This thesis presents methods for quantitative MRI analysis of brain injury, repair and degeneration in multiple sclerosis (MS) that provide new insights into disease pathogenesis and evolution. / Demyelinated and inflammatory white-matter lesions are hallmark features of MS. A methodology is described to detect regions of acute white-matter lesions that undergo myelin destruction and repair based on analysis of magnetization transfer ratio (MTR) images. Validation is performed based on histopathology and error is assessed based on same-day scans. To quantify the spatial extent and temporal evolution of myelin destruction and repair, data from a 3-year clinical trial is analyzed using this method. Approximately 20% of acute lesion voxels show some repair over the initial 7 months. In subsequent months, there is little further repair, but some increases in the lesion volume undergoing demyelination. / Although less conspicuous on conventional MRI, there is considerable MS pathology in the brain tissue outside of white-matter lesions. An image-processing methodology was developed to obtain accurate metrics that quantify change over time in whole-brain MTR (associated with changes in myelin-density) and in T2 relaxation time (associated with changes in inflammatory edema). These metrics, in addition to metrics of brain atrophy and axonal integrity, were used to quantify brain injury and degeneration following immunoablation and autologous hematopoietic stem cell transplantation therapy for MS. Pronounced brain volume loss was detected immediately following therapy, associated with decreased myelin density and not resolution of edema. / Post-mortem histopathology has revealed abnormalities in the cortical grey-matter of MS patients that appear to be independent of white-matter lesions. A methodology to quantify neocortical injury and degeneration that yields cross-sectional and longitudinal metrics of cortical thickness and grey-matter/white-matter interface integrity both globally and regionally is presented and validated. MS patients with progressive disability showed greater decreases in cortical metrics compared to MS patients with stable disability. / The quantitative MRI analysis methods presented in this thesis are applicable to MRI data obtained in clinical trials of therapies for MS, have the necessary sensitivity and specificity to assess therapeutic efficacy, and provide new insights into disease pathogenesis and evolution.

This study was designed to clarify some of the issues surrounding the nature of hemispheric contributions to the processing of emotional and linguistic prosody, as well as to examine the relative contribution of different sensory modalities in processing prosodic structures. Ten healthy young participants were presented with semantically neutral sentences expressing affective or linguistic prosody solely through the use of non-verbal cues (intonation, facial expressions) while undergoing tMRI. The sentences were presented under auditory, visual, as well as audio-visual conditions. The emotional prosody task required participants to identify the emotion of the utterance (happy or angry) and the linguistic prosody task required participants to identify the type of utterance (question or statement). Core peri-sylvian, frontal and occipital areas were activated bilaterally in all conditions suggesting that processing of affective and linguistic prosodic structures is supported by overlapping networks. The strength of these activations may, in part, be modulated by task and modality of presentation.

Brain atrophy has been used as a marker for disease progression in Multiple Sclerosis (MS). SIENA, an automated tool for measuring brain volume change, was tested to see whether MRI slice thickness and gap presence affect longitudinal atrophy measures. Isotropic global scan-rescan images were used to simulate 3 mm and 5 mm axial slice thicknesses with 1 and 2mm gaps, respectively. SIENA remained accurate and precise with increasing slice thickness and gap presence. Furthermore, symmetric pre-registration was crucial for scans with larger slice-thickness and gaps. / SIENA was used to observe atrophy in children who have experienced a Clinically Isolated Syndrome (CIS) of the type leading to MS (CIS-MS). Brain atrophy was present within the first three months after a CIS event, and then subsided over the rest of the year. If the first acute episode was excluded, there was no significant difference in atrophy rates between the CIS-MS group and the CIS group, and no significant difference between those with T2-weighted brain lesions versus those who had none.

