Structural and diffusion imaging patterns that can be evaluated using MRI in patients with cognitive deficits are the central theme of the proposed work. First, the clinical and neuroimaging background of dementias has been reviewed in a broader context, with a special focus on Alzheimer's disease (AD) and differential diagnoses. The second part of this thesis contains four consecutive experimental studies. The primary objective of the first two studies was to obtain structural and microstructural information on the neurodegenerative processes characteristic for AD on global and regional levels. For this purpose, several complementary approaches were used and the focus was shifted from grey to white matter (GM/WM). The following two studies focused on the differential context of WM microstructural alterations in normal pressure hydrocephalus (NPH) and distinctive patterns of WM disintegrity in temporal lobe epilepsy (TLE). The most important conclusion of our studies is that structural and diffusion imaging proved to be useful in identifying regionally specific and disproportionate loss of brain volume and microstructure in several pathological processes underlying cognitive deterioration. The use of distinctive morphometric methods yielded complementary information on AD-related atrophy patterns,...

A significant subset of women plagued with breast cancer continue to experience chronic neuropathic pain (CNP) long after undergoing cancer treatment. Medical interventions such as pharmacotherapy and/or surgery have been most widely used to abate painful symptoms with limited efficacy. Other alternatives are required given a heavy reliance on pharmaceuticals can lead to tolerance, dependence and severe side effects. Possibilities include cognitive behavioural therapy (CBT), physical therapy, and mindfulness interventions to supplement pharmacotherapies. Mindfulness practice in particular has been offered to a variety of chronic pain groups including breast cancer patients, however evidence is lacking to support its effectiveness in CNP for breast cancer survivors (BCS). The purpose of the present study was to explore the benefits a mindfulness-based stress reduction program (MBSR) may have on altering the underlying neuronal correlates linked with pain-related symptoms associated with CNP in BCS. The primary objective was to investigate how mindfulness training might possibly mediate the brain’s capacity for emotional reactivity, white matter integrity, and activation of the default mode network (DMN) and how these changes may correlate with levels of pain severity and pain interference, improving overall quality of life. To achieve these results, several brain imaging techniques were used in order to observe the correlation between the subjective experience of pain and the objective manifestation of brain changes that may be potentiated by MBSR training. A total of 23 participants were placed in either an 8 week MBSR intervention group (n=13) or a waitlist control group (n =10). All women were scanned with MRI before and after the 8 week intervention regardless of group allotment. The following neuroimaging modalities were used for each scanning session: resting state fMRI (rsfMRI) to monitor changes to functional connectivity in the default mode network (DMN); Diffusion Tensor Imaging (DTI) to assess the structural integrity of white matter tracts; and the Emotional Stroop Task (EST) to examine emotional reactivity in response to pain related stimuli. Exploratory results from this pilot study indicate that improvements to functional connectivity were apparent in the MBSR group relative to control, indicative of more efficient communication in areas related to attention, self-awareness, emotion regulation and pain. Improvements were also noted as increased cerebral white matter health and reduced emotional reactivity to pain related stimuli in the group of MBSR trained participants relative to control. Additionally, these functional and structural changes correlated with the self-reported pain measures in the MBSR group, suggesting that the MBSR group demonstrated improvements to ratings of pain severity and pain interference whereas the opposite occurred with the control group. The results have been interpreted as improvements to patients’ perception of pain and quality of life post MBSR training, however, were not limited to the subjective experience of pain. The inclusion of neuroimaging modalities provides objective and empirical support for MBSR training as it highlights the underlying brain mechanisms that were altered as part of MBSR treatment. Ultimately, the evidence suggests that MBSR could be incorporated as part of the treatment protocol for women experiencing CNP post breast cancer treatment.

