Ischaemic stroke is a leading cause of death and disability in the developed world. Despite that considerable advances in experimental research enabled understanding of the pathophysiology of the disease and identified hundreds of potential neuroprotective drugs for treatment, no such drug has shown efficacy in humans. The failure in the translation from bench to bedside has been partially attributed to the poor quality and rigour of animal studies. Recently, it has been suggested that multicentre animal studies imitating the design of randomised clinical trials could improve the translation of experimental research. Magnetic resonance imaging (MRI) could be pivotal in such studies due to its non-invasive nature and its high sensitivity to ischaemic lesions, but its accuracy and concordance across centres has not yet been evaluated. This thesis focussed on the use of MRI for the assessment of late infarct size, the primary outcome used in stroke models. Initially, a systematic review revealed that a plethora of imaging protocols and data analysis methods are used for this purpose. Using meta-analysis techniques, it was determined that T2-weighted imaging (T2WI) was best correlated with gold standard histology for the measurement of infarctbased treatment effects. Then, geometric accuracy in six different preclinical MRI scanners was assessed using structural phantoms and automated data analysis tools developed in-house. It was found that geometric accuracy varies between scanners, particularly when centre-specific T2WI protocols are used instead of a standardised protocol, though longitudinal stability over six months is high. Finally, a simulation study suggested that the measured geometric errors and the different protocols are sufficient to render infarct volumes and related group comparisons across centres incomparable. The variability increases when both factors are taken into account and when infarct volume is expressed as a relative estimate. Data in this study were analysed using a custom-made semi-automated tool that was faster and more reliable in repeated analyses than manual analysis. Findings of this thesis support the implementation of standardised methods for the assessment and optimisation of geometric accuracy in MRI scanners, as well as image acquisition and analysis of in vivo data for the measurement of infarct size in multicentre animal studies. Tools and techniques developed as part of the thesis show great promise in the analysis of phantom and in vivo data and could be a step towards this endeavour.

Low back pain is the most common cause of disability in the United Kingdom with health care costs of more than 1 billion pounds per year. One reason associated with low back pain is the degeneration of intervertebral discs due to loads on the spine. Daily postures such as standing and sitting produce different loads on the discs. Previously, many studies investigated the stress and pressure within the disc in these postures. The results do not agree with each other and the experiments have many limitations. The aim of this project was to assess the feasibility of incorporating magnetic resonance (MR) imaging and finite element (FE) analysis to predict the pressure and stresses developed by different daily postures in an individual. Transient and non-transient subject specific 2D models of nine individuals in standing and sitting were created based on previously acquired MR images. The geometry of these FE models was based on supine MR images. The sitting and standing boundary conditions were calculated by comparing their MR images with the supine posture. The results showed that for six subjects sitting created more intradiscal pressure compared to standing and in one subject standing more than sitting. For two of the subjects the pressure was nearly the same in sitting and standing. Because of the 2D model’s limitations, 3D models of an individual were developed. Both transient and non-transient models of the individual were created. The intradiscal pressure results were three times lower compared to the 2D models. This was due to consideration of out of plane deformation in the 3D models. These results were in the range of in-vivo and in-vitro measurements available in the literature. In conclusion, it was possible to create kinematic transient subject specific FE models based on the MR images in different postures. 2D models provide a method for comparing the postures but 3D models may be more realistic.

There is no single test clinically available that is independently diagnostic for multiple sclerosis (MS). Currently MS is diagnosed using a combination of clinical evaluation and investigations including magnetic resonance imaging (MRI), interpreted in accordance with diagnostic criteria, to demonstrate the requisite dissemination of lesions in (anatomical) space and time. Lesions comprising inflammatory demyelination in the central nervous system are a core pathological feature of MS. Ultra-high field (e.g. 7 Tesla or 7T) T2*-weighted MRI can demonstrate in vivo a central vein in most of these lesions. This is a histopathologically specific feature which could be exploited to improve diagnostic workup in cases of suspected inflammatory demyelination. Central nervous system white matter not involved in demyelinating lesions is nevertheless affected in MS. The mechanisms inflicting injury to this normal appearing white matter (NAWM) and how they relate to focal lesions are unclear. Damage to NAWM seems important, because it correlates well with disability. Any association between cortical lesions, focal white matter lesions (WML) and diffuse damage to NAWM is difficult to investigate in vivo in MS, principally because MRI is relatively insensitive to cortical lesions. Investigation of such associations may also be confounded by the presence of small focal lesions within the “NAWM” that may remain undetected when using conventional MRI to define NAWM. Advantages inherent to ultra-high field MRI might help mitigate both of these problems.

ANDRADE NETO, Davino Machado. Magnetic ressonance imaging contrast agents obtained by fast sonochemistry approach. 2016. 84 f. Dissertação (Mestrado em Química)-Universidade Federal do Ceará, Fortaleza, 2016. / Submitted by Aline Mendes (alinemendes.ufc@gmail.com) on 2017-01-25T19:35:32Z No. of bitstreams: 1 2016_dis_dmandradeneto.pdf: 4658452 bytes, checksum: 4d05fbe6bccc67518a89306c468793a6 (MD5) / Approved for entry into archive by Jairo Viana (jairo@ufc.br) on 2017-01-26T20:28:31Z (GMT) No. of bitstreams: 1 2016_dis_dmandradeneto.pdf: 4658452 bytes, checksum: 4d05fbe6bccc67518a89306c468793a6 (MD5) / Made available in DSpace on 2017-01-26T20:28:31Z (GMT). No. of bitstreams: 1 2016_dis_dmandradeneto.pdf: 4658452 bytes, checksum: 4d05fbe6bccc67518a89306c468793a6 (MD5) Previous issue date: 2016 / Functionalized Fe3O4 nanoparticles (NPs) have emerged as a promising contrast agent for magnetic resonance imaging (MRI). Their synthesis and functionalization methodology strongly affects their performance in vivo. Although thermal decomposition is the most commonly used growth methodology reported in the literature, it has proven to be time-consuming, expensive, and laborious. Therefore, this work describes a rapid and facile sonochemical methodology to synthesize and functionalize Fe3O4 NPs with excellent physico-chemical properties for MRI. In this work, a sonochemistry approach was used to produce, in 12 min, Fe3O4 NPs functionalized with polysodium acrylate (PAANa), trisodium citrate (CIT), branched polyethylenimine (BPEI), and sodium oleate. X-ray diffraction and transmission electron microscopy demonstrated that the NPs were composed of a single inverse spinel phase with an average diameter of 9–11 nm and a narrow size distribution. It was confirmed by Mössbauer spectroscopy and magnetic measurements that the obtained NPs were transitioning to the superparamagnetic regime and possessed excellent magnetization saturation values (59–77 emu/g). Fourier transform infrared spectroscopy proved that the sonochemistry approach provided conditions that induced a strong interaction between Fe3O4 and the capping agents. Furthermore, dynamic light scattering experiments evidenced that samples coated with PAANa, CIT, and BPEI possess colloidal stability in aqueous solvents. Emphasis must be placed on PAANa-coated NPs, which also presented remarkable colloidal stability under simulated physiological conditions. Finally, the obtained NPs exhibited great potential to be applied as an MRI contrast agent. The transverse relaxativity values of the NPs synthesized in this work (277–439 mM-1s-1) were greater than those of commercial NPs and those prepared using other methodologies. Therefore, this work represents significant progress in the preparation of Fe3O4 NPs, providing a method to prepare high-quality materials in a rapid, cost-effective, and facile manner. / Nanopartículas (NPs) funcionalizadas emergiram como promissores candidatos para serem aplicadas como agente de contraste para imagem por ressonância magnética nuclear e sua metodologia de síntese e funcionalização afetam fortemente sua performance in vivo. A metodologia mais utilizada para a produção dessas NPs funcionalizadas é a decomposição térmica, a qual tem provado ser financeiramente desfavorável, laboriosa além de requisitar longos tempos de execução. Portanto, este trabalho tem como objetivo descrever uma metodologia fácil e rápida, através do método sonoquímico, para a síntese e funcionalização de NPs de Fe3O4 com excelentes propriedades físico-químicas com objetivo de serem aplicadas como agente de contraste para imagem por ressonância magnética nuclear. Neste trabalho, o método sonoquímico foi usado para produzir, em 12 min, NPs de Fe3O4 funcionalizadas com policrilato de sódio, citrato de sódio, polietilenamina ramificada e oleato de sódio. Difração de raios-X e microscopia eletrônica de transmissão demonstraram que as NPs produzidas são compostas de uma única fase de espinélio inverso de 9-11 nm de diâmetro e uma distribuição de tamanho estreita. Foi confirmado por meio da espectroscopia Mössbauer e medidas magnéticas que as NPs sintetizadas estão em transição para o regime superparamagnético e que possuem excelente valor de magnetização de saturação (59-77 emu/g) para aplicações biomédicas. Espectroscopia de infravermelho por transformada de Fourier provou que a radiação sonoquímica forneceu condições adequadas para que acontecesse uma interação forte entre o núcleo magnéticos e os agentes fucionalizantes. Além disso, experimentos de espalhamento dinâmico de luz confirmaras que as amostras recobertas com moléculas orgânicas hidrofílicas possuem estabilidade coloidal em solventes aquosos. Destaque deve ser dado a nanopartícula magnética recoberta com poliacrilato de sódio, que demonstrou excelente estabilidade coloidal em condições fisiológicas simuladas. Finalmente, as NPs obtidas se mostraram serem promissores candidatos a agentes de contraste. Uma vez que seus valores de relaxatividade transversal foram maiores que os agentes de contraste comerciais e daqueles preparados por outras metodologias sintéticas. Portanto, este trabalho trás um grande avanço no que se refere a preparação de NPs de Fe3O4 funcionalizadas para aplicações biológicas, uma vez que materiais de alta qualidade foram preparados de forma rápida e fácil.

Made available in DSpace on 2014-06-11T19:35:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-09-01Bitstream added on 2014-06-13T20:46:40Z : No. of bitstreams: 1 zuccamatthes_ag_dr_botfm.pdf: 4650039 bytes, checksum: 6a9fb0651a7f4d26c5b24e701691a9e0 (MD5) / Avon / Um dos principais objetivos da quimioterapia neoadjuvante é converter carcinomas mamários localmente avançados(CMLA) em tumores operáveis ou aumentar o número de pacientes que possam ser submetidas ao tratamento conservador da mama (TCM). Um planejamento cirúrgico ideal envolve a tentativa radiológica de predizer a área de tumor residual pós-quimoterapia, possibilitando a ressecção de uma grande quantidade de tecido mamário com segurança oncológica. Poucos dados estão disponíveis no que diz respeito aos exames preditores de tumor residual e à cirurgia oncoplástica em tumores mamários localmente avançados tratados com quimioterapia neoadjuvante. Avaliar o uso de exames pré e pós-quimioterapia, que favoreçam o TCM, em mulheres com CMLA, sobretudo em cirurgias oncoplásticas. Um ensaio clínico prospectivo (www.clinicaltrials.gov) realizado em mulheres com câncer de mama, estádio clínico III, submetidas à quimioterapia neoadjuvante, com base em quatro ciclos de AC (doxorrubicina 60mg/m2 + ciclofosfamida 600 mg/m2) e 4 ciclos de T (paclitaxel 175mg/m2). Em todas as pacientes foi realizada a delimitação das medidas tumorais pré-operatórias por tatuagem. Comparou-se o exame físico (EF), mamografia (MG), ultrassom (US) e ressonância magnética mamária (RNM) no pré-operatório e no pós-operatório. Estes achados foram correlacionados com o anatomopatológico (AP). Para a correlação entre diferentes medidas foi utilizado o índice de correlação intraclasses(ricc). Além disso foi feita correlação entre a média das medidas realizadas por cada método. Às pacientes foram oferecidas cirurgias oncológicas e oncoplásticas em conformidade com a imagem clínica anterior à quimioterapia, a resposta à quimioterapia, a localização, o tamanho do tumor, o volume mamário, a segurança, a comorbidades do paciente e a experiência do cirurgião. 