Introdução: A perfusão miocárdica de estresse pela tomografia (PMT) é um método emergente e não-invasivo para detecção de isquemia miocárdica. O objetivo deste estudo foi avaliar a acurácia diagnóstica da PMT em pacientes com bloqueio de ramo esquerdo (BRE) que estavam em pesquisa diagnóstica de doença arterial coronariana (DAC) e o valor adicional da PMT sobre a tomografia computadorizada com múltiplos detectores (ATC) usando tomógrafo com 320 detectores, e compará-los com a cintilografia de perfusão miocárdica (SPECT) para detecção de isquemia miocárdica com estenose coronariana significativa (estenose >- 70%), utilizando a angiografia coronariana quantitativa (QCA) e a angiografia coronariana pela tomografia computadorizada com múltiplos detectores como referências. Material e Métodos: Quarenta e dois pacientes com BRE e SPECT ( < 2 meses) em avaliação diagnóstica de DAC foram encaminhados para realizar o protocolo de tomografia que incluiu o escore de cálcio, PMT, ATC e realce tardio do miocárdio. Trinta pacientes foram encaminhados para angiografia coronária invasiva. As imagens foram interpretadas por observadores independentes e alheios aos resultados dos exames e aos dados clínicos. Foram realizadas análises por paciente e por território. O estudo obteve a aprovação da comissão de ética e todos os pacientes assinaram consentimento informado. Resultados: A idade média dos pacientes foi 63 +- 10 anos e, destes, 67% mulheres (28 pacientes). A dose média de radiação total foi de 9,3 +- 4,6 mSv. Na análise por paciente, sensibilidade, especificidade, valores preditivos positivo e negativo foram de 86%, 89%, 80 e 93% para a PMT (p=0,001) (kappa 0,74) e 63%, 91%, 65% e 90% (p < 0,001) na análise por território (kappa 0,55), respectivamente. Em ambas as análises, o ATC mostrou excelente precisão, com área sob a curva ROC=0,9. Considerável concordância foi demonstrada entre SPECT e o QCA (kappa 0,32 e 0,26) nas análises por paciente e por território, respectivamente. A avaliação combinada da ATC com a PMT permitiu melhorar a acurácia diagnóstica para detecção de estenose coronariana com redução luminal hemodinamicamente significativa ( >= 70%) comparando-se com a ATC, PMT ou SPECT isolados, demonstrado por valores de sensibilidade, especificidade, e valores preditivos positivos e negativos de 93%, 87%, 87%, 93% (p < 0,0001) na avaliação combinada por paciente, e 85%, 90%, 79%, 93% (p < 0,0001) na avaliação combinada por território. Conclusão: O uso do protocolo tomográfico de estresse é viável e possui boa acurácia para diagnóstico de DAC em pacientes com BRE com resultados superiores ao SPECT. A combinação da PMT e ATC permitiu melhorar a acurácia diagnóstica da avaliação de obstrução coronariana significativa em pacientes com BRE / Introduction: Stress computed tomography myocardial perfusion (CTP) is an emerging and non-invasive method to detect myocardial ischemia. The objective of this study was to evaluate diagnostic accuracy of CTP in patients with left bundle branch block (LBBB) who were being evaluated for coronary artery disease (CAD) and the additional value of CTP on computed tomography angiography (CTA) using 320-row detector CT scanner and compare them with single-photon emission computed tomography (SPECT) for detection of myocardial ischemia with significant coronary stenosis >= 70% using quantitative invasive coronary angiography (QCA) and coronary CT angiography as references. Material and Methods: Forty two LBBB patients with SPECT ( < 2 months) in diagnostic evaluation for CAD were referred to stress CT protocol which included calcium score, CTP, CTA and myocardial delayed enhancement. Thirty patients were referred to invasive coronary angiography. Independent blinded observers performed analyses of the images. Per-patient and perterritory analyses were conducted. Ethical committee aproval was obtained and all patients gave informed consent. Results: The mean age was 63 +- 10 years. 67% were women (28 patients). The total mean radiation dose was 9,3 +- 4,6 mSv. In per-patient sensitivity, specificity, positive and negative values were 86%, 89%, 80 and 93%, for CTP (p=0,001) (kappa 0.74) and 63%, 91% 65% and 90% (p < 0,001) in per-territory analysis (kappa 0.55), respectively. In both analyses, CTA showed excellent accuracy with area under receiver operating curve (AUC) = 0.9. Fair agreement was demonstrated between SPECT and QCA (kappa 0,32 e 0,26) in per-patient and per-territory analyses, respectively. The combined analysis of CTA with CTP, improved diagnostic accuracy for detection of coronary stenosis with hemodynamically significant luminal reduction ( >= 70%) compared with CTA, CTP or SPECT alone, demonstrated by sensitivity, specificity, and positive and negative predictive values of 93%, 87%, 87%, 93% (p < 0,0001) in the combined evaluation by patient and 85%, 90%, 79%, 93% (p < 0,0001) in the combined evaluation by territory. Conclusion: The use of customized stress CT protocol is feasible and has good accuracy for the diagnosis of CAD in patients with LBBB with results better than SPECT. The combination of PMT and ATC has improved the diagnostic accuracy of the assessment of significant coronary obstruction in patients with LBBB

