Physical Chemistry

Lund University

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Multidimensional diffusion MRI

Diffusion MRI is a powerful non-invasive method for studying molecular motion on the micrometer length scale and millisecond time scale. By measuring the self-diffusion of molecules in biological tissues, we obtain information about microscopic structures that are too small to resolve in conventional images. In this project, we use principles from multidimensional solid-state NMR spectroscopy to design new MRI pulse sequences and data processing methods for quantifying cell shape, heterogeneity, alignment, and membrane permeability. The structure of biological tissues can be mimicked by carefully designed colloidal model systems such as emulsions, gels, and liquid crystals. The new MRI methods are first tested by computer simulations, subsequently applied to colloidal model systems, simple cellular systems and excised tissue, and finally implemented on clinical MRI equipment.

Software for setup and analysis of multidimensional diffusion MRI

Commercialization of multidimensional diffusion MRI


J. P. de Almeida Martins, C. M. W. Tax, F. Szczepankiewicz, D. K. Jones, C.-F. Westin, and D. Topgaard. Transferring principles of solid-state and Laplace NMR to the field of in vivo brain MRI. Magn. Reson. 1, 27-43 (2020).

A. Reymbaut, P. Mezzani, J. P. de Almeida Martins, and D. Topgaard. Accuracy and precision of statistical descriptors obtained from multidimensional diffusion signal inversion algorithms. NMR Biomed., (Accepted).

D. Topgaard. Multiple dimensions for random walks. J. Magn. Reson. 306, 150-154 (2019).

D. Topgaard. Diffusion tensor distribution imaging. NMR Biomed. 32, e4066 (2019).

N. Moutal, M. Nilsson, D. Topgaard, and D. Grebenkov. The Kärger vs bi-exponential model: Theoretical insights and experimental validations. J. Magn. Reson. 296, 72-78 (2018).

J. P. de Almeida Martins and D. Topgaard. Multidimensional correlation of nuclear relaxation rates and diffusion tensors for model-free investigations of heterogeneous anisotropic porous materials. Sci. Rep. 8, 2488 (2018).

S. Lasič, H. Lundell, D. Topgaard, and T. B. Dyrby. Effects of imaging gradients in sequences with varying longitudinal storage time – case of diffusion exchange imaging. Magn. Reson. Med. 79, 2228-2235 (2018).

M. Nilsson, J. Larsson, D. Lundberg, F. Szczepankiewicz, T. Witzel, C.-F. Westin, K. Bryskhe, and D. Topgaard. Liquid crystal phantom for validation of microscopic diffusion anisotropy measurements on clinical MRI systems. Magn. Reson. Med. 79, 1817-1828 (2018).

S. Eriksson, K. Elbing, O. Söderman, K. Lindkvist-Petersson, D. Topgaard, and S. Lasič. NMR quantification of diffusional exchange in cell suspensions with relaxation rate differences between intra and extracellular compartments. PLOS ONE 12, e0177273 (2017).

D. Topgaard. Multidimensional diffusion MRI. J. Magn. Reson. 275, 98-113 (2017).

D. Topgaard. NMR methods for studying microscopic diffusion anisotropy. Diffusion NMR of Confined Systems: Fluid Transport in Porous Solids and Heterogeneous Materials, 226-259 (2016), Royal Society of Chemistry, Cambridge, UK.

D. Topgaard. Director orientations in lyotropic liquid crystals: Diffusion MRI mapping of the Saupe order tensor. Phys. Chem. Chem. Phys. 18, 8545-8553 (2016).

C.-F. Westin, H. Knutsson, O. Pasternak, F. Szczepankiewicz, E. Özarslan, D. van Westen, C. Mattisson, M. Bogren, L. O'Donnell, M. Kubicki, D. Topgaard, and M. Nilsson. Q-space trajectory imaging for multidimensional diffusion MRI of the human brain. Neuroimage 135, 345-362 (2016).

A. Ahlgren, L. Knutsson, R. Wirestam, M. Nilsson, F. Ståhlberg, D. Topgaard, and S. Lasič. Quantification of microcirculatory parameters by joint analysis of flow-compensated and non-flow-compensated intravoxel incoherent motion (IVIM) data. NMR Biomed. 29, 640-649 (2016).

S. Lasič, S. Oredsson, S. C. Partridge, L. H. Saal, D. Topgaard, M. Nilsson, and K. Bryskhe. Apparent exchange rate (AXR) for breast cancer characterization. NMR Biomed. 29, 631-639 (2016).

J. P. de Almeida Martins and D. Topgaard. Two-dimensional correlation of isotropic and directional diffusion using NMR. Phys. Rev. Lett. 116, 087601 (2016).

N. Shemesh, S. N. Jespersen, D. C. Alexander, Y. Cohen, I. Drobnjak, T. B. Dyrby, J. Finsterbusch, M. A. Koch, T. Kuder, F. Laun, M. Lawrenz, H. Lundell, P. P. Mitra, M. Nilsson, E. Özarslan, D. Topgaard, and C.-F. Westin. Conventions and nomenclature for double diffusion encoding (DDE) NMR and MRI. Magn. Reson. Med. 75, 82-87 (2016).

J. Sjölund, F. Szczepankiewicz, M. Nilsson, D. Topgaard, C.-F. Westin, and H. Knutsson. Constrained optimization of gradient waveforms for generalized diffusion encoding. J. Magn. Reson. 261, 157-168 (2015).