<p>An objective measure of muscular low back pain (LBP) symptoms eludes clinicians. This study assessed efficacy of magnetic resonance imaging (MRI) of the lumbar multifidus using diffusion tensor imaging (DTI), blood oxygen level dependent (BOLD) signal fractal dimension (FD) analysis and muscle cross sectional area (CSA) in LBP assessment. MRI results were compared to two questionnaires, the Oswestry disability index (ODI) and visual analog score (VAS).</p> <p>Right-left asymmetry in both DTI metrics and T2-weighted (T2W) CSA were greater in the injured. Also, asymmetry measures were correlated with body mass index (BMI) but not age, height, or level of physical activity (measured via Godin activity questionnaire). The relationship between asymmetry and LBP symptoms in T2W and DTI scans increased for subjects with BMI below 35kg/m².</p> <p>BOLD FD did not scale with LBP symptoms. However, FD analysis showed promise following therapeutic Swedish massage, hypothesized as being related to local perfusion changes, indicating that FD is sensitive to changes in the lumbar muscle, just not LBP symptoms. Thus the BOLD FD does change with treatment, just not with the symptoms of LBP.</p> <p>When combining data from multiple scan types, the symptoms of LBP correlated best with the unweighted mean of DTI fractional anisotropy (FA) and T2W CSA asymmetry, and the correlation was greatest (R²=0.88) when only <em>symptomatic (not both symptomatic and control)</em> subjects with BMIs from 18-25kg/m² were considered. From these results there appears to be clinical utility in characterizing the symptoms of non-acute LBP using DTI and CSA.</p> / Doctor of Philosophy (PhD)

L’IRM de diffusion (IRMd) est l’unique technique non invasive qui permet l’exploration de la microstructure cérébrale. En plus d’une large utilisation pour les applications médicales, l’IRMd est aussi utilisée en neuroscience pour comprendre l’organisation et le fonctionnement du cerveau. Toutefois, sa faible résolution spatiale et sa sensibilité aux artéfacts limitent son utilisation chez le primate non humain.L’objectif de cette étude est de développer une nouvelle approche qui permette d’acquérir des données d’IRMd à très haute résolution spatiale sur des cerveaux de macaques anesthésiés. Cette méthode est basée sur un balayage 3D de l’espace de Fourier avec un module de lecture d’Echo Planar-segmenté.Cette méthode a été tout d’abord implémentée sur une machine IRM 3 Tesla (Prisma, Siemens), puis validée et optimisée in-vitro et in-vivo. Par rapport à la méthode d’acquisition classique, un gain de sensibilité de l’ordre de 3 pour la substance grise cérébrale et de 4.7 pour la substance blanche cérébrale a été obtenu grâce à la méthode développée.Cette méthode a permis de réaliser l’IRMd du cerveau de Macaque avec une résolution spatiale isotrope de 0.5 mm jamais atteinte auparavant. L’intérêt de réaliser des données d’IRMd à une telle résolution pour visualiser et analyser in-vivo des structures fines non détectables avec la méthode d’acquisition classique comme les sous-champs de l’hippocampe ou encore la substance blanche superficielle, a été démontré dans cette étude. Des résultats préliminaires très encourageants ont également été obtenus chez l’homme / Diffusion MRI (dMRI) is the unique non-invasive technique that allows exploring the cerebral microstructure. Besides a wide use for medical applications, dMRI is also employed in neuroscience to understand the brain organization and connectivity. However, the low spatial resolution and the sensitivity to artefacts limit its application to non-human primates.This work aims to develop a new approach that allows to acquire dMRI at very high spatial resolution on anesthetized macaque brains. This method is based on a 3D sampling of Fourier space with a segmented Echo Planar imaging readout module. This method has been firstly implemented on a 3 Tesla MR scanner (Prisma, Siemens), validated and optimized in-vitro and