Apparent exchange rate imaging: On its applicability and the connection to the real exchange rate

Ludwig, Dominik; Laun, Frederik Bernd; Ladd, Mark E.; Bachert, Peter; Kuder, Tristan Anselm

doi:10.1002/mrm.28714

Cited by 10 publications

(13 citation statements)

References 64 publications

(129 reference statements)

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“…Such spins escape the suppression by the mobility filter (Figure 2) and contribute to the recovery of diffusion coefficient when moving in areas with less restricted diffusion. In contrast to previous simulation studies focused on packing of simple objects, 8,26 our main interest was in synthetic random media inspired by the complexity of brain gray matter (Figure 5). The complex geometry of such media results in the emergence of the typical FEXI pattern of gradual recovery of the diffusion coefficient towards its unperturbed value.…”

Section: Discussionmentioning

confidence: 99%

“…The present revival of interest in such measurements is inspired by possible biomedical applications. The method was validated in numerical simulations, 7,8 yeast cell suspension 5,7 and human embryonic kidney cells 9 . Implemented on clinical MRI scanners, 7 it has been applied to investigation of human brain tissue, 10‐13 brain tumors 14 and breast cancer, 15 see also a review 16 .…”

Section: Introductionmentioning

confidence: 99%

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What does FEXI measure?

et al. 2022

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Summary Filter‐exchange imaging (FEXI) has already been utilized in several biomedical studies for evaluating the permeability of cell membranes. The method relies on suppressing the extracellular signal using strong diffusion weighting (the mobility filter causing a reduction in the overall diffusivity) and monitoring the subsequent diffusivity recovery. Using Monte Carlo simulations, we demonstrate that FEXI is sensitive not uniquely to the transcytolemmal exchange but also to the geometry of involved compartments: complex geometry offers locations where spins remain unaffected by the mobility filter; moving to other locations afterwards, such spins contribute to the diffusivity recovery without actually permeating any membrane. This exchange mechanism is a warning for those who aim to use FEXI in complex media such as brain gray matter and opens wide scope for investigation towards crystallizing the genuine membrane permeation and characterizing the compartment geometry.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

What does FEXI measure?

et al. 2022

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“…It is "exchange", in agreement with the principle of FEXI, but purely diffusive, without any membrane permeation. Note that the possible dependence on compartment geometry was only briefly mentioned in the literature [5].…”

Section: Discussionmentioning

confidence: 99%

“…In this context, FEXI is commonly considered as a way to access the cell membrane permeability for water. The method was validated in numerical simulations [4,5], yeast cell suspension [3,4] and human embryonic kidney cells [6]. Implemented on clinical magnetic resonance imaging (MRI) scanners [4], it has been applied to investigation of human brain tissue [7,8], brain tumors [9] and breast cancer [10].…”

Section: Introductionmentioning

confidence: 99%

What Does FEXI Measure?

Khateri¹,

Reisert²,

Sierra³

et al. 2022

Preprint

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Filter-exchange imaging (FEXI) has already been utilized in several biomedical studies for evaluating the permeability of cell membranes. The method relies on suppressing the extracellular signal using strong diffusion weighting (the mobility filter causing a reduction in the overall diffusivity) and monitoring the subsequent diffusivity recovery. Using Monte Carlo (MC) simulations, we demonstrate that FEXI is not uniquely sensitive to the transcytolemmal exchange but also to the geometry of involved compartments: Complicated geometry offers locations where spins remain unaffected by the mobility filter; moving to other locations afterward, such spins contribute to the diffusivity recovery without actually permeating any membrane. This exchange mechanism challenges the interpretation of FEXI in complex media such as brain gray matter and opens large room for investigation towards crystallizing the genuine membrane permeation and characterizing the compartment geometry.

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“…DEXSY is thus a valuable tool for the noninvasive study of porous materials such as biological tissue. DEXSY and DEXSY-based methods are ideally suited for studying transmembrane water transport in cells and tissues [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Disentangling the Effects of Restriction and Exchange With Diffusion Exchange Spectroscopy

et al. 2022

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Diffusion exchange spectroscopy (DEXSY) is a multidimensional NMR technique that can reveal how water molecules exchange between compartments within heterogeneous media, such as biological tissue. Data from DEXSY experiments is typically processed using numerical inverse Laplace transforms (ILTs) to produce a diffusion-diffusion spectrum. A tacit assumption of this ILT approach is that the signal behavior is Gaussian—i.e., the spin echo intensity decays exponentially with the degree of diffusion weighting. The assumptions that underlie Gaussian signal behavior may be violated, however, depending on the gradient strength applied and the sample under study. We argue that non-Gaussian signal behavior due to restrictions is to be expected in the study of biological tissue using diffusion NMR. Further, we argue that this signal behavior can produce confounding features in the diffusion-diffusion spectra obtained from numerical ILTs of DEXSY data—entangling the effects of restriction and exchange. Specifically, restricted signal behavior can result in broadening of peaks and in the appearance of illusory exchanging compartments with distributed diffusivities, which pearl into multiple peaks if not highly regularized. We demonstrate these effects on simulated data. That said, we suggest the use of features in the signal acquisition domain that can be used to rapidly probe exchange without employing an ILT. We also propose a means to characterize the non-Gaussian signal behavior due to restrictions within a sample using DEXSY measurements with a near zero mixing time or storage interval. We propose a combined acquisition scheme to independently characterize restriction and exchange with various DEXSY measurements, which we term Restriction and Exchange from Equally-weighted Double and Single Diffusion Encodings (REEDS-DE). We test this method on ex vivo neonatal mouse spinal cord—a sample consisting primarily of gray matter—using a low-field, static gradient NMR system. In sum, we highlight critical shortcomings of prevailing DEXSY analysis methods that conflate the effects of restriction and exchange, and suggest a viable experimental approach to disentangle them.

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Apparent exchange rate imaging: On its applicability and the connection to the real exchange rate

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 10 publications

References 64 publications

What does FEXI measure?

What does FEXI measure?

What Does FEXI Measure?

Disentangling the Effects of Restriction and Exchange With Diffusion Exchange Spectroscopy

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