Daniel Topgaard

Lund University, Lund, Skåne, Sweden

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Publications (93)323.72 Total impact

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    ABSTRACT: We introduce a nuclear magnetic resonance method for quantifying the shape of axially symmetric microscopic diffusion tensors in terms of a new diffusion anisotropy metric, DΔ, which has unique values for oblate, spherical, and prolate tensor shapes. The pulse sequence includes a series of equal-amplitude magnetic field gradient pulse pairs, the directions of which are tailored to give an axially symmetric diffusion-encoding tensor b with variable anisotropy bΔ. Averaging of data acquired for a range of orientations of the symmetry axis of the tensor b renders the method insensitive to the orientation distribution function of the microscopic diffusion tensors. Proof-of-principle experiments are performed on water in polydomain lyotropic liquid crystals with geometries that give rise to microscopic diffusion tensors with oblate, spherical, and prolate shapes. The method could be useful for characterizing the geometry of fluid-filled compartments in porous solids, soft matter, and biological tissues.
    The Journal of Chemical Physics 03/2015; 142(10):104201. DOI:10.1063/1.4913502 · 3.12 Impact Factor
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    ABSTRACT: Molecular dynamics (MD) simulations give atomically detailed information on structure and dynamics in amphiphilic bilayer systems on timescales up to about 1 μs. The reorientational dynamics of the C-H bonds is conventionally verified by measurements of (13)C or (2)H nuclear magnetic resonance (NMR) longitudinal relaxation rates R1, which are more sensitive to motional processes with correlation times close to the inverse Larmor frequency, typically around 1-10 ns on standard NMR instrumentation, and are thus less sensitive to the 10-1000 ns timescale motion that can be observed in the MD simulations. We propose an experimental procedure for atomically resolved model-free estimation of the C-H bond effective reorientational correlation time τe, which includes contributions from the entire range of all-atom MD timescales and that can be calculated directly from the MD trajectories. The approach is based on measurements of (13)C R1 and R1ρ relaxation rates, as well as (1)H-(13)C dipolar couplings, and is applicable to anisotropic liquid crystalline lipid or surfactant systems using a conventional solid-state NMR spectrometer and samples with natural isotopic composition. The procedure is demonstrated on a fully hydrated lamellar phase of 1-palmitoyl-2-oleoyl-phosphatidylcholine, yielding values of τe from 0.1 ns for the methyl groups in the choline moiety and at the end of the acyl chains to 3 ns for the g1 methylene group of the glycerol backbone. MD simulations performed with a widely used united-atom force-field reproduce the τe-profile of the major part of the acyl chains but underestimate the dynamics of the glycerol backbone and adjacent molecular segments. The measurement of experimental τe-profiles can be used to study subtle effects on C-H bond reorientational motions in anisotropic liquid crystals, as well as to validate the C-H bond reorientation dynamics predicted in MD simulations of amphiphilic bilayers such as lipid membranes.
    The Journal of Chemical Physics 01/2015; 142(4):044905. DOI:10.1063/1.4906274 · 3.12 Impact Factor
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    ABSTRACT: Macroscopic properties of pasta, such as the texture, are formed during cooking by a complex interplay of water and heat with the structuring agents starch and gluten. The impact of the starch-to-gluten ratio on microstructure and water distribution in pasta was analyzed by a multi-scale approach combining magnetic resonance imaging (MRI) and light microscopy. The cooking process and thus the water distribution was monitored non-invasively using 1H MRI in real-time with a temporal resolution of 45 s. Our MRI set-up allowed following the water ingress by imaging the reduction of the uncooked core. The water ingress rate was neither dependent on pasta composition nor on the presence of salt in the cooking media (0.7% NaCl). Starch-rich samples showed a more homogeneous water distribution in the gelatinized zone, which was mirrored in a more homogeneous microstructure. In contrast, gluten-rich samples showed both a heterogeneous water distribution and microstructure. Thus, the gluten content affected local water content in the gelatinized zone but not the water ingress.
