This thesis describes the electrical and physiological characterization of cardiac tissue with myocardial infarction (MI) responsible for abnormal cardiac rhythms such as ventricular tachycardia (VT), using a newly-developed magnetic resonance imaging (MRI) electrophysiology system. In electrophysiology (EP), radiofrequency (RF) catheter ablation combined with cardioverter-defibrillator implantation is a first-line action to manage ventricular VT. Unfortunately, this therapy is known to have sub-optimal success rates in a large number of patients because of difficulties to accurately identifying the arrhythmic target regions. Currently, characterization of post-MI scars is performed by using catheters to measure electrical signals of the endocardial tissue (electroanatomical mapping), under x-ray fluoroscopy guidance. Prolonged radiation exposure to both the cardiologist and the patient have made the use of MRI extremely attractive; further, unlike x-ray imaging, MRI provides post-MI scars with direct visualization, characterization in three dimensions and the ability to visualize ablation lesions. Although recent research has focused on registration between pre-acquired MR images and electroanatomical maps, a potentially more useful approach is to use real-time MRI to directly locate and characterize potential arrhythmogenic regions during the EP procedure. A real-time MR-guided EP system was developed and validated to perform EP diagnostic procedures, such as mapping and pacing. In a series of animal studies, the system demonstrated the ability to use active catheter tracking and intra-procedural MR imaging to navigate to specific regions in the left ventricle and record intracardiac electrical signals. A study correlating myocardial fibrotic scar detected by multicontrast late enhancement (MCLE) MRI and electroanatomical voltage mapping demonstrated that MRI information (transmurality, tissue classification, and relaxation rate) can accurately predict areas of myocardial fibrosis identified with bipolar voltage mapping. Finally, MCLE-derived gray zone was shown to have a high correspondence to regions with a high proportion of abnormal intracardiac signals. The methods described in this thesis help advance the understanding of infarcted tissue responsible for ventricular tachycardia. Further studies are proposed to perform RF ablation lesions and correlate pre- and post-ablation tissue electrophysiological properties with MRI.

This dissertation is comprised of four studies investigating the hypothesis that adults and children who stutter differ from their same-age fluent peers in the neuroanatomy and neurophysiology underlying auditory speech processing. It has been consistently reported that adults who stutter demonstrate unique functional neural activation patterns during speech production, including reduced auditory activation, relative to nonstutterers. The extent to which these functional differences are accompanied by abnormal morphology of the brain in stutterers is unclear. The first study in this dissertation examined the neuroanatomical differences in speech-related cortex between adults who do and do not stutter using magnetic resonance imaging and voxel-based morphometry analyses. Adults who stutter were found to have localized grey matter volume increases in auditory and motor speech related cortex. The second study extended this line of research to children who stutter, who were found to have localized grey matter volume decreases in motor speech related cortex. Together, these studies suggest an abnormal trajectory of regional grey matter development in motor speech cortex of people who stutter. The last two studies investigated the mechanism underlying the repeated findings of reduced auditory activation during speech in people who stutter in more detail. Magnetoencephalography was used to investigate the hypothesis that people who stutter have increased speech induced suppression of early evoked auditory responses. Adults and children who stutter demonstrated typical levels of speech induced suppression relative to fluent peers. However, adults and children who stutter showed differences from peers in the timing of cortical auditory responses. Taken together, the studies demonstrate structural and functional abnormalities in brain regions related to auditory processing and point to the possibility that people who stutter have difficulty forming the neural representations of speech sounds necessary for fluent speech production.

