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Neuroimaging

Applications of fMRI in translational medicine and clinical practice

Key Points

  • Functional MRI (fMRI) has had a major impact in cognitive neuroscience. It now has promising applications in clinical and translational medicine.

  • fMRI can assess changes in relative blood oxygenation accompanying increased blood flow in regions of the brain that are active while a task (for example, hand movement) is performed. The most well-established clinical application of fMRI is for presurgical mapping; this guides a neurosurgeon to spare brain tissue that, if injured, would cause new clinical deficits or limit good recovery.

  • In combination with simultaneously acquired electroencephalography (EEG), fMRI can image blood oxygenation state changes that accompany spontaneously generated changes in brain state in order to localize the source of seizure-inducing activity in epilepsy. The spatial definition of MRI allows this to be done at a much higher resolution than with EEG alone.

  • A frontier area for fMRI is in the identification of neurophysiologically based intermediate phenotypes in ways that can characterize even disorders that do not show structural changes in the brain. Recent applications suggest that functional intermediate phenotypes could better define heterogeneity in psychotic and affective disorders, and could be used to predict treatment outcomes.

  • In some instances, intermediate phenotypes that are heritable are endophenotypes. Because endophenotypes can be determined by smaller numbers of genes than conventional clinical phenotypes, in some cases plausible allelic associations have been identified with sample sizes smaller than those required in usual association studies.

  • By defining functional anatomy that is related to behavioural or perceptual states, fMRI can also help to directly understand the genesis of symptoms. For example, fMRI dissection of the subjective experience of pain into anatomically distinct activities of different functional systems provides a rationale for treatment approaches that are based on the modulation of different, interacting pathways.

  • Applications of fMRI as a pharmacodynamic (or pharmacokinetic) measure (pharmacological fMRI or phMRI) suggest that it might assume an important role in drug development. There are already several examples in which fMRI has been shown to be sensitive to change after a therapeutic intervention.

  • However, there remain practical problems that need to be resolved before fMRI can be used routinely. Signal changes are small, there are many confounds affecting the signal-to-noise ratio and the underlying physiological response itself is highly variable.

  • The promise of this new technique is substantial, but it is clear that the widespread introduction of clinical fMRI will demand new skills and working methods in clinical neuroradiology if this promise is to be delivered.

Abstract

Functional MRI (fMRI) has had a major impact in cognitive neuroscience. fMRI now has a small but growing role in clinical neuroimaging, with initial applications to neurosurgical planning. Current clinical research has emphasized novel concepts for clinicians, such as the role of plasticity in recovery and the maintenance of brain functions in a broad range of diseases. There is a wider potential for clinical fMRI in applications ranging from presymptomatic diagnosis, through drug development and individualization of therapies, to understanding functional brain disorders. Realization of this potential will require changes in the way clinical neuroimaging services are planned and delivered.

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Figure 1: Applications of multimodal MRI to brain lesion characterization.
Figure 2: Integrated electroencephalography and fMRI for epilepsy.
Figure 3: Pharmacological functional MRI (phMRI) allows drug effects in the brain to be defined from their modulation of activity.
Figure 4: Monitoring of long-term brain activity changes with a chronic treatment intervention.

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Acknowledgements

The authors are grateful to L. Lemieux, I. Tracey, H. Laufs, R. Wise and S. Sunaert for sharing images for figures. P.M.M. gratefully acknowledges the Medical Research Council and the Multiple Sclerosis Society of Great Britain and Northern Ireland for research support in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain.

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P.M.M. and E.T.B. are employees of GlaxoSmithKline.

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DATABASES

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Huntington's disease

schizophrenia

Glossary

Positron emission tomography

(PET). A technique that images the distribution of positron-emitting tracer isotopes (for example, 11C-choline) incorporated into compounds of interest by tomographical mapping that is based on photons emitted from positron collisions.

Functional MRI

(fMRI). An application of magnetic resonance to image physiological changes rather than structure. Use of blood-oxygen-level-dependent (BOLD) contrast is currently the most popular type.

Diffusion MRI

An application of magnetic resonance to image the moility (diffusion) of tissue water, an index of microstructure sensitive to many pathologies.

Functional neurosurgery

Neurosurgical procedures directed towards altering brain function through the ablation of tissue or implantation of stimulation electrodes.

Voxel

A voxel is the three-dimensional (3D) equivalent of a pixel; a finite volume within 3D space. This corresponds to the smallest element measured in a 3D anatomical or functional brain image volume.

Transcranial magnetic stimulation

A method by which a single or series of brief magnetic pulses that are applied externally to the skull focally modulate brain function through the generation of intracortical electrical currents. Effects can be stimulatory or inhibitory depending on the approach.

Functional connectivity

A measure typically derived from the relative temporal correlation of brain regions in a physiological image that is interpreted to express the degree to which regions are functionally interacting.

Functional plasticity

Changes in the functional association of activity in a brain region, provoked by alterations of intrinsic brain function rather than by the context of the activities alone.

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Matthews, P., Honey, G. & Bullmore, E. Applications of fMRI in translational medicine and clinical practice. Nat Rev Neurosci 7, 732–744 (2006). https://doi.org/10.1038/nrn1929

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