    Food Research International 12/2014; 66:132–139. DOI:10.1016/j.foodres.2014.09.007 · 3.05 Impact Factor
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    ABSTRACT: Abstract The anisotropy of water diffusion in brain tissue is affected by both disease and development. This change can be detected using diffusion MRI and is often quantified by the fractional anisotropy (FA) derived from diffusion tensor imaging (DTI). Although FA is sensitive to anisotropic cell structures, such as axons, it is also sensitive to their orientation dispersion. This is a major limitation to the use of FA as a biomarker for “tissue integrity”, especially in regions of complex microarchitecture. In this work, we seek to circumvent this limitation by disentangling the effects of microscopic diffusion anisotropy from the orientation dispersion. The microscopic fractional anisotropy (μFA) and the order parameter (OP) were calculated from the contrast between signal prepared with directional and isotropic diffusion encoding, where the latter was achieved by magic angle spinning of the q-vector (qMAS). These parameters were quantified in healthy volunteers and in two patients; one patient with meningioma and one with glioblastoma. Finally, we used simulations to elucidate the relation between FA and μFA in various micro-architectures. Generally, μFA was high in the white matter and low in the gray matter. In the white matter, the largest differences between μFA and FA were found in crossing white matter and in interfaces between large white matter tracts, where μFA was high while FA was low. Both tumor types exhibited a low FA, in contrast to the μFA which was high in the meningioma and low in the glioblastoma, indicating that the meningioma contained disordered anisotropic structures, while the glioblastoma did not. This interpretation was confirmed by histological examination. We conclude that FA from DTI reflects both the amount of diffusion anisotropy and orientation dispersion. We suggest that the μFA and OP may complement FA by independently quantifying the microscopic anisotropy and the level of orientation coherence.
    NeuroImage 10/2014; 104:241-252. DOI:10.1016/j.neuroimage.2014.09.057 · 6.13 Impact Factor
  • Daniel Topgaard
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    ABSTRACT: Microscopic diffusion anisotropy in porous materials can be quantified from diffusion NMR data acquired with a combination of directional and isotropic diffusion encoding. A drawback with current pulses sequences for isotropic encoding is that they all rely on spin echo sequences, which are only applicable to pore liquids with long transverse relaxation times and porous materials with negligible internal magnetic field gradients. To mitigate these problems, we introduce a pulse sequence based on consecutive stimulated echo blocks with bipolar gradient pulse pairs giving equal diffusion encoding in three successive directions. By varying the angles between these directions, the pulse sequence can be tuned to give either directional or isotropic diffusion encoding. We demonstrate the new pulse sequence by experiments on detergent/water liquid crystals with lamellar, bicontinuous cubic, and reverse 2D hexagonal structures.
    Microporous and Mesoporous Materials 08/2014; 205. DOI:10.1016/j.micromeso.2014.08.023 · 3.21 Impact Factor
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    ABSTRACT: A combination of NMR Chemical Shift Imaging and self-diffusion experiments is shown to give a detailed molecular picture of the events that occur when drug-loaded tablets of hydrophobically modified poly(acrylic acid) swell in water in the presence or absence of surfactant. The hydrophobic substituents on the polymer bind and trap the surfactant molecules in mixed micelles, leading to a slow effective transport of the surfactant. The transport occurs via a small fraction of individually dissolved surfactant molecules in the water domain. Due to the efficient binding of surfactant, the penetrating water is found to diffuse past the penetrating surfactant into the polymer matrix, pushing the surfactant front outwards as the matrix swells. The added surfactant has little effect on the transport of griseofulvin, because both undissolved solid drug and surfactant-solubilized drug functions as reservoirs that essentially follow the polymer as it swells. However, the added surfactant nevertheless has a strong indirect effect on the release of griseofulvin, through the effect of the surfactant on the solubility and erosion of the polymer matrix. The surfactant effectively solubilizes the hydrophobically modified polymer, making it fully miscible with water, leading to a more pronounced swelling and a slower erosion of the polymer matrix.
    The Journal of Physical Chemistry B 07/2014; 118(32). DOI:10.1021/jp501288u · 3.38 Impact Factor
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    ABSTRACT: The ability of lyotropic liquid crystals to form intricate structures on a range of length scales can be utilized for the synthesis of structurally complex inorganic materials, as well as in devices for controlled drug delivery. Here we employ magnetic resonance imaging (MRI) for non-invasive characterization of nano-, micro-, and millimeter scale structures in liquid crystals. The structure is mirrored in the translational and rotational motion of the water, which we assess by measuring spatially resolved self-diffusion tensors and [Formula: see text] spectra. Our approach differs from previous works in that the MRI parameters are mapped with spatial resolution in all three dimensions, thus allowing for detailed studies of liquid crystals with complex millimeter-scale morphologies that are stable on the measurement time-scale of 10 hours. The [Formula: see text] data conveys information on the nanometer-scale structure of the liquid crystalline phase, while the combination of diffusion and [Formula: see text] data permits an estimate of the orientational distribution of micrometer-scale anisotropic domains. We study lamellar phases consisting of the nonionic surfactant C10E3 in [Formula: see text]O, and follow their structural equilibration after a temperature jump and the cessation of shear. Our experimental approach may be useful for detailed characterization of liquid crystalline materials with structures on multiple length scales, as well as for studying the mechanisms of phase transitions.