50 pacientes foram... / One of the goals of neoadjuvant chemotherapy was to convert locally advanced breast tumors into operable tumors or increase the number of patients who may be treated with breast-conservative surgery (BCS). An ideal surgical approach involves attempting to predict the radiological area of residual tumor after chemotherapy, allowing the resection of a large amount of breast tissue safely oncology. Few data are available regarding the examinations predictors of residual tumor and oncoplastic surgery in locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy. To evaluate, the use of pre and post-chemotherapy exams in women with CMLA to promote BCS, especially oncoplastic surgery. A prospective clinical trial (www.clinicaltrials.gov) surveyed women with breast cancer, clinical stage III, submitted to neoadjuvant chemotherapy based on four cycles of AC (doxorubicin 60mg/m2 + ciclofosfamide 600 mg/m2) and 4 cycles of T (175mg/m2 paclitaxel). In all patients was carried out the demarcation of the tumor pre-operative measures by tattooing. The measurement of postoperative pathologic finding was correlated with physical examination (PE), mammography (MG), ultasound (US) and magnetic resonance (MRI). To determine the correlation between various measures we used the intraclass correlation (ricc). A correlation between the measures was also made and carried out on the average of each method. Oncoplastic surgery were offered to the patients in accordance with the clinical picture prior to chemotherapy, response to chemotherapy, location, tumor size, breast volume, security, co-morbidities of the patient and surgeon experience. 50 women completed the proposed treatment and were undergone surgery. The size of tumor ranges from... (Complete abstract click electronic access below)

This thesis describes the first application of ultra-fast magnetic resonance imaging (MRI) towards the characterisation of bubbly flow systems. The principle goal of this study is to provide a hydrodynamic characterisation of a model bubble column using drift-flux analysis by supplying experimental closure for those parameters which are considered difficult to measure by conventional means. The system studied consisted of a 31 mm diameter semi-batch bubble column, with 16.68 mM dysprosium chloride solution as the continuous phase. This dopant served the dual purpose of stabilising the system at higher voidages, and enabling the use of ultra-fast MRI by rendering the magnetic susceptibilities of the two phases equivalent. Spiral imaging was selected as the optimal MRI scan protocol for application to bubbly flow on the basis of its high temporal resolution, and robustness to fluid flow and shear. A velocimetric variant of this technique was developed, and demonstrated in application to unsteady, single-phase pipe flow up to a Reynolds number of 12,000. By employing a compressed sensing reconstruction, images were acquired at a rate of 188 fps. Images were then acquired of bubbly flow for the entire range of voidages for which bubbly flow was possible (up to 40.8%). Measurements of bubble size distribution and interfacial area were extracted from these data. Single component velocity fields were also acquired for the entire range of voidages examined. The terminal velocity of single bubbles in the present system was explored in detail with the goal of validating a bubble rise model for use in drift-flux analysis. In order to provide closure to the most sophisticated bubble rise models, a new experimental methodology for quantifying the 3D shape of rising single bubbles was described. When closed using shape information produced using this technique, the theory predicted bubble terminal velocities within 9% error for all bubble sizes examined. Drift-flux analysis was then used to provide a hydrodynamic model for the present system. Good predictions were produced for the voidage at all examined superficial gas velocities (within 5% error), however the transition of the system to slug flow was dramatically overpredicted. This is due to the stabilising influence of the paramagnetic dopant, and reflects that while drift-flux analysis is suitable for predicting liquid holdup in electrolyte stabilised systems, it does not provide an accurate representation of hydrodynamic stability. Finally, velocity encoded spiral imaging was applied to study the dynamics of single bubble wakes. Both freely rising bubbles and bubbles held static in a contraction were examined. Unstable transverse plane vortices were evident in the wake of the static bubble, which were seen to be coupled with both the path deviations and wake shedding of the bubble. These measurements demonstrate the great usefulness for spiral imaging in the study of transient multiphase flow phenomena.