As doenças cardiovasculares permanecem como principal causa de mortalidade entre mulheres de vários países, entre eles, o Brasil. A doença arterial coronária ocorre duas a três vezes mais nas mulheres na pós-menopausa que na pré-menopausa, fato possivelmente explicado pela proteção estrogênica. A estratificação de risco pelos escores tradicionais, como o de Framingham, muitas vezes, apresenta-se falha, havendo constante busca por métodos auxiliares (clínicos, laboratoriais ou de imagem) que ajudem na identificação precoce das mulheres mais predispostas a apresentar um evento cardiovascular. O objetivo principal deste estudo foi determinar a prevalência da aterosclerose subclínica em mulheres na pós-menopausa com risco baixo e intermediário pelo escore de risco de Framingham (ERF), avaliando, nas artérias coronárias, o escore de cálcio, na aorta, a presença de calcificação e, nas artérias carótidas, a espessura mediointimal (EMI), a presença de placas ateroscleróticas e a rigidez arterial pela velocidade de onda de pulso (VOP). Os objetivos secundários foram: 1. Avaliar a EMI e presença de placas na artéria subclávia direita, identificando sua correlação com dados clínicos e laboratoriais; e 2. Avaliar associação entre a expressão do mRNA dos genes TNFA, IL6, NOS3 e ESR1 com a presença de aterosclerose subclínica. Foram incluídas 138 mulheres na pós-menopausa. A idade média foi de 56,15 ± 4,93 anos, tempo médio de pós-menopausa foi 8,25 ± 5,97 anos, idade na menopausa, 48,08 ± 5,17 anos e o ERF foi de 2,64 ± 2,13% (mediana: 2%). A prevalência da EMI carotídea aumentada, placas nas carótidas, presença de EMI e/ou placas carotídeas, escore de cálcio maior que zero, calcificação aórtica (CA) e VOP elevada foi de 45,7%, 37,7%, 62,3%, 23,9%, 45,7% e 25,4% respectivamente; e 18,8% não apresentaram alteração em nenhum sítio avaliado. A presença de aterosclerose subclínica (presença de, pelo menos, um exame de imagem alterado) relacionou-se de forma independente com a idade (OR: 1,144; IC95%: 1,032 - 1,369; p=0,011), pressão arterial sistólica (PAS) (OR: 1,041; IC95%: 1,003 - 1,081; p=0,034) e ApoA1 (OR: 0,973; IC95%: 0,952-0,994; p=0,011). Os exames de imagem relacionaram-se entre si, com dados clínicos e laboratoriais. A prevalência de placas na artéria subclávia direita foi 38,4%. A EMI e a presença de placas na artéria subclávia direita relacionaram-se com a EMI e placas de carótidas, VOP, idade, ERF e PAS. A EMI da artéria subclávia relacionou-se também com a CA. A maior expressão mRNA do TNFA e do IL6 relacionou-se com a presença de aterosclerose subclínica, EMI carotídea aumentada e dislipidemia. Maior expressão do IL6 relacionou-se com a VOP. Houve correlação entre expressão do mRNA do NOS3 e EMI carotídea (r=0,20; p=0,01). Concluímos que a prevalência da aterosclerose subclínica foi de 81,2% nas mulheres na pós-menopausa com risco baixo e intermediário (ERF). A EMI e a presença de placas ateroscleróticas na artéria subclávia direita relacionaram-se com valores mais elevados da idade, ERF e PAS. Houve associação entre maior expressão do mRNA dos genes TNFA e IL6 com a presença de aterosclerose subclínica. A expressão do mRNA do gene NOS3 correlacionou-se positivamente com a EMI carotídea. / Cardiovascular diseases remain the leading cause of mortality among women in several countries, including Brazil. Coronary artery disease in women occurs two to three times more after menopause than in premenopausal and can be explained by estrogen protection. Risk stratification by traditional scores such as Framingham score, often presents itself fails; there is a constant search for methods (clinical, laboratory or imaging) that could help in early identification of women that are more predisposed to suffer a cardiovascular event. The aim of this study was to determine the prevalence of subclinical atherosclerosis in postmenopausal women with low and intermediate risk by Framingham risk score (FRS), evaluating calcium score in the coronaries arteries, presence of aortic calcification, carotid intima-media thickness (IMT) and/or presence of atherosclerotic plaque and arterial stiffness by pulse wave velocity (PWV). Other objectives were: 1. Evaluate the IMT and the presence of plaques in right subclavian artery, identifying its correlation with clinical and laboratory data. 2. Evaluate the association between mRNA expression of TNFA, IL6, NOS3 and ESR1 genes with the presence of subclinical atherosclerosis. We analyzed 138 postmenopausal women. The mean age was 56,15 ± 4,93 years, time of postmenopausal was 8,25 ± 5,97 years, age at menopause, 48,08 ± 5,17 years and the ERF was 2,64 ± 2,13 (median: 2). The prevalence of increased carotid IMT, carotid plaques, the presence of IMT and/or carotid plaques, calcium score greater than zero, aortic calcification (AC) and elevated PWV was 45,7%, 37,7%, 62,3%, 23,9%, 45,7% and 25,4%, respectively, 18,8 % did not exhibit any evidence of subclinical atherosclerosis. The presence of subclinical atherosclerosis (presence of at least one positive imaging test) was related by logistic regression with age (OR: 1,144, 95% CI: 1,032 to 1,369, p = 0,011), systolic blood pressure (SBP) (OR: 1,041, 95% CI: 1,003 to 1,081, p = 0,034) and ApoA1 (OR: 0,973, 95% CI: 0,952 to 0,994, p = 0,011). Imaging tests were related with each other, with clinical and laboratory data. The prevalence of plaques in the right subclavian artery was 38.4%. The IMT and presence of plaques in the right subclavian artery were related to carotid IMT and plaques, PWV, age, FRS and SBP. Higher values of TNFA and IL6 mRNA expression were related to the presence of subclinical atherosclerosis, dyslipidemia and increased carotid IMT. Higher IL6 mRNA expression was related to PWV. There was correlation between mRNA expression of NOS3 and carotid IMT (r = 0,20; p = 0,01). We conclude that the prevalence of subclinical atherosclerosis in postmenopausal women with low and intermediate risk was 81.2% (FRS). IMT and right subclavian artery atherosclerotic plaques were related to higher values of age, ERF and SBP. Higher mRNA gene expression of TNFA and IL6 were associated with the presence of subclinical atherosclerosis. There was a positive correlation between mRNA gene expression of NOS3 and carotid IMT.

