"Magnetic resonance imaging (MRI) has increasingly become the preferred imaging modality in modern day research to study disease. MRI presents an imaging technique that is practically non-invasive and without any ionizing radiation. This dissertation presents the use of contrast agents in MRI studies to differentiate compartments, to study dose dependence of relaxation times, and to characterize tumors using signal amplifying enzymes in the brain. Differentiating compartments in the brain can be useful in diffusion studies to detect stroke at an early stage. Diffusion-weighted NMR techniques have established that the apparent diffusion coefficient (ADC) of cerebral tissue water decreases during ischemia. However, it is unclear whether the ADC change occurs due to changes in the intracellular (IC) space, extracellular (EC) space, or both. To better understand the mechanism of water ADC changes in response to ischemic injury, making IC and EC compartment specific measurements of water diffusion is essential. The first study was done where manganese (Mn2+) was used as an IC contrast agent. Mn2+ uptake by cells causes shortening of the T1 relaxation time of IC water. The relative difference in T1 relaxation times between the IC and EC compartments can be used to discriminate between the MR signals arising from water in the respective compartments. Mn2+ is also widely used in manganese-enhanced MRI (MEMRI) studies to visualize functional neural tracts and anatomy in the brain in vivo. In animal studies, the goal is to use a dose of Mn2+ that will maximize the contrast while minimizing its toxic effects. The goal of dose study was to investigate the MRI dose response of Mn2+ in rat brain following SC administration of Mn2+. The dose dependence and temporal dynamics of Mn2+ after SC injection can prove useful for longitudinal in vivo studies that require brain enhancement to persist for a long period of time to visualize neuroarchitecture like in neurodegenerative disease studies. Contrast agents, in addition to their use in compartmental differentiation and dose studies, can be used for imaging tumors. The last study in this dissertation focuses on imaging EGF receptors in brain tumors. We tested a novel pretargeting imaging approach that includes the administration of humanized monoclonal antibody (anti-EGFR mAb, EMD72000) linked to enzymes with complementing activities that use a low-molecular weight paramagnetic molecule (diTyr-GdDTPA) as a reducing substrate administered following the mAb conjugates. We analyzed the differential MR tumor signal decay in vivo using orthotopic models of human glioma. The patterns of MR signal change following substrate administration revealed differences in elimination patterns that allowed distinguishing between non-specific and specific modes of MR signal decay. "

Research applications of nuclear magnetic resonance (NMR) span a broad range of fields and disciplines. The work presented in this dissertation attests to this fact. Specifically, the research topics discussed in the body of this work employ NMR spectroscopy and imaging to characterize the water diffusion and NMR relaxation times ex vivo in rabbit Achilles tendon and, in a clinical setting, employ functional magnetic resonance imaging (fMRI) to investigate the behavior of different neural networks over a period of sustained activity. In the ex vivo rabbit Achilles tendon work, a series of studies were performed. First, the diffusion-time dependence of the water apparent diffusion coefficient (ADC) was characterized in a spectroscopic mode with the samples subjected to different states of tensile loading. The results of this study demonstrated: (1) the anisotropy of the diffusion of water through tendon; (2) the ADC is diffusion-time dependent; (3) the values of the ADC(tdif) curve increased with tensile loading; (4) a change at the short diffusion-time points that is consistent with the interpretation of a load-induced increase in the collagen fibril packing density; and (5) an increase in the water ADC at long diffusion times is hypothesized to be due to T1 editing. To further investigate these issues, another series of ex vivo rabbit Achilles tendon experiments was performed that employed NMR imaging to spatially characterize the water ADC, T1 and T2 relaxation time constants. As with the spectroscopic work, these studies were also conducted with the tendon samples subjected to different states of tensile loading. The results from these imaging experiments demonstrate: (1) two regions with distinct differences in signal intensity across the tendon: a thin region of high signal intensity at the peripheral rim of the tendon that encircles a region of low signal intensity in the central core of the tendon; (2) a higher diffusion anisotropy ratio in the tendon central core relative to the peripheral rim; (3) upon tensile loading, significant increases in the ADC of water in the peripheral rim region and a corresponding increase in a measure of the change in proton density in the rim region, consistent with the hypothesis that tensile loading causes extrusion of water from the core to the rim region of the tendon; (4) this water extrusion is not uniformly distributed throughout the tendon rim region; and (5) the long-diffusion-time ADC behavior is consistent with the T1 spin editing hypothesis of the spectroscopic work. From the clinical fMRI studies, an analysis method was presented for observing dynamic changes in brain regions involved in different neural network processes during a period of sustained activity. The results from these studies are consistent with the idea that over time, brain regions adapt to the given task demands through either recruitment or discharge of adjacent areas of tissue. These results also indicate that traditional analysis of block design fMRI studies may underestimate dynamic changes in brain regions during a sustained task. The analysis method may be useful as an exploratory tool to observe region specific variations in activation that may allow inferences to be made regarding how different brain regions adapt to and interact with one another during periods of extended activity.

The evaluation of the remodeling of soft biomaterial implants often involves surgical removal of the implant for subsequent histological assessment. This approach is very resource intensive, often destructive, and imposes practical limitations on how effectively these materials can be evaluated. Magnetic resonance imaging (MRI) has the potential to non-invasively monitor the remodeling of collagen sponges, specifically the biodegradation, cellular infiltration, extracellular matrix deposition and angiogenesis within the sponge. This project involves the development of an in vivo model system for the evaluation of collagen-sponge remodeling using MRI and conventional histological techniques. Collagen sponges made using insoluble bovine collagen, and subjected various crosslinking treatments, were implanted subcutaneously into rats. Changes in water T2 relaxations times, water apparent diffusion coefficients (ADC), and MRI contrast agent uptake/washout were collected using spin-echo and diffusion-weighted MRI pulse sequences. These measurements were compared with histological assessments of sponge remodeling. Regions of differential cellularity were distinguished using calculated T2 maps and confirmed by histology. Calculated ADC maps corroborated these results and showed a decreasing trend with increased tissue in-growth. Results from MRI-contrast-agent studies were consistent with the development of angiogenesis within the sponge over time. The MRI approach allows for longitudinal studies that significantly reduce the resources required to evaluate these materials as well as improves the quality of the statistical information obtained from these studies.

A common approach to segment an MRI dataset is to use a standard atlas to identify different regions of interest. Existing 2D atlases, prepared by freehand tracings of templates, are seldom complete for 3D volume segmentation. Although many of these atlases are prepared in graphics packages like Adobe Illustrator® (AI), which present the geometrical entities based on their mathematical description, the drawings are not numerically robust. This work presents an automatic conversion of graphical atlases suitable for further usage such as creation of a segmented 3D numerical atlas. The system begins with DXF (Drawing Exchange Format) files of individual atlas drawings. The drawing entities are mostly in cubic spline format. Each segment of the spline is reduced to polylines, which reduces the complexity of data. The system merges overlapping nodes and polylines to make the database of the drawing numerically integrated, i.e. each location within the drawing is referred by only one point, each line is uniquely defined by only two nodes, etc. Numerous integrity diagnostics are performed to eliminate duplicate or overlapping lines, extraneous markers, open-ended loops, etc. Numerically intact closed loops are formed using atlas labels as seed points. These loops specify the boundary and tissue type for each area. The final results preserve the original atlas with its 1272 different neuroanatomical regions which are complete, non-overlapping, contiguous sub-areas whose boundaries are composed of unique polylines

Collagen implants are widely used in clinical practice and are an active area of research. The continued development of collagen-based implants often relies on histological techniques to fully evaluate the host response post implantation. These destructive, end-point analyses limit the rate that data can be obtained from samples. Magnetic resonance imaging has the potential to non-invasively monitor the remodeling of collagen scaffolds. In this study, scaffolds prepared from insoluble bovine collagen, with varied and predictable tissue responses were implanted in rats and evaluated using both histological and MRI techniques. Treatment of scaffolds with a carbodiimide crosslinker was found to slow the degradation and cellular infiltration into the scaffolds compared to uncrosslinked scaffolds. Angiogenesis was observed in core regions of crosslinked scaffolds, but not uncrosslinked scaffolds. Conjugation of chondroitin sulfate to the collagen scaffolds in combination with crosslinking improved both the cellular infiltration and angiogenesis compared to uncrosslinked and crosslinked scaffolds. Correlations between histology and MRI analyses showed that statistically significant relationships existed between cellular density, void area, T2 and apparent diffusion coefficient (ADC) measurements demonstrating that MRI is sensitive to specific remodeling parameters. Understanding the relationship between histology and MRI parameters may be used to help guide the interpretation of MRI data as well as to reliably detect changes within the implants using the MRI data alone, reducing the need for scaffold harvesting and destructive testing.

Resumo: 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... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: 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) / Orientador: Gilberto Uemura / Coorientador: René Aloísio da Costa Vieira / Banca: José Ricardo Paciência / Banca: Alfredo Barros / Banca: Selma Bauab / Banca: Maria Aparecida Azevedo Koike Folgueira / Doutor

With conventional oil reserves in decline, energy companies are increasingly turning to enhanced oil recovery (EOR) processes to extend the productive life of oilfield wells. Laboratory-scale core floods, in which one fluid displaces another from the pore space of a rock core, are widely used in petroleum research for oilfield evaluation and screening EOR processes. Achieving both macro- and pore-scale understandings of such fluid displacement processes is central to being able to optimise EOR strategies. Many of the mechanisms at play, however, are still poorly understood. In this thesis nuclear magnetic resonance (NMR) has been used for quantitatively, non-invasively and dynamically studying laboratory core floods at reservoir-representative conditions. Spatially-resolved relaxation time measurements (L-T1-T2) have been applied to studying a special core analysis laboratory (SCAL) protocol, used for simulating reservoir oil saturations following initial oil migration (primary drainage) and characterising core samples (capillary pressure curves). Axial heterogeneities in pore filling processes were revealed. It was demonstrated that upon approaching irreducible water saturation, brine saturation was reduced to a continuous water-wetting film throughout the pore space; further hydrocarbon injection resulted in pore pressure rise and wetting film thinning. L-T1-T2 techniques were also applied to a xanthan gum polymer-EOR flood in a sandstone core, providing a continuous measurement of core saturation and pore filling behaviours. A total recovery of 56.1% of the original oil in place (OOIP) was achieved, of which 4.9% was from xanthan. It was demonstrated that deposition of xanthan debris in small pores resulted in small-pore blocking, diverting brine to larger pores, enabling greater oil displacement therein. L-T1-T2, spectral and pulsed field gradient (PFG) approaches were applied to a hydrolysed polyacrylamide (HPAM)-EOR flood in a sandstone core. A total recovery of 62.4% of OOIP was achieved, of which 4.3% was from HPAM. Continued brine injection following conventional recovery (waterflooding) and EOR procedures demonstrated most moveable fluid saturation pertained to brine, with a small fraction to hydrocarbon. Increases in residual oil ganglia size was demonstrated following HPAM-EOR, suggesting HPAM encourages ganglia coalescence, supporting the "oil thread/column stabilisation" mechanism proposed in the literature. NMR relaxometry techniques used for assessing surface interaction strengths (T1/T¬2) were benchmarked against an industry-standard SCAL wettability measurement (Amott-Harvey) on a water-wet sandstone at magnetic field strengths comparable to reservoir well-logging tools (WLTs). At 2 MHz, T1/T2 was demonstrated to be weakly sensitive to the core wettability, although yielded wettability information at premature stages of the Amott-Harvey cycle. This suggests the potential for NMR to deliver faster wettability measurements, in SCAL applications or downhole WLT in situ reservoir characterisation.

Os métodos minimamente invasivos têm sido cada vez mais utilizados para o tratamento do leiomioma e, a embolização da artéria uterina, tem se destacado como método seguro e efetivo. O objetivo deste estudo foi avaliar, pela ressonância magnética da pelve, os fatores preditores da diminuição dos leiomiomas de pacientes submetidos a embolização da artéria uterina. Métodos: Estudaram-se 50 mulheres sintomáticas com leiomioma uterino, na menacme, que foram submetidas a embolização da artéria uterina. Acompanhou-se, por meio da ressonância magnética o volume do útero e dos leiomiomas. Foram examinados 179 leiomiomas nestas pacientes, um mês antes e seis meses depois do procedimento. Resultados: Seis meses após o tratamento, a redução média do volume uterino foi de 38,91%, enquanto os leiomiomas tiveram redução de 55,23%. Nos leiomiomas submucosos e/ou com a relação nódulo/músculo em T2 mais elevada, a redução do volume foi ainda maior (maior que 50,00%). Conclusões: As pacientes portadoras de leiomiomas e submetidas à embolização da artéria uterina apresentaram redução de volume dos nódulos superior a 50,00%, à ressonância magnética, quando eram submucosos e/ou tinham uma relação nódulo/músculo em T2 mais elevada / Objective : Minimally invasive methods are being an alternative to treat leiomyomas, including the uterine artery embolization that has emerged as a safe and effective method. The aim of this study was to evaluate the magnetic resonance imaging predictors of decrease in leiomyomas of patients who underwent uterine artery embolization. Methods: This study followed 50 symptomatic premenopausal women with uterine leiomyoma who underwent uterine artery embolization. Treatment was accompanied by magnetic resonance imaging of both the volume of the uterus and the leiomyomas. We examined 179 leiomyomas in that 50 patients, one month before and six months after of the procedure. Results: Six months after treatment, the mean reduction in uterine was 38.91%, while leiomyomas decreased by 55.23%. In submucosal leiomyomas and/or with a higher node/muscle ratio in T2, the volume reduction was even higher (greater than 50.00%). Conclusions: The patients with leiomyomas and underwent uterine artery embolization, showed reductions in the volume of nodes greater than 50,00%, on the magnetic resonance imaging, when they were submucosal and / or had a higher node-to-muscle ratio in T2

A imagem por ressonância magnética (IRM) é a primeira escolha como ferramenta complementar no diagnóstico das anormalidades dos tecidos moles da articulação temporomandibular (ATM). No entanto, a literatura tem mostrado baixa reprodutibilidade na interpretação deste exame. Neste estudo foi desenvolvido e testado um Objeto Digital de Aprendizagem (ODA) para potencializar as habilidades do profissional na interpretação da ATM avaliada em IRM para ser utilizado tanto no ensino da graduação como na educação continuada dos profissionais da área da saúde. O ODA é composto por sessões, nas quais o usuário estuda o conteúdo, interage com o aplicativo, e interpreta imagens digitais das ressonâncias magnéticas da ATM. Os diagnósticos realizados pelo usuário são conferidos automaticamente com aqueles previamente estabelecidos por concordância entre três profissionais especialistas. Após a validação do conteúdo, o ODA foi testado com alunos do curso de graduação da Faculdade de Odontologia da Universidade Federal do Rio Grande do Sul, separados em dois grupos: teste (aprendizagem interativa) e controle (aprendizagem convencional) A eficácia do uso do objeto de aprendizagem foi observada por meio de prova objetiva. Os resultados mostraram diferença significativa entre os grupos, tendo o grupo controle apresentado melhor desempenho. No entanto, quando comparadas com as avaliações iniciais, verificou-se que os dois grupos melhoraram seus desempenhos significativamente. Desta forma, levando em consideração os resultados e a complexidade do assunto, devese pensar em trabalhar o ODA juntamente com a presença de um professor ou tutor, isto é, utilizando um sistema de formação misto, também chamado de blended learning. A usabilidade (efetividade, eficiência e satisfação) do ODA foi avaliada pelos usuários por meio de um questionário estruturado baseado no System Usability Scale (SUS) e atingiu o escore 89, considerado excelente. / Magnetic resonance imaging (MRI) is the first choice as complementary tool in the diagnosis of abnormalities in soft tissues of the temporomandibular joint (TMJ). In spite of that, current literature reports poor reproducibility in the interpretation of results this tool generates. The present study describes the development and testing of a Digital Learning Object (DLO) as a system to improve MRI interpretation capabilities concerning TMJ dysfunctions, applicable both in the teaching of undergraduate students and in extension education of health professionals. The DLO developed is divided in sections where the user studies the content, interacts with the application, and interprets digital MRI of the TMJ. The diagnoses made by users are automatically checked against previous diagnoses established in agreement by three specialist professionals. After validation of the content, the DLO was tested by undergraduate dentistry students of the Federal University of Rio Grande do Sul, divided in two groups, test group (interactive learning), and control group (conventional learning). The efficacy of the DLO was assessed by an objective test. The results revealed a significant difference between groups, and showed that the control group performed better. Yet, when results are compared with baseline evaluations (before application of the DLO), it was observed that the two groups improved significantly performance. In this sense, considering the results and the complexity of the subject, the DLO should be applied under the supervision of a professor or instructor, that is, following a mixed training system, also called blended learning. The applicability (efficacy, efficiency and satisfaction) of DLO was assessed by users according to a structured questionnaire based on the System Usability Scale (SUS), reaching score 89, considered excellent.

Magnetic resonance imaging (MRI) has transformed the world of non-invasive imaging for diagnostic purposes. Modern techniques such as diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), and diffusion spectrum imaging (DSI) have been used to reconstruct fiber pathways of the brain - providing a graphical picture of the so-called "connectome." However, there exists controversy in the literature as to the accuracy of the diffusion tractography reconstruction. Although various attempts at histological validation been attempted, there is still no 3D histological pathway validation of the fiber bundle trajectories seen in diffusion MRI. Such a validation is necessary in order to show the viability of current DSI tractography techniques in the ultimate goal for clinical diagnostic application. This project developed methods to provide this 3D histological validation using the rhesus monkey motor pathway as a model system. By injecting biotinylated dextran amine (BDA) tract tracer into the hand area of primary motor cortex, brain section images were reconstructed to create 3D fiber pathways labeled at the axonal level. Using serial coronal brain sections, the BDA label was digitized with a high resolution digital camera to create image montages of the fiber pathway with individual sections spaced at 1200 micron intervals through the brain. An MRI analysis system, OSIRX, was then used to reconstruct these sections into a 3D volume. This is an important technical step toward merging the BDA fiber tract histology with diffusion MRI tractography of the same brain, enabling identification of the valid and inaccurate aspects of diffusion fiber reconstruction. This will ultimately facilitate the use of diffusion MRI to quantify tractography, non-invasively and in vivo, in the human brain.