The basis of MRI technology rests on the magnetic properties of the hydrogen atom, which, as a component of water, is found ubiquitously in organic tissues (water constitutes roughly 80% of brain weight). The nucleus of a hydrogen atom, a single proton, is characterized by an intrinsic magnetic moment, called spin. The protons in tissue are normally oriented in random directions, but if an external magnetic field is applied, they will tend to align with the field. Quantum mechanics and statistical physics dictate that spins can orient either in the direction of the applied field (parallel) or in the direction opposite to it (anti-parallel), but on average the parallel orientation will gain a weak majority. This situation will result in a net magnetic moment induced by the external field in the tissue; in other words, the tissue will become slightly magnetized. The external (or main) field in an MR environment is provided by a powerful electromagnet whose intensity is typically 1.5 tesla for clinical scanners (for comparison, the electromagnets used in car demolition lots have a similar strength), and up to 7 tesla for human research scanners. The intensity of the induced magnetization is dependent on the proton distribution (i.e., on the local molecular characteristic of the tissue). Although this induced magnetization could, in principle, provide a contrast signal resolving different type of tissues (e.g., gray matter, white matter, cerebrospinal fluid) into an image of anatomical detail, the magnitude of this effect is in practice so small that it does not lend itself to direct measurement.
The way in which MRI actually recovers its signal is by first perturbing the examined system. This instrumental perturbation is performed by applying short radiofrequency (RF) pulses that, when appropriately tuned, are able to transiently tip the orientation of the spins away from the applied magnetic field. However, the tendency of the spins is to return to the orientation coherent with the applied magnetic field, given that the latter state is characterized by a lower energy. The relaxation process occurs through the emission of an RF wave that is detected by the same RF hardware that emits the excitation pulses. In MR terminology, this is referred to as the RF coil, which has the form of a small cylindrical cage that surrounds the subject's head in the scanner. The emitted RF wave—or, more precisely, the temporal signature of its decay as the excited spins relax—constitutes the actual MR signal and depends on the molecular characteristics of the local tissue, as well on the particular sequence of excitation pulses employed. The details of the physics that specify how appropriate pulse sequences can be engineered to acquire images of the brain system with different physiological meaning are beyond the scope of this discussion, and the interested reader is directed elsewhere (e.g., Buxton 2002).
The spin relaxation measured with MRI can be decomposed into longitudinal and transverse components, which are only partially related. The measurement of the relaxation time of the longitudinal component, called T1, provides images in which the contrast between different types of tissue (notably, gray matter, white matter, and cerebrospinal fluid) is maximized. Such T1-weighted images are capable of defining the anatomy of the living brain with great precision and are therefore used as an anatomical reference for most of the neuroimaging studies. An image of the entire brain, with a resolution, or voxel size, of 1 mm3 (voxel stands for "volume pixel," the unitary element of a three-dimensional image), can be acquired on a 1.5-tesla clinical scanner in less than 6 minutes.
The measurement of the relaxation time of the transverse component, which can be further split between the T2 and the T2* characteristic times, provides images that are influenced by the local inhomogeneity of the magnetic field, which in turn is increased by the local blood perfusion. In particular, T2*-weighted images are characterized by a contrast that highlights changes in vascular dynamics that accompany neural activity and are thus employed in functional mapping studies. The advent of a very fast technique for the acquisition of T2*-weighted images, called echoplanar imaging (EPI), allows the collection of an entire brain volume in 3-4 seconds and has been instrumental in the rapid development of functional MRI. The ultrarapid acquisition of EPI images and the nature of the detected T2* signal, which tends to become negligible when integrated over very small voxels, limit the resolution of standard EPI images, which typically have a voxel size of 3-4 mm per side. The use of particular technical and experimental arrangements has allowed, in special cases, the achievement of submillimetric precision, such as that required for the imaging of the columnar organization of visual cortex (Menon and Goodyear 1999). Table 10-2 includes the multiple applications of MR-based technologies in psychopharmacology.
TABLE 10-2. Use of magnetic resonance imaging (MRI) in psychopharmacology research
Type of imaging Technique
Method of analysis
Structural MRI Voxel-based morphometry (VBM) Automated (sMRI)
Functional MRI (fMRI)
Functional connectivity analysis
Diffusion tensor tractography
Magnetic resonance spectroscopy
Region of interest (ROI) analysis Manual
BOLD technique (described in text)
Resting-state activity, independent component analysis (ICA), structural equation modeling
Diffusion-weighted, perfusion-weighted, diffusion tensor imaging (DTI)
DTI-based imaging and fiber tracking
Detect concentration of specific metabolites in cerebral regions
Computerized algorithms, statistical models
Automated and voxel based (manual)
Innovative in vivo magnetic resonance approaches
Neuroimaging genomics fMRI activations to challenges in various genotypes
Computerized genotyping sMRI + fMRI
Virtual reality (VR)-fMRI
Data fusion using joint independent component analysis (jICA) of simultaneously recorded structural and functional data
VR-based cognitive challenges
Online linkage of two fMRI scanners in different locations
Used to measure
Volume of brain regions in brain disorders and ischemic lesions
Same as above to measure volumes and ischemic brain lesions (hyperintensities)
Area of activation in response to cognitive/affective challenge
Connectivity between different components of neural network during various mental states
Tissue integrity by imaging water diffusion in restricted and free space, used in diagnosis of stroke and neurodegeneration
Anatomical white matter tract connectivity between brain locations
Neuronal/glial metabolic abnormalities in localized in single or multiple voxels
Identifying candidate disease-associated genes among genetically distinct populations (COMT, BDNF, 5-HTTLPR polymorphisms)
Structural and functional disconnection in mental disorders
Cerebral activation in real-life scenarios (spatial recognition memory)
Cerebral activation changes during social interactions (social neuroscience technique)
Note. 5-HTTLPR = serotonin transporter-linked polymorphic region; BDNF = brain-derived neurotrophic factor; BOLD = blood oxygenation level-dependent; COMT = catechol-O-methyltransferase.
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