Intervention orthophonique et neurobiologie du cerveau : apports de la neuroimagerie à la prise en charge de l’aphasie chronique

L’aphasie est un trouble acquis du langage entraînant des problèmes de communication pouvant toucher la compréhension et/ou l’expression. Lorsque l’aphasie fait suite à un accident vasculaire cérébral, une régression des déficits communicatifs s'observe initialement, mais elle peut demeurer sévère pour certains et est considérée chronique après un an. Par ailleurs, l’aphasie peut aussi être observée dans l’aphasie progressive primaire, une maladie dégénérative affectant uniquement le langage dans les premières années. Un nombre grandissant d’études s’intéressent à l’impact de la thérapie dans l’aphasie chronique et ont démontré des améliorations langagières après plusieurs années. L’hémisphère gauche semble avoir un rôle crucial et est associé à de meilleures améliorations langagières, mais la compréhension des mécanismes de plasticité cérébrale est encore embryonnaire. Or, l’efficacité de la thérapie dans l’aphasie progressive primaire est peu étudiée. À l’aide de la résonance magnétique fonctionnelle, le but des présentes études consiste à examiner les mécanismes de plasticité cérébrale induits par la thérapie Semantic Feature Analysis auprès de dix personnes souffrant d’aphasie chronique et d’une personne souffrant d’aphasie progressive primaire. Les résultats suggèrent que le cerveau peut se réorganiser plusieurs années après une lésion cérébrale ainsi que dans une maladie dégénérative. Au niveau individuel, une meilleure amélioration langagière est associée au recrutement de l’hémisphère gauche ainsi qu’une concentration des activations. Les analyses de groupe mettent en évidence le recrutement du lobule pariétal inférieur gauche, alors que l’activation du gyrus précentral gauche prédit l’amélioration suite à la thérapie. D’autre part, les analyses de connectivité fonctionnelle ont permis d’identifier pour la première fois le réseau par défaut dans l’aphasie. Suite à la thérapie, l’intégration de ce réseau bien connu est comparable à celle des contrôles et les analyses de corrélation suggèrent que l’intégration du réseau par défaut a une valeur prédictive d’amélioration. Donc, les résultats de ces études appuient l’idée que l’hémisphère gauche a un rôle prépondérant dans la récupération de l’aphasie et fournissent des données probantes sur la neuroplasticité induite par une thérapie spécifique du langage dans l’aphasie. De plus, l’identification d’aires clés et de réseaux guideront de futures recherches afin d’éventuellement maximiser la récupération de l’aphasie et permettre de mieux prédire le pronostic.

Cross-Linguistic Transfer (CLT) in Bilingual Speakers : Neural Correlates of Language Learning