abstract: The goal of the works presented in this volume is to develop a magnetic resonance imaging (MRI) probe for non-invasive detection of extracellular matrix (ECM) underlying fenestrated endothelia. The ECM is the scaffold that supports tissue structure in all organs. In fenestrated structures the such as the kidney glomerulus and the hepatic sinusoid the ECM serves a unique role in blood filtration and is directly exposed to blood plasma. An assessment of the ECM in fenestrated organs such as the kidney and liver reports on the organ's ability to filter blood - a process critical to maintaining homeostasis. Unfortunately, clinical assessment of the ECM in most organs requires biopsy, which is focal and invasive. This work will focus on visualizing the ECM underlying fenestrated endothelia with natural nanoparticles and MRI. The superparamagnetic ferritin protein has been proposed as a useful naturally-derived, MRI-detectable nanoparticle due to its biocompatibility, ease of functionalization, and modifiable metallic core. We will show that cationized ferritin (CF) specifically binds to the anionic proteoglycans of the ECM underlying fenestrated endothelia and that its accumulation is MRI-detectable. We will then demonstrate the use of CF and MRI in identifying and measuring all glomeruli in the kidney. We will also explore the toxicity of intravenously injected CF and consider other avenues for its application, including detection of microstructural changes in the liver due to chronic liver disease. This work will show that CF is useful in detected fenestrated microstructures in small animals and humans alike, indicating that CF may find broad application in detecting and monitoring disease in both preclinical and clinical settings. / Dissertation/Thesis / Ph.D. Bioengineering 2012

Les pathologies cardiovasculaires et leurs conséquences représentent actuellement un problème de santé publique majeur dont la prise en charge pourrait être considérablement améliorée par le développement de nouvelles méthodes de diagnostic non invasives. Ce projet doctoral vise à développer des microparticules polysaccharides injectables dans la circulation sanguine permettant l’imagerie moléculaire des pathologies artérielles. Grâce à un procédé d’émulsion-réticulation, nous avons synthétisé ces microparticules qui sont d’une part fonctionnalisées avec du fucoïdane afin de pouvoir cibler la P-Sélectine qui est une molécule d’adhésion exprimée au niveau de la paroi artérielle lésée, et d’autre part, conjuguées à des agents de contraste afin d’apporter un signal en imagerie. Nous avons alors développé 2 outils d’imagerie moléculaire propres à 2 modalités classiques d’imagerie médicale. Afin de suivre les microparticules en tomographie par émission monophotonique de positons (TEMP), nous les avons radiomarquées avec du technétium 99m et pour les détecter en imagerie par résonance magnétique (IRM), nous les avons chargées avec des nanoparticules d’oxyde de fer superparamagnétiques. Nous avons ensuite validé l’efficacité de ces 2 outils d’imagerie moléculaire avec des essais précliniques en imagerie in vivo chez le petit animal sur des modèles de pathologies artérielles. Les résultats obtenus sont très encourageants et ces 2 outils d’imagerie moléculaire ont un fort potentiel clinique pour le diagnostic des pathologies artérielles. Nous avons également observé que les microparticules migrent dans la paroi artérielle dégradée au niveau des pathologies étudiées. Cette propriété singulière pourrait s’avérer très intéressante pour les futurs travaux qui consisteront à utiliser ce support pour véhiculer des molécules thérapeutiques au cœur des différentes pathologies artérielles. / Cardiovascular diseases and their consequences constitute nowadays a major health issue. Their treatment could be substantially improved with the development of new non invasive diagnostic techniques. The aim of this doctoral project is to develop injectable into blood stream polysaccharide microparticles that would permit molecular imaging of arterial pathologies. From an emulsion- crosslinking process, we synthesized these microparticles which are on the one hand functionalized with fucoidan to target P-Selectin which is expressed at damaged arterial wall, and on the other hand combined with contrast agents to bring an imaging signal. We developed 2 molecular imaging tools dedicated to 2 classical medical imaging modalities. In order to track the microparticles by single photon emission computed tomography, we radiolabeled them with technetium 99m and to detect them by MRI, we loaded them with superparamagnetic nanoparticles of iron oxide. We then have validated the efficiency of these 2 molecular imaging tools with preclinical studies of in vivo small animal imaging of arterial disease models. The obtained results are very promising and these 2 molecular imaging tools have a strong clinical potential for the diagnosis of arterial pathologies. We also have observed that the microparticles tend to migrate though the damaged arterial wall. This specific property could turn out to be very interesting for future works which will consist in using this technology to convey therapeutic molecules directly into the core of the arterial pathologies.