in-vivo. Compared to the conventional acquisition method, a gain of sensitivity of 3 for the cerebral grey matter and of 4.7 for the white matter was obtained with the proposed approach.This method allowed us to acquire dMRI data on the macaque brain with a spatial isotropic resolution of 0.5 mm ever reached before. The interest to acquire dMRI data with such a spatial resolution to visualize and analyze in-vivo fine structures not detectable with the classical acquisition method, like the sub-fields of hippocampus and the superficial white matter, has also illustrated in this study. Finally, very encouraging preliminary results were also obtained in humans

Dans la pratique du rugby à XV, l’intégrité de la moelle épinière (ME) est menacée par les rares macro-traumatismes du rachis cervical, et par les chargements répétitifs entrainant l’apparition de pathologies dégénératives. Comment quantifier ces altérations, quels sont les mécanismes qui les président ?Pour aborder ces questions, la faisabilité et l’intérêt d’un protocole IRM multiparamétrique en contexte dégénératif ont tout d’abord été investigués. Puis, une récente technique de relaxométrie T1 3D et une acquisition ihMT multi-coupes à multiples orientations permettant d’évaluer le contenu macromoléculaire des tissus, en particulier la myéline, ont été développées pour évaluer le caractère diffus des altérations. Préliminairement appliqué sur quelques joueurs, ce protocole a ainsi démontré la faisabilité d’une exploration approfondie par IRM multiparamétrique de la ME cervicale dans le rugby.En complément de cela, une étude préliminaire utilisant un modèle éléments finis (MEF) détaillé a été menée pour évaluer la réponse mécanique des sous-régions de la ME soumises à des chargements mécaniques primaires. Par la suite, une étude préliminaire des risques neurologiques liés à un canal vertébral étroit (observé chez certains joueurs) a été conduite en modifiant la géométrie du MEF. A l’interface entre l’IRM et la biomécanique, ces travaux préliminaires ont posé les premiers jalons pour une caractérisation fine et robuste des altérations tissulaires au niveau médullaire dans le rugby. A terme, cette approche permettrait de proposer de nouveaux éléments pour une éventuelle amélioration du bilan d’aptitude des joueurs et de proposer des programmes préventifs améliorés. / In Rugby Union practice, the cervical spinal cord (CSC) could be involved in rare cervical spine (CS) traumatic injuries and also be threatened by the neck exposure to repetitive impacts assumed to induce early degenerative tissue alterations. How to quantify these impairments? What are the underlying pathophysiological mechanisms? To answer these questions, efforts were first directed towards the investigative potential of an advanced multiparametric Magnetic Resonance Imaging (MRI) protocol in degenerative contexts. Then, a new MRI protocol covering the whole CSC, including a recent 3D T1 relaxometry technique and a multi-slice multi-angle ihMT acquisition evaluating tissue myelin-content, was optimized. Preliminarily-applied to few players, this new optimized protocol showed the feasibility of a fine and diffuse CSC characterization in rugby. In parallel and as a complement, preliminary finite element modelling (FEM) analyses were also conducted to evaluate the mechanical responses of CSC sub-regions under primary loading mechanisms. Then, the same loading mechanisms were applied to a geometrically-modified FEM reproducing a narrow vertebral canal, reported to occur in some players therefore allowing to evaluate the effect of rugby-related CS degenerative changes on the CSC mechanical response under traumatic loadings. These preliminary, interdisciplinary and complementary works lay the ground for a fine structural and mechanical characterization of CSC tissues in rugby players, which would eventually allow to propose improved aptitude-to-play evaluation criteria as well as improved preventive programs.

Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI)-based technique that has frequently been used for the identification of brain biomarkers of neurodevelopmental and neurodegenerative disorders because of its ability to assess the structural organization of brain tissue. In this work, I present (1) preclinical findings of a longitudinal DTI study that investigated asymptomatic high school football athletes who experienced repetitive head impact and (2) an automated pipeline for assessing the quality of DTI images that uses a convolutional neural network (CNN) and transfer learning. The first section addresses the effects of repetitive subconcussive head trauma on the white matter of adolescent brains. Significant concerns exist regarding sub-concussive injury in football since many studies have reported that repetitive blows to the head may change the microstructure of white matter. This is more problematic in youth-aged athletes whose white matter is still developing. Using DTI and head impact monitoring sensors, regions of significantly altered white matter were identified and within-season effects of impact exposure were characterized by identifying the volume of regions showing significant changes for each individual. The second section presents a novel pipeline for DTI quality control (QC). The complex nature and long acquisition time associated with DTI make it susceptible to artifacts that often result in inferior diagnostic image quality. We propose an automated QC algorithm based on a deep convolutional neural network (DCNN). Adaptation of transfer learning makes it possible to train a DCNN with a relatively small dataset in a short time. The QA algorithm detects not only motion- or gradient-related artifacts, but also various erroneous acquisitions, including images with regional signal loss or those that have been incorrectly imaged or reconstructed.

Made available in DSpace on 2016-01-26T12:51:31Z (GMT). No. of bitstreams: 1 joserobertolopesferrazfilho_tese.pdf: 1409103 bytes, checksum: de6715f2f3059b0c5617f571b89bfdbd (MD5) Previous issue date: 2011-10-21 / Neurofibromatosis type 1 (NF1) in children and adolescents is frequently associated with the appearance of focal lesion hyperintensities on T2-weighted images seen in the brain which are called Unidentified Bright Objects (UBOs). These lesions are not an accepted criterion in the diagnosis of NF1 and the exact nature of UBOs remains unclear. Objectives: article 1: This study employed diffusion tensor imaging (DTI) to evaluate the relation among fractional anisotropy (FA) patterns with the findings of T2 sequences in individuals with NF1; article 2: To evaluate the evolution of UBOs in individuals with NF1 by serial MRI, and to relate this to regional fractional anisotropy (FA); article 3: To evaluate the metabolic patterns by magnetic resonance spectroscopy (MRS) of the brain, in the presence of UBOS in patients with NF1. Methods: article 1: Forty-four individuals with NF1 and 20 control subjects were evaluated. The comparative analysis of FA between NF1 and control groups was based on four pre-determined anatomic regions of the brain and related to the presence or absence of UBOs; article 2: The signal pattern of the T2-weighted sequences in the basal ganglia, thalamus, brain stem, and cerebellum for 27 NF1 individuals and a control group were analyzed by DTI. The presence or absence of UBOs in 2 consecutive MRI examinations were related to FA. article 3: Forty-two individuals with NF1 and 25 control subjects were evaluated by examination of ERM univoxel placed in the region of the globus pallidus. Automated quantitative analysis was made of the relationship of the metabolites choline/creatine (Co / Cr), N-acetyl aspartate/creatine (NAA / Cr) and myoinositol/creatine (MI / Cr) and related to the occurrence of UBOS in region of the globus pallidus. Results: article 1: The FA values between the