A model for extra‐axonal diffusion spectra with frequency‐dependent restriction

Lam, Wilfred; Jbabdi, Saâd; Miller, Karla L.

doi:10.1002/mrm.25363

Cited by 16 publications

(14 citation statements)

References 61 publications

(101 reference statements)

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“…For the extracellular space, we use a simple tortuosity model which has been previously used for estimating axonal indices in the human brain . In some situations that model can become inaccurate, for example, if extracellular space exhibits restricted diffusion as observed experimentally by or at long diffusion times where the diffusion constant may become time dependent . A future challenge will be to include this in our modelling of the extracellular space.…”

Section: Discussionmentioning

confidence: 99%

PGSE, OGSE, and sensitivity to axon diameter in diffusion MRI: Insight from a simulation study

Drobnjak

Zhang

Ianuş

et al. 2015

Magnetic Resonance in Med

111

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PurposeTo identify optimal pulsed gradient spin‐echo (PGSE) and oscillating gradient spin‐echo (OGSE) sequence settings for maximizing sensitivity to axon diameter in idealized and practical conditions.MethodsSimulations on a simple two‐compartment white matter model (with nonpermeable cylinders) are used to investigate a wide space of clinically plausible PGSE and OGSE sequence parameters with trapezoidal diffusion gradient waveforms. Signal sensitivity is measured as a derivative of the signal with respect to axon diameter. Models of parallel and dispersed fibers are investigated separately to represent idealized and practical conditions.ResultsSimulations show that, for the simple case of gradients perfectly perpendicular to straight parallel fibers, PGSE always gives maximum sensitivity. However, in real‐world scenarios where fibers have unknown and dispersed orientation, low‐frequency OGSE provides higher sensitivity. Maximum sensitivity results show that on current clinical scanners (G max = 60 mT/m, signal to noise ratio (SNR) = 20) axon diameters below 6 µm are indistinguishable from zero. Scanners with stronger gradient systems such as the Massachusetts General Hospital (MGH) Connectom scanner (G max = 300 mT/m) can extend this sensitivity limit down to 2–3 µm, probing a much greater proportion of the underlying axon diameter distribution.ConclusionLow‐frequency OGSE provides additional sensitivity to PGSE in practical situations. OGSE is particularly advantageous for systems with high performance gradients. Magn Reson Med 75:688–700, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Discussionmentioning

confidence: 99%

PGSE, OGSE, and sensitivity to axon diameter in diffusion MRI: Insight from a simulation study

Drobnjak

Zhang

Ianuş

et al. 2015

Magnetic Resonance in Med

111

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“…Because of the complexity of extracellular structure, it is challenging to derive a general analytical equation to describe the diffusion spectra arising from the extracellular space. An empirical model for extracellular diffusion has been proposed recently to describe packed cylindrical axons . However, previous studies have found that if only a narrow range of relatively low gradient frequencies is used (such as 0, 40, and 80 Hz used in the current work), the extracellular diffusion coefficient can be approximated as a linear function of gradient frequency .…”

Section: Methodsmentioning

confidence: 96%

Impact of transcytolemmal water exchange on estimates of tissue microstructural properties derived from diffusion MRI

Jiang

Xie

et al. 2016

Magn. Reson. Med.

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Purpose To investigate the influence of transcytolemmal water exchange on estimates of tissue microstructural parameters derived from diffusion MRI using conventional PGSE and IMPULSED methods. Methods Computer simulations were performed to incorporate a broad range of intracellular water life times τin (50 – ∞ ms), cell diameters d (5 – 15 μm), and intrinsic diffusion coefficient Din (0.6 – 2 μm2/ms) for different values of signal to noise ratio (10 to 50). For experiments, murine erythroleukemia (MEL) cancer cells were cultured and treated with saponin to selectively change cell membrane permeability. All fitted microstructural parameters from simulations and experiments in vitro were compared with ground-truth values. Results Simulations showed that, for both PGSE and IMPULSED methods, cell diameter d can be reliably fit with sufficient SNR (≥ 50), while intracellular volume fraction fin is intrinsically underestimated due to transcytolemmal water exchange. Din can be reliably fit only with sufficient SNR and using the IMPULSED method with short diffusion times. These results were confirmed with those obtained in the cell culture experiments in vitro. Conclusion For the sequences and models considered in this study, transcytolemmal water exchange has minor impacts on fittings of d and Din with physiologically relevant membrane permeabilities if SNR is sufficient (> 50), but fin is intrinsically underestimated.

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“…Timeand frequency-dependencies of the diffusion coefficient have been studied in porous media [24] as well as in biological systems [25][26][27][28]. Several theoretical frameworks relate timedependent behaviours to specific morphological features, such as pore size [29][30][31][32] as well as the internal disorder and packing [27,33,34]. Oscillating Diffusion Encoding (ODE) can be used to probe short time scales, and have demonstrated superior tensor contrasts [35], as well as sensitivity to surface-to-volume ratio [36,37] and restriction size in elongated pores [38][39][40].…”

Section: Introductionmentioning

confidence: 99%

Accurate estimation of microscopic diffusion anisotropy and its time dependence in the mouse brain

et al. 2018

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Microscopic diffusion anisotropy (μA) has been recently gaining increasing attention for its ability to decouple the average compartment anisotropy from orientation dispersion. Advanced diffusion MRI sequences, such as double diffusion encoding (DDE) and double oscillating diffusion encoding (DODE) have been used for mapping μA, usually using measurements from a single b shell. However, the accuracy of μA estimation vis-à-vis different b-values was not assessed. Moreover, the time-dependence of this metric, which could offer additional insights into tissue microstructure, has not been studied so far. Here, we investigate both these concepts using theory, simulation, and experiments performed at 16.4T in the mouse brain, ex-vivo. In the first part, simulations and experimental results show that the conventional estimation of microscopic anisotropy from the difference of D(O)DE sequences with parallel and orthogonal gradient directions yields values that highly depend on the choice of b-value. To mitigate this undesirable bias, we propose a multi-shell approach that harnesses a polynomial fit of the signal difference up to third order terms in b-value. In simulations, this approach yields more accurate μA metrics, which are similar to the ground-truth values. The second part of this work uses the proposed multi-shell method to estimate the time/frequency dependence of μA. The data shows either an increase or no change in μA with frequency depending on the region of interest, both in white and gray matter. When comparing the experimental results with simulations, it emerges that simple geometric models such as infinite cylinders with either negligible or finite radii cannot replicate the measured trend, and more complex models, which, for example, incorporate structure along the fibre direction are required. Thus, measuring the time dependence of microscopic anisotropy can provide valuable information for characterizing tissue microstructure.

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A model for extra‐axonal diffusion spectra with frequency‐dependent restriction

Cited by 16 publications

References 61 publications

PGSE, OGSE, and sensitivity to axon diameter in diffusion MRI: Insight from a simulation study

PGSE, OGSE, and sensitivity to axon diameter in diffusion MRI: Insight from a simulation study

Impact of transcytolemmal water exchange on estimates of tissue microstructural properties derived from diffusion MRI

Accurate estimation of microscopic diffusion anisotropy and its time dependence in the mouse brain

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