Orientador: Li Li Min / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-09T01:31:47Z (GMT). No. of bitstreams: 1 Mariusso_PaulaDatti_M.pdf: 3069704 bytes, checksum: 388a16e406036f52b01473bcc1885f76 (MD5) Previous issue date: 2007 / Resumo: Introdução: Estudos demonstram que transtornos psiquiátricos apresentam causas genéticas, biológicas e psicossociais. A atrofia de determinadas áreas do córtex cerebral é apontada como um dos fatores biológicos associados ao Transtorno Depressivo Maior (TDM). Objetivo: Investigar e quantificar as possíveis alterações morfométricas encontradas no córtex de pessoas com TDM através do método de Morfometria Baseada em Voxels (VBM). Relacionar as alterações encontradas com a gravidade do transtorno. Método: Estudamos 25 pacientes (média=34,9±8,34 anos) com TDM, diagnosticados pelos critérios de DSM-IV e CID-10, e 30 controles (média=32,2±9,25 anos) sem transtornos psiquiátricos. Utilizamos a escala HAD e o Inventário de Depressão de Beck como ferramentas diagnósticas auxiliares. Os sujeitos foram submetidos a exame de ressonância magnética (Elscint Prestige 2T, Haifa Israel) ponderados em T1, com voxels isotrópicos de 1mm e sem gap. As imagens foram processadas e analisadas pelos softwares SPM2, VBM2 e MarsBar5. O teste T-Student foi empregado para determinar diferenças no volume/concentração de substância cinzenta entre os grupos e Correlação Simples1 para determinar a correlação entra a gravidade TDM e as alterações encontradas. Resultados: Através da análise com o SPM2, foram observadas diminuições significativas distribuídas em todo o córtex dos pacientes com TDM que foram confirmadas e ampliadas pelo estudo de ROI VBM com MarsBar5. As áreas mais afetadas foram: pólo temporal superior direito (p=0,0005) e a parte média do giro do cíngulo tanto esquerdo quanto direito (p=0,0002). Os resultados apresentaram uma correlação negativa maior com a escala HAD2 (giro temporal inferior esquerdo: p=0,0009, R=-0,64; giro fusiforme direito: p=0,0003; R=-0,68) do que com o inventário de Depressão de Beck (giro temporal inferior esquerdo: p=0,0048; R=-0,57). Conclusão: As estruturas acometidas nesse estudo são responsáveis por funções que se encontram alteradas em portadores de TDM, isso sugere que a atrofia é um dos fatores biológicos que compõem a natureza multifatorial desse transtorno. A diminuição do volume/concentração de substância cinzenta apresenta uma correlação com a gravidade do TDM / Abstract: Introduction: Psychiatric disorders are known to have genetic, biological and psychosocial causes. The atrophy of specific areas in the brain cortex is presented as one of the multiple biological causes associated with Major Depressive Disorder. Objective: To investigate and quantify possible morphometric changes in the brain cortex of subjects with Major Depressive Disorder using the Voxel-Based Morphometry method and correlate these changes with the disorder intensity. Methods: We have studied 25 subjects (average = 34,9±8,34 year) with MDD, diagnosed using the DSM-IV and CID-10 criteria, and 30 control subjects (average = 2,2±9,25 years), without psychiatric disorders. The HAD1 scale and the Beck Depression Inventory were used as auxiliary tools. The subjects were submitted to Magnetic Resonance Imaging (T1, Elscint Prestige 2T, Haifa Israel), with 1mm isotropic voxels and no gap. The images were than processed and analyzed using SPM2, VBM2 and MarsBar5 softwares. The T-Students test was used to find volume/concentration differences of gray matter among the groups and Simple Correlation2 to find correlation between the intensity of the Disorder and the intensity of the alterations. Results: The SPM2 analysis showed significative shrinking distributed among the cortex of the MDD subjects. This shrinking was confirmed by the ROI VBM