groups demonstrated statistically significant differences (p &#8804; 0.05) for the cerebellum and thalamus in NF1 patients, independent of the occurrence of UBOs; article 2: We demonstrated statistically significant differences in FA for the basal ganglia, cerebellum, and thalamus between NF1 patients and controls (P &#8804; 0.05), even with a reduction or disappearance of UBOs; article 3: We demonstrated statistically significant differences between of patients with NF1 and control groups as the average values Mi/Cr and Co/Cr (P<0.05) in the region of the globus pallidus. Conclusions: article 1: MR imaging using DTI technique suggests that UBOs are due to microstructural defect of the brain tissue in NF1 patients. article 2: MRI allows for adequate monitoring of the temporal and spatial distribution of UBOs in patients with NF1. DTI confirmed changes in FA despite the disappearance or reduction of UBOs. article 3: MR spectroscopy allows the characterization of the tissue abnormalities not demonstrable in the conventional MR sequences of patients with NF1 by analysis of metabolites Co and Mi. / A neurofibromatose tipo 1 (NF1) em crianças e adolescentes está frequentemente associada com o aparecimento ou desaparecimento de lesões focais de hipersinal no encéfalo na ponderação T2 (FHE-T2). Estas lesões não são aceitas como critério diagnóstico para NF1 e sua natureza exata ainda não está clara. Objetivos: artigo 1: Avaliar a relação entre a presença dos FHE-T2 e padrões de anisotropia fracionada (FA) em uma série de pacientes com NF1; artigo 2: Demonstrar o padrão de evolução dos FHE-T2 por exame de Ressonância Magnética (RM) em indivíduos com NF1 e relacionar com o valor regional de FA; artigo 3: Avaliar os padrões metabólicos por meio da espectroscopia por ressonância magnética (ERM) do encéfalo na presença dos FHE-T2 em pacientes com NF1. Métodos: artigo 1: Analisou-se uma série de 44 indivíduos com NF1, e 20 controles. A análise quantitativa do FA foi definida em quatro regiões anatômicas pré-determinadas e relacionada à presença de FHE-T2; artigo 2: Analisou-se com imagem de tensor de difusão (DTI) a evolução dos FHE-T2 nas regiões de núcleos da base, tálamos, cerebelo e tronco encefalico de um grupo de 27 pacientes com NF1 e 20 controles. A presença de FHE-T2 em dois exames de RM encefálica consecutivos foram relacionados com o valor de FA; artigo 3: Analisou-se 42 indivíduos com NF1, e 25 controles saudáveis por exame de ERM univoxel na região do globo pálido. Foi feita análise automatizada quantitativa da relação dos metabólitos colina/creatina (Co/Cr), N-acetil aspartato/creatina (Naa/Cr) e Mioinositol/creatina (Mi/Cr) e relacionada à ocorrência de FHE-T2 na região do globo pálido. Resultados: artigo 1: Os FHE-T2 foram diagnosticados em 50% dos pacientes com NF1. Observou-se redução do valor de FA nas regiões do cerebelo e tálamo de aparência normal ou com FHE-T2 de pacientes com NF1 em relação ao controle (P &#8804;.05); artigo 2: Houve redução significativa no valor de FA nas regiões de núcleos da base, cerebelo e tálamos em pacientes com NF1 em relação ao grupo controle (P &#8804;.05) mesmo com redução ou desaparecimento dos FHE-T2; artigo 3: Houve diferença estatisticamente significante entre os grupos de pacientes com NF1 e o controle quanto aos valores médios ( ) de Mi/Cr e Co/Cr (P<0,05) na região do globo pálido. Conclusões: artigo 1: A técnica de DTI confirma que os FHE-T2 estejam relacionados às alterações da microestrutura do tecido cerebral em pacientes NF1. artigo 2: A RM possibilita o adequado monitoramento da distribuição no tempo e espaço dos FHE-T2 em pacientes com NF1. DTI evidencia alterações no valor de FA mesmo com o desaparecimento ou redução dos FHE-T2; artigo 3: A ERM permite a caracterização de anormalidades teciduais não demonstráveis nas sequências convencionais de RM de pacientes com NF1 por meio da análise dos metabólitos Co e Mi.

