Measurement of apparent exchange rates in biological tissue by double diffusion-weighted magnetic resonance imaging

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Diffusion-weighted imaging is a widely applied magnetic resonance technique in medical imaging, especially for tumor and stroke diagnosis. The measured diffusion coefficients allow one to deduce indirectly information about the tissue structure. If, for example, the cell membranes are damaged, this can be observed through an increased diffusion coefficient. However, it is often difficult to obtain a direct relation between the measured diffusion coefficient and microstructural parameters such as membrane permeability. An approach in this regard is the recently proposed double diffusion-weighted imaging technique. Here, the standard experiment is extended by applying a second diffusion weighting sequence block, which is applied after the first diffusion weighting separated by the mixing time. If several compartments with differing diffusion coefficients are present, these are weighted differently by the first filter diffusion weighting. The compartment with higher diffusivity is suppressed. During the mixing time, an exchange between the different compartments can occur due to membrane permeability. Consequently, the diffusion coefficient measured using the second diffusion weighting depends on the mixing time and approaches an equilibrium values for large mixing time. By varying the mixing time, an apparent exchange rate between the compartments can be measured.In our own preparatory work, initial measurements on cell cultures were successful. Firstly, however, a stable in vivo application is not yet possible. Secondly, the relation between the measured parameters and the tissue structure is still poorly understood. One aim of this proposal is thus to develop a stable double diffusion-weighted sequence. To this end, a more flexible sequence shall be developed, with which it becomes possible to determine optimized timing and sequence parameters. Additional gradients shall be implemented to minimize eddy current artifacts. For the cell culture experiments, decoupled phantom fixation devices shall be developed to make the measurements less prone to vibration artifacts. To reduce pulsation artifacts, triggering on the heart cycle is planned to be implemented to ensure that both diffusion weightings are always applied during the diastole.The currently used models for the description of the exchange rate contrast are very simplifying and neglect the influence of the cell membranes on the diffusion process. In order to come to a useful interpretation of the acquired data, extensive simulations and theoretical investigations are to be performed, whose focus will be on the influence of membrane geometry and permeability. The aim is to investigate the relationship between true exchange rates, e.g. between intra- and extracellular space, and the measured, apparent exchange rates.Finally, the potential of exchange rate measurements for tissue characterization shall be evaluated by measurements on healthy subjects and tumor patients.