analysis provided by MasBar5. The areas that were affected the most were: right superior temporal pole (p=0.0005) and bilateral middle part of cingullum (p=0.0002). The results present a bigger negative correlation with HAD scale (left temporal inferior gyrus: p=0.0009, R=-0.64; right fusiform gyrus: p=0.0003; R=-0.68) than Beck Depression Inventory (left temporal inferior gyrus: p=0.0048; R=-0.57) Conclusion: The structures that have a decreased volume in this work are responsible for changed functions in MDD patients, this shows that the atrophy is one of many biological factors in this multi factorial disease. The decreased of gray matter volume is correlated with gravity of DDM / Mestrado / Neurociencias / Mestre em Fisiopatologia Médica

Orientador: Roberto José Maria Covolan / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-25T18:35:31Z (GMT). No. of bitstreams: 1 Beltramini_GuilhermeCoco_D.pdf: 12819168 bytes, checksum: 3ea327ddb4007610872637f91cf058e4 (MD5) Previous issue date: 2014 / Resumo: Epilepsia é uma doença neurológica que afeta pessoas no mundo todo, atingindo em torno de 1% da população mundial. Aproximadamente 30% dos pacientes não respondem bem ao tratamento com medicamentos. A abordagem cirúrgica é uma alternativa recomendada somente quando se localiza, de forma precisa, a região epileptogênica, razão pela qual os pacientes são submetidos a diversas avaliações invasivas e não-invasivas, incluindo exames de neuroimagem estrutural e funcional. A técnica de EEG-RMf simultâneos surgiu da combinação do EEG, de uso consagrado em pacientes com epilepsia, com a RMf, procedimento cada vez mais aplicado em estudos funcionais do cérebro, tendo sido encarada desde sua concepção inicial com a perspectiva de se constituir em um novo exame não invasivo na avaliação pré-cirúrgica em epilepsia. As dificuldades instrumentais inerentes a esta técnica têm sido superadas mais rapidamente do que o desenvolvimento de métodos empregados na análise e interpretação dos resultados gerados através dela. Isto ocorre em parte devido à complexidade e diversidade de causas da epilepsia, que afeta o cérebro do ponto de vista estrutural e funcional, podendo atingi-lo desde o âmbito genético até níveis macroscópicos. Neste trabalho, estabelecemos uma sequência de procedimentos para a aquisição e análise de dados de EEG-RMf, possibilitando o uso deste exame como uma informação adicional na avaliação pré-cirúrgica. Criamos um programa de computador chamado SAfE (Straightforward Analysis of fMRI and EEG-fMRI), que permite realizar as análises de experimentos de EEG-RMf de forma direta e segura. Após aplicar as correções no sinal do EEG e realizar a marcação da atividade epileptiforme, mapas estatísticos de RMf podem ser obtidos através de uma interface gráfica simples, com pouca intervenção do usuário. Para observar simultaneamente os aspectos temporais e espaciais das alterações hemodinâmicas relacionadas com os diferentes tipos de atividade epileptiforme de cada paciente, foi proposta e incorporada ao SAfE uma forma original de se descrever os resultados. São gerados mapas estatísticos para diferentes posições do pico da função resposta hemodinâmica, que são então analisados sequencialmente, observando-se diferentes parâmetros, tais como o valor de T máximo e número de voxels acima do limiar. A abordagem aqui proposta para a análise dos dados de EEG-RMf sugere que os mapas estatísticos dos pacientes sejam examinados preferencialmente de forma individual, pois parte importante da informação pode ser perdida quando se combinam os resultados em análises de grupo. Os resultados obtidos revelam a alta complexidade dos mecanismos geradores de atividade epileptiforme, pois as redes cerebrais envolvidas mostram um elevado grau de heterogeneidade entre os pacientes e entre os