Le but de cette thèse est d'étudier les corrélats comportementaux et neuronaux du transfert inter-linguistique (TIL) dans l'apprentissage d’une langue seconde (L2). Compte tenu de nos connaissances sur l'influence de la distance linguistique sur le TIL (Paradis, 1987, 2004; Odlin, 1989, 2004, 2005; Gollan, 2005; Ringbom, 2007), nous avons examiné l'effet de facilitation de la similarité phonologique à l’aide de la résonance magnétique fonctionnelle entre des langues linguistiquement proches (espagnol-français) et des langues linguistiquement éloignées (persan-français). L'étude I rapporte les résultats obtenus pour des langues linguistiquement proches (espagnol-français), alors que l'étude II porte sur des langues linguistiquement éloignées (persan-français). Puis, les changements de connectivité fonctionnelle dans le réseau langagier (Price, 2010) et dans le réseau de contrôle supplémentaire impliqué dans le traitement d’une langue seconde (Abutalebi & Green, 2007) lors de l’apprentissage d’une langue linguistiquement éloignée (persan-français) sont rapportés dans l’étude III. Les résultats des analyses d’IRMF suivant le modèle linéaire général chez les bilingues de langues linguistiquement proches (français-espagnol) montrent que le traitement des mots phonologiquement similaires dans les deux langues (cognates et clangs) compte sur un réseau neuronal partagé par la langue maternelle (L1) et la L2, tandis que le traitement des mots phonologiquement éloignés (non-clang-non-cognates) active des structures impliquées dans le traitement de la mémoire de travail et d'attention. Toutefois, chez les personnes bilingues de L1-L2 linguistiquement éloignées (français-persan), même les mots phonologiquement similaires à travers les langues (cognates et clangs) activent des régions connues pour être impliquées dans l'attention et le contrôle cognitif. Par ailleurs, les mots phonologiquement éloignés (non-clang-non-cognates) activent des régions usuellement associées à la mémoire de travail et aux fonctions exécutives. Ainsi, le facteur de distance inter-linguistique entre L1 et L2 module la charge cognitive sur la base du degré de similarité phonologiques entres les items en L1 et L2. Des structures soutenant les processus impliqués dans le traitement exécutif sont recrutées afin de compenser pour des demandes cognitives. Lorsque la compétence linguistique en L2 augmente et que les tâches linguistiques exigent ainsi moins d’effort, la demande pour les ressources cognitives diminue. Tel que déjà rapporté (Majerus, et al, 2008; Prat, et al, 2007; Veroude, et al, 2010; Dodel, et al, 2005; Coynel, et al ., 2009), les résultats des analyses de connectivité fonctionnelle montrent qu’après l’entraînement la valeur d'intégration (connectivité fonctionnelle) diminue puisqu’il y a moins de circulation du flux d'information. Les résultats de cette recherche contribuent à une meilleure compréhension des aspects neurocognitifs et de plasticité cérébrale du TIL ainsi que l'impact de la distance linguistique dans l'apprentissage des langues. Ces résultats ont des implications dans les stratégies d'apprentissage d’une L2, les méthodes d’enseignement d’une L2 ainsi que le développement d'approches thérapeutiques chez des patients bilingues qui souffrent de troubles langagiers.

Functional Multiparametric Magnetic Resonance Imaging of the Kidneys Using Blood Oxygen Level-Dependent and Diffusion-Weighted Sequences: a Reliable Tool for Monitoring Acute Upper Urinary Tract Obstruction.

PURPOSE Little data is available on noninvasive MRI-based assessment of renal function during upper urinary tract (UUT) obstruction. In this study, we determined whether functional multiparametric kidney MRI is able to monitor treatment response in acute unilateral UUT obstruction. MATERIAL AND METHODS Between 01/2008 and 01/2010, 18 patients with acute unilateral UUT obstruction due to calculi were prospectively enrolled to undergo kidney MRI with conventional, blood oxygen level-dependent (BOLD) and diffusion-weighted (DW) sequences on emergency admission and after release of obstruction. Functional imaging parameters of the obstructed and contralateral unobstructed kidneys derived from BOLD (apparent spin relaxation rate [R2*]) and DW (total apparent diffusion coefficient [ADCT], pure diffusion coefficient [ADCD] and perfusion fraction [FP]) sequences were assessed during acute UUT obstruction and after its release. RESULTS During acute obstruction, R2* and FP values were lower in the cortex (p=0.020 and p=0.031, respectively) and medulla (p=0.012 and p=0.190, respectively) of the obstructed compared to the contralateral unobstructed kidneys. After release of obstruction, R2* and FP values increased both in the cortex (p=0.016 and p=0.004, respectively) and medulla (p=0.071 and p=0.044, respectively) of the formerly obstructed kidneys to values similar to those found in the contralateral kidneys. ADCT and ADCD values did not significantly differ between obstructed and contralateral unobstructed kidneys during or after obstruction. CONCLUSIONS In our patients with acute unilateral UUT obstruction due to calculi, functional kidney MRI using BOLD and DW sequences allowed for the monitoring of pathophysiologic changes of obstructed kidneys during obstruction and after its release.

