Herramienta de modelado disfuncional tridimensional basado en estudios de neuroimagen

El modelado disfuncional basado en estudios de neuroimagen mejora la comprensión de los cambios estructurales provocados ante la presencia de lesiones cerebrales. Actualmente, existen numerosas herramientas para el análisis y procesado de estudios de neuroimagen. Algunas de ellas, como el 3D Slicer, BrainVoyager y el FreeSurfer permiten la creación y navegación sobre modelos tridimensionales cerebrales sin alteraciones estructurales. Sin embargo, no se han detectado herramientas que permitan modelar tridimensionalmente lesiones a partir de estudios de neuroimagen, concretamente de estudios de resonancia magnética. El objetivo de este trabajo es el diseño de una metodología que permite la creación de este tipo de modelos y su visualización y navegación

The relationships between interoception and alexithymic trait. The Self-Awareness Questionnaire in healthy subjects

Interoception is the basic process enabling evaluation of one's own bodily states. Several previous studies suggested that altered interoception might be related to disorders in the ability to perceive and express emotions, i.e., alexithymia, and to defects in perceiving and describing one's own health status, i.e., hypochondriasis. The main aim of the present study was to investigate the relationships between alexithymic trait and interoceptive abilities evaluated by the "Self-Awareness Questionnaire" (SAQ), a novel self-report tool for assessing interoceptive awareness. Two hundred and fifty healthy subjects completed the SAQ, the Toronto Alexithymia Scale-20 items (TAS-20), and a questionnaire to assess hypochondriasis, the Illness Attitude Scale (IAS). The SAQ showed a two-factor structure, with good internal consistency (Cronbach's alpha = 0.88). We observed significant direct correlations between SAQ, TAS-20 and two of its subscales, and the IAS. Regression analysis confirmed that the difficulty in identifying and expressing emotions is significantly related with awareness for one's own interoceptive feelings and with a tendency to misinterpret and amplify bodily sensations. From a clinical point of view, the assessment of interoceptive awareness by the SAQ could be pivotal in evaluating several psychopathological conditions, such as the somatoform disorders

The relationships between interoception and alexithymic trait. The Self-Awareness Questionnaire in healthy subjects

Interoception is the basic process enabling evaluation of one's own bodily states. Several previous studies suggested that altered interoception might be related to disorders in the ability to perceive and express emotions, i.e., alexithymia, and to defects in perceiving and describing one's own health status, i.e., hypochondriasis. The main aim of the present study was to investigate the relationships between alexithymic trait and interoceptive abilities evaluated by the "Self-Awareness Questionnaire" (SAQ), a novel self-report tool for assessing interoceptive awareness. Two hundred and fifty healthy subjects completed the SAQ, the Toronto Alexithymia Scale-20 items (TAS-20), and a questionnaire to assess hypochondriasis, the Illness Attitude Scale (IAS). The SAQ showed a two-factor structure, with good internal consistency (Cronbach's alpha = 0.88). We observed significant direct correlations between SAQ, TAS-20 and two of its subscales, and the IAS. Regression analysis confirmed that the difficulty in identifying and expressing emotions is significantly related with awareness for one's own interoceptive feelings and with a tendency to misinterpret and amplify bodily sensations. From a clinical point of view, the assessment of interoceptive awareness by the SAQ could be pivotal in evaluating several psychopathological conditions, such as the somatoform disorders

Otimização de sequências e ferramentas de processamento para quantificação do ferro (QSM)