Doctor of Philosophy (PhD) / Schizophrenia is a severe mental illness that affects approximately 1% of the population worldwide, and which typically has a devastating effect on the lives of its sufferers. The characteristic symptoms of the disease include hallucinations, delusions, disorganized thought and reduced emotional expression. While many of the early theories of schizophrenia focused on its psychosocial foundations, more recent theories have focused on the neurobiological underpinnings of the disease. This thesis has four primary aims: 1) to use magnetic resonance imaging (MRI) to identify the structural brain abnormalities present in patients suffering from their first episode of schizophrenia (FES), 2) to elucidate whether these abnormalities were static or progressive over the first 2-3 years of patients’ illness, 3) to identify the relationship between these neuroanatomical abnormalities and patients’ clinical profile, and 4) to identify the normative relationship between longitudinal changes in neuroanatomy and electrophysiology in healthy participants, and to compare this to the relationship observed between these two indices in patients with FES. The aim of Chapter 2 was to use MRI to identify the neuroanatomical changes that occur over adolescence in healthy participants, and to identify the normative relationship between the neuroanatomical changes and electrophysiological changes associated with healthy periadolescent brain maturation. MRI and electroencephalographic (EEG) scans were acquired from 138 healthy participants between the ages of 10 and 30 years. The MRI scans were segmented into grey matter (GM) and white matter (WM) images, before being parcellated into the frontal, temporal, parietal and occipital lobes. Absolute EEG power was calculated for the slow-wave, alpha and beta frequency bands, for the corresponding cortical regions. The age-related changes in regional tissue volumes and regional EEG power were inferred with a regression model. The results indicated that the healthy participants experienced accelerated GM loss, EEG power loss and WM gain in the frontal and parietal lobes between the ages of 10 and 20 years, which decelerated between the ages of 20 and 30 years. A linear relationship was also observed between the maturational changes in regional GM volumes and EEG power in the frontal and parietal lobes. These results indicate that the periadolescent period is a time of great structural and electrophysiological change in the healthy human brain. The aim of Chapter 3 was to identify the GM abnormalities present in patients with FES, both at the time of their first presentation to mental health services (baseline), and over the first 2-3 years of their illness (follow-up). MRI scans were acquired from 41 patients with FES at baseline, and 47 matched healthy control subjects. Of these participants, 25 FES patients and 26 controls returned 2-3 years later for a follow-up scan. The analysis technique of voxel-based morphometry (VBM) was used in conjunction with the Statistical Parametric Mapping (SPM) software package in order to identify the regions of GM difference between the groups at baseline. The related analysis technique of tensor-based morphometry (TBM) was used to identify subjects’ longitudinal GM change over the follow-up interval. Relative to the healthy controls, the FES patients were observed to exhibit widespread GM reductions in the frontal, parietal and temporal cortices and cerebellum at baseline, as well as more circumscribed regions of GM increase, particularly in the occipital lobe. Furthermore, the FES patients lost considerably more GM over the follow-up interval than the controls, particularly in the parietal and temporal cortices. These results indicate that patients with FES exhibit significant structural brain abnormalities very early in the course of their illness, and that these abnormalities progress over the first few years of their illness. Chapter 4 employed the same methodology to investigate the white matter abnormalities exhibited by the FES subjects relative to the controls, both at baseline and over the follow-up interval. Compared to controls, the FES patients exhibited volumetric WM deficits in the frontal and temporal lobes at baseline, as well as volumetric increases at the fronto-parietal junction bilaterally. Furthermore, the FES patients lost considerably more WM over the follow-up interval than did the controls in the middle and inferior temporal cortex bilaterally. While there is substantial evidence indicating that abnormalities in the maturational processes of myelination play a significant role in the development of WM abnormalities in FES, the observed longitudinal reductions in WM were consistent with the death of a select population of temporal lobe neurons over the follow-up interval. The aim of Chapter 5 was to investigate the clinical correlates of the GM abnormalities exhibited by the FES patients at baseline. The volumes of four distinct cerebral regions where 31 patients with FES exhibited reduced GM volumes relative to 30 matched controls were calculated and correlated with patients’ scores on three primary symptom dimensions: Disorganization, Reality Distortion and Psychomotor Poverty. The results indicated that the greater the degree of atrophy exhibited by the FES patients in three of these four ‘regions-of-reduction’, the less severe their degree of Reality Distortion. These results suggest that an excessive amount of GM atrophy may in fact preclude the formation of hallucinations or highly systematized delusions in patients with FES. The aim of Chapter 6 was to identify the relationship between the longitudinal changes in brain structure and brain electrophysiology exhibited by 19 FES patients over the first 2-3 years of their illness, and to compare it to the normative relationship between the two indices reported in Chapter 2. The methodology employed for the parcellation of the MRI and EEG data was identical to Chapter 2. The results indicated that, in contrast to the healthy controls, the longitudinal reduction in GM volume exhibited by the FES patients was not associated with a corresponding reduction in EEG power in any brain lobe. In contrast, EEG power was observed to be maintained or even to increase over the follow-up interval in these patients. These results were consistent with the FES patients experiencing an abnormal elevation of neural synchrony. Such an abnormality in neural synchrony could potentially form the basis of the dysfunctional neural connectivity that has been widely proposed to underlie the functional deficits present in patients with schizophrenia. The primary aim of Chapter 7 was to assimilate the findings from the preceding empirical chapters with the theoretical framework provided in the literature, into an integrated and testable model of schizophrenia. The model emphasized dysfunctions in brain maturation, specifically in the normative processes of synaptic ‘pruning’ and axonal myelination, as playing a key role in the development of disintegrated neural activity and the subsequent onset of schizophrenic symptoms. The model concluded with the novel proposal that disintegrated neural activity arises from abnormal elevations in the synchrony of synaptic activity in patients with first-episode schizophrenia.