(1)H magnetic resonance spectroscopy imaging of the hippocampus in patients with panic disorder

Recent theories of panic disorder propose an extensive involvement of limbic system structures, such as the hippocampus, in the pathophysiology of this condition. Despite this, no prior study has examined exclusively the hippocampal neurochemistry in this disorder. The current study used proton magnetic resonance spectroscopy imaging ((1)H-MRSI) to examine possible abnormalities in the hippocampus in panic disorder patients. Participants comprised 25 panic patients and 18 psychiatrically healthy controls. N-acetylaspartate (NAA, a putative marker of neuronal viability) and choline (Cho, involved in the synthesis and degradation of cell membranes) levels were quantified relative to creatine (Cr, which is thought to be relatively stable among individuals and in different metabolic condition) in both right and left hippocampi. Compared with controls, panic patients demonstrated significantly lower NAA/Cr in the left hippocampus. No other difference was detected. This result is consistent with previous neuroimaging findings of hippocampal alterations in panic and provides the first neurochemical evidence suggestive of involvement of this structure in the disorder. Moreover, lower left hippocampal NAA/Cr in panic disorder may possibly reflect neuronal loss and/or neuronal metabolic dysfunction, and could be related to a deficit in evaluating ambiguous cues. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Combined magnetic resonance imaging and magnetic resonance spectroscopy imaging in the diagnosis of prostate cancer: a systematic review and meta-analysis

CONTEXT: Magnetic resonance imaging (MRI) combined with magnetic resonance spectroscopy imaging (MRSI) emerged as a promising test in the diagnosis of prostate cancer and showed encouraging results. OBJECTIVE: The aim of this systematic review is to meta-analyse the diagnostic accuracy of combined MRI/MRSI in prostate cancer and to explore risk profiles with highest benefit. EVIDENCE ACQUISITION: The authors searched the MEDLINE and EMBASE databases and the Cochrane Library, and the authors screened reference lists and contacted experts. There were no language restrictions. The last search was performed in August 2008. EVIDENCE SYNTHESIS: We identified 31 test-accuracy studies (1765 patients); 16 studies (17 populations) with a total of 581 patients were suitable for meta-analysis. Nine combined MRI/MRSI studies (10 populations) examining men with pathologically confirmed prostate cancer (297 patients; 1518 specimens) had a pooled sensitivity and specificity on prostate subpart level of 68% (95% CI, 56-78%) and 85% (95% CI, 78-90%), respectively. Compared with patients at high risk for clinically relevant cancer (six studies), sensitivity was lower in low-risk patients (four studies) (58% [46-69%] vs 74% [58-85%]; p>0.05) but higher for specificity (91% [86-94%] vs 78% [70-84%]; p<0.01). Seven studies examining patients with suspected prostate cancer at combined MRI/MRSI (284 patients) had an overall pooled sensitivity and specificity on patients level of 82% (59-94%) and 88% (80-95%). In the low-risk group (five studies) these values were 75% (39-93%) and 91% (77-97%), respectively. CONCLUSIONS: A limited number of small studies suggest that MRI combined with MRSI could be a rule-in test for low-risk patients. This finding needs further confirmation in larger studies and cost-effectiveness needs to be established.

A new methodical approach in neuroscience: assessing inter-personal brain coupling using functional near-infrared imaging (fNIRI) hyperscanning

Since the first demonstration of how to simultaneously measure brain activity using functional magnetic resonance imaging (fMRI) on two subjects about 10 years ago, a new paradigm in neuroscience is emerging: measuring brain activity from two or more people simultaneously, termed "hyperscanning". The hyperscanning approach has the potential to reveal inter-personal brain mechanisms underlying interaction-mediated brain-to-brain coupling. These mechanisms are engaged during real social interactions, and cannot be captured using single-subject recordings. In particular, functional near-infrared imaging (fNIRI) hyperscanning is a promising new method, offering a cost-effective, easy to apply and reliable technology to measure inter-personal interactions in a natural context. In this short review we report on fNIRI hyperscanning studies published so far and summarize opportunities and challenges for future studies.

