Review
Technical aspects and utility of fMRI using BOLD and ASL

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Abstract

Functional magnetic resonance imaging (fMRI) is an emerging methodology which provides various approaches to visualizing regional brain activity non-invasively. Although the exact mechanisms underlying the coupling between neural function and fMRI signal changes remain unclear, fMRI studies have been successful in confirming task-specific activation in a variety of brain regions, providing converging evidence for functional localization. In particular, fMRI methods based on blood oxygenation level dependent (BOLD) contrast and arterial spin labeling (ASL) perfusion contrast have enabled imaging of changes in blood oxygenation and cerebral blood flow (CBF). While BOLD contrast has been widely used as the surrogate marker for neural activation and can provide reliable information on the neuroanatomy underlying transient sensorimotor and cognitive functions, recent evidence suggests perfusion contrast is suitable for studying relatively long term effects on CBF both at rest or during activation. New developments in combining or simultaneously measuring the electrophysiological and fMRI signals allow a new class of studies that capitalize on dynamic imaging with high spatiotemporal resolution. This article reviews the biophysical bases and methodologies of fMRI and its applications to the clinical neurosciences, with emphasis on the spatiotemporal resolution of fMRI and its coupling with neurophysiology under both normal and pathophysiological conditions.

Introduction

The goal of functional neuroimaging is to map the activity of the living brain in space and time. Electrophysiological methods including magnetoencephalography (MEG) and electroencephalography (EEG) offer direct measurements of neural activity with high temporal resolution, but are limited by difficulties in defining the spatial extent of activation. Although more indirect, neuroimaging methods based on metabolic and vascular parameters provide excellent spatial resolution for imaging brain function along with precise matching with anatomical structures. In particular, functional magnetic resonance imaging (fMRI) has enabled imaging of changes in blood oxygenation and perfusion, and has been gaining increasing popularity over other methods for its total non-invasiveness and wide availability. Over the past several years fMRI has become the most widely used modality for visualizing regional brain activation in response to sensorimotor or cognitive tasks, and is now widely used in cognitive, systems and clinical neuroscience.

As compared to positron emission tomographic (PET) scanning, fMRI is completely non-invasive, does not require exposure to ionizing radiation, and is much more widely available. fMRI also provides superior temporal and spatial resolution, and increased sensitivity for detecting task activation in individual subjects through signal averaging. PET still provides a much greater repertoire of image contrasts. Whereas fMRI is primarily sensitive to hemodynamic changes, PET images can reflect blood flow, glucose utilization, oxygen consumption, and receptor binding. The latter occurs at concentrations well below the sensitivity of MRI, and can only be measured in vivo with radioactive tracers, though fMRI can be used to visualize pharmacological effects indirectly (Nguyen et al., 2000, Stein, 2001, Zhang et al., 2001). PET also provides a silent environment that is not affected by electromagnetic interference or the presence of ferrous objects. However, PET scanning is less widely available and significantly more costly than fMRI due to the need for on-line tracer synthesis.

In this review, we will discuss the physiological bases and contrast mechanisms underlying the susceptibility-based and perfusion-based fMRI signals with emphasis on the coupling with neurophysiology and the spatiotemporal resolution in each modality. A brief review of the applications of fMRI particularly in clinical neuroscience will also be provided.

Section snippets

Blood oxygenation level dependent (BOLD) contrast

The primary contrast mechanisms exploited for fMRI are BOLD contrast and perfusion contrast obtained using arterial spin labeling (ASL) techniques. These contrast mechanisms are illustrated schematically in Fig. 1. BOLD signal is the result of a complex interaction between changes in blood flow, blood volume, and oxygenation consumption accompanying neural activity (Kwong et al., 1992, Ogawa et al., 1993, Mandeville et al., 1999). Functional contrast is obtained because the ferrous iron on the

Activation-flow coupling

Most imaging studies of task-specific activation, including BOLD and perfusion fMRI, rely on the existence of a close coupling between regional changes in brain metabolism and regional CBF, herein termed activation-flow coupling (AFC). Changes in blood flow and metabolism occur with excitatory or inhibitory neurotransmission, both of which are energy consuming processes (Nudo and Masterson, 1986). Since regional CBF changes are used as a surrogate marker for changes in regional brain metabolism

Selected applications of fMRI

The advent of fMRI has greatly expanded opportunities for the application of functional neuroimaging to basic and clinical neuroscience. A comprehensive review of existing applications is well beyond the scope of any single review article, so this section will focus on selected previous and potential future applications of relevance to clinical neurophysiologists. The reader is referred to other reviews for applications in cognitive neuroscience (Cabeza and Nyberg, 2000, D'Esposito, 2000,

Conclusions

fMRI methods provide a relatively inexpensive and non-invasive means of measuring regional brain function, and is now available widely. Over the past decade, methods for acquiring and analyzing fMRI data have evolved considerably, resulting in improved reliability. fMRI is currently the primary method used for studying regional brain responses to cognitive tasks. An increasing body of evidence indicates that BOLD fMRI can reliably detect regional task activation due to sensorimotor and language

Acknowledgments

Grant support: NS37488, MH59934, and HD39621.

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