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Le immagini mentali sono un analogo della percezione? Studiando i pazienti con danni cerebrali, abbiamo visto che le menomazioni percettive sono spesso associate a limitazioni nella capacità di creare immagini (Farah 1988, 2000). Nella recente letteratura tuttavia sono riportati casi di doppia dissociazione, in cui funzioni percettive sono preservate e quelle immaginative danneggiate, o viceversa, funzioni percettive danneggiate ma intatta capacità immaginativa. Nel seguente studio l’obiettivo è indagare i rapporti tra la percezione e immaginazione in pazienti con danno cerebrale, in 5 diversi domini: forme, colori, volti, materiale ortografico e relazioni spaziali. Nel primo studio l'obiettivo era di esplorare le immagini mentali e la capacità di percezione visiva in pazienti con lesioni cerebrali attraverso una batteria di test sviluppata da Bachoud Levi, Bartolomeo, Chokron nel 2001 e adattata per il campione italiano da Antonietti, Oliveri, Incorpora et al. (2008). In un secondo studio abbiamo indagato le relazioni tra imagery e stile cognitivo visualizzatore/verbalizzatore, proponendo 2 questionari (VVQ e QSVV). Infine in un terzo studio, attraverso indagini strumentali (DTI, TAC, RMN) in un gruppo di pazienti con danno focale e deficit specifici di imagery, abbiamo individuato le correlazioni tra deficit nei diversi domini dell’imagery e della percezione con i danni corrispondenti a livello neurale. / Is imagery an analogous of perception? By studying patients with brain damage we saw that perceptual impairments are often associated to limitations in the ability to create images (Farah 1988, 2000). In recent literature we found cases of double dissociation, in which perceptual functions are preserved and those imaginative impaired or, vice versa, there are damaged perception functions but intact imaginative capacity. We aim to investigate the relationships between perception and imagery in patients with brain damage, in 5 different domains: shapes, colour, faces, orthographic material and spatial relationships. In the first study the aim was to explore mental imagery and visual perception skills in patients with brain injury through a battery of tests developed by Bachoud-Lèvi, Bartolomeo, Chokron in 2001, and readapted for the Italian sample by Antonietti, Oliveri, Incorpora et aal (2008). In a second study we investigated the relationships between imagery test performance and visualizer/verbalizer cognitive style, detected by proposing 2 questionnaires (VVQ and QSVV). Finally in a third study, through instrumental investigations (DTI, TAC, MRI) in a group of patient with focal damage and specific imagery deficit, we aimed to correlate imagery and perception deficits to corresponding impairment in neural correlates.

Diffusion-weighted magnetic resonance imaging (MRI) has allowed unprecedented non-invasive mapping of brain neural connectivity in vivo by means of fiber tractography applications. Fiber tractography has emerged as a useful tool for mapping brain white matter connectivity prior to surgery or in an intraoperative setting. The advent of high angular resolution diffusion-weighted imaging (HARDI) techniques in MRI for fiber tractography has allowed mapping of fiber tracts in areas of complex white matter fiber crossings. Raw HARDI images, as a result of elevated diffusion-weighting, suffer from depressed signal-to-noise ratio (SNR) levels. The accuracy of fiber tractography is dependent on the performance of the various methods extracting dominant fiber orientations from the HARDI-measured noisy diffusivity profiles. These methods will be sensitive to and directly affected by the noise. In the first part of the thesis this issue is addressed by applying an objective and adaptive smoothing to the noisy HARDI data via generalized cross-validation (GCV) by means of the smoothing splines on the sphere method for estimating the smooth diffusivity profiles in three dimensional diffusion space. Subsequently, fiber orientation distribution functions (ODFs) that reveal dominant fiber orientations in fiber crossings are then reconstructed from the smoothed diffusivity profiles using the Funk-Radon transform. Previous ODF smoothing techniques have been subjective and non-adaptive to data SNR. The GCV-smoothed ODFs from our method are accurate and are smoothed without external intervention facilitating more precise fiber tractography. Diffusion-weighted MRI studies in amyotrophic lateral sclerosis (ALS) have revealed significant changes in diffusion parameters in ALS patient brains. With the need for early detection of possibly discrete upper motor neuron (UMN) degeneration signs in patients with early ALS, a HARDI study is applied in order to investigate diffusion-sensitive changes reflected in the diffusion tensor imaging (DTI) measures axial and radial diffusivity as well as the more commonly used measures fractional anisotropy (FA) and mean diffusivity (MD). The hypothesis is that there would be added utility in considering axial and radial diffusivities which directly reflect changes in the diffusion tensors in addition to FA and MD to aid in revealing neurodegenerative changes in ALS. In addition, applying adaptive smoothing via GCV to the HARDI data further facilitates the application of fiber tractography by automatically eliminating spurious noisy peaks in reconstructed ODFs that would mislead fiber tracking.