| 1. |
- Einarsson, Emma, et al.
(författare)
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The role of cartilage glycosaminoglycan structure in gagCEST
- 2020
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:5
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Tidskriftsartikel (refereegranskat)abstract
- Glycosaminoglycan (GAG) chemical exchange saturation transfer (gagCEST) is a potential method for cartilage quality assessment. The aim of this study was to investigate how the gagCEST effect depends on the types and molecular organization of GAG typically found in articular cartilage. gagCEST was performed on different concentrations of GAG in various forms: free chains of chondroitin sulfate (CS) of different types (-A and -C) and GAG bound to protein in aggregated and nonaggregated aggrecan extracted from calf articular cartilage. The measured magnetization transfer ratio asymmetry (MTRasym ) was compared with known GAG concentrations or GAG concentrations determined through biochemical analysis. The gagCEST effect was assessed through the linear regression coefficient with 95% confidence interval of MTRasym per GAG concentration. We observed a lower gagCEST effect in phantoms containing a mixture of CS-A and CS-C compared with phantoms containing mainly CS-A. The difference in response corresponds well to the difference in CS-A concentration. GAG bound in aggrecan from calf articular cartilage, where CS-A is assumed to be the major type of GAG, produed a similar gagCEST effect as that observed for free CS-A. The effect was also similar for aggregated (ie, bound to hyaluronic acid) and nonaggregated aggrecan. In conclusion, our results indicate that the aggrecan structure in itself does not impact the gagCEST effect, but that the effect is strongly dependent on GAG type. In phantoms, the current implementation of gagCEST is sensitive to CS-A while for CS-C, the main GAG component in mature human articular cartilage, the sensitivity is limited. This difference in gagCEST sensitivity between GAG types detected in phantoms is a strong motivation to also explore the possibility of a similar effect in vivo.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- Han, Zheng, et al.
(författare)
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Dynamic contrast-enhanced CEST MRI using a low molecular weight dextran
- 2022
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 35:3
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Tidskriftsartikel (refereegranskat)abstract
- Natural and synthetic sugars have great potential for developing highly biocompatible and translatable chemical exchange saturation transfer (CEST) MRI contrast agents. In this study, we aimed to develop the smallest clinically available form of dextran, Dex1 (molecular weight, MW ~ 1 kDa), as a new CEST agent. We first characterized the CEST properties of Dex1 in vitro at 11.7 T and showed that the Dex1 had a detectable CEST signal at ~1.2 ppm, attributed to hydroxyl protons. In vivo CEST MRI studies were then carried out on C57BL6 mice bearing orthotopic GL261 brain tumors (n = 5) using a Bruker BioSpec 11.7 T MRI scanner. Both steady-state full Z-spectral images and single offset (1.2 ppm) dynamic dextran-enhanced (DDE) images were acquired before and after the intravenous injection of Dex1 (2 g/kg). The steady-state Z-spectral analysis showed a significantly higher CEST contrast enhancement in the tumor than in contralateral brain (∆MTRasym 1.2 ppm = 0.010 ± 0.006 versus 0.002 ± 0.008, P = 0.0069) at 20 min after the injection of Dex1. Pharmacokinetic analyses of DDE were performed using the area under the curve (AUC) in the first 10 min after Dex1 injection, revealing a significantly higher uptake of Dex1 in the tumor than in brain tissue for tumor-bearing mice (AUC[0-10 min] = 21.9 ± 4.2 versus 5.3 ± 6.4%·min, P = 0.0294). In contrast, no Dex1 uptake was foundling in the brains of non-tumor-bearing mice (AUC[0-10 min] = -1.59 ± 2.43%·min). Importantly, the CEST MRI findings were consistent with the measurements obtained using DCE MRI and fluorescence microscopy, demonstrating the potential of Dex1 as a highly translatable CEST MRI contrast agent for assessing tumor hemodynamics.
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| 5. |
- Knutsson, Linda, et al.
(författare)
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Imaging of sugar-based contrast agents using their hydroxyl proton exchange properties
- 2023
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 36:6
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Tidskriftsartikel (refereegranskat)abstract
- The ability of CEST MRI to detect the presence of millimolar concentrations of non-metallic contrast agents has made it possible to study, noninvasively, important biological molecules such as proteins and sugars, as well as drugs already approved for clinical use. Here, we review efforts to use sugar and sugar polymers as exogenous contrast agents, which is possible based on the exchange of their hydroxyl protons with water protons. While this capability has raised early enthusiasm, for instance about the possibility to image D-glucose metabolism with MRI in a way analogous to PET, experience over the past decade has shown that this is not trivial. On the other hand, many studies have confirmed the possibility to image a large variety of sugar analogues, each with potentially interesting applications to assess tissue physiology. Some promising applications are the study of (i) sugar delivery and transport to assess blood brain barrier integrity, (ii) sugar uptake by cells for their characterization (e.g. cancer vs healthy), as well as (iii) clearance of sugars to assess tissue drainage for instance through the glymphatic system. To judge these opportunities and their challenges, especially in the clinic, it is needed to understand the technical aspects of detecting the presence of rapidly exchanging protons through the water signal in MRI, especially as a function of magnetic field strength. We expect that novel approaches in terms of MRI detection (both saturation transfer and relaxation based), MRI data analysis, and sugar design will push this young field forward in the next decade.