Fast magnetic resonance temperature imaging for focused ultrasound thermal therapy

The current standard for temperature sensitive imaging using magnetic resonance (MR) is 2-D, spoiled, fast gradient-echo (fGRE) phase-difference imaging exploiting temperature dependent changes in the proton resonance frequency (PRF). The echo-time (TE) for optimal sensitivity is larger than the typical repetition time (TR) of an fGRE sequence. Since TE must be less than TR in the fGRE sequence, this limits the technique's achievable sensitivity, spatial, and temporal resolution. This adversely affects both accuracy and volume coverage of the measurements. Accurate measurement of the rapid temperature changes associated with pulsed thermal therapies, such as high-intensity focused ultrasound (FUS), at optimal temperature sensitivity requires faster acquisition times than those currently available. ^ Use of fast MR acquisition strategies, such as interleaved echo-planar and spiral imaging, can provide the necessary increase in temporal performance and sensitivity while maintaining adequate signal-to-noise and in-plane spatial resolution. This research explored the adaptation and optimization of several fast MR acquisition methods for thermal monitoring of pulsed FUS thermal therapy. Temperature sensitivity, phase-difference noise and phase-difference to phase-difference-to noise ratio for the different pulse sequences were evaluated under varying imaging parameters in an agar gel phantom to establish optimal sequence parameters for temperature monitoring. The temperature sensitivity coefficient of the gel phantom was measured, allowing quantitative temperature extrapolations. ^ Optimized fast sequences were compared based on the ability to accurately monitor temperature changes at the focus of a high-intensity focused ultrasound unit, volume coverage, and contrast-to-noise ratio in the temperature maps. Operating parameters, which minimize complex phase-difference measurement errors introduced by use of the fast-imaging methods, were established. ^

In vivo magnetic resonance vascular imaging using laser-polarized 3He microbubbles

Laser-polarized gases (3He and 129Xe) are currently being used in magnetic resonance imaging as strong signal sources that can be safely introduced into the lung. Recently, researchers have been investigating other tissues using 129Xe. These studies use xenon dissolved in a carrier such as lipid vesicles or blood. Since helium is much less soluble than xenon in these materials, 3He has been used exclusively for imaging air spaces. However, considering that the signal of 3He is more than 10 times greater than that of 129Xe for presently attainable polarization levels, this work has focused on generating a method to introduce 3He into the vascular system. We addressed the low solubility issue by producing suspensions of 3He microbubbles. Here, we provide the first vascular images obtained with laser-polarized 3He. The potential increase in signal and absence of background should allow this technique to produce high-resolution angiographic images. In addition, quantitative measurements of blood flow velocity and tissue perfusion will be feasible.

Whole-brain patterns of 1H-magnetic resonance spectroscopy imaging in Alzheimer's disease and dementia with Lewy bodies

Acknowledgments We thank Craig Lambert for his help in processing the MRS data. The study was funded by the Sir Jules Thorn Charitable Trust (grant ref: 05/JTA) and was supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre and the Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust and Newcastle University and the NIHR Biomedical Research Centre and Biomedical Research Unit in Dementia based at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Automated detection and classification of brain injury lesions on structural magnetic resonance imaging