Οι τεχνικές απεικόνισης μοριακής διάχυσης (DWI) και τανυστή διάχυσης (DTI) είναι από τις πιο δημοφιλείς τεχνικές μαγνητικής τομογραφίας (MRI) στην έρευνα του εγκεφάλου. Διάχυση (ή θερμική κίνηση Brown) είναι ένα τυχαίο φαινόμενο το οποίο περιγράφει τη μεταφορά υλικού (π.χ μόρια νερού) από μία χωρική θέση σε άλλη με την πάροδο του χρόνου. Η διάχυση του νερού σε βιολογικούς ιστούς παρατηρείται μέσα, έξω, γύρω από τις κυτταρικές δομές και είναι αποτέλεσμα της θερμικής ενέργειας των μορίων. Η κάθε τεχνική υποστηρίζεται από τον δικό της αλγόριθμο από τους οποίους προκύπτουν και οι αντίστοιχοι παραμετρικοί χάρτες. Πιο συγκεκριμένα από την τεχνική διάχυσης προκύπτει ο δείκτης της φαινόμενης σταθεράς διάχυσης (ADC-Apparent Diffusion Coefficient) , ενώ από την τεχνική του τανυστή διάχυσης προκύπτει ο δείκτης της κλασματικής ανισοτροπίας (FA-Fractional Anisotropy). Η παράμετρος ADC δείχνει πόσο διαφέρει η διάχυση στην περιοχή ενδιαφέροντος σε σχέση με την μέση τιμή διάχυσης. Η κλασματική ανισοτροπία (FA) είναι δείκτης μέτρησης του βαθμού ανισοτροπίας της διάχυσης και η τιμή της εξαρτάται άμεσα από την ακεραιότητα των νευρικών ινών. Το φάσμα εφαρμογής των δύο τεχνικών είναι ευρύ (εφαρμογή σε απομυελινωτικές νόσους, ισχαιμικά επεισόδια, εγκεφαλικοί όγκοι). Ο κύριος λόγος είναι ότι η διάχυση των μορίων νερού είναι ιδιαίτερα ευαίσθητη σε τυχόν αλλοιώσεις στη δομή των ινών της Λευκής ουσίας. Σκοπός της παρούσας ερευνητικής είναι η εφαρμογή των τεχνικών Τανυστή Διάχυσης (DTI) και Μοριακής Διάχυσης (DWI) σε τρείς κατηγορίες εγκεφαλικών όγκων (μηνιγγιώματα, γλοιώματα υψηλής και χαμηλής κακοήθειας, εγκεφαλικούς μεταστατικούς όγκους) με σκοπό τον διαχωρισμό αυτών. / The brain is a highly organized organ with a complex microstructural organization . The microstructural organization of brain tissue affects the molecular motion (diffusion) of water. Diffusion therefore reflects the structural organization of tissue. Diffusion imaging is a Magnetic Resonance (MR) imaging technique that allows the quantification to the molecular motion of water. Magnitude and directionality (anisotropy) of molecular motion of water can be described. Measurements of the magnitude of diffusion have been used to identify abnormal tissue in tumors, stroke, multiple sclerosis and status epilepticus. Diffusion tensor imaging (DTI) is a relatively new technique that allows rotationally invariant measurements of both magnitude and directionality of water diffusion. DTI sequences with calculation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) scalars allow characterization of the shape and magnitude of the diffusion ellipsoid. These parameters consequently reflect the microstructural architecture of the human brain. In addition, quantification of diffusion can be especially helpful as it may allow early diagnosis of pathology . The purpose of this study was to correlate the changes in FA and ADC between three different brain tumors and outline the probability of presurgical tumor differentiation.