Introdução: Na investigação não invasiva da doença arterial coronariana (DAC), destacam-se como métodos anatômicos de acurácia elevada a tomografia computadorizada (TC) para avaliação do Escore de Cálcio (EC) e a angiotomografia de coronárias (Angio-TC), e como método funcional a tomografia por emissão de pósitrons com Rubídio-82 (PET com 82Rb). As informações destes métodos se complementam e apresentam grande capacidade de ajudar na decisão terapêutica. Entretanto, muitas vezes, apenas um destes métodos está disponível na prática clínica, com destaque para a recente expansão da Angio-TC. Objetivos: Avaliar dois métodos diagnósticos não invasivos de referência quanto a análise anatômica e funcional coronariana e demonstrar a correlação entre a carga aterosclerótica pelo EC e o grau de obstrução coronariana pela Angio-TC com alterações de perfusão miocárdica através do PET com 82Rb. Material e Métodos: Estudo de corte transversal que incluiu 96 pacientes com suspeita de DAC significativa que realizaram PET com 82Rb sob estresse farmacológico no Departamento de Radiologia/Medicina Nuclear do InCor-HCFMUSP no período de junho a outubro de 2013, e que foram submetidos a Angio-TC dentro de até 30 dias. Placas coronarianas pela Angio-TC foram caracterizadas quando extensão, severidade e composição. Isquemia pelo PET com 82Rb foi definido como diferença entre os escores de estresse e repouso (SDS) maior ou igual a 2, e reserva de fluxo miocárdico (RFM) reduzido quando menor que 2. Resultados: Houve equilíbrio na distribuição do sexo (51% feminino), com média de idade de aproximadamente 59 anos. A hipertensão foi o fator de risco predominante (85%), seguida de dislipidemia (72%) e diabetes (35%). Angina foi o sintoma mais frequente (48%). As doses totais de radiação dos exames de TC foram relativamente baixas, sobretudo quando realizado no aparelho de 320 detectores (média de 2,79 mSv). A média do EC foi de 209,98 ± 488,68. O EC, principalmente quando maior que 400, teve forte associação com isquemia (razão de chances: 35,2; intervalo de confiança [IC] de 95%: 6,4 - 193,4). Estenose coronariana obstrutiva ( > 50%) pela Angio-TC também se correlacionou com maior risco de isquemia, especialmente quando a lesão detectada foi maior que 70% (razão de chances: 24,8; IC 95%: 7,6 - 80,3). Após ajustes para demais variáveis, tanto EC quanto estenose coronariana permaneceram associadas de forma independente. A combinação destas duas avaliações teve bom desempenho no diagnóstico de isquemia (área sobre a curva: 0,85; IC 95%: 0,74 - 0,95). Com relação à composição de placas, pacientes com RFM diminuída tiveram uma proporção significativamente maior de placas não-calcificadas e mistas do que aqueles com RFM preservada (p=0,006). Mais importante, estes tipos de composição de placa estiveram de forma independente associados com redução da RFM (razão de chances: 1,48; IC 95% 1,11 - 2,04). Conclusão: A Angio-TC e o EC se mostraram importantes preditores anatômicos, isolados e associados, na identificação de isquemia utilizando o PET com 82Rb como referência. Placas mistas e não-calcificadas se correlacionam com redução de RFM. Estas informações tem um importante papel na estratificação de risco cardiovascular de pacientes com DAC / Background: In the investigation of coronary artery disease (CAD), two highly accurate non-invasive methods play central roles, being the Coronary Computed Tomography (CTA) with Calcium Score (CS) the preferred exam for anatomical assessment, and Rubidium-82 PET-CT (82Rb PET/CT) for functional perfusional analysis. This information enables decision-making for clinicians on most settings, but unfortunately, only one of these exams is available on most medical centers, mostly CTA, which is now widely used worldwide. Objectives: To evaluate two reference non-invasive methods for CAD assessment, and demonstrate the correlation between plaque burden and anatomical stenosis degree, seen on CTA with CS, with the perfusional profile seen on 82Rb PET/CT. Methods: 96 individuals who performed 82Rb PET/CT for the evaluation of significant CAD at the Nuclear Medicine Department of the Heart Institute (InCor) of the University of Sao Paulo Medical School from June to October 2013 were included. CTA was performed during PET or scheduled during the next 30 days on a different scanner for the remaining patients. Coronary plaques on CTA/CS were then evaluated regarding extension, composition and flow-limiting stenosis degree. 