El daño cerebral adquirido (DCA) es un problema social y sanitario grave, de magnitud creciente y de una gran complejidad diagnóstica y terapéutica. Su elevada incidencia, junto con el aumento de la supervivencia de los pacientes, una vez superada la fase aguda, lo convierten también en un problema de alta prevalencia. En concreto, según la Organización Mundial de la Salud (OMS) el DCA estará entre las 10 causas más comunes de discapacidad en el año 2020. La neurorrehabilitación permite mejorar el déficit tanto cognitivo como funcional y aumentar la autonomía de las personas con DCA. Con la incorporación de nuevas soluciones tecnológicas al proceso de neurorrehabilitación se pretende alcanzar un nuevo paradigma donde se puedan diseñar tratamientos que sean intensivos, personalizados, monitorizados y basados en la evidencia. Ya que son estas cuatro características las que aseguran que los tratamientos son eficaces. A diferencia de la mayor parte de las disciplinas médicas, no existen asociaciones de síntomas y signos de la alteración cognitiva que faciliten la orientación terapéutica. Actualmente, los tratamientos de neurorrehabilitación se diseñan en base a los resultados obtenidos en una batería de evaluación neuropsicológica que evalúa el nivel de afectación de cada una de las funciones cognitivas (memoria, atención, funciones ejecutivas, etc.). La línea de investigación en la que se enmarca este trabajo de investigación pretende diseñar y desarrollar un perfil cognitivo basado no sólo en el resultado obtenido en esa batería de test, sino también en información teórica que engloba tanto estructuras anatómicas como relaciones funcionales e información anatómica obtenida de los estudios de imagen. De esta forma, el perfil cognitivo utilizado para diseñar los tratamientos integra información personalizada y basada en la evidencia. Las técnicas de neuroimagen representan una herramienta fundamental en la identificación de lesiones para la generación de estos perfiles cognitivos. La aproximación clásica utilizada en la identificación de lesiones consiste en delinear manualmente regiones anatómicas cerebrales. Esta aproximación presenta diversos problemas relacionados con inconsistencias de criterio entre distintos clínicos, reproducibilidad y tiempo. Por tanto, la automatización de este procedimiento es fundamental para asegurar una extracción objetiva de información. La delineación automática de regiones anatómicas se realiza mediante el registro tanto contra atlas como contra otros estudios de imagen de distintos sujetos. Sin embargo, los cambios patológicos asociados al DCA están siempre asociados a anormalidades de intensidad y/o cambios en la localización de las estructuras. Este hecho provoca que los algoritmos de registro tradicionales basados en intensidad no funcionen correctamente y requieran la intervención del clínico para seleccionar ciertos puntos (que en esta tesis hemos denominado puntos singulares). Además estos algoritmos tampoco permiten que se produzcan deformaciones grandes deslocalizadas. Hecho que también puede ocurrir ante la presencia de lesiones provocadas por un accidente cerebrovascular (ACV) o un traumatismo craneoencefálico (TCE). Esta tesis se centra en el diseño, desarrollo e implementación de una metodología para la detección automática de estructuras lesionadas que integra algoritmos cuyo objetivo principal es generar resultados que puedan ser reproducibles y objetivos. Esta metodología se divide en cuatro etapas: pre-procesado, identificación de puntos singulares, registro y detección de lesiones. Los trabajos y resultados alcanzados en esta tesis son los siguientes: Pre-procesado. En esta primera etapa el objetivo es homogeneizar todos los datos de entrada con el objetivo de poder extraer conclusiones válidas de los resultados obtenidos. Esta etapa, por tanto, tiene un gran impacto en los resultados finales. Se compone de tres operaciones: eliminación del cráneo, normalización en intensidad y normalización espacial. Identificación de puntos singulares. El objetivo de esta etapa es automatizar la identificación de puntos anatómicos (puntos singulares). Esta etapa equivale a la identificación manual de puntos anatómicos por parte del clínico, permitiendo: identificar un mayor número de puntos lo que se traduce en mayor información; eliminar el factor asociado a la variabilidad inter-sujeto, por tanto, los resultados son reproducibles y objetivos; y elimina el tiempo invertido en el marcado manual de puntos. Este trabajo de investigación propone un algoritmo de identificación de puntos singulares (descriptor) basado en una solución multi-detector y que contiene información multi-paramétrica: espacial y asociada a la intensidad. Este algoritmo ha sido contrastado con otros algoritmos similares encontrados en el estado del arte. Registro. En esta etapa se pretenden poner en concordancia espacial dos estudios de imagen de sujetos/pacientes distintos. El algoritmo propuesto en este trabajo de investigación está basado en descriptores y su principal objetivo es el cálculo de un campo vectorial que permita introducir deformaciones deslocalizadas en la imagen (en distintas regiones de la imagen) y tan grandes como indique el vector de deformación asociado. El algoritmo propuesto ha sido comparado con otros algoritmos de registro utilizados en aplicaciones de neuroimagen que se utilizan con estudios de sujetos control. Los resultados obtenidos son prometedores y representan un nuevo contexto para la identificación automática de estructuras. Identificación de lesiones. En esta última etapa se identifican aquellas estructuras cuyas características asociadas a la localización espacial y al área o volumen han sido modificadas con respecto a una situación de normalidad. Para ello se realiza un estudio estadístico del atlas que se vaya a utilizar y se establecen los parámetros estadísticos de normalidad asociados a la localización y al área. En función de las estructuras delineadas en el atlas, se podrán identificar más o menos estructuras anatómicas, siendo nuestra