Diffusion MRI with free gradient waveforms on a high-performance gradient system: Probing restriction and exchange in the human brain

Chakwizira, Arthur; Zhu, Ante; Foo, Thomas; Westin, Carl-Fredrik; Szczepankiewicz, Filip; Nilsson, Markus

doi:10.1016/j.neuroimage.2023.120409

Cited by 6 publications

(5 citation statements)

References 93 publications

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“…The observations of elevated 𝐾 𝜇 in grey matter and stroke lesions are consistent with previous reports of fast exchange in these tissues 79,85,86 and thus the reported values of 𝐾 𝜇 may reflect exchange. To empirically determine the degree to which exchange influences 𝐾 𝜇 , a protocol featuring variable mixing times for parallel DDE acquisitions as well as variable diffusion times can be used.…”

Section: Discussionsupporting

confidence: 91%

“…More recent work has demonstrated the utility of free gradient waveforms for mapping exchange in the human brain unconfounded by restricted diffusion 51,79 . The general consensus regarding exchange in the brain is that it is small and potentially negligible between the intra-and extra-axonal spaces in healthy myelinated white matter at clinically-accessible diffusion times and this finding is explained by the presence and low permeability of myelin sheaths [80][81][82][83][84] .…”

Section: Discussionmentioning

confidence: 99%

“…7-8). This approach may provide a good candidate for an analysis framework in cases where both exchange and microscopic kurtosis are expected to be relevant, such as in grey matter 68,79 . However, as highlighted earlier, the theory has an innate degeneracy at very low exchange rates (Fig.…”

Section: Discussionmentioning

confidence: 99%

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The interplay between exchange and microscopic kurtosis as measured by diffusion MRI with double diffusion encoding: Theory and simulations

Chakwizira,

Szczepankiewicz,

Nilsson

2024

Preprint

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Double diffusion encoding (DDE) makes diffusion MRI sensitive to a wide range of microstructural features, and the acquired data can be analysed using different approaches. Correlation tensor imaging (CTI) uses DDE to resolve three components of the diffusional kurtosis: isotropic, anisotropic, and microscopic. The microscopic kurtosis is estimated from the contrast between single diffusion encoding (SDE) and parallel DDE signals at the same b-value. Another approach is multi-Gaussian exchange (MGE), which employs DDE to measure exchange. Sensitivity to exchange is obtained by contrasting SDE and DDE signals at the same b-value. CTI and MGE exploit the same signal contrast to quantify microscopic kurtosis and exchange, and this study investigates the interplay between these two quantities. We perform Monte-Carlo simulations in different geometries with varying levels of exchange and study the behaviour of the parameters from CTI and MGE. We conclude that microscopic kurtosis from CTI is sensitive to the exchange rate. In an attempt to separate microscopic kurtosis from exchange, we propose a heuristic signal representation referred to as µMGE (MGE incorporating microscopic kurtosis) that accounts for both effects, by exploiting the distinct signatures of exchange and microscopic kurtosis with varying mixing time: exchange causes a dependence of the signal on mixing time while microscopic kurtosis does not. We find that applying µMGE to data acquired with multiple mixing times for both parallel and orthogonal DDE allows estimation of exchange as well as all three sources of kurtosis.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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The interplay between exchange and microscopic kurtosis as measured by diffusion MRI with double diffusion encoding: Theory and simulations

Chakwizira,

Szczepankiewicz,

Nilsson

2024

Preprint

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“…However, somewhat lower exchange rates of 3.5-8.7 s −1 have recently been obtained for cerebellar cortex using free gradient wave forms. 26 For tumors, in contrast, we calculate much smaller values of R * KM = 2 to 4 s −1 , which are consistent with the explicit fits to a simple version of the KM performed by Zhang et al 13 who obtain exchange times ranging from 70 to 128 ms for the same dataset. Taking into account the term in their fits related to eigenvectors of G with eigenvalues equal to zero, their results correspond to R KM = 4.0 s −1 for the glioma model, R KM =5.1 s −1 for the mammary tumor model, and R KM =9.7 s −1 for the breast tumor model.…”

Section: Discussionsupporting

confidence: 90%

“…Taken all together, these two prior studies along with our results, provide strong support for a high rate of water exchange occurring within gray matter. However, somewhat lower exchange rates of 3.5–8.7