82Rb PET/CT perfusion impairment was defined as present when rest and stress score difference (SDS) was >= 2, or when quantitative myocardial flow reserve (MFR) was under 2. Results: Mean age was 59 years old, and gender was balanced in the sample (female 51%). Hypertension was the most prevalent CAD risk factor (85%), followed by dyslipidemia (72%) and diabetes (35%). Chest pain was present in almost half the population (48%). Effective radiation exposure was low, especially when CTA was performed on the 320MDCT scanner (mean 2,79 mSv). Mean calcium score was 209,98 ± 488,68, demonstrating a strong association with ischemia, especially when above 400 (odds ratio: 35,2; 95% confidence interval [95%CI]: 6,4 - 193,4). Flow-limiting coronary stenosis (> 50%) seen on CTA also correlated with ischemia, especially when superior to 70% (odds ratio: 24,8; 95%CI: 7,6 - 80,3). After adjustment for other independent variables, either CS and CTA remained independently associated with ischemia. The combination of these two variables had a good performance for the detection of ischemia (area under curve: 0,85; 95%CI: 0,74 - 0,95). Regarding plaque composition, patients with mixed or noncalcified plaques were more likely to present decreased MFR (p=0,006). More importantly, these plaques were independently associated to reduced MFR (odds ratio: 1,48; 95%CI: 1,11 - 2,04). Conclusions: CTA and CS were important anatomical predictors of ischemia, either isolated or in association, using 82Rb PET/CT as reference. The presence of mixed or noncalcified plaques was significantly associated to decrease in MFR. These information are of emerging importance for DAC evaluation and management

In translational medicine, complementary functional and morphological imaging techniques are used extensively to observe physiological processes in vivo and to assess structural changes as a result of disease progression. The combination of magnetic resonance imaging (MRI) and positron emission tomography (PET) provides excellent soft tissue contrast from MRI with exceptional sensitivity and specificity from PET. This thesis explores the use of sequentially acquired PET and MR images to improve the quantification of small animal PET data. The primary focus was to improve image-based estimates of the arterial input function (AIF), which defines the amount of PET tracer within blood plasma over time. The AIF is required to produce physiological parameters quantifying key processes such as metabolism or perfusion from dynamic PET images. The gold standard for AIF measurement, however, requires serial blood sampling over the course of a PET scan, which is invasive in rat studies but prohibitive in mice due to small total blood volumes. To address this issue, the geometric transfer matrix (GTM) and recovery coefficient (RC) techniques were applied using anatomical MR images to enable the extraction of partial volume corrected image based AIFs from mouse PET images. A non-invasive AIF extraction method was also developed for rats, beginning with the optimization of an automated voxel selection algorithm to assist in extracting MR contrast agent signal time courses from dynamic susceptibility contrast (DSC) MRI data. This procedure was then combined with dynamic contrast enhanced (DCE) MRI to track a combined injection of Gadolinium-based contrast agent and PET tracer through the rat brain. By comparison with gold standard tracer blood sample data, it was found that normalized MRI-based AIFs could be successfully converted into PET tracer AIFs in the first pass phase when fitted with gamma variate functions. Finally, a MR image segmentation method used to provide PET attenuation correction in mice was validated using the Cambridge split magnet PET/MR scanner?s transmission scanning capabilities. This work recommends that contributions from MR hardware in the PET field of view must be accounted forto gain accurate estimates of tracer uptake and standard uptake values (SUVs). This thesis concludes that small animal MR data taken in the same imaging session can provide non-invasive methods to improve PET image quantification, giving added value to combined PET/MR studies over those conducted using PET alone.

This thesis deals with the magnetic resonance perfusion data analysis especially DCEMRI. In its introduction the thesis describes the problem of DCE-MRI data aquisition, the necessity of appropriate contrast agent and basic principles of perfusion analysis. The dynamic behavior of contrast agent vascular distribution can be described by arterial input function (AIF). The shape of the curves close to the area of interest is affected by dispersion which is called vascular transport function (VTF) due to the distribution of the contrast agent to the region of interest. Finally the tissue residual function describes system behavior of tissue. The practical part of the diploma thesis is aimed at implementation of model curves AIF, VTF and TRF. Furthermore, a simulation program was created for easy manipulation with introduced models moreover the program is used to perform an estimation of perfusion parameters based on nonblind deconvolution. The method is validated on synthetic data and illustrated on clinical data of the renal cell carcinoma patient.

