image data.The theory and simulation of image quality, detection tasks, and gamma-ray imaging are presented. Assessments of ideal observer detection task performance are used to optimize imaging hardware for SPECT systems as well as to rank different imaging system designs.