Modelling Brain Tissue using Magnetic Resonance Imaging

    Research output: Book/ReportPh.D. thesis

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    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking models then use the directions of greatest diffusion as estimates of white matter fibre orientation. Several fibre tracking algorithms have emerged in the last few years that provide reproducible visualizations of three-dimensional fibre bundles. One class of these algorithms is probabilistic tractography. Although probabilistic tractography currently holds great promise as a powerful non-invasive connectivity-measurement tool, its accuracy and limitations remain to be evaluated. Probabilistic tractography was assessed post mortem in an in vitro environment. Postmortem DWI benefits from the possibility of using high-field experimental MR scanners and long scanning times, thereby significantly improving the signal-to-noise ratio (SNR) and anatomical resolution. Moreover, many of the degrading effects observed in vivo, such as physiological noise, are no longer present. However, the post mortem environment differs from that of in vivo both due to a lowered environmental temperature and due to the fixation process itself. We argue that the perfusion fixation procedure employed in this thesis ensures that the postmortem tissue is as close to that of in vivo as possible. Different fibre reconstruction models were tested on a range of different b-values (a b-value is a summary measurement of the strength of the applied diffusion gradients). We conclude that for robust reconstruction of fibre directions, and subsequently for tractography, b-values in the range of ~2000 s/mm2 and ~8000 s/mm2 should be used. Within a two year period, no statistical inter- or intra-brain difference in the diffusion coefficient was found in perfusion fixated minipig brains. However, a decreasing tendency in the diffusion coefficient was found at the last time points about 24 months post mortem and might be explained by an ongoing chemical reaction due to the fixative used. Short-term instabilities within the first 15 hours of DWI scanning were observed and found likely to be caused by the preparation of the postmortem tissue prior to MR scanning. This artefact can be avoided e.g. by simply excluding DW-volumes obtained in the first time period of the scanning session. Probabilistic tractography was validated against two invasive in vivo neuronal tracers that were used to derive a gold standard. A high spatial agreement between tractography and the gold standard was found, and some of the widely known limitations of tractography methods could be confirmed e.g. uncertainty in regions containing crossing fibres, and definition of tract termination. In the thesis we delve behind the published results to describe all the practical issues that had to be considered in order to ensure a reliable outcome, and a successful experiment. This includes the selection of independent anatomical data to be used to derive a gold standard, the selection of a gyrated animal model in place of the human brain, objective selection of the seed region to initiate, and a waypoint region to constrain the tractography results.
    Original languageEnglish
    Publication statusPublished - Nov 2008
    SeriesDTU Compute PHD

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