    PLoS ONE 06/2014; 9(6):e98752. DOI:10.1371/journal.pone.0098752 · 3.53 Impact Factor
  • ISMRM, Milan, Italy; 05/2014
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    ABSTRACT: In this work we present the first in vivo experiments employing magic angle spinning of the q-vector (qMAS) to map the microscopic anisotropy of the brain. This technique allows for the parameterization of anisotropy that is unaffected by the orientation dispersion. This means that the anisotropy is probed on a sub-voxel scale, and can potentially be useful in complex white matter geometries and gray matter, where conventional metrics such as FA are confounded by the tissue micro architecture.
    ISMRM, Milan, Italy; 05/2014
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    ABSTRACT: The outermost layer of the skin, the stratum corneum (SC), is a lipid-protein membrane that experiences considerable osmotic stress from a dry and cold climate. The natural moisturizing factor (NMF) comprises small and polar substances, which like osmolytes can protect living systems from osmotic stress. NMF is commonly claimed to increase the water content in the SC and thereby protect the skin from dryness. In this work we challenge this proposed mechanism, and explore the influence of NMF on the lipid and protein components in the SC. We employ natural-abundance (13)C solid-state NMR methods to investigate how the SC molecular components are influenced by urea, glycerol, pyrrolidone carboxylic acid (PCA), and urocanic acid (UCA), all of which are naturally present in the SC as NMF compounds. Experiments are performed with intact SC, isolated corneocytes and model lipids. The combination of NMR experiments provides molecularly resolved qualitative information on the dynamics of different SC lipid and protein components. We obtain completely novel molecular information on the interaction of these NMF compounds with the SC lipids and proteins. We show that urea and glycerol, which are also common ingredients in skin care products, increase the molecular mobility of both SC lipids and proteins at moderate relative humidity where the SC components are considerably more rigid in the absence of these compounds. This effect cannot be attributed to increased SC water content. PCA has no detectable effect on SC molecular mobility under the conditions investigated. It is finally shown that the more apolar compound, UCA, specifically influences the mobility of the SC lipid regions. The present results show that the NMF components act to retain the fluidity of the SC molecular components under dehydrating conditions in such a way that the SC properties remain largely unchanged as compared to more hydrated SC. These findings provide a new molecular insight into how small polar molecules in NMF and skin care products act to protect the human skin from drying.
    Soft Matter 05/2014; 10(25). DOI:10.1039/c4sm00137k · 4.15 Impact Factor
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    ABSTRACT: Diffusion tensor imaging (DTI) is the method of choice for non-invasive investigations of the structure of human brain white matter (WM). The results are conventionally reported as maps of the fractional anisotropy (FA), which is a parameter related to microstructural features such as axon density, diameter, and myelination. The interpretation of FA in terms of microstructure becomes ambiguous when there is a distribution of axon orientations within the image voxel. In this paper, we propose a procedure for resolving this ambiguity by determining a new parameter, the microscopic fractional anisotropy (μFA), which corresponds to the FA without the confounding influence of orientation dispersion. In addition, we suggest a method for measuring the orientational order parameter (OP) for the anisotropic objects. The experimental protocol is capitalizing on a recently developed diffusion nuclear magnetic resonance (NMR) pulse sequence based on magic-angle spinning of the q-vector. Proof-of-principle experiments are carried out on microimaging and clinical MRI equipment using lyotropic liquid crystals and plant tissues as model materials with high μFA and low FA on account of orientation dispersion. We expect the presented method to be especially fruitful in combination with DTI and high angular resolution acquisition protocols for neuroimaging studies of gray and white matter.
    Frontiers of Physics 02/2014; 2(11). DOI:10.3389/fphy.2014.00011 · 1.36 Impact Factor
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    ABSTRACT: The influence of the monomer diallyldimethylammonium chloride (D) on the lamellar liquid crystal formed by the anionic surfactant Aerosol OT (AOT) and water is investigated, determining the lamellar spacings by SAXS and the quadrupolar splittings by deuterium NMR, as a function of the D or AOT concentrations. The cationic monomer D induces a destabilization of the AOT lamellar structure such that at a critical concentration higher than 5 wt%, macroscopic phase separation takes place. When the monomer, which is dissolved in the AOT lamellae, is polymerized in situ by X-ray initiation, a new collapsed lamellar phase appears, corresponding to the complexation of the surfactant with the resulting polymer. A theoretical model is employed to analyze the variation of the interactions between the AOT bilayers and the stability of the lamellar structure.