As doenças neurodegenerativas, como o caso das doenças de Parkinson, Huntington e Tremor Essencial não possuem, atualmente, terapias de cura, mas sim tratamentos que prolongam a vida e melhoram a qualidade de vida dos pacientes. Todavia, têm vindo a ser feitos esforços por parte de investigadores para descobrir os mecanismos da génese destas patologias de modo a tornar possível o seu diagnóstico precoce e com isso estudar estratégias de implementação de novas soluções. Assim, esta dissertação surge no seguimento de uma serie de trabalhos que se focaram particularmente na caracterização destas doenças. Especificamente, este estudo utilizou dados de pacientes do Hospital Santa Maria (Lisboa) submetidos a protocolos de sequências de aquisição de imagens multi-eco de ressonância magnética de 3T em 2D e 3D ponderadas em T2 e T2* para diagnóstico da doença de Parkinson tendo-se concentrado na otimização destes, na otimização de ferramentas e mecanismos para o seu pós-processamento. Focou-se também na quantificação do ferro como um biomarcador relevante nas regiões normalmente afetadas, como é o caso dos núcleos da base (globo pálido, putamen, núcleo caudado, substantia nigra e núcleo rubro). Nestes núcleos ocorre acumulação anómala de ferro ligada à progressão da neurodegeneração, segundo estudos recentes. Nesta tese foi utilizada uma técnica conhecida como mapeamento quantitativo de suscetibilidade magnética (QSM – Quantitative Susceptibility Mapping), que avalia a diferença de suscetibilidades magnéticas entre tecidos, que por sua vez indicam o balanço entre paramagnetismo e diamagnetismo das espécies moleculares presentes. Utilizando software designado para este fim, criado por investigadores de Cornell MRI Research Lab, que se baseia no algoritmo MEDI (Morphology Enabled Dipole Inversion) geraram-se, depois de algumas adaptações ao código original, os mapas das suscetibilidades, cujos volumes de interesse foram em seguida segmentados de forma automática e manual, de modo a se estimarem os valores de suscetibilidade (médias e desvios padrão) das estruturas segmentadas. Compararam-se os resultados obtidos das suscetibilidades entre os vários ecos, as várias estruturas, entre as aquisições 2D e 3D e entre pacientes considerados como controlo e aqueles com sinais de neurodegeneração, tendo sido demonstrada a viabilidade dos parâmetros de aquisição, métodos de processamento e ferramentas de mapeamento e segmentação utilizadas e comprovada a acumulação de ferro nos volumes de interesse, proporcional aos valores de suscetibilidade obtidos

Trustworthy Deep Learning for Medical Image Segmentation

Despite the recent success of deep learning methods at achieving new state-of-the-art accuracy for medical image segmentation, some major limitations are still restricting their deployment into clinics. One major limitation of deep learning-based segmentation methods is their lack of robustness to variability in the image acquisition protocol and in the imaged anatomy that were not represented or were underrepresented in the training dataset. This suggests adding new manually segmented images to the training dataset to better cover the image variability. However, in most cases, the manual segmentation of medical images requires highly skilled raters and is time-consuming, making this solution prohibitively expensive. Even when manually segmented images from different sources are available, they are rarely annotated for exactly the same regions of interest. This poses an additional challenge for current state-of-the-art deep learning segmentation methods that rely on supervised learning and therefore require all the regions of interest to be segmented for all the images to be used for training. This thesis introduces new mathematical and optimization methods to mitigate those limitations.Comment: PhD thesis successfully defended on 1st July 2022. Examiners: Prof Sotirios Tsaftaris and Dr Wenjia Ba