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| 6. |
- Lasič, Samo, et al.
(författare)
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Motion-compensated b-tensor encoding for in vivo cardiac diffusion-weighted imaging
- 2020
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 33:2
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Tidskriftsartikel (refereegranskat)abstract
- Motion is a major confound in diffusion-weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo-based DWI commonly employs gradient moment-nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2-nulled). However, current M2-nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b-tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof-of-concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2-nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2-nulled LTE, where diffusion-weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal-to-noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.
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| 7. |
- Li, Jing-Rebecca, et al.
(författare)
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Practical computation of the diffusion MRI signal of realistic neurons based on Laplace eigenfunctions
- 2020
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Ingår i: NMR in Biomedicine. - : John Wiley and Sons Ltd. - 0952-3480 .- 1099-1492. ; 33:10
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Tidskriftsartikel (refereegranskat)abstract
- The complex transverse water proton magnetization subject to diffusion-encoding magnetic field gradient pulses in a heterogeneous medium such as brain tissue can be modeled by the Bloch-Torrey partial differential equation. The spatial integral of the solution of this equation in realistic geometry provides a gold-standard reference model for the diffusion MRI signal arising from different tissue micro-structures of interest. A closed form representation of this reference diffusion MRI signal called matrix formalism, which makes explicit the link between the Laplace eigenvalues and eigenfunctions of the biological cell and its diffusion MRI signal, was derived 20 years ago. In addition, once the Laplace eigendecomposition has been computed and saved, the diffusion MRI signal can be calculated for arbitrary diffusion-encoding sequences and b-values at negligible additional cost. Up to now, this representation, though mathematically elegant, has not been often used as a practical model of the diffusion MRI signal, due to the difficulties of calculating the Laplace eigendecomposition in complicated geometries. In this paper, we present a simulation framework that we have implemented inside the MATLAB-based diffusion MRI simulator SpinDoctor that efficiently computes the matrix formalism representation for realistic neurons using the finite element method. We show that the matrix formalism representation requires a few hundred eigenmodes to match the reference signal computed by solving the Bloch-Torrey equation when the cell geometry originates from realistic neurons. As expected, the number of eigenmodes required to match the reference signal increases with smaller diffusion time and higher b-values. We also convert the eigenvalues to a length scale and illustrate the link between the length scale and the oscillation frequency of the eigenmode in the cell geometry. We give the transformation that links the Laplace eigenfunctions to the eigenfunctions of the Bloch-Torrey operator and compute the Bloch-Torrey eigenfunctions and eigenvalues. This work is another step in bringing advanced mathematical tools and numerical method development to the simulation and modeling of diffusion MRI.
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| 8. |
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| 9. |
- Sandvig, Ioanna, et al.
(författare)
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In vivo MRI of olfactory ensheathing cell grafts and regenerating axons in transplant mediated repair of the adult rat optic nerve
- 2012
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Ingår i: NMR in Biomedicine. - Malden, MA, USA : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 25:4, s. 620-631
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to use magnetic resonance imaging (MRI) as a tool for monitoring transplant-mediated repair of the adult rat visual pathway. We labelled rat olfactory ensheathing cells (OECs) using micron-sized particles of iron oxide (MPIO) and transplanted them by: i) intravitreal injection (ivit) and ii) intra-optic nerve (ON) injection (iON) in adult rats with ON crush (ONC) injury. We applied T2-weighted MRI and manganese-enhanced MRI (MEMRI) to visualise transplanted cells and ON axons at specific times after injury and cell engraftment. Our findings demonstrate that ivit MPIO-labelled OECs are unequivocally detected by T2-weighted MRI in vivo and that the T1-weighted 3D FLASH sequence applied for MEMRI facilitates simultaneous visualisation of Mn2+-enhanced regenerating retinal ganglion cell (RGC) axons and MPIO-labelled OEC grafts. Furthermore, analysis of MRI data and ultrastructural findings supports the hypothesis that iON OEC transplants mediate regeneration and remyelination of RGC axons post injury.
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| 10. |
- Seidemo, Anina, et al.
(författare)
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Tissue response curve shape analysis of dynamic glucose enhanced (DGE) and dynamic contrast enhanced (DCE) MRI in patients with brain tumor
- 2023
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 36:6
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic glucose enhanced (DGE) MRI is used to study the signal intensity time course (tissue response curve) after D-glucose injection. D-glucose has potential as a biodegradable alternative or complement to gadolinium-based contrast agents, with DGE being comparable to dynamic contrast enhanced (DCE) MRI. However, the tissue uptake kinetics as well as the detection methods of DGE differ from DCE, and it is relevant to compare these techniques in terms of spatiotemporal enhancement patterns. This study aims to develop a DGE analysis method based on tissue response curve shapes, and to investigate whether DGE MRI provides similar or complementary information to DCE MRI. Eleven patients with suspected gliomas were studied. Tissue response curves were measured for DGE and DCE MRI at 7 tesla and the area under curve (AUC) was assessed. Seven types of response curve shapes were postulated and subsequently identified by deep learning to create color-coded “curve maps” showing the spatial distribution of different curve types. DGE AUC values were significantly higher in lesions than in normal tissue (p
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