diferentes tipos de atividade epileptiforme considerados. Possivelmente sistemas locais e remotos interagem de forma a causar alterações crônicas que afetam a propagação da crise e da atividade epileptiforme. A técnica de EEG-RMf tem se mostrado uma aplicação com valor clínico promissor, porém requer validação através da comparação com procedimentos mais bem estabelecidos. Embora os benefícios desta técnica sejam limitados em pacientes com atividade epileptiforme de difícil detecção, entende-se que seu desenvolvimento deverá contribuir para tornar mais robusta a avaliação pré-cirúrgica realizada atualmente / Abstract: Epilepsy is a neurological disease that affects people worldwide, reaching about 1% of the world population. Approximately 30% of the patients do not respond well to treatment with medication. The surgical approach is an alternative recommended only when the epileptogenic region can be precisely localized. For this reason patients are subjected to various invasive and non-invasive assessments, including structural and functional neuroimaging exams. Simultaneous EEG-fMRI recordings originated from the combination of EEG, which has traditional use in epilepsy patients, with fMRI, a procedure increasingly applied to functional studies of the brain. This technique has been treated since its conception as a potential new non-invasive exam in the presurgical evaluation in epilepsy. Its inherent instrumental difficulties have been overcome more rapidly than the development of methods employed in the analysis and interpretation of the results. This is partly due to the complexity and diversity of causes of epilepsy, which affects the brain from the structural and functional standpoints, possibly disturbing it from genetic to macroscopic levels. In this work, we established a sequence of procedures for the acquisition and data analysis of EEG-fMRI, enabling the use of this technique as an additional exam in the presurgical evaluation. We created a computer program called SAfE (Straightforward Analysis of fMRI and EEG-fMRI), which allows straightforward and safe EEG-fMRI data analysis. After performing the EEG signal correction and identifying the epileptiform activity, fMRI statistical maps can be obtained through a simple graphical interface with little user input. An original form of describing the results was proposed and integrated in SAfE, in order to simultaneously examine the temporal and spatial aspects of the hemodynamic changes associated with the different types of epileptiform activity of each patient. Statistical maps are generated for different peak positions of the hemodynamic response and are then sequentially analyzed considering different parameters such as the maximum T value and the number of voxels above threshold. The approach proposed here for the EEG-fMRI data analysis suggests that the statistical maps of the patients should preferably be examined individually, because important information can be lost when the results are combined in group analyses. The obtained results reveal the high complexity of the mechanisms that generate epileptiform activity, because the brain networks involved show an elevated degree of heterogeneity among patients and among the different types of epileptiform activity. Possibly local and remote systems interact in such a way to cause chronic changes that affect the spread of the seizure and epileptiform activity. The EEG-fMRI technique has shown to be an application with promising clinical value, but requires validation via comparison with more established procedures. Although the benefits of this technique are limited in patients whose epileptiform activity is difficult to detect, its development is expected to make the current presurgical evaluation more robust / Doutorado / Física / Doutor em Ciências