Magnetic resonance perfusion imaging is a today's very promising method for medicine diagnosis. This thesis deals with a sparse representation of signals, low-rank matrix recovery and compressed sensing, which allows overcoming present physical limitations of magnetic resonance perfusion imaging. Several models for reconstruction of measured perfusion data is introduced and numerical methods for their software implementation, which is an important part of the thesis, is mentioned. Proposed models are verified on simulated and real perfusion data from magnetic resonance.

This thesis deals with the possibilities of determining perfusion parameters of vascular system, using contrast-enhanced ultrasound imaging, which is non-invasive method. Properties of ultrasonography and use of contrast agents are briefly summarized. The methods selected for perfusions analysis were Bolus-tracking¬¬, Burst-replenishment and both of them combined – Bolus&Burst. Parametric models based on these methods were created for modelling an approximation of set perfusion parameters with the use of blind deconvolution.

The diploma thesis deals with the image registration using evolutionary algorithms from metaheuristic optimization techniques which are considered recent and widely used. The frst part of the thesis contains theoretical description of components in image registration and later focuses on the ultrasound images. In that part, the thesis explains chosen evolutionary algorithms. Three optimization methods have been implemented, in particular genetic algorithm, particle swarm optimization and frey algorithm. Chosen similarity metrics for optimization are sum of squared dierences, cosine similarity and correlation coefcient. The main part of thesis includes testing of proposed methods with the evaluation of obtained results. These parameters are later used for optimization of real ultrasound sequences obtained by the contrast imaging.

Die zerebrale Perfusion ist eine wichtige physiologische Größe, die den Blutfluss in grauer bzw. weißer Hirnsubstanz beschreibt. Zur Perfusionsmessung in der klinischen Anwendung hat sich pseudo-kontinuierliches Arterielles Spin-Labeling (pCASL) als nichtinvasive Methode in der Magnetresonanzbildgebung etabliert. Das Anliegen der vorliegenden Arbeit ist es, pCASL zu charakterisieren und die Ursache für dessen Empfindlichkeit gegenüber intrinsischen Magnetfeldgradienten zu untersuchen. Anhand von Simulationen mit der Bloch-Gleichung konnten optimale Messparameter abgeleitet werden, um das Verfahren in dieser Hinsicht robuster zu machen. Die damit unabhängig von intrinsischen Magnetfeldgradienten bei 3\,T vorhergesagte hohe Labeling-Effizienz von 90\,\% wurde in vivo mittels eines eigens dafür entwickelten Messverfahrens experimentell validiert. / Cerebral perfusion is an important physiological parameter that describes the blood flow in brain tissue. To measure perfusion in a clinical setting, pseudo-continuous arterial spin labeling (pCASL) has been established as noninvasive method in magnetic resonance imaging. The purpose of this work is to characterize pCASL and to investigate its susceptibility to intrinsic magnetic field gradients. By simulations based on the Bloch equation, optimal parameter settings could be derived with particular focus on robustness against their impairing influence. As a result, a high labeling efficiency of 90\% was predicted independently of magnetic field gradients at 3\,T. This finding could finally be validated in vivo by a dedicated experimental approach.