    The Journal of Physical Chemistry B 01/2014; 118(4). DOI:10.1021/jp411894e · 3.38 Impact Factor
  • Biophysical Journal 01/2014; 106(2):41a. DOI:10.1016/j.bpj.2013.11.301 · 3.83 Impact Factor
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    ABSTRACT: In traditional diffusion MRI, short pulsed field gradients (PFG) are used for the diffusion encoding. The standard Stejskal-Tanner sequence uses one single pair of such gradients, known as single-PFG (sPFG). In this work we describe how trajectories in q-space can be used for diffusion encoding. We discuss how such encoding enables the extension of the well-known scalar b-value to a tensor-valued entity we call the diffusion measurement tensor. The new measurements contain information about higher order diffusion propagator covariances not present in sPFG. As an example analysis, we use this new information to estimate a Gaussian distribution over diffusion tensors in each voxel, described by its mean (a diffusion tensor) and its covariance (a 4th order tensor).
    Medical Image Computing and Computer-Assisted Intervention – MICCAI 2014, Edited by Golland, Polina and Hata, Nobuhiko and Barillot, Christian and Hornegger, Joachim and Howe, Robert, 01/2014: pages 209-216; Springer International Publishing., ISBN: 9783319104423
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    ABSTRACT: Polarization transfer solid-state NMR is shown to give molecular-level information about both dissolved and solid cellulose in aqueous dissolution media with sodium hydroxide or tetrabutylammonium hydroxide, thus paving the way for future studies of the molecular details of cellulose dissolution.
    RSC Advances 01/2014; 4(60-60):31836-31839. DOI:10.1039/C4RA04415K · 3.71 Impact Factor
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    ABSTRACT: The structure of the lamellar phase of pentaethyleneglycol mono n-dodecyl ether (C12E5) surfactant at various temperatures and molar fractions is studied by using united atom molecular dynamics simulations and nuclear magnetic resonance measurements. Namely, the simulation model is used to interpret the magnitude and temperature dependence of experimental C-H order parameter profiles in terms of molecular conformation and orientation. Our simulations suggest that the low order parameters that are generally measured in poly(ethylene oxide) surfactant bilayers are due to the presence of bilayer pores throughout the entire lamellar phase region.
    Langmuir 12/2013; 30(2). DOI:10.1021/la404684r · 4.38 Impact Factor
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    ABSTRACT: Amyloid deposits from several human diseases have been found to contain membrane lipids. Co-aggregation of lipids and amyloid proteins in amyloid aggregates, and the related extraction of lipids from cellular membranes, can influence structure and function in both the membrane and the formed amyloid deposit. Co-aggregation can therefore have important implications for the pathological consequences of amyloid formation. Still, very little is known about the mechanism behind co-aggregation and molecular structure in the formed aggregates. To address this, we study in vitro co-aggregation by incubating phospholipid model membranes with the Parkinson's disease-associated protein, α-synuclein, in monomeric form. After aggregation, we find spontaneous uptake of phospholipids from anionic model membranes into the amyloid fibrils. Phospholipid quantification, polarization transfer solid-state NMR and cryo-TEM together reveal co-aggregation of phospholipids and α-synuclein in a saturable manner with a strong dependence on lipid composition. At low lipid to protein ratios, there is a close association of phospholipids to the fibril structure, which is apparent from reduced phospholipid mobility and morphological changes in fibril bundling. At higher lipid to protein ratios, additional vesicles adsorb along the fibrils. While interactions between lipids and amyloid-protein are generally discussed within the perspective of different protein species adsorbing to and perturbing the lipid membrane, the current work reveals amyloid formation in the presence of lipids as a co-aggregation process. The interaction leads to the formation of lipid-protein co-aggregates with distinct structure, dynamics and morphology compared to assemblies formed by either lipid or protein alone.
