The BOLD Signal in Functional MRI

Functional MRI exploits the fact that deoxyhemoglobin has paramagnetic properties and oxyhemoglobin does not. Deoxyhemoglobin disturbs the local magnetic environment, causing the surrounding protons to dephase even faster than they would otherwise (Figure 10-3).

FIGURE 10-3. Schematic diagram of the effect of hemoglobin (Hb) on the local magnetic field of brain tissue.

FIGURE 10-3. Schematic diagram of the effect of hemoglobin (Hb) on the local magnetic field of brain tissue.

Only deoxyhemoglobin (deoxyHb) has paramagnetic properties and locally distorts the field, leading to faster spin dephasing.

Source. Reprinted from Pagnoni G, Berns GS: "Brain Imaging in Psychopharmacology," in The American Psychiatric Publishing Textbook of Psychopharmacology, 3rd Edition. Edited by Schatzberg AF, Nemeroff CB. Washington, DC, 2003, pp. 163-172. Copyright 2003, American Psychiatric Publishing, Inc. Used with permission.

Because neuronal activity leads to an overactive increase in blood flow, this actually decreases the amount of deoxyhemoglobin relative to oxyhemoglobin. Because less deoxyhemoglobin means less rapid spin dephasing, this increase in blood flow appears as an increase in MR signal. This is called the blood oxygenation level-dependent (BOLD) signal. In response to a regionally specific neuronal activation, the BOLD signal will usually increase by an amount on the order of 1% on a standard 1.5-tesla clinical scanner. The intensity of the signal is proportional to the strength of the main magnetic field—for example, it will double in the case of a 3-tesla scanner.

The temporal resolution of fMRI is determined both by the hemodynamic response and the physical constraints of the scanner magnetic fields. The hemodynamic response generally lags the neural activity by 3-5 seconds and may extend upward to 10-15 seconds (Figure 10-4). The rate at which the scanner can acquire images is influenced by the desired resolution. Generally, the more slices and the finer the resolution within each slice, the longer a whole-brain acquisition takes. While an individual slice can be acquired in as little as 60 milliseconds, whole-brain imaging usually requires about 2-3 seconds.

FIGURE 10-4. Relative blood oxygenation level-dependent (BOLD) response to 1-second visual stimulation.

FIGURE 10-4. Relative blood oxygenation level-dependent (BOLD) response to 1-second visual stimulation.

Pulsating Bold Response

Copyright © American Psychiatric Publishing, Inc., or American Psychiatric Association, unless otherwise indicated in figure legend, All rights reserved.

These functional magnetic resonance imaging (fMRI) data are from the occipital cortex and were obtained in a healthy volunteer in a 3-tesla scanner. The amplitude of the signal is about 2%, with the peak 5-8 seconds after the stimulus.

Source. Reprinted from Pagnoni G, Berns GS: "Brain Imaging in Psychopharmacology," in The American Psychiatric Publishing Textbook of Psychopharmacology, 3rd Edition. Edited by Schatzberg AF, Nemeroff CB. Washington, DC, 2003, pp. 163-172. Copyright 2003, American Psychiatric Publishing, Inc. Used with permission.

Whereas fMRI measurements are easy to perform, there are specific limitations with BOLD imaging.

1. The BOLD effect originates from venous vessels (capillaries, venules, and veins), so the signal is not exactly collocated either with the locus of neural activity or with the arterial supply. This spatial error may, however, be negligible for brain-mapping studies employing a standard spatial resolution (voxel size ~50 mm3).

2. Bulk head motion and physiological pulsation (heart pulse, respiration) artifacts. For the motion, head movement should be restrained while maintaining a comfortable situation for the subject.

3. Susceptibility artifacts. The fact that BOLD detects local changes in magnetic susceptibility (due to the variation in deoxyhemoglobin concentration) renders it vulnerable to the large discontinuity that exists at the interfaces between bone/air and bone/liquid. In these regions, the steep variations in tissue density cause a distortion of the local magnetic field, resulting in both a spatial distortion of the image and a drop in the BOLD signal. This makes it difficult to detect the small changes associated with deoxyhemoglobin variations. The problematic regions are notably the orbitofrontal cortex and the inferior part of the temporal lobes, which unfortunately are the locus of many interesting neuropsychological processes.

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