Introdução: A avaliação e detecção precoce dos defeitos de perfusão miocárdica permite estratificar o risco cardiovascular e auxiliar a tomada de decisão terapêutica nos pacientes com DAC estabelecida ou suspeita. O PET/CT com Rb-82 na avaliação da perfusão e função miocárdica não invasiva é uma ferramenta de elevada acurácia diagnóstica. O presente trabalho procura estabelecer uma avaliação de performance de diagnóstica, entre dois métodos na medicina nuclear - SPECT com 99mTc-Sestamibi e PET/CT com Rb-82. Métodos: Avaliação da perfusão e da função do ventrículo esquerdo em 42 pacientes submetidos ao PET-CT com Rb-82 e SPECT com MIBI com mesmo estresse farmacológico (Dipiridamol), utilizando-se das variáveis de perfusão (SSS, SDS, SRS, fluxo sanguíneo e reserva coronariana) e de função (FEVE, DeltaFEVE, VDF, VSF - no repouso e no estresse), considerando o CATE como o método de referência. Resultados: No escore SDS, o Rb-82 apresentou valores médios próximos ao dobro do MIBI no grupo dos alterados (7,6 vs 3,9). Obteve-se um valor de sensibilidade do Rb-82 de 90,9%, com VPP de 88,2% (p=0,012) para o SSS e de 87,8%, com VPP de 87,8% (p= 0,012) para o SDS. As áreas sobre curva demonstraram superioridade do Rb-82 com maior exatidão e acurácia do método em relação ao MIBI na amostra avaliada. No escore de reversibilidade (SDS), houve maior sensibilidade em cut-off de menor valor e maior especificidade em cut-off de maior valor. FEVE em repouso e estresse, assim como, VDF e VSF em repouso e estresse apresentaram valores de concordância altos. Os valores de SSS, SRS e SDS apresentaram concordâncias moderadas. Houve aparente queda do DeltaFEVE no Rb-82, contudo similar tendência não foi observada no MIBI, considerando que as diferenças não foram significativas com relação ao número de vasos com estenose em ambos os radioisótopos (p > 0,05). Em outra análise, entre uma variável de função ventricular e a CFR global foi evidenciada diferença significativa (p=0,024) entre os grupos normal e alterado. No grupo alterado com CFR global < 2,0 houve redução do DeltaFEVE em 2,7%.Conclusão: O PET-CT com 82Rb apresenta maior exatidão e acurácia diagnóstica na avaliação perfusional miocárdica em relação ao SPECT com MIBI, inclusive com reclassificação dos grupos avaliados que passaram de defeito perfusional de pequena para moderada extensão. A FEVE estresse na população geral sugere valor mais alto no 82Rb (aquisição do exame no pico do estresse).Haveria uma sugestão de que no grupo com CATE alterado, a CFR global seria reduzida; que em maiores graus de estenose coronariana ao CATE, a CFR global decresceria; que existiria queda da DeltaFEVE no 82Rb quanto maior fosse o número de vasos obstruídos ao CATE. A relação entre a FEVE reserva e a CFR global no 82Rb foi significativa com queda da DeltaFEVE no grupo com CFR global alterada / Background: The evaluation and early detection of myocardial perfusion defects allows to stratify cardiovascular risk and it helps therapeutic decision-making in patients with established or suspected CAD. Rb-82 PET/CT in perfusion evaluation and noninvasive myocardial function is a tool of high diagnostic accuracy. The present study seeks to establish a diagnostic performance evaluation between two methods in nuclear medicine - 99mTc-Sestamibi SPECT and Rb-82 PET/CT. Methods: Evaluation of perfusion and left ventricular function in 42 patients submitted to Rb-82 PET-CT and MIBI SPECT with the same pharmacological stress (Dipyridamole), using perfusion variables (SSS, SDS, SRS, blood flow and coronary reserve) and function (LVEF, DeltaLVEF, EDV, ESV - in rest and stress), considering CAG as the reference method. Results: In the SDS score, Rb-82 presented mean values close to double the MIBI in the altered group (7.6 vs 3.9). A Rb-82 sensitivity of 90.9% was obtained, with PPV of 88.2% (p = 0.012) for SSS and 87.8% for PPV of 87.8% (p = 0.012) for or SDS. The areas on the curve indicated superiority of Rb-82 with greater accuracy and accuracy of the method in relation to the MIBI in the sample evaluated. In the reversibility score (SDS), there was greater sensitivity in the lower cut-off value and greater specificity in the higher cut-off value. LVEF at rest and stress, as well as VDF and VSF at rest and stress had high agreement values. The values of SSS, SRS and SDS presented moderate agreement. There was an apparent decrease of DeltaLVEF in Rb-82, however a similar trend was not observed in the MIBI, considering that the differences were not significant in relation to the number of vessels with stenosis in both radioisotopes (p > 0.05). In another analysis, a significant difference (p = 0.024) between the normal and altered groups was found of ventricular function variable and global CFR. In the altered group with global CFR < 2.0 there was a reduction of DeltaLVEF in 2.7%.Conclusion: 82Rb PET-CT has a greater accuracy and diagnostic accuracy of myocardial perfusion assessment in relation to MIBI SPECT, including reclassification of the evaluated groups that went from small to moderate perfusion defect extension. The LVEF stress in the general population suggests a higher value in 82Rb (acquisition of the exam at peak stress). There would be a suggestion that if the CAG group changed, the overall CFR would be reduced; in which greater degrees of coronary stenosis to CAG, the global CFR would decrease; and there would be a decrease of DeltaLVEF in 82Rb, the greater the number of vessels obstructed to CAG. The relation to reserve LVEF and overall CFR in 82Rb was significant with decrease in DeltaLVEF of the group with altered global CFR