metodología independiente del atlas seleccionado. En general, esta tesis doctoral corrobora las hipótesis de investigación postuladas relativas a la identificación automática de lesiones utilizando estudios de imagen médica estructural, concretamente estudios de resonancia magnética. Basándose en estos cimientos, se han abrir nuevos campos de investigación que contribuyan a la mejora en la detección de lesiones. ABSTRACT Brain injury constitutes a serious social and health problem of increasing magnitude and of great diagnostic and therapeutic complexity. Its high incidence and survival rate, after the initial critical phases, makes it a prevalent problem that needs to be addressed. In particular, according to the World Health Organization (WHO), brain injury will be among the 10 most common causes of disability by 2020. Neurorehabilitation improves both cognitive and functional deficits and increases the autonomy of brain injury patients. The incorporation of new technologies to the neurorehabilitation tries to reach a new paradigm focused on designing intensive, personalized, monitored and evidence-based treatments. Since these four characteristics ensure the effectivity of treatments. Contrary to most medical disciplines, it is not possible to link symptoms and cognitive disorder syndromes, to assist the therapist. Currently, neurorehabilitation treatments are planned considering the results obtained from a neuropsychological assessment battery, which evaluates the functional impairment of each cognitive function (memory, attention, executive functions, etc.). The research line, on which this PhD falls under, aims to design and develop a cognitive profile based not only on the results obtained in the assessment battery, but also on theoretical information that includes both anatomical structures and functional relationships and anatomical information obtained from medical imaging studies, such as magnetic resonance. Therefore, the cognitive profile used to design these treatments integrates information personalized and evidence-based. Neuroimaging techniques represent an essential tool to identify lesions and generate this type of cognitive dysfunctional profiles. Manual delineation of brain anatomical regions is the classical approach to identify brain anatomical regions. Manual approaches present several problems related to inconsistencies across different clinicians, time and repeatability. Automated delineation is done by registering brains to one another or to a template. However, when imaging studies contain lesions, there are several intensity abnormalities and location alterations that reduce the performance of most of the registration algorithms based on intensity parameters. Thus, specialists may have to manually interact with imaging studies to select landmarks (called singular points in this PhD) or identify regions of interest. These two solutions have the same inconvenient than manual approaches, mentioned before. Moreover, these registration algorithms do not allow large and distributed deformations. This type of deformations may also appear when a stroke or a traumatic brain injury (TBI) occur. This PhD is focused on the design, development and implementation of a new methodology to automatically identify lesions in anatomical structures. This methodology integrates algorithms whose main objective is to generate objective and reproducible results. It is divided into four stages: pre-processing, singular points identification, registration and lesion detection. Pre-processing stage. In this first stage, the aim is to standardize all input data in order to be able to draw valid conclusions from the results. Therefore, this stage has a direct impact on the final results. It consists of three steps: skull-stripping, spatial and intensity normalization. Singular points identification. This stage aims to automatize the identification of anatomical points (singular points). It involves the manual identification of anatomical points by the clinician. This automatic identification allows to identify a greater number of points which results in more information; to remove the factor associated to inter-subject variability and thus, the results are reproducible and objective; and to eliminate the time spent on manual marking. This PhD proposed an algorithm to automatically identify singular points (descriptor) based on a multi-detector approach. This algorithm contains multi-parametric (spatial and intensity) information. This algorithm has been compared with other similar algorithms found on the state of the art. Registration. The goal of this stage is to put in spatial correspondence two imaging studies of different subjects/patients. The algorithm proposed in this PhD is based on descriptors. Its main objective is to compute a vector field to introduce distributed deformations (changes in different imaging regions), as large as the deformation vector indicates. The proposed algorithm has been compared with other registration algorithms used on different neuroimaging applications which are used with control subjects. The obtained results are promising and they represent a new context for the automatic identification of anatomical structures. Lesion identification. This final stage aims to identify those anatomical structures whose characteristics associated to spatial location and area or volume has been modified with respect to a normal state. A statistical study of the atlas to be used is performed to establish which are the statistical parameters associated to the normal state. The anatomical structures that may be identified depend on the selected anatomical structures identified on the atlas. The proposed methodology is independent from the selected atlas. Overall, this PhD corroborates the investigated research hypotheses regarding the automatic identification of lesions based on structural medical imaging studies (resonance magnetic studies). Based on these foundations, new research fields to improve the automatic identification of lesions in brain injury can be proposed.