S. Eriksson, S. Lasič, M. Nilsson, C.-F. Westin, and D. Topgaard. NMR diffusion encoding with axial symmetry and variable anisotropy: Distinguishing between prolate and oblate microscopic diffusion tensors with unknown orientation distribution. J. Chem. Phys. 142, 104201 (2015).

F. Szczepankiewicz, S. Lasič, D. van Westen, P. C. Sundgren, E. Englund, C.-F. Westin, F. Ståhlberg, J. Lätt, D. Topgaard, and M. Nilsson. Quantification of microscopic diffusion anisotropy disentangles effects of orientation dispersion from microstructure: Applications in healthy volunteers and in brain tumors. NeuroImage 104, 241-252 (2015).

D. Topgaard. Isotropic diffusion weighting using a triple-stimulated echo pulse sequence with bipolar gradient pulse pairs. Microporous Mesoporous Mater. 205, 48-51 (2015).

D. Bernin, V. Koch, M. Nydén, and D. Topgaard. Multi-scale characterization of lyotropic liquid crystals using 2H and diffusion MRI with spatial resolution in three dimensions. PLOS ONE 9, e98752 (2014).

S. Lasič, F. Szczepankiewicz, S. Eriksson, M. Nilsson, and D. Topgaard. Microanisotropy imaging: quantification of microscopic diffusion anisotropy and orientational order parameter by diffusion MRI with magic-angle spinning of the q-vector. Front. Physics 2, 11 (2014).

D. Topgaard. Isotropic diffusion weighting in PGSE NMR: Numerical optimization of the q-MAS PGSE sequence. Microporous Mesoporous Mater. 178, 60-63 (2013).

M. Nilsson, J. Lätt, D. van Westen, S. Brockstedt, S. Lasič, F. Ståhlberg, and D. Topgaard. Noninvasive mapping of water diffusional exchange in the human brain using filter-exchange imaging. Magn. Reson. Med. 69, 1573-1581 (2013).

S. Eriksson, S. Lasič, and D. Topgaard. Isotropic diffusion weighting by magic-angle spinning of the q-vector in PGSE NMR. J. Magn. Reson. 226, 13-18 (2013).

S. Lasič, I. Åslund, C. Oppel, D. Topgaard, O. Söderman, and M. Gradzielski. Investigations of vesicle gels by pulsed and modulated gradient NMR diffusion techniques. Soft Matter 7, 3947-3955 (2011).

I. Åslund, B. Medronho, D. Topgaard, O. Söderman, and C. Schmidt. Homogeneous length scale of shear-induced multilamellar vesicles. J. Magn. Reson. 209, 291-299 (2011).

S. Lasič, M. Nilsson, J. Lätt, F. Ståhlberg, and D. Topgaard. Apparent exchange rate (AXR) mapping with diffusion MRI. Magn. Reson. Med. 66, 356-365 (2011).

I. Åslund and D. Topgaard. Determination of the self-diffusion coefficient of intracellular water using PGSE NMR with variable gradient pulse length. J. Magn. Reson. 201, 250-254 (2009).

I. Åslund, A. Nowacka, M. Nilsson, and D. Topgaard. Filter-exchange PGSE NMR determination of cell membrane permeability. J. Magn. Reson. 200, 291-295 (2009).

S. Lasič, I. Åslund, and D. Topgaard. Spectral characterization of diffusion with chemical shift resolution: Highly concentrated water-in-oil emulsion. J. Magn. Reson. 199, 166-172 (2009).

I. Åslund, C. Cabaleiro-Lago, O. Söderman, and D. Topgaard. Diffusion NMR for determining the homogeneous length scale in lamellar phases. J. Phys. Chem. B 112, 2782-2794 (2008).

J. Lätt, M. Nilsson, C. Malmborg, H. Rosquist, R. Wirestam, F. Ståhlberg, D. Topgaard, and S. Brockstedt. Accuracy of q-space related parameters in MRI: Simulations and phantom measurements. IEEE Trans. Medical Imaging 26, 1437-1447 (2007).

C. Malmborg, M. Sjöbeck, S. Brockstedt, E. Englund, O. Söderman, and D. Topgaard. Mapping the intracellular fraction of water by varying the gradient pulse length in q-space diffusion MRI. J. Magn. Reson. 180, 280-285 (2006).

D. Topgaard. Probing biological tissue microstructure with magnetic resonance diffusion techniques. Curr. Opin. Colloid Interface Sci. 11, 7-12 (2006).

C. Malmborg, D. Topgaard, and O. Söderman. NMR diffusometry and the short gradient pulse approximation. J. Magn. Reson. 169, 85-91 (2004).

D. Topgaard and O. Söderman. Experimental determination of pore size and shape using q-space NMR microscopy in the long diffusion-time limit. Magn. Reson. Imaging 21, 69-76 (2003).

C. Malmborg, D. Topgaard, and O. Söderman. Diffusion in an inhomogeneous system: NMR studies of diffusion in highly concentrated emulsions. J. Colloid Interface Sci. 263, 270-276 (2003).

D. Topgaard, C. Malmborg, and O. Söderman. Restricted self-diffusion of water in a highly concentrated W/O emulsion studied using modulated gradient spin-echo NMR. J. Magn. Reson. 156, 195-201 (2002).