{\mathrm{s}}^{-1}

have recently been obtained for cerebellar cortex using free gradient wave forms 26 …”

Section: Discussionmentioning

confidence: 99%

Diffusional kurtosis time dependence and the water exchange rate for the multi‐compartment Kärger model

Jensen

2023

Magnetic Resonance in Med

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PurposeTo demonstrate an analytic formula giving the time dependence of the diffusional kurtosis for the Kärger model (KM) with an arbitrary number of exchanging compartments and its application in estimating the mean KM water exchange rate.Theory and MethodsThe general formula for the kurtosis is derived from a power series solution for the multi‐compartment KM. A lower bound on the exchange rate is established from the observation that the kurtosis is always a logarithmically convex function of time. Both the kurtosis time dependence and the lower bound are illustrated with numerical calculations. The lower bound is also applied to previously published data for the time dependence of the kurtosis in both brain and tumors.ResultsThe kurtosis for the multi‐compartment KM is given by a sum in which each term is associated with an eigenvector of the exchange rate matrix. The lower bound is determined from the most negative value for the logarithmic derivative of the kurtosis with respect to time. In the cerebral cortex, the lower bound is found to vary from 15 to 76 s−1, depending on the experimental details, while for the tumors considered, it varies from 2 to 4 s−1.ConclusionThe time dependence of the kurtosis for the multi‐compartment KM has a simple analytic solution that allows a lower bound for the mean KM water exchange rate to be determined directly from experiment. This may be useful in tissues with complex microstructure that is difficult to model explicitly.

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Tuned exchange imaging: Can the filter exchange imaging pulse sequence be adapted for applications with thin slices and restricted diffusion?

Lasič,

Chakwizira,

Lundell

et al. 2024

NMR in Biomedicine

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Filter exchange imaging (FEXI) is a double diffusion‐encoding (DDE) sequence that is specifically sensitive to exchange between sites with different apparent diffusivities. FEXI uses a diffusion‐encoding filtering block followed by a detection block at varying mixing times to map the exchange rate. Long mixing times enhance the sensitivity to exchange, but they pose challenges for imaging applications that require a stimulated echo sequence with crusher gradients. Thin imaging slices require strong crushers, which can introduce significant diffusion weighting and bias exchange rate estimates. Here, we treat the crushers as an additional encoding block and consider FEXI as a triple diffusion‐encoding sequence. This allows the bias to be corrected in the case of multi‐Gaussian diffusion, but not easily in the presence of restricted diffusion. Our approach addresses challenges in the presence of restricted diffusion and relies on the ability to independently gauge sensitivities to exchange and restricted diffusion for arbitrary gradient waveforms. It follows two principles: (i) the effects of crushers are included in the forward model using signal cumulant expansion; and (ii) timing parameters of diffusion gradients in filter and detection blocks are adjusted to maintain the same level of restriction encoding regardless of the mixing time. This results in the tuned exchange imaging (TEXI) protocol. The accuracy of exchange mapping with TEXI was assessed through Monte Carlo simulations in spheres of identical sizes and gamma‐distributed sizes, and in parallel hexagonally packed cylinders. The simulations demonstrate that TEXI provides consistent exchange rates regardless of slice thickness and restriction size, even with strong crushers. However, the accuracy depends on b‐values, mixing times, and restriction geometry. The constraints and limitations of TEXI are discussed, including suggestions for protocol adaptations. Further studies are needed to optimize the precision of TEXI and assess the approach experimentally in realistic, heterogeneous substrates.

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Diffusion MRI with free gradient waveforms on a high-performance gradient system: Probing restriction and exchange in the human brain

Cited by 6 publications

References 93 publications

The interplay between exchange and microscopic kurtosis as measured by diffusion MRI with double diffusion encoding: Theory and simulations

The interplay between exchange and microscopic kurtosis as measured by diffusion MRI with double diffusion encoding: Theory and simulations

Diffusional kurtosis time dependence and the water exchange rate for the multi‐compartment Kärger model

Tuned exchange imaging: Can the filter exchange imaging pulse sequence be adapted for applications with thin slices and restricted diffusion?

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