Assessing white matter microstructural changes in idiopathic normal pressure hydrocephalus using voxel-based R2* relaxometry analysis

BackgroundR2* relaxometry and quantitative susceptibility mapping can be combined to distinguish between microstructural changes and iron deposition in white matter. Here, we aimed to explore microstructural changes in the white matter associated with clinical presentations such as cognitive impairment in patients with idiopathic normal-pressure hydrocephalus (iNPH) using R2* relaxometry analysis in combination with quantitative susceptibility mapping.MethodsWe evaluated 16 patients clinically diagnosed with possible or probable iNPH and 18 matched healthy controls (HC) who were chosen based on similarity in age and sex. R2* and quantitative susceptibility mapping were compared using voxel-wise and atlas-based one-way analysis of covariance (ANCOVA). Finally, partial correlation analyses were performed to assess the relationship between R2* and clinical presentations.ResultsR2* was lower in some white matter regions, including the bilateral superior longitudinal fascicle and sagittal stratum, in the iNPH group compared to the HC group. The voxel-based quantitative susceptibility mapping results did not differ between the groups. The atlas-based group comparisons yielded negative mean susceptibility values in almost all brain regions, indicating no clear paramagnetic iron deposition in the white matter of any subject. R2* and cognitive performance scores between the left superior longitudinal fasciculus (SLF) and right sagittal stratum (SS) were positively correlated. In addition to that, R2* and gait disturbance scores between left SS were negatively correlated.ConclusionOur analysis highlights the microstructural changes without iron deposition in the SLF and SS, and their association with cognitive impairment and gait disturbance in patients with iNPH

Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis

Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response

Towards in vivo g-ratio mapping using MRI: Unifying myelin and diffusion imaging

BACKGROUND: The g-ratio, quantifying the comparative thickness of the myelin sheath encasing an axon, is a geometrical invariant that has high functional relevance because of its importance in determining neuronal conduction velocity. Advances in MRI data acquisition and signal modelling have put in vivo mapping of the g-ratio, across the entire white matter, within our reach. This capacity would greatly increase our knowledge of the nervous system: how it functions, and how it is impacted by disease. NEW METHOD: This is the second review on the topic of g-ratio mapping using MRI. RESULTS: This review summarizes the most recent developments in the field, while also providing methodological background pertinent to aggregate g-ratio weighted mapping, and discussing pitfalls associated with these approaches. COMPARISON WITH EXISTING METHODS: Using simulations based on recently published data, this review reveals caveats to the state-of-the-art calibration methods that have been used for in vivo g-ratio mapping. It highlights the need to estimate both the slope and offset of the relationship between these MRI-based markers and the true myelin volume fraction if we are really to achieve the goal of precise, high sensitivity g-ratio mapping in vivo. Other challenges discussed in this review further evidence the need for gold standard measurements of human brain tissue from ex vivo histology. CONCLUSIONS: We conclude that the quest to find the most appropriate MRI biomarkers to enable in vivo g-ratio mapping is ongoing, with the full potential of many novel techniques yet to be investigated

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