Cardiac magnetic resonance imaging in the diagnosis and determination of outcome of pulmonary hypertension

Pulmonary hypertension (PH) is a rare but serious condition that causes progressive right ventricular (RV) failure and death. PH may be idiopathic, associated with underlying connective-tissue disease or hypoxic lung disease, and is also increasingly being observed in the setting of heart failure with preserved ejection fraction (HFpEF). The management of PH has been revolutionised by the recent development of new disease-targeted therapies which are beneficial in pulmonary arterial hypertension (PAH), but can be potentially harmful in PH due to left heart disease, so accurate diagnosis and classification of patients is essential. These PAH therapies improve exercise capacity and pulmonary haemodynamics, but their overall effect on the right ventricle remains unclear. Current practice in the UK is to assess treatment response with 6-minute walk test and NYHA functional class, neither of which truly reflects RV function. Cardiac magnetic resonance (CMR) imaging has been established as the gold standard for the evaluation of right ventricular structure and function, but it also allows a non-invasive and accurate study of the left heart. The aims of this thesis were to investigate the use of CMR in the diagnosis of PH, in the assessment of treatment response, and in predicting survival in idiopathic and connective-tissue disease associated PAH. In Chapter 3, a left atrial volume (LAV) threshold of 43 ml/m2 measured with CMR was able to distinguish idiopathic PAH from PH due to HFpEF (sensitivity 97%, specificity 100%). In Chapter 4, disease-targeted PAH therapy resulted in significant improvements in RV and left ventricular ejection fraction (p<0.001 and p=0.0007, respectively), RV stroke volume index (p<0.0001), and left ventricular end-diastolic volume index (p=0.0015). These corresponded to observed improvements in functional class and exercise capacity, although correlation coefficients between Δ 6MWD and Δ RVEF or Δ LVEDV were low. Finally, in Chapter 5, one-year and three-year survival was worse in CTD-PAH (75% and 53%) than in IPAH (83% and 74%), despite similar baseline clinical characteristics, lung function, pulmonary haemodynamics and treatment. Baseline right ventricular stroke volume index was an independent predictor of survival in both conditions. The presence of LV systolic dysfunction was of prognostic significance in CTD-PAH but not IPAH, and a higher LAV was observed in CTD-PAH suggesting a potential contribution from LV diastolic dysfunction in this group.

Magnetic resonance imaging of the vocal tract: techniques and applications

Magnetic resonance (MR) imaging has been used to analyse and evaluate the vocal tract shape through different techniques and with promising results in several fields. Our purpose is to demonstrate the relevance of MR and image processing for the vocal tract study. The extraction of contours of the air cavities allowed the set - up of a number of 3D reconstruction image stacks by means of the combination of orthogonally oriented sets of slices for e ach articulatory gesture, as a new approach to solve the expected spatial under sampling of the imaging process. In result these models give improved information for the visualization of morphologic and anatomical aspects and are useful for partial measure ments of the vocal tract shape in different situations. Potential use can be found in Medical and therapeutic applications as well as in acoustic articulatory speech modelling.

High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets.

OBJECTIVE-We studied whether manganese-enhanced high-field magnetic resonance (MR) imaging (MEHFMRI) could quantitatively detect individual islets in situ and in vivo and evaluate changes in a model of experimental diabetes.RESEARCH DESIGN AND METHODS-Whole pancreata from untreated (n = 3), MnCl(2) and glucose-injected mice (n = 6), and mice injected with either streptozotocin (STZ; n = 4) or citrate buffer (n = 4) were imaged ex vivo for unambiguous evaluation of islets. Exteriorized pancreata of MnCl(2) and glucose-injected mice (n = 6) were imaged in vivo to directly visualize the gland and minimize movements. In all cases, MR images were acquired in a 14.1 Testa scanner and correlated with the corresponding (immuno)histological sections.RESULTS-In ex vivo experiments, MEHFMRI distinguished different pancreatic tissues and evaluated the relative abundance of islets in the pancreata of normoglycemic mice. MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice. However, in the latter measurements the loss of beta-cells was undervalued under the conditions tested. The experiments on the externalized pancreata confirmed that MEHFMRI could visualize native individual islets in living, anesthetized mice.CONCLUSIONS-Data show that MEHFMRI quantitatively visualizes individual islets in the intact mouse pancreas, both ex vivo and in vivo. Diabetes 60:2853-2860, 2011

Three-dimensional black-blood cardiac magnetic resonance coronary vessel wall imaging detects positive arterial remodeling in patients with nonsignificant coronary artery disease.

