Investigating exchange, structural disorder and restriction in Gray Matter via water and metabolites diffusivity and kurtosis time-dependence

Water diffusion MRI is a very powerful tool for probing tissue microstructure, but disentangling the contribution of compartment-specific structural disorder from cellular restriction and inter-compartment exchange remains an open challenge. Here, we use diffusion MR spectroscopy (dMRS) of water and metabolites as a function of diffusion time in vivo in mouse Gray Matter (GM) to shed light on: which of these concomitant mechanisms dominates the MR measurements and with which specific signature. We report the diffusion time-dependence of water with excellent SNR conditions up to 500 ms. Water kurtosis decreases with increasing diffusion time, showing the concomitant influence of both structural disorder and exchange. Despite the excellent SNR, we were not able to identify clearly the nature of the structural disorder (i.e. 1D versus 2D/3D short-range disorder). Measurements of intracellular metabolites diffusion time-dependence (up to 500 ms) show opposite behavior to water, with metabolites kurtosis increasing as a function of diffusion time. We show that this is a signature of diffusion restricted in the intracellular space from which cellular microstructural features can be estimated. Finally, by comparing water and metabolites diffusion time-dependencies, we attempt to disentangle the effect of intra/extracellular exchange and structural disorder of the extracellular space (both impacting water diffusion only). Our results suggest a relatively short intra/extracellular exchange time (1-50 ms) and short-range disorder (still unclear if 1D or 2D/3D) most likely coming from the extracellular compartment. This work provides novel insights to interpret water diffusion time-dependent measurements in terms of the underlying GM microstructure and suggests that diffusion time-dependent measurements of intracellular metabolites may offer a new way to quantify microstructural restrictions in GM

Investigating exchange, structural disorder and restriction in Gray Matter via water and metabolites diffusivity and kurtosis time-dependence

Water diffusion-weighted MRI is a very powerful tool for probing tissue microstructure, but disentangling the contribution of compartment-specific structural disorder from cellular restriction and inter-compartment exchange remains an open challenge. In this work we use diffusion-weighted MR spectroscopy (dMRS) of water and metabolite as a function of diffusion time in vivo in mouse gray matter to shed light on: i) which of these concomitant mechanisms (structural disorder, restriction and exchange) dominates the MR measurements and ii) with which specific signature. We report the diffusion time-dependence of water with excellent SNR conditions as provided by dMRS, up to a very long diffusion time (500 ms). Water kurtosis decreases with increasing diffusion time, showing the concomitant influence of both structural disorder and exchange. However, despite the excellent experimental conditions, we were not able to clearly identify the nature of the structural disorder (i.e. 1D versus 2D/3D short-range disorder). Measurements of purely intracellular metabolites diffusion time-dependence (up to 500 ms) show opposite behavior to water, with metabolites kurtosis increasing as a function of diffusion time. We show that this is a signature of diffusion restricted in the intracellular space, from which cellular microstructural features such as soma’s and cell projections’ size can be estimated. Finally, by comparing water and metabolite diffusion time dependencies, we attempt to disentangle the effect of intra/extracellular exchange and structural disorder of the extracellular space (both impacting water diffusion only). Our results suggest a relatively short intra/extracellular exchange time (~1-50 ms) and short-range disorder (still unclear if 1D or 2D/3D) most likely coming from the extracellular compartment. This work provides novel insights to help interpret water diffusion-time dependent measurements in terms of the underlying microstructure of gray matter and suggests that diffusion-time dependent measurements of intracellular metabolites may offer a new way to quantify microstructural restrictions in gray matter

Etude par IRM, de l'interaction dipolaire présente dans un tissu riche en macromolécules : application sur le cartilage

National audienceL'arthrose est une maladie dégénérative du cartilage qui touche en France une personne sur six. La visualisation et l'identification de la composition des différentes couches de cartilage est un enjeu important dans le suivi des stades de la maladie. L'outil non invasif le plus performant dans ce contexte est l'IRM, mais dans le cas de tissus très denses en macromolécules, cette technique ne permet pas d'obtenir beaucoup d'informations sur le plan physiologique. Nous avons mis au point une méthode IRM innovante qui devrait permettre de résoudre ce problème en étudiant l'interaction dipolaire subie par les protons de l'eau entourant ses macromolécules.Ce processus a été découvert par Redfield[1] et repris par Matsui[2]. Grenier[3] a ensuite élaboré une séquence permettant d'utiliser cette interaction pour pondérer le signal IRM en fonction de la composante dipolaire perçue par les protons. Dans les tissus contenant des macromolécules comme les protéoglycanes, les protons des molécules d'eau sont soumis à un phénomène physique bien connu des praticiens, qui est à l'origine d'artefacts nommés « angle magique ». Cet hypersignal est la signature de l'interaction dipolaire présente dans les tissus riches en macromolécules structurées, et correspond à l'annulation de l'interaction dipolaire dans les tissus ordonnés suivant un angle donné. La séquence de contraste dipolaire (ou T2ρ) suscitée, permet de moduler l'interaction dipolaire jusqu'à pouvoir l'annuler (Fig.1). Ainsi, le signal provenant des zones qui subissaient cette interaction devient plus intense. Par soustraction, de deux images acquises avec et sans interaction dipolaire (Fig.2b et Fig.2a resp.), nous avons accès à la composante dipolaire (Fig.2c) du signal. Les premiers résultats sur le cartilage montrent une augmentation du signal de plus de 100% (Fig.3). Le rehaussement de signal confère à T2ρ un grand intérêt applicatif in-vivo, car le signal reçu du cartilage devient équivalent à celui des zones liquides. Nous avons couplé un module de T2ρ sur une séquence Echo Planar Imaging pour diminuer considérablement le temps d'acquisition et la déposition d'énergie, grâce à une acquisition « single-shot ». Il nous est apparu intéressant, pour quantifier notre technique, de comparer les effets de T2ρ à ceux d'une autre séquence, permettant de détecter indirectement le réservoir dipolaire.[1] Ag Redfield, Physical Review 98, no. 6 (1955): 1787–1809.[2] S. Matsui, Chemical Physics Letters 179, no. 1–2 (April 12, 1991): 187–90.[3] D. Grenier, O. Pascui, and A. Briguet, Journal of Magnetic Resonance 147, no. 2 (December 2000): 353–56

Assessing potential correlation between T ₂ relaxation and diffusion of lactate in the mouse brain

International audienceWhile diffusion and T 2 relaxation are intertwined, little or no correlation exists between diffusion and T 2 relaxation of intracellular metabolites in the rodent brain, as measured by diffusion-weighted MRS at different TEs. However, situation might be different for lactate, since it is present in both extracellular and intracellular spaces, which exhibit different diffusion properties and may also exhibit different T 2. Such a TE dependence would be crucial to account for when interpreting or modeling lactate diffusion. Here we propose to take advantage of a new diffusion sequence, where J-modulation of lactate is canceled even at long TE, thus retaining excellent signal, to assess potential T 2 dependence on diffusion of lactate in the mouse brain. Methods: Using a frequency-selective diffusion-weighted spin-echo sequence that removes J-modulation at 1.3 ppm, thus preserving lactate signal even at long TE, we investigate the effect of TE between 50.9 and 110.9 ms (while keeping diffusion time constant) on apparent diffusivity and kurtosis in the mouse brain. Results: Regardless of the metabolites, no difference appears for the diffusion-weighted signal attenuation with increasing TE. For lactate, apparent diffusivity and kurtosis remain unchanged as TE increases. Conclusion: No significant TE dependence of diffusivity and kurtosis is measured for lactate in the 50-110 ms TE range, confirming that potential T 2 effects can be ignored when interpreting or modeling lactate diffusion

Binomial shape-RF in magic echo sandwich for imaging

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Relationship between signal enhancement with dipolar technique and viscoelasticity of tissues containing macromolecules

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AUGMENTATION DU SIGNAL IRM DANS LES TISSUS DENSES EN MACROMOLECULES : LIEN AVEC L’ELASTICITE

International audienceA l’heure de la radiomique, le champ d’application de l’IRM est de plus en plus étendu. Cette technique permet d’accéder facilement à de multiples types d’informations morphologiques, physiologiques et fonctionnelles. Notre étude porte sur l’analyse des propriétés d’une séquence IRM (appelée T2ρ), qui permet d’augmenter, dans certains tissus, l’intensité du signal de l’eau. Cette séquence, basée sur la théorie de Redfield [1], a donné des résultats remarquables sur certains tissus en montrant un rehaussement de signal important dans les régions riches en macromolécules [2]. Le degré de liaisons entre ces dernières et l’eau peut refléter les propriétés viscoélastiques des tissus de l’organisme. Nous voulons corréler le rehaussement de signal obtenu par T2ρ à la viscoélasticité du milieu, sur des fantômes calibrés.1. A.G.Redfield, Phys. Rev.,DOI: 10.1103/PhysRev.98.17872. D. Grenier et al., DOI: 10.1006/jmre.2000.218

Magic Sandwich to Stimulated Echo Relative change to identify sign and intensity of dipolar interaction in anisotropic tissue

International audienceAmong the MR techniques playing on dipolar interaction (Hd), the magic sandwich echo sequence (MSE) is very seldom used in biological application. So far, the magic echo has been compared to the spin echo. However, MSE is closer to a stimulated echo thus a Magic Sandwich to Stimulated echo relative change (MaSteR) is of interest to study. The MaSteR evolution with spin-lock intensity increase was studied for thawed tendon for different orientations within B0 to modulate the dipolar interaction. We show that MaSteR is correlated to dipolar interaction, sample composition and its evolution with orientation is sensitive to Hd sign. Summary (250 characters): A marker of macromolecular dipolar interactions (Hd) is introduced as the Magic Sandwich to Stimulated Echo relative change (MaSteR). Different B1 spin lock intensities are used to modulate Hd. MaSteR is sensitive to Hd sign and fiber orientation