Analysis of diffusion processes in the human body by means of magnetic resonance imaging, spectroscopy and tractography
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Abstract
The experiments presented in this thesis were designed to study diffusion processes in the human body under two distinct environmental conditions, i.e. free and restricted diffusion.
In the typical timescales of milliseconds in magnetic resonance imaging (MRI), the diffusion of contrast agent molecules in blood vessels can be regarded as isotropic. However, reliably measured values of the diffusion coefficients have not been reported so far. With this thesis, a new approach to assess the diffusivity of Gd-DOTA as the most commonly used MRI contrast agent is presented. In order to enable direct observation of the complex by means of 1H NMR spectroscopy, the paramagnetic Gd3+ ion of Gd-DOTA was replaced by Ga3+. The diffusion coefficient of Ga-DOTA in D2O at body temperature was measured with high precision using 2D DOSY NMR experiments: D = 4.38(0.04)10e10 m2/s. The hydrodynamic similarity of Ga-DOTA and Gd-DOTA was verified using dielectric relaxation spectroscopy. Consequently, the diffusion coefficient of Ga-DOTA as a hydrodynamic analogue of Gd-DOTA is also valid for the MRI contrast agent. Direct diffusion measurements in human blood were not feasible due to the strong 1H signal background. However, an estimate of the diffusivity in human blood plasma at body temperature was derived using the Stokes-Einstein relation to
correct for the higher solvent viscosity: D_plasma = 2.92(0.25)10e10 m2/s.
Within the framework of the “Panini Project”, anisotropic diffusion along neuron fiber tracts in fixed post mortem human brain specimens was investigated. Using a highly optimized setup, unprecedented spatial resolutions of up to 350μm on a full-bore human 3T MRI system were achieved. Reconstruction of fiber pathways based on the local diffusion orientation distributions showed an impressive level of detail. However, tissue fixation imposed a strong limitation on the achievable angular resolution in the reconstruction of complex neuron microstructures. Using fixed and fresh pig hearts, the proposed method was transferred to cardiac imaging and the impact of tissue fixation on signal intensity and diffusion contrast
was studied. The existence of a structurally stable state in unfixed tissue was demonstrated and allowed for continuous image acquisition over 13h. The helical structure of myocardial fiber bands was accurately reconstructed as were the vessel walls of the aorta, pulmonary trunk and right coronary artery. Analysis of spherical harmonic energy spectra and fractional anisotropy confirmed an increased angular resolution in data sets of unfixed tissue compared to fixed tissue. In a pilot study, the feasibility of high-resolution tractography of unfixed human tissue specimens was investigated. In the human brain, major white matter pathways were successfully reconstructed at 0.9mm isotropic resolution. Fiber reconstructions in the human heart were less accurate as a consequence of shorter relaxation times.
However, both ventricles and parts of several vessel walls were identified in the reconstruction.