BACKGROUND: Direct noninvasive visualization of the coronary vessel wall may enhance risk stratification by quantifying subclinical coronary atherosclerotic plaque burden. We sought to evaluate high-resolution black-blood 3D cardiovascular magnetic resonance (CMR) imaging for in vivo visualization of the proximal coronary artery vessel wall. METHODS AND RESULTS: Twelve adult subjects, including 6 clinically healthy subjects and 6 patients with nonsignificant coronary artery disease (10% to 50% x-ray angiographic diameter reduction) were studied with the use of a commercial 1.5 Tesla CMR scanner. Free-breathing 3D coronary vessel wall imaging was performed along the major axis of the right coronary artery with isotropic spatial resolution (1.0x1.0x1.0 mm(3)) with the use of a black-blood spiral image acquisition. The proximal vessel wall thickness and luminal diameter were objectively determined with an automated edge detection tool. The 3D CMR vessel wall scans allowed for visualization of the contiguous proximal right coronary artery in all subjects. Both mean vessel wall thickness (1.7+/-0.3 versus 1.0+/-0.2 mm) and wall area (25.4+/-6.9 versus 11.5+/-5.2 mm(2)) were significantly increased in the patients compared with the healthy subjects (both P<0.01). The lumen diameter (3.6+/-0.7 versus 3.4+/-0.5 mm, P=0.47) and lumen area (8.9+/-3.4 versus 7.9+/-3.5 mm(2), P=0.47) were similar in both groups. CONCLUSIONS: Free-breathing 3D black-blood coronary CMR with isotropic resolution identified an increased coronary vessel wall thickness with preservation of lumen size in patients with nonsignificant coronary artery disease, consistent with a "Glagov-type" outward arterial remodeling. This novel approach has the potential to quantify subclinical disease.

Endorectal Magnetic Resonance Imaging and Spectroscopy Are Useful for Selecting Candidates for Biopsy among Patients with Persistently Elevated Prostate Specific Antigen

To evaluate the efficacy of endorectal Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spetroscopic Imaging (MRSI) combined with total prostate-specific antigen (tPSA) and free prostate-specific antigen (fPSA) in selecting candidates for biopsy. Subjects and Methods: 246 patients with elevated tPSA (median: 7.81 ng/ml) underwent endorectal MRI and MRSI before Transrectal Ultrasound (TRUS) biopsy (10 peripheral + 2 central cores); patients with positive biopsies were treated with radical intention; those with negative biopsies were followed up and underwent MRSI before each additional biopsy if tPSA rose persistently. Mean follow-up: 27.6 months. We compared MRI, MRSI, tPSA, and fPSA with histopathology by sextant and determined the association between the Gleason score and MRI and MRSI. We determined the most accurate combination to detect prostate cancer (PCa) using receiver operating curves; we estimated the odds ratios (OR) and calculated sensitivity, specificity, and positive and negative predictive values. Results: No difference in tPSA was found between patients with and without PCa (p = 0.551). In the peripheral zone, the risk of PCa increased with MRSI grade; patients with high-grade MRSI had the greatest risk of PCa over time (OR = 328.6); the model including MRI, MRSI, tPSA, and fPSA was more accurate (Area under Curve: AUC = 95.7%) than MRI alone (AUC = 85.1%) or fPSA alone (AUC = 78.1%), but not than MRSI alone (94.5%). In the transitional zone, the model was less accurate (AUC = 84.4%). The association (p = 0.005) between MRSI and Gleason score was significant in both zones. Conclusions: MRSI is useful in patients with elevated tPSA. High-grade MRSI lesions call for repeated biopsies. Men with negative MRSI may forgo further biopsies because a significantly high Gleason lesion is very unlikely