Assessment of MRI scanner performance for preclinical functional studies

Functional Magnetic Resonance Imaging (fMRI) based studies are rapidly expanding in the field of preclinical research. The majority of these studies use Echo Planar Imaging (EPI) to measure Blood Oxygenation Level Dependent (BOLD) signal contrasts in the brain. In such studies the magnitude and statistical significances of these contrasts are then related to brain function and cognition. It is assumed that any observed signal contrast is ultimately due to differences in biological state and that scanner performance is stable and repeatable between subjects and studies. However, due to confounding issues introduced by in vivo subjects, little work has been undertaken to test this basic assumption. As the BOLD signal contrasts generated in such experiments are often very low, even small changes in scanner performance may dominate the BOLD contrast, distorting any biological conclusions drawn. A series of fMRI phantoms were produced to measure scanner performance independent of biological subjects. These phantoms produce specified signal contrast levels on demand during an fMRI scan by means of current-induced magnetic field gradients. These were used to generate data sets that emulated the BOLD signal contrast of in vivo imaging. Two studies examining scanner performance were then conducted on high-field preclinical MRI scanners. Firstly, in a longitudinal study on a single scanner, measurements were taken over a number of days across a week long period and then every two months over a year long period. Secondly, the behaviour of four preclinical scanners (three at 7T, one at 9.4T) was comparatively assessed. Measurements of several imaging parameters including contrast generated and functional contrast to noise ratio (fCNR) were obtained in both studies. If the scanners involved are truly comparable then they should generate similar measurement values. Across both studies parameter measurements showed significant differences for identical contrast settings on the phantom. Although signal contrast itself proved very comparable across the studies fCNR proved to be highly variable. As well as these measurements of longer tem behaviour proving variable, short and mid-term signal stability displayed a wide range of variability. Variations in the level and quality of both signal and noise were observed. Modelling of signal changes based on fundamental physical principles was also performed for comparison. The impact of these behaviours and variations on in vivo studies could result in skewed biological conclusions at any single site, with some sites exhibiting greater problems than others. The multisite results suggest potential difficulties when comparing biological conclusions between sites, even when using identical imaging parameters. In summary, these results suggest that a cautious approach should be taken with the conclusions of both fMRI and associated resting state connectivity studies that use EPI as their acquisition sequence. Improvements to both the experimental design of studies and regular quality monitoring of scanners should be undertaken to minimise these effects. Clinical MRI scanners should also be assessed for similar aberrations in behaviour

MSSEG-2 challenge proceedings: Multiple sclerosis new lesions segmentation challenge using a data management and processing infrastructure

International audienceThis proceedings book gathers methodological papers describing the segmenta-tion methods evaluated at the second MICCAI Challenge on Multiple Sclerosisnew lesions segmentation challenge using a data management and processinginfrastructure. This challenge took place as part of an effort of the OFSEP1(French registry on multiple sclerosis aiming at gathering, for research purposes,imaging data, clinical data and biological samples from the French populationof multiple sclerosis subjects) and FLI2(France Life Imaging, devoted to setupa national distributed e-infrastructure to manage and process medical imagingdata). These joint efforts are directed towards automatic segmentation of MRIscans of MS patients to help clinicians in their daily practice. This challengetook place at the MICCAI 2021 conference, on September 23rd 2021.More precisely, the problem addressed in this challenge is as follows. Con-ventional MRI is widely used for disease diagnosis, patient follow-up, monitoringof therapies, and more generally for the understanding of the natural history ofMS. A growing literature is interested in the delineation of new MS lesions onT2/FLAIR by comparing one time point to another. This marker is even morecrucial than the total number and volume of lesions as the accumulation of newlesions allows clinicians to know if a given anti-inflammatory DMD (disease mod-ifying drug) works for the patient. The only indicator of drug efficacy is indeedthe absence of new T2 lesions within the central nervous system. Performingthis new lesions count by hand is however a very complex and time consumingtask. Automating the detection of these new lesions would therefore be a majoradvance for evaluating the patient disease activity.Based on the success of the first MSSEG challenge, we have organized aMICCAI sponsored online challenge, this time on new MS lesions detection3.This challenge has allowed to 1) estimate the progress performed during the2016 - 2021 period, 2) extend the number of patients, and 3) focus on the newlesions crucial clinical marker. We have performed the evaluation task on a largedatabase (100 patients, each with two time points) compiled from the OFSEPcohort with 3D FLAIR images from different centers and scanners. As in ourprevious challenge, we have conducted the evaluation on a dedicated platform(FLI-IAM) to automate the evaluation and remove the potential biases due tochallengers seeing the images on which the evaluation is made

