| 1. |
- Ahlgren, André, et al.
(författare)
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Quantification of microcirculatory parameters by joint analysis of flow-compensated and non-flow-compensated intravoxel incoherent motion (IVIM) data.
- 2016
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 29:5, s. 640-649
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to improve the accuracy and precision of perfusion fraction and blood velocity dispersion estimates in intravoxel incoherent motion (IVIM) imaging, using joint analysis of flow-compensated and non-flow-compensated motion-encoded MRI data. A double diffusion encoding sequence capable of switching between flow-compensated and non-flow-compensated encoding modes was implemented. In vivo brain data were collected in eight healthy volunteers and processed using the joint analysis. Simulations were used to compare the performance of the proposed analysis method with conventional IVIM analysis. With flow compensation, strong rephasing was observed for the in vivo data, approximately cancelling the IVIM effect. The joint analysis yielded physiologically reasonable perfusion fraction maps. Estimated perfusion fractions were 2.43 ± 0.81% in gray matter, 1.81 ± 0.90% in deep gray matter, and 1.64 ± 0.72% in white matter (mean ± SD, n = 8). Simulations showed improved accuracy and precision when using joint analysis of flow-compensated and non-flow-compensated data, compared with conventional IVIM analysis. Double diffusion encoding with flow compensation was feasible for in vivo imaging of the perfusion fraction in the brain. The strong rephasing implied that blood flowing through the cerebral microvascular system was closer to the ballistic limit than the diffusive limit. © 2016 The Authors NMR in Biomedicine published by John Wiley & Sons Ltd.
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| 2. |
- Andersen, Kasper Winther, et al.
(författare)
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Disentangling white-matter damage from physiological fibre orientation dispersion in multiple sclerosis
- 2020
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 2:2, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis leads to diffuse damage of the central nervous system, affecting also the normal-appearing white matter. Demyelination and axonal degeneration reduce regional fractional anisotropy in normal-appearing white matter, which can be routinely mapped with diffusion tensor imaging. However, the standard fractional anisotropy metric is also sensitive to physiological variations in orientation dispersion of white matter fibres. This complicates the detection of disease-related damage in large parts of cerebral white matter where microstructure physiologically displays a high degree of fibre dispersion. To resolve this ambiguity, we employed a novel tensor-valued encoding method for diffusion MRI, which yields a microscopic fractional anisotropy metric that is unaffected by regional variations in orientation dispersion. In 26 patients with relapsing-remitting multiple sclerosis, 14 patients with primary-progressive multiple sclerosis and 27 age-matched healthy controls, we compared standard fractional anisotropy mapping with the novel microscopic fractional anisotropy mapping method, focusing on normal-appearing white matter. Mean microscopic fractional anisotropy and standard fractional anisotropy of normal-appearing white matter were significantly reduced in both patient groups relative to healthy controls, but microscopic fractional anisotropy yielded a better reflection of disease-related white-matter alterations. The reduction in mean microscopic fractional anisotropy showed a significant positive linear relationship with physical disability, as reflected by the expanded disability status scale. Mean reduction of microscopic fractional anisotropy in normal-appearing white matter also scaled positively with individual cognitive dysfunction, as measured with the symbol digit modality test. Mean microscopic fractional anisotropy reduction in normal-appearing white matter also showed a positive relationship with total white-matter lesion load as well as lesion load in specific tract systems. None of these relationships between normal-appearing white-matter microstructure and clinical, cognitive or structural measures emerged when using mean fractional anisotropy. Together, the results provide converging evidence that microscopic fractional anisotropy mapping substantially advances the assessment of cerebral white matter in multiple sclerosis by disentangling microstructure damage from variations in physiological fibre orientation dispersion at the stage of data acquisition. Since tensor-valued encoding can be implemented in routine diffusion MRI, microscopic fractional anisotropy mapping bears considerable potential for the future assessment of disease progression in normal-appearing white matter in both relapsing-remitting and progressive forms of multiple sclerosis as well as other white-matter-related brain diseases.
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| 3. |
- Brabec, Jan, et al.