Ischaemic stroke is a major cause of death and disability worldwide. Cerebral autoregulation, which can be impaired during acute stroke, and collateral flow to brain tissue through the circle of Willis, both play a role in preventing tissue infarction. The configuration of the arterial circle varies between individuals. Thus, personalised modelling of the cerebral arterial network, to determine the potential for collateral flow, can be of significant value in the clinical context of stroke. The interaction between autoregulation and collateral flow remains poorly understood. In this study, steady-state physiological models of the cerebral arterial network, including several common variants of the circle of Willis, were coupled to a spatially variable mathematical representation of cerebral autoregulation. The resulting model was used to simulate various arterial occlusions, as well as bilateral and unilateral impairment of autoregulation, in each structural variant. The work identified few circle of Willis variants that present either particularly high-risk or particularly low-risk of cerebral ischaemia. Instead it was found that most variants are dependent upon the bilateral function of autoregulation to facilitate collateral flow and preserve cerebral blood flows. When autoregulation was impaired unilaterally, downstream of an occlusion, blood flows in the contralateral hemisphere were preserved at the expense of the ipsilateral tissue at risk. Arterial network models have in the past been personalised using structural, rather than functional, angiography measurements. This thesis presents a novel model-based method for absolute blood volume flow rate quantification in short arterial segments using dynamic magnetic resonance angiography data. The work also investigated the additional information that can be obtained from such functional angiography. The flow quantification technique was found to accurately estimate flows in shorter arterial segments than an existing technique. However, improvements to noise performance, and strategies for rejection of contaminating signals from overlapping vessels within the imaging plane, are required before the technique can be applied to personalised cerebral arterial network modelling.

L’imagerie par résonance magnétique est une technique non invasive et non ionisante permettant de caractériser la structure anatomique des tissus biologiques mous via la localisation des signaux de résonance magnétique nucléaire (RMN) des molécules mobiles. Cependant, l’application de l’IRM pour l’étude des matériaux rigides reste difficile dû aux forts élargissements des raies de résonances inhérents aux matériaux solides qui diminuent la résolution et le rapport signal sur bruit des images obtenues par encodage fréquentiel.La rotation à l’angle magique (MAS) permet de moyenner efficacement les interactions anisotropes de l’état solide par une rotation de l’échantillon, réduisant ainsi la largeur des raies de résonance. Dans ce manuscrit la possibilité de combiner la rotation à l’angle magique et l’IRM pour effectuer de la micro-imagerie multidimensionnelle et multi-nucléaire (¹H, ³¹P, ²⁷Al et ⁵¹V) à très haut champ magnétique (17,6 T) de matériaux solides avec une résolution et un rapport signal sur bruit largement supérieur à ceux obtenus en condition statique est démontrée. Une large gamme de matériaux (polymères, céramiques et tissus calcifiés biologiques) a été étudiée. Des images avec une résolution comprise entre 30 et 300 μm ont pu être obtenues pour des fréquences de rotation MAS allant jusqu’à 20 kHz, en utilisant des séquences IRM d’écho ou à temps d’écho nul. La possibilité d’utiliser un schéma de sous-échantillonnage associé à des algorithmes de reconstruction est aussi abordée.L’utilisation de séquences de RMN solide tels que la polarisation croisée pour augmenter le contraste et ainsi mettre en évidence des variations physico-chimiques localisées dans des tissus calcifiés biologiques est aussi démontrée. L’utilisation de gradients de champ magnétique pulsés combinés à la rotation à l’angle magique rend aussi possible la spectroscopie RMN de haute résolution localisée spatialement. Cette méthode a été utilisée pour étudier in vivo et dans chacun des segments du corps le métabolome de drosophiles modèles de pathologies neurodégénératives. / Magnetic Resonance Imaging (MRI) is a non-invasive and non-ionizing powerful tool widely used to characterize the structure and function of biological soft tissues through the localization of the NMR signal of mobile species. In contrast, the application of MRI in rigid solids remains challenging as they usually exhibit strong line broadening which decreases both the sensitivity and the