Sunday, 11 March 2012

Functional MRI of the brain

Learning objectives

After reading this chapter, you should be able:
  • Describe the cascade of phenomena linking neuronal activation and BOLD contrast
  • List the MRI sequences adapted to functional explorations
  • Present the basic steps of a functional MRI study: design of activation tasks, choice of paradigm, data acquisition, signal processing and statistical analysis of the results

Key points

  • Functional MRI will only detect brain activation very indirectly, as variations in the T2* signal, following changes in the oxyHb/deoxyHb ratio, after neurovascular coupling triggered by neuronal activity.
  • Data acquisition is carried out in T2*-weighted ultrafast sequences of the echo planar type, sensitive to BOLD contrast, during a succession of different repeated tasks following a paradigm.
  • The signal variations are very weak and their analysis is based on a statistical comparison between different states of activation.
  • The temporal resolution of fMRI, combined with the possibilities of morphological imaging, make MRI a modality of choice in the neurosciences.
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References

  1. Habas. . Journal de radiologie. 2002 Nov;83(11):1737-41.
  2. Le Bihan and Lehericy. . Journal of neuroradiology. 1999 Mar;26(1 Suppl):S54-8.
  3. Gore. Principles and practice of functional MRI of the human brain. The Journal of clinical investigation. 2003 Jul;112(1):4-9.
  4. Voss, Zevin. Functional MR imaging at 3.0 T versus 1.5 T: a practical review. Neuroimaging clinics of North America. 2006 May;16(2):285-97, x.
  5. Golay, de Zwart. Parallel imaging techniques in functional MRI. Top Magn Reson Imaging. 2004 Aug;15(4):255-65.
  6. Di Salle, Esposito. High field functional MRI. European journal of radiology. 2003 Nov;48(2):138-45.
  7. Delmaire, Krainik. . Journal de radiologie. 2007 Mar;88(3 Pt 2):497-509

Functional MRI of the brain

Functional MRI (fMRI) is an indirect method of imaging brain activity at high temporal resolution. The principle relies on detecting the transient hemodynamic response provoked by neuronal activity (neurovascular coupling).

Physiological basis of brain activation and BOLD contrast

The neuronal metabolism is dependent on blood oxygen supply, as the production of energy from glucose is mainly of the aerobic type. Neuronal activity provokes an increase in oxygen consumption and an even higher increase in local blood flow (neurovascular coupling).
As the increase in flow exceeds the increase in oxygen consumption, neuronal activity is expressed as a relative increase in oxyhemoglobin compared to deoxyhemoglobin in the activated zones. The relative decrease in deoxyhemoglobin concentration, which has a paramagnetic effect, can be detected by MRI as a weak transient rise in the T2* weighted signal. This is the BOLD contrast principle (Blood Oxygenation Level Dependent).

Data acquisition in functional MRI

To cope with the constraints of temporal resolution and T2* sensitivity, functional MRI sequences are generally of the ultrafast echo planar type (GE-EPI), with small matrixes (and thus weaker spatial resolution). The BOLD contrast obtained is very poor (low percentage of signal variation). Acquisitions need to be repeated in time, for different activation tasks, in order to conduct a statistically correlated comparative study of the signal variations measured in each pixel and variations in task. Differences in activation will thus relate to the difference between the two tasks.
The task sequence and mode of repetition constitute the activation paradigm. It consists of at least one reference task, and another task whose only difference is in the activity we wish to study (figures 14.2 and 14.3).
For instance, for motor activities, rest could be the reference activity, and repeated finger movements, the activity. For cognitive activities (language, interpretation, memory...), the protocols are more complex and the design of relevant tasks more subtle. It is also possible to simultaneously record data on patient responses during the examination (frequency of movements, stimulus-response time, correct or incorrect response...) to be integrated into the statistical analysis model.

Experimental paradigms in functional MRI

  • Block design: the activities are organized into blocks of several seconds’ duration, alternating at regular intervals. Within the same block, the hemodynamic responses will overlap and accumulate before reaching a plateau.
  • Event-related design: activities or stimuli that are either single or presented in short repetition, in a sequence that may be pseudo-random (to avoid the phenomenon of anticipation), possibly including measurement of response performance (response delay and accuracy…). The local hemodynamic response is thus evaluated for the different activities.
The theoretical curves of the hemodynamic response and the BOLD signal are established according to the type of design chosen and the time course of the sequence of conditions or tasks. They namely take account of the interval between neuronal activation and the measured hemodynamic response. In the case of rapidly repeated tasks, the sum of their effects results in a hemodynamic plateau response. This model forms the basis for statistical analysis, focused on pixels whose signal changes are linked to the paradigm.

The limitations and disadvantages of BOLD contrast functional MRI are linked to:
  • the distance between activated neurons and vascular variation in the oxyHb/deoxyHb ratio, leading to imprecisions in locating the activation zone
  • movement artifacts (movements of the head, vascular pulsations, breathing…) and magnetic susceptibility (signal distortion and loss at interfaces with the bones, the air, hematoma or at post-operational stage).
As in MRA, diffusion and perfusion MRI, parallel acquisition techniques will increase temporal resolution and reduce the artifacts in echo planar sequences by reducing echo time.

Functional MRI by spin labeling


This functional MRI technique consists in applying the spin labeling method used in perfusion MRI to detect variations in perfusion after brain activation.
This alternative to functional MRI by BOLD contrast is effective (more sensitive and less variable) for tasks repeated at low frequency. However less volume is explored in spin labeling.

Analysis of functional MRI data

Raw functional MRI data must undergo several critical processing steps before yielding the (indirect) brain activation images:
  • Preprocessing: the images are smoothed to reduce noise and the artifacts (movements, orientation and spatial distortion) are corrected.
  • Normalization: this is necessary to compare patient examinations that are different or performed at different times. The images are repositioned either between two examinations, or to match a reference atlas (Talairach), to overlap in the same spatial coordinate.
  • Statistical analysis: this is based on mathematical modeling of the expected hemodynamic response, which will depend on the paradigm used. The most common type of model is the generalized linear model (GLM). This model will examine each pixel to detect those whose signal variation in time is linked to the sequence of different activation tasks. The pixels considered as statistically significant can then be represented overlapping high-resolution morphological imaging for better location.

Applications of functional MRI

In research, functional MRI is widely used in neuropsychological and cognitive studies.
In clinical practice, functional MRI is currently applied to localizing functional regions of motricity and language for pre-operational purposes before a neurosurgical excision, to determine the hemispheric dominance of language (to calculate the laterality index) and assess the possibilities of functional recuperation.

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