Consistência e fiabilidade de aplicações informáticas em Neuroimagem

Dissertação de mestrado integrado em Engenharia BiomédicaCom os avanços tecnológicos atuais foram sendo desenvolvidas ferramentas informáticas capazes de efetuar uma análise estrutural ou funcional dos dados neuroimagiológicos de ressonância magnética. As aplicações atuais fornecem aos seus utilizadores uma oportunidade única de análise e visualização sem precedentes. No entanto estas carecem de padronização, daí que muitos dos resultados obtidos numa aplicação não possam ser reproduzidos noutra. Esta falta de interoperabilidade nos resultados obtidos surge então como um problema de difícil resolução. Com o objetivo de facilitar a seleção do software de análise ideal, foi feito um estudo comparativo entre ferramentas informáticas aplicadas a diversos casos de estudo tendo por base a segmentação cerebral e a análise funcional de neuroimagens. Além dos casos práticos analisados foi feito um levantamento bibliográfico relacionado com a ressonância magnética estrutural e funcional, assim como com as aplicações que lhes estão relacionadas. Os resultados obtidos no estudo estrutural foram analisados segundo os parâmetros das médias, desvio-padrão e dispersão dos dados. Relativamente aos resultados da análise funcional, estes foram avaliados em termos de número de clusters ativos detetados, a localização dos mesmos na anatomia cerebral e a significância estatística dessas ativações, verificando-se que a aplicação mais indicada para segmentação cerebral é o FreeSurfer e para a análise funcional de neuroimagens o SPM. A conclusão deste trabalho salienta a necessidade de padronizar as diferentes ferramentas e técnicas utlizadas em estudos funcionais e estruturais de neuroimagens de forma a aproveitar todas as potencialidades da técnica de ressonância magnética.With the current technological advances, tools capable of performing a structural or functional analysis of neuroimagiological data from MRI have been developed. Current applications provide its users a unique opportunity of unprecedented visualization and analysis. However, there is a lack of standardization, so many of the results obtained in an application may not be reproduced in another. This lack of interoperability of obtained results then arises as a problem of difficult resolution. Aiming to facilitate the selection of the ideal analysis software, a comparative study between tools applied to several case studies based on brain segmentation and analysis of functional neuroimaging was made. In addition to the case studies analyzed, a bibliographical survey related to structural and functional magnetic resonance imaging was made, as well as with the applications that are related to them. Regarding the results obtained in the study, these were analyzed according to the structural parameters of the averages, standard deviation and dispersion of the data. Relatively to the results of the functional analysis, these have been assessed in terms of the number of active clusters detected, their location in the brain anatomy and the statistical significance of these activations, verifying that the application best suited to brain segmentation is the FreeSurfer and to the analysis of functional neuroimaging is the SPM. The conclusion of this work emphasizes the need to standardize the different tools and techniques used in functional and structural neuroimaging studies in order to take advantage of the full potential of MRI modalities

Análisis de la conectividad efectiva y funcional en los paradigmas de memoria de trabajo, anticipación a la recompensa y reconocimiento facial de emociones: un estudio de resonancia magnética funcional (FMRI)

En muchos estudios se ha establecido el grupo de regiones cerebrales que se ven presentes o ausentes en poblaciones clínicamente enfermas, generalmente, por medio de técnicas de conectividad cerebral cubriendo un solo proceso cognitivo a la vez. Lo anterior ha servido para lograr caracterizar esas redes neuronales, sin embargo, hay muy pocos trabajos donde se realiza un panorama más completo de la red neuronal implicada en dicho proceso cognitivo y que implementan más de un tipo de técnica de conectividad cerebral para caracterizar dicha red. El objetivo del presente estudio fue caracterizar las redes neuronales implicadas en los procesos de memoria de trabajo, anticipación a la recompensa, y procesamiento emocional aversivo mediante conectividad funcional y conectividad efectiva. Se evaluaron 10 sujetos adultos voluntarios sanos (5H, 5M) mediante fMRI utilizando los paradigmas N-Back (carga de memoria de trabajo 0-Back y 2- Back), Monetary Incentive Delay task (MIDt, anticipación a la recompensa) y Face Matching task (FMt, procesamiento emocional aversivo). Se caracterizaron las redes neuronales implicadas en estos procesos cognitivos mediante Imagenología por Resonancia Magnética funcional (fMRI), Análisis de Componentes Independientes (ICA) para medir la conectividad funcional y para estimar las dinámicas (conectividad efectiva ) que se producen entre algunas de las regiones involucradas en los procesos mencionados anteriormente se implementó la técnica del Modelado Causal Dinámico (DCM). El resultado del análisis de la conectividad efectiva de N-Back indica una fuerte conexión de la corteza dorso lateral Prefrontal a la corteza parietal en ambas direcciones, así mismo, de la corteza parietal a la visual, mientras que no se detectó alguna influencia significativa por parte de las perturbaciones externas. El resultado del análisis de la conectividad efectiva de N-Back indica una fuerte conexión de la corteza dorso lateral Prefrontal a la corteza parietal en ambas direcciones, así mismo, de la corteza parietal a la visual, mientras que no se detectó alguna influencia significativa por parte de las perturbaciones externas. El resultado del modelo de MIDt indicó que hubo una fuerte influencia de las perturbaciones externas (estímulos de ganar y perder) sobre el tálamo, así como, una fuerte conexión entre el tálamo y el núcleo accumbens. Los resultados del modelado del FMt mostraron que solo la perturbación externa con los estímulos neutrales fue significativa, así como, las conexiones de la amígdala al giro fusiforme y de la amígdala a la corteza Orbitofrontal. Del ICA, no se encontró ningún componente independiente dentro de la red del N-back, mientras que para el MIDt se encontró un solo componente independiente que representa la conectividad dentro de esta red neuronal y para el FMt encontramos dos componentes que representan la conectividad neuronal. Para la obtención de los componentes independientes significativos se implementó el algoritmo de FastICA con 20 iteraciones para darle validez. En resumen, las técnicas de conectividad funcional y conectividad efectiva nos permitieron denotar las regiones cerebrales involucradas en los tres procesos cognitivos de nuestro interés. En el caso del Modelado Causal Dinámico, para la memoria de trabajo, nuestro modelo mostro conexiones endógenas significativas entre la corteza dorsolateral prefrontal (dlPFC) y la corteza parietal (PC), así como, en la corteza parietal con la corteza visual. Para la anticipación a la recompensa solo se encontró significativa la conexión endógena del tálamo al núcleo accumbens y las perturbaciones externas con los estímulos de ganar y perder. Mientras que para el reconocimiento emocional aversivo se encontraron conexiones endógenas significativas entre la amígdala (AMI) y el giro fusiforme (GF), y, entre la amígdala y la corteza orbito frontal (OFC); solo las perturbaciones externas con contenido emocional neutral fueron significativas. A pesar de coincidir en varias características 5 con los modelos de otros autores consideramos que los resultados para este tipo de análisis no son concluyentes debido a distintos factores, entre ellos, el reducido número de la muestra. Para el Análisis por Componentes Independientes (ICA), de la memoria de trabajo, no se pudo representar la red neuronal con ningún componente independiente, lo anterior, puede atribuirse a la complejidad de la carga de memoria utilizada en el experimento provocando que las modulaciones entre ambas cargas de memoria (0-Back y 2-Back) sean muy similares entre sí. En el caso de la anticipación a la recompensa y del procesamiento emocional aversivo se comprueba la existencia del conjunto de regiones cerebrales subyacentes a estos procesos. La red neuronal “Centraltemporal”, representada por el componente independiente encontrado, IC11, se encuentra modulada positivamente para los estímulos de ganar dentro del proceso de anticipación a la recompensa. Por otro lado, la red neuronal “Fusiforme-Parahipocampal”, representada por el componente independiente, IC10, y la red neuronal “Temporal superior-Central-Insular”, representada por el componente independiente, IC16, ambas dentro del proceso emocional aversivo, se encuentran moduladas positivamente para los estímulos con contenido facial e imágenes neutrales, respectivamente. Siendo estas tres redes neuronales bajo estos dos procesos cognitivos las aportaciones más notables de este estudio