resolution obtained with frequency encoding and short transverse relaxation time prohibiting the use of echo MRI sequences.Magic Angle Spinning (MAS) provides an efficient averaging of the an isotropic interactions in the solid statethrough a macroscopic rotation of the sample and allows obtaining narrow resonances. In this manuscript,we show the potentialities of combining MAS and MRI to carry out multi-nuclei (¹H, ³¹P, ²⁷Al or ⁵¹V) multidimensional micro-imaging in rigid solids, at very high magnetic field (17.6 T), with greatly improved SNR and spatial resolution when compared to static conditions. This is exemplified on a wide range of materials(polymers, oxide ceramics, biomaterials and hard tissues) for which the use of MAS at frequencies up to 20 kHz with spin-echo or Zero Echo Time (ZTE) MRI sequences allow obtaining images with spatialre solutions ranging from 30 to 300 μm. It is also demonstrated that solid state NMR sequences such as Cross-Polarization (CP) can be employed to enhance contrast and to further depict spatially localized chemical variations in bones and related materials. The possibility of using under sampled acquisition scheme with reconstruction algorithms is also addressed.The combination between pulsed field gradients and MAS also offers the possibility to perform high resolution localized spectroscopy. This methodology is used to study, in vivo and at the organ level, the metabolism of neuro degenerative pathologies drosophila models.

Le visage humain joue un rôle important dans la communication interpersonnelle. La dysfonction du visage ou le défigurement due aux traumatismes ou pathologies peuvent entraver les activités sociales normales. Le traitement chirurgical est souvent nécessaire. De nos jours, le résultat du traitement chirurgical et l’état d’établissement ne sont estimé qu’avec les méthodes qualitatives telles que l’observation visuelle et la palpation. Dans l’attente de fournir des critères quantitatifs, cette thèse a pour l’objectif de modéliser la mimique faciale utilisant MEF (Méthode d’Éléments Finis) sur la base des données d’IRM (Imagerie par Résonance Magnétique). Un modèle sujet-spécifique du visage a été construit sur la base de la segmentation des données IRM ; il contient des parties osseuses, muscles de la mimique (p.ex. le muscle grand zygomatique), les tissues mous sous-cutanées et la peau. L’identification des tissus mous biologiques a été réalisée via des essais de traction bi-axiale et la modélisation numérique. Ensuite, le modèle géométrique a été maillé pour effectuer des calculs EF simulant trois mouvements mimiques du visage (sourire, prononciation du son « Pou » et « O »). Les muscles ont été modélisés comme un matériau quasi-incompressible, transversalement isotrope et hyperélastique, avec la capacité d’activation. Des informations pertinentes (p.ex. l’amplitude de contraction du muscle) utilisées dans la simulation ont été extraites de la mesure des données d’IRM. Il est à noter que les mêmes données expérimentales d’IRM telles qu’ils ont utilisées dans la modélisation ont été prises comme une référence de validation pour les résultats de simulation. Cette étude peut être appliquée cliniquement dans l’évaluation du traitement faciale et le rétablissement postopérative. / Human face plays an important role interpersonal communication. Facial dysfunction or disfigurement due to trauma or pathologies may impede normal social activities. Surgical treatment is often necessary. Nowadays, treatment outcome and rehabilitation condition are estimated only by qualitative methods, such as visual observation and palpation. In expectation of providing quantitative criteria, this thesis proposes to model facial mimics using FEM (Finite Element Method) on the basis of MRI (Magnetic Resonance Imaging) data. A subject-specific face model was reconstructed based on segmentation of MRI data; it contains bony parts, mimic muscles (e.g. zygomaticus major muscle), subcutaneous soft tissues and skin. Identification of biological soft tissues was conducted through bi-axial tension tests and numerical modeling. Then the geometric model was meshed to conduct FE calculations simulating three facial mimic movements (smile, pronunciation of sound “Pou” and “O”). Muscle was modeled as quasi-incompressible, transversely-isotropic, hyperelastic material, with activation ability. Relevant information (e.g. contraction amplitude of muscle) used in simulation was extracted from measurement of MRI data. It is to be noted that the same experimental MRI data as used in modeling was taken as validation reference for simulation results. This study can be applied clinically in evaluation of facial treatment andpostoperative recovery.

