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T₁ relaxation and inhomogeneous magnetization transfer in brain : physics and applications Manning, Alan Patrick


A major goal of the Magnetic Resonance Imaging (MRI) community is quantifying myelin in white matter. MRI contrast depends on tissue microstructure, so quantitative models require detailed understanding of Nuclear Magnetic Resonance (NMR) physics in white matter's complex, heterogeneous environment. In this thesis, we study the underlying physics behind two different ¹H contrast mechanisms in white and grey matter tissue: T₁ relaxation and the recently developed inhomogeneous Magnetization Transfer (ihMT). Using ex-vivo white and grey matter samples of bovine brain, we performed a comprehensive solid-state NMR study of T₁ relaxation under six diverse initial conditions. For the first time, we used lineshape fitting to quantify the non-aqueous magnetization during relaxation. A four pool model describes our data well, matching with earlier studies. We also show examples of how the observed T₁ relaxation behaviour depends upon the initial conditions. ihMT's sensitivity to lipid bilayers, like those in myelin, was originally thought to rely upon hole-burning in the supposedly inhomogeneously-broadened lipid lineshape. Our work shows that this is incorrect and that ihMT only requires the presence of dipolar couplings, not a specific kind of line broadening. We developed a simple explanation of ihMT using a spin-1 system. Using solid-state NMR, we then performed measurements of ihMT and T₁D (dipolar order relaxation time) on four samples: a multilamellar lipid system (Prolipid-161), wood, hair, and bovine tendon. ihMT was observed in all samples, even those with homogeneous broadening (wood and hair). Moreover, we saw no evidence of hole-burning. Lastly, we present results from ihMT experiments with CPMG acquisition on the bovine brain samples. We show that myelin water has a higher ihMT signal than water outside the myelin. It was determined that this was due to the unique thermal motion in myelin lipids. In doing so, we developed a useful metric for determining the relative contributions from magnetization transfer and dipolar coupling to ihMT. Also, we applied a qualitative four pool model with dipolar reservoirs. Together, our results are consistent with myelin lipids having a T₁D which is appreciably longer than the T₁D of non-myelin lipids, despite recent measurements to the contrary.

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