Intracellular metabolites in the primate brain are primarily localized in long fibers rather than in cell bodies, as shown by diffusion-weighted magnetic resonance spectroscopy

Najac, Chloé; Marchadour, Charlotte; Guillermier, Martine; Houitte, Diane; Slavov, V.; Brouillet, Emmanuel; Hantraye, Philippe; Lebon, Vincent; Valette, Julien

doi:10.1016/j.neuroimage.2013.12.045

Cited by 30 publications

(51 citation statements)

References 44 publications

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“…The non-monoexponential signal attenuation of intracellular metabolites in the mouse brain can be essentially described by diffusion in long and thin cylinders, yielding realistic D intra and fiber diameters, thus consolidating the view that metabolites diffusion is characteristic of diffusion in long and thin fibers, as previously proposed based on ADC measurements performed at long t d (and low b) (15–17). However, this simple model seems to require some small “corrections” for NAA at very high b, under the form of a small fraction of the NAA signal originating from a highly restricted (with short T 2 ) compartment, e.g.…”

Section: Discussionsupporting

confidence: 62%

Modeling diffusion of intracellular metabolites in the mouse brain up to very high diffusion‐weighting: Diffusion in long fibers (almost) accounts for non‐monoexponential attenuation

Palombo

Ligneul

Valette

2016

Magnetic Resonance in Med

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The non-monoexponential signal attenuation of intracellular metabolites in the mouse brain can be described by diffusion in long and thin cylinders, yielding realistic D and fiber diameters. However, this simple model may require small "corrections" for NAA, in the form of a small fraction of the NAA signal originating from a highly restricted compartment. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

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Section: Discussionsupporting

confidence: 62%

Modeling diffusion of intracellular metabolites in the mouse brain up to very high diffusion‐weighting: Diffusion in long fibers (almost) accounts for non‐monoexponential attenuation

Palombo

Ligneul

Valette

2016

Magnetic Resonance in Med

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“…) , consistent with the human study that used diffusion times ranging from 92 to 712 ms . The ADC measurements were fitted to the two models, and the fitting results were compared with anatomical knowledge of soma, axon, and dendrite diameters . The “neurite” model, but not the “cell body” model, was found to provide biologically valid estimates .…”

Section: Diffusion Mrs Studies In Brainsmentioning

confidence: 63%

In vivo diffusion MRS investigation of non‐water molecules in biological tissues

Cao¹,

2016

NMR in Biomedicine

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Diffusion MRS of non-water molecules offers great potential in directly revealing various tissue microstructures and physiology at both cellular and subcellular levels. In brain, H diffusion MRS has been demonstrated as a new tool for probing normal tissue microstructures and their pathological changes. In skeletal muscle, H diffusion MRS could characterize slow and restricted intramyocellular lipid diffusion, providing a sensitive marker for metabolic alterations, while P diffusion MRS can measure ATP and PCr diffusion, which may reflect the capacity of cellular energy transport, complementing the information from frequently used P MRS in muscle. In intervertebral disk, H diffusion MRS can directly monitor extracellular matrix integrity by quantifying the mobility of macromolecules such as proteoglycans and collagens. In tumor tissue, C diffusion MRS could probe intracellular glycolytic metabolism, while H diffusion MRS may separate the spectrally overlapped lactate and lipid resonances. In this review, recent diffusion MRS studies of these biologically relevant non-water molecules under normal and diseased conditions will be presented. Technical considerations for diffusion MRS experiments will be discussed. With advances in MRI hardware and diffusion methodology, diffusion MRS of non-water molecules is expected to provide increasingly valuable and biologically specific information on tissue microstructures and physiology, complementing the traditional diffusion MRI of small and ubiquitous water molecules. Copyright © 2016 John Wiley& Sons, Ltd.

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“…In this context, DW-MRS offers a unique noninvasive tool to specifically probe each of these cellular compartments and to link the cellular architecture with the macroscopic signal being measured and vice versa. Here we decided to elaborate on our recent finding that metabolite diffusion measured at long diffusion times t d (up to ∼1 s) is fairly stable in the monkey (20) and in the human brain (21), suggesting that metabolites are not significantly confined in subcellular regions or organelles but are instead diffusing in the long fibers typical of neuron and astrocyte morphology. However, because axons, dendrites, and astrocytic processes are not infinite, metabolites should start experiencing long-range structure as t d keeps increasing.…”

Section: Resultsmentioning

confidence: 99%

“…An 18-× 18-× 18-mm 3 (5.8-mL) voxel was positioned in the region of interest. The methodology used is exactly the same as described in our recent work in the primate brain (20), i.e., spectra were acquired with a diffusion contrast Δb = 3,000 s/mm 2 using a STEAM (stimulated echo acquisition mode) sequence modified for diffusion weighting, and t d was changed by changing the mixing time. Rodent experiments were performed on healthy C57/BL6 male mice (body weight ∼ 30 g) anesthetized at low isoflurane dose (<1.5%), using an 11.7-T MRI scanner (Bruker BioSpec).…”

Section: Methodsmentioning

confidence: 99%

New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo

Palombo

Ligneul

Najac

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The brain is one of the most complex organs, and tools are lacking to assess its cellular morphology in vivo. Here we combine original diffusion-weighted magnetic resonance (MR) spectroscopy acquisition and novel modeling strategies to explore the possibility of quantifying brain cell morphology noninvasively. First, the diffusion of cellspecific metabolites is measured at ultra-long diffusion times in the rodent and primate brain in vivo to observe how cell long-range morphology constrains metabolite diffusion. Massive simulations of particles diffusing in synthetic cells parameterized by morphometric statistics are then iterated to fit experimental data. This method yields synthetic cells (tentatively neurons and astrocytes) that exhibit striking qualitative and quantitative similarities with histology (e.g., using Sholl analysis). With our approach, we measure major interspecies difference regarding astrocytes, whereas dendritic organization appears better conserved throughout species. This work suggests that the time dependence of metabolite diffusion coefficient allows distinguishing and quantitatively characterizing brain cell morphologies noninvasively.cell morphology | noninvasive histology | diffusion-weighted NMR spectroscopy | numerical simulations | metabolites T he brain is one of the most complex organs, and it has defined an inexhaustible field of research over the last centuries. Unfortunately, brain's complexity is paralleled by the difficulty in examining it noninvasively. Some fundamental questions regarding morphological modifications of neurons and astrocytes along brain development, aging, or disease, as well as interspecies differences, can only be investigated postmortem using histology, the current gold standard to study cellular morphology. The development of a noninvasive neuroimaging tool to evaluate and monitor brain cell morphology under normal and pathological conditions in vivo would thus represent a major breakthrough.MRI and magnetic resonance spectroscopy (MRS) techniques have opened new doors for examining brain tissues in vivo at both meso-and macroscales. Diffusion-weighted (DW)-MRI and -MRS, which allow the investigation of the diffusion process of endogenous molecules in biological tissues at these scales (1), have made it clear that cell architecture has a critical influence on molecular displacement (2-5). To quantitatively evaluate the impact of cell structure on measured molecular diffusion, mainly two modeling strategies have been developed. The first approach consists in performing numerical simulations of many particles diffusing in arbitrary geometries (e.g., defined by 3D meshes) mimicking "realistic" cell architectures (6-9). Because these realistic geometries are generally built directly from microscopy data rather than being described and generated by a (small) set of parameters, and because simulations are extremely computationally demanding, this approach does not seem adapted to fit experimental data. The second approach consists in simplifying cell architec...

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Intracellular metabolites in the primate brain are primarily localized in long fibers rather than in cell bodies, as shown by diffusion-weighted magnetic resonance spectroscopy

Cited by 30 publications

References 44 publications

Modeling diffusion of intracellular metabolites in the mouse brain up to very high diffusion‐weighting: Diffusion in long fibers (almost) accounts for non‐monoexponential attenuation

Modeling diffusion of intracellular metabolites in the mouse brain up to very high diffusion‐weighting: Diffusion in long fibers (almost) accounts for non‐monoexponential attenuation

In vivo diffusion MRS investigation of non‐water molecules in biological tissues

New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo

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