No description available.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18872号 / 医博第3983号 / 新制||医||1008(附属図書館) / 31823 / 京都大学大学院医学研究科医学専攻 / (主査)教授 河野 憲二, 教授 古川 壽亮, 教授 髙橋 良輔 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

Mikrochips zur Tierkennzeichnung bestehen aus verschiedenen metallischen Materialien. Diese treten in der Magnetresonanztomographie in Wechselwirkung mit den elektromagnetischen Feldern. So verursachen die ferromagnetischen Materialen der Mikrochips gravierende fokale Bildstörungen. Diese Suszeptibilitätsartefakte können die Beurteilbarkeit der Halsregion erheblich einschränken. Ziel der Studie war, den Einfluss des Sequenztyps auf die Größe des Artefakts zu untersuchen und herauszufinden, welche Möglichkeiten zur Artefaktreduktion bei Veränderung bestimmter Sequenzparameter bestehen. Zusätzlich sollte geklärt werden, wie groß der Abstand zwischen Spinalkanal und Mikrochip mindestens sein muss, um spinale Strukturen beurteilen zu können. In das Untersuchungsgut der Studie gingen die Kadaver von 26 Katzen und 2 Hunden ein. An einem 0,5-Tesla-MRT wurde für verschiedene Sequenztypen (SE-Sequenzen, TSE-Sequenzen, GRE-Sequenzen) und Kombinationen modifizierter Sequenzparameter (Echozeit (TE), Voxelgröße, Ausleserichtung) das Ausmaß der Artefakte ermittelt. Berechnet wurde der Flächeninhalt des Artefakts (cm2). Dieser wurde dann als prozentualer Anteil zur Fläche des Halsquerschnitts angegeben. Diese Berechnung erfolgte für alle untersuchten Einstellungen an transversalen Aufnahmen. Eine ergänzende computertomografische Untersuchung dienste dazu, die Distanz zwischen Spinalkanalund Mikrochip zu messen. Die Untersuchungen der Studie haben gezeigt, dass TSE-Sequenzen wegen ihrer geringeren Artefaktanfälligkeit den SE- und GRE-Sequenzen vorgezogen werden sollten. Besonders kleine Artefakte konnten bei einer T1-TSE-Sequenz mit kleiner TE (10 ms) und kleiner Voxelgröße (große Akquisitionsmatrix von 256 x 256 Pixel, kleines Field of View (FOV) von 160 mm, geringe Schichtdicke (ST) von 2 mm) erreicht werden. Durch Anpassung der Kodierrichtung war es möglich, die Form und Richtung des Artefaktes zu beeinflussen. Lag das Zentrum des Mikrochips näher als 19 mm von der Mitte des Wirbelkanals entfernt, ließen sich auch mit dieser optimierten Sequenz die spinalen Strukturen auf Höhe des Mikrochips nicht beurteilen. Die Größe und Form der Suszeptibilitätsartefakte konnten durch die Wahl des Sequenztyps und Modifikation von Sequenzparametern verändert werden. Dies ist besonders bei kleinen Tieren von Bedeutung. Bei diesen kann es aufgrund der geringen Distanz zwischen Mikrochip und Wirbelsäule zur Beeinträchtigung der MR-Bildauswertung kommen. Eine T1-gewichtete TSE-Sequenz mit kleiner Echozeit (10 ms) und kleiner Voxelgröße (Akquisitionsmatrix 256 x 256 Pixel, FOV 160 mm, ST 2 mm) bietet bei 0,5 Tesla das größte Potenzial zur Artefaktreduktion.