(författare)
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Time-dependent diffusion in undulating thin fibers : Impact on axon diameter estimation
- 2020
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:3
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Tidskriftsartikel (refereegranskat)abstract
- Diffusion MRI may enable non-invasive mapping of axonal microstructure. Most approaches infer axon diameters from effects of time-dependent diffusion on the diffusion-weighted MR signal by modeling axons as straight cylinders. Axons do not, however, propagate in straight trajectories, and so far the impact of the axonal trajectory on diameter estimation has been insufficiently investigated. Here, we employ a toy model of axons, which we refer to as the undulating thin fiber model, to analyze the impact of undulating trajectories on the time dependence of diffusion. We study time-dependent diffusion in the frequency domain and characterize the diffusion spectrum by its height, width, and low-frequency behavior (power law exponent). Results show that microscopic orientation dispersion of the thin fibers is the main parameter that determines the characteristics of the diffusion spectra. At lower frequencies (longer diffusion times), straight cylinders and undulating thin fibers can have virtually identical spectra. If the straight-cylinder assumption is used to interpret data from undulating thin axons, the diameter is overestimated by an amount proportional to the undulation amplitude and microscopic orientation dispersion of the fibers. At higher frequencies (shorter diffusion times), spectra from cylinders and undulating thin fibers differ. The low-frequency behavior of the spectra from the undulating thin fibers may also differ from that of cylinders, because the power law exponent of undulating fibers can reach values below 2 for experimentally relevant frequency ranges. In conclusion, we argue that the non-straight nature of axonal trajectories should not be overlooked when analyzing and interpreting diffusion MRI data.
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| 4. |
- Chakwizira, Arthur, et al.
(författare)
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Diffusion MRI with pulsed and free gradient waveforms : effects of restricted diffusion and exchange
- 2023
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 36:1
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Tidskriftsartikel (refereegranskat)abstract
- Monitoring time-dependence with diffusion MRI yields observables sensitive to compartment sizes (restricted diffusion) and membrane permeability (water exchange). However, restricted diffusion and exchange have opposite effects on the diffusion-weighted signal, which can lead to errors in parameter estimates. In this work, we propose a signal representation that incorporates the effects of both restricted diffusion and exchange up to second order in b-value and is compatible with gradient waveforms of arbitrary shape. The representation features mappings from a gradient waveform to two scalars that separately control the sensitivity to restriction and exchange. We demonstrate that these scalars span a two-dimensional space that can be used to choose waveforms that selectively probe restricted diffusion or exchange, eliminating the correlation between the two phenomena. We found that waveforms with specific but unconventional shapes provide an advantage over conventional pulsed and oscillating gradient acquisitions. We also show that parametrisation of waveforms into a two-dimensional space can be used to understand protocols from other approaches that probe restricted diffusion and exchange. For example, we found that the variation of mixing time in filter-exchange imaging corresponds to variation of our exchange-weighting scalar at a fixed value of the restriction-weighting scalar. The proposed signal representation was evaluated using Monte Carlo simulations in identical parallel cylinders with hexagonal and random packing as well as parallel cylinders with gamma-distributed radii. Results showed that the approach is sensitive to sizes in the interval 4 - 12 μm and exchange rates in the simulated range of 0 to 20 s -1 , but also that there is a sensitivity to the extracellular geometry. The presented theory constitutes a simple and intuitive description of how restricted diffusion and exchange influence the signal as well as a guide to protocol design capable of separating the two effects.
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| 5. |
- Eriksson, Stefanie, et al.
(författare)
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Isotropic diffusion weighting in PGSE NMR by magic-angle spinning of the q-vector.
- 2013
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Ingår i: Journal of Magnetic Resonance. - : Elsevier BV. - 1096-0856 .- 1090-7807. ; 226, s. 13-18
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Tidskriftsartikel (refereegranskat)abstract
- When PGSE NMR is applied to water in microheterogeneous materials such as liquid crystals, foodstuffs, porous rocks, and biological tissues, the signal attenuation is often multi-exponential, indicating the presence of pores having a range of sizes or anisotropic domains having a spread of orientations. Here we modify the standard PGSE experiment by introducing low-amplitude harmonically modulated gradients, which effectively make the q-vector perform magic-angle spinning (MAS) about an axis fixed in the laboratory frame. With this new technique, denoted q-MAS PGSE, the signal attenuation depends on the isotropic average of the local diffusion tensor. The capability of q-MAS PGSE to distinguish between pore size and domain orientation dispersion is demonstrated by experiments on a yeast cell suspension and a polydomain anisotropic liquid crystal. In the latter case, the broad distribution of apparent diffusivities observed with PGSE is narrowed to its isotropic average with q-MAS PGSE in a manner that is analogous to the narrowing of chemical shift anisotropy powder patterns using magic-angle sample spinning in solid-state NMR. The new q-MAS PGSE technique could be useful for resolving size/orientation ambiguities in the interpretation of PGSE data from, e.g., water confined within the axons of human brain tissue.
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| 6. |
- ERIKSSON, STEFANIE, et al.
(författare)
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NMR diffusion-encoding with axial symmetry and variable anisotropy: Distinguishing between prolate and oblate microscopic diffusion tensors with unknown orientation distribution
- 2015
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Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 142:10, s. 104201-
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Tidskriftsartikel (refereegranskat)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, D-Delta, 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 b(Delta). 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. (C) 2015 Author(s).
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| 7. |
- Eriksson, Stefanie, et al.
