Compartmental diffusion and microstructural properties of human brain gray and white matter studied with double diffusion encoding magnetic resonance spectroscopy of metabolites and water

Abstract

Highlights Compartment and cell-specific microscopic anisotropy are measured with DDES. The intracellular space is highly anisotropic in white (WM) and gray matter (GM). The extracellular space in GM is isotropic, while that of WM is highly anisotropic. Water and metabolites intracellular mean diffusivities are lower in GM than in WM. Intracellular tortuosity derived from water and tNAA is higher in GM than WM.

Mapping complex cell morphology in the grey matter with double diffusion encoding MR: A simulation study

“…Our results at slow diffusivity (i.e. mimicking metabolites diffusion) are in good agreement with experimental evidences from previously published SDE ( Valette et al., 2018 ; Ingo et al., 2018 ; Palombo et al., 2016 ; Pfeuffer et al., 2000 ; Ellegood et al., 2005 ; Valette et al., 2007 ; Kan et al., 2012 ; Deelchand and Auerbach, 2018 ; Ercan et al., 2015 ; Ligneul and Valette, 2017 ; Marchadour et al., 2012 ; Marjańska et al., 2019 ; Döring et al., 2018 ; Najac et al., 2016 ; Najac et al., 2014 ) and DDE ( Lundell et al., 2020 ; Shemesh et al., 2017 ; Shemesh et al., 2014 ; Vincent et al., 2020 ; Lundell et al., 2021 ) measurements of metabolites diffusion through dMRS.…”

Diffusion time dependence, power-law scaling, and exchange in gray matter

“…8 ). In summary, the findings of ( Lundell et al., 2021 ) supports the notion of substantial neurite exchange in human GM in vivo and indicates that the effect could be quantified by varying the diffusion encoding time.…”

“…Consistent with the above, the GM water μFA was found to increase with b-value and be similar to the WM water μFA and NAA μFA at b ≈ 7.2 ms/μm 2 , where the extracellular and exchanged neurite water is suppressed, leaving non-exchanged neurite water (including possibly water in myelinated neurites) as the dominant signal contributor. To be consistent with substantial neurite exchange in GM, this would entail an accordingly substantial decrease in S(b) which was in fact observed (( Lundell et al., 2021 ) Fig. 8 ).…”

“…The decrease is more subtle than reported here though, as expected due to the use of much smaller b-values (see Section 2.3 ). Recently, ( Lundell et al., 2021 ) employed double diffusion encoding to compare microscopic anisotropy (μFA) ( Jespersen et al., 2013 ; Lasič et al., 2014 ) in human WM and GM from metabolites and water after applying a diffusion filter with increasing b-values. Their results inform on both structure and exchange and are thus relevant to our findings, but the diffusion encoding was on a timescale of ≈ 180 ms and thus likely probes a different regime than in our case with diffusion encoding below ≈ 30 ms. N-acetyl-aspartate (NAA) is predominantly present in neurons and NAA diffusion is thus sensitive to neuron structure, but not permeability, thereby providing unique insights into both when compared with water.…”

“…also found a large/small WM/GM water μFA at b ≈ 0.9 ms/μm 2 . This can be partly explained by differing extracellular μFA in WM and GM ( Lundell et al., 2021 ) but, considering that the neurite volume fraction is typically larger in GM than in WM and vice versa for extracellular water ( Jelescu et al., 2020 ), it also indicates that the water μFA has a much smaller contribution from neurites in GM. Their result thus supports the notion of substantial neurite water exchange since the fraction of exchanged neurite water will contribute to a low μFA similarly to the extracellular water.…”