The distinction between cavernous haemangiomas of the liver (which are the second most common hepatic mass lesions) from malignant lesions, is often difficult. An incorrect diagnosis of cavernous haemangioma, in a patient with malignancy, may adversely influence the outcome of subsequent treatment in these patients, due to delay in therapy. Although previous studies have suggested that ⁹⁹ᵐTc erythrocyte blood pool scintigraphy is both highly sensitive and specific for haemangiomas, a basic flaw in all previous studies has been the small number of control patients studied. Bayesian analysis clearly shows that specificity for a test is dependant on the pre-test probability of the lesion being present. Thus all the studies done to date, may reflect an inappropriately high specificity for ⁹⁹ᵐTc scintigraphy, in diagnosing cavernous haemangiomas, because they have mainly studied patients with haemangiomas and relatively few patients with other lesions. This study was thus undertaken to clarify the true accuracy of this technique, in distinguishing haemangiomas from other hepatic mass lesions, by studying a large number of patients with haemangiomas and other hepatic mass lesions.

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Foram avaliados 50 pacientes com esquizofrenia, através de escalas e de Ressonância magnética, feita também em 30 controles normais. Foi observado maior grau de comprometimento da crítica em pacientes não ocupados e que recebiam associação de antipsicóticos. Foi encontrada correlação positiva entre maior comprometimento da crítica e mais desorganização, excitação, hostilidade e total de sintomas negativos, além de correlação negativa com ansiedade, sentimento de culpa e depressão. Houve correlação entre comprometimento da crítica e diminuição do volume de substância cinzenta no giro lingual no lobo occipital, que não se manteve após correção para comparações múltiplas. Foi observada atrofia de substância cinzenta em área de 27 cm3 em insula, lobos frontal, temporal e parietal, nos pacientes com esquizofrenia / Fifth patients with schizophrenia were evaluated with psychopathological and insight scales and cerebral magnetic ressonance (made also on thirty normal controls). There was a greater insight impairment on unemployed patients and on these receiving two or more antipsychotics. There was a positive correlation between greater insight impairment and disorganization, excitation, hostility and total negative symptoms, besides a negative correlation with anxiety, guilt feelings, preoccupation and depression. Patients with less insight had a reduction of gray matter volume on the lingual gyrus, occipital lobe, that disappeared when correction for multiple comparisons was made. Schizophrenic patients had gray matter reduction in an 27 cm3 area in insula and frontal, temporal and parietal lobes