    PLoS ONE 10/2013; 8(10):e77235. DOI:10.1371/journal.pone.0077235 · 3.53 Impact Factor
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    ABSTRACT: A new technique has been developed using NMR Chemical Shift Imaging (CSI) to monitor water penetration and molecular transport in initially dry polymer tablets that also contain small low-molecular weight compounds to be released from the tablets. Concentration profiles of components contained in the swelling tablets could be extracted via the intensities and chemical shift changes of peaks corresponding to protons of the components. The studied tablets contained hydrophobically modified poly (acrylic acid) (HMPAA) as the polymer component and griseofulvin and ethanol as hydrophobic and hydrophilic, respectively, low-molecular weight model compounds. The water solubility of HMPAA could be altered by titration with NaOH. In the pure acid form, HMPAA tablets only underwent a finite swelling until the maximum water content of the polymer-rich phase, as confirmed by independent phase studies, had been reached. By contrast, after partial neutralization with NaOH, the polyacid became fully miscible with water. The solubility of the polymer affected the water penetration, the polymer release and the releases of both ethanol and griseofulvin. The detailed NMR CSI concentration profiles obtained highlighted the clear differences in the disintegration/dissolution/release behavior for the two types of tablet and provided insights into their molecular origin. The study illustrates the potential of the NMR CSI technique to give information of importance for the development of pharmaceutical tablets and, more broadly, for the general understanding of any operation that involves the immersion and ultimate disintegration of a dry polymer matrix in a solvent.
    Langmuir 10/2013; 29(45). DOI:10.1021/la4024458 · 4.38 Impact Factor
  • Daniel Topgaard
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    ABSTRACT: Isotropic diffusion weighting is employed in diffusion NMR and MRI for rapid determination of the trace of the diffusion tensor and for showing the presence of microscopic diffusion anisotropy in a globally isotropic material. In the recently introduced q-MAS PGSE sequence, short gradient pulses define the beginning and the end of the diffusion time by quickly increasing and reducing the magnitude of the q-vector, while isotropic diffusion weighting is achieved by low-amplitude harmonically modulated gradients that make the q-vector rotate at the magic angle from an axis fixed in the lab frame. While efficient and easily implemented on microimaging systems with high-gradient capabilities, the previous version of q-MAS PGSE is too demanding for clinical MR scanners. Here, we present numerically optimized smooth gradient waveforms yielding maximum diffusion weighting for a given maximum gradient strength and echo time.
    Microporous and Mesoporous Materials 09/2013; 178:60-63. DOI:10.1016/j.micromeso.2013.03.009 · 3.21 Impact Factor
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    ABSTRACT: The stratum corneum (SC) is an effective permeability barrier. One strategy to increase drug delivery across skin is to increase the hydration. A detailed description of how hydration affects skin permeability requires characterization of both macroscopic and molecular properties and how they respond to hydration. We explore this issue by performing impedance experiments on excised skin membranes in the frequency range 1 Hz to 0.2 MHz under the influence of a varying gradient in water activity (aw). Hydration/dehydration induces reversible changes of membrane resistance and effective capacitance. On average, the membrane resistance is 14 times lower and the effective capacitance is 1.5 times higher when the outermost SC membrane is exposed to hydrating conditions (aw = 0.992), as compared to the case of more dehydrating conditions (aw = 0.826). Molecular insight into the hydration effects on the SC components is provided by natural-abundance (13)C polarization transfer solid-state NMR and x-ray diffraction under similar hydration conditions. Hydration has a significant effect on the dynamics of the keratin filament terminals and increases the interchain spacing of the filaments. The SC lipids are organized into lamellar structures with ∼ 12.6 nm spacing and hexagonal hydrocarbon chain packing with mainly all-trans configuration of the acyl chains, irrespective of hydration state. Subtle changes in the dynamics of the lipids due to mobilization and incorporation of cholesterol and long-chain lipid species into the fluid lipid fraction is suggested to occur upon hydration, which can explain the changes of the impedance response. The results presented here provide information that is useful in explaining the effect of hydration on skin permeability.
    Biophysical Journal 06/2013; 104(12):2639-50. DOI:10.1016/j.bpj.2013.05.008 · 3.83 Impact Factor

Publication Stats

1k Citations
323.72 Total Impact Points

Institutions

  • 2001–2015
    • Lund University
      • Department of Physical Chemistry
      Lund, Skåne, Sweden
  • 2010
    • University of Coimbra
      Coímbra, Coimbra, Portugal
    • University of Oslo
      • Department of Chemistry
      Kristiania (historical), Oslo County, Norway
  • 2005–2009
    • University of California, Berkeley
      • Department of Chemistry
      Berkeley, California, United States
  • 2004
    • KTH Royal Institute of Technology
      • Division of Applied Physical Chemistry
      Stockholm, Stockholm, Sweden