(författare)
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NMR quantification of diffusional exchange in cell suspensions with relaxation rate differences between intra and extracellular compartments
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Water transport across cell membranes can be measured non-invasively with diffusion NMR. We present a method to quantify the intracellular lifetime of water in cell suspensions with short transverse relaxation times, T2, and also circumvent the confounding effect of different T2 values in the intra- and extracellular compartments. Filter exchange spectroscopy (FEXSY) is specifically sensitive to exchange between compartments with different apparent diffusivities. Our investigation shows that FEXSY could yield significantly biased results if differences in T2 are not accounted for. To mitigate this problem, we propose combining FEXSY with diffusion-relaxation correlation experiment, which can quantify differences in T2 values in compartments with different diffusivities. Our analysis uses a joint constrained fitting of the two datasets and considers the effects of diffusion, relaxation and exchange in both experiments. The method is demonstrated on yeast cells with and without human aquaporins.
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| 8. |
- Lasič, Samo, et al.
(författare)
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Apparent exchange rate for breast cancer characterization.
- 2016
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 29:5, s. 631-639
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Tidskriftsartikel (refereegranskat)abstract
- Although diffusion MRI has shown promise for the characterization of breast cancer, it has low specificity to malignant subtypes. Higher specificity might be achieved if the effects of cell morphology and molecular exchange across cell membranes could be disentangled. The quantification of exchange might thus allow the differentiation of different types of breast cancer cells. Based on differences in diffusion rates between the intra- and extracellular compartments, filter exchange spectroscopy/imaging (FEXSY/FEXI) provides non-invasive quantification of the apparent exchange rate (AXR) of water between the two compartments. To test the feasibility of FEXSY for the differentiation of different breast cancer cells, we performed experiments on several breast epithelial cell lines in vitro. Furthermore, we performed the first in vivo FEXI measurement of water exchange in human breast. In cell suspensions, pulsed gradient spin-echo experiments with large b values and variable pulse duration allow the characterization of the intracellular compartment, whereas FEXSY provides a quantification of AXR. These experiments are very sensitive to the physiological state of cells and can be used to establish reliable protocols for the culture and harvesting of cells. Our results suggest that different breast cancer subtypes can be distinguished on the basis of their AXR values in cell suspensions. Time-resolved measurements allow the monitoring of the physiological state of cells in suspensions over the time-scale of hours, and reveal an abrupt disintegration of the intracellular compartment. In vivo, exchange can be detected in a tumor, whereas, in normal tissue, the exchange rate is outside the range experimentally accessible for FEXI. At present, low signal-to-noise ratio and limited scan time allows the quantification of AXR only in a region of interest of relatively large tumors. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.
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| 9. |
- Lasic, Samo, et al.
(författare)
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Apparent exchange rate mapping with diffusion MRI.
- 2011
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 66, s. 356-365
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Tidskriftsartikel (refereegranskat)abstract
- Water exchange through the cell membranes is an important feature of cells and tissues. The rate of exchange is determined by factors such as membrane lipid composition and organization, as well as the type and activity of aquaporins. A method for noninvasively estimating the rate of water exchange would be useful for characterizing pathological conditions, e.g., tumors, multiple sclerosis, and ischemic stroke, expected to be associated with a change of the membrane barrier properties. This study describes the filter exchange imaging method for determining the rate of water exchange between sites having different apparent diffusion coefficients. The method is based on the filter-exchange pulsed gradient spin-echo NMR spectroscopy experiment, which is here modified to be compatible with the constraints of clinical MR scanners. The data is analyzed using a model-free approach yielding maps of the apparent exchange rate, here being introduced in analogy with the concept of the apparent diffusion coefficient. Proof-of-principle experiments are performed on microimaging and whole-body clinical scanners using yeast suspension phantoms. The limitations and appropriate experimental conditions are examined. The results demonstrate that filter exchange imaging is a fast and reliable method for characterizing exchange, and that it has the potential to become a powerful diagnostic tool. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.
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| 10. |
- Lasic, Samo, et al.
(författare)
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Investigations of vesicle gels by pulsed and modulated gradient NMR diffusion techniques
- 2011
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 7:8, s. 3947-3955
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Tidskriftsartikel (refereegranskat)abstract
- Vesicle gels are surfactant systems that form stiff gels with rather low amounts of surfactant. So far their structures have mostly been investigated using scattering techniques, which are generally appropriate for the study of structures on the nm-length-scale. Here we examine these gels using two complementary diffusion NMR techniques, which are both sensitive to structures on the mu m-scale. The presented results imply structural features on the mm-scale, indicating a more complex structure than just that of densely packed small vesicles, as previously found for these systems. It is demonstrated that a combination of the diffusion NMR methods, described here, can provide useful insights, when morphological features extend over a wide range of length scales.
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