Diffusion tensor imaging
Water molecules flowing in biological tissues are the basis of a novel imaging technique that has leaped to prominence recently.
Diffusion-tensor magnetic resonance imaging (DTMRI) is an advanced magnetic resonance imaging technology that measures the three-dimensional mobility of water molecules, non-invasively and in vivo as well as ex vivo.
Water molecules generally diffuse fastest along the direction of fibres, such as those in central nervous system white matter or in cardiac muscle, and slowest perpendicular to the fibre direction.
DTMRI measures these diffusion rates and provides high-resolution images showing the structure and architecture of deep white matter, such as the corpus callosum and brain stem. This exciting imaging technique is already being applied to studies of ageing and cognition, neuropsychiatric disorders (e.g. schizophrenia), HIV infection, multiple sclerosis, surgical planning and treatment evaluation for brain tumours.
Because of its non-invasive nature, DTMRI has real potential to replace certain animal experiments with safe, highly relevant human volunteer studies, investigating relationships between brain structure, function, genes and behaviour — in health and disease.
Until recently, more was known about brain connectivity in monkeys than in humans, because the information was obtained through invasive and usually terminal experiments on animals (such as electrode studies and tract-tracing). Apart from the ethical issues of animal research, species differences can complicate interpretation of such data [1].
For example, before the advent of DTMRI detailed information about brain circuitry between motor areas and the striatum was available only from experiments on animals. Now, comparable connections have been mapped directly in human volunteers [2].
DTMRI can also be combined with other techniques. According to Kelvin Lim of the University of Minnesota, DTMRI of schizophrenia patients, supplemented with data on single nucleotide polymorphisms of myelination-related genes, may provide new gene targets for therapy.
David Laidlaw and Song Zhang of Brown University, USA, in collaboration with Mark Bastin of the University of Edinburgh, are developing imaging protocols and mathematical models to visualise human brain white matter tracts and quantify how their structure is affected by brain tumours [3]. They have used red ‘streamtubes’ to represent white matter fibre bundles and green ‘streamsurfaces’ to indicate regions where fibres cross.
DTMRI is also improving mathematical models of human physiology. The ambitious aim of research at Johns Hopkins University is to develop integrated computer simulations of the human cardiovascular system, using information from human heart-cell biopsies as well as diffusion tensor images of the human heart. Better computer models will also help to replace animal experiments.
With technical developments moving fast, researchers are starting to see how this safe, high-resolution, non-destructive imaging method could impact on their work.
References and information
1. Yamamoto T, Nishimura Y, Matsuura T et al (2004). Cerebellar activation of cortical motor regions: Comparisons across mammals. Prog Brain Res 143:309-317.
2. Lehericy S, Ducros M, Krainik A et al (2004). 3-D diffusion tensor axonal tracking shows distinct SMA and pre-SMA projections to the human striatum. Cereb Cortex 14:1302-1309.
3. Zhang S, Bastin M, Laidlaw DH et al (2004). Visualization and analysis of white matter structural asymmetry in diffusion tensor MRI data. Magn Reson Med 51:140-147.
(Originally published in the Dr Hadwen Trust’s Science Review 2004)