The UTE and ZTE Sequences at Ultra-High Magnetic Field Strengths: A Survey

UTE (Ultrashort Echo Time) and ZTE (Zero Echo Time) sequences have been developed to detect short T2 relaxation signals coming from regions that are unable to be detected by conventional MRI methods. Due to the high dipole-dipole interactions in solid and semi-solid tissues, the echo time generated is simply not enough to produce a signal using conventional imaging method, often leading to void signal coming from the discussed areas. By the application of these techniques, solid and semi-solid areas can be imaged which can have a profound impact in clinical imaging. High and Ultra-high field strength (UHF) provides a vital advantage in providing better sensitivity and specificity of MR imaging. When coupled with the UTE and ZTE sequences, the image can recover void signals as well as a much-improved signal quality. To further this strategy, secondary data from various research tools was obtained to further validate the research while addressing the drawbacks to this approach. It was found that UTE and ZTE sequences coupled with some techniques such as qualitative imaging and new trajectories are very crucial for accurate image depiction of the areas of the musculoskeletal system, neural system, lung imaging and dental imaging

Quantitative MRI in leukodystrophies

Leukodystrophies constitute a large and heterogeneous group of genetic diseases primarily affecting the white matter of the central nervous system. Different disorders target different white matter structural components. Leukodystrophies are most often progressive and fatal. In recent years, novel therapies are emerging and for an increasing number of leukodystrophies trials are being developed. Objective and quantitative metrics are needed to serve as outcome measures in trials. Quantitative MRI yields information on microstructural properties, such as myelin or axonal content and condition, and on the chemical composition of white matter, in a noninvasive fashion. By providing information on white matter microstructural involvement, quantitative MRI may contribute to the evaluation and monitoring of leukodystrophies. Many distinct MR techniques are available at different stages of development. While some are already clinically applicable, others are less far developed and have only or mainly been applied in healthy subjects. In this review, we explore the background, current status, potential and challenges of available quantitative MR techniques in the context of leukodystrophies

Deep Gray Matter Demyelination Detected by Magnetization Transfer Ratio in the Cuprizone Model

Abstract In multiple sclerosis (MS), the correlation between lesion load on conventional magnetic resonance imaging (MRI) and clinical disability is weak. This clinico-radiological paradox might partly be due to the low sensitivity of conventional MRI to detect gray matter demyelination. Magnetization transfer ratio (MTR) has previously been shown to detect white matter demyelination in mice. In this study, we investigated whether MTR can detect gray matter demyelination in cuprizone exposed mice. A total of 54 female C57BL/6 mice were split into one control group () and eight cuprizone exposed groups (Ns~6). The mice were exposed to 0:2% (w/w) cuprizone for up to six weeks. MTR images were obtained at a 7 Tesla Bruker MR-scanner before cuprizone exposure, weekly for six weeks during cuprizone exposure, and once two weeks after termination of cuprizone exposure. Immunohistochemistry staining for myelin (anti-Proteolopid Protein) and oligodendrocytes (anti-Neurite Outgrowth Inhibitor Protein A) was obtained after each weekly scanning. Rates of MTR change and correlations between MTR values and histological findings were calculated in five brain regions. In the corpus callosum and the deep gray matter a significant rate of MTR value decrease was found, 0:96% per week (pv:0001) and 0:39% per week (pv:0001) respectively. The MTR values correlated to myelin loss as evaluated by immunohistochemistry (Corpus callosum: R 2~: 43, pv:0001. Deep gray matter: R 2~: 21, pv:001), but did not correlate to oligodendrocyte density. Significant results were not found in the cerebellum, the olfactory bulb or the cerebral cortex. This study shows that MTR can be used to detect demyelination in the deep gray matter, which is of particular interest for imaging of patients with MS, as deep gray matter demyelination is common in MS, and is not easily detected on conventional clinical MRI

An interactive meta-analysis of MRI biomarkers of myelin

Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analysed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization (https://neurolibre.github.io/myelin-meta-analysis). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology

Myelin imaging and characterization by magnetic resonance imaging

280 p.Los axones neuronales están recubiertos de una membrana lipídica llamada mielina, que protege a los axones y posibilita una transmisión rápida y eficiente del impulso eléctrico. En ciertas patologías como la lesión cerebral traumática, la isquemia o principalmente, en la esclerosis múltiple, la pérdida de mielina o desmielinización da lugar a la muerte neuronal y por consiguiente a la pérdida de capacidades cognitivas. Este estado puede ser revertido por medio de la remielinización, en la que los oligodendrocitos mielinizantes del sistema nervioso central regeneran la vaina de mielina, evitando la degeneración de las neuronas. En los últimos años se ha realizado un esfuerzo considerable en el desarrollo de terapias remielinizantes. Para ello, es imprescindible el desarrollo de técnicas para la evaluación no-invasiva de estas terapias y una caracterización profunda de los procesos de desmielinización y remielinización. En este contexto, la imagen por resonancia magnética (IRM) juega un papel fundamental por su carácter no-invasivo, alta resolución y versatilidad.Los principales objetivos de esta tesis han sido el desarrollo de protocolos de IRM para la cuantificación de mielina y la caracterización de los procesos de remielinización y desmielinización a través de resonancia magnética funcional en reposo. Para ello se ha utilizado como base el modelo murinocuprizona, en la que la administración del tóxico da lugar a la desmielinización en el cerebro, seguido por la remielinización. Los datos y conclusiones obtenidas se han contrastado en otros modelos de ratón, como en modelos de Alzheimer o en ratones sanos envejecidos.A grandes rasgos, hemos podido concluir que la imagen ponderada en peso T2 es la más específica y sensible para la cuantificación de mielina en el modelo cuprizona. Por ello, en este trabajo se propone la utilización de la imagen ponderada en peso T2 para la evaluación de terapias remielinizantes en el modelo cuprizona. Sin embargo, el interés de realizar imagen multiparamétríca ha quedado al descubierto al realizar imagen de modelos de ratón de Alzheimer, pudiendo detectar patología no relacionada con pérdida de mielina en zonas de materia blanca.Así mismo, hemos podido comprobar como la desmielinización conlleva la pérdida de la conectividad y función cerebral y la remielinización posibilita la recuperación por medio de la resonancia magnética funcional en reposo. Además, el potencial agente remielinizante clemastina, ha demostrado su capacidad de promover la remielinización a nivel anatómico y funcional tras 2 semanas de tratamiento. Finalmente, se ha realizado un estudio para determinar el efecto del envejecimiento en la conectividad del cerebro. Hemos podido observar que en ratones sanos, se ha observado un incremento de la conectividad cerebral hasta el mes 8, seguido de un descenso hasta el mes 13, probablemente debido a la neurodegeneración.En este trabajo hemos contribuido al desarrollo de terapias remielinizantes, por un lado, desarrollando protocolos de imagen para la cuantificación de mielina en modelos animales y por otro lado, caracterizando la desmielinización y remielinización a nivel funcional y anatómico

Quantification de la microstructure de la moelle épinière humaine par IRM et application chez des patients avec sclérose en plaques

Les pathologies degeneratives de la moelle epiniere sont encore aujourd'hui mal diagnostiquees et laissent les patients dans un etat de souffrance et de doute. L'imagerie par resonance magnetique (IRM) permet d'obtenir des informations quantitatives sur la microstructure de la matiere blanche. Nous avons demontre la faisabilité d'estimer la densite et le diametre des axones dans la moelle epiniere humaine en utilisant une IRM unique au monde installee a Boston, le "scanner Connectom", capable d'atteindre des gradients de champ magnetique de r@@mT/m. Cependant cette methode ne donne qu'une information partielle de la microstructure de la matiere blanche et ne tient pas compte de la gaine de myeline entourant les axones. Cette gaine de myeline permet d'assurer une bonne conductivite des axones et peut degenerer dans certaines pathologies comme la sclerose en plaques. Nos collaborateurs de l'université McGill ont proposé de combiner cette technique avec l'IRM quantitative de la myeline afin de mesurer son g-ratio, ou ratio du diametre interne sur externe de la myeline. Durant cette these, j’ai mis en place les techniques d’IRM de la microstructure, j’ai valide ces methodes en utilisant l’histologie a large champ de vue, puis je les ai appliquees chez des patients avec sclerose en plaques pour une application clinique.----------ABSTRACT Degenerative pathologies of the spinal cord are still difficult to diagnose today, leaving patients in a state of constant suffering and constant doubt about their future. Magnetic Resonance Imaging (MRI) can gather quantitative information about the white matter microstructure by playing on the phase and relaxation of the spins. Using a unique MRI system capable of magnetic gradients of r@@mT/m, the “Connectom scanner”, we showed that neuronal fibers (axons) density and diameter can be measured in the human spinal cord in vivo using diffusion MRI. Although very informative, this method only provides a partial description of the tissue and no direct information about the myelin sheath that surrounds the axons is extracted. The myelin sheath improves the speed and frequency of action potentials that are transmitted through the axons, and an alteration of myelin integrity leads to paralysis in diseases such as multiple sclerosis. Our collaborators at McGill University proposed to combine the diffusion technique with quantitative myelin imaging technique in order to measure the thickness of the myelin sheath. In this thesis, I developed quantitative MRI techniques in the spinal cord, I validated these methods using large-scale histology, and I applied them on patients with multiple sclerosis

Longitudinal evaluation of demyelinated lesions in a multiple sclerosis model using ultrashort echo time magnetization transfer (UTE-MT) imaging

Alterations in myelin integrity are involved in many neurological disorders and demyelinating diseases, such as multiple sclerosis (MS). Although magnetic resonance imaging (MRI) is the gold standard method to diagnose and monitor MS patients, clinically available MRI protocols show limited specificity for myelin detection, notably in cerebral grey matter areas. Ultrashort echo time (UTE) MRI has shown great promise for direct imaging of lipids and myelin sheaths, and thus holds potential to improve lesion detection. In this study, we used a sequence combining magnetization transfer (MT) with UTE ("UTE-MT", TE ​= ​76 ​μs) and with short TE ("STE-MT", TE ​= ​3000 ​μs) to evaluate spatial and temporal changes in brain myelin content in the cuprizone mouse model for MS on a clinical 7 ​T scanner. During demyelination, UTE-MT ratio (UTE-MTR) and STE-MT ratio (STE-MTR) values were significantly decreased in most white matter and grey matter regions. However, only UTE-MTR detected cortical changes. After remyelination in subcortical and cortical areas, UTE-MTR values remained lower than baseline values, indicating that UTE-MT, but not STE-MT, imaging detected long-lasting changes following a demyelinating event. Next, we evaluated the potential correlations between imaging values and underlying histopathological markers. The strongest correlation was observed between UTE-MTR and percent coverage of myelin basic protein (MBP) immunostaining (r2 ​= ​0.71). A significant, although lower, correlation was observed between STE-MTR and MBP (r2 ​= ​0.48), and no correlation was found between UTE-MTR or STE-MTR and gliosis immunostaining. Interestingly, correlations varied across brain substructures. Altogether, our results demonstrate that UTE-MTR values significantly correlate with myelin content as measured by histopathology, not only in white matter, but also in subcortical and cortical grey matter regions in the cuprizone mouse model for MS. Readily implemented on a clinical 7 ​T system, this approach thus holds great potential for detecting demyelinating/remyelinating events in both white and grey matter areas in humans. When applied to patients with neurological disorders, including MS patient populations, UTE-MT methods may improve the non-invasive longitudinal monitoring of brain lesions, not only during disease progression but also in response to next generation remyelinating therapies