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Looking into the functional architecture of the brain with diffusion MRI

Key Points

  • The basic principles of diffusion MRI (dMRI) were introduced in the mid-1980s. This method is deeply rooted in the concept that, during their diffusion-driven displacements, molecules probe tissue structure on a microscopic scale, well beyond the usual (millimetric) image resolution.

  • During diffusion times of about 50 ms, water molecules move in the brain over distances of around 10 μm on average, bouncing off, crossing or interacting with many tissue components, such as cell membranes, fibres or macromolecules. The observation of this displacement distribution, on a statistical basis, provides unique clues to the structural features and the geometric organization of neural tissues, and to changes in those features with physiological or pathological states.

  • Potential clinical applications of dMRI were indicated early on, but the most successful application since the early 1990s has been in brain ischaemia. Water diffusion decreases significantly immediately after ischaemic injury, possibly because of changes in membrane permeability or cell swelling. With its unmatched sensitivity, dMRI provides some patients with the opportunity to receive suitable treatment at a stage when brain tissue might still be salvageable.

  • Diffusion is a three-dimensional process, and molecular mobility in tissues might not be the same in all directions. Diffusion anisotropy was observed at the end of the 1980s in brain white matter, where it reflects the specific organization into bundles of myelinated axonal fibres running in parallel. It quickly became apparent that this feature could be exploited to map out the orientation in space of the white matter tracks in the brain.

  • With the introduction of the more rigorous formalism of diffusion tensor MRI (DTI), diffusion anisotropy effects could be fully extracted, characterized and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fibre tracking in the brain, which, in combination with functional MRI, opens a new window on the important issue of brain connectivity. DTI is also a promising tool for examining aspects of brain development and maturation, especially the myelination process, as well as changes in brain connectivity in disorders such as dyslexia.

  • Recent data indicate that dMRI could also be used to image brain activation by directly visualizing dynamic tissue changes associated with neuronal activation, an exciting departure from current functional imaging methods, which are based on the local modulation of cerebral blood flow. With the advent of very-high-field magnets, which will push the spatial and temporal limits of MRI, it seems likely that new advances will be made in the already flourishing field of diffusion imaging.

Abstract

Water diffusion magnetic resonance imaging (dMRI) allows tissue structure to be probed and imaged on a microscopic scale, providing unique clues to the fine architecture of neural tissues and to changes associated with various physiological and pathological states, such as acute brain ischaemia. Because diffusion is anisotropic in brain white matter, reflecting its organization in bundles of fibres running in parallel, dMRI can also be used to map the orientation in space of the white matter tracks in the brain, opening a new window on brain connectivity and brain maturation studies. This article provides an introduction to the key physical concepts that underlie dMRI, and reviews its potential applications in the neurosciences and associated clinical fields.

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Figure 1: Water diffusion and tissue microstructure.
Figure 2: Principles of diffusion magnetic resonance imaging (dMRI).
Figure 3: Diffusion-weighting.
Figure 4: Acute brain ischaemia.
Figure 5: Water diffusion and brain activation.
Figure 6: Anisotropic diffusion.
Figure 7: Fibre orientation.
Figure 8: Fibre tracking: connecting voxels.

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DATABASE

OMIM

Alzheimer disease

CADASIL

Hydrocephalus

Multiple sclerosis

FURTHER INFORMATION

Encyclopedia of Life Science

AIDS and the nervous system

Dyslexia

Human immunodeficiency viruses

Migraine

Schizophrenia

Stroke

Glossary

ANISOTROPY

The characteristic of a medium in which physical properties have different values when measured along axes orientated in different directions.

VASOGENIC OEDEMA

The accumulation of extracellular fluid that results from changes in capillary permeability, allowing for the seepage of plasma molecules and water.

CYTOTOXIC OEDEMA

Swelling of cellular elements and reduction in extracellular space that are commonly associated to anoxia and ischaemia. The underlying mechanism is a failure of the ATP-dependent Na+/K+ pumps, and the subsequent accumulation of intracellular sodium and water. By contrast to vasogenic oedema, capillary permeability is not impaired in cytotoxic oedema.

VOXEL-BASED MORPHOMETRY

Technique that uses a voxel-by-voxel comparison of the local concentration of grey and white matter between different groups of subjects. It involves the spatial normalization of the images to the same stereotactic space, segmenting the grey and white matter, smoothing the segments, and comparing the smoothed images between the different groups.

ECLAMPSIA

Seizures that occur in pregnant or puerperal women in association with hypertension, proteinuria or oedema.

LEUKOARAIOSIS

A Periventricular increase in the intensity of the white matter that is revealed by magnetic resonance imaging. Leukoaraiosis is frequently found in elderly people, and is commonly unrelated to any clinical manifestations.

WALLERIAN DEGENERATION

A form of degeneration occurring in nerve fibres as a result of their division. Named after A. V. Waller, who published an account of it in 1850.

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Le Bihan, D. Looking into the functional architecture of the brain with diffusion MRI. Nat Rev Neurosci 4, 469–480 (2003). https://doi.org/10.1038/nrn1119

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