A ressonância magnética (RM) tem sido amplamente utilizada no diagnóstico por imagem de alterações de glândulas salivares. No entanto, a presença de aspectos similares nas imagens com técnicas convencionais de RM dificulta a distinção do diagnóstico entre patologias inflamatórias e neoplásicas. O objetivo deste estudo foi comparar valores dos coeficientes de difusão aparentes (ADC - Apparent Diffusion Coefficient) de imagem ponderada em difusão (DWI - Difusion Weighted Imaging) com ressonância magnética, entre glândulas salivares normais, casos com sialoadenite e com adenoma pleomórfico das glândulas salivares maiores. Vinte e dois pacientes (totalizando 44 glândulas salivares maiores) diagnosticados com sialoadenite unilateral (em glândula parótida ou submandibular) ou adenoma pleomórfico (apenas em parótida) foram selecionados. Todas as glândulas contralaterais não afetadas também foram analisadas. Imagens de RM ponderadas em T1, T2 e DWI foram obtidas utilizando sequências de pulso spin-eco (SE) com um aparelho de ressonância magnética de 1.5 Tesla. Primeiramente, a performance diagnóstica (sensitividade, especificidade e acurácia) foi calculada para três observadores após analisarem imagens de RM e DWI, separadamente. Em seguida, os valores médios de ADC foram comparados entre os três grupos analisados (glândulas normais contralateral, sialoadenite e adenoma pleomórfico). O uso da DWI rendeu uma melhor performance diagnóstica em geral para todos os observadores. Além disso, casos de adenoma pleomórfico apresentaram os maiores valores de ADC do estudo. Dentro das limitações deste estudo, os resultados sugerem que DWI permite a diferenciação entre sialoadenite e adenoma pleomórfico. / Alterations of the salivary glands are usually detected by conventional magnetic resonance imaging (MRI) techniques. However, their imaging presentation may present similar aspects. The aim of this study was to compare apparent diffusion coefficient (ADC) values from diffusion-weighted MRI (DWI) among normal salivary glands, cases with sialadenitis and with pleomorphic adenoma of major salivary glands. Twenty-two patients (totaling 44 major salivary glands) diagnosed with either unilateral sialadenitis (on either parotid or submandibular gland) or parotid gland pleomorphic adenoma were selected. Contralateral non-affected glands (normal) were also analyzed. DWI images were achieved using a spin-echo (SE) pulse sequence with a 1.5T MRI device. Mean ADC values were compared among the three groups analyzed (contralateral normal glands, sialadenitis and pleomorphic adenoma). Furthermore, diagnostic performance of MRI and DWI were calculated for three observers. DWI also presented better diagnostic performance results. In addition, cases of pleomorphic adenoma presented the highest ADC values of the study. Within the limitations of this study, the present results suggest that DWI allows for differentiation between parotid sialadenitis and pleomorphic adenoma.

Diffusion-weighted magnetic resonance imaging (dMRI) has been used to non-invasively investigate the integrity of white matter and the connectivity of the brain. In this work, high angular resolution diffusion imaging (HARDI), an advanced dMRI methodology was developed and employed in bonnet macaque monkeys to study the connectivity of the orbitofrontal cortex (OFC) and amygdala, two gray matter regions involved in making reward-guided decisions. With age, it is believed that there is a decline in the white matter connectivity between these two regions, also known as uncinate fasciculus (UF), and that this affects reward-value assignment and feedback learning in older adults. The analysis pipeline involved correction for distortions due to eddy currents and field inhomogeneity, noise reduction using a local principal component analysis based technique and subsequent registration to the high-resolution T1-weighted images. Gray matter regions corresponding to OFC and amygdala were identified on the T1-weighted images and probabilistic tractography was carried out to delineate the tracts belonging to UF. The output connectivity map from tractography was used to extract imaging parameters of interest such as fractional anisotropy, axial and radial diffusivity along the UF. A significant reduction in the fractional anisotropy index and the axial diffusivity index along the UF tract was observed with increased age of monkeys. Compared to the left hemisphere, stronger trends were observed in the right hemisphere of the monkeys, indicating possible laterality.

Chronic musculoskeletal pain is a leading cause of disability worldwide yet the mechanisms of chronification and neural responses to effective treatment remain elusive. Non-invasive imaging techniques are useful for investigating brain alterations associated with health and disease. Thus the overall goal of this dissertation was to investigate the white (WM) and grey matter (GM) structural differences in patients with musculoskeletal pain before and after psychotherapeutic intervention: cognitive behavioral therapy (CBT). To aid in the interpretation of clinical findings, we used a novel porcine model of low back pain-like pathophysiology and developed a post-mortem, in situ, neuroimaging approach to facilitate translational investigation. The first objective of this dissertation (Chapter 2) was to identify structural brain alterations in chronic pain patients compared to healthy controls. To achieve this, we examined GM volume and diffusivity as well as WM metrics of complexity, density, and connectivity. Consistent with the literature, we observed robust differences in GM volume across a number of brain regions in chronic pain patients, however, findings of increased GM volume in several regions are in contrast to previous reports. We also identified WM changes, with pain patients exhibiting reduced WM density in tracts that project to descending pain modulatory regions as well as increased connectivity to default mode network structures, and bidirectional alterations in complexity. These findings may reflect network level dysfunction in patients with chronic pain. The second aim (Chapter 3) was to investigate reversibility or neuroplasticity of structural alterations in the chronic pain brain following CBT compared to an active control group. Longitudinal evaluation was carried out at baseline, following 11-week intervention, and a four-month follow-up. Similarly, we conducted structural brain assessments including GM morphometry and WM complexity and connectivity. We did not observe GM volumetric or WM connectivity changes, but we did discover differences in WM complexity after therapy and at follow-up visits. To facilitate mechanistic investigation of pain related brain changes, we used a novel porcine model of low back pain-like pathophysiology (Chapter 6). This model replicates hallmarks of chronic pain, such as soft tissue injury and movement alteration. We also developed a novel protocol to perform translational post-mortem, in situ, neuroimaging in our porcine model to reproduce WM and GM findings observed in humans, followed by a unique perfusion and immersion fixation protocol to enable histological assessment (Chapter 4). In conclusion, our clinical data suggest robust structural brain alterations in patients with chronic pain as compared to healthy individuals and in response to therapeutic intervention. However, the mechanism of these brain changes remains unknown. Therefore, we propose to use a porcine model of musculoskeletal pain with a novel neuroimaging protocol to promote mechanistic investigation and expand our interpretation of clinical findings.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22735号 / 医博第4653号 / 新制||医||1046(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 羽賀 博典, 教授 伊達 洋至, 教授 万代 昌紀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The semester thesis describes the basic principles of MRI, methods for measuring diffusion coefficients and creating DWI and DTI images. As a result a practical implementation of program was implemented in Matlab, based on theoretical knowledge of the problem.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18128号 / 医博第3848号 / 新制||医||1001(附属図書館) / 30986 / 京都大学大学院医学研究科医学専攻 / (主査)教授 福山 秀直, 教授 戸井 雅和, 教授 平岡 眞寛 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19172号 / 医博第4014号 / 新制||医||1010(附属図書館) / 32164 / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 平岡 眞寛, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20232号 / 医博第4191号 / 新制||医||1019(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 戸井 雅和, 教授 武田 俊一, 教授 鈴木 実 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13218号 / 論医博第2165号 / 新制||医||1033(附属図書館) / 京都大学大学院医学研究科内科系専攻 / (主査)教授 溝脇 尚志, 教授 黒田 知宏, 教授 鈴木 実 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23567号 / 医博第4781号 / 新制||医||1054(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 花川 隆, 教授 永井 純正, 教授 渡邊 直樹 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM