Investigating Brain Tissue Microstructure using Quantitative Magnetic Resonance Imaging

Abstract

In recent years there has been a considerable research effort in improving the specificity of magnetic resonance imaging (MRI) techniques by employing quantitative methods. These methods offer greater reproducibility over traditional acquisitions, and hold the potential for obtaining improved information at the microstructural level. However, they typically require a longer duration for the experiments as the quantitative information is often obtained from multiple acquisitions. Here, a multi-echo extension of the MP2RAGE pulse sequence for the simultaneous mapping of T1, T2* (and magnetic susceptibility) is introduced, optimized and validated. This acquisition technique can be faster than the separate acquisition of T1 and T2*, and has the advantage of producing intrinsically co-localized maps. This is helpful in reducing the preprocessing complexity, but most importantly it removes the need for image alignment (registration) which is shown to introduce significant bias in quantitative MRI maps. One of the reasons why the knowledge of T1 and T2* is of relevance in neuroscience is because their reciprocal, R1 and R2*, have been shown to predict quantitatively myelin and iron content in ex vivo experiments using a linear model of relaxation. However, the post-mortem results cannot be applied directly to the in vivo case. Therefore, an adaptation of the linear relaxation model to the in vivo case is proposed. This is capable of predicting (with some limitations) the myelin and iron contents of the brain under in vivo conditions, by using prior knowledge from the literature to calibrate the linear coefficients. The dependence of the relaxation parameters from the biochemical composition in brain tissues is further explored with ex vivo experiments. In particular, the hyaluronan component of the extracellular matrix is investigated. The contribution to T1 and T2* is measured with a sophisticated experiments that allow for a greater control over experimental conditions compared to a typical MRI experiment. The result indicate a small but appreciable contribution of hyaluronan to the relaxation parameters. In conclusion, this work develops a method for measuring T1 and T2* maps simultaneously. These are then used to quantify myelin and iron under in vivo conditions using a linear model of relaxation. In parallel, the hyaluronan-based extracellular matrix was shown to be a marginal but measurable component in T